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Paloma Fautley
Paloma Fautley is an Engineering Intern at Make Magazine. She is currently pursuing a degree in Robotics Engineering. She is a regular contributor to the Sci-Fi web series Make: Believe.
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|Active Cavity Radiometer Irradiance Monitor
Click on figures for high resolution pdf version
Total Solar Irradiance (TSI) Monitoring
Figure 1 TSI monitoring by satellite experiments
Updated April, 2013
The Earth's weather and climate regime is determined by the total solar irradiance (TSI) and its interactions with the Earth's atmosphere, oceans and landmasses. Evidence from both 34 years of direct satellite monitoring and historical proxy data leaves no doubt that solar luminosity in general, and TSI in particular, are intrinsically variable phenomena. Subtle variations of TSI resulting from periodic changes in the Earth's orbit (Milankovich cycles: ~20, 40 and 100 Kyrs) cause climate change ranging from major ice ages to the present inter-glacial, clearly demonstrating the dominance of TSI in climate change on long timescales. TSI monitoring, cosmogenic isotope analyses and correlative climate data indicate that variations of the TSI have been a significant climate forcing during the current inter-glacial period (the last ~ 10 Kyrs.). Phenomenological analyses of satellite TSI monitoring results, TSI proxies during the past 400 years and the records of surface temperature show that TSI variation has been the dominant forcing for climate change during the industrial era. The periodic character of the TSI record indicates that solar forcing of climate change will likely be the dominant variable contributor to climate change in the future.
A series of Active Cavity Radiometers (ACRs), a new generation of sensors with the precision required for compiling a long term TSI database for climate, were developed at the Jet Propulsion Laboratory (JPL) of the California Institute of Technology under the direction of ACRIM Principal Investigator, Dr. Richard C. Willson. Their use in a series of Active Cavity Radiometer Irradiance Monitor (ACRIM) space flight experiments has provided a precise and traceable component of the TSI database during more than 90 % of its 34 year history. The ACRIM Science Team moved its operation to Columbia University in 1995 and then back to the Jet Propulsion Laboratory under contract in 2008. The ACRIM Instrument Team, directed by ACRIMSAT Program Manager Sandy Kwan, operates the ACRIMSAT satellite, ACRIM instrument and ground telemetry instrumentation at JPL.
A contiguous TSI database of satellite observations extends from late 1978 to the present, covering more than three solar magnetic cycles. It's comprised of the observations of seven independent experiments: Nimbus7/ERB1, SMM/ACRIM12, ERBS/ERBE3, UARS/ACRIM24, SOHO/VIRGO5, ACRIMSAT/ACRIM36 and SORCE/TIM7. A composite database combining these results using overlapping, in-flight comparisons has begun to provide new insights into the variability of total solar irradiance and its implications for climate change.
Monitoring TSI variability is clearly an important component of climate change research, particularly in the context of understanding the relative forcings of natural and anthropogenic processes. The requirements for a long-term, climate TSI database can be inferred from a National Research Council study which concluded that gradual variations in solar luminosity of as little as 0.1 % was the likely forcing for the 'little ice age' that persisted in varying degree from the late 14th to the mid 19th centuries. A centuries-long TSI database will have to be calibrated by either precision or accuracy to a small fraction of this value to be of use in assessing the magnitude of solar forcing. The current TSI database is shown in Figure 1.
Instrumentation used in spaceflight TSI monitoring to date has utilized sensors operating at ambient temperature (~ 20C). They provide the only practicable satellite instrument technology presently available for extended flight experiments. The 'native scale', on which the results of each experiment's TSI observations are reported, is based on the metrology of their individual cavity sensor properties in the International System of units (SI).
The de-facto, redundant, overlap TSI monitoring approach that has provided a contiguous record since 1978 resulted from the deployment of multiple, overlapping TSI satellite experiments. The traceability of this database is at the mutual precision level of overlapping experiments. This is typically orders of magnitude smaller than the 'absolute uncertainty' of observations in the international system of units (SI). ACRIM3 results have demonstrated a residual annual traceability of ~ 5 ppm during its 13 year mission. A carefully implemented redundant, overlap strategy should therefore be capable of producing a climate timescale (decades to centuries and longer) TSI record with useful traceability for assessing climate response to TSI variation.
• A redundant, overlapping TSI measurement strategy using existing 'ambient temperature' instrumentation can provide the long term traceability required by a TSI database for climate change on climate time scales.
The state of the art measurement uncertainty for flight observations on an 'absolute scale' in the international system of units (SI) has not been demonstrated to be significantly less than 1000 parts per million (ppm). The results of TSI monitoring experiments are reported on their 'native scales' as defined in SI by the 'self-calibration' features of their sensor technologies. Systematic uncertainties in the metrology used to relate their observations to SI caused the ± 0.25 % spread of results during the first decade of monitoring. The tighter clustering of results after 1990 is attributable to dissemination of more accurate sensor metrology among the various experiments and national standards labs.
A new approach to calibrating TSI sensors has been developed by several laboratories including Absolute Cryogenic Infrared Radiometry at the at the National Institute of Standards and Technology (NIST) LBIR facility and the TSI Radiometer Facility (TRF) at the Laboratory for Atmospheric and Space Physics (LASP) of the University of Colorado. High powered lasers are calibrated in SI units using self-calibrating cryogenic irradiance detectors, similar in design to the self-calibrating ambient temperature sensors employed by satellite TSI monitors, but operated at LHe temperature. Self-calibrating irradiance sensors are thermal detectors that compare the heating effects of solar irradiance and electrical heating on a cavity detector. The uncertainty of their ability to define irradiance in SI units is temperature dependent. When cooled to LHe temperatures self-calibrating irradiance sensors can define irradiance at the 1 TSI level with uncertainties approaching a few hundred ppm. The calibrated lasers are used as transfer standards to irradiate ambient temperature satellite TSI sensors and compare their basic 'self-calibrated' SI scales to that defined by the LHe cryogenic detector's. The effects of scattering and diffraction on sensor calibrations can also be determined by varying the beam size of the laser. The SI uncertainty of TRF calibrations can be on the order of 500 parts per million (ppm) or less, with the SI scale traceable to NIST. However, the ability of satellite TSI sensors to reproduce TRF calibrations on orbit has yet to be determined experimentally. The LASP TSI Radiometry Facility (TRF) has been used to calibrate TSI sensors equivalent to the SORCE/TIM, ACRIMSAT/ACRIM3 and SOHO/VIRGO satellite sensors. The results calibrate the basic scale of these sensors' operation in SI as well as the scattering and diffraction effects of their field-of-view defining instrumentation.
Preliminary LASP/TRF testing of ACRIM3 flight backup instrument found a net ~ 5000 ppm difference between ACRIM3 and the TRF cryo-radiometer defined SI scale caused by scattering (~ 3500 ppm), diffraction (~1200 ppm) and a basic SI scale difference (~300 ppm). Application of the TRF corrections to the ACRIM3 observations has resulted in close scale agreement with those of the SORCE/TIM experiment. Similar results have been obtained for the SOHO/VIRGO instrument. Additional testing is planned to decrease the uncertainties of the ACRIM3 results and apply the same type of TRF characterizations to the results of representative sensors of the SMM/ACRIM1 and UARS/ACRIM2 satellite instruments.
• Preflight calibration of satellite TSI monitors does not guarantee in-flight observations with the laboratory level of SI uncertainty. Flight experiments with LHe cryogenic sensors need to be implemented to calibrate the effects of launch and flight environments on preflight calibrations.
1. Nimbus7/Earth Radiation Budget experiment (1978 - 1993)
2. Solar Maximum Mission/Active Cavity Radiometer Irradiance Monitor 1 (1980 - 1989)
3. Earth Radiation Budget Satellite/Earth Radiation Budget Experiment (1984 - 1999)
4. Upper Atmosphere Research Satellite/Active cavity Radiometer Irradiance Monitor 2 (1991 - 2001)
5. Solar and Heliospheric Observer/Variability of solar Irradiance and Gravity Oscillations (1996 --->)
6. ACRIM Satellite/Active cavity Radiometer Irradiance Monitor 3 (2000 --->)
7. Solar Radiation and Climate Experiment/Total Irradiance Monitor (2003 --->)
8. NASA-NIST TSI WORKSHOP 18-20 July, 2005.
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Tillberg & Reyes Group Co., Limited
Company Registration No.: 2400408
The company was incorporated on 2016-07-08 with Private company limited by shares
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And the company is running: 4 years, 2 months, 19 days.
As the company is Live, the company must be submitted Annual Return (Form NAR1) to the Companies Registry within 42 days after July 8 each year!
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Tillberg & Reyes Group Co., Limited
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The Business Registration is due for renewal at a cost of HK$250 per annum. (Branch Business Registration is HK$323) Late renewal will attract a penalty of HK$300. Further delay will result in court proceeding and extra fine.
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Difference between revisions of "2013 Group 5 Project"
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| '''1996'''
| '''1996'''
| The study carried out by MR Paddy and co-workers revealed the rearrangements the nuclear lamina undergoes and furthermore they observed that this process takes place in conjunction with the movements of [[#Glossary |'''centrosomes''']] and [[#Glossary |'''microtubules''']]. While these dynamics were observed via the technique of Time-resolved, two-component, three-dimensional fluorescence light microscopy imaging,the study did not cast a light on the significance of these structural dynamics. <ref><pubmed>8907705</pubmed></ref>
| The study carried out by MR Paddy and co-workers revealed the rearrangements the nuclear lamina undergoes and furthermore they observed that this process takes place in conjunction with the movements of [[#Glossary |'''centrosomes''']] and [[#Glossary |'''microtubules''']]. While these dynamics were observed via the technique of Time-resolved, two-component, three-dimensional fluorescence light microscopy imaging,the study did not cast a light on the significance of these structural dynamics. <ref ><pubmed>8907705</pubmed></ref>
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====Outer Nuclear Membrane====
====Outer Nuclear Membrane====
Structurally continuous with and comparable in composition to the peripheral endoplasmic reticulum is the [[#Glossary |'''outer nuclear membrane''']]. <ref><pubmed>22307332</pubmed></ref> <ref name="PMID22863006"/> As reviewed in Lynn et al, (1984), it is thought that the outer membrane could be a site of membrane-bound synthesis of glycoproteins. Ribosomes are also found on the cytoplasmic surface of the outer nuclear membrane which is continous with the ER. Since there is a significant similarity between the endoplasmic reticulum and the outer nuclear membrane, it is thought that NE is a more elaborate form of ER. <ref><pubmed>2985606</pubmed></ref><
Structurally continuous with and comparable in composition to the peripheral endoplasmic reticulum is the [[#Glossary |'''outer nuclear membrane''']]. <ref><pubmed>22307332</pubmed></ref> <ref name="PMID22863006"/> As reviewed in Lynn et al, (1984), it is thought that the outer membrane could be a site of membrane-bound synthesis of glycoproteins. Ribosomes are also found on the cytoplasmic surface of the outer nuclear membrane which is continous with the ER. Since there is a significant similarity between the endoplasmic reticulum and the outer nuclear membrane, it is thought that NE is a more elaborate form of ER. <ref><pubmed>2985606</pubmed></ref><ref> However, the outer nuclear membrane also has sites that assist with nuclear positioning.<ref><pubmed>16912077</pubmed></ref>
====Inner Nuclear Membrane====
====Inner Nuclear Membrane====
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===Semi-closed Mitosis===
===Semi-closed Mitosis===
Classification of mitosis in eukaryotes into open or closed forms can be limiting as some organisms have been found to have varying extents of nuclear envelope breakdown (NEBD) and the timing of the breakdown can also be atypical of open mitosis. <ref name=PMC2829850><pubmed>PMC2829850</pubmed></ref> <ref name=PMC2043359><pubmed>PMC2043359</pubmed></ref> For example, a study conducted by Paddy et.al. (1996) on early ''Drosophila'' embryos, using time-resolved 3D fluorescence light microscopy imaging, showed that there was an abnormally long period during mitosis where a large fraction of lamins remained intact and localised around the periphery of the nucleus. This semi-disassembled envelope persisted long into [[#Glossary |'''metaphase''']] spindle formation and eventually the lamins dispersed just before chromosomal segregation. They also observed an extensive series of structural rearrangements in the lamina which appeared to be linked to or driven by the movements of chromosomes and [[#Glossary |'''spindle fibres''']]. Paddy and peers (1996) state that this behaviour isn't characteristic of neither open nor closed mitosis but instead appears to be of an intermediate form, <ref name=PMID8907705
Classification of mitosis in eukaryotes into open or closed forms can be limiting as some organisms have been found to have varying extents of nuclear envelope breakdown (NEBD) and the timing of the breakdown can also be atypical of open mitosis. <ref name=PMC2829850><pubmed>PMC2829850</pubmed></ref> <ref name=PMC2043359><pubmed>PMC2043359</pubmed></ref> For example, a study conducted by Paddy et.al. (1996) on early ''Drosophila'' embryos, using time-resolved 3D fluorescence light microscopy imaging, showed that there was an abnormally long period during mitosis where a large fraction of lamins remained intact and localised around the periphery of the nucleus. This semi-disassembled envelope persisted long into [[#Glossary |'''metaphase''']] spindle formation and eventually the lamins dispersed just before chromosomal segregation. They also observed an extensive series of structural rearrangements in the lamina which appeared to be linked to or driven by the movements of chromosomes and [[#Glossary |'''spindle fibres''']]. Paddy and peers (1996) state that this behaviour isn't characteristic of neither open nor closed mitosis but instead appears to be of an intermediate form, <ref name=PMID8907705/> one of [[#Glossary |'''semi-closed mitosis''']] until after metaphase. <ref name=PMC2829850><pubmed>PMC2829850</pubmed></ref>
==The Nuclear Envelope At the Onset of Mitosis==
==The Nuclear Envelope At the Onset of Mitosis==
Revision as of 17:08, 30 May 2013
2013 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7
- 1 The Nuclear Envelope During Cell Division
- 1.1 Introduction
- 1.2 Historical Background
- 1.3 Structure of the Nuclear Envelope
- 1.4 The Different Forms of Mitosis
- 1.5 The Nuclear Envelope At the Onset of Mitosis
- 1.6 Breakdown of the Nuclear Envelope
- 1.7 The Dispersal of Nuclear Envelope Components
- 1.8 Mitotic Functions of Nuclear Envelope Components
- 1.9 Reformation of the Nuclear Envelope
- 1.10 Abnormalities in Nuclear Envelope Breakdown and Reformation
- 1.11 Current and Future Research
- 1.12 Glossary
- 1.13 Images
- 1.14 References
The Nuclear Envelope During Cell Division
The nuclear envelope (NE) is a highly specialised membrane that outlines the nucleus [1] and is a key physical compartment that defines eukaryotic cells. It has been described as a highly organised and regulated double membrane that compartmentalises the cell's genome. [2]
It is composed of two concentric membranes, the outer nuclear membrane and the inner nuclear membrane, which are joined by Nuclear Pore Complexes (NPC) that span both membranes. [3] The outer membrane is continuous with the membrane of the Endoplasmic Reticulum (ER), [4] while the inner membrane is attached to the lamina and chromatin of the nucleus. [3]
The NE serves to maintain the structure of the nucleus and its position in the cell by providing anchoring sites for its attachment to the cell's cytoskeleton. [3] More importantly it serves to separate nuclear and cytoplasmic activities,[5] including transcription from translation, protecting genetic material from the highly metabolic environment of the cytoplasm. [6] It acts as a selective barrier between the cytoplasm and nuclear contents, with the NPCs contributing to this diffusion barrier by regulating the passage of proteins, RNA and ribonuleoprotein complexes in and out of the nucleus. [5] In addition, more recent studies have shown the inner membrane proteins to play various important roles in the function of the nucleus including chromatin organization, gene expression and DNA metabolism. [2]
Changes to the NE's structure occur at the onset of mitosis, these changes are very slight in lower eukaryotes and in higher eukaryotes result in the complete disassembly of the nuclear membrane. [7] This complete or partial breakdown is necessary in order to form the mitotic spindle on condensed chromosomes. [5] Higher eukaryotes must consequently reassemble the NE around the genetic material of the daughter cells each time a cell divides in order to re-establish the nuclear compartment. [2] This page aims to explore the process of the breakdown and reassembly of the NE and its role in cell division.
Links: Cell Nucleus
Historical Background
Timeline of Historical Research On The Nuclear Envelope
|The Nuclear Envelope was described as a double membrane that encloses the genome by G.L Kite. [8]
|First EM study on the NE by Callan and Tomlin revealed that they contained pores. Furthermore they reported the nuclear envelope having two layers, a continuous internal layer and an outer porous layer. [9] [10]
|Watson reported that the nuclear envelope is continuous with the endoplasmic reticulum by carrying out an electron microscopy study of thin sections of interphase cells. He hypothesised that there were two communicating pathways between the cytoplasm and the nucleus; the perinuclear space and the cavities of the ER and the the NPCs. [11]
|Gall and co-workers discovered that NPCs had an octagonal structure. They did this by using negative staining on the NE from starfish, frogs and newts. [12]
|Hans Ris set in motion research of the function and structure of NPCs after developing high resolution electron micrographs. These micrographs were able to reveal the existence of nucleoporins. [13]
|A study was carried out using high resolution scanning electron microscopy (HRSEM) and the findings revealed a fibrous lattice attached to the Nuclear Pore Complex Basket. [14]
|The discovery of mutations in a gene encoding for nuclear proteins being the causative agent of Emery-Dreifuss muscular dystrophy. This lead to the idea of laminopathies, human diseases caused by abnormal functioning of NE proteins. [15]
|The study carried out by MR Paddy and co-workers revealed the rearrangements the nuclear lamina undergoes and furthermore they observed that this process takes place in conjunction with the movements of centrosomes and microtubules. While these dynamics were observed via the technique of Time-resolved, two-component, three-dimensional fluorescence light microscopy imaging,the study did not cast a light on the significance of these structural dynamics. [16]
|It was hypothesised that the nuclear lamina plays an important role in the nuclear disassembly during mitosis by P.Collas through the investigation of mitotic extract from sea urchins. [17]
|2000 and onwards studies on the specific mechanism and functions of the nuclear envelope as well as its role and interaction with other processes and factors such as proteins were investigated. The NE was also observed in conjunction with viruses and abnormal cells leading to a broader understanding of the normal and abnormal functioning of the NE. [18] [19]
Structure of the Nuclear Envelope
The (NE)is an important structure that covers the nucleus with a double membrane. The prominent constituents of the NE include the nuclear lamina, NPCs and nuclear membranes [20] . The nuclear membrane is made up of distinctive but unified domains: the outer nuclear membrane (ONM) and the inner nuclear membrane (INM) [21] It is the small pore membranes that join the INM with the outer ONM together and the double membrane is separated by an intermembrane space. Moreover, the NE forms a partition between the nucleus and the cytoplasm and also allows attachment sites for structures such as the cytoskeleton to the nuclear periphery [21] [22]
Outer Nuclear Membrane
Structurally continuous with and comparable in composition to the peripheral endoplasmic reticulum is the outer nuclear membrane. [23] [21] As reviewed in Lynn et al, (1984), it is thought that the outer membrane could be a site of membrane-bound synthesis of glycoproteins. Ribosomes are also found on the cytoplasmic surface of the outer nuclear membrane which is continous with the ER. Since there is a significant similarity between the endoplasmic reticulum and the outer nuclear membrane, it is thought that NE is a more elaborate form of ER. [24]Cite error: Closing
</ref> missing for
<ref> tag
Inner Nuclear Membrane
The Inner Nuclear membrane (INM), neighbouring with the endoplasmic reticulum membrane, is connected with the lamina and the chromatin [25]. It is in close contact with the genetic material of the nucleus and has various proteins attached to it. These proteins are manufactured on the rough endoplasmic reticulum and have important implication in human diseases which will be discussed later. [26] In recent years there has been an increase in the number of discoveries of various INM proteins mainlydue to the proteomic and computational approaches. [27] One such group of proteins include transmembrane proteins that are associated with the INM and they usually interact with chromatin and/or lamina. [28]
It is thought that these transmemberane proteins direct the chromatin to the membrane; this is essential during the reformation of the NE after mitosis. [28] Furthermore, important intermediate proteins called lamins are attached with one another to form 10nm-diameter filaments and these lamins make up an important network called the nuclear lamina. This structure, the Nuclear Lamina, is important because it not only supplies rigidity to the nucleus but also has other roles in the cell [29] [30] Ulbert et al.(2006), through their research on transmemberane proteins, have illustrated that interaction of Lem2 with chromatin or lamins are crucial to the maintenance of NE. Ulbert et al. (2006) have also demonstrated that (from the interaction of Lem2 and its partners) that this transmemberane protein has an essential function in the structural integrity of NE . Furthermore, a reduction in the transmemberane protein leads to aggregation of cells with deformed nuclei and ultimately cell death. [28]
Nuclear Pore Complexes
One of the most essential components of the NE are the Nuclear Pore Complexes (NPCs) which are embedded in the nuclear envelope and they are necessary for proper cell functioning since they control the entrance and exit of macromolecules between the nucleus to the cytoplasm. [31] [32] The NPCs are composed of numerous copies of ~30 nucleoporins and span the nuclear envelope at junctions of the inner and outer nuclear membranes. [33] [34] The NPC has an estimate mass of 125MD in vertebrates and in a yeast, the NPC is found to have approximately 100nm ringed-shaped diameter. The NPC also has a central channel that is about 30nm in diameter. [33]
Moreover, as reviewed in DeGrasse et al. (2009), the NPC in eukaryotes have eight spokes around the central tube which serves as the medium for the bidirectional movement of macromolecules. [35] As reviewed in Akey (1985), it is thought that the NPCs have structural plasticity as its flexible nuclear pore diameter assists with the movement of specific macromolecules. [36]
Links: Structure of the NPCs
The Different Forms of Mitosis
Comparing Open and Closed Mitosis
Typically eukaryotic cells undergo one of the two forms of mitosis; higher eukaryotes (metazoans) go through open mitosis, while lower eukaryotes including yeast and other types of fungi undergo closed mitosis. [37] The distinction between open and closed mitosis can be made by focusing on the behaviour of the NE which separates the nuclear contents from the cytoplasm and is split to form daughter nuclei. [38] Open mitosis is so named because the nuclear envelope completely breaks down at the transition from G2 stage to M stage of the cell cycle [37] and the nuclear content, including the genetic material, is "open" to mix with cytoplasmic macromolecules [39] until the nuclear envelope is reassembled after chromosomal segregation during telophase. [37] [39] In contrast, during closed mitosis the nuclear envelope remains intact and mitosis continues within the nucleus resulting in the fission of the NE after chromosomal segregation. [38]
In open mitosis the entire NE, including the NPCs, breakdown allowing the attachment of the spindles to the chromosomes [5] as well as their interaction with cytoplasmic macromolecules needed for mitosis. This means that the transport of molecules in and out of the nucleus through NPCs is not required during open mitosis. [40] In contrast, the NE of eukaryotes undergoing closed mitosis remains intact, with the continual function of its NPCs that are important in maintaining the connection between the nucleus and cytoplasm so that tubulin and proteins, that are necessary for the regulation of entry into mitosis, are allowed to enter the nucleus. [37]
The importance of the maintenance of the NPCs in closed mitosis is evident in a study conducted by Louk et.al (2002) where fluorescent microscopy was used to analyse the NE and NPCs of the yeast Saccharomyces cerevisiae. They found a link between components of yeast NPCs and the mitotic checkpoint machinery, showing that the Mad1p and Mad2p proteins, required for the establishment of the spindle checkpoint, were mostly found at NPCs throughout the cell cycle. They observed that once the spindle checkpoint was activated, a build up of Mad2p at the kinetochores occurred which coincided with the hyperphosphorylation of Mad1p mediated by the nucleoporin sub-complex Nup53. These observations led Louk and his peers to suggest a model where the association of Mad1p to Nup53p-containing NPCs traps Mad2p until it is primed for release by the spindle checkpoint activation. In addition they suggest that the bond between Nup53p and Mad1p has a role in the aid of transport through the NE. [40]
In addition, it has been established that in order for a eukaryotic cell to undergo mitosis successfully microtubules need to gain access to the chromosomes so they can be evenly distributed among the daughter cells. As previously explained, this is made possible through the breakdown of the NE in open mitosis. Under closed mitotic conditions, where the nuclear envelope remains intact, the spindle poles or microtubule organising centres (from which the microtubules arise) are embedded in the NE, hence, the microtubules form within the nuclear compartment and so are able to gain access to the kinetochores of the chromosomes. [41]
Semi-closed Mitosis
Classification of mitosis in eukaryotes into open or closed forms can be limiting as some organisms have been found to have varying extents of nuclear envelope breakdown (NEBD) and the timing of the breakdown can also be atypical of open mitosis. [38] [37] For example, a study conducted by Paddy et.al. (1996) on early Drosophila embryos, using time-resolved 3D fluorescence light microscopy imaging, showed that there was an abnormally long period during mitosis where a large fraction of lamins remained intact and localised around the periphery of the nucleus. This semi-disassembled envelope persisted long into metaphase spindle formation and eventually the lamins dispersed just before chromosomal segregation. They also observed an extensive series of structural rearrangements in the lamina which appeared to be linked to or driven by the movements of chromosomes and spindle fibres. Paddy and peers (1996) state that this behaviour isn't characteristic of neither open nor closed mitosis but instead appears to be of an intermediate form, [16] one of semi-closed mitosis until after metaphase. [38]
The Nuclear Envelope At the Onset of Mitosis
Just before the onset of mitosis the nuclear envelope begins to undergo processes that will eventually lead to the tearing and breakdown of the NE. This involves centrosome migration and microtubule interactions with the NE. Preparation for the breakdown of the NE occurs in late G2/early prophase and involves an early structural deformation at particular sites of the NE. [42]
The review by Guttinger et.al explains that the indentations which form around the centrosomes (microtubule organising centre) are induced by the pulling forces of the microtubules that have attached to the outer surface of the NE. These stretching forces ultimately lead to the development of fenestrations on the distal side of the nucleus and are observed in the fragmentation of the nuclear lamina. [43] The microtubule motor protein, dynein is required to participate in this process and it associates with the NE at the end of the G2 stage of interphase. [7] The interactions of the microtubules with the NE facilitate NEBD as well as the rupturing of NE. [43] Observations made in a particular study give evidence as to the involvement of microtubules at the entry into mitosis, this includes: the placement of sister chromosomes and microtubule asters directly at two indentations of the NE during early and mid-prophase, the correlation between microtubule growth toward the NE and the deepening of the nuclear indentations that ultimately lead to the fenestrations in the NE, and lastly the absence of focal nuclear indentations in cells with experimentally induced disassembled microtubules [44]
Moreover chromatin condensation occurs before NEBD and the rate of condensation increases by three-fold after the NE is made permeable. This supports the ideas that changes in the NE constitute changes of other elements in cell division [43]
A study conducted by Raaijmakers JA and colleagues further found that the microtubule motor protein kinesin-5 (Eg5) is also important in centrosome separation. Furthermore the study showed that with the absence of Eg5 the cell still undergoes mitotic activity. They discovered that the cell uses the MT motor protein dynein to carry out centrosome separation. [45]
Breakdown of the Nuclear Envelope
The breakdown of the NE only occurs in higher eukaryotes/metazoans like plants and animals. The entry of these types of cells into mitosis (prophase) is defined by the condensation of chromatin and the events leading up to the loss of compartmentalisation of the nuclear content [41] [2] and it not only involves the removal of the inner and outer nuclear membranes but also the disassembly of the underlying lamina and NPCs. [43] "By prometaphase, the NE has largely dispersed and the nuclear contents are released into the cytoplasm." [41]
Metazoans form spindle microtubules which are located in the cytoplasm and are vital in mitosis for the segregation of chromosomes, therefore the disassembly of the NE is required in order for these microtubules to gain access to the kinetochores of the chromosomes. [43]
The precise mechanism by which the NE is broken down has not been established,[42] as studies have revealed various high order eukaryotic species to have different ways in which their NE disassembles; therefore there are a number of proposed methods by which this occurs. In addition the order in which the different components of the nuclear envelope are disassembled is also unclear.
What is clear, however, is the involvement of mitotic kinases in the breakdown of the nuclear envelope. Such kinases as the Maturation/Mitosis Promoting Factor (MPF) containing cyclin-dependant kinase 1 (CDK1), also known as p34, are responsible for the phosphorylation of NE proteins, which eliminates protein-protein interactions, and the consequent disintegration and dispersal of all major NE structural components. [42]
Reviews such as those by Kutay and Hetzer (2008) describe the breakdown of the NE as involving three key processes: the disassembly of NPCs and the subsequent increase in nuclear envelope permeability, the depolymerisation and consequent breakdown of the nuclear lamina and the disassociation of the NE from the chromatin. [7] The breakdown culminates in the dispersal of most of the disassociated components into the ER. [46] It has also been suggested that NE vesiculation and spindle microtubule mechanism are other contributing methods for NE disassembly. [42]
Microtubule Involvement in Nuclear Envelope Breakdown
Microtubules not only function in the separation of chromosome pairs but studies of mammalian cells using multicolour confocal 4D imaging have also shown growing microtubules to contribute to the breakdown of the NE, particularly through their role in membrane indentation and consequent fragmentation. [44] [46] As mentioned in the previous section, the forces exerted by microtubules onto the NE are suggested to result in its deformation as well as its stretching in preparation for its consequent breakdown.
Observations on dividing mammalian cells made using quantitative 4D imaging in conjunction with fluorescence photobleaching techniques showed that the stretching of the NE led to the "formation of holes in the NE at the site of maximal tension" and hence can be thought of as a tearing of the envelope. These tearing sites were found to be located opposite the force producing centres, the centrosomes and after this tearing the NE collapsed releasing the tension produced by the stretch. [42]
Other studies have found that microtubule action is not essential for the breakdown of the NE. One study used Nocodazole, which inhibits the assembly of microtubules, and found that even though the extension of microtubules had ceased, the disassembly of the NE continued, however, it was noted that upon the addition of this inhibitor, the breakdown rate of the envelope was slowed and disordered and so they therefore concluded that microtubules aid but are not pivotal to the deconstruction of the NE. [46]
The breakdown of the NE has been proposed to be the catalyst which causes both the accelerated condensation of the chromosomes, as a result of the loss of the balance of forces that maintained the spherical integrity of the nucleus; and the dissociation of lamins, inner nuclear membrane proteins and NPCs through the activity of multiple kinases that enter the nuclear space. [42]
The Disassembly of the Nuclear Pore Complexes
One of the initial steps in the breakdown of the nucleus is the disassembly of the NPCs through the loss of nucleoporins (Nups), [2] which are removed in the form of nucleoporin sub-complexes and are released into the mitotic cytoplasm. [47]
It has been observed that this process is very rapid in living mammalian cells being completed within minutes [48] and removes the permeability barrier of the NE resulting in the mixing of nuclear and cytoplasmic components. [49] The process of removing nucleoporins from NPCs is achieved through phosphorylation of their proteins which involves the activity of a number of kinases, mainly CDK1 with the help of members of the NIMA-related kinase (Nek) family [49] [50]
Kenetic analysis of single living, dividing cells using confocal-time-lapse microscopy has revealed that the disassembly of NPCs occurs faster than their assembly after cell division and in addition it has uncovered that the removal of the majority of nucleoporins occurs in a synchronous matter except for one which is lost very early on in mitosis. [48]
Studies of living mammalian cells and starfish oocytes reveal that the first nucleoporin to clearly disassociate from the NPCs is Nup98. [48] [51] Nup98 is a peripheral nucleoporin that is found symmetrically on both sides (i.e. cytoplasmic and nucleoplasmic sides) of the NPC with GLFG-type Phe-Gly (FG) repeats that are thought to be important in the formation of the NPC permeability barrier. [49] [47]
Studies conducted by Laurell and peers (2011) aimed to explore the role of phosophorylation in NPC disassembly, they found that the hyperphosphorylation of 13 different phosphosites (phosphorylation sites) in human GLFG Nup93 is required for successful dissociation of Nup98 from NPCs and is a very important step in the breakdown of NPCs. The mitotic kinases which were identified as being responsible for this hyperphosorylation include CDK1, Nek kinases and Plk1 and they proposed that the involvement of multiple kinases could be a mechanism which ensures that only those cells which are entering mitosis undergo NPC disassembly. They also discovered that mutations of phosphorylation sites on Nup98 lead to the slowing down of NPC disassembly and inhibition of the vital kinase CDK1 resulted in the cessation of NPC breakdown, therefore it was concluded that the hyperphosphorylation of Nup98 is the rate-limiting step needed in mitotic NPC disassembly to initiate the breakdown of the NE selectivity barrier [47]
The removal of Nup98 from the complex is proposed to be the trigger for the wave of nucleoprin dissociations from NPCs that follows. [43] It is suggested that the order in which nucleoporins are phosphorylated and removed may reflect their position within the NPCs, such that those on the periphery are solubilised first as they are more accessible to the mitotic kinases, this is followed by the more internal nucleoporins. [52] This is consistent with the dissociation of the first nucleoporin, Nup98, which is located on the periphery of the NPC.
Separate studies conducted on live starfish oocytes and live mammalian cells reveal Nup153 as another nucleoporin which dissociates early on in the disassembly process of NPCs. This is followed by the removal of Nup214 (situated on the cytoplasmic side of the complex) and Nup133 which occurs during the middle of the disassembly process, this precedes the detachment of the Nup107-160 complex, leaving the Nup62 complex (nup50 and Nup58) and POM121, which are the longest remaining core components of the NPC and the last to be removed. [51] [48]
The Depolymerisation of the Nuclear Lamina
The NE is stabilized by the underlying tight meshwork of intermediate filaments known as the nuclear lamina, which is disassembled after the NE is broken down. [42]
The nuclear lamina is composed of A-, B1- and B2-type lamin polypeptides that are associated with the inner nuclear membrane [44] and serve as anchoring sites for chromatin during interphase. During the disassembly of the nuclear envelope these lamins undergo reversible depolymerisation into monomers which are dispersed in the cytoplasm, the reversibility has been suggested to regulate the NE disassembly and reassembly. [53]
The depolymerisation and consequent deconstruction of the lamina is achieved through the phosphorylation of the three key lamins by the main kinase in NE breakdown, CDK1. [42] The necessity of depolymerisation by CDK1 is shown in a study where mutations in the sites of phosphorylation on the lamins, prevent the disassembly of the nuclear lamina during mitosis. [54] PKC-βII kinase has also been identified to phosphorylate B-type lamins in various species during mitosis. [55] [56]
Experiments on the three different types of lamins revealed that their disassembly pattern differs from one another, showing that the A-type depolymerises quite early on in mitosis (during early/mid-prophase). [44] Additionally, these lamin residues are no longer membrane associated, i.e. they have become disassociated from the inner nuclear membrane, as well as being depolymerised into their monomeric form and released into the cytoplasm. [57] [56] In contrast, most of the B-type lamin appears to be focally deformed and somewhat fragmented, yet continues to be associated with their inner nuclear membrane anchorage sites until prometaphase. This layer of B-type lamins lining the NE in early mitotic cells is proposed to function in sustaining the membrane's elasticity and form until prometaphase when they dissociate and disperse into the ER. [44] [56] The majority of the depolymerised lamin residues are recycled to form the lamina of daughter cells, hence highlighting the reversibility of the depolymerisation of the lamins. [57]
The Disassociation of the Nuclear Envelope From Chromatin
The majority of the NE has been disassembled by prometaphase, however, studies like one conducted by Beaudouin et.al (2002) revealed that there are some fragments of the envelope, containing LAP2β (lamin protein), B1 type lamin and POM121 (NPC protein), that remain attached to the chromosomes. These fragments were observed to disassociate from the chromosomes and "migrate" towards the centrosomes in a vectorial manner and in a way that resembled microtubule motor-dependant stop-and-start movement, hence, leading to the conclusion that after the breakdown of the NE, microtubules continue their involvement in the disassociation of NE structures by pulling the remaining chromosome-associated fragments in a minus-ended-direction towards the centrosomes, completing the disassembly of the NE. [42]
The Dispersal of Nuclear Envelope Components
Two different methods have been proposed for the dispersal of NE structures, one involves the encapsulation of NE proteins in NE-derived vesicles and the other involves the dispersal of the envelope components into the ER. [58]
Studies on Xenopus eggs and starfish eggs, as well as some mammalian cells, had shown the nuclear membrane to be budding off as vesicles which were released into the cytoplasm. [59] [58] [60] It has been reported that the B-type lamins remained attached to these vesicles while the A-type were dissociated and released into the cytoplasm in some organisms. [61] These vesicles are then recycled for the reassembly of the NE after cell division. [46]
Distribution into the Endoplasmic Reticulum
More recent studies of mammalian cells have shown the ER to remain intact and to be responsible for taking in the disassembled nuclear membranes and their proteins. [62] This is made possible by the previous disassembly of the lamina and the phosphorylation of the inner-membrane proteins and those associated with the chromatin. [43]
As mentioned previously, the outer nuclear membrane of the NE is continuous with the ER. This close association allows the ER to play an important part in the breakdown of the NE. During interphase the ER has a dominant sheet-like layered appearance, and in some eukaryotes, this is dramatically reorganised to form branched tubular networks that will function in the absorption of NE structures. [62]
The fate of nuclear membranes after NE breakdown was examined in a study conducted on cultured mammalian cells using light and electron microscope immunolocalisation. This study specifically tracked the movement of several integral nuclear membrane proteins using immunofluorescence staining, these proteins included LAP1 and LAP2 of the inner nuclear membrane, and the NPC protein gp210. These three nuclear envelope markers are representative of almost all NE membrane proteins and were found to become dispersed throughout the ER after the breakdown of the envelope in prometaphase. It was observed that they remained there until they became recycled to re-form the NEs of the daughter cells in telephase. [58]
Links: Dissociation of lamin filaments | Vesiculation of the nuclear membranes | NPC architecture and nucleoporin localization
Mitotic Functions of Nuclear Envelope Components
As mentioned above there is substantial evidence to suggest that the NE is reabsorbed into the ER [63] which is continuous border with the NE [64]69 70. It has been postulated that the NE proteins are dispersed through the ER during nuclear replication. [65] Using fluorescence time-lapse microscopy in living cells NE and Inner Nuclear Membrane Proteins (INM's) have been found throughout the ER during mitosis [63] [66]. Ultimately the true nature of ER activity in reference to NE breakdown (NEBD) is unknown [2].
What we know more about are the functions of membrane proteins in mitosis. Nucleoporins (NUPS) are involved in the assembly and function of the nuclear pore, [67] other NUPS have a variety of roles in assembly and spindle formation of microtubules [68]. Nuclear lamins have been show to facilitate intermediate filament formation, and it has been indicated that spindle-associated membrane protein 1 (SAMP1) in functionally connected with the cytoskeleton[69]. Unfortunately research has not determined the exact mechanisms for these nuclear membrane proteins, however deficiencies in these products result in irregularity of cellular function and replication. [2]
Reformation of the Nuclear Envelope
In higher cells, the membranes of the NE (which breaks down during prophase) have the remarkable ability to reassemble themselves at the end of mitosis in the two daughter cells. The organization and control of NE re-formation is imperative to proper cell functioning. [70][71] The exact mechanisms involved in NE reconstruction are unappreciatively complex and thus the precise process of NE assembly is not yet fully understood. [72] The majority of studies on NE have been carried out in a cell free extract based on the Xenopus Laevis egg extracts. [73] The process of NE reformation is not the same in different types of eukaryotic cells; in higher eukaryotes open mitosis occurs which is marked by significant alterations to nuclear structural design. [5] The NE reconstruction occurs at the end of mitosis and it is characterised with the immediate build-up of membranes near the chromatin. [70] Studies have shown that this initial process occurs in just minutes, however, the successive growth and stabilisation of the NE tends to take more than an hour. [63]
According to Ulbert et al. (2005), membrane attachment can occur with no energy and the membrane vesicles have a somewhat degree of freedom as to where they attach on the chromatin. Though the de-condensation of the chromatin is crucial before the NE assembly can occur because it is thought that de-condensation allows for the binding sites of the chromatin to be adequately presented to the membrane vesicles. [70] The attraction and thus subsequent attachment of the membrane vesicles to the binding sites relies heavily upon transmemberane proteins and is further assisted by mitotic phosphorylation. [74][75] For example, lamina-associated polypeptide 2β and lamin B receptor (LBR) are two important tansmembrane proteins that have been clearly found in vitro to assist with the binding of the decondensed chromatin. [70] [76] Collase et al. (1996) showed the crucial role of LBR in binding of ER to chromatin. Their experiments on Sea Urchin showed that in order for an ER-derviced vesicle to bind to chromatin during the NE reconstruction (in vitro), it needed the assistance of LBR. [77]
Proposed Models of Nuclear Envelope Reformation
Although many would argue that in open mitosis the majority of the NE is sourced from ER, there is nonetheless, no single mechanism that is unanimously considered to be the correct representation of the processes that occur in NE reassembly. [78] [5]
The first model proposes that the re-organisation of the endoplasmic reticulum, near the end stage of cell division, encapsulates the chromosomes to form the NE in the absence of any assistance from the membrane vesicle fusions. [79] It suggests that the binding of the ER tubules to the de-condensed chromatin surface (with the help of specific proteins), is pursued by the straightening of these membranes against the surface of the chromatin and thus fully surrounding it. The residual 'holes' that subsequently form in the membrane are filled through the inclusion of NPCs. [72] Membrane fusion has little role in this proposed model as its main role if to replenish and repair the ER. Recent study conducted by Andreson et al. (2007) on this particular mechanism of NE reformation propose that proteins of the ER such as reticulon 4a (Rtn4a), are mainly accountable for binding to chromatin [80] . Their studies further predicts that nuclear membrane proteins of the NE are scattered in the ER during cell division in animals.
The second model primarily suggests that reassembly of the NE occurs through the binding of the membrane vesicles, which formed when the NE was breaking down, to chromosome surfaces. This association is thought to come about as a result of interactions between the chromosomes and both lamins and integral membrane proteins of the vesicles. The vesicles then fuse around individual chromosomes creating a double membrane around them and then these in turn fuse together to create a single nucleus. [81] In addition, fusion of the membrane vesicles and ER membranes consequently leads to coating and covering of chromatin to result in the double membrane of the NE. [72]
Reassembly of the NPC during NE reformation
It is argued that a complete closure of the NE cannot take place if the NPCs are not incorporated into the fusing membranes [72] The nucleoporin POM121 is vital to bringing the assembly of the NE with that of the NPCs. The study conducted by Antonin et al. (2005) illustrated that the POM121 is necessary in order for membrane vesicles to fuse during NE re-assembly. [74] Further studies have shown that in addition to POM121, Nup107 complex is mandatory in order for the nuclear pores to be successfully incorporated into the NE during its reformation [74] [82] As reviewed in Prunske and Ullman [72] there is a strong interaction between Nup107 complex and POM121 as they somewhat direct membrane recruitment, membrane fusion and NPC assembly.
The Nuclear Lamina during NE reformation
The Nuclear Lamina is a mesh-like network of fibres on the inner surface of the inner nuclear membrane that has mainly been studied by indirect immunofluorescence and by confocal microscopy. [83] As reviews in Brian et al. (1986) the nuclear lamina is thought to play a pivotal role in nuclear envelope reassembly and that the process is affected by dephosphorylation. Lamins are associated with the re-organisation of the chrmoatins in nuclear envelope reformation reactivities [84] It was illustrated by Gerace and Blobel (1980) [57] that the nuclear lamina breaks apart during the prophase stage. Furthermore, according to Chaudhary and Courvalin (1993) [85] , the polypeptides, lamins A and C were found to be soluble whereas lamin B was associated with mitotic membranes . It was further observed that lamins A, B, and C transform into the nuclear lamina during late mitosis. Lamins continue to enter the nucleus via the nuclear pores. [86]
Links: The breakdown and re-formation of the NE during mitosis | Reformation of the NE from membrane vesicles
Abnormalities in Nuclear Envelope Breakdown and Reformation
In recent years diseases linked to the LMNA gene have come to the forefront of cell biology. These diseases collectively known as laminopathies include; dilated cardiomyopathy with variable muscular dystrophy, mandibulolacral dysplasia and Hutchinson-Gilford progeria syndrome. All of these diseases are linked to mutations or alternate splicing of the LMNA gene (Lamin A) and provide valuable insight to the function of lamins (product of the LMNA gene) and the function of the NE (lamins main target) [87]. As of today no human diseases have been linked to mutations in Lamin B. One study inserted a gene trap into the Lamin B1 gene which lead to mouse death at birth. The mice presented with abnormal tissue in their skeletal muscle as well as poor nuclear morphology. The study concluded the B1 Lamin is crucial in proliferation and embryogenesis [88].
Complications Resulting from Laminopathies
Alterations to the nuclear lamins has been linked to a wide variety of disease [87]. Research compiled by Sullivan et al. 1998 showed that mutations in the LMNA gene lead to skeletal muscle disease inside two months of life. [89]A hypothesis for the mechanism behind this disease is that nuclear lamins (in this case type A lamins) play a role in providing structural support for the nuclear envelope, a defective lamina could lead the cell unable or less able to support its NE [90]. More research suggests that the cytoskeleton could also be affected by mutation of the cytoskeleton, which disrupts inter and intracellular transport[87] .
While mutations in Lamins result in very rare diseases there is research to suggest that the study of these conditions can enlighten us on other diseases and processes of aging [87] . It has been postulated that polymorphic variants of these genes be predispositions to more common conditions like insulin resistance, diabetes mellitus, and metabolic syndrome [91] [92] [93]
Current and Future Research
The NE is an important structure of the cell that is now being profusely investigated by scientists. This is partly due to the lack of knowledge we have on the processes carried out with association with the NE. There is incomplete knowledge regarding the breakdown of the NE. While the scientific community now knows certain aspects of NEBD we have still yet to draw the boundaries of the overall process.
Nuclear rupturing as well as abnormal morphologies of the Nucleus is a well known characteristic of cancer cells. Thus the study of the NE in oncotic cells may offer an explanation or a perspective on the treatment or prevention of cancer. The research article 'Transient nuclear envelope rupturing during interphase in human cancer cells' explores the rupturing of the nuclear envelope in cancer cells using various techniques such as cell culture, siRNA transfection as well as live and confocal imaging and the use of the electron microscope. Cancer cells can be diagnosed by the presence of nuclear envelope invaginations and extrusions. However despite this clinical pattern it is unclear why changes in structure of the nuclear envelope is present in cancer cells. The findings of the paper illustrate that the nuclear lamina, intermediate filaments that provide support to the nuclear envelope, was not properly formed in cancer cells that had ruptured nuclear envelopes. Furthermore it was found that nuclear envelope rupture occurred when there was an entrapment of cytoplasmic in the nuclear interior [94]. As there is a clinical correlation between abnormal nuclear envelope and cancer cells it is important to gain an understanding into the causation of this relationship.
Moreover C.D Capo-chichi and co-workers investigated the expression of NE proteins A/C in ovarian cancer.The investigation uses techniques such as siRNA and immunofluorescence microscopy to look at nuclear morphology in conjunction with flow cytometry to investigate cellular DNA content. The study found that the proteins lamin A/C are absent in 47% of ovarian cancer cells which indicates that there may be an underlying relationship between the absence of these proteins and the occurrence of ovarian cancer. The study concludes that the loss of proteins lamin A/C may lead to a morphological change in the nuclear envelope and that this then leads to the diagnostic characteristics of cancer. [95]
There is a substantial amount of research going into this area as mutations in genes coding for NE proteins have been shown to cause not just cancer but a range of human diseases. As the scientific community lacks the understanding of the processes involved in a normally functioning cell to become abnormal and cancerous this area of research has become prevalent investigation in the scientific community.
A popular direction that future research is interested in is the role vesicles have in the reformation or re-assembly of the NE. The study conducted on the NE assembly by Q.Lu and co-workers discovered that NLS(Nuclear localization sequence) proteins act as docking sites for nucleoporins and NE precursor membrane vesicles through importin-α and -β. [96]. As the mechanisms behind NE breakdown and assembly are not fully understood the research area has significant prospect in future research of the NE.
Cell cycle: a series of events that occur in cells leading up to their division and replication. It's divided into two main parts, Interphase and a Mitotic or M phase. Interphase is further subdivided into three phases including: G1, S and G2. Each phase has different events occurring within them
Cell division: an essential process that occurs in almost all living things. It is characterised by the separation of a cell into two daughter cells. In metazoans, it involves separation of the nucleus and of the cytoplasm
Centromere: Confined portion of a mitotic chromosome where sister chromatids are attached and from which kinetochore fibers extend toward a spindle pole. It is essential for correct chromosome segregation during mitosis
Chromatin:it is made up of histones, non-histone proteins and DNA which condenses to form eukaryotic chromosomes
Chromosome: a single molecule of DNA which is highly organised and tightly packed around proteins (histones)
Chromosomal segregation: process by which chromosomes or chromosome pairs align then separate to opposite ends of the cell
Closed Mitosis: one of the forms of mitosis where the nuclear envelope remains intact during cell division and it occurs in lower eukaryotes
Cytoskeleton: a network of protein filaments and tubules located in the cytoplasm of cells and serves to maintain a cell's shape and internal structure
Depolymerization: process by which a polymer broken up into its component monomers
Disease: A pathological condition of an organism which disrupts the normal bodily functions that often leads to feeling of weakness, and usually associated with symptoms.
Dynein: Minus end-directed motor protein that uses energy in the form of ATP and converts it to mechanical energy for movement. It functions to transport cell cargo along microtubules towards its minus-end. It has an important function in cell division as well
Endoplasmic Reticulum (ER): an organelle of eukaryotic cells that is made up of an interconnected network of membranes and is classified into two types, Rough and Smooth ER. It's located near the nucleus, with part of it being continuous with the nuclear envelope (rough ER)
Eukaryotes: almost all organisms (except viruses and Prokaryotes) are considered to be this. A eukaryote is an organism that is characterised by having one or more cells and a membrane-bound nucleus and organelles
Fluorescence microscopy: a cell biology technique that uses a high intensity light source from a specialised microscope and this excites a fluorescent specimens, resulting in the emission of a lower energy light of longer wavelength that produces a magnified image
G2 stage: this stage of the cell cycle is the third subphase of interphase preceding mitosis. During this phase rapid cell growth and protein synthesis is occurring and the cell prepares for cell division
Hyperphosphorylation: a state that occurs when phosphorylation sites are fully saturated/phosphorylated
Inner nuclear membrane:it is the innermost of the two nuclear membranes. It has binding sites for nuclear lamina and the chromatin on its internal face.
Intermediate filaments: one of the principle elements pf the cytoskeleton of the cell. It has a diameter of ~10nm and function in providing mechanical strength to cells and tissues
Interphase: longest phase of the cell cycle where the cell spends the majority of its time and where it's performing the majority of its functions including gene expression and prepares for cell division
Kinase: an enzyme that catalyzes the transfer of phosphate groups from a donor, such as ATP or ADP, to a specific acceptor molecule
Kinetochore: a protein structure that forms on chromatids and is where the spindle fibers attach during cell division to pull sister chromatids appart
Lamina: a dense network of fibres composed of intermediate filaments made up of lamin proteins and lamin-associated proteins
Lamin A/C is an LMNA protein that is associated with the lamina of the nuclear envelope.
M stage: or Mitotic phase is the stage in the cell cycle where the cell undergoes mitosis and divides into two identical daughter cells
Metaphase: the third stage of mitosis where the chromosomes align in the center of the cell at the metaphase plate ready for segregation and the spindles are fully developed
Metazoans: multicellular animals whose cells are arranged in layers or groups to form specialised tissues or organs. They make up the majority of the animal kingdom
Microtubules: fibrous, hollow rods that function as support structures for the cell shape. Also used to move organelles around and aggregate to form spindles that segregate the chromosomes
Microtubule aster: microtubules arranged in a star array around each centrosome during mitosis
Microtubule organising center (Centrosome): organelle in eukaryotic cells from which microtubules organise themselves into tubular structures which in turn are arranged in a specific pattern
Mitosis: one of the types of cell division where a non-germ cell divides its chromosomes, cytoplasm, membranes and organelles evenly among its two identical daughter cells. This division produces daughter cells that are genetically identical to the parent cell
Mitosis promoting factor: a protein containing Cyclin-dependant Kinase (CDK1) that stimulates the progression into the M phase of the cell cycle by phosphorylating multiple proteins needed during mitosis
Mitotic checkpoint machinery: a complex composed of many proteins that functions to inhibit the anaphase-promoting complex, stopping the advance into anaphase
Monomer: a molecule that is capable of reacting with the same or different types of molecules to form a polymer
Nocodazole: an agent that inhibits the polymerisation and hence the formation of microtubules
Nek: NimA related kinases, a family of kinases involved in cell cycle regulation in eukaryotic cells
Nuclear envelope: A double-layered membrane that envelopes the nucleus of motozoan cells. separating the materials of the nucleus from the cytoplams
Nuclear lamina: it is made up of lamin filaments and it can be found on the inner surface of the INM in eukaryotic cells. It not only provides mechanical support for the cell but also regulates essential cellular events such as cell division
Nuclear Pore Complex (NPC): Very large protein complexes spanning through the outer nuclear and inner nuclear membranes creating gated channels that allow for transport of substances between the cytoplasm and nucleus
Nuclear Pore Complex Basket: A region of the Nuclear Pore Complex which extends into the nucleoplasm.
Nucleoporin: protein building block of nuclear pore complexes
Nucleus: is a relatively big membrane-bounded organelle that is found in eukaryotic cells and contains DNA which are organized into chromosomes. Additionally, the creation and processing of RNA and ribosome assembly occur in the nucleus
Oncotic Cells are cells that undergo oncotic necrosis, programmed cell death.
Open Mitosis: one of the forms of mitosis where the nuclear envelope is completely disassembled and removed from the chromatin. This occurs in the somatic cells of higher eukaryotes
Organelle: a structure that is bound by a membrane and normally found in the cytoplasm of multi-cellular organisms
Outer nuclear membrane: it is the outermost of the two nuclear membranes and it is continuous with the endoplasmic reticulum
Phosphorylation: action of adding a phosphate group to an organic compound
PKC-βII: a Protein Kinase C isoform that controls the function ofother proteins through phosphorylation
Plk-1: Polo-like Kinase 1 is an enzyme involved in phosphorylation of NPCs
Prometaphase: the stage in mitosis following prophase and preceding metaphase where the nuclear envelope breaks down and the microtubules attach to the kinetochores of chromosomes
Prophase: stage in mitosis where the chromatin condenses into chromosomes becoming visible
Protein: is made up of amino acids that are joined together in a specific order to make a polymer of a certain length. Proteins make up the essential structural components in cells and take part in nearly all cellular activities
Plasma membrane: this is the membrane that encapsulates the entire cell and isolates it from the external environment. The plasma membrane is made up of a typical phospholipid bilayer and associated proteins
Rate-limiting step: the slowest step of a pathway or reaction that determines the rate of reaching the desired outcome
Reformation: the act of reforming or the state of being reformed
Ribonuleoprotein:is a nucleoprotein that consist of RNA, that is it is an association that combines ribonucleic acid and protein together
Saccharomyces cerevisiae: a species of yeast
Semi-closed Mitosis: a form of mitosis, occurring in selected higher eukaryotes, where the nuclear envelope only partially dissociates
Spindle fibers: form from aggregates of microtubules and are resposible for separating chromosomes into daughter cells during cell division
Telophase: the final or penultimate stage in cell division where the duplicated genetic material has been segregated into the separating daughter cells and a the nuclear compartment/envelope forms around the genetic material of each daughter cell. Cytokenesis will then split the cells and their cytoplasm.
Transcription: the process by which a DNA sequence is transferred to messenger RNA (mRNA), which is complementary strand of nucleic acids (with only uracil replacing thymine)that will exit the nucleus through the NPCs. This is the first step of gene expression
Translation: the process in which the mRNA is converted to an amino acid chain or polypeptide, through the action of ribosomes, which will later fold to form a protein
Tubulin: a globular protein that is the main component of microtubules in living cells
- ↑ <pubmed>16389459</pubmed>
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 <pubmed>PMC2829960</pubmed>
- ↑ 3.0 3.1 3.2 <pubmed>16212499</pubmed>
- ↑ <pubmed>PMC2223813</pubmed>
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 <pubmed>PMC3501164</pubmed>
- ↑ Evans D, Hutchison C & Bryant J (2004) The Nuclear Envelope, Garland Science/BIOS Scientific Publishers, New York
- ↑ 7.0 7.1 7.2 <pubmed>PMC2713602</pubmed>
- ↑ <pubmed>PMC2829960</pubmed>
- ↑ <pubmed>14786306</pubmed>
- ↑ <pubmed>PMC2079843</pubmed>
- ↑ <pubmed>PMC2223813</pubmed>
- ↑ <pubmed>PMC2107261</pubmed>
- ↑ <pubmed>11879632</pubmed>
- ↑ <pubmed>PMC2289746</pubmed>
- ↑ <pubmed>7894480</pubmed>
- ↑ 16.0 16.1 <pubmed>8907705</pubmed>
- ↑ <pubmed>9547309</pubmed>
- ↑ <pubmed>16222336</pubmed>
- ↑ <pubmed>13130095</pubmed>
- ↑ <pubmed>3501164</pubmed>
- ↑ 21.0 21.1 21.2 <pubmed>22863006</pubmed>
- ↑ <pubmed>9182656 </pubmed>
- ↑ <pubmed>22307332</pubmed>
- ↑ <pubmed>2985606</pubmed>
- ↑ <pubmed>11593002</pubmed>
- ↑ <pubmed>21518795</pubmed>
- ↑ <pubmed>17097643</pubmed>
- ↑ 28.0 28.1 28.2 <pubmed>17097643</pubmed> Cite error: Invalid
<ref>tag; name "PMID17097643" defined multiple times with different content Cite error: Invalid
<ref>tag; name "PMID17097643" defined multiple times with different content
- ↑ <pubmed>19720741</pubmed>
- ↑ <pubmed>19730674</pubmed>
- ↑ <pubmed>11593002</pubmed>
- ↑ <pubmed>2742445</pubmed>
- ↑ 33.0 33.1 <pubmed>19730674</pubmed>
- ↑ <pubmed>3431207</pubmed>
- ↑ <pubmed>19525551</pubmed>
- ↑ <pubmed>7739040</pubmed>
- ↑ 37.0 37.1 37.2 37.3 37.4 <pubmed>PMC2043359</pubmed>
- ↑ 38.0 38.1 38.2 38.3 <pubmed>PMC2829850</pubmed>
- ↑ 39.0 39.1 <pubmed>22064471</pubmed>
- ↑ 40.0 40.1 <pubmed>12473689</pubmed>
- ↑ 41.0 41.1 41.2 <pubmed>11792324</pubmed>
- ↑ 42.0 42.1 42.2 42.3 42.4 42.5 42.6 42.7 42.8 <pubmed>11792323</pubmed>
- ↑ 43.0 43.1 43.2 43.3 43.4 43.5 43.6 <pubmed>19234477</pubmed>
- ↑ 44.0 44.1 44.2 44.3 44.4 <pubmed>9378763</pubmed>
- ↑ <pubmed>PMC3492733</pubmed>
- ↑ 46.0 46.1 46.2 46.3 <pubmed>17467734</pubmed>
- ↑ 47.0 47.1 47.2 <pubmed>21636979</pubmed>
- ↑ 48.0 48.1 48.2 48.3 <pubmed>PMC2265396</pubmed>
- ↑ 49.0 49.1 49.2 <pubmed>21335236</pubmed>
- ↑ <pubmed>7814383</pubmed>
- ↑ 51.0 51.1 <pubmed>PMC2172766</pubmed>
- ↑ <pubmed>11707513</pubmed>
- ↑ <pubmed>3965465</pubmed>
- ↑ <pubmed>2344612</pubmed>
- ↑ <pubmed>9261138</pubmed>
- ↑ 56.0 56.1 56.2 <pubmed>PMC3444782</pubmed>
- ↑ 57.0 57.1 57.2 <pubmed>7357605</pubmed>
- ↑ 58.0 58.1 58.2 <pubmed>9182656</pubmed>
- ↑ <pubmed>9298976</pubmed>
- ↑ <pubmed>423323</pubmed>
- ↑ Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Nucleus during Mitosis. Available from: http://www.ncbi.nlm.nih.gov/books/NBK9890/
- ↑ 62.0 62.1 <pubmed>18056408</pubmed>
- ↑ 63.0 63.1 63.2 <pubmed>PMC2132565</pubmed>
- ↑ Méndez-López I, Worman HJ Inner nuclear membrane proteins: impact on human disease. Chromosoma. 2012 Apr;121(2):153-67 PMID: 2230733
- ↑ <pubmed>PMC30959</pubmed>
- ↑ <pubmed>PMC2099207</pubmed>
- ↑ D'Angelo MA, Anderson DJ, Richard E, Hetzer MW Nuclear pores form de novo from both sides of the nuclear envelope Science. 2006 Apr 21;312(5772):440-3 PMID: 16627745
- ↑ Galy V, Askjaer P, Franz C, López-Iglesias C, Mattaj IW MEL-28, a novel nuclear-envelope and kinetochore protein essential for zygotic nuclear-envelope assembly in C. elegans Curr Biol. 2006 Sep 5;16(17):1748-56 PMID: 16950114
- ↑ <pubmed>PMC1949412</pubmed>
- ↑ 70.0 70.1 70.2 70.3 <pubmed>PMC2063857</pubmed>
- ↑ <pubmed>19416062</pubmed>
- ↑ 72.0 72.1 72.2 72.3 72.4 <pubmed>16364623</pubmed>
- ↑ <pubmed>3058324</pubmed>
- ↑ 74.0 74.1 74.2 <pubmed>15629719</pubmed>
- ↑ <pubmed>1993730</pubmed>
- ↑ <pubmed> 15056654</pubmed>
- ↑ <pubmed>8991085</pubmed>
- ↑ <pubmed> 18187447</pubmed>
- ↑ Prunuske AJ, Ullman KS The nuclear envelope: form and reformation Curr Opin Cell Biol. 2006 Feb;18(1):108-16 PMID: 16364623
- ↑ Anderson DJ, Hetzer MW Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum Nat Cell Biol. 2007 Oct;9(10):1160-6 PMID: 17828249
- ↑ Evans D, Hutchison C & Bryant J (2004) The Nuclear Envelope, Garland Science/BIOS Scientific Publishers, New York
- ↑ <pubmed>12718872</pubmed>
- ↑ <pubmed>8505362</pubmed>
- ↑ <pubmed>3948244</pubmed>
- ↑ PMC2119651</pubmed>
- ↑ <pubmed>3056713</pubmed>
- ↑ 87.0 87.1 87.2 87.3 <pubmed>PMC2828284</pubmed>
- ↑ Vergnes L, Péterfy M, Bergo MO, Young SG, Reue K Lamin B1 is required for mouse development and nuclear integrity Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10428-33 PMID: 15232008
- ↑ <pubmed>PMC2196334</pubmed>
- ↑ <pubmed>PMC1965451</pubmed>
- ↑ Duesing K, Charpentier G, Marre M, Tichet J, Hercberg S, Froguel P, Gibson F Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids Diabetologia 2008 Jan;51(1):76-81 PMID: 17994215
- ↑ Wegner L, Andersen G, Sparsø T, Grarup N, Glümer C, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O Common variation in LMNA increases susceptibility to type 2 diabetes and associates with elevated fasting glycemia and estimates of body fat and height in the general population: studies of 7,495 Danish whites Diabetes. 2007 Mar;56(3):694-8 PMID: 17327437
- ↑ Mesa JL, Loos RJ, Franks PW, Ong KK, Luan J, O'Rahilly S, Wareham NJ, Barroso I Lamin A/C polymorphisms, type 2 diabetes, and the metabolic syndrome: case-control and quantitative trait studies Diabetes. 2007 Mar;56(3):884-9 PMID: 1732746
- ↑ <pubmed>22567193</pubmed>
- ↑ <pubmed>17467691</pubmed>
- ↑ <pubmed>22847741</pubmed>
2013 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7
- Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G


text:
- Fondo
- 1921
This fonds consists of one Moose Jaw Evening Times printing template. The template is page 3 of the August 10, 1921 newspaper.
Moose Jaw Evening Times
This fonds consists of one Moose Jaw Evening Times printing template. The template is page 3 of the August 10, 1921 newspaper.
Moose Jaw Evening Times
Moose Jaw Council of Women fonds
The first accession consists of constitutions of the various levels of the Council's of Women, minutes, financial records, annual reports, lists of local women's organizations and scrapbooks containing photographs and press clippings. Annual Meeti...
Moose Jaw Council of Women
This fonds is composed of three series. Included is a mission statement, rules and regulations for medical staff, an invitation to a Nursing School graduation and a program from a fund-raising event. There is material related to the building ser...
Providence Hospital
Wilson MacDonald Poetry Society fonds
This fonds contains five series published articles, poems, original letters of the poet, various event programmes and a minute book from the Wilson MacDonald Poetry Society.
MacDonald, Wilson Pugsley
This fonds contains materials pertaining to the training and graduation of Elizabeth Burns from the Moose Jaw Training School for Nurses. Such materials include a diploma, a Moose Jaw General Hospital Alumnae Association certificate, a case contai...
Burns, Elizabeth
This fonds contains two journals and a scrapbook kept by John Walker from 1925 to 1967. They all portray Mr. Walker's enjoyment of bird watching as well as his involvement in the Saskatchewan Natural History Society. Also included are newslet...
Walker, John
Moose Jaw General Hospital fonds
The fonds consists of material pertaining to the administration and history of the Moose Jaw General Hospital. Such material includes photocopied meeting minutes of the Moose Jaw Hospital Board, correspondences, reports, and meeting minutes of the...
Moose Jaw General Hospital
Several original copies of the newspaper have been transferred to the Moose Jaw Public Library newspaper holdings. The balance consists of some copies, reprints and loose items that accompanied the papers.
Moosejaw News
This fonds consists of 20 issues of "Normal Echoes", the official newsletter of the students' assembly of the Moose Jaw Normal School, published between 1928 and 1931. The inaugural issue of February 17, 1928 is included. The set i...
Moose Jaw Normal School
Moose Jaw Wild Animal Park fonds
This fonds consists of minutes, correspondence, leases, permits and materials relating to the history of the Moose Jaw Wild Animal Park.
Moose Jaw Wild Animal Park


text:
Evan Oberg Signs One-Year Extension with Bolts
TAMPA BAY – The Tampa Bay Lightning have re-signed defenseman Evan Oberg to a one-year, two-way contract, vice president and general manager Steve Yzerman announced today. That leaves just goaltenders Anders Lindback and Jaroslav Janus as the team's only remaining unsigned restricted free agents. Recently acquired forward Benoit Pouliot also remains unsigned, but was not qualified by the team and now has unrestricted free agent status. Pouliot is expected to sign with the Lightning amid multiple reports from team and agent indicating that deal would be done.
Oberg, 24, played in three games with the Lightning last season, recording a plus-2 rating. He was acquired by the Lightning with Mike Kostka from the Florida Panthers on December 2 in exchange for James Wright and Mike Vernace. He made his Lightning debut on January 24 against the Columbus Blue Jackets. Oberg has skated in seven career NHL games with the Vancouver Canucks and Lightning.
The 6-foot, 191-pound defenseman also played in 54 games this past season in the American Hockey League with the Norfolk Admirals and San Antonio Rampage. The Forestburg, Alberta native skated in 42 games with the Admirals, recording seven goals and 23 points to go along with a plus-15 rating. Oberg played in 12 games with the Rampage, posting two assists and 14 penalty minutes. He also appeared in 18 Calder Cup playoff games with Norfolk, notching two goals and 10 points, helping them to their first Calder Cup Championship. Oberg ranked tied for fourth on the Admirals in assists with eight during the playoffs.
Oberg has played in 167 career AHL games with Norfolk, San Antonio, the Rochester Americans and the Manitoba Moose, collecting 17 goals and 64 points, to go along with 138 penalty minutes. He has also skated in 23 career Calder Cup playoff games, collecting three goals and 12 points.
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text:
West Yorkshire Advanced Motorcyclists (WYAM's) are a friendly and very active club with membership currently standing at over 150 strong. Our passion covers all things motorcycle related, with many of our people possessing a wealth of knowledge that is freely shared across the group - all in the name of increasing your motorcycling enjoyment.
Bikers wishing to join us do so through IAM RoadSmart's 'Advanced Rider' programme. This gives them Associate status for one year, during which they are expected to train and take the Advanced Motorcycling Test. Once passed, this entitles them to full IAM Roadsmart membership for life, providing annual subs to IAM Roadsmart central and the chosen local club are maintained.
One of IAM RoadSmart's key goals is to help its Members and Associates develop the advanced skills that help make riding a more enjoyable and rewarding experience.
Being an advanced rider is a journey of continuous learning, and one of its key stages is the internationally recognised Advanced Test. Pioneered by the IAM Roadsmart, it is this for which we are perhaps best known.
We are a sociable club holding regular rides and social events.


text:
I recently bought an Adaptec 39320 SCSI card from ebay so I could connect a tape drive to my VMware ESXi server. What arrived was a Dell-branded 39320 (model ASC-39320/DELL), which I didn't think would be a problem (famous last words…). I installed the card, and the Adaptec BIOS picked up the tape drive during boot as expected. However, ESXi refused to recognise the card or the tape drive, even after multiple reboots and re-scans of the storage devices. A quick google search gave me the answer straight away – I needed to disable HostRAID on the SCSI card in order to put the 39320 in "plain old SCSI mode". No problems – or so I thought…
When I went into the SCSI BIOS, the option to disable HostRAID was missing! It turns out that Dell removed the option to disable HostRAID on this card with their OEM firmware – meaning it would never work with ESXi After a bit of googling I found a forum post (in German) that described how to re-flash the Dell card to turn it back into a regular Adaptec 39320 card. Some kind soul on the forum provided me with the files I needed, and it worked
I went back and took some pictures so I can describe the process and also provide the files needed. You will need a floppy disc; you can either use this image file to automatically make a bootable floppy using WinImage, or if you already have a bootable floppy you can just download the files you need and put them on the floppy.
The first step is to boot your machine from the floppy disc, and the SCSI utility should start automatically:
The next step is to back up the SEEPROM (in case this process doesn't work):
Now we need to reboot the computer so that the new SEEPROM takes effect. Boot from the floppy disc again, and it's time to update the BIOS:
NB: I take no responsibility for the success or failure of this process. It worked for me (and many others), but your mileage may vary If you took a backup of the files as directed, you should be able to recover your card, but I make no promises as I'm not an Adaptec engineer!Exit the utility and you now have a "vanilla" Adaptec 39320 SCSI card Exit the SCSI utility, remove the floppy disc and reboot – your card should now appear as an Adaptec 39320! You can now disable HostRAID by pressing CTRL-A and then:


text:
MONTPELIER, Vt. (AP) — When the Vermont Health CO-OP was launched 15 months ago, it was hailed as a consumer-governed alternative to the commercial insurance that would be offered under the new marketplace being set up under the federal health overhaul.
But as Blue Cross Blue Shield of Vermont and MVP Health Care prepare to begin offering coverage through the marketplace, the CO-OP remains in limbo, hoping for two green lights from state and federal agencies that are key to its survival.
It likely won't even hit the Oct. 1 date that companies offering coverage through the Patient Protection and Affordable Care Act (PPACA) public exchange system were supposed to be ready to begin signing up subscribers, CO-OP CEO Christine Oliver said Monday.
"We won't hit that. We won't hit it for Oct. 1," she said.
And as for the beginning of next year, when the coverage is to become effective: "January's probably not likely, either," she said of the CO-OP, which stands for "consumer operated and oriented plan."
The CO-OP needs the state Department of Financial Regulation to reverse a decision that denied the CO-OP a state license. The agency said its rates were too high to be competitive and criticized a governance structure it said created conflicts of interest.
Since then, the CO-OP has lowered its rates, retooled its governance and submitted a request for reconsideration to the state agency. The state agency could not comment about a pending application, spokeswoman Dale Schaft said Monday.
Meanwhile, Oliver said she expects to hear by the end of the month what the Centers for Medicare & Medicaid Services (CMS) planned to do about a nearly $34 million loan agreement announced at the CO-OP's founding last summer.
A CMS spokeswoman said Monday the agency had stopped payments after disbursing $4.8 million of the $6.3 million the CO-OP was to get in startup financing, and had done the same after disbursing $9.8 million of a projected $27.5 million in what's known as solvency financing.
The latter category was to create a fund of the type that insurance companies dip into when extraordinary claims create a cash flow problem by exceeding money coming in through premiums.
Both Oliver and CMS spokeswoman Tasha Bradley said they could not provide details of the talks between the federal agency and the CO-OP.
Bradley said in an email that CMS takes steps to guard against waste, fraud and abuse. "One of the most important is that startup loans are disbursed incrementally and after the CO-OP reaches agreed-upon milestones. Licensure is a significant milestone."
Oliver said a decision by CMS to end the loan agreement and demand repayment of the money disbursed so far would kill the CO-OP's chances for survival.
"Nobody here is starting an insurance company with the money in their pockets," Oliver said.
But she said she still believed the CO-OP can satisfy the state and federal agencies that it can be viable. "We remain hopeful. We're still plugging along here."
See also:


text:
Blind Item #5
Despite all the eyes watching her, this A list tweener/singer hasn't stopped using coke in public places. She is going to crash hard from the lofty position she got herself to this year. Her show is at a tipping point right now. A coke bust will see the show go bye and a long time before she gets another.


text: Optometrist Optometrists are important to everyone because they are the first line of defense one has against deteriorating eye conditions. Albuquerque optometrist specialize in helping consumers understand how they can correct fading eyesight and other common afflictions of the eye through the use of eye glasses, contact lenses, and other nonmedical corrective devices. Stop by your local optometrist to receive a comprehensive eye exam.


text:
"Ex-Slave of Page Wants to Hear of People Long Dead"
From the Sept. 21, 1928 issue of the PN&C
Mary Powell of Columbus, Ohio, an aged colored woman who seems to have belonged to the Almonds of this county in slave times, some time ago wrote a letter addressed to 'The Old Baptist Church and David Almond, Luray, Va.' in which she made inquiry of the people she knew in her younger days spent in Page. In our Aug. 31 issue reference was made to this old woman in an article dealing with the old ex-slaves of the county, who are still living. That article based on information given by John P. Washington, colored, said that Mary Powell left here about 1867, and lived for years with a family at Wheeling, W.Va. who made provision for her support in an institution for the aged in Ohio, Washington's report that she is 109 years old is not sustained in the letter which is reproduced below:
This letter makes inquiry of people who without an exception have passed away , some of them fifty years ago. It well shows how the minds of the old dwell in the past. The letter was doubtless written for the old woman by some one else.
Columbus, Ohio, Nov. 29, 1928
Mr. Almond: – I felt like I wanted to write to you to know who all is living. Is Tommy and Ida living and is their mother living? Is Mrs. Bell Borst living? Is her husband living? Is Mrs. Betty Ashby living? Is Dr. Almond living. Are any of the Lionbergers and Jordans living? Any of the Buracker family?
I am putting all of the old pastors of the church down by name. I want you to know that I have not forgotten all of the old pastors. There was Ambrose Booton, Is preacher Lauck living?
The 18th of last May I was 96 years old, and the only letter I had was from this church. Give my best regards to anyone I ever knew. I expect to die in the Lord. If any of the boys are living tell them to send me something for Christmas.
Mary Powell
Henry Powell's widow
1240 E. Long St.
Columbus, O.


text:
Talacker 358001 Zürich
Auf der Karte anzeigen
Vorndran Mannheims Capital (formerly known as Ventizz Capital Partners) was formed in 2000 and has offices in St. Gallen, Zurich, Dusseldorf, and Vienna. The company exclusively advises private equity funds which invest in buy-out transactions and high-growth opportunities in small and medium-sized high-tech companies in the german-speaking region. VMCap has 5 partners: Dr. Helmut Vorndran, Willi Mannheims, Dr. Björn Söndgerath, Nico Helling and Andreas Marty. Together with a team of 16 professionals they currently advise four funds with capital totalling EUR 675 million. To date, VMCap has invested in 50 companies focusing on renewable energy, medical technology, information and communication technology and on other branches of industry offering high value-added. In addition to a large number of trade sales, VMCap has successfully placed four of its participating interests (Ersol, SAF, PV Crystalox Solar, exceet Group) on stock.
Hilf anderen Stellensuchenden und sei der Erste, der diese Firma bewertet.


text:
19-21 Milner Rd Artarmon Sydney
Quiet, but so close to everything. Sleeps 9 people. Milner Gardens is a quality accommodation offering guests a spacious self-contained air conditioned Townhouse for the price of a hotel or motel room. The Townhouse accommodates comfortably up to 9 people
10 Sandridge Street, Bondi Beach Sydney
Exclusive designer beachside apartments, located next to world famous Bondi Beach. Nightly rates vary from $269 to $699 depending on length of stay and day of week. Minimum 3 nights stay on Friday and Saturday nights. Stunning interiors with crisp whit
59 Obrien Street Bondi Beach Sydney
Ultimate Apartments Bondi Beach is a brand new (completed in October 2005) Bondi Beach property, offering executive quality apartment accommodation, at the best price on the beach.
150 Liverpool Street Sydney
For 4 people. Sleek, stylish & ultra chic. Spacious, funky designer 2 bedroom apartments, fully fitted out. Fantastic discounts on weekly stays. Nightly rates from $249 to $699 depending on the length of stay and day of week. Minimum 7 nights stay over
1 Hosking Place, Sydney Sydney
Medina Classic Martin Place is ideally located in the heart of Sydney's vibrant CBD and shopping precinct, only one block north of Martin Place (off Castlereagh Street).
167 Willoughby Road, Crows Nest Sydney
Ideally located in the midst of the business district of the Lower North Shore. These apartments surround a central courtyard & entertaining area featuring a swimming pool & BBQ area.
74-80 Ivy Streets, Chippendale Sydney
Featuring 41 spacious and modern one, two and three bedroom apartments and studio rooms, with all apartments offering fully equipped kitchens, laundries and lounge/dining areas.
359 Crown Street, Surry Hills Sydney
Situated just 2km from the CBD, Adina on Crown offers spacious 1 & 2 bedroom apartments. Lifestyle facilities include pool, spa, gym and leafy BBQ area while the well known cafes & restaurants of Crown Street are within easy walking distance.
Encuentre guías y servicios para cada país en expatfinder.com para facilitar su expatriación.


text:
|We Live Together
Click here to visit site
|Short review: Sexy damsels seduce girls back to their flat to party. WeLiveTogether.com is a internet site for boys who love watching sensual fillies enjoying the chick on chick sessions. Women can live their lesbian or acey-deucey female fancies as they watch other sweet chics licking crotch or playing with diverse playthings. Clit arousal is doubtlessly a winner when it comes to raunchy young ladies picking up lassies to party with.


text:
As mentioned briefly on the site a couple of weeks ago, Element Skateboards are bringing their "Make It Count" contest series back to the UK at the end of the month, for a day long competition that's open for literally everybody to enter. Taking place in the familiar surroundings of Central Skatepark, Manchester on Saturday February 25th, entry to the park is set to be free all day. With the categories consisting of 13 and under, 14 to 16, 17 and older, and sponsored, and the comps following the tried and tested Best Trick format on a variety of ramps across the park, there's no reason for you to not get involved!
In addition to a mountain of gear to be won from Element and Dakine, the national overall contest winner will win a trip to the European finals in Madrid, where they will be competing for a trip to the world finals at the Element YMCA camp in June.
See the poster below for more info, and hit up the Element site for further details and whatnot.


text:
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Full Bloom is an effective odor neutralizer but without a heavy fragrance. It's ideal for use in homes, offices, meeting halls and more. Its dual odor counteractant system quickly neutralizes odors.
Because it leaves no residue, it's versatile enough to use virtually anywhere. Try it in any room of the house and on fabric, drapes, bedspreads, carpet, closets, lockers, chests, shoes, luggage, showers, and garbage cans.


text:
Do you need to find the perfect footwear or apparel gift for a friend, family member or co-worker? Well, Footlocker.com just made your decision a lot easier. A Footlocker.com e-Gift Card guarantees that they'll get exactly what they want. Footlocker.com has over 20,000 products online and everything is in stock and ready to go!
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text:
Syracuse stops Herd
One miscue was all Syracuse needed on Wednesday night.
A third-inning Bisons' error helped the Chiefs plate two of their three runs in a 3-1 victory over the Herd from Coca-Cola Field. The defeat, their 11th of the season to Syracuse, snapped Buffalo's three-game win streak.
The error turned into two unearned runs for southpaw Mark Cohoon, who pitched well but fell in defeat.
With the game scoreless, Bisons second baseman Luis Hernandez threw wide of the base while attempting to turn a doubleplay. Instead of two out, there were two on for the Chiefs and both baserunners came around to score.
The Bisons lone run was scored in the sixth inning as Jesus Feliciano pulled a home run down the right field line. The blast was the veteran's 370th hit of his Bisons career, tying him with Greg Tubbs for second most in the modern era (Bill Selby, 378).
Maybe the most intriguing play of the night occurred two batters after Feliciano's home run. Catcher Raul Chavez smoked a liner off the glove of shortstop Seth Bynum. Bynum retrieved the ball, but threw wild to first base. As the ball rolled to the Bisons dugout, home plate umpire John Conrad ruled that pitching coach Ricky Bones interfered with the play. Although he was credited with a base hit, Chavez was ruled out.
The Chiefs bullpen made the lead stand up. Josh Wilkie, the fifth of five Syracuse relievers, pitched the ninth inning for his 15th save of the season.
Cohoon allowed just won earned run in 6.1 innings of work but suffered the loss.
Buffalo wraps up the home portion of the 2011 schedule on Thursday night with Fan Appreciation Night at 6:05 p.m. against the Chiefs.
BISONS NOTES: Just prior to the game, the Bisons activated outfielder Mike Baxter and placed infielder Zach Lutz on the disabled list…After going hitless in back-to-back games for the first time as a Bison, Josh Satin went 2-4 with a double…The Bisons need a win on Thursday to finish the season with an even 36-36 record at Coca-Cola Field.