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Difference between revisions of "2011 Group 4 Project"
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* [[#Current_Research | '''Current research''']] projects and techniques
* [[#Current_Research | '''Current research''']] projects and techniques
'''Early 19th Century''' : Light microscopes allowed for the detection of desmosomes within cells.
'''Early 19th Century''' : Light microscopes allowed for the detection of desmosomes within cells.
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'''1990''' Green analyses the amino acid sequence of desmoplakin protein. It was predicted that desmoplakin would have a central alpha-helical, coiled-coil region. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/1689290]|Green KJ, Parry DA, Steinert PM, Virata ML, Wagner RM, Angst BD, Nilles LA. (1990) Structure of the human desmoplakins. Implications for function in the desmosomal plaque. '''Journal of Biological Chemistry'''15;265(5):2603-12.</ref>
'''1990''' Green analyses the amino acid sequence of desmoplakin protein. It was predicted that desmoplakin would have a central alpha-helical, coiled-coil region. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/1689290]|Green KJ, Parry DA, Steinert PM, Virata ML, Wagner RM, Angst BD, Nilles LA. (1990) Structure of the human desmoplakins. Implications for function in the desmosomal plaque. '''Journal of Biological Chemistry'''15;265(5):2603-12.</ref>
'''1990''' : Koch isolated and characterised the cDNA encoding desmoglein. When screened with cDNA libraries, it was found that they had a high level of homology with cadherins, and as such identified it as a part of the cadherin superfamily. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/1706270]|Koch PJ, Walsh MJ, Schmelz M, Goldschmidt MD, Zimbelmann R, Franke WW.Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules. '''European Version of Cell Biology''' 53(1):1-12.</ref>
'''1990''' : Koch isolated and characterised the cDNA encoding desmoglein. When screened with cDNA libraries, it was found that they had a high level of homology with cadherins, and as such identified it as a part of the cadherin superfamily. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/1706270]|Koch PJ, Walsh MJ, Schmelz M, Goldschmidt MD, Zimbelmann R, Franke WW.Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules. '''European Version of Cell Biology''' 53(1):1-12.</ref>
'''1991''' : Desmocollin, another transmembrane protein in desmosome is isolated and characterised by Collins. Desmocollin has an a form and b form within the cytoplasm, which are produced by alternative splicing of mRNA. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/2010468]|Collins JE, Legan PK, Kenny TP, MacGarvie J, Holton JL, Garrod DR. (1991) Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains. '''Journal of Cell Biology''' 113(2):381-91.</ref>
'''1991''' : Desmocollin, another transmembrane protein in desmosome is isolated and characterised by Collins. Desmocollin has an a form and b form within the cytoplasm, which are produced by alternative splicing of mRNA. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/2010468]|Collins JE, Legan PK, Kenny TP, MacGarvie J, Holton JL, Garrod DR. (1991) Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains. '''Journal of Cell Biology''' 113(2):381-91.</ref>
Revision as of 07:15, 26 May 2011
- 1 Desmosomes
- 1.1 Introduction
- 1.2 History
- 1.3 Structure
- 1.4 Function
- 1.5 Hemidesmosomes
- 1.6 Regulation
- 1.7 Desmosomes and Disease
- 1.8 Current Associated Research
- 1.9 Glossary
- 1.10 Images and Videos
- 1.11 Reference List
Cell junctions occur at points of contact between cells and between cells and the matrix. These junctions are important in the integrity of tissues, cell communication and transport. Cell junctions can be grouped into three main classifications:
- Occluding junctions that hold epithelial cells together to prevent the leaking of small molecules from one side to the other.
- Anchoring junctions attach cells to adjacent cells as well as the extracellular matrix.
- Communicating junctions allow for the transmission of chemical and electrical signals between cells [1]
Desmosomes are classified as anchoring junctions, reasons for which will be explained below.
Desmosome originates from the greek terms desmo meaning bond and soma meaning body. [2] This etymology reveals the main function of desmosomes which is to bind cells to one another. [3] Desmosomes, also known as macula adhaerens, have a number of other roles including strengthening the internal structure of a cell, sensing environmental cues, regulating tissue homeostasis and assisting in tissue morphogenesis. By indirectly connecting intermediate filaments of adjoining cells, they produce a strong adhesive force which can resist great shear forces. Hence, they are found in such tissues as the myocardium, the bladder, the gastrointestinal mucosa and many epithelia. [4]
This webpage will look into a number of areas to help in the understanding of what desmosomes are, how they work, and what can go wrong when these desmosomes don't work properly. These areas include:
- The history of desmosomes
- The structure of demsmosomes
- The specific function of desmosomes
- Hemidesmosomes
- Regulation of the cell junction
- Diseases that are related to desmosomes
- Current research projects and techniques
Early 19th Century : Light microscopes allowed for the detection of desmosomes within cells.
1864 : Giulio Bizzozero gives the first description of the desmosome. He commented on the small, dense areas that were seen between cells and suggested that these were points of adhesion between adjacent cells. [5]
1920 : Josef Schaffer names the structure being seen under the microscope, 'desmosome.' From a greek origin, the name comes from two words meaning 'bond' and 'body.' [6]
1956 : After biological sciences were revived after the world wars, Porter viewed cells using electron microscopy to note that between adjacent cells there were electron dense areas that branched off into cells with fibrous strands. [7] [8]
1974 : By developing new techniques, Skerrow and Matoltsky isolated desmosomes from other cellular components. [9] After running biochemical tests to identify their molecular characteristics, the pair found that the structures had a high glycoprotein content, and that it was these glycoproteins that were responsible for the cell-cell interactions. In doing this, they were able to confirm the hypothesis from 30 years earlier, that desmosomes were in fact junctions between cells. [10]
1981 : Franke and Steinberg characterized and purified the components of desmosomes. [11]
1983 : Using specific antibodies, Cowin and Garrod identify the localisation of desmosomes and note that desmosome distribution is similar between all vertebrates. [12] [13]
1985 : Steinberg, along with his colleagues, begin to isolate plaque proteins. [14]
1988 : Green isolated and analyzed the desmoplakin coding sequence. [15]
1990 : Blaschuk identifies that cadherins contain a tripeptide motif that is crucial in cell adhesion. [16]
1990 Green analyses the amino acid sequence of desmoplakin protein. It was predicted that desmoplakin would have a central alpha-helical, coiled-coil region. [17]
1990 : Koch isolated and characterised the cDNA encoding desmoglein. When screened with cDNA libraries, it was found that they had a high level of homology with cadherins, and as such identified it as a part of the cadherin superfamily. [18]
1991 : Desmocollin, another transmembrane protein in desmosome is isolated and characterised by Collins. Desmocollin has an a form and b form within the cytoplasm, which are produced by alternative splicing of mRNA. [19]
1991 : Amagai explained the pathogenesis of S. aureus bullous impetigo which is caused by toxin-mediated damage to desmosomes. This was achieved by using antibody immunotherapy. [20] [21]
1992 : Stappenbeck and Green define the functional domains of desmoplakin. [22]
1994 : Kouklis demonstrates that the interactions between desmoplakins and intermediate filaments are direct. [23]
1997 : McGrath describes that mutations in Plakophilin-1 leads to ectodermal dysplasia. [24]
1998 : Desmosomal cadherin attachments can be inhibited by peptides that correspond to desmocollin and desmoglein receptor sites (Tselepis). [25]
1999 : Structural studies of the demoplakin gene confirm that the carboxyl terminus acts as an intermediate filament binding site (Kowalczyk). [26]
2001 : Vasioukhin saw that epithelial cells rely on desmoplakin for integrity. [27] [28]
2002 : Windoffer suggests that desmosome structure is dynamic, using fluorescence recovery. [29] [30]
2003 : Kljuic identifies the genes for desmogleins and desmocollins on the q arm of chromosome 18 in humans. [31] [32]
2003 : He generates a three-dimensional image of a desmosome. [33][34]
2004 : Grossman confirmed the necessity for plakophilin in desmosomal plaques. [35] [36]
2005 : Kimura discovers that desmosomes can be switched from an adhesive and hyper-adhesive state by activation and suppression of Protein Kinase C [37]
2007 : Chidgey and Dawson investigate the role of desmosomes in cancers transforming from tumours to invasive malignancies [38]
2007 : Schmidt suggests that abnormalities that occur within the body may be influenced by changes in signalling properties of desmosomes. [39]
2011 : Al-AMoudi and others show the 3-dimensional structure of a demosomal plaque. [40]
Structure on a Cellular Level
The desmosome, ~300nm in diameter, consists of two distinct domains - the extracellular core domain, ~30-35nm in diameter, and the dense cytoplasmic plaque, ~30-40nm in diameter. [41]
The extracellular core domain, also known as the desmoglea, is made up of the transmembrane proteins - cadherins. [42] There are two types of desmosomal cadherins: desmogleins (DSGs) and desmocollins (DSCs). They extend from the plaque to the extracellular core where they connect to the adjacent cell's cadherins.
The disc shaped plaque, situated parallel to the inner leaflet of the cell membrane, is composed of an outer dense plaque and an inner dense plaque separated by a space of ~8nm. [41] The outer dense plaque is located closer to the plasma membrane than the inner dense plaque and links cadherin tails to desmosomal anchor proteins. [41]
The linker proteins involved are plakoglobin (PG), plakophilin (PKP) and desmoplakin (DP). Extending out from the outer dense plaque are the desmosomal anchor proteins desmoplakins. These form the majority of the inner dense plaque. On the other side of the inner dense plaque is where the intermediate filament network of the cytoskeleton attaches. [43]
Structure on a Molecular Level
Extracellular Domain
As outlined above, the extracellular domain consists of desmosomal cadherins: desmogleins (DSGs) and desmocollins (DSCs). Cadherins are arranged along the mid-line in ~7nm intervals, with alternating cis (interaction between same cell surface) and trans (interaction between different cell surfaces) dimers causing a tightly packed zipper formation. They are each made up of four extracellular immunoglobulin domains (EC1-4), an immunoglobin extracellular anchor (EA), a transmembrane domain (TM), an intracellular anchor (IA) and additional cytoplasmic domains, which distinguish the cadherin isoforms. [41] Each immunoglobin domain is connected end to end by three calcium ions, forming a curved structure of about 100 degrees. Along the domains are disulfide bonds, O-linked sugars and N-linked sugars. [44]
The cadherin isoforms are composed of different additional cytoplasmic domains as follows [41]:
|Cadherin Isoform
|5 subunits
|6 subunits
|2 subunits
|3 subunits
There are three isoforms of DSC (1-3), however they splice alternatively into two transcript variants named DSCa and DSCb.
ICS is an intracellular cadherin-like sequence, which binds to plakoglobin.
IPL is an intracellular proline-rich linker.
RUD is repeat unit domains.
DTD is a desmoglein terminal domain
Tyrosinase-related protein 2 (Trp2) mediates the cis and trans interactions and is most likely responsible for the binding of cadherins to the plaque. [44] However it is currently unknown whether heterophilic cis and trans or homophobic cis and trans interactions are the main cause of cell adhesion. [45]
The extracellular domain mediates adhesion and whilst the mechanical structure is extremely strong, it is still dynamic since the attachment of both types of cadherins are reliant on Ca2+ levels. During embryonic development of the desmosome, the link between the two cells remains weak. Eventually the link strengths and the cell becomes hyperadhesive. This latter stage is calcium independent, as once protein kinase C is activated by Ca2+ it is able to remain activated in the long-term. Hence this hyperadhesive state will not be affected by changes in Ca2+ concentration. However, the desmosome is able to revert to the earlier state when responding to certain environmental signals to allow for such things as cell migration if regeneration of the epithelia is necessary. [44] [42] The primary morphological attribute which indicates calcium independence is a distinct electron-dense midline that bisects adjoining cell's extracellular core domains. [46] Whereas when desmosomes are calcium dependent the midline is lost and the diameter of the intercellular space decreases by 10%. Potentially this is caused by Ca2+ ions becoming trapped to the cadherins and securing their position into an ordered structure. [46]
Outer Dense Plaque
The dense plaque is made up of two electron-dense zones: an outer dense plaque and an inner dense plaque. The outer dense plaque being lower in density that the inner dense plaque. They are separated by an electron-lucent zone, ~8nm in diameter. The outer dense plaque is located in the cytoplasm, parallel to the plasma membrane. [46] It is ~15-20nm in diameter and characterised by two zones: a ~4nm zone located ~10nm from the plasma membrane and a ~8nm zone located ~20nm from the plasma membrane. The major plaque proteins are plakoglobin (PG), plakophilin (PKP) and desmoplakin (DP).21464301(Please note permission was sought and granted for citing of PNAS Article: The three-dimensional molecular structure of the desmosomal plaque)
Plakoglobin and plakophilin, from the armadillo family of proteins, help to mediate: the attachment of desmoplakin to the intermediate filaments, the arrangement of the plaque components and the signalling in some transduction pathways.
The structure of the major plaque proteins is as follows [41]:
|Plaque Proteins
|Arm Repeats
|Arm Repeats
|Present (C-tail)
|Present (C-tail)
Head is an amino-globular head domain with a N terminus.
Tail is a caboxy-terminal tail with a C terminus. In desmoplakin, the tail constits of three plakin repeat domains.
GSR is a glycerine-serine-arginine rich domain.
Insert is a rigid structure producing the bent angle.
The two isoforms of plakophilin, PKP1 and PKP2, both splice into PKPa and PKPb. PKPa is shorter in length than PKPb. For PKPb in comparison to PKPa: in arm repeat three PKP1 version has an additional 21 amino acids, and in arm repeat four PKP2 version has an additional 44 amino acids.
The isoforms of desmoplakin, DP1 and DP2, are characterised by the length of their rod domain - the DP1 rod being ~2/3 longer than the DP2 rod.
Plakoglobin and desmoplakin complexes form an alternating arrangement which acts as a base for the desmosomal cadherins to attach. The cadherin tails bind to the N terminus of desmoplakin before they connecting to the adjoining cell's desmosomal cadherins. Formation of this initial structure is mediated by plakoglobin and plakophilin. For reinforcement the remaining space between the plaque and the plasma membrane is filled by plakophilins. 21464301
Inner Dense Plaque
The inner dense plaque, alike the outer dense plaque, is ~15-20nm in diameter. It is primarily comprised of the junctional complexes, desmoplakins, which tether to the intermediate filaments.[46] The molecular structure of desmoplakin is outlined in the above 'Outer Dense Plaque' section, as the protein spans through both parts of plaque. The leading theory is that the glycine-serine-arginine domain, adjacent to the carboxy-tail terminus of desmoplakin, regulates the attachment of the keratin intermediate filaments. The molecular structure of the plaque with its components having both medial and lateral connections, is thought to be one of the main reasons for the desmosome's adhesive strength.21464301
The desmosome as a cellular adhesion junction
- Establishes confluence or a continuous sheet of bonded cells
- Stabilises cellular positioning
- Strenghthens epithelium
- Desmosome component proteins function in cellular regulatory pathways
Desmosomes are important components of many epithelia, occuring with greater or lesser prevalence in them. In a normal state, desmosomes establish continuity or confluence of epithelial sheets. [47] Desmosomes contribute to the barrier function of epithelia, a function that is largely brought about by the Zonula Adherens. [48] Desmosomes are normally permanent and prevent leaking of small molecules through the surface as well as resisting shearing forces. [49] Shearing forces encountered, for example particularly in the stratified, squamous, keratinised epithelium of the palmar or plantar epidermis as well as in muscular layers of the heart (myocardium).
- Multiple desmosome adhesion complexes located on the plasma membrane bond cells to each other and in this way a confluent epithelial sheet is formed.
Importantly, once cells are bonded to each other their position in the sheet of epithelium becomes stabilised.
- A sound epithelial structure is thus created.
There are many aspects of the structure of demosomes that are still not completely understood.
However, it is known that cytoplasmic surface molecular interactions, link a) extracellular transmembrane cadherins (desmoglein and desmocolin) with, b) intermediate keratin filaments located inside cells as part of the their cytostructure.[50] An attachment plaque is the go-between or bondage site that mediates the adhesion of the keratin filaments with the cadherin proteins that insert their tails into the plasma membrane. [51]
Electron microscopy (EM) and specialised staining techinques makes it possible to view these structures. It has become possible to hypothesise how desmoglein and desmocollin bond in a zipper-like fashion at the midline between the cells. Then as stated, the tails of these calcium mediated and dependent cadherins bind through the plasma membrane into the cytoplasm of the adjacent cells, forming a connection with the plaque located therein thus anchoring two cells together.[52]
Desmoplakin, plakoglobin and plakophilin are the proteins that form this dense plaque (each cell in question has one and one for every desmosome complex formed) that functions as the bondage site for the intermediate keratin filaments and the cadherins. [53]
The desmosome has linked the cytostructure of two separate individual cells together as one.
By having numerous desmosomes the cells in effect are riveted together in many ways like two bean bags side by side. Numerous desmosomes, above and below an imaginary midline plane running laterally through the epithelial sheet, means forces such as encountered in a mild sliding abrasion can be effectively countered.
- In this way different physical stresses slightly above and below and along a lateral plane encountered by the organic material as whole can be withstood. Such stresses such as chafing of the epidermis, or the continuous muscular beating of rounded heart myocardium.
Desmosome protein composition can differ in the presence of the isoforms of core and other accessory proteins, and to their relative amount present. [54]
- It is in this way that desmosomes can influence the specific way cells bind to the cytoskeleton of another, thus influencing tissue supracellular architecture.[55] [56]
For instance meningothelia of the meninges differs from myocardium in terms of desmosome protein composition and amount contained. Desmosome adhesive qualities in these contrasted tissues differs significantly, in that one is much more robust than the other, enabling differing functions in the body. [59]
Changes in adhesive state influence function of epithelia
The adhesive state of the desmosome can change in accordance with the state of the epithelia in which they are found[60]
During embryogenisis, epithelial differentiation and wound healing the adhesives qualties of the proteins were found to change.[61] The desmosome allowed cellular movement. For example in wound healing the dissolving of desmosomes allowed keratinocytes to migrate into areas of epithelial injury. [62]
Hemidesmosomes like the name suggests are extremely similar to the desmosomes in the fact that they are specialized junctional complexes. However unlike desmosomes which specialises in cell to cell adhesion hemidesosomes contribute to the attachment of epithelial cells to the underlying basement membrane in stratified and other complex epithelia, such as the skin, the cornea and both parts of the respiratory and gastrointestinal tract.[63] Hemidesomosomes are multiprotein complexes and it is these proteins that help determine the cell – stromal coherence of the hemidesomoses. The proteins also provide the cells with cues critical for the polarization, the spatial organization and for tissue architecture. The functional activity can be modulated however the regulation of the adhesive interaction between the hemidesmosomes and the basement membrane below is essential in various normal biologic processes, such as wound healing and tissue morphogenesis.[64] The importance of these complexes is attested by the fact that an altered expression of hemidesmosomal constituents results in several types of blistering disorder of the skin and is thus likely to be involved in the development and progression of certain cancers. The function of hemidesmosomes may be regulated via many different factors for example extracellular matrix (ECM) proteins and growth factors. To add to this the α6β4 integrins in the hemidesmososme also act as regulatory components and this done by transducing signals that profoundly affect the cellular function. Thus hemidesmosomes are not only structural adhesion complexes but also serve as signalling devices via the α6β4 integrin which affecting cell phenotype.[65][66]
Morphology and Molecular Organisation of Hemidesmosomes
Hemidesmosomes in electron microscopic images appear as small electron dense domains approximately 0.5 m in size located on the plasma membrane of the ventral surface of basal keratinocytes in human skin. The most noticeable feature on the hemidesmosome is the tripartite cytoplasmic plaque, to which the bundles of intermediate filaments are attached. Hemidesmosomes are actually associated with sub-basal dense plates in the lamina lucida and are connecter via what looks like a fine thread-like anchoring filament to the lamina densa. The laminar densa is then anchored to the papillary dermis which underlies the laminar densa by cross banded anchoring fibrils. The morphological structures listed above which include the Intermediate Filaments, Hemidesomal Plaques, Anchoring Filaments and Anchoring Fibrils constitute the so called Hemidesmosmal adhesion complex which stably adheres the keratinocytes to the underlying epidermal basement membrane.[67]
The so called molecular organisation of Hemidesmosomes is actually based on three main classes of protein and these include the cytoplasmic plaque protein which acts as the linker for elements of the cytoskeleton at the cytoplasmic surface of the plasma membrane, the transmembrane proteins which serve as cell receptors connecting the cell interior to the to the Extracellular matrix and last but not least the basement membrane – associated proteins of the extra cellular membrane.[68]
Similarities and Differences Between Desmosomes and Hemidesmosomes
Calcium ion levels are integral in junction assembly. In vitro, extracellular calcium levels have been found to trigger the formation of the junctions. [70] After cells that have been incubated in low calcium medium, were switched into a medium containing standard calcium concentrations, the formation of desmosomes was seen as soon as 5 minutes. [71] The deregulation of calcium levels within cells have been associated with junctional defects. Hailey-Hailey disease and Darier's disease are caused by defects in Golgi and ER calcium pumps. [72] These both lead to a loss of integrity in skin epithelium, due to a lack of cell-cell attachment via desmosomes. [73] [74]
It has been suggested that regulation of desmosome assembly is closely associated with the assembly of adherens junctions. [75] Desmoplakin is the only protein, so far identified, that is common to both junctions. In vitro, cells that did not express desmoplakin were unable to localise the proteins specific for the adherens junctions and the desmosomes. [76] Thus, it has been suggested that it plays a role in segregating the proteins relative to each junction and so affecting assembly.
Phosphorylation has been found to be largely involved in activating and deactivating desmosome assembly. It has been suggested that protein kinase C (PKC) is involved in the regulation of this action. [77] PKC inhibition is required for desmosome assembly to occur, that is, dephosphorylation encourages formation. Phosphorylation onto serine of desmoplakin by protein kinase C can lead to the disassembly of the cytoskeleton, junctions, and a loss of cell-cell contact. An increase in level of serine phosphorylation has also been linked with an increase in junction solubility of the desmoplakin. This suggests that phosphorylation may play an integral role in the dissociation of the desmosomal plaque from the keratin filaments. [78] The outcome of plakoglobin (an important desmosomal protein) is also largely dependent on its phosphorylation. [79]
Desmosomes and Disease
Investigations into function through knock out gene models
Knock out gene animal model investigations into the absence of desmosome protein isoforms in various epithelia have shown how they may be involved in associated disease states of the epithelia in which they are located, thus giving a window into their non pathological function. It has been suggested that the distribution of one or other desmosome protein isoforms in various epithelia is due to the degree of adhesion necessary according to any stresses encountered at that location. [80]
Studies into the function of these protein isoforms has also suggested they may act as influencing the function of the associated epithelia itself outside of the mere adhesive function.
An example of this is desmoplakin 1 which is found in all desmosomes including the endothelial cells of of capillaries. [81]
During tumourous cancer growth, in such cancers as oropharyngeal and breast cancer, desmoplakin type 1 function becomes down regulated and aids tumour growth by stimulating angiogenesis or the growth of new blood vessels from existing vascular structures [82]
This down regulation means that now the desmosomes may function in tumour cell proliferation.
It is the abnormal over or under functioning of desmosome proteins that highlights its specialised adhesion function.
Related Diseases
|Bullous Impetigo
|Impetigo is a skin condition common in school children, especially those who play close contact sports. This skin condition is also known as school sores and is caused by a bacterial infection. Bullous Impetigo causes fluid-filled blisters in the skin, primarily on the trunk, arms and legs. These blisters are painless and scab over before they heal. [83]
Staphylococcous aureas is the bacteria responsible for inducing bullous impetigo through its release of exfoliative toxins. When mice are injected with exfoliative toxin from S. aureas blistering of the skin is noticed and under an electron microscope it is possible to see that the desmosomes within the epithelia have been torn apart. [84] Exfoliative toxin A has been proven to cause the blistering through its serine protease activity. The blisters of Bullous Impetigo are localised to the superficial epidermis, and as such it is possible to confirm that the exfoliative toxin A is specific to Desmoglein-1. Desmoglein -1 is present not only in the superficial layers of epithelium but also in the deeper layers. Desmoglein-3 however is not present in the superficial layer. Given that blistering does not occur in the deeper layers it is possible to assume that Desmoglein-3 compensates for the destruction of Desmoglein-1. Experimental results have shown that on injection of exfoliative toxin A, Desmoglein-1 was damaged while Desmoglein-3 remained unaltered. This was done by addition of antibodies for Desmoglein-1 and Desmoglein-3 followed by immunoflurorescence. [85]
Bullous Impetigo has similar symptoms to many drug reaction symptoms. The differentiation between these is possible through a skin biopsy. Bullous impetigo will only have blistering on the superficial layers while a drug reaction will see blistering in the lower layers of the epithelium as well as necrotic keratinocytes. Treatment usually consists of a course of antibiotics but it is important to consider that antibiotic-resistant strains of S.aureas are quite common. [86]
|Palmoplantar Keratoderma
|Desmoplakin is the most abundant protein in desmosomal plaques, therefore having an important role in linking the intermediate filaments to the plasma membrane of cells in the epidermis and heart. Palmoplantar Keratoderma is skin condition that results from a mutation on the gene that encodes desmoplankin. Mutations can either lead to a loss of the gene completely, or cause haploinsufficiency. This genetic disorder was noted in patients who were affected by this skin condition. [87]
Palmoplantar Keratoderma is a rare condition. It is characterised by hyperkeratosison the palms of the hands and soles of the feet. This leads to a distinctive thickening of the skin, often in a striated pattern. When viewed under a light microscope, affected areas showed an increase in space between the keratinocytes. Moreover, the desmosomes appeared to be smaller and less were found when compared to a normal section of skin from the same patient. [88]
|Arrhythmogenic Right Ventricular Cardiomyopathy
|Arrhythmogenic Right Ventricular Cardiomyopathy is a cardiomyopathy is related to the functioning of desmosomes. When cell adhesions are compromised, the cardiac tissue loses its integrity. As a result of this, the body attempts to repair the damage by replacing the tissue with fibrofatty tissues. This presents a number of problems for the cardiovascular system and results in some fatal complications. [89] This condition is more common in individuals under the age of 30. Clinical symptoms present with misarrhythmias or in some cases, sudden death. Most prominent symptoms are seen during or after intense physical activity when the heart is put under stress.
Current Associated Research
Human Epidermal Desmosome-Enriched Tissue Fractions for Analytical and Prospective Studies (2011)
This report written by Sandjeu et al. describes a method that has now been adapted to the human epidermis which allows for the isolation of desmosomes in small tissue fractions as the previous methods which were developed for animal epidermis did not work as efficiently on human tissue. In the process, the desmosomes are initially enriched by the association of a two incubation step in acidic solution which consisted of the detergent NP-40 at 2 different concentrations. This was then followed by sonication. The suspension was then centrifuged twice: the first time was to remove heavy cell fragments. It was the centrifuged again at 16000g on a discontinuous sucrose gradient. A desmosome enriched fraction was then collected at approximate 30-50% sucrose gradient levels. Both immunoelectron microscopy and western blotting technique was then used on the desmosome enriched fraction to show that the central part of the desmosomes are preserved as well as retaining their antigenicity. This method can be used to both immunise animals as well as creating new antibodies that are directed toward the desmosomal components. The hope of this study is that it allows for new studies to be done on a not well understood topic: The incorporation of molecules into the desmosome core which could as a result be targeted more easily.[90]
Lack Of Plakoglobin Leads To Lethal Congenital Epidermolysis Bullosa: A Novel Clinico-Genetic Entity (2011)
As stated above epidermal integrity is essential for skin functions. This integrity is actually maintained by adhesive structures between keratinocytes, mainly the desmosomes and adherens junctions. These adhesive structures provide resistance against mechanical stress and regulate the formation of the skin barrier. Plakoglobin is one of the constituents in both types of intracellular junctions and thus has a numerous number of interaction partners. Studies into genetic mutations associated with plakoglobin has associated this with mild cutaneous disease, keratoderma and arrthythmogenic heart disease for example.
In this article, Pigros et al. report a so called novel lethal phenotype cause by a nonsense mutation in the gene that codes for plakoglobin [Junction Plakoglobin (JUP)] however this mutation and its effects have never been described before in either human or murine. The patient in this article suffered from a severe congenital skin fragility, with generalised epidermolysis and substantial transcutaneous fluid loss. Yet the patient did not ever present to health care professionals with cardiac dysfunction. It was noticed when immunofluroescence and immunoblot analysis was done that unlike JUP mutations before where truncated plakoglobin was present, here there was a complete loss of plakoglobin in the skin. Thus only a few abnormal desmosomes were formed and no adhesion structures between keratinocytes were recognisable. The role of distribution of desmosomal components was extremely affected which suggest that plakoglobin plays an essential role for plakoglobin in demosomal assembly. This current research reinforces the fundamental role of plakoglobin in epidermal cohesion. [91]
Wide Spectrum of Desmosomal Mutations in Danish Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (2010)
In the study performed by Christensen et al. , 65 unrelated patients with Arrhythmogenic right ventricular cardiomyopathy (ARVC), a lethal disease which is characterised by Ventricular tachyarrhythmias with right and/or left ventricular involvement and fibro fatty infiltrations in the myocardium were screened for mutations in the number of genes that code for desmosomes which include desmocollin-2 (DSC2), desmoglein-2 (DSG2), desmoplakin (DSP), plakoglobin (JUP) and plakophilin-2 (PKP2) and TGFb3. The results of the study were the identification of 19 different mutations with all genes that code for desmosomes being affected apart from TGFb3 which showed no genomic rearrangements or mutations. The conclusion of the study was that 33% of patients in this Danish cohort with ARVC carried desmosomal mutations with a surprisingly wide mutation spectrum. A substantial proportion of patients carried more than one mutation. The results achieved in this study supports comprehensive desmosomal mutation screening beyond the first encountered mutation, whereas routine screening for genomic rearrangements does not seem indicated.[92]
Desmosomes: new perpetrators in tumour suppression (2011)
Adherens Junctions, which are intercellular adhesive complexes that are crucial for maintaining epithelial homeostasis, are down regulated in many cancers to promote tumour progression. However the role of desmosomes - adhesion complexes that are related to adherens junctions – in carcinogenesis has remained elusive. This study conducted by Dusek et al. has using a mouse genetic approach uncovered a role for desmosomes in tumour suppression which demonstrates that the down regulation of desmosomes occur before adherens junctions drive tumour development and early invasion. Thus also suggesting that there is a two – step model of adhesion dysfunction in cancer progression. [93]
The three-dimensional molecular structure of the desmosomal plaque (2011)
Until now, the exact structure of desmosomal plaques has remained a mystery. Although the proteins involved in the structure have previously been identified, the architechture was unknown. Al-Amoudi et al, used cyroelectron tomography of epithelial desmosomes to acheive this goal. The main advantage of this technique, was that no heavy metal staining was used, and so a higher resolution image could be produced. However, due to the cutting of cyrosections to observe the structure, artifacts such as knife marks, were prominent. These artifacts and challenges were eventually overcome, and 3D imaging was used to produce a detailed image, never seen before. [94]
Alpha Helix a secondary structural motif of proteins. The amino acids are arranged in a right-handed helix. The backbone it made up of N-H, contributing hydrogen bonds to strengthen the structure.
Anchoring Junctions a type of cell junction that attache cells to adjacent cells as well as to the extracellular matrix.
Antibody a protein produced by B cells that are used to identify and neutralize foreign material in the body
Cadherin a group of proteins that cross the membrane. They are heavily involved in cell adhesions. As the name suggests, they are dependant on calcium for their regulation
Carboxy Terminus the end of an amino acid chain with a free carboxyl group.
cDNA also known as complementary DNA. It is produced from mature mRNA by reverse transcriptase and DNA polymerase.
Communicating Junctions allow for the transmission of chemical and electrical signals between cells.
Desmocollin a cadherin specific for desmosomes. Refers to the human genes DSC1, DC2 and DSC3
Desmoglein a member of the cadherin family. They are involved in the formation of desmosomes and expressed by genes DSG1, DSG2, DSG3 and DSG4
Desmoplakin a protein associated with desmosomes, anchoring the intermediate filaments to the desmosomal plaques.
Desmosomes are a type of cell junction that indirectly connect the intermediate filaments of adjoining cells. Their main function is to bind cells to one another.
Dysplasia ''Dysplasia''' refers to abnormal development. It is usually associated with a neoplastic process
Electron Microscopy the use of an electron microscope. An electron microscope uses a beam of electrons to illuminate a specimen.
Epithelium a basic type of tissue that lines the cavities of the body as well as glands.
Fluorescence Recovery a useful mechanism to investigate the motion and diffusion of macromolecules. A specimen is exposed to an intense burst of laser light and then the recovery of the area is observed.
Glycoprotein a protein that has a carbohydrate attached to it
Hemidesmosomes are a type of cell junction that attaches epithelial cells to the underlying basement membrane in stratified and other complex epithelia.
Homology describes how different animals have the same organs but may vary in form and function
Hyper-adhesion very strong adhesion adopted by desmosomes
Immunotherapy treating a disease by influencing the immune response. This may be by inducing, enhancing or supressing the response
Intermediate Filaments a family of proteins that make up part of the cytoskeleton. They are around 10nm in diameter and found in the cytoskeleton and nucleus.
Malignancy describes how some diseases are likely to lead to death, often by invasion and metastasis.
mRNA Splicing a modification of mRNA after transcription that results in the removal of introns and the connection of adjacent exons.
Occluding Junctions hold epithelial cells together to prevent the leaking of small molecules from one side to the other.
Pathogenesis The chain of events involved in a disease from origin to death/recovery
Plakophilin proteins of the cytoskeleton. Expressed on genes PKP1 and PKP2
Transmembrane Proteins are proteins that cross the cellular membrane. In desmosomes the transmembrane proteins are the cadherins, desmoglein and desmocollin, and make up the extracellular core domain.
Tripeptide is a peptide. It consists of three amino acids attached by peptide bonds.
Images and Videos
[http://www.pnas.org/content/early/2011/03/30/1019469108.full.pdf The three-dimensional molecular structure of the desmosomal plaque]
Reference List
- ↑ [1]| Cell Junctions- Molecular Biology of the cell
- ↑ 20672011</pubmed>
- ↑ Molecular Biology of the Cell Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002|Gethin R Owen, David L Stokes Exploring the Nature of Desmosomal Cadherin Associations in 3D. Dermatol Res Pract: 2010, 2010(1);930401
- ↑ <pubmed>20066089</pubmed>
- ↑ [2]|Culkins CC, Setzer S (2007) Spotting Desmosomes: The First 100 Years. Journal of Investigative Dermatology Jan 30;127(E1):E2-E3.
- ↑ [3]|Culkins CC, Setzer S (2007) Spotting Desmosomes: The First 100 Years. Journal of Investigative Dermatology Jan 30;127(E1):E2-E3.
- ↑ Porter KR (1956) Observations on the fine structure of animal epidermis. Proceedings of the International Congress on Electron Microscopy, London, July 1954. Royal Microscopical Society, London, p 539
- ↑ [4]|Culkins CC, Setzer S (2007) Spotting Desmosomes: The First 100 Years. Journal of Investigative Dermatology Jan 30;127(E1):E2-E3.
- ↑ [5]|Skerrow CJ, Matoltsy AG. (1974) Chemical characterization of isolated epidermal desmosomes. Journal of Cell Biology 63(2 Pt 1):524-30.
- ↑ [6]|Skerrow CJ, Matoltsy AG.(1974) Journal of cell biology(2 Pt 1):524-30.
- ↑ [7]|Gorbsky G, Steinberg MS. (1981) Isolation of the intercellular glycoproteins of desmosomes. Journal of Cell Biology 90(1):243-8.
- ↑ [8]
- ↑ [9]| Cowin P, Garrod DR. (1983) Antibodies to epithelial desmosomes show wide tissue and species cross-reactivity. Nature;302(5904):148-50.
- ↑ [10]|Gorbsky G, Cohen SM, Shida H, Giudice GJ, Steinberg MS. (1985) Isolation of the non-glycosylated proteins of desmosomes and immunolocalization of a third plaque protein: desmoplakin III. Proceedings National Academy of Science USA.82(3):810-4.
- ↑ [11]|Green KJ, Goldman RD, Chisholm RL. (1988)Isolation of cDNAs encoding desmosomal plaque proteins: evidence that bovine desmoplakins I and II are derived from two mRNAs and a single gene. Proceedings National Academy of Science U.S.A. 85(8):2613-7.
- ↑ [12]|Blaschuk OW, Sullivan R, David S, Pouliot Y. (1990) Identification of a cadherin cell adhesion recognition sequence. Developmental Biology 139(1):227-9.
- ↑ [13]|Green KJ, Parry DA, Steinert PM, Virata ML, Wagner RM, Angst BD, Nilles LA. (1990) Structure of the human desmoplakins. Implications for function in the desmosomal plaque. Journal of Biological Chemistry15;265(5):2603-12.
- ↑ [14]|Koch PJ, Walsh MJ, Schmelz M, Goldschmidt MD, Zimbelmann R, Franke WW.Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules. European Version of Cell Biology 53(1):1-12.
- ↑ [15]|Collins JE, Legan PK, Kenny TP, MacGarvie J, Holton JL, Garrod DR. (1991) Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains. Journal of Cell Biology 113(2):381-91.
- ↑ [16]| Amagai M, Klaus-Kovtun V, Stanley JR. (1991) Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell 67(5):869-77.Simpson CL, Green KJ. Identification of Desmogleins as Disease Targets. Journal of Investigative Dermatology 127(E1):E15-E16.
- ↑ [17]
- ↑ [18]|Stappenbeck TS, Green KJ. (1992) The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. Journal of Cell Biology 116(5):1197-209.
- ↑ [19]|Kouklis PD, Hutton E, Fuchs E. Making a connection: direct binding between keratin intermediate filaments and desmosomal proteins.Jounral of Cell Biology 127(4):1049-60.
- ↑ [20]|McGrath JA, McMillan JR, Shemanko CS, Runswick SK, Leigh IM, Lane EB, Garrod DR, Eady RA. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nature Genetics 17(2):240-4.
- ↑ [21]|Tselepis C, Chidgey M, North A, Garrod D.Desmosomal adhesion inhibits invasive behavior. Proceedings National Academy U.S.A. 95(14):8064-9.
- ↑ [22]
- ↑ [23]Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E. (2001) Desmoplakin is essential in epidermal sheet formation. Nature Cell Biology 3(12):1076-85.
- ↑ [24]|Hopkins G, Kimura TE, Garrod DR. Desmoplakin Is Essential for Epidermal Sheet Formation. Journal for investigative dermatology 127(E1):E12.
- ↑ <pubmed>11950889</pubmed>
- ↑ <pubmed>2127080</pubmed>]
- ↑ [25]
- ↑ [26]
- ↑ [27]
- ↑ [28]
- ↑ [29]
- ↑ [30]
- ↑ [31]
- ↑ [32]
- ↑ [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633677/}
- ↑ [33]
- ↑ 41.0 41.1 41.2 41.3 41.4 41.5 Cite error: Invalid
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- ↑ 42.0 42.1 Cite error: Invalid
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- ↑ <pubmed>20671997</pubmed>
- ↑ 44.0 44.1 44.2 Cite error: Invalid
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- ↑ <pubmed>21098030</pubmed>
- ↑ 46.0 46.1 46.2 46.3 <pubmed>20626351</pubmed>
- ↑ [34]
- ↑ [35]
- ↑ [36]
- ↑ [37]
- ↑ [38]
- ↑ [39]
- ↑ [40]
- ↑ [41]
- ↑ [42]
- ↑ [43]
- ↑ [44]
- ↑ [45]
- ↑ [46]
- ↑ [47]
- ↑ [48]
- ↑ [49]
- ↑ </10367727>
- ↑ </8666164>
- ↑ </10201522>
- ↑ </16757171>
- ↑ </10201522>
- ↑ </10201522>
- ↑ </8666164>
- ↑ <pubmed>6209289</pubmed>
- ↑ [50]
- ↑ [51]
- ↑ [52]
- ↑ [53]
- ↑ [54]
- ↑ [55]
- ↑ [56]
- ↑ [57]
- ↑ [58]
- ↑ [59]
- ↑ [60]
- ↑ [61]
- ↑ http://www.nhs.uk/conditions/Impetigo/Pages/Introduction.aspx
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/15363804
- ↑ http://www.nature.com/nm/journal/v6/n11/abs/nm1100_1275.html
- ↑ John R. Stanley, M.D., and Masayuki Amagai, M.D., Ph.D. Pemphigus, Bullous Impetigo, and the Staphylococcal Scalded-Skin Syndrome. N Engl J Med 2006; 355:1800-1810October 26, 2006
- ↑ D. Keith B. Armstrong*, Kevin E. McKenna1, Patricia E. Purkis2, Kathleen J. Green3, Robin A. J. Eady4, Irene M. Leigh2 and Anne E. Hughes. Haploinsufficiency of Desmoplakin Causes a Striate Subtype of Palmoplantar Keratoderma. Human Molecular Genetics. (1999) 8 (1): 143-148.
- ↑ Neil V Whittock, Gabrielle H S Ashton, Patricia J C Dopping-Hepenstal, Matthew J Gratian, Fiona M Keane, Robin A J Eady and John A McGrath. Striate Palmoplantar Keratoderma Resulting from Desmoplakin Haploinsufficiency. Nature. (1999) 113: 940-946.
- ↑ http://content.onlinejacc.org/cgi/reprint/38/7/1773.pdf
- ↑ [62]
- ↑ [63]
- ↑ <pubmed>20864495</pubmed>
- ↑ [64]
- ↑ [65]
Coordinator Comment to all Groups
I will add a general comment that will be the same to all groups under this heading.
Referencing Extension Problem
--Mark Hill 13:16, 3 May 2011 (EST) As mentioned in the lecture, I am aware of the referencing extension problem on your project pages. I have the following temporary solution, of removing the extension, so that groups can continue to add content to their project pages. I am also giving everyone a 1 week extension before the peer assessment.
This should only be done if your project page is not allowing you to save changes!
A. The Easy Way....
The following 4 steps can be done on the webpage or select all content in edit mode, copy and paste into a text editor. All steps must be completed before you attempt to save.
- In page edit mode, find all <pubmed> reference tags.
- Replace this tag with [http://www.ncbi.nlm.nih.gov/pubmed/ Note, there should be no spaces between the internet address and the pmid number.
- Now find all </pubmed> reference tags.
- Replace this second tag with ]
This will generate a numbered reference list that we can later fix up.
B. The Better Looking Result....
Whatever is between the <ref> </ref></pubmed> tags is what will appear in your reference list, so you can format the reference and link to appear in your reference list.
|2011 Projects: Synaptic Junctions | Gap Junctions | Tight Junctions | Desmosomes | Adherens Junctions | Neuromuscular Junction


text:
4 heroes honored for saving 2 people from fire
Officials say heroes saved brother, sister from Darlington Township fire
Four people were honored Monday night for saving a woman and her brother from a burning building.
Officials said two passers-by and two volunteer firefighters saved the two victims from a burning Darlington Township home in January.
On Monday, the community honored Stephanie DeRuscia, Ryan O'Hara, Michael Draybick and Brock Crawford for their heroism.
"I don't really remember opening the door but I guess I opened the door because she wasn't able to walk," DeRuscia said.
Draybick, one of the firefighters, said "Made me feel like I did my job. Like I did what I was trained to do. Makes me feel good."
The other firefighter, Crawford, said, "It's something I will always remember and cherish for as long as I'm in the fire service."
O'Hara said he was proud of his community, "The community really came together and I really respect that. There's not a lot of than going on around here anymore."
The quartet was awarded plaques for bravery.

subset: commoncrawl


text:
Welcome message
Dear Community Board Members,
On behalf of the Community Boards Executive, welcome to the Methven 2017 Community Boards Conference website. I want to thank the Ashburton District Council and the Methven Community Board for offering to host the conference and for all the work that they have done to make it happen.
The theme of the 2017 conference is "Making 1 + 1 = 3" or, how can we as boards achieve more for our communities with the resources we are given. With the conference being held at the start of the new triennium, it is very appropriate that we challenge each other to expand our horizons in the work that we do on our boards, and in doing so, provide increased benefits to both our ratepayers and our parent councils.
We have gathered a range of exceptional speakers for the conference who are certain to inspire us and provide us, not only with confirmation that we are doing a top job in our communities, but more importantly, challenge us to do more in ways that we have not tried before.
The last two conferences at Wanaka and Waitangi have certainly provided stimulation for those who have attended, and I am sure that what we have for you in 2017 will be bigger and better.
We have this opportunity to get together once every two years, and I encourage you all to take advantage of this conference to build on the work you do, set up networks for the future and leave the conference inspired to drive your board in new directions.
I look forward to renewing old acquaintances and meeting many new first time attendees at the conference in Methven.
Mick Lester
NZ Community Board Executive Committee
Press Release
See what the Ashburton Guardian had to say.
Methven is a 75 minute drive from Christchurch airport. Coach transfers will be available from the Airport to Methven on Thursday and Friday, returning to the Airport on Saturday and Sunday. Cost is $45 per person each way. Pre booking is essential.
See the schedule in place to consider when booking flights and make your reservation during the registration process.


text:
The Hope College Great Performance Series will feature the highly acclaimed chamber ensemble, Concertante, on Friday, Nov. 9, at 7:30 p.m. in Dimnent Memorial Chapel.
The unique arrangement of the sextet allows the ensemble to perform great works rarely heard live. The six musicians carry a wealth of varied experience and degrees from such prestigious institutions as Juilliard, Curtis Institute of Music, and the Shanghai Conservatory of Music.
As solo performers, the musicians have won major national and international music competitions, and graced the premier stages of the world from New York's Carnegie Hall to London's Royal Festival Hall to Shanghai's Grand Theatre. Concertante has performed a wide array of repertoire ranging from works by established masters to less commonly performed composers.
"Concertante has created a cohesive and beautifully polished sound," "The New York Times" has said.
The ensemble's performance at Hope College will feature the works of Richard Strauss, Arnold Schoenberg and Pytor Tchaikovsky.
Concertante has also recorded many highly regarded CDs and won rave reviews for its live appearances.
"The fantastically talented Concertante proved... that the future of classical music is in fine hands," said "The Orgeonian."
Tickets for the performance are on sale at the ticket office in the DeVos Fieldhouse and cost $17 for regular admission, $12 for senior citizens, and $6 for children 18 and under. The ticket office is open weekdays from 10 a.m. to 5 p.m. and can be called at (616) 395-7890.
The ticket office is in the main lobby of the DeVos Fieldhouse, which is located at 222 Fairbanks Ave., between Ninth and 11th streets. Dimnent Memorial Chapel is located at 277 College Ave., on College Avenue at 12th Street.
Additional information may be obtained online by visiting www.concertante.org or www.hope.edu/gps.


text:
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- Searching for jobs can be hard work, so why not let the jobs come to you?
- Create a profile and publish your CV so recruiters and headhunters can find you and get in touch.
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text:
"The hour of independence of the State of Palestine has arrived," were the final words of Palestinian President Mahmoud Abbas's speech at the 69th annual meeting of the United Nations General Assembly (UNGA).
In his outspoken address, Abbas referred to the latest Israeli military operation in Gaza as a "genocide" carried out by the "racist occupying State (of Israel)." He argued that the difference with former Israeli military assaults like Operation Pillar of Defense (2012) and Operation Cast Lead (2008/9) was the scale of the crimes and the unprecedented list of killed, wounded and disabled.
Israel's 50-day assault on Gaza, dubbed Operation Protective Edge, killed more than 2,0104 Palestinians, nearly 70% percent of which were civilians according to the latest UN statistics.
The Palestinian President continued with critical remarks towards the international community, stating that the Israeli crimes were carried out "before the eyes and ears of the entire world (…) in a manner that makes it unconceivable that anyone today can claim that they did not realize the magnitude and horror of the crime." He argued that supporting Israel's right to self-defense cannot equate with ignoring the fate of Palestinian victims, whose lives are "as precious as the life of any other human being."
Apart from his criticism, Abbas applauded the worldwide demonstrations that condemned the Israeli military offensive and the grassroots support for the international boycott campaign. "These manifestations of true solidarity constituted an important message to those who were facing genocide in Gaza, helping them to feel that they were not alone," he said.
Abbas reaffirmed his support for a two-state solution in various instances. He explicitly listed what foundations the State of Palestine should be built upon, including "a sovereign and independent State living in peace (…) that deepens the Palestinian enlightened traditions of tolerance, coexistence and non-exclusion (…) and cares for the needs and interests of its people."
International pressure
In the speech, Abbas was critical towards future negotiations. He expressed that the objective of any negotiations should be to end Israeli occupation and to create a State of Palestine "with East-Jerusalem as its capital on the entire Palestinian Territory occupied in the 1967 war."
"There is no value in negotiations which are not linked to a firm timetable for the implementation of this goal," he said, while refraining from including details on what this timetable should entail.
Abbas also reaffirmed his plans to present a resolution to the UN Security Council (UNSC) on the issue, as he had announced last week during a press conference with French President Francois Hollande. It is expected however that the United States, which is one of the permanent members of the UNSC, will veto the resolution. The US holds presidency of the Council at the moment and has vetoed many other UNSC-resolutions on the Palestinian question, the most recent being a 2011-resolution that called a halt to illegal Israeli settlement construction.
The main US-argument has been that a solution should be found through direct negotiations between Israeli and Palestinian representatives instead of via the UN. Jen Psaki, spokeswoman of the US State Department, was therefore quick to condemn Abbas's speech at the UNGA. "Abbas's speech included offensive characterizations that were deeply disappointing and which we reject," she said. "Such provocative statements are counterproductive and undermine efforts to (…) restore trust between the parties."
Senior officials in Netanyahu's office also denounced Abu Mazen's speech "of incitement filled with lies." Right-wing Israeli Foreign Minister Avigdor Lieberman even called the speech "diplomatic terrorism" which showed that Abbas "does not want to be, and cannot be, a partner for a logical diplomatic solution."
Bleak future
Abbas did not, however, set a deadline for the birth of the State of Palestine, as many believed he would. Aides close to the Palestinian president suggest the PA is looking at 2017 as the official birth year of the Palestinian state.
Hanan Ashrawi, a leading member of the Palestine Liberation Organization, said earlier this month that the PLO was looking at a three-year statehood deadline.
In his address on Friday, Abbas asserted that despite years of negotiations, Israel continues to forge ahead with settlements and land theft, all the while maintaining its blockade of the Gaza Strip.
"The future proposed by the Israeli government for the Palestinian people is at best isolated ghettos for Palestinians on fragmented lands," Abbas said.
"At worst it will be a most abhorrent form of apartheid," he warned, in reference to the racist regime that ruled South Africa up until 1994.
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text:
Just purchased a StimTracker and using the interface to neuroscan EEG (http://www.cedrus.com/support/stimtracker/tn1469_neuroscan.htm). So seems like I should have 8 event marker/trigger bits with which to send events from Matlab.So using serial.m in Matlab my commands are:
s1 = serial('/dev/cu.usbserial-AH01NEJ7', 'BaudRate', 115200,'DataBits', 8, 'StopBits', 1, 'FlowControl', 'none', 'Parity', 'none', 'Terminator','CR', 'Timeout', 400, 'InputBufferSize', 16000);
But now I get a little confused. Say I want to send a 10ms pulse, so first thing I need to do is set the pulse duration. According to the cedrus documentation (http://www.cedrus.com/support/stimtracker/tn1450_st_commands.htm) to set the time I need to use a "four byte binary value indicating the number in milliseconds" forming a "32-bit unsigned integer". So if I use matlab's decimal-to-binary converter for 10 I get:
ans =
But this is not a four byte binary value. To make this four bytes then I guess I need to add a bunch of 0's. Also from what I read, bits are read from right to left so the 0's should be placed on the left of 1010. So then to set the pulse duration to 10ms I would execute the command:
Then say I want to have this 10ms pulse on channel 3 (out of the 8 possible event channels available to me). The documentation states "mh followed by two 'bit mask' bytes (a binary value). In the first byte, each bit corresponds to an output line. The second byte is currently ignored". So if I understand things correctly in the first byte each bit represents the state of each channel - so to have all 8 channels off would be:
Then to turn on channel 3 (and remembering bits are read right to left) would be:
and then taking this and adding a second bit mask byte that is ignored, so will just make it all zeros:
means the Matlab command should ultimately look like this (since read right to left, the ignored byte is supposed to be second, so will add it to the left):
Is my understanding of this correct? If not, could someone else explicitly give their fprint() statements for 1) setting a pulse duration for some time (like 10ms), and 2) sending an event to one of the channels? It would be extremely helpful! (and ultimately I want to use IOPort.m commands since they apparently are more precise, but to begin with I figure I should understand serial.m commands)
Thanks so much!


text:
green juice
Since having the baby my time for making meals has nearly disappeared, plus I've got to do more with just one hand so we have been making lots of fruit & vegetable juice and smoothies. I know there's a million recipes for juices online but I thought I'd share my personal favorite.
It's not the most complex but it certainly is tasty and a good way to get some green while having something sweet.
Juice 3 apples.
Pour the juice into a blender with 3 large stalks of kale, blend until kale is chopped finely.
Add 1 banana and 3 large strawberries and blend together.
In case you're wondering, glass is from Ikea and tea towel from Kollekt.
Other Stories
12 comments:
mmmhhh - looks tasty! :)ReplyDelete
That sounds delicious! I love kale in my smoothies. I do a similar one only sub out the banana for a pear.ReplyDelete
sounds delicious. i'm loving green smoothies lately & haven't tried any with apples, so i will have to!ReplyDelete
Wow that sounds amazing and super healthy. I must start using my blender more! xReplyDelete
- AnonymousFebruary 18, 2014
That sounds delicious! What kind of juicer do you use? And do you recommend it? :)ReplyDelete
Yummmm!! Neither I do have time for big breakfasts... it's so sad because BF is my favorite part of the day and I love to enjoy it. My boss takes delicious green juices (and lately she prepares delicious grapefruit juices also), she's so lucky because we work at her place, and despite we're confident I still can't go like HEY I ALSO WANNA HAVE ONE! hahaReplyDelete
I was always a bit intimidating by the "greenness" of these smoothies, but once I sucked it up and gave it a go I realized they are actually delicious!ReplyDelete
xXo, Lexi of http://www.prettyandfresh.com/
Sounds great! I recently tried out this smoothie recipe, and it is AMAZINGLY delicious! I totally recommend it:ReplyDelete
-a handful of kale
-one date
-a little bit of coconut shreds
-a cup of almond milk
-a banana
-protein powder
It's so sweet, and it fills me up for hours!
Such a treat! We can't wait to try. The images are stunning!ReplyDelete
can't wait to try this!ReplyDelete
yum, sound terrific.ReplyDelete
- AnonymousMarch 05, 2014
I just made this and it is one of the BEST things I've ever made!! I did a couple of things differently because of texture preferences. I juiced the kale as well as the apples, then added all that to my blender. I used a frozen banana and my frozen strawberries, did not need ice. I'm having this for lunch tomorrow!!ReplyDelete
Thank you for your comments, I love hearing from you!
Questions, comments or sponsorship inquires, please contact me via the 'contact' link.


text:
[This is a re-post of my review from the 2012 Toronto International Film Festival. Hyde Park on Hudson opens today in limited release.]
Hyde Park on Hudson is two stories: one is a bizarre, deeply misguided "love story" about a mistress; the other is a charming fish-out-of-water story set on a historical stage. Blended together, they make a film that's unintentionally funny in its brazen schizophrenia where the plotlines overlap in terms of setting and nothing else. Director Roger Michell doesn't seem to notice how different these stories are, and instead of choosing the superior one, his vacillation makes the picture a captivating train wreck where I couldn't help but wonder if Michell was being subversively hilarious. How else do you explain a scene featuring cinema's most romantic handjob?
Margaret Suckley (Laura Linney) is a fifth cousin of President Franklin D. Roosevelt (Bill Murray). She is called away from her country home by the President to come and keep him company at his mother's home in Hyde Park on Hudson. In their first encounter, they talk about stamp collecting, which can be deeply seductive provided one of the participants is the President of the United States. Margaret becomes smitten with the President, and the two begin an affair that she believes is a deep, magical romance. Margaret wistfully narrates the story, and because she sees herself as the centre of the universe, she deserves equal attention to something actually important: King George VI (Samuel West) and Queen Elizabeth (Olivia Colman) visiting America to entreat FDR's help against Hitler's Germany.
I simply cannot fathom why these two stories would be put together other than perhaps to serve a blandly-written FDR character that's wasted on the talented Murray. The actor gives a fine performance, but it's not particularly memorable and certainly nowhere near his best work. We see that no one, not fifth cousins nor the King of England, can resist the charms of the Roosevelt. But these charms don't mean anything other than duping Margaret into thinking that she had a special relationship with FDR.
If Hyde Park on Hudson was clever, it would have some element of mocking Margaret's deluded beliefs. There are times when it seems like the Michell has to be mocking Margaret, like when he shows a picturesque scene of her and FDR in his car, in the middle of a pastoral field, looking off into the distance of a cerulean sky while she jerks him off. But the rest of her story is played completely straight. Michell is truly on Margaret's side, and Hyde Park comes off as preposterous as a result, especially since he has a much better movie with the King's visit.
Even though King George VI has been immortalized on film by Colin Firth's memorable performance in The King's Speech, that doesn't mean no other actor can play the part. West gives a fine performance, and he has the benefit of playing off Colman, who is terrific as the stodgy Elizabeth. George VI's visit to Hyde Park was the first time British royalty had come to visit America, and that's a fun historical tale which doesn't need the distraction of a mistress' recollections (she's even more distracting when you consider that Margaret has nothing to do with most scenes involving George). It feels silly to watch FDR charm Margaret with the mighty power of stamp collecting, but it feels like a crucial moment of bonding when he's with King George. It's intentionally entertaining when we see George and Elizabeth puzzle over what a hot dog is, and if George should eat one. A movie completely free of Margaret Suckley would have been a welcome treat.
Watching Hyde Park on Hudson is like listening to the memoir of a ridiculously vain person who believes the world literally revolves around her. At one point, Margaret says something along the lines of "This weekend would change the fate of two men, the world, and, most importantly, me." Perhaps Michell believes that the eighty years distance between the present day and the events of the film somehow turn Margaret's affair with FDR into something romantic. Maybe fifty years from now, some director will make a sappy historical drama about American's involvement in the Bosnian War as seen through the eyes of Monica Lewinsky.
Rating: C-


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|Land Matters Discussion Area Discussion Relating to Your Land/Legislative Issues
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CBD on new Forest Planning Rule
Center for Biological Diversity
January 26, 2012
Contact: Taylor McKinnon (928) 310-6713
Obama's Forest Service Weakens National Forest Wildlife Protections
WASHINGTON The U.S. Forest Service today released a new proposal for the nations 193-million-acre national forest system that will weaken rules protecting fish and wildlife from logging, livestock grazing, mining and off-road vehicles. The new proposal, which was released as part of the final environmental impact statement for the rule, is the Forest Services fourth attempt since 2000 to revise nationwide regulations governing national forests. All three previous attempts were challenged in court by the Center for Biological Diversity and allies, and all three prior attempts were found unlawful. Like the 2000, 2005 and 2008 rules, the Obama administrations planning rule would decrease longstanding protections for wildlife on national forests.
Todays rule is a step up from the Bush administrations rule, but its protections are still a far cry from Reagan-era regulations that the Forest Service has been trying to weaken for 12 years, said Taylor McKinnon, public lands campaigns director at the Center. Our publicly owned national forests should be a safe haven for wildlife. In the face of unprecedented global climate change and other threats to species, the Forest Service should be trying to strengthen, not weaken, protections for wildlife on our public lands.
Congress enacted the National Forest Management Act in 1976 to guide management of the national forest system, which consists of 155 national forests and 20 national grasslands. In 1982, the Forest Service adopted national regulations to provide specific direction for activities such as logging, mining, livestock grazing and recreation. That rule included strong, mandatory protections for fish and wildlife, requiring the Forest Service to monitor and maintain viable populations.
The Clinton administration in 2000, and the Bush administration in 2005 and 2008, issued new rules to revise the 1982 regulation. Each of these efforts was found unlawful and were not implemented. The Obama administration is again trying to weaken the long-standing 1982 regulations by requiring that the Forest Service only maintain viable populations for species of conservation concern, and only at the discretion of local forest supervisors.
Like the Bush rules that were defeated, the new Obama rule would also not apply to the thousands of site-specific projects and activities that the Forest Service approves each year; rather it would only apply to forest plan amendments and revisions. And, like earlier attempts, the new rule seeks to replace the longstanding administrative appeal process with less formal pre-decisional objections.
According to the Forest Service, a notice of availability for the final environmental impact statement will be published in the federal register on Feb. 3 with a record of decision selecting the final planning rule not less than 30 days thereafter.
Dave Walters
Tri-Cities Peak Putters
Land Use Coordinator
WOHVA Board member
It's a Scout thing
This is gonna get tied up in court till **** freezes over...
Dave Walters
Tri-Cities Peak Putters
Land Use Coordinator
WOHVA Board member
It's a Scout thing
Naw, it will be a quick decision, and they will get to start over again.
Blue Mtns. Plan revision will get done under the 1982 rule (still 2 years out to the ROD) before they get something that will appease the environuts.
1981 Cherokee W/T, 360, T-18, Warn 8274 in custom bumper/deer strainer (tested and approved)
1988 Cherokee 4 door, 3" Rancho lift, custom sliders/steps, custom roof rack, custom camo paint, custom camo headliner, custom bumpers and Warn 9500 HS, 31-10.50's
Only 31's, but can drag self with either rig
BLM John Day/Snake RAC-OHV/Recreation Representative
Wolfpack 4x4's - Region 5 - "Cave Lupum"
Pres.- Outcast Land Use Review Team
Wish someone would get it in their heads the biggest reason these loons spend so much on lawsuits is because it's our money, not theirs. I've posted a piece in the forums about this (Enviro Gravy), but it didn't seem to register! Find it and read it, folks. They're wasting our money due to a law that needs repealed...
Dave Walters
Tri-Cities Peak Putters
Land Use Coordinator
WOHVA Board member
It's a Scout thing
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AMC's "Mad Men" and FX's "American Horror Story" lead the 2012 Emmy field with 17 nominations each. "Girls," the polarizing new HBO series about four twenty-somethings in Brooklyn received 5 nods, 3 of which going to show creator and star Lena Dunham. But a nomination is no guarantee of a win. Just ask Angela Lansbury.
Soon after Jimmy Kimmel takes the stage Sunday as host of the 64th annual Primetime Emmy Awards, those numbers will become wins or losses, adding to the haul of some long-running series and leaving more than few first time and return nominees out in the cold.
Here's a look at how the numbers stack for the 2012 race, and a glance back at some of the winning shows and actors that took home a statue or 37, and kept us tuning in year after year.
U.S. & World
2012 Top Five Series Nominees
17 Noms - "Mad Men" (AMC) and "American Horror Story" (FX)
16 - "Downton Abbey" (PBS) and "Hatfields and McCoys" (History)
15 - "Hemingway & Gellhorn" (HBO)
14 - "Modern family" (ABC) and "Saturday Night Live" (NBC)
13 - "Breaking Bad" (AMC), " "30 Rock" (NBC) and "Sherlock: A Scandal in Belgravia" (PBS)
2012 Most Acting Nominations for a Single Series
7 - For the "Modern Family" cast: Show leads Jesse Tyler Ferguson, Sofia Vergara, Eric Stonestreet, Ty Burrell, Julie Bowen and Ed O'Neill are all up for a statue along with guest actor Greg Kinnear.
2012 Top Five Network Nominees
2012 Most Nominated Individual
7 - Actor/comedian Louis C.K. earned that number for his multi-hyphenate work. He's up for best actor, best writing and best directing for FX's "Louie," and his comedy special "Live at the Beacon Theater" also earned four nods.
2012 Nominations for "The Office" and "House"
0 - It's the first time the crew from Dunder Mifflin have been shut out since the sitcom debuted in 2005 and the first time "House" has ever failed to receive a nod. That "House" wrapped its eighth and final season in May and star Hugh Laurie is a six-time Emmy bridesmaid for his role as Dr. Gregory House just makes it all the more painful.
Percentage of AMC's 2012 Nominations Belonging to "Mad Men"
50% - 17 of the networks' 34 belongs to the men and women of Sterling Cooper Draper Pryce.
Most Nominated Series in Emmy History
156 - "Saturday Night Live" (NBC) Over it's 37-year history the groundbreaking NBC comedy sketch show has won 32 Emmys. It received 14 nods this year.
117 - "Cheers" (NBC) 1982-1993
Show with the Most Wins
37 - "Frazier" (NBC) 1993-2004
Series with the Most Wins in the Same Category
9 - "The Daily Show" (Comedy Central) Best Variety Show 2003-2011 and "The Amazing Race" (CBS) Best Reality Competition 2001-2009, 2011
6 - "The Late Show with David Letterman" (CBS) Best Variety Show 1994, 1998-2002
5 - "Frazier" Best Comedy 1994-1998
Most Wins by a Performer - Different Roles
8 - Cloris Leachman
7 - Betty White, Ed Asner, Mary Tyler Moore
6 - Tyne Daly
Most Wins by a Performer - Same Role, Same Series
5 - Candice Bergen, Best Actress Comedy for "Murphy Brown" (CBS) 1989-1990, 1992, 1994-1995 and Don Knotts, Best Supporting Actor for "The Andy Griffith Show" (CBS) 1961-1963, 1966-1967
Most Wins by a Series in its First Season
9 - "The West Wing" (NBC) 2000


text: We wanted to create something special for our Facebook fans. Since most of our users are small business owners and/or non-profits we put together this business toolkit. When you like our page on Facebook, it will reveal links to some great content. So if you like AnyMeeting, be sure to "Like" AnyMeeting.


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I came to FRESHYSITES 2 years ago to redo my website and make it mobile-friendly. Ben and his staff made this transition easy. As an artist/musician I had very clear, visual ideas about how the site should look and unfold. They gave me what I was looking for and more, handling my requests and directions with speed and precision. If you are looking for an excellent website design company you have arrived at your destination.
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March 2, 2013
Armed with cameras, the crowds along King Street capture the parade.
Stories this photo appears in:
The Ballyshaner's St. Patrick's Day Parade
St. Patrick's Day Parade pays tribute to Vietnam veterans.
In what was perhaps the biggest turnout since its inception, Alexandria celebrated its Irish heritage March 2 and paid tribute to Vietnam Veterans in the 32nd annual St. Patrick's Day Parade. Sponsored by The Ballyshaners, the parade was founded by Pat Troy, who officially stepped down as organizer following this year's event.
Use the comment form below to begin a discussion about this content.


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The Church will be City Winery Chicago tomorrow night and July 4. The Australian band formed in 1980 and is best known for its international hit "Under The Milky Way."
Also coming up at City Winery Chicago is An Evening Of John Lennon featuring Phil Angotti, Tommi Zender, and Casey McDonough. Singer-guitarist Angotti's new Such Stories album is available on iTunes.
The Arcada Theatre has added another power pop feather to its cap by bringing back The Smithereens on September 16. Pat DiNizio and the boys have previously played the St. Charles venue as part of a 1980s showcase with The Romantics, Marshall Crenshaw, and Tommy Tutone, and for a solo gig. As previously mentioned here on BHT, there's a triple bill of Shoes, Pezband, and Dwight Twilley coming up at The Arcada on August 11.
Secret Colours, a young but nevertheless major power on Chicago's psychedelic music scene, has a record release party for its new Dream Dream album coming up on July 15 at Martyrs' on Lincoln Avenue. Yoko And The Oh No's, a good band with a not so good name, and Soft Candy, a quartet that lists The Zombies and The Kinks among its influences, are also on the bill that night.
Thanks to John D. Kolonel of The Raine for tagging me in a Facebook post about wearing his Broken Hearted Toy button during the Material Reissue/Cliff Johnson and The Raine show at the Wire club in Berwyn. I had the pleasure of meeting Mr. Kolonel at the Cover Palooza show at The Gallery Cabaret a while and gave him a button. So here's the deal: if I give you a BHT button and you post a picture of yourself on Facebook wearing it, I'll give your post a "Like." Cliff Johnson and The Raine's next gig is on July 29 at Reggies Music Joint on State Street just south of downtown in Chicago. The Jay Goeppner Band is also on the bill that night.
The Yep Roc 20 Festival, an offshoot of the indie record label, will be held October 19 – 21 in Carrboro and Hillsborough, NC. The lineup so far comprises Nick Lowe; Dave and Phil Alvin with The Guilty Ones; Los Straitjackets; Tony Joe White; and the Stray Birds, with more to be announced. Tickets are already available on the official Yep Roc site and there are VIP packages available for $175.
Former WXRT and WLUP air personality Rob Skafish will be at the Chicagoland Record And CD Collectors Show in Hillside from 8:45 a.m. to noon on Sunday, July 16 to sell and sign copies of his book We Have Company: Four Decades Of Rock And Roll Encounters. Skafish, along with his fellow XRT DJ Terri Hemmert, were among the first Chicago radio people to embrace punk and new wave music when it emerged in the mid-1970s. In my yet-to-be-published rock novel, there's a local radio DJ character who's sort of a mix of Skafish, Hemmert, and Chrissie Hynde.
Speaking of Terri Hemmert, she focused on Ringo Starr's birthday on her Breakfast With The Beatles show this morning on XRT. The Beatle drummer's 77th birthday comes next Friday, and he'll celebrate at the Capitol Records Building in Hollywood, CA from noon to 4:00 p.m. I'm still kicking myself for missing the birthday bash he had in Chicago a number of years back.
As reported in an Associated Press article in the Chicago Tribune, The Rock And Roll Hall Of Fame in Cleveland has a brand new exhibit called "The Power Of Rock." It uses smoke, laser lights and hidden speakers to amp up film clips of induction ceremony performances from over 30 years. The article also mentioned that The Rock And Roll Hall Of Fame is undergoing a $15 million dollar remodeling. Hopefully, that means more Hollies memorabilia.
Random Name Generator: In honor of the Wilco song by that name, here's a new BHT feature of shout-outs (and occasionally shout-ats) addressed toward the famous and not so famous around the globe. It could become a regular part of Slumgullion, a stand-alone post, or just pass into oblivion. Fasten your seatbelts, 'cause here we go:
Chicago Tribune critic Kerry Reid's review of City Lit Theater's production of London Assurance was so well written and researched it makes me want to go see it. As much as I'll miss Wendy Rice doing Saturday Morning Flashback on WXRT, I have no doubt that new rotating hosts (and longtime XRT air personalities) Johnny Mars and Frank E. Lee will do a great job. Lily Aldridge is the Victoria's Secret model I think I could most easily be friends with. I've never seen the Talking Heads tribute band Big Suit but their ad on page 42 of the new Illinois Entertainer for an upcoming show at the Addison Rock 'N Wheels event on July 20 is so cool it makes me want to check them out. Father Michael Pfleger made a valid point when he told the Chicago Sun-Times that athletes from Chicago's major teams should visit with city kids in low income neighborhoods the way Derrick Rose and Joakim Noah did when they played for The Bulls. My wife Pam and I go to the cafe at Mariano's in Palatine every Saturday because we like the beverages and the friendly service from Hailey, Matt, Michelle, and Deb. To Mr. I-Fly-The-W-Flag-All-The-Time-No-Matter-How-The-Cubs-Are-Doing: if you don't understand the rules, don't play the game. Boris Boden, a guy I met back in the mid-1970s when we both hung out at the Harlow's club on Chicago's southwest side, does a great power pop show called Secret Weapon on Woody Radio. Critics have been praising Baby Driver as a well-made and clever action flick with a wall-to-wall soundtrack of classic rock, but I haven't heard if it actually uses the Simon And Garfunkel song by that name.


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Ben Goeke graduated from Iowa State University with a degree in Landscape Architecture in 1981. From 1981 to 1989 Ben worked with various commercial landscape firms on such projects as Leadership Square, the Meriad Gardens, and One Bell Central. In 1989 Ben went out on his own and started what was originally called Goeke Landscape and Design and has now matured into Redbud Design and Landscape. During this metamorphosis Ben also became a registered licensed landscape architect.
Since the creation of Redbud Design, Ben has at one time or another found himself in most all of the subdivisions in the metro area, Tulsa, Bartlesville and as far away as Chicago, IL and Fort Worth, TX.
Over the past several years Ben has been published several times in the daily Oklahoman featuring a number of his residential projects.
Ben continually strives to enhance the lives of others through his artistic and naturalistic approach to landscape design.


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2833 E. Fort Lowell
Just east of the main entrance to Winterhaven
Festival of Lights at Fort Lowell & Christmas Ave
Tucson, AZ 85716
CHECK YOUR DATE AND TIME - Please bring a can of food or more or cash for Community Food Bank. All CASH given goes to Community Food Bank! TROLLEY TUCSON is a division of LIMOPORT TRANSPORTATION, LLC. Credit card charges will bill as LIMOPORT TRANSPORTATION, LLC. Best parking, food, hot chocolate is at Piezano.s Pizza 2921 E. Ft. Lowell Rd. 85716


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Harmut Haenchen conducts Wagner's potent early opera starring Peter Seiffert, Emma Bell, Christian Gerhaher and Sophie Koch, in Tim Albery's acclaimed production.
In Venus's domain of the Venusberg, the great singer Tannhäuser tires of Venus's love and escapes. In a song contest at home on the subject of love, Tannhäuser argues for the importance of physical desire – revealing his sin with Venus, to the people's horror. Elisabeth, whose heart he won long ago, intercedes on his behalf. Tannhäuser is ordered to make a pilgrimage to the Pope to seek redemption.
Tannhäuser bitterly returns home – the Pope has refused him salvation. He vows to return to Venus. News arrives that Elisabeth is dead; she has sacrificed herself for Tannhäuser's sake. Tannhäuser realizes the extent of her love and his soul is saved.
Tannhäuser is not available to book, please sign up to our newsletter for updates and offers on forthcoming and available shows.
Sung in German with English surtitles.
Find out more about the venue for your show: Directions, Transport options and facilities.
(3 mins) The Royal Opera House is off Covent Garden piazza, which is visible from the tube station exit. There is a revolving door entrance at the piazza.


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Bellport United Methodist Church
Tuesday, September 22, 2020
He who abides in love, abides in God.
Chris and Friends
Date: Sunday, January 19, 2020
Time: 9:00 AM -
Live Music!!
You are invited!
Live Music!!
God does so much for us And He loves you
Beyond all measure
Let us sing and celebrate together with our
Worship and Praise!!
In The Bellport Methodist Sanctuary
Bring a Friend - Bring your family
Let's celebrate our gift of salvation Together as
One family in Christ Jesus!
Please join us and sing along or just listen as
"Chris Gradilone and friends"
Praise Our Lord with Music and Song
Preparing our Hearts for The Living Word of God
And every Third Sunday Morning from 9:00 till 9:30 AM
Psalms 147:1 Praise the LORD. How good it is to sing praises to our God, how pleasant and fitting to praise him!
God Bless You!


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Sunday, Sept. 30, 2012
Students & Sondheim: 'Putting it Together'
on Staten Island's Main Stage
by MICHAEL J. FRESSOLA
There are simpler ways to ease into a theater season than with a Stephen Sondheim revue, but a less challenging start would be a mistake, according to Drew Scott Harris and Lauri Young, director and music director of Wagner College's upcoming "Putting It Together."
Everyone involved, students and profs, is learning.
"I can listen to this music over and over and find new things to appreciate," said Young, "I look forward to rehearsal every night. As the accompanist, I am approaching the score the way I would a chamber music recital: Practice, practice, practice and pay attention to details."
"Putting It Together" extracts songs from lesser-known Sondheim works like "Frogs," as well as better-known material like "Company," "A Little Night Music" and "Sunday in the Park with George."
The first version of the revue opened 20 years ago in London; a different assortment surfaced on Broadway in 1999.
Wagner's Wednesday through Oct. 14 production represents yet another variation, approved last month by the composer/lyricist himself.
The cast of nine includes Wagner faculty member Amy Williams and seniors Elana Abt, Alex Boniello, Eric Petillo, Michael Garamoni, Robert Haltiwanger and Olivia Puckett. They'll handle 30 songs. The show will inaugurate the newly refurbished Main Stage theater.
Director Drew Scott Harris discussed his theory of revues, his dealings with Sondheim, and his favorite number:
Q: Calling "Putting It Together" a revue seems almost sadistic. Revues are breezy and fun. This show seems to gather up all the tricky numbers from 10 shows, but even then, it has to come off without visible strain, shouldn't it?
A: For me, sitting through a "breezy and fun" revue, say something like "The Lawrence Welk Show" or a cruise ship, high-voltage revue — where songs modulate up a half-step with every repetition — is as close to the Marquis de Sade as I would ever want to be.
The numbers in "Putting It Together" are complex and sometimes labyrinthine, but I wouldn't call them tricky. Doing this show has shown me how remarkably beautiful and emotionally moving Sondheim's work really is, and, that the generalizations about his writing being only intellectual are just that — generalizations.
There are a couple of songs in this show that regularly move me to tears, for the right reasons. And don't ask me which ones. A director must retain some shred of mystery in his life.
Q: Which version are you doing — London or Broadway — and why?
A: We're doing a combination of both the London and Broadway versions. Through Music Theatre International, I was in contact with Sondheim and sent a proposal of changes to the show especially conceived for this Wagner production.
Overall there were about a dozen changes that dealt with the fact that this is a college show and the material will be presented by 19 to 21 year olds.
He was kind enough to read through all the material, consider it and surprisingly for me — because I've worked with several established and famous Broadway writers/composers who are, shall we say, less than flexible — agreed to all the changes.
The only thing he asked was that we not make a cut in "Country House," a number I believed at the time to be way over the heads of the students because it deals with a middle-aged (or older) couple whose marriage is going down the tubes.
Ironically, this number has become one of my favorites and the students get it completely. Sadly, disillusionment and loss of love are not only restricted to the over-40 crowd.
Q: Would you say that the advantage of the austere piano arrangement makes the beauty of the music/sparkle of the lyrics that much clearer?
A: Both an austere piano arrangement and a full symphonic arrangement work beautifully with Sondheim's work. Listening to recordings of both has proven this to me. What's more important than the arrangement, is the performer's understanding of the material and the ability to present it with emotional connection and depth without any schmaltz.
Q: The Sondheim state of mind seems so cocktail hour/grown up. Is it an easy fit for 21-year-old actor-singer-dancers in 2012?
A: Nothing is easy about Sondheim. He challenges, and the challenge pays off. We put these kids through a grueling audition process to see who could sight read, hold onto a complex harmony line and bring emotion to a song that they understood on an intellectual level. They were also asked what they liked about Sondheim's work and why (a la "A Chorus Line"). Students, even in 2012, love to give as good as they get.
Q: Some acting/singing teachers have been known to say that doing justice to Sondheim is a very big hurdle and that most other assignments won't be so challenging (unless its Wagner or Rossini). What do you say?
A: If you've got talent, challenging material is your chocolate cake. But the truth of the matter is, even a supposedly simple tune like "Amazing Grace," to be presented simply and beautifully is a very, very hard and rare accomplishment — I'm thinking now of Judy Collins. As for Wagner — the composer, not the college — personally, in the case of "Das Rheingold," I prefer to leave after the overture. For me that's earth-shakingly wonderful, gorgeous and moving, and all that follows is downhill.
Q: Are your personal faves in the "Putting it Together" mix?
A: One is. I asked if we could include "I Remember" (from "Evening Primrose"). The composer said yes. My life is full.


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Read here – sounds like the Pack may be quite concerned both about Flynn's shoulder injury and Brohm's apparent talent injury.
Packers looking at Tampa QBs?
19 Responses to "Packers looking at Tampa QBs?"
Ron La Canne Says:
August 27, 2009 at 10:42 pm |
Just finished watching the 1st half of the Bucs v. Dolphins. Mc Kown is 0-4 and Leftwich is 8-17. Neither would be worth much in my opinion. Leftwich fires the ball over everyone's head on a regular basisi and Mc Kown looks like Brohm.
I do know this. If Rodgers goes down the season is over. Flynn is still not a legitimate backup and Brohm, well, what can be said? I'd wait for the release date and see what else might be there.
Trav Says:
August 27, 2009 at 10:48 pm |
Andy – Way to end the day on a high note. "talent injury". Well done.
The Bill Simmons podcast from yesterday had Mike Lombardi from the National Football Post at the end. He picked a rematch of Super Bowl XXXI for this season: Pats – Packers. Lots of love for Rodgers, Colin Cole, Kampman, the potential of Caper's D schemes and what it brings to GB. Hope they can live up to some of the hype as the podcast got me jacked up on all the possibilities for this season.
Trav Says:
August 27, 2009 at 10:57 pm |
RLC – Agree on both TB QB's. Leftwich is serviceable, at best. McKown is less than that. Either one doesn't add anything in terms of a back-up.
A-Rodg showed something in playing through some pain last year so hopefully our new O-line can keep him protected and we don't have to go to Plan B, C, D… for a starting quarterback
Dave in Tucson Says:
August 27, 2009 at 11:35 pm |
The problem with Leftwich is it looks like he's the closed thing Tampa Bay has to a starting QB right now, which means they're probably not going to be willing to give him up.
Cindy V Says:
August 28, 2009 at 9:25 am |
The Pack really need a backup QB. I think either QB from the Bucs is better than an injured Flynn and a bust like Brohm. I'm not sure who else is out there right now. The Pack was lucky last season in that Rodgers' injury wasn't worse.
Aaron Rogders Says:
August 28, 2009 at 10:23 am |
I thought Flynn's shoulder was just sore. Is the injury worse then what was originally thought? I haven't seen anything on Packers site saying any different. I think it is just the media blowing this one up. If Flynn is healthy, I feel comfortable with him being our #2.
Joe Says:
August 28, 2009 at 11:17 am |
I agree with Aaron Rodgers – Flynn if healthy is a legitimate number 2.
56Coop Says:
August 28, 2009 at 12:01 pm |
Agree with everything said here. Nothing at the Bucs we need, Flynn will be a decent backup but I wouldn't be real disappointed to see Brohm cut if anyone else comes available. "Talent injury" — nice call
Schaefer Says:
August 28, 2009 at 12:36 pm |
Hayes, I can't believe you didn't suggest a trade for Tarvaris Jackson…
DaveK Says:
August 28, 2009 at 12:54 pm |
If you don't think Brohm is ever going to develop into a solid NFL QB then you obviously replace him. But, the #3 QB slot is for development and if you think Brohm has potential then you keep him around. The season is shot if the #3 plays regardless. The real questions is if Flynn can come in and finish a game or even start a game or two and play good enough to win. The chances of Brohm seeing the field are slim. The chances of Flynn having to play is much more likely. So, bringing in another QB is more about Flynn then Brohm in my opinion. I think the Packers still have hope for Brohm and are willing to keep him as a #3 QB. I also think they believe Flynn can come in and finish a game or two. All speculation on my part but I doubt they add another QB.
Ron La Canne Says:
August 28, 2009 at 3:55 pm |
MM says Dr. Mac wants Flynn out one more week. His injury is not joint related but muscle mass related.
If Rodgers doen't go down for more than a game Flynn will be adequate. An extended in jury will be very difficult.
56Coop Says:
August 28, 2009 at 5:34 pm |
What about Tyler Thigpen?
Ron La Canne Says:
August 28, 2009 at 7:07 pm |
Not a bad idea. The big question of the day is, will I be able to keep this geezer like body awake beyond the first half. Do I have to? Prpbably not ! Thank God for the DVR!
DreamPipe Says:
August 28, 2009 at 7:31 pm |
What about the other Bucs QB, Simms!? I've always liked the guy, really tough, despite many serious injuries. I know it's risky, but I could see him being a capable backup… thoughts?
Trav Says:
August 28, 2009 at 10:28 pm |
Simms actually is with Denver now and injured. He was backing up Orton and was hurt in a preseason game this week. Denver actually picked up former Packer draft pick, Ingle Martin.
56Coop Says:
August 29, 2009 at 11:56 am |
Your'e probably right about the costs Andy & Ron I know how you feel. Hell, I finally got around to watching the last 1/2 of the 4th qtr of the Bills game last night—-
56Coop Says:
August 29, 2009 at 12:02 pm |
Appears Chiefs want at least a 3rd round pick for Thigpen.
56Coop Says:
August 30, 2009 at 5:03 pm |
OK, just a thought here, it is being reported that O'Connel is being cut by the Pats & that the likely scenario is the Cheifs will pick him up & cut Thigpen
I want to say I am not on some sort of Thigpen soapbox here but considering Brohm's performance of late is a 3rd rounder too much to pay for him? Granted he did not do much the other day when Cassell went down but he would have the benefit of MM's QB school. Just throwin it out ther to see if it sticks (Kinda like they do at PFT).
Sure wish we could see more of Flynn.


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Among the benefits you'll receive as an Internet2 Industry member are:
- Executive leadership interactions and introductions to higher ed decision makers
- Connections with 450+ member institutions and 2M+ network subscribers
- Programs to facilitate dialogue with the global Internet2 ecosystem
- Priority opportunities and visibility at Internet2 conferences
- Opportunities to leverage higher ed relationships to collaborate on tomorrow's tech roadmap
Industry and Internet2 NET+
Our industry members are key partners in the extension of advanced networking excellence to the cloud through the Internet2 NET+ initiative—the creation of "a better cloud," a unified, integrated portfolio of cloud and trust solutions, blending both commercial services and community offerings, that enables the research and education community to work in a new way.
For more information on the winning combination of industry and the Internet2 community, contact email@example.com.
Internet2 Industry Members are committed to promoting the development and deployment of advanced Internet applications and network services. Internet2 industry partners and industry sponsors make significant commitments to collaborating with Internet2 higher education members.
Contact firstname.lastname@example.com for more.
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|Unicon, Inc.