text:
Page 1
published: 25 March 2013
doi: 10.3389/fnagi.2013.00014
Biometals in rare neurodegenerative disorders of
Sarah J. Parker1, Jari Koistinaho1, Anthony R. White2and Katja M. Kanninen1,2*
1Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
2Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
Edited by:
Peter Crouch, University
of Melbourne, Australia
Reviewed by:
Paula I. Moreira, University
of Coimbra, Portugal
Junming Wang, University of
Mississippi Medical Center, USA
Katja M. Kanninen, Department of
Neurobiology, A.I. Virtanen Institute
for Molecular Sciences,
University of Eastern Finland,
Yliopistonranta 1, 70211 Kuopio,
e-mail: email@example.com
Copper, iron, and zinc are just three of the main biometals critical for correct functioning of
the central nervous system (CNS). They have diverse roles in many functional processes
including but not limited to enzyme catalysis, protein stabilization, and energy production.
The range of metal concentrations within the body is tightly regulated and when the
balance is perturbed, debilitating effects ensue. Homeostasis of brain biometals is mainly
controlled by various metal transporters and metal sequestering proteins. The biological
roles of biometals are vastly reviewed in the literature with a large focus on the connection
to neurological conditions associated with ageing. Biometals are also implicated in a
variety of debilitating inherited childhood disorders, some of which arise soon following
birth or as the child progresses into early adulthood. This review acts to highlight what we
know about biometals in childhood neurological disorders such as Wilson's disease (WD),
Menkes disease(MD), neuronal ceroid lipofuscinoses(NCLs), and neurodegeneration with
brain iron accumulation (NBIA). Also discussed are some of the animal models available
to determine the pathological mechanisms in these childhood disorders, which we hope
will aid in our understanding of the role of biometals in disease and in attaining possible
therapeutics in the future.
Keywords: metals, neurodegeneration, childhood, copper, iron, zinc
The significance of biometals for the correct functioning of the
human brain has long been discovered. The importance of met-
als such as iron, zinc, and copper results from the numerous roles
that they have, such as stabilization of proteins and transcription
factors, acting as co-factors for metallochaperones for cellular
transport and their role in enzyme catalysis (Markossian and
Kurganov, 2003; Butterworth, 2010). Deviations of metal home-
ostasis have been linked to neurodegenerative disorders such as
Alzheimer's disease (AD), Parkinson's disease, Amyotrophic lat-
eral sclerosis, and Huntington's disease (HD) (Dexter et al., 1993;
Deibel et al., 1996; Jomova et al., 2010; Skjorringe et al., 2012). A
risk factor in the development of many of these disorders appears
to be an increase in age. Although the pathological characteristics
of the disease are in most cases well-understood, the exact causes
are often unknown.
Neurodegeneration is not restricted to an ageing popula-
tion. Several debilitating neurodegenerative disorders affecting
children have been identified. These include neurodegeneration
with brain iron accumulation (NBIA), ATPase pathologies such
as Wilson's/Menkes disease and neuronal ceroid lipofuscinoses
(NCLs). These disorders share several pathological features with
more common neurodegenerative diseases, including protein
aggregation and oxidative stress. Aberrant biometal homeostasis
has also been identified in children suffering from these diseases
(Table 1). What is not clear is whether the distinct changes in
metal levels cause neurodegeneration or occur as a result of the
neurodegeneration. In some cases, the pathology associated with
childhood disorders is clearly evident and often fatal at an early
age. Changes in metal levels have also been identified in children
with Autism spectrum disorder (ASD) which affects the behav-
ior of children more so than hinder them physically. Dissecting
the roles that biometals haveinthese disordersis fundamental for
finding potential therapeutics to reduce or inhibit neuropatho-
logicalchanges associated withaltered metal homeostasis (Yasuda
et al., 2011).
Since biometal homeostasis plays a major role in neurodegen-
erativedisease,theaimofthisreviewistohighlighttheeffects that
metals have on the developing brain. Multiple childhood disor-
ders arise from defects in the concentrations of metals within the
corrected or prevented to avoidor ameliorate disease. Whilemost
of the childhood disorders are inherited and disease progression
canoccurnotlongafterbirth,itiscriticalto determinethemolec-
ular disease characteristics and metal alterations within the brain
and other tissues for the development of therapeutic treatments
to provide these children with a chance at life.
Wilson's disease (WD) is an autosomal recessive disease affecting
coppermetabolism (Bearnand Kunkel, 1954). Copper is involved
in neurotransmitter synthesis, cellular respiration, scavenging of
toxic free-radicals, and has an important role in maintaining
homeostasis of other trace elements such as iron (Butterworth,
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Parker et al. Biometals in childhood neurodegeneration
Table 1 | Biometal alterations in childhood disorders.
Wilson's disease
Menkes disease
Neuronal ceroid
At least 10 genes
Copper ↑
Copper ↓
Zinc, manganese, copper,
iron, cobalt, sodium ↑
Potassium, magnesium ↓
Iron ↑
disorders with iron
At least 7 genes
2010). However, in abundance, copper is toxic and thus strict
regulation of levels is critical. Free copper ions are virtually non-
existent in human blood (Linder and Hazegh-Azam, 1996) and
are usually bound to a multitude of proteins and chaperones
for transport around the body. WD presents in patients typically
between the ages of 6–20 years, and has an estimated incidence of
1 in 30,000 (Reilly et al., 1993).
The defective gene involved in WD is ATPase Cu(2+)
transporting beta polypeptide (ATP7B), which encodes for a
membrane bound copper-transporting ATPase protein primarily
located within the liver cells, as part of the trans golgi network
(Cox and Moore, 2002). To date, approximately 300 mutations
within ATP7B have been associated with WD (Merle et al.,
2010). Normal copper metabolism involves the transfer of cop-
per molecules to ceruloplasmin for transport into the plasma so
it can circulate to other tissues or when in excess, to the bile for
excretion (Terada et al., 1998, 1999). ATP7B is involved in trans-
porting the copper molecules to ceruloplasmin. When ATP7B is
non-functional, copper accumulates to toxic levels and severely
damages the liver. The liver therefore releases copper directly
into the bloodstream where copper continues to cause damage
to other tissues, in particular the CNS. In the brain, accumula-
tion of copper is most evident in the basal ganglia, the region
whichco-ordinates movement (DeLongetal.,1984), making WD
primarily a movement disorder. This neuropathology caused by
the build up of copper leads to patients suffering tremors of the
arms or hands, unpredictable movement, difficulty with speak-
ing, swallowing, and walking as well as confusion, dementia,
and various psychological problems (Rosencrantz and Schilsky,
2011). Some cognitive deficits have also been noted (Middleton
and Strick, 2000), and could arise due to disruptions of projec-
tions of the basal ganglia to the prefrontal cortex (Bolam et al.,
2000). Gliosis is also observed in the brains of patients suffering
from WD (Anzil et al., 1974). The mechanism for neurologi-
cal damage caused by excess copper is still not fully understood.
However, it is known that copper is involved in the produc-
tion toxic free radicals (Samuele et al., 2005), and excess copper
has been shown to inhibit Inhibitor of apoptosis proteins (IAPs)
caused by toxic deposits of intracellular copper (Mufti et al.,
WD is a progressive disorder and was ultimately a fatal dis-
ease until the discovery of the first treatment in 1951 (Denny-
Brown and Porter, 1951). With the copper-chelating agent,
dimercaptopropanol, the disease is now treatable (Denny-Brown
and Porter, 1951). The most common treatment to date is the use
of zinc salts, which block enteral copper absorption in the stom-
ach. Various drugs are currently available for WD and ongoing
compliance with treatment is necessary.
The Long Evans Cinnamon (LEC) rat is one model used for
in vivo studies of WD. Since showing symptoms of liver failure in
1987 (Yoshida et al., 1987), the rats were first used as a model for
liver cancer and hepatitis. Upon further characterization, accu-
mulation of hepatic copper and decreased ceruloplasmin activity
were found. Years later when the gene responsible for WD was
discovered, the rathomolog atp7bwas foundto bemutated in the
LEC rats, with a significant deletion at the 3?end of the gene (Wu
et al., 1994). Although there are similarities in liver pathogenesis
between the LEC rat and humans, this rodent model shows min-
imal evidence of neuropathology (Terada and Sugiyama, 1999).
In contrast to the LEC rat model, ATP7B knockout mice exhibit
both neuro- and liver pathology. In these mice, copper levels are
dramatically low at birth with a gradual increase by 2 months
of age, where hepatic copper levels are approximately 50times
higher compared to wild-type controls (Buiakova et al., 1999).
Another interesting model for WDis thetoxic milk mouse, which
also has an autosomal recessive inheritance (Theophilos et al.,
1996). Female mice with the tx milk mutation produce copper-
deficient milk, which is fatal to their pups. The tx mice have a
single nucleotide change in the ATP7B gene, and studies have
shown this to cause changes in the ATP7B localization in the
mammary gland, therefore leading to impaired copper trans-
port and little to no copper given to the pups. The tx mothers
retain this copper in the liver (Rauch, 1983; Michalczyk et al.,
Both the LEC rat and tx milk mouse models arose from
spontaneous mutations. There is only one genetically engineered
mouse model for WD, the ATP7b−/−mouse, which was gener-
ated by Buiakova et al. (1999). ATP7b−/−mice are born copper-
deficient and display neurological symptoms such as tremors
and abnormal locomotor behavior. If nursed by a homozygous
ATP7b−/−mother, the pups will die at around 2 weeks of age.
However, if nursed by a heterozygous mother, copper concentra-
tions begin to rise to toxic levels in the liver by the age of 6 weeks,
irrespective of initial birth concentration. Similar to human dis-
ease, these mice accumulate copper in the liver due to impaired
export of copper into the bile, making these mice an invaluable
model for the study of WD (Lutsenko, 2008).
Menkes disease (MD) is an inherited disease related to copper
metabolism, but in contrast to WD, it is characterized by a sig-
nificant reduction in normal copper levels in the blood, liver,
and brain (Danks et al., 1973). Disease progression is also more
rapid than in WD (de Bie et al., 2007). The reduction of cop-
per is due to decreased absorption of copper from the intestine
and therefore reduced transfer to copper-requiring proteins and
enzymes (Danks, 1988). Symptoms present within the first year
of life, generally within 3 months of birth and without treatment,
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Parker et al.Biometals in childhood neurodegeneration
death is likely before the third year of life. MD is a rare childhood
disease with an estimated worldwide incidence of 1 in 300,000
(Tonnesen et al., 1991), but can be higher in certain countries
suchas Australia(1 in50,000 to 1in 100,000)(Tumer andMoller,
MD has an X-linked mode of inheritance and is more preva-
lent in males than females (Kodama and Murata, 1999). At birth,
babies appear normal, although premature labor has been docu-
mented (Uriu-Adams et al., 2010). An early sign in a baby with
MD is the presence of sparse and abnormal hair, which looks
fragile and twisted and appears to have a "kink" in it (Kaler,
2011). MD is thus also referred to as "Kinky Hair Syndrome."
The baby begins to exhibit normal cognitive behavior with smil-
ing and normal childhood dialogue; however, these behaviors do
not progress further. Babies do not exhibit increases in muscle
tone and over time generally become weaker and spasticity of
the limbs is observed. Toward the end of the babies' short life,
they succumb to blindness and respiratory failure and premature
death is often due to infection or the extreme neuronal degen-
eration observed. A less-severe form of MD is called occipital
horn syndrome (OHS) which is also an X-linked recessive inher-
ited disorder with mutations in ATP7A. These patients exhibit
fewer neurologicabnormalitiesandhavealongerlifespan(Tumer
and Moller, 2010). Connective tissue abnormalities tend to be
the focus of this disorder with calcification of the occipital bulb,
leading to horn-like structures at the base of the brain.
This detrimental disease is caused by a mutation in the gene
encoding the Copper transporting ATPase-1 (ATP7A) protein
(Fatemi and Sarkar, 2002), which is also a "P-type" ATPase
protein similar to ATP7B. To date, there are over 200 known
mutations scattered throughout the gene (His and Cox, 2004).
Although both ATP7A and ATP7B are involved in the transport
of copperto secreted enzymes and metalloproteins, ATP7A is also
involved in the absorption of intestinal copper and can trans-
port copper to all cell types and vital structural enzymes (Barry
et al., 2011). ATP7B is predominantly involved in the exit of cop-
per from hepatocytes. These differences in protein function are
demonstrated by the fact that MD patients exhibit a variable
range of symptoms throughout the body as opposed to mainly
liver damage seen in patients with WD. The neurological dam-
age caused by mutant ATP7A is due to the decreased activity
of the copper-dependent enzymes. Decreased cytochrome c oxi-
dase leads to a reduction in ATP production by the mitochondria
and causes apoptotic cell death (Borm et al., 2004). Dopamine-
β-hydroxylase is necessary for neurotransmitter synthesis and its
activity is decreased in response to low copper levels (Kaler et al.,
1995). Superoxide dismutase 1 (SOD1) is a free-radical scavenger
the activity of which has been linked to several neurodegenera-
tive disorders, particularly ALS. Copper is a co-factor imperative
for SOD1 activity. Levels of SOD1 are decreased in MD patients,
contributing to lower protection against toxic oxidative species
within the brain (Kaler, 1994). Collectively, the reduced activity
of copper-dependentenzymes is thought to beresponsible for the
observed neurological damage in MD.
The cellular location of ATP7A is sensitive to the concentra-
tion of copper; when copper levels are low ATP7A remains on the
membrane of the Golgi but when levels are increased, ATP7A is
located to the plasma membrane where it can "pump" copper to
other proteins and cuproenzymes (Hasan et al., 2012). In MD,
where copper levels are low, it is essentially located to the Golgi
and there is a deficiency of copper transport to essential enzymes,
and other tissues.
The therapeutic benefit of injection of copper histidine as a
copper replacement to humans has provided mixed results and is
dependent on the mutation within the ATP7A gene (Kaler et al.,
1995; Christodoulou et al., 1998). Some studies have shown that
early administration ofcopper to babies canprevent the observed
neurological decline but this is likely to be in patients with muta-
tions in ATP7A that still allow for some transfer of copper to
copper-requiring enzymes, but not severe mutations affecting
initial absorption from the intestine (Tumer et al., 1996).
Spontaneous mutations in the mouse homolog of ATP7A, atp7a,
have been used for modeling defective ATP7A in humans (Kuo
et al., 1997). These mice are called mottled mice and different
mutations in the atp7agenecausedifferent neurological andcon-
nective tissue anomalies. The two mottled mice mutations mot-
tled brindled (Mobr) and mottled macular (Moml) show severe
reductions in copper within the liver (Hunt and Clarke, 1983),
and die within 1–3 weeks of birth (Lenartowicz et al., 2012). This
prematuredeathcanbeprevented withinjected copperwithinthe
first week of birth, as well as transgenic over expression of atp7a
(Danks, 1986).
The NCLs are a group of fatal autosomally-inherited neurode-
generative diseases occurring in childhood. The NCLs are also
classified as lysosomal storage disorders since one of the main
pathological characteristics is the accumulation of autofluores-
cent granules which contain lipids and proteins (lipopigments)
in the lysosomes. Currently at least ten forms of NCLs have
been described. Each form is distinguished by different defec-
tive genes (CLNs) and the age of onset (Cooper, 2003; Mitchison
et al., 2004). Collectively, it is the most common neurodegen-
erative disorder of childhood with an estimated incidence of
up to 1:12,500 (Rider and Rider, 1999). Although mutations in
different genes cause different forms of the disease, all NCLs
share common clinical symptoms; progressive loss of vision lead-
ing to blindness, motor and mental retardation, seizures, and
finally premature death (Siintola et al., 2006). The exact func-
tion of these genes is still unknown (Tyynela et al., 2004).
These genes encode soluble proteins and membrane-bound pro-
teins, for example, CLN6 is a transmembrane protein which
is localized to the endoplasmic reticulum (Heine et al., 2004).
Children with defective CLN6 present with symptoms at the
age of 3–5 years and tend to only live until 8–12 years of age.
Currently there is no cure for any form of NCL (Sharp et al.,
In NCLs, early reports have described some changes to metal
levels, includingironandzinc,inbloodcells ofpatients withNCL
(Johansson et al., 1990). In a larger study of NCL patients, no
associationbetween "looselybound"ironorcopperlevelsincere-
brospinal fluid could be found (Heiskala et al., 1988). There is
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Parker et al.Biometals in childhood neurodegeneration
some evidence that altered metal homeostasis may also occur in
other NCL models. A recent study reported changes in expres-
sion of the metal transporter, ZnT6, in both CLN3 and CLN6
mouse cerebellar neuron precursor cell lines (Cao et al., 2011).
Furthermore, reduction in expression of the gene causing CLN7
NCL disease was observed in the brains of mice fed a high-iron
diet (Johnstone and Milward, 2010), suggestive of a heightened
sensitivity of NCL brains to fluxes in metal concentrations.
Recently, alinkbetweenbrainbiometalhomeostasisandCLN6
diseasewasdiscovered.Sheep harboringanaturalmutationinthe
CLN6 gene show significant increases in manganese and more
so, zinc levels in all brain regions except the cerebellum and
brain stem (Kanninen et al., 2013). In the CLN6 sheep model,
the accumulation of biometals was evident at the symptomatic
age of 12–14 months. Early studies on the metal contents of
lipopigments from CLN6 sheep revealed no obvious association
between metal contents and disease progression (Palmer et al.,
1988). Metal contents were variable between lipopigments from
different tissues in line with the normal role of lysosomes as
storage depots for metals, indicating the lysosomal origin of the
lipopigments. Changes in the metal contents of retina and retinal
pigment epithelial cells of CLN6 sheep have been reported, and
an association with lipopigment accumulation and altered man-
ganese levels with increasing photoreceptor cell loss suggested
(Jolly et al., 1989).
ANIMAL MODELS OF NCLs
To understand the pathogenesis of NCLs, gene-specific mutant
mice have been engineered which contain mutations in Cln1,
Cln2, Cln3, Cln5, Cln7, and Cln10 genes (Cooper et al., 2006).
Naturally occurring mutations in Cln6 and Cln8 have also been
identified (Lonka et al., 2000; Gao et al., 2002). Many of these
mousemodels sharephenotypic featuresincommonwithhuman
patients such as neurological and motor deficits, seizures and
neuronal loss, and as such, are valuable tools to study dis-
ease mechanisms and potential therapeutic approaches. Like
the human form, the mouse models display variance in tim-
ing and sequence of events toward disease progression, high-
lighting the genetic differences between the NCLs (Cooper
et al., 2006). As the function of the majority of these genes
is still unknown, using these animal models will prove invalu-
able in elucidating the function and mechanism behind NCL
pathologies. The naturally occurring mutation in the CLN6
gene of sheep mentioned above share a similar disease pro-
gression and phenotypic features similar to that of the human
CLN6 NCL form (Jolly et al., 1989; Kay et al., 2011), mak-
ing them an excellent model of NCL disease due to their
complex CNS. However, with large animal models it may be
challenging to obtain sufficient numbers of animals for assess-
ment due to difficulties in breeding and housing such large
As with copper and zinc mentioned above, levels of iron within
the brain need to be tightly regulated. Iron homeostasis is
regulated by proteins involved in absorption, transport, influx,
and storage in tissues (Zhang and Enns, 2009). Increases in brain
ironlevelsaretypicallyassociatedwithageingandis highlypreva-
lent in AD and HD. Neurodegenerative disorders with brain
iron accumulation (NBIA) refers to a wide group of disorders
affecting children, withsimilar outcomes:neurodegenerationand
the accumulation of iron. The disease is caused by mutations
in seven genes (Ke and Ming Qian, 2003). At birth, brain iron
is not present, but levels rapidly increase until 20 years of age
with an uneven distribution over time (Zorzi et al., 2012). The
most recognized gene defects are mutations in pantothenate
kinase (PANK2), which is an enzyme located within the mito-
chondria and regulates the formation of Coenzyme A, which is
essential for deriving cellular energy via the tricarboxylic acid
cycle (Leoni et al., 2012). PANK2 phosphorylates pantothen-
ate and requires N-pantothenoyl-cysteine and pantetheine. The
exact mechanism how mutations in PANK2 lead to iron accu-
mulation is not fully understood, but one hypothesis is that if
cysteine cannot be utilized within the cell by PANK2, it accu-
mulates over time. Cysteine can bind iron, and over time this
may explain the observed accumulation of iron (Gregory and
Hayflick, 2005). Although the mutation in PANK2 directly does
not cause neurodegeneration, it is the increased iron which con-
tributes to the production of toxic and tissue-damaging reactive
oxygen species (Ke and Ming Qian, 2003). Increases in iron have
also been linked to several neurological disorders such as AD
and PD (Batista-Nascimento et al., 2012). There are over 100
mutations in this gene and PANK2 disorders account for over
half of all NBIA cases (Gregory and Hayflick, 2005). PANK2-
specific NBIA, referred to as pantothenate kinase-associated neu-
rodegeneration (PKAN) was formally called Hallervorden–Spatz
syndrome before the name was changed to divert any associ-
ation with the unethical euthanization of mentally ill patients
during World War II by Dr. Hallervorden (Dooling et al., 1974).
PKAN disease is autosomally inherited and presents in child-
hood as either the classical, early onset or atypical, late onset
form (Hayflick et al., 2003). The extent of iron accumula-
tion can be easily visualized and quantified using magnetic
resonance imaging (MRI). The pattern exhibited by MRI-T2
weighted images shows the increased iron as "darkened spots"
and provides a novel "eye of the tiger" image, making MRI an
important diagnostic tool for NBIA (Schenck and Zimmerman,
The symptoms of classical PKAN disease become apparent
within the first 10 years of life, with symptoms usually start-
ing between 3 and 4 years of age. Affected children begin to
have difficulty with walking and other movements, which is
attributed to the build up of iron in the basal ganglia (Gregory
and Hayflick, 2005), a region of the brain highly important in
movement. Rigidity, spasticity, and speech difficulties soon fol-
low (Dooling et al., 1974). Children become wheelchair bound
within only a few years of diagnosis. Atypical PKAN disease
begins later in life, with an average age of onset of 13–14
years and disease progression unfolds slowly over many years
(Chan et al., 2008). Patients present firstly with behavioral prob-
lems such as depression and personality changes with move-
ment and speech impediments following later. The symptoms
of atypical PKAN can be highly variable from case to case.
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Parker et al. Biometals in childhood neurodegeneration
Treatment for NBIA had been aimed at symptoms rather than
the genetic defect causing the iron build up and severe neurode-
generation. Drugs aimed at reducing abnormal movement are
widely prescribed, but to date, there is no preventative for NBIA
disorders. Recently, reducing the accumulation of iron has been
the target for treatment using iron-chelators, however this is met
with varying efficacy (McNeill and Chinnery, 2011). Deferiprone
is anironchelator which actsto redistributeironwithinthebrain,
by donating built-up iron to transferrin for transport elsewhere
(Brittenham, 1992).Thepromisingfeatureofthisdrugistheabil-
ity to cross the blood-brain barrier, necessary for targeting the
build up of iron in CNS. However, no conclusive results can be
drawn from these clinical studies due to the small number of
patients trialed (Forni et al., 2008; Zorzi et al., 2011).
Unlike the other childhood disorders discussed in this review,
PKAN-NBIA does not have a suitable murine model of disease.
A PANK2 knockout mouse was generated which showed retinal
degeneration and growth retardation, but no defects on move-
ment and gait were evident (Kuo et al., 2005; Brunetti et al.,
2012). However, Drosophila melanogaster have been a powerful
tool for understanding the biochemical basis of PANK2 muta-
tions. Mutations in the homolog of PANK, fumble (fbl) exhibited
a shortened lifespan, progressive locomotion defect, and degen-
erations in both central nervous system and retina (Gregory and
Hayflick, 2005). Interestingly, mutations in PANK2 in both the
Drosophila and mouse led to male sterility (Wu et al., 2009).
The importance of metals in neurological disease has been out-
lined in numerous reviews over many decades, however, the exact
mechanisms leading to aberrant metal homeostasis and why this
is so detrimental to the brain remain poorly understood. While
the brain is still developing during childhood, it is highly sus-
ceptible to slight changes in metal levels as outlined above with
discussion of various childhood neurodegenerative disorders.
Although certain therapeutics exist for some of these disorders,
they mainly target disease symptoms and prolong the disease,
rather than being preventative. It is the work forthcoming from
in vitro, animal and clinical studies, which aim to add insight into
theroleofmetalchangesandconsequencessopotential therapeu-
tics canbetested and hopefullyonedayappliedto preventdisease
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Cox, D., and Moore, S. (2002). Copper
and human disease. J. Bioenerg.
Biomembr. 34, 333–338.
Danks, D. (1986). Of mice and men,
metals and mutations. J. Med.
Genet.23, 99–106.
Danks, D. (1988). Copper deficiency
in humans. Annu. Rev. Nutr. 8,
Danks, D., Cartwright, E., Stevens, B.,
and Townley, R. (1973). Menkes'
of the defect in copper transport.
Science 179, 1140–1142.
de Bie, P., Muller, P., Wijmenga, C., and
Klomp, L. (2007). Molecular patho-
genesis of wilson and menkes dis-
ease: correlation of mutations with
molecular defects and disease phe-
notypes. J. Med. Genet.44, 673–688.
P-type ATPases
Markesbery, W. (1996). Copper,
iron,and zinc
severely degenerated brain regions
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DeLong, M.,
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R. (1984). Role of basal ganglia in
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Frontiers in Aging Neurosciencewww.frontiersin.org
March 2013 | Volume 5 | Article 14 | 5


text: Happily Ever After Wedding Tea Towel by Old English Company £9.95$21.56€14.72$16.36 5 customer reviews(5) In stock £3.45$7.47€5.10$5.67 delivery to United States Receive this item 5-10 working days from dispatch International delivery available add wedding cardadd wedding cardAdd wedding card (+ £2.50)No wedding cardadd wedding cardAdd wedding card (+ $5.41)No wedding cardadd wedding cardAdd wedding card (+ €3.69)No wedding cardadd wedding cardAdd wedding card (+ $4.11)No wedding card quantity by Old English Company Location: Lincolnshire, GB read seller's profile see seller's complete range more items from this seller London Map Tea Towel £9.95$21.56€14.72$16.36 new 'Pina To My Colada' Print £14$30.33€20.71$23.03 'Call Dad' Card £2.50$5.41€3.69$4.11 Floral Wedding Invite £2$4.33€2.95$3.29 Things We Love About Print £14$30.33€20.71$23.03 'Happily Ever After' Wedding Print £14$30.33€20.71$23.03 view all you may also like PRODUCT DETAILS CUSTOMER REVIEWS DELIVERY RETURNS Made in Britain exclusive eco-friendly ask seller a question save for later A bold and romantic kitchen wedding tea towel, it makes a unique gift for any wedding day. A charming kitchen wedding tea towel which has been hand drawn with the lovely quote 'and they lived happily ever after'. Designed to make you smile and perfect for any home or kitchen. This kitchen tea towel would make a fantastic thoughtful and unique wedding gift for any newlywed couple, the tea towel would even make a great gift for your partner on your anniversary. Complete the perfect wedding gift with the option to add a beautiful wedding card to your order at a reduced price. Dimensions are 15x15cm, made from recycled card and comes with its own kraft envelope. made from: This wedding print tea towel is made in Britain using bright white 100% cotton which makes it super absorbent. The kitchen tea towel design has been screen printed on in black using high quality ink. The tea towel comes with hanging loop and wash care label. This kitchen tea towel is machine washable. dimensions: Hemmed on the two long sides they measure approximately 78cm x 48cm (30in x 19in). product code: 256009 5 customer reviews Wed 16 Sep 2015 Arrived promptly. Wed 09 Sep 2015 Anniversary gift for my brother, really nice item Tue 06 May 2014 No comment supplied. Sun 03 Nov 2013 No comment supplied. Thu 29 Aug 2013 Lovely product, great to buy something a little different/thoughtful to add to the standard John Lewis wedding gift list present but without going completely off the gift list! see all customer reviews hide some customer reviews read about our product rating system ratings guide trusted independent customer feedbackforum excellent bad good poor This product is dispatched to you by Old English Company. MAINLAND UK order now and receive this item by price Standard Delivery Tuesday 20 October £0.95$2.05€1.40$1.56 Tracked Next Day Delivery Thursday 15 October £5.90$12.78€8.73$9.70 NON-MAINLAND UK estimated delivery price Highlands & Islands of Scotland 2-5 working daysfrom dispatch £0.95$2.05€1.40$1.56 Northern Ireland 2-5 working daysfrom dispatch £0.95$2.05€1.40$1.56 Other UK Islands 2-5 working daysfrom dispatch £0.95$2.05€1.40$1.56 INTERNATIONAL DELIVERY estimated delivery price Western Europe 2-5 working daysfrom dispatch £2.75$5.95€4.06$4.52 Rest of Europe 5-10 working daysfrom dispatch £2.75$5.95€4.06$4.52 USA & Canada 5-10 working daysfrom dispatch £3.45$7.47€5.10$5.67 Asia & Australasia 5-10 working daysfrom dispatch £3.45$7.47€5.10$5.67 Rest of the world 5-14 working daysfrom dispatch £3.45$7.47€5.10$5.67 You have 28 days, from receipt of cancellable goods, to notify the seller if you wish to cancel your order or exchange an item. Please note: goods that are personalised, bespoke or made-to-order to your specific requirements, perishable products and personal items sold with a hygiene seal (cosmetics, underwear) in instances where the seal is broken are non-refundable, unless faulty. Read more about our returns policy.Should you choose to return or exchange your order you will need to deliver the item(s) to the UK, where this seller is based. Old English Company's return policy

subset: commoncrawl


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October 4th the 1st Grade Outdoor Classroom Event was held at Johnson's Farm near Keokuk. Click here to see highlights of the day!!
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The Latest from Highlands
All the newest blog posts from the Highlands community of writers can be found right here. We hope they are a help to you as you seek to live faithfully.
The Cure for Ingratitude
What We Need My in-laws have just completed the long and painful renovation of their home in anticipation of selling it and moving closer to their nine grandchildren in Bristol, Virginia. In doing so they were in constant communication with their realtor who was advising them on paint colors and features that she knew her buyers were looking for. Of course, the whims of buyers are constantly changing but not as much as since the advent of HGTV. Home and Garden television (mostly home) is the cable channel dedicated to inflaming the lusts of each and every American woman. Features. . .
Read more »
Grab a 6-Pack of Movies When You Join the Club Today!
JOIN the CLUB Now & Bring Home a 6-Pack of Movies! LIMITED TIME—October 8-19 When you join the YOU GET EVERYTHING Club you get every resource we produce while you are a member! Join by October 19 and you also get a 6-pack of movies produced by Colin Gunn! Colin's excellent documentary films challenge our thinking on important cultural issues: HEALTHCARE EDUCATION MEDIA & TECHNOLOGY ROLES of MEN & WOMEN HOMOSEXUALITY Part of living the good life is being able to recognize the bad when we see it. Our culture is deeply confused in many areas. Gunn explores the nuts. . .
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Getting Rest
One of the hardest things for a mother to do is get enough rest. Kara & Steve talk about the necessity of rest & some practical ways to make sure you are (or your wife is) getting enough.
We are Making History
Experiencing Old Culture Having just recently returned from a trip to Europe I am finding that everything they say about international jet-lag is true. Well, maybe it's not just getting used to the time adjustment as much as all those croissants. Yes, the food was great, the coffee was excellent, but the big takeaway was the history of buildings, cemeteries, streets, and statues. Any American is immediately aware of the fact that they are visiting in the Old World having traveled from the New. You are surrounded by manifestations of older culture. Here is where the "Melting Pot" of American. . .
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Racer by Pacoma
So I'm really into The Amazing Race and I understand it has various versions in different nations.
What scent would you take with you across the globe that might fit into many cultures, situations and time of day?
sent via commodore 64
*explore your world on a bicycle*
Racer by Pacoma
Something light, that everyone likes, that wouldn't kill people when I start to sweat like a race horse.
Expect the unexpected.
I'd bring along Terre d'Hermes - it would go well with the dirt, & versatile enough to fit various occasions.
Probably none, it would be one of the few occasions when I wouldn't wear any frag
Creed Aventus, seems appropriate.
The hunt for a Signature Fragrance is not an easy one! I see the light at the end of the tunnel! Edit: 2015... I've given up and given in
Want to buy or swap: A*men Ultra Zest, Bentley Intense, Mont Blanc Legend Intense, Paco Rabanne Invictus,
Nothing too strong for sitting on an airplane with strangers next to you...Acqua di Parma Colonia would probably work.
Polo Explorer?
***My SALE thread***My TRADE thread***
Frag addicted? Join the support group We are too but dam we smell good!
L'Artisan Navegar
"Embrace those things which give you pleasure, after all, there is so much mediocrity to endure elsewhere." -- Inselaffe
Thanks for your input, I like the play on words of the scents' name.
sent via commodore 64
*explore your world on a bicycle*


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|Gate Prices
|Child (3-12)
Recently voted #4 Amusement Park in the World, and #1 Amusement Park in California by TripAdvisor
Celebrate the 50th Anniversary of the world-famous Studio Tour and go behind the scenes to explore real film sets where Hollywood movies are made.
Face action head-on in heart-pounding rides, shows and attractions that put you inside some of the world's most popular TV shows and movies – including Despicable Me Minion Mayhem. And now, hold on tight for the Studio Tour's all-new grand finale, Fast & Furious–Supercharged – an exhilarating high-speed chase that catapults you into the high-stakes underworld of fast cars and international crime cartels.
Comments about Smart Destinations Universal Studios Hollywood:
Best place to go with kids with disabilities!My son is autistic and the staff where so kind ALL THE TIME!
[4 of 4 customers found this review helpful]
Comments about Smart Destinations Universal Studios Hollywood:
the long walk down Citywalk should be able to be avoided; but the studio made up for it. We didn't go on the tour but I heard good things about it. The Tranformers and Mummy rides were amazing. Transformers was probably the most intense 3D I've ever seen. Mummy ride had some cheesy effects but the ride was pretty intense too. Jurassic Park was way too short but the end was worth it.
[0 of 1 customers found this review helpful]
Comments about Smart Destinations Universal Studios Hollywood:
Beautiful park with lot of exciting attractions


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Say I have a
DetailsView with a bunch of fields, and I want only certain kinds of users to edit a few of them. They're too few to split them into another
DetailsView, so what I'm thinking is to find some way to only allow a user to edit them based on some code-behind logic, effectively making them read-only at will.
I feel it's important to mention that the fields are both
TemplateFields, not normal
BoundFields with
ReadOnly properties.
Any ideas? For some reason the required functions don't jump at me from reading the documentation.
Oh and I need eveyone to see their specific values, I just want to restrict edit access to them.


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March 25, 2008
Youngsters dominate Rivals.com AA Teams
Andrew Skwara
Rivals.com College Basketball
The youth movement continues to grow stronger in college basketball.
For the second consecutive season, a freshman � this time, Kansas State's Michael Beasley � was selected Rivals.com's National Player of the Year. Kevin Durant ran away with the honor last season. Beasley edged out North Carolina's Tyler Hansbrough this time.
Beasley is third in the nation in scoring and became just the third freshmen ever to lead the nation in rebounding while leading Kansas State to its first win in the NCAA Tournament in two decades.
Hansbrough and Mississippi State second-teamer Jamont Gordon are the only two returnees from Rivals.com's 2006-07 All-America teams.
The Pac-10 leads the way with four selections this season, followed by the Big 12 and SEC with three apiece. The ACC, Big East and Big Ten each had one selection.
Eight of the selections are playing for teams that have advanced to the Sweet 16 in the NCAA Tournament. All 15 were on teams that made the NCAA field.
Talk about it in The Main Board
Football Recruiting News
Jones sure of one official visit
BC grabs Texas receiver
Crawford back from Oregon
IMG Day 1: Top performers defense
Rivals.com is your source for: College Football | Football Recruiting | College Basketball | Basketball Recruiting | College Baseball | High School | College Merchandise
Site-specific editorial/photos �2012 Yahoo! Inc. All rights reserved. This website is an officially and independently operated source of news and information not affiliated with any school or team.
About | Advertise with Us | Contact | Privacy Policy | About our Ads | Terms of Service | Copyright/IP policy | Yahoo! Sports - NBC Sports Network
Statistical information �2007 STATS LLC All Rights Reserved.


text:
Centre for Astrophysics Research (CAR)
- Find out more
- People
- Projects
- Publications
CAR carries out research on a broad range of key science questions in astronomy.
Our research programmes mainly feature observational astronomy, and span the electromagnetic spectrum from X-rays to radio wavelengths. We study many sizescales, ranging from the properties of dust grains, up through stars and exoplanets through to entire galaxies and clusters of galaxies in the near- and high-redshift Universe. Survey astronomy is a particular strength. Our computing facilities also permit extensive in-house computer modelling and simulation, and we have a track record of instrument development for astronomical polarimetry.
A number of projects are jointly supported by CAR and the Centre for Atmospheric and Instrumentation Research (CAIR), based on their shared strengths in light scattering and instrumentation.
Extragalactic astronomy
We carry out research in galaxy and structure formation over all cosmic epochs....Read more about extragalactic astronomy
Galactic astronomy
We study the formation and evolution of stars and sub-stellar objects....Read more about galactic astronomy
UH is a leader in survey astronomy, particularly at optical, near-infrared and submillimetre wavelengths....Read more about surveys
CAR Facilities
CAR is actively involved in new observatory instruments and facilities....Read more about car facilities
UH astronomers benefit from excellent local computing facilities....Read more about computing
We are world-leading in the design and construction of polarimeters....Read more about instrumentation


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Discovery Teams: Summary
Hall, Monena
Mathews, Brian
MetadataShow full item record
In February 2012 Brian Mathews, Associate Dean for Learning and Outreach, put together a proposal to boost the Library's research and development efforts and gather insight into students' potential desires concerning upcoming renovations. He put out a call to the library and library partners across campus to participate in Discovery Teams that would observe and talk with students "in the act of scholarship." Throughout March and April of 2012, teams of faculty and staff from across the University walked around Newman Library and the Blacksburg campus to engage with students.
- Newman Renovations [12]
- Research Presentations, University Libraries [90]
- Hall, Monena [6]
- Mathews, Brian [13]


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Hard Candy Sheer Envy Primer
381 reviews
66% would repurchase
Package Quality: 4.1
Price: $$
Package Quality: 4.1
Price: $$
INGREDIENTSCyclopentasiloxane, Dimethicone, Dimethicone Crosspolymer, Synthetic Fluorphlogopite, Silica Dimethicone/Vinyl Dimethicon Crosspolymer, Dimethiconol, 1,2-Hexanediol, Caprylyl Glycol, Mica, Titanium Dioxide,dkl
on 12/3/2011 8:16:00 PM
Age: 19-24
Skin: Combination, Medium, Not Sure
Hair: Brown, Wavy, Medium
Eyes: Brown
Works really well, feels nice and smooth when you apply it. make sure you dont put too much on your face, a little pea-sized amount should do. Its also extremely affordable.
on 12/1/2011 5:51:00 PM
Age: 30-35
Skin: Normal, Fair, Cool
Hair: Brown, Wavy, Medium
Eyes: Blue
I have used this primer for a few months now but didn't realize how addicted I've become to it until I forgot to put it on a few times in the past couple of weeks. I have noticed that without it my foundation seems to stick to my skin and doesn't want to smooth out and cover evenly. The first couple of times I didn't realize until after I was done with my makeup routine that I had left the primer out...and then it made sense. So a couple of days ago when my foundation was 'sticking' to where I originally put it, I realized I hadn't used the primer and I considered whether to keep going or retreat....so I took one of my kids' wet wipes that we keep in the bathroom and started again from scratch...it makes that much difference with applying foundation!
This primer does separate a bit every so often...the first time I wondered who had let water into my container...but it's happened maybe a half dozen times since then and I now know just to give it a quick up/down before using it and no worries. I have never used any other type of primer so I can't compare, but I am definitely converted to using primer under my foundation! And I love the silky smooth indulgent feel of putting it on in the mornings!
I usually smooth a bit of Aveeno (or the off-brand version) on my skin since I tend toward dryer skin, then maybe 30 seconds later (after brushing my hair) I put on the primer, and then maybe 30 seconds later (after taking my allergy meds) I put on foundation and get the ball really rolling. Not inconvenient at all, and worth the effort and $6 I spent at Walmart for it (and I expect to get at least 6 months worth out of it, if not quite a bit more...I only use a pea-sized amount each time and it spreads beautifully!)
on 11/25/2011 8:13:00 PM
Age: 18 & Under
Skin: Dry, Fair, Not Sure
Hair: Brown, Other, Other
Eyes: Blue
Leaves a silky feel, and makes my makeup go on so smooth. However, it separates a little, so sometimes it needs to be shaken. It makes my skin soft, and for $8, I will repurchase!
on 11/19/2011 8:15:00 PM
Age: 18 & Under
Skin: Combination, Fair-Medium, Not Sure
Hair: Brown, Other, Other
Eyes: Green
I like it. Sometimes it needs a good shake though.
on 11/8/2011 2:06:00 AM
Age: 25-29
Skin: Combination, Fair, Neutral
Hair: Brunette, Wavy, Fine
Eyes: Brown
After hearing many "YouTube" gurus rave about this primer I made the purchase. The consistency reminded me of Smashbox Photo finish primer very silky and nice but almost immediately (2 days) my face broke out. I did notice that it helped "smooth" my fine lines and acne scars but it only lasted about an hour or so. After that, I just looked greasy! A few weeks after my purchase I noticed the consistency turned from silky to oily. The formula changed and separated...really gross. If I didn't shake the bottle before using it the product was white and oily. Will not purchase again!
on 10/31/2011 12:46:00 PM
Age: 19-24
Skin: Combination, Fair, Cool
Hair: Blond, Straight, Fine
Eyes: Blue
The first primer I tried was the L'Oreal Magic Base primer. It lead me to believe that primers were a waste of money, as it did almost nothing. I picked this up at Wal-Mart after hearing some good things, thinking maybe I should take another shot at primers, and I'm glad I did. My face stays oil free longer, it smooths my skin out, and does help a little with foundation application. My make up also looks fresh for longer than it would without this, and it lasts longer as well.
When I'm out and about running around in the heat, Hard Candy's Sheer Envy Primer+ Revlon Colorstay in Oily/Combo looks flawless for about four hours, when I have to powder, and then everything looks fabulous again. I've worn this combination for about thirteen hours before and my face still looks fantastic. Much better then the results I've gotten without the primer.
on 10/30/2011 2:19:00 AM
Age: 18 & Under
Skin: Oily, Fair-Medium, Neutral
Hair: Black, Wavy, Other
Eyes: Brown
cute packaging. i got this in a kit along with a bronzer, lipgloss, and a face and body illuminator, all for $8. this primer is smoothening and really makes the pores on my nose area disappear! love it! :)
on 10/11/2011 5:02:00 PM
Age: 19-24
Skin: Oily, Fair-Medium, Neutral
Hair: Brunette, Wavy, Medium
Eyes: Hazel
I'm on my 2nd tube of this. I haven't tried many primers but this is the only one I have repurchase. The texture is...weird. Its hard to describe, but you get a lot of product for cheap! $8 for 1.6 oz. Does a good job at controlling my oily skin and it fills in my pores. It leaves my skin silky and smooth, it helps my foundation goes on smoother and last all day. I dont think its the best, but for the price, its phenomenal and I recommended it to all my friends and family. I feel it would be great for any skin type. Definitely worth a try!
Oh! I recommend shaking it before you use it and a little goes a long way!
on 10/11/2011 4:42:00 PM
Age: 25-29
Skin: Acne-prone, Fair, Cool
Hair: Red, Straight, Fine
Eyes: Blue
i've owned this for a while, and though i don't feel the need to use it everyday, i still love it! it makes my face so soft and smooth and evens out the texture. i use it mostly on special occasions or when i really need to make my makeup stay on. i am a product junkie so i have a few other that i use, including a trial size of Benefit (which of course is far more costly to buy in full size), and i think i like the hard candy better. the Benefit tends to be really liquid-y and doesn't make my face as soft. also, avon makes a decent one as well.
on 9/20/2011 2:23:00 AM
Age: 18 & Under
Skin: Combination, Olive, Warm
Hair: Brunette, Other, Other
Eyes: Brown
I used this product for months and LOVED it, for the most part it kept me matte and my make up looking fresh with no breakouts. The tube i bought lasted for months. The reason I no longer use this product is because I use the Monistat chaffing gel now.
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Hard Candy Sheery Envy Primer Review by AtomicNony


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Reach tens of thousands of people instantly by advertising with Ekklesia. Find out more
The head of Ethiopia's Lutheran church has welcomed government efforts to curb a spate of attacks on Christians in the country.
Yesterday the BBC made what the Independent newspaper called "a comprehensive and humiliating apology" for unfounded allegations made eight months ago that millions of pounds of Band Aid and Live Aid money intended for victims of the Ethiopian famine was diverted into arms sales.
The leader of the Ethiopian Evangelical Church, Makane Yesus. has welcomed the leadership role of the WCC within the wider ecumenical community.
The General Secretary of the WCC has had separate meetings with the partriarch of the Ethiopian Orthodox Tewahedo Church and with the country's president.
An eyewitness humanitarian worker has refuted allegations that aid agency funds were misused in Tigray during the 1984-5 Ethiopian famine.
UK-based international development agency Christian Aid has criticised claims about aid for the 1984 Ethiopian famine being diverted by rebels to buy weapons.
International aid agency Oxfam has warned of dire consequences from the drought that has hit parts of East Africa for the sixth year in a row. Its comments come after the failure of both rainy seasons in 2009.
Big change is required, but it can start in small but significant ways. That was the message that development agency World Vision issued for World Environment Day 2009, highlighting one project that symobolises part of the way forward.
March 22 is the UN's World Water Day, so I wanted to mention a remarkable book by a good friend of Ekklesia (and an Ekklesia Partner) Annette Allen, which she is using to help raise funds for clean wa


text:
Opens Friday, Oct 16, 2015
A Brooklyn lawyer finds himself thrust into the center of the Cold War when the CIA sends him to negotiate the release of a captured American pilot.
Movie Details Play Trailers
Young author Edith Cushing discovers that her charming new husband is not who he appears to be.
A young kid teams up with the niece of young adult horror author R.L. Stine after the writer's imaginary demons are set free on the town of Greendale, Maryland.
Opens Friday, Oct 23, 2015
Chef Adam Jones (Bradley Cooper) had it all – and lost it.
Strange events plague a family in their new home.
The last witch hunter (Vin Diesel) is all that stands between humanity and the combined forces of the most horrifying witches in history.
A small-town girl catapults from underground video sensation to global superstar.
A has-been rock manager from Van Nuys, California stumbles upon a once-in-a-lifetime voice in a remote Afghan cave in Rock the Kasbah, a dramatic comedy inspired by stranger-than-fiction, real-life events and directed by Oscar winner Barry Levinson.
Opens Friday, Oct 30, 2015
A Bolivian presidential candidate failing badly in the polls enlists the firepower of an elite American management team, led by the deeply damaged but still brilliant strategist "Calamity" Jane Bodine.
Three scouts, on the eve of their last camp-out, discover the true meaning of friendship when they attempt to save their town from a zombie outbreak.
Opens Friday, Nov 6, 2015
A cryptic message from Bond's past sends him on a trail to uncover a sinister organisation.


text:
Ford Repair in Ronkonkoma
Our master mechanics identify the best Ford repair shops in Ronkonkoma. Edit search×
- Early Bird Dropoff
- Service Guarantee
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- Early Bird Dropoff
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- Open Saturday
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- Muffler & Exhaust
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- Scheduled Maintenance
- Service & Repair
- Timing Belts
- Tire Sales/Repair
Real Customer Review(s)
At Goodyear Auto Service Centers, our certified car care professionals can provide everything from basic oil changes to major engine repairs. With convenient locations and a range of expertise, your vehicle will get the quality service it deserves. Schedule an appointment online for services such as:
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- 29-Point General Inspection
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Welcome to Stevens Ford! Located in Patchogue, NY, Stevens Ford is proud to be one of the premier dealers_twohips in the area. From the moment you walk into our showroom, you'll know our commitment to Customer Service is second to none. We strive to make your experience with Stevens Ford a good one for the life of your vehicle. Whether you need to Purchase, Finance, or Service a New or Pre-Owned Ford, you've come to the right place.
There are 55 Ford service shops and mechanics in Ronkonkoma. Edit searchSee other Ford repair shops and dealerships
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The shops listed below are not committed to the fair price guarantee and minimum warranty of RepairPal Certified shops. When taking your car to a shop that has not passed RepairPal's inspection, we recommend that you:
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Ford repair shops and dealerships near Ronkonkoma.
"My wife's car broke down and I had it towed here. I found Imran and his mechanics to be competent and efficient. They..."
"My family has been going to City Tire in Centereach since they opened in 1976. Steve and john run a very professional..."
" Had a vibration going on in my Dodge, went on a few forums and thru discussions there it was decided it was drive..."
"I purchased a vehicle at this establishment. They were to do a NYS Inspection, put two new tires on, install a new b..."
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Octopus www.crimson.spreadshirt.com
This great custom product in white from our department Women and T-Shirt category can be printed just for you in the size and style you like. The design Octopus was created by TATTOO23 and uploaded to Spreadshirt for you to have printed on a T-Shirt. Next to a host of other great customized designs, you can find this Octopus design in Spreadshirt's Marine Life category. If you are interested in topics like Marine Life or Tshirt, then you'll love Octopus designs by TATTOO23. Spreadshirt also offers a huge selection of custom t-shirts, hoodies and accessories for the category Marine Life as well as top art clothing. TATTOO23's designs have already impressed many of our customers, so we are sure that we've got right stuff for you! Spreadshirt is your destination for great designs of all kinds – whether it's Marine Life, Tshirt or art. We are sure that you will find something nice in our shop, there are many amazing custom Marine Life t-shirts, hoodies, or accessories for you to find! Tags: Design ID: 10717625
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Village Life Section :: Page 44
Drilling effects on groundwater questioned
Despite a yearlong campaign by Yellow Springs and Miami Township residents and environmental activists urging that area landowners not lease their land for oil and gas drilling, three residents northwest of the village in Miami Township have signed lease agreements.
Glen trails get makeover
When spring comes and Glen Helen fills up with hikers, they may notice that the nature preserve is easier to traverse, with new stairs, boardwalks and rails along its most-traveled trail.
Yellow Springs history in spotlight
Robin Heise, a graduate student in public history at Wright State, will give a talk this Sunday at 2 p.m. at the Senior Center on her research on local historical buildings.
Cultivating global green thumbs
For many, yard work can be a chore. For Nadia Malarkey, the care and cultivation of her backyard labyrinth of trees, vines and plants is perennially a joy. At their best, gardens can be places of respite, connection and, above all, environmental stewardship.
Local kale for the K–12 crowd? Lessons in fresh food service
Three years into the Columbus-area school's local food initiative, its cafeteria regularly serves up healthy meals prepared on-site using raw, organic ingredients, about 40 percent of which are sourced from within 125 miles of the school.
Lucky local wins Senior Center raffle
Local resident Alicia Erfe won the 2004 Toyota Siena mini-van in the Yellow Springs Senior Center raffle last week.
At winter market, greens in the gray
The Yellow Springs Winter Farmers Marketlaunched its third season last Saturday, Jan. 7, in the basement of the First Methodist Church.
New Liberty raises local food IQ
Seven-year-old Sampson is one lucky goat, according to his caretaker, Abby Dant of Xenia. Sampson was the demonstration goat at a workshop last weekend at the United Methodist Church, the first of six winter food and farming events organized by New Liberty Farms.
A therapy dog in need of some help
Recently, Diane Davis discovered that her dog has a congenital malformation on her left knee, which causes pain and lameness. Consequently, Raskel can't walk on slippery hospital floors like other service dogs.
Get your greens at the winter market
The Yellow Springs Winter Farmers Market, located in the basement of the United Methodist Church, is now open each Saturday from 9–noon. Villagers who go can purchase fresh greens, root vegetables and a variety of other local foods.


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Dodgers don't mind calling for help
L.A. bullpen a strength going into NLCS rematch with the Phillies
Originally Published: October 15, 2009By Eric Neel | ESPN.com
LOS ANGELES -- Figure out a way to win the game.
These were Dodgers general manager Ned Colletti's words to the team's pitching staff coming out of spring training in March.
It was an all-for-one-one-for-all, check-your-stats-and-ego-at-the-door thing. Team building. Scrap, fight, play as one, pick each other up.
But for the Dodgers, whose starting rotation has (to put it charitably) been in flux for much of the 2009 season, "figure out a way to win the game" has been more ...
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Was anyone able to do immediate skin-to-skin/kangaroo care after having a c-section? Any tips for facilitating this process? Did you run into pushback from your care team on this?
I'm being induced Wednesday and am hopeful for a regular ole' vaginal birth, but knowing that this does increase the odds that I'll wind up with a c-section, I want to be prepared.
I've read the evidenced based birth articles on skin-to-skin after c-sections, but would love some input from any BTDT mammas who did it successfully.


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They're predicting snow! (up high…)
I heard that there was a chance of snow high in the mountains! It's time to start thinking positive thoughts! It's going to be a great ski year!
The NNSC website is awake and ready for this year's ski season. Please look around for information on the first general meeting (Thursday, Oct. 1) and the first outdoor events, our yearly trail work parties. (Sept 19, 26 & Oct 17). Further information will be posted as it becomes available.


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The Buysy v1.1 Lost is an American drama TV series that follows the lives of the survivors of a plane crash happened somewhere in the South Pacific on its route from Sydney to Los Angeles. The popularity of this show has grown to a level that in most parts of the world it is seen and also the Lost action figures are sold worldwide.
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Women's UGG® Australia Dominique
Gold Washed Leather
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Product Details
Getting back to basics never looked or felt as good as it does in the UGG® Australia Dominique sandal. This women's high-heeled platform wedge slide sandal has a metallic leather upper, a suede-topped, Poron® foam-cushioned footbed, and cork-wrapped midsole for lightweight and a light-hearted look. The UGG® Australia Dominique platform slide sandal is finished with a rubber sole and inclined forefoot to encourage a natural stride.
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Marquess of Queensberry Rules
John Sholto Douglas, 9th Marquess of Queensberry (20 July 1844 - 31 January 1900) was a Scottish nobleman, remembered for lending his name and patronage to the Marquess of Queensberry Rules that formed the basis of modern boxing. Formulated by John Graham Chambers, the Rules were first introduced in 1867 when the Queensberry Challenge Cups were competed for by amateur lightweights (130lbs), Middleweights (158lbs) and heavyweights (wearing gloves) at the Lillie Bridge Grounds, Brompton Road, London. As professional boxing with gloves took off in the 1870s the Queensberry Rules gradually replaced the revised London Prize Ring Rules that had governed bare-knuckle fighting from 1853.
1) To be a fair stand-up boxing match in a 24-foot ring, or as near that size as practicable. No wrestling or hugging (clinching) allowed.
2) The rounds to be of three minutes duration, and one minute's time between rounds. 3) If either man falls through weakness or otherwise, he must get up unassisted, 10 seconds to be allowed him to do so, the other man meanwhile to return to his corner, and when the fallen man is on his legs the round is to be resumed and continued until the three minutes have expired. If one man fails to come to the scratch in the 10 seconds allowed, it shall be in the power of the referee to give his award in favour of the other man. 4) A man hanging on the ropes in a helpless state, with his toes off the ground, shall be considered down. 5) No seconds or any other person to be allowed in the ring during the rounds. 6) Should the contest be stopped by any unavoidable interference, the referee to name the time and place as soon as possible for finishing the contest; so that the match must be won and lost, unless the backers of both men agree to draw the stakes. 7) The gloves to be fair-sized boxing gloves of the best quality and new. 8) Should a glove burst, or come off, it must be replaced to the referee's satisfaction. 9) A man on one knee is considered down and if struck is entitled to the stakes. 10) That no shoes or boots with spikes or sprigs be allowed. [6] 11) The contest in all other respects to be governed by revised London Prize Ring Rules.


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Justice to Release New Live Album
By Carrie Battan on March 26, 2013 at 10:15 a.m. EDT
Justice are making a chronicle of their spastic, high-voltage live act once again. Following 2008's live release A Cross the Universe, they'll release a new live album recorded during their latest tour for Audio, Video, Disco (more specifically, at their July 19, 2012 show in France). It's called Access All Arenas and it's out on May 7 through Ed Banger.
Listen: Chemical Brothers, Justice Remix Boys Noize
By Carrie Battan on March 15, 2013 at 1:04 p.m. EDT
Boys Noize: "XTC" (The Chemical Brothers Remix) (via SoundCloud)
Boys Noize: "Ich R U" (Justice Remix) (via SoundCloud)
Veteran electronic duo the Chemical Brothers have taken on "XTC", a track from German partier Boys Noize. The remix, along with a version of "ICH R U" from Justice, will appear on a 12" out March 18 through Boysnoize Records (the label's 100th release). Both tracks originally appeared on the Boys Noize record Out of the Black.
The Avalanches, Justice, Massive Attack's Robert Del Naja Contribute to King Kong Musical Score
By Evan Minsker on October 7, 2012 at 9:20 p.m. EDT
"We've made some music for a giant, robot ape!" That's the Avalanches' Twitter account, referring to an upcoming musical adaptation of King Kong. In the Mix reports (via Consequence of Sound) that the Avalanches, Justice, and Massive Attack's Robert Del Naja will contribute music to the score of the musical, which will premiere June 2013 in Melbourne. Below, watch an interview with Justice about the musical.
Watch Justice's Bloody "New Lands" Video
By Jenn Pelly on July 11, 2012 at 12:55 p.m. EDT
Justice have shared the video for "New Lands" from last year's Audio Video Disco. (They also recently released a they "New Lands" remix EP.) The film was created by the Spanish collective Canada. It takes place at a football game that quickly morphs into a futuristic, action-packed fight scene. (Note: There is blood.)
Justice Announce Tour, Release New EP
By Jenn Pelly on June 25, 2012 at 1:55 p.m. EDT
Justice: "New Lands" [Falcon Remix] (via SoundCloud)
Justice: "New Lands" [A-Trak Remix] (via SoundCloud)
Justice have followed up last year's Audio, Video, Disco with a five-track EP featuring versions and remixes of album cut "New Lands". It's out today on Ed Banger. Check out A-Trak and Falcon's remixes above, as well as the cover art, and the tracklist below.
Jack White, the Weeknd, Justice, Die Antwoord to Play Lollapalooza?
By Evan Minsker on March 27, 2012 at 9:14 p.m. EDT
It looks like the people behind Lollapalooza are dropping hints about the festival's lineup via Chicago's public transportation system. Wine & Pop points to advertisements at train stations containing lyrics by Jack White, the Weeknd, Justice, and Die Antwoord, accompanied by the word "#Lolla," suggesting the four artists are included in the festival's roster. It takes place in Chicago's Grant Park from Aug. 3-5, and the official lineup will be announced on April 11.
NSFW Video: Justice: "On'n'On"
By Jenn Pelly on January 20, 2012 at 3:09 p.m. EST
Justice have released a NSFW new video for their Audio, Video, Disco single "On'n'On", which was accompanied by some controversial cover artwork, if you recall. It's directed by Alexandre Courtes.
People Are Mad About the Naked Lady on the Cover of the New Justice Single
By Carrie Battan on December 14, 2011 at 3:15 p.m. EST
As reported, Justice is releasing a single for the song "On'n'On" (featuring a Rick Rubin remix). The cover of that single features a nude woman (see above, in case you missed it). Apparently, the artwork angered quite a few people, provoking Ed Banger Records' Pedro Winter to post this statement on the label's Facebook page:
Rick Rubin to Remix Justice
By Carrie Battan on December 13, 2011 at 4:35 p.m. EST
In late January, Ed Banger Records will release Justice's "On'n'On", off their new album Audio, Video, Disco, as a single. According to Ed Banger's Facebook, that release will include a Rick Rubin remix of "On'n'On". It'll also feature remixes of the track by Brodinski and Video Village, and remixes of the song "Canon" by Erol Alkan and Tiga.
And yes, that's the cover art for the single up there.
Justice Announce World Tour
By Carrie Battan on November 28, 2011 at 3:20 p.m. EST
Photo by Erez Avissar
French dance giants Justice have announced a world tour beginning on New Year's Day, which includes a U.S. leg for the first time in two years. In support of their recent album Audio, Video, Disco, the duo will tour in Australia, Japan, Europe, the UK, the U.S. and Canada through April.
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HN-NATC156 National Tree Company
48 in. Norwood Fir Pre-lit LED WreathItem # HN-NATC156
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Choose from classic soft white bulbs or vibrant multi-colored bulbs on the 48 in. Norwood Fir Pre-lit LED Wreath for your holiday decorating needs. This 4-foot diameter wreath is a gorgeous addition to your home, business, or community. And because it is all PVC, you know it will last for years looking good as new.About National Christmas ProductsNational Christmas Products isn't quite Santa's workshop, but they're getting closer with each passing year. A variety of holiday d&eac


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Invisible Lives: The Erasure of Transsexual and Transgendered People
University of Chicago Press, Dec 15, 2000 - Social Science - 340 pages
Invisible Lives is the first scholarly study of transgendered people—cross-dressers, drag queens and transsexuals—and their everyday lives.
Through combined theoretical and empirical study, Viviane K. Namaste argues that transgendered people are not so much produced by medicine or psychiatry as they are erased, or made invisible, in a variety of institutional and cultural settings. Namaste begins her work by analyzing two theoretical perspectives on transgendered people—queer theory and the social sciences—displaying how neither of these has adequately addressed the issues most relevant to sex change: everything from employment to health care to identity papers. Namaste then examines some of the rhetorical and semiotic inscriptions of transgendered figures in culture, including studies of early punk and glam rock subcultures, to illustrate how the effacement of transgendered people is organized in different cultural sites. Invisible Lives concludes with new research on some of the day-to-day concerns of transgendered people, offering case studies in violence, health care, gender identity clinics, and the law.
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Invisible lives: the erasure of transsexual and transgendered peopleUser Review - Not Available - Book Verdict
The author, a transsexual/transgendered (TS/TG) health services coordinator based in Montreal, has broken new ground with one of the first sociological studies of the TS/TG community. Disdaining the ... Read full review
Review: Invisible Lives: The Erasure of Transsexual and Transgendered PeopleUser Review - Josie Boyce - Goodreads
seminal book on trans issues, from a bit of a detached, but not dispassionate writer. Read full review
TRAGIC MISREADINGS Queer Theorys Erasure of Transgender Subjectivity
THEORY TROUBLE Social Scientific Research and Transgendered People
BEYOND TEXTUALIST AND OBJECTIVIST THEORY Toward a Reflexive Poststructuralist Sociology
A GANG OF TRANNIES Gendered Discourse and Punk Culture
GENDERED NATIONALISMS AND NATIONALIZED GENDERS The Use of Metaphor in Mass Culture and US Transsexual Activism
GENDERBASHING Sexuality Gender and the Regulation of Public Space
ACCESS DENIED The Experiences of Transsexuals and Transgendered People with Health Care and Social Services in Toronto
CLINICAL RESEARCH OR COMMUNITY HEALTH? Transsexual Perceptions of Gender Identity Clinics
THE ADMINISTRATION OF ERASURE The Bureaucracy of Legal Sex a Vicious Circle of Administration and HIVAIDS in Quebec
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Invisible Lives: The Erasure of Transsexual and Transgendered People
Viviane Namaste
Limited preview - 2000
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References to this book
Becoming a Visible Man
Jamison Green
No preview available - 2004
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Research in Personnel and Human Resources Management
Joseph J. Martocchio
No preview available - 2004


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Filmmaker Michael Moore, the outspoken political activist whose documentary-style movies frequently condemn capitalism, reportedly owns nine different homes — including a $2 million mansion in Torch Lake, Michigan.
The Smoking Gun first reportedMr. Moore's house collection.
Among Mr. Moore's homes are the 10,000-square-foot lakefront residence in Michigan and a condominium in Manhattan that was once split into three separate condos, the Detroit News reported. He also owns seven other residences at various locations.
Mr. Moore's holdings were revealed in divorce papers from his wife of 22 years, Kathy Glynn. CelebrityNetWorth.com lists the couple's collective wealth at $50 million.


text: Cyan filter is used for gray filter glass door in my durst is M +Y+C filter and then color paper is not lighted. In this head 2 pack of filter one operated from head and second operated from computer and both cyan filters is dead. Filter from head I don't need but I need second filter.


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Part-time, 22 year old babysitter from Fort Thomas, KY with 6 years of experience and a background check available upon request
Fort Thomas, KY | 22 yrs old
6 years experience
part-time <$10-15/hr
Fort Thomas, KY | 22 yrs old | 6 years experience | part-time <$10-15/hr
Meet Allison
I have completed and had hands on working experiences with children in the following classes in high school Parenting/Child Development, Child Care Services, and Peer Tutoring. Also, I worked in my church nursery and I have done countless baby sitting jobs through church. I have worked with all age ranges, from 5 months all the way up to 12 years old. I have also had experience being around children and teenagers who have mental or intellectual disabilities. I have a true passion for working with kids and I am going to college to be a pediatric nurse.
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