text:
JNK3 as a therapeutic target for neurodegenerative diseases.
ABSTRACT c-Jun N-terminal kinases (JNKs) and in particular JNK3 the neuronal specific isoform, have been recognized as important enzymes in the pathology of diverse neurological disorders. Indeed, several efforts have been made to design drugs that inhibit JNK signaling. The success that characterized the new generation of cell permeable peptides raise the hope in the field of neurodegeneration for new therapeutic routes. However, in order to design new and more efficient therapeutical approaches careful re-examination of current knowledge is required. Scaffold proteins are key endogenous regulators of JNK signaling: they can modulate spatial and temporal activation of the JNK signaling and can thus provide the basis for the design of more specific inhibitors. This review focuses on delineating the role of scaffold proteins on the regulation of JNK signaling in neurons. Furthermore the possibility to design a new JNK3 cell permeable peptide inhibitor by targeting the β-arrestin-JNK3 interaction is discussed.
- SourceAvailable from: Masoud Rahmati
Dataset: Modulation of SYD gene expression in sensory neurons of rats with diabetic neuropathy following endurance training
Article: Modulation of SYD gene expression in sensory neurons of rats with diabetic neuropathy following endurance training[Show abstract] [Hide abstract]
ABSTRACT: Abstract Introduction: Diabetic neuropathy leads to sensory neurons abnormality. But, injury signaling mechanisms are not well documented. So, the aim of present study was to investigate SYD gene expression in spinal nerve of wistar male rats with diabetic neuropathy. Methods: 12 wistar male rats randomly assigned in 3 groups: diabetic trained, diabetic untrained and healthy control. For inducing diabetes, intraperitoneal injection of STZ solution (45 mg/Kg) method was used. Two weeks after STZ injection, diabetic neuropathy was demonstrated with mechanical allodynia and thermal hyperalgesia tests, after which moderate endurance training protocol was performed for 6 weeks. 24 hours after final training session, the rats were dissected and L4-L6 sensory neurons of spinal cord tissue were removed. Also SYD gene expression was performed with Real time- PCR methods. Findings: SYD gene expression in diabetic untrained group was higher than healthy control group (p=0/001). Also, compared with diabetic untrained group, training significantly decreased SYD gene expression and blood glucose levels in diabetic trained group. (P=0/001 and P=0/0001, respectively). Conclusion: In sensory neurons of diabetic rats mRNA SYD up-regulation, is involved in neuronal injury signaling and training as a non-pharmacotherapy strategy can modulate and get it close to normal levels. So, it is suggested that SYD should be noted as a novel treatment in diabetes disease, however there are other related points which should be explained by future studies. Key words: Diabetic neuropathy, Endurance training, Gene expression, SYDIranian Journal of Diabetes and Lipid Disorders 01/2013; 12(4):292-301.
- [Show abstract] [Hide abstract]
ABSTRACT: Although arrestins bind dozens of non-receptor partners, the interaction sites for most signaling proteins remain unknown. Here we report the identification of arrestin-3 elements involved in binding MAP kinase JNK3α2. Using purified JNK3α2 and MBP fusions containing separated arrestin-3 domains and peptides exposed on the non-receptor-binding surface of arrestin-3 we showed that both domains bind JNK3α2 and identified one element on the N-domain and two on the C-domain that directly interact with JNK3α2. Using in vitro competition we confirmed that JNK3α2 engages identified N-domain element and one of the C-domain peptides in the full-length arrestin-3. The 25-amino acid N-domain element has the highest affinity for JNK3α2, suggesting that it is the key site for JNK3α2 docking. The identification of elements involved in protein-protein interactions paves the way to targeted redesign of signaling proteins to modulate cell signaling in desired ways. The tools and methods developed here to elucidate the molecular mechanism of arrestin-3 interactions with JNK3α2 are suitable for mapping of arrestin-3 sites involved in interactions with other partners.Cellular signalling 01/2014; · 4.09 Impact Factor
Page 1
Journal of Alzheimer's Disease 24 (2011) 633–642
IOS Press
JNK3 as a Therapeutic Target for
Neurodegenerative Diseases
Xanthi Antonioua, Mattia Falconib, Daniele Di Marinoband Tiziana Borselloa,∗
aIstituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy
bDepartment of Biology and CIBB, Center of Biostatistics and Bioinformatics, University of Rome "Tor Vergata",
Rome, Italy
enzymes in the pathology of diverse neurological disorders. Indeed, several efforts have been made to design drugs that inhibit
JNK signaling. The success that characterized the new generation of cell permeable peptides raise the hope in the field of
neurodegeneration for new therapeutic routes. However, in order to design new and more efficient therapeutical approaches
careful re-examination of current knowledge is required. Scaffold proteins are key endogenous regulators of JNK signaling:
they can modulate spatial and temporal activation of the JNK signaling and can thus provide the basis for the design of more
Furthermore the possibility to design a new JNK3 cell permeable peptide inhibitor by targeting the ?-arrestin-JNK3 interaction
is discussed.
Keywords: JNK3, JIP1, ?-arrestin-2, Alzheimer disease, signalling pathways, neuroprotection
kinases. There are ten different JNK isoforms, which
are formed by alternate splicing of the three genes,
in their substrate specificity in vitro [2], although the
details of this are still unclear, but they have much
in common and can all phosphorylate members of the
ferent targets, both nuclear and cytoplasmic [1, 3–10]
summarized in Fig. 1.
Whereas JNK1 and JNK2 have a broad tissue dis-
tribution, JNK3 is mainly localized in neurons and to
a lesser extent in the heart and the testis [11].
∗Correspondence to: Tiziana Borsello, Neuronal Death and Neu-
roprotection Unit, Neuroscience Department, Istituto di Ricerche
Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milano,
Italy. Tel.: +39 02 39014469/39014592; Fax: +39 02 3546277;
E-mail: firstname.lastname@example.com.
JNK3 is a multifunctional enzyme important in
controlling brain functions under both normal and
pathological conditions.
The loss of JNK3 is not embryonic lethal. Nev-
ertheless JNK3 is implicated in processes such as
brain development [12], neurite formation and plastic-
ity (repair and regeneration) [13, 14] but also memory
and learning [15, 16].
Under pathological conditions, JNK3 has been
considered as a degenerative signal transducer. Sev-
eral evidences exist to support this idea. The JNK3
knockout (-/-) mice showed reduced apoptosis of
hippocampal neurons and reduced seizure induced
by kainic acid, a glutamate-receptor agonist [17].
JNK3-/- mice are also protected against ischemia.
Such studies have been performed both in neonatal
and adult rats, further reinforcing the contribution of
JNK3 in ischemia [18, 19]. In accordance with the
above, Kuan et al., reported that in vitro and follow-
ing oxygen-glucose deprivation hippocampal neurons
from JNK3-null mice are more resistant compared to
ISSN 1387-2877/11/$27.50 © 2011 – IOS Press and the authors. All rights reserved
Page 2
X. Antoniou et al. / JNK3 in Neurodegeneration
Fig. 1. Simplified diagram: JNK's targets in the different neuronal compartments: nucleus, cytoplasm, mitochondria and synapse. JNK can
phosphorylate a range of substrates that are located in different parts of the neuron. In some cases, the consequences of JNK phosphorylation
could be ascribed to normal/positive effects while in others to pathological/negative/effects. In some cases the consequences have not yet been
defined. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/JAD-2011-091567)
Page 3
X. Antoniou et al. / JNK3 in Neurodegeneration
WT mice. The authors provided evidence for a critical
of cytochrome c from mitochondria [18].
JNK3 activation is associated with chronic neu-
rodegenerative diseases. In MPTP, a mouse model
of Parkinson's Disease, elimination of JNK3 (-/-)
prevented 50% of the triggered neurotoxicity; in this
model JNK2 also played a role [16, 20]. JNK3
activation is also described in Alzheimer's disease
(AD). In fact JNK3 is highly expressed and acti-
from Alzheimer's disease [21]. Neurons derived (ex
vivo) from mice lacking JNK3 are resistant to A?-
induced apoptosis when compared with neurons from
normal mice. Cleary et al. [22] demonstrated that
JNK3 is the major kinase for Beta-Amyloid Precur-
sor Protein (APP) phosphorylation at T668. This is an
tous transmembrane glycoprotein strongly implicated
in the pathogenesis of AD and the toxic soluble
oligomers species (A? 1-42 oligomers) are produced
by the cleavage of this protein. Some reports subse-
quently confirmed that this phosphorylation, mediated
by JNK3, regulates APP cleavage by inducing the
amyloidogenic processing of the protein, while JNK
inhibition by blocking APP phosphorylation is reduc-
ing the rate of amyloidogenic processing in favor of
the non-amyloidogenic one in vitro further underlying
the important role of JNK3 in AD pathology [21, 23–
the contribution of JNK3 on tau hyperphosphorylation
Last but not least the ablation of JNK3 protected
against neuronal death in a model of axotomy [16, 27]
of regeneration of the CNS.
Altogether these results indicate JNK3 as a specific
key modulator in stressed neurons and in degenerative
conditions in the CNS.
together with its selective over-activation by stress-
in stress-induced signaling during degeneration in the
nervous system and thus an attractive target for the
development of therapeutical strategies.
Scaffold proteins have no enzymatic activity but act
as central organizers of diverse signaling pathways.
These proteins can concentrate, isolate and accelerate
shared substrates:
c-Jun, Jun D, ATF2,
Bcl-2, Bad, 14-3-3, etc
Neuronal death
brain ischemia
seizures (KA)
AD (b-amilyod-APP)
nerve growth factor deprivation
JNK's Triggers
Liver damage
cardiac cell death
tumor growth
Fig. 2. Schematic representation of the different stress stimuli and
how they affect JNK signaling. Different stimuli that could acti-
vate JNK1, 2 & 3 isoforms. JNK3 is mainly modulated by CNS
tance, autoimmune or inflammatory diseases and cancer [16, 18, 20,
72–77]. All JNKs exert their functions by acting on common targets
(only some representative examples are given). (Colours are visible
in the online version of the article; http://dx.doi.org/10.3233/JAD-
regulation of JNK signaling. The specificity of JNK
signaling is partially controlled by scaffold proteins
[28]. Emerging evidence indicates that scaffold pro-
teins may provide critical tools for manipulation of the
"signalosome" and the cellular response to different
IKAP, ?-arrestin-2, POSH [28, 30–32,] and filamin
JNK's scaffolds: the JNK-interacting proteins (JIPs)
and ?-arrestin-2 [28, 34].
The JIP group of scaffold proteins is highly ex-
pressed in the brain [28]. JIPs were initially identi-
fied as proteins that bind with mixed-lineage protein
kinases (MLKs), MKK7 or MKK4 and JNKs [35]. In
mammals, there are four genes encoding JIP family
members: JIP1, JIP2, JIP3 and JIP4. These proteins
are all related in structure.
Additionally, all JIPs have the JNK binding domain
(JBD) and link to the light chain of Kinesin-1 via the
tetratricopeptide repeat (TPR) domain [36].
JIP1 and 2 are very similar, they contain the SH3
and PTB domains and they can also hetero-dimerize
under certain conditions [37]. On the other hand, JIP3
and 4 have in common the coiled-coil domain and the
trans-membrane domain [38].
Page 4
internalization and sequestration in endosomes. The
?-arrestins molecules have important functions in the
termination of heterotrimeric G protein activation by
GPCRs [48].
However, ?-arrestins may also recruit other sig-
nalling modules. Presently we know that they can act
as scaffolds for the mitogen-activated protein (MAP)
kinase signaling pathways [49], including ERK, p38
and JNK signaling pathway [50].
Notably, ?-arrestin-2 acts as a scaffold of the JNK
signaling pathway and more specifically of JNK3.
In neurons, ?-arrestin-2 binds to JNK3 and recruits
the signal-regulating kinase 1 (ASK1) and mitogen-
activated protein kinase (MAPK) kinase 4 [32, 51].
Importantly, ?-arrestin-2 has a unique characteristic:
although it can bind to all JNK isoforms through the
common docking motif, binding to the N-terminus of
JNK3 leads to its specific activation without affecting
X. Antoniou et al. / JNK3 in Neurodegeneration
JIP1, 2 and 3 aggregate three-kinase components
of the JNK cascade and facilitate signal transmission
in cells. Interestingly, despite the structural similarity
seems to be an activator of the p38 pathway [36].
JIPs may contribute to modulate stress-signals [39,
axonal transport [42], sprouting and regeneration [43].
More generally the JIP family, by regulating the
subcellular localization of JNK's cascade via the
kinesin-1 motor, may also interfere with the local-
ization and trafficking of molecules, like the APP,
that are strongly implicated in neurodegenerative
disease. In fact JIP-1 interacts with APP via the
phosphotyrosine-interaction-domain (PID) [44] and
regulates its trafficking and processing [24, 25, 46].
Furthermore, JIP1 colocalizes with amyloid deposits
and neurofibrillary tangles in AD patients [46].
The ?-arrestin family consists of four members:
?-arrestin from 1 to 4, that are almost exclusively
expressed in the retina, and ?-arrestin1 and 2 (also
known as arrestin 2 and 3 respectively) that are ubiq-
uitously expressed [47].
G-protein-coupled receptor signaling. It is now known
that ?-arrestins bind to G-protein-coupled receptors
(GPCRs) following ligand engagement and phos-
phorylation by GPCR kinases (GRKs). The adapter
proteins block the interaction of GPCRs with het-
erotrimeric G proteins and may induce receptor
JNK1 and 2 activity [51]. This is of relevant interest in
the CNS where JNK3 is highly expressed.
Moreover ?-arrestins were recently designated as
important adaptors that link receptors to the clathrin-
dependent pathway of internalization [52]. For this
it has been proposed that ?-arrestin-2 may also con-
tribute to the regulation of synaptic receptors.
Together, these studies establish that ?-arrestin-2
represents an important scaffold protein of the JNK3
cascade in the CNS.
An open question on the JNK3 signaling pathway is
how a particular stimulus elicits the correct response.
The JNK3 specificity is remarkable when one consid-
ers the diverse range of cellular responses that JNKs
mediate in the CNS (from growth to death).
Spatial and temporal changes of JNK3 activation
may affect the neuronal response and the scaffolds
proteins provide one mechanism by which this can be
In fact scaffolds facilitate interactions and propaga-
tion of the signal inside cells but they also sequester
the same kinase from other pathways thus preventing
cross talks between pathways [53]. This also implies
that a scaffold protein can direct the activation of a
ment (nucleus, mitochondria, axon, synapses) [54, 55]
and subsequently lead to a powerful effect/modulation
activation inside the cell.
In polarized cells such as the neurons, scaffold
proteins may make the difference in regulating the
signaling response to a stimulus.
For instance, JNK3 specificity in neurons could be
modulated by both JIPs and ?-arrestin-2. These two
neurons [11, 56] and this can result in different reg-
ulation of the JNK modules. Moreover the different
the JNK isoforms can provide different signalosome
It has been proven that JIP1 links preferentially
MLK3, MKK7 but also MKK4 and all JNKs (JNK1-
2-3) [28], while ?-arrestin-2 assembles AKT, MKK4
and JNK3. The different partners would suggest that
these scaffolds are regulating very different cellular
responses but also distinct signalosome inside diverse
cellular compartments.
Page 5
X. Antoniou et al. / JNK3 in Neurodegeneration
The combination of extracellular signals, com-
partmentalization and molecular scaffolds creates an
intricate system utilized by neurons to regulate their
response to the environmental signals.
pharmacological and potentially therapeutical agents.
as SP600125, CC-401, CEP-1347) that block JNK
activity by interfering with the ATP catalytic pocket
or on upstream activators [57]. Such inhibitors have
been proven useful for elucidating the role of JNK sig-
naling in neurodegeneration and some have entered
clinical trials (CC-401 developed by Celgene), how-
ever a more detailed analysis is beyond the scope of
this review.
(CPPs). These peptides share one characteristic: they
derive from the JIP scaffold protein. Of those the most
studied ones are: TAT-c Jun peptide, TI-JIP, L-JNKI
and D-JNKI1 [58–60].
of action led to the production of the most specific and
strong JNK inhibitor.
As already mentioned, JIP1 presents a consensus
sequence, the JBD motif, that is the same domain that
JNK uses to link c-Jun [28]. This motif is a natural
blocker of JNK activity and in fact its over-expression
prevents apoptosis [61]. Successively the JBD of JIP1
has been engineered as a cell permeable inhibitor pep-
tide namely D-JNKI1 [59].
This inhibitor is very strong and selective on JNKs
and differs from all common chemical inhibitors. In
particular, D-JNKI1 inhibits JNK1, JNK2 and JNK3
with Kinhibitionvalues of 3.3?M, 430nM, and 540nM
respectively (Dr. Sylvie Guenat, Xigen, personal com-
munication). It should also be noted that D-JNKI1
Fig. 3. Schematic simplified diagram of D-JNKI1 peptide mode of
action. The JIP-1 scaffold protein interacts with JNK via the JNK
targets. Following a stimulus, JIP1 (red shape) acts by recruiting
MLK3, MKK7 and JNK (blue shapes). Black arrow indicates the
peptide (green oval shapes) acts by blocking the access of JNK to
JIP1 and to all its JBD-dependent substrates. (Colours are visible
in the online version of the article; http://dx.doi.org/10.3233/JAD-
and thus by inhibiting protein-protein interactions
mediated by the JBD domain (Fig. 3).
To further determine the specificity of the peptide
in blocking JNK action, we characterized the effects
of the peptide on the activity of 40 different kinases
(10?M peptide, 10?M ATP) towards their respective
the activities of the other kinases [62, 63] proving its
exceptional superiority.
The protective action of D-JNKI1 has subsequently
been tested in several experimental models of disease
including cerebral ischemia [62, 64], auditory hair cell
loss [65], spinal nerve legation [66], viral encephali-
tis [67], myocardial ischemia-reperfusion injury [68],
TBI [69] and in intra-timpanic treatment after acute
that D-JNKI1 is able to interfere with AD pathogen-
esis and more specifically with APP phosphorylation
in cortical neurons as well as in an AD in vitro model
[24, 25], underlying the potential application of this
inhibitor in AD models.
Due to the very promising results achieved by D-
JNKI1 administration in several experimental models,
the efficacy of this drug is currently at clinical phase
I/II trials in Switzerland and France (see web site:
Page 6
ther specificity. Last but not least, specificity could be
accomplished by targeting only JNK3 and not JNK1
and JNK2. Such an approach is particularly appealing
mechanisms and is highly expressed in the CNS.
In light of these data, the interaction between ?-
arrestin-2 specifically with JNK3 represents a new and
interesting possibility to develop a specific inhibitor of
JNK3 to combat neurodegenerative disorders.
X. Antoniou et al. / JNK3 in Neurodegeneration
It should be noted however that D-JNKI1 treatment
provides only a transient pain relief after spinal nerve
ligation, and no protection in myocardial ischemia-
reperfusion injury when administered at the time of
reperfusion [68].
tective action of D-JNKI1 in the CNS as opposed to
other tissues.
JNK inhibitor compounds still have some limita-
tions. Chemical agents are too general, and they lack
are more specific, allowing inhibition of specific pro-
tein interactions. Still, today's CPPs lack tissue and
isoform specificity. Furthermore, because JNKs regu-
lates myriad cellular functions, inhibiting total JNK
activity is likely to affect multiple processes, some
not linked to the patho-physiology of diseases. This
could probably generate unwanted side-effects, espe-
cially when targeting chronic conditions. Therefore,
new approaches are being explored to enhance thera-
peutic specificity of JNKs inhibitors.
JNK-protein scaffolds remain conceptually attrac-
tive therapeutical targets for a number of reasons. In
particular, scaffolds can regulate the localization of
many JNK's components. Thus modulation of scaf-
fold proteins may allow regulation of the JNK action,
directing the cellular response to a particular func-
tion without influencing global JNK activity in the
neuron as a whole. Additionally by targeting the scaf-
fold protein, inhibition of JNK signaling in a specific
According to the literature, ?-arrestin-2 is able to
specifically bind only JNK3 and not JNK1 and JNK2,
this opened the perspective of designing a JNK3 spe-
cific competitor peptide. Miller and colleagues [49]
showed that the ?-arrestin-2 region important for this
interaction is mapped in the C-terminal region of
the protein that is arranged to form an antiparallel
eight-stranded ?-sandwich. In particular they found a
short sequence in this region that is very similar to
the conserved docking motif present in many JNK
Kinase-binding proteins (D-domain) [49]. Guo and
collaborators mapped the residues of JNK3 essen-
tial for the binding to ?-arrestin-2 that correspond
to nine residues of the non-conserved N-terminus of
JNK3 [51]. Moreover, this group demonstrated that
JNK3 does not directly bind to the putative D-domain
of ?-arrestin-2 but instead binds in another portion
of the C-terminal region [51]. However, residues
within the D-domain determine the specificity of ?-
arrestin-2 binding to JNK3 and in particular they
underline the importance of Ser198 in ?-arrestin-2
interaction, the structural and functional properties of
lar modeling strategies, thus providing the opportunity
for setting up a possible inhibition strategy. Regret-
tably the development of small molecules, capable
of modulating such interaction, is tricky because the
design of an inhibitory compound able to bind ten
residues, i.e. the interacting sequence of the JNK3 N-
terminal tail, is a very hard task. Indeed, up today, to
hypothesize which will be the JNK3 N-terminal tail
conformation, when this portion of the protein is in
contact with ?-arrestin-2, is over the reasonable lim-
its of the modeling. On the other hand, the flexibility
and plasticity of the amino acids building blocks can
inspire other strategies in the development of a novel
Our suggestion is to generate a JNK3 inhibitor pep-
?-arrestin-2. We propose to reduce, as much as pos-
sible, the sequence of this protein to create a mini
?-arrestin-2 able to fold, as observed in the complete
ing indeed is more suitable for the interaction than
the JNK3 co-evolved molecular partner. The natural
strategy of recognition obviously should be separated
from the whole structure-function of the ?-arrestin-2
machinery. As is known, the protein modeling strat-
egy enhances its achievements when it emulates the
structural features applied by the natural molecules
and this suggestion, although very complex and not
without uncertainties, respects this dogma.
Page 7
X. Antoniou et al. / JNK3 in Neurodegeneration
One of the most intriguing open questions is to
understand how JNK can induce a specific response to
a particular stimulus, considering the different cellular
functions that this enzyme can control. Scaffold pro-
teins may be responsible for the specific regulation of
JNK's functions, functions that may be very important
in some pathological conditions.
In fact some compounds, D-JNKI1 (XG-102 by
Xigen) and CC-401 (by Celgene) that inhibit the JNK
pathway have been successful and are progressing in
clinical trials. Still it is difficult to predict potential
side-effects of this systemic inhibition and for chronic
Transgenic knockouts of JNK isoforms have pro-
isoform. It has been established that JNK1 and JNK2
have important roles in the modulation of immune
cell function and in the development of the embry-
onic nervous system. A study using JNK1 knockout
mice demonstrated that JNK1 has a regulatory role
and maintains physiological functions in the CNS,
while JNK2 knockout established that JNK2 may
additionally participate in some physiological func-
tions and in particular in the Long Term Potentation
(LTP)[71]. JNK3 seems to be more involved in over-
activation of JNK after stress-stimuli in adult brain
(ischemia, PD, AD, hypoxia, epilepsies). If JNK1, 2
are more implicated in the regulation of physiological
cesses the development of a selective JNK3 inhibitor
is preferable for the treatment of neurodegenerative
lenge will be to increase tissue and isoform specificity
of JNK inhibition. The fact that JNK3 is specifically
expressed in the CNS and activated by stress-stimuli
renders it an attractive, and potential target for treating
many different neurodegenerative mechanisms form
acute (stroke) to chronic disease (AD and PD).
We speculate that JNK3 specific inhibition will
reduce the possible side-effects of a systemic JNK
inhibition and is more appropriate for the treatment
of neurodegenerative diseases in the adult CNS.
Considering the diverse neuronal functions that are
regulated by JNK3, its inhibition will also help us to
understand better the specific response of this enzyme
in the brain. In fact until now it is very difficult to
discriminate against the 10 different isoforms of the
JNK family, which are formed by alternate slicing of
the three genes, Jnk1, Jnk2, Jnk3 [1]. This is partially
substrate specificity in vitro [2] in vivo, JNK isoforms
share many common substrates (see Fig. 1 and 2).
only known modulators of JNK3 specific activation
described in the literature. Targeting the ?-arrestin-
be one way to improve biological selectivity. In fact,
such inhibition acts not by blocking the active site of
this signaling enzyme (ATP pocket), but by inhibiting
interactions with substrates and scaffolding proteins.
Focusing on ?-arrestin-2/JNK3 interaction will thus
prevent only partially JNK3 action and may result in
preventing just the pathological activity with regard to
some substrates but not others.
However, the hypothesis that targeting such sites
might lead to the design of inhibitors with improved
efficacy and performance, while appealing, remains
largely untested.
Despite the complexities of this field, JNK3 specific
inhibitor represents an attractive target for pharmaco-
logical therapy.
Authors declare no potential conflicts of interests.
This was supported by the Marie Curie Industry-
Academia Partnerships and Pathways (IAPP) cPADS.
Special thanks to Architettura Laboratorio Commu-
nication and to Daniele Cardinetti for the graphics
[1]Davis RJ (2000) Signal transduction by the JNK group of
MAP kinases. Cell 103, 239-252.
Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK,
tein kinase isoforms with transcription factors. EMBO J 15,
Ip YT, Davis RJ (1998) Signal transduction by the c-Jun N-
terminal kinase (JNK)–from inflammation to development.
Curr Opin Cell Biol 10, 205-219.
Zhang Y, Zhou L, Miller CA (1998) A splicing variant of a
death domain protein that is regulated by a mitogen-activated
kinase is a substrate for c-Jun N-terminal kinase in the human
central nervous system. Proc Natl Acad Sci U S A 95, 2586-
Phelan DR, Price G, Liu YF, Dorow DS (2001) Activated
JNK phosphorylates the c-terminal domain of MLK2 that
Page 8
Brecht S, Kirchhof R, Chromik A, Willesen M, Nicolaus T,
D, Kuan CY, Vaudano E, Behrens A, Wagner E, Flavell RA,
Davis RJ, Herdegen T (2005) Specific pathophysiological
functions of JNK isoforms in the brain. Eur J Neurosci 21,
Yang DD, Kuan CY, Whitmarsh AJ, Rincon M, Zheng
TS, Davis RJ, Rakic P, Flavell RA (1997) Absence of
excitotoxicity-induced apoptosis in the hippocampus of mice
lacking the Jnk3 gene. Nature 389, 865-870.
Kuan CY, Whitmarsh AJ, Yang DD, Liao G, Schloemer AJ,
Dong C, Bao J, Banasiak KJ, Haddad GG, Flavell RA, Davis
RJ, Rakic P (2003) A critical role of neural-specific JNK3 for
ischemic apoptosis. Proc Natl Acad Sci U S A 100, 15184-
Pirianov G, Brywe KG, Mallard C, Edwards AD, Flavell
RA, Hagberg H, Mehmet H (2007) Deletion of the c-Jun
Hunot S, Vila M, Teismann P, Davis RJ, Hirsch EC, Przed-
X. Antoniou et al. / JNK3 in Neurodegeneration
is required for MLK2-induced apoptosis. J Biol Chem 276,
Chauhan D, Hideshima T, Treon S, Teoh G, Raje N, Yoshi-
himito S, Tai YT, Li W, Fan J, DeCaprio J, Anderson KC
Cancer Res 59, 1192-1195.
Chow CW, Rincon M, Cavanagh J, Dickens M, Davis RJ
(1997) Nuclear accumulation of NFAT4 opposed by the JNK
signal transduction pathway. Science 278, 1638-1641.
Donovan N, Becker EB, Konishi Y, Bonni A (2002) JNK
phosphorylation and activation of BAD couples the stress-
Chem 277, 40944-40949.
Kim MJ, Futai K, Jo J, Hayashi Y, Cho K, Sheng M (2007)
Synaptic accumulation of PSD-95 and synaptic function reg-
ulated by phosphorylation of serine-295 of PSD-95. Neuron
56, 488-502.
Edbauer D, Cheng D, Batterton MN, Wang CF, Duong DM,
Yaffe MB, Peng J, Sheng M (2009) Identification and char-
acterization of neuronal mitogen-activated protein kinase
substrates using a specific phosphomotif antibody. Mol Cell
Proteomics 8, 681-695.
of neurodegenerative disorders. Drug Discov Today 9, 932-
Kuan CY, Yang DD, Samanta Roy DR, Davis RJ, Rakic P,
Flavell RA (1999) The Jnk1 and Jnk2 protein kinases are
required for regional specific apoptosis during early brain
development. Neuron 22, 667-676.
Waetzig V, Zhao Y, Herdegen T (2006) The bright side of
JNKs-Multitalented mediators in neuronal sprouting, brain
development and nerve fiber regeneration. Prog Neurobiol
80, 84-97.
Eminel S, Roemer L, Waetzig V, Herdegen T (2008) c-
Jun N-terminal kinases trigger both degeneration and neurite
outgrowth in primary hippocampal and cortical neurons. J
Neurochem 104, 957-969.
Bevilaqua LR, Kerr DS, Medina JH, Izquierdo I, Cammarota
M (2003) Inhibition of hippocampal Jun N-terminal kinase
enhances short-term memory but blocks long-term memory
formation and retrieval of an inhibitory avoidance task. Eur J
Neurosci 17, 897-902.
of cyclooxygenase 2 is required for neurodegeneration in a
101, 665-670.
Savage MJ, Lin YG, Ciallella JR, Flood DG, Scott RW
(2002) Activation of c-Jun N-terminal kinase and p38 in an
Alzheimer's disease model is associated with amyloid depo-
sition. J Neurosci 22, 3376-3385.
Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM,
Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural
oligomers of the amyloid-beta protein specifically disrupt
cognitive function. Nat Neurosci 8, 79-84.
Davis RJ, Shirasaki Y, Greenberg ME (2001) Beta-amyloid
induces neuronal apoptosis via a mechanism that involves the
c-Jun N-terminal kinase pathway and the induction of Fas
ligand. J Neurosci 21, 7551-7560.
Colombo A, Repici M, Pesaresi M, Santambrogio S, Forloni
G, Borsello T (2007) The TAT-JNK inhibitor peptide inter-
feres with beta amyloid protein stability. Cell Death Differ
14, 1845-1848.
Colombo A, Bastone A, Ploia C, Sclip A, Salmona M, For-
loni G, Borsello T (2009) JNK regulates APP cleavage and
33, 518-525.
Vogel J, Anand VS, Ludwig B, Nawoschik S, Dunlop J,
ogy 57, 539-550.
Crocker SJ, Wigle N, Liston P, Thompson CS, Lee CJ, Xu D,
Roy S, Nicholson DW, Park DS, MacKenzie A, Korneluk
RG, Robertson GS (2001) NAIP protects the nigrostriatal
dopamine pathway in an intrastriatal 6-OHDA rat model of
Parkinson's disease. Eur J Neurosci 14, 391-400.
Whitmarsh AJ, Cavanagh J, Tournier C, Yasuda J, Davis RJ
(1998) A mammalian scaffold complex that selectively medi-
ates MAP kinase activation. Science 281, 1671-1674.
277, 693-696.
Holmberg C, Katz S, Lerdrup M, Herdegen T, Jaattela M,
Aronheim A, Kallunki T (2002) A novel specific role for I
signaling. J Biol Chem 277, 31918-31928.
McDonald PH, Chow CW, Miller WE, Laporte SA, Field
ME, Lin FT, Davis RJ, Lefkowitz RJ (2000) Beta-arrestin
2: a receptor-regulated MAPK scaffold for the activation of
JNK3. Science 290, 1574-1577.
Tapon N, Nagata K, Lamarche N, Hall A (1998) A new rac
target POSH is an SH3-containing scaffold protein involved
in the JNK and NF-kappaB signalling pathways. EMBO J 17,
Jeon YJ, Choi JS, Lee JY, Yu KR, Ka SH, Cho Y, Choi EJ,
Baek SH, Seol JH, Park D, Bang OS, Chung CH (2008)
induced c-Jun NH2-terminal kinase signaling pathway. Mol
Biol Cell 19, 5116-5130.
naling modules by scaffold proteins in mammals∗. Annu Rev
Cell Dev Biol 19, 91-118.
Whitmarsh AJ, Davis RJ (1998) Structural organization of
MAP-kinase signaling modules by scaffold proteins in yeast
and mammals. Trends Biochem Sci 23, 481-485.
Kelkar N, Standen CL, Davis RJ (2005) Role of the
JIP4 scaffold protein in the regulation of mitogen-activated
Page 9
X. Antoniou et al. / JNK3 in Neurodegeneration
protein kinase signaling pathways. Mol Cell Biol 25, 2733-
Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ
(1999) The JIP group of mitogen-activated protein kinase
scaffold proteins. Mol Cell Biol 19, 7245-7254.
Whitmarsh AJ (2006) The JIP family of MAPK scaffold pro-
teins. Biochem Soc Trans 34, 828-832.
Centeno C, Repici M, Chatton JY, Riederer BM, Bonny C,
Nicod P, Price M, Clarke PG, Papa S, Franzoso G, Borsello
T (2007) Role of the JNK pathway in NMDA-mediated
excitotoxicity of cortical neurons. Cell Death Differ 14, 240-
Whitmarsh AJ, Kuan CY, Kennedy NJ, Kelkar N, Haydar
TF, Mordes JP, Appel M, Rossini AA, Jones SN, Flavell
RA, Rakic P, Davis RJ (2001) Requirement of the JIP1 scaf-
Dajas-Bailador F, Jones EV, Whitmarsh AJ (2008) The JIP1
rons. Curr Biol 18, 221-226.
Koushika SP (2008) "JIP"ing along the axon: the complex
roles of JIPs in axonal transport. Bioessays 30, 10-14.
Anguelova E, Boularand S, Nowicki JP, Benavides J,
stress and apoptosis in a rat model of hippocampal degenera-
tion. J Neurosci Res 59, 209-217.
Matsuda S, Matsuda Y, D'Adamio L (2003) Amyloid beta
protein precursor (AbetaPP), but not AbetaPP-like protein
2, is bridged to the kinesin light chain by the scaffold pro-
tein JNK-interacting protein 1. J Biol Chem 278, 38601-
X11alpha modulates secretory and endocytic trafficking and
of the YENPTY sequence. Neuroscience 120, 143-154.
Beeler N, Riederer BM, Waeber G, Abderrahmani A (2009)
Role of the JNK-interacting protein 1/islet brain 1 in cell
degeneration in Alzheimer disease and diabetes. Brain Res
Bull 80, 274-281.
tion by interfering with Ras-mitogen-activated protein kinase
MAPK signaling. J Biol Chem 278, 50273-50282.
Miller WE, McDonald PH, Cai SF, Field ME, Davis RJ,
Lefkowitz RJ (2001) Identification of a motif in the carboxyl
J Biol Chem 276, 27770-27777.
the termination and transduction of G-protein-coupled recep-
tor signals. J Cell Sci 115, 455-465.
Guo C, Whitmarsh AJ (2008) The beta-arrestin-2 scaffold
protein promotes c-Jun N-terminal kinase-3 activation by
binding to its nonconserved N terminus. J Biol Chem 283,
Shenoy SK, Lefkowitz RJ (2005) Seven-transmembrane
receptor signaling through beta-arrestin. Sci STKE 2005,
Garrington TP, Johnson GL (1999) Organization and regula-
tion of mitogen-activated protein kinase signaling pathways.
Curr Opin Cell Biol 11, 211-218.
signalling. Cell Signal 21, 462-469.
[55] Haeusgen W, Boehm R, Zhao Y, Herdegen T, Waetzig V
(2009) Specific activities of individual c-Jun N-terminal
kinases in the brain. Neuroscience 161, 951-959.
Gelderblom M, Eminel S, Herdegen T, Waetzig V (2004)
c-Jun N-terminal kinases (JNKs) and the cytoskeleton–
functions beyond neurodegeneration. Int J Dev Neurosci 22,
Bogoyevitch MA, Boehm I, Oakley A, Ketterman AJ, Barr
RK (2004) Targeting the JNK MAPK cascade for inhibition:
1697, 89-101.
of the critical features of a small peptide inhibitor of JNK
activity. J Biol Chem 277, 10987-10997.
Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF
(2001) Cell-permeable peptide inhibitors of JNK: novel
blockers of beta-cell death. Diabetes 50, 77-82.
Holzberg D, Knight CG, Dittrich-Breiholz O, Schneider H,
of the c-JUN-JNK complex by a cell-permeable peptide con-
taining the c-JUN delta domain induces apoptosis and affects
a distinct set of interleukin-1-induced inflammatory genes.
J Biol Chem 278, 40213-40223.
Harding TC, Xue L, Bienemann A, Haywood D, Dickens
M, Tolkovsky AM, Uney JB (2001) Inhibition of JNK by
overexpression of the JNL binding domain of JIP-1 prevents
apoptosis in sympathetic neurons. J Biol Chem 276, 4531-
Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M,
Schorderet DF, Bogousslavsky J, Bonny C (2003) A peptide
inhibitor of c-Jun N-terminal kinase protects against excito-
toxicity and cerebral ischemia. Nat Med 9, 1180-1186.
Borsello T, Bonny C (2004) Use of cell-permeable peptides
to prevent neuronal degeneration. Trends Mol Med 10, 239-
A, Borsello T (2007) Time-course of c-Jun N-terminal kinase
activation after cerebral ischemia and effect of D-JNKI1 on
c-Jun and caspase-3 activation. Neuroscience 150, 40-49.
Wang J, Van De Water TR, Bonny C, de Ribaupierre F, Puel
JL, Zine A (2003) A peptide inhibitor of c-Jun N-terminal
kinase protects against both aminoglycoside and acoustic
trauma-induced auditory hair cell death and hearing loss.
J Neurosci 23, 8596-8607.
Zhuang ZY, Wen YR, Zhang DR, Borsello T, Bonny C,
Strichartz GR, Decosterd I, Ji RR (2006) A peptide c-Jun N-
terminal kinase (JNK) inhibitor blocks mechanical allodynia
after spinal nerve ligation: respective roles of JNK activation
in primary sensory neurons and spinal astrocytes for neu-
ropathic pain development and maintenance. J Neurosci 26,
Beckham JD, Goody RJ, Clarke P, Bonny C, Tyler KL (2007)
Novel strategy for treatment of viral central nervous system
infection by using a cell-permeating inhibitor of c-Jun N-
terminal kinase. J Virol 81, 6984-6992.
Milano G, Morel S, Bonny C, Samaja M, von Segesser
LK, Nicod P, Vassalli G (2007) A peptide inhibitor of
c-Jun NH2-terminal kinase reduces myocardial ischemia-
Circ Physiol 292, H1828-H1835.
C, Stocchetti N, Borsello T, De Simoni MG (2009) c-Jun
N-terminal kinase pathway activation in human and exper-
imental cerebral contusion. J Neuropathol Exp Neurol 68,
Page 10
X. Antoniou et al. / JNK3 in Neurodegeneration
[70]Suckfuell M, Canis M, Strieth S, Scherer H, Haisch A (2007)
Intratympanic treatment of acute acoustic trauma with a cell-
permeable JNK ligand: a prospective randomized phase I/II
study. Acta Otolaryngol 127, 938-942.
Chen JT, Lu DH, Chia CP, Ruan DY, Sabapathy K, Xiao ZC
(2005) Impaired long-term potentiation in c-Jun N-terminal
kinase 2-deficient mice. J Neurochem 93, 463-473.
Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT,
Maeda K, Karin M, Hotamisligil GS (2002) A central role
for JNK in obesity and insulin resistance. Nature 420, 333-
Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L,
Manning AM, Firestein GS (2001) c-Jun N-terminal kinase
tion in inflammatory arthritis. J Clin Invest 108, 73-81.
Tsuiki H, Tnani M, Okamoto I, Kenyon LC, Emlet DR,
Holgado-Madruga M, Lanham IS, Joynes CJ, Vo KT, Wong
AJ (2003) Constitutively active forms of c-Jun NH2-terminal
kinase are expressed in primary glial tumors. Cancer Res 63,
Han Z, Chang L, Yamanishi Y, Karin M, Firestein GS (2002)
Joint damage and inflammation in c-Jun N-terminal kinase 2
knockout mice with passive murine collagen-induced arthri-
tis. Arthritis Rheum 46, 818-823.
Keramaris E, Vanderluit JL, Bahadori M, Mousavi K, Davis
RJ, Flavell R, Slack RS, Park DS (2005) c-Jun N-terminal
kinase 3 deficiency protects neurons from axotomy-induced
phorylation. J Biol Chem 280, 1132-1141.
tosis but not oxidative stress in nerve growth factor-deprived
sympathetic neurons. J Neurochem 78, 298-303.


text:
GA Tech - Men of Principle Scholarship
Beta Theta Pi is a men's fraternity dedicated to developing men of principle for a principled life, and offer the Men of Principle Scholarship for $500 to undergraduate non-Greek men who strive for academic success, are dedicated to their communities and serve as good role models for others. Betas believe in a strong commitment to community and this is a way to give back to Georgia Tech. Applications for incoming freshman to GA Tech are available Download Men of Principle Scholarship
Posse Scholarship for Juniors
The Posse Scholarship is a highly selective scholarship that offers a full ride to select colleges. Nominations for the Posse Scholarship must be completed by the School Counselor in May. The colleges that receive the Posse Scholarship are: Bard College, Boston University, Brandeis University, Texas A & M., The College of Wooster and Syracuse. If a Junior is interested in applying to any of these colleges and the Posse Scholarship, they must see their School Counselor to ask to be nominated by May 9th.
Summer Employment
Property Masters is looking for summer employment for a landscape yard assistant and landscape manintenance technician. Information about the postions are available here Download Landscape Assistant Download Yard Assistant

subset: commoncrawl


text:
DULUTH, MN (KDAL) - An old 16 inch water main broke in downtown Duluth late Tuesday afternoon leaving the roadway in the area of Superior Street and Lake Avenue under water. Crews were able to shut off the water supply and repairs are underway. Some traffic restrictions may be needed in the area. The pipe that broke was around 125 years old.
Free Talk Live 6:00 PM - 9:00 PM
On Air Now.


text:
Compare Products: Check up to four products with to see a side-by-side comparison
Your search did not find any results. Try entering a different search term, removing some search filters or click here to view this page with no search filters.
Choose models that accommodate standard size breads, or bagel sizes from popular manufacturers. These conveyor toasters are perfect in areas where high volume use is common, like college dining halls and breakfast buffets, or behind the counter in a bakery, bagel shop, café, coffee shop, or deli! Help make the job even easier by picking up a butter spreader for bagels and breads. And be sure to check out other bread knives and handheld butter and cream cheese spreaders.
Other Cooking Equipment
- Commercial Gas Restaurant Ranges with Oven
- Manual Fryer Oil Filtration Machines
- Commercial Gas Restaurant Ranges with Storage Base
- Countertop Electric Ranges
- Fryer Oil Stabilizer and Fryer Filter Powder
- Fryer Parts and Accessories
- Countertop Electric Commercial Charbroilers
- Tilt Skillets / Braising Pans
- Outdoor Fryer Accessories
- Waffle Cone Makers
- Griddle Parts and Accessories
- BBQ Basting Accessories
- Charbroiler Condiment Rails
- Charbroiler Heat Shields
- Charbroiler Racks
- Cooking / Grilling Accessories


text:
Heavy Duty Fuse Holder
Rugged screw type in-line fuse holder accepts standard 1/4" (dia.) x 1-1/4" (L) glass type fuses up to 20A. Molded ABS housing is perfect for a variety of automotive and security applications. Attached lead is 12AWG stranded wire, covered with red insulation.
Quick Delivery and product works excellent
Login Here to rate and review this product.
21-7636 - Safety Glasses - Clean Lens Black Frame
96-2195 - Self Centering Tape Measure
Using the Lufkin® Self-Centering 25' tape is amazingly simple. To find the center of the object you're measuring, you just measure it, reading from the top row of black numbers. Then, you look directly opposite the black numbers to a row o...
33-7701 - DirecTV Standard Receiver D12
With the DIRECTVreg; D12 receiver, you can access over 250 digital-quality channels, plus access interactive capabilities and a customizable on-screen program guide. Explore and personalize all of your viewing options quickly and easily with the included remote co...
555-6635 - 7 in Weather Resistant PA Horn
Weather Resistant PA Horn
Weather resistant, double re-entrant loudspeakers are available for medium and high powered sound distribution. Perfect in any paging application in warehouses, outdoor lots, and public facilities. Screwdriver tap adjustment allows easy ...
21-1040 - Rosin Core Solder - 60/40 Tin/Lead - 1LB
Rosin Core Solder(one pound)
Ideal for general purpose electronic repair and assembly use. Tin/lead formulation provides the lowest possible melting point.
MCM Cat 57, Page 724
MCM Cat 56, Page 661


text:
free shippingon orders over $49*
|Bold lines and strong patterns define the Fulham Road Collection. The striped patterns and rich colors will give your room a very warm and mature finish. This collection can be the perfect match for both the simple and sophisticated tastes. All products in this collection are made with the meticulous care that defines the Mystic Valley Traders name.


text:
RALEIGH, NC—Following Rick Santorum's announcement Tuesday that he would end his bid for the Republican presidential nomination, candidate Newt Gingrich called upon frontrunner Mitt Romney to drop out of the race so the former House speaker could concentrate on the general election. "While I respect my challenger's right to fight through to the bitter end, the time has now come to unite behind one man so we can take back the White House in November," said Gingrich, addressing a crowd of 35 supporters at the Raleigh County Public Library. "My opponent should be congratulated on running a fine campaign. But I need him to swallow his pride, come back to reality, and tell all Republicans to throw their support behind Newt Gingrich as the next president of the United States." Gingrich noted that Romney's withdrawal would bolster Gingrich's fundraising efforts as he seeks to eliminate some of the $4.5 million in debt he has amassed thus far in his victorious campaign.
More News in Brief
Poll: 89% Of Illegal Immigrants Would Prefer Path To Corporate Status
WASHINGTON—A new survey published Friday by Gallup researchers revealed that an overwhelming majority of illegal immigrants residing in the U.S.
Secretary Of Interior Says Knocking Down Rocky Mountains Could Really Open Nation Up
WASHINGTON—Saying the renovation project will give the country a more modern look, U.S. Secretary of the Interior Sally Jewell told reporters Friday that ...
Koch Brothers Encouraging Youth To Make Voices Heard By Registering Super PAC
WICHITA, KS—Saying that perspectives of young Americans are rarely represented in today's political discourse, Koch Industries executives Charles and David Koch released a ...


text:
No WAY Jose.
Lame, I don't know if I will be on tonight. Got invited to a paaaaaartayyyy.
Or how about you just get on Steam you ****.
I re-added you. Try anything funny, and I'll be the one fookin you in the ****.
Pew pew pew
Didn't think I'd do it, huh? You're on a 1 month time-out. Then I will think about it.
million internets to you, sir.
nice **** girl
Awesome GIF is awesome. :D
Well, it shoots bullets, that's all I need. It's comfortable more than anything else. And girls tend to look at you more than usual. Great success.
Senior Member
Banned user
Potential Getaway Driver
Antithesis of the mankind
only exposed
Suspended for infractions
Slappa Da Bass


text:
Upload Photo
In a dramatically dark space with a decor that evokes Frank Lloyd Wright, you'll find what may be the smokiest, most flavorsome vegetable burger going. This is Houston's, at Roosevelt Field in Garden City.
10 DIY backpack design ideas 15 places to cool off on LI 30 tips from teachers for a successful school year The 10 best steak houses on Long Island 10 must-try rides on Long Island LI clam shacks: A dozen to dive into 15 stylish backpack alternatives 101 new restaurants on LI 15 fun things to do with kids this summer Our favorite candy through the years LI wedding venues: unique spots to get married LI's 10 best barbecue restaurants


text:
Action, The
Sixth National Jazz and Blues Festival, Windsor: Jazz on a Summer's Weekend
Live Review by uncredited writer, Melody Maker, August 1966
A washout, but still swinging ...
Underground: The Writing is on the Wall for Pete Brown and Action!
Profile and Interview by Hugh Nolan, Disc and Music Echo, November 1968
WAY BACK in 1960 Pete Brown gave everything up to try to make a living writing poetry. Not surprisingly, it wasn't too easy — five ...
Book Excerpt by Michael Lydon, 'Boogie Lightning' , 1974
IN THE FALL OF 1966 the Action were at their zenith, one short step above complete obscurity. For one all too brief moment they had ...
back to LIBRARY


text:
Brain Parade brings developers together for Autism Speaks
This blog post is by Jim McClafferty, Brain Parade Founder and President.
... More...
Weekly Whirl - Our Favorite Tweets!
If anyone knows how hectic life can get – WE DO! That's why we have created the Autism Speaks Weekly Whirl to fill you in on all of the highlights of the week! The last thing we want is for you to be left out of the loop! Please sh... More...
Autism America Radio - Saturday January 21st
Autism America Radio welcomes special guests, author and athlete Rodney Peete and attorney Valerie Vanaman.
Join hosts Matthew Asner and special guest host, author Monica Holloway for two hours of talk and interviews this Saturday 6:... More...
[ Canada | Middle East | 한국어 | En Español | Privacy | Terms of Service | State Fundraising Notices |
Community Guidelines | Affiliate Program | Contact Us | Site Map | Employees | RSS ]
© 2014 Autism Speaks Inc. Autism Speaks and Autism Speaks It's Time To Listen & Design are registered trademarks owned by Autism Speaks Inc. All rights reserved.


text:
Bottega Veneta Extremely Limited Special Edition Intrecciato Sac Tresse Lizard Tote Bag. Available for your consideration is a magnificent, timeless and Authentic Bottega Veneta Special Limited Edition Intrecciato Lizard Sac Tresse Bag. It is number 74 of only 200 produced. From Bottega Veneta's 2006 collection, the bag was crafted in Italy of exotic, intricately woven Intrecciato lizard leather with antique-finished silver metal pieces. The Bottega Veneta Intrecciato Sac Tresse in lizard is the crown jewel of tote bags everywhere. Purveyors of luxury handbags, who demand the best, recognize it as being in a class of its own. The bag is so irresistible that all others pale in comparison. In 2006, the Bottega Veneta Special Limited Edition Intrecciato Lizard Sac Tresse Tote Bag retailed for $7,800.00.
The bag measures approximately 12" high x 15" wide x 2.5" deep. The comfortable and adjustable rolled leather handles have a fall length of between approximately 5" and 7". The interior of the bag includes a sizable zip pocket. The bag is in excellent, previously worn condition. The antique-finished silver metal pieces have some faint scratches.
The magnificent and exceedingly upscale Bottega Veneta Special Limited Edition Intrecciato Lizard Sac Tresse Bag will come to you safely tucked inside its Bottega Veneta signature dust cover and box. You will also receive the Bottega Veneta Controllato Card and booklet.


text:
Evelyn Lozada reveals the sex of her baby & she's having a...
For the last few months, Evelyn Lozada has been announcing a LOT of happy news.
Back in November, the Basketball Wives star announced that she was expecting her second child. Then in early December, Lozada revealead the identity of the baby's father--Los Angeles Dodgers outfielder, Carl Crawford! nd over Christmas break she made ANOTHER announcement: that she and Crawford got engaged over the holidays!
Now, Lozada is making yet ANOTHER major announcement: her second child will be a ...
Read more ¿Qué más? Evelyn Lozada is engaged, SEE her huge rock!
...boy! The reality star broke the news with People Magazine, saying: "I found out when I had my first trimester screening. I was about 13 weeks when they told me the sex! My daughter Shaniece was with me and we were both soooooo happy!"
She also told People that she was hoping she would have a baby boy. "I have wanted to have a son for years!" said Lozada. "There are all girls on my side of the family, so this will be our first boy. My family is over the MOON!"
And what does her 20-year-old daughter Shaniece think? Well, she couldn't be more excited that it's a boy. "Shaniece is just happy that she can still be the princess of the family," jokes Lozada. "I can't tell you how excited she is. Her brother is already her BFF in her head."
And although she and fiancé Carl Crawford have yet to decide on a name, Lozada says they plan to celebrate their baby news with a lavish baby shower on February 8 in Los Angeles, hosted by Lozada's daughter Shaniece and Evelyn's close friends Shaunie O'Neal, Danika Berry and Teresa Caldwell.
Lozada is seven months pregnant and due in March.
Evelyn, we are SO happy for you and we know you're going to be a great mom. Congrats!
Image via Evelyn Lozada
Keep Reading
- Neymar Says Back Injury From World Cup Is Nearly Completely Healed - Fox News Latino
- More Unmarried Women Over Age 35 Having Babies - Fox News Latino
- Jasmine V Wants Domestic Abuse Victims To Know They 'Have A Voice' - Fox News Latino
- J.Lo Takes A Selfie In The Bathtub - Huffington Post Latino Voices
- Student Filmed Hundreds of Women in Bathroom: Cops - Newser


text:
Advanced Placement Credit
School of Management Policy
School of Management students may receive advanced placement credit by achieving a qualifying score on the appropriate advanced placement subject-matter examination administered by the College Entrance Examination Board (CEEB) or by the American College Testing (ACT) Program. The School of Management does not give credit for College-Level Examination Program (CLEP) exams. Depending on the score achieved on an advanced placement subject-matter test, a student may receive academic credit.


text:
7″ Vinyl is now shipping!
Our new 7-inch records are now shipping! They look and sound awesome! Order yours today!
Our Daytrotter session is now up! You can check it out right here.
The time has come for another UMS. We will be at Illegal Petes on South Boradway at 11:59PM on Saturday 7/26. Don't be a knuckle head, come eat a burrito and listen to some rock n roll. More info here.
Pre-Order your seven inch vinyl right here.
Tour Kick Off
UMS 2014 Bands Announced!!!
Root 40 Music Festival 2014
Root 40 Music Festival is next week! We play Saturday May 26th on the Argonaut main stage at 2pm. Be there ya big wierdo!!! Find all the info you need right here.
Tough Kids makes Westword's "Ten Best Denver Album Covers 2013″
El Presidente Remix Project
In honor of Presidents Day, we decided to put together a little remix project for our song, "El Presidente." Download the track stems, play around with them, and then send your remix to us at email@example.com via hightail or dropbox or similar service, and we'll add it to the album for free download. Head on over to the album page to get started: https://choosetheoutfit.bandcamp.com/album/el-presidente-remix-project


text:
- Microsemi delivers a solid fiscal third quarter and guides to a slightly better fourth quarter as markets like aerospace, defense, and medical seem to be picking up.
- Microsemi's underrated FPGA business outgrew the market this quarter.
- I estimate a fair value of $32 for Microsemi, making it one of the cheapest non-distressed chip stocks out there.


text:
Connect with us.
Written by P.D. Eastman
Written by Tish Rabe
Written by Vince Vawter
Written by Sharon KaneIllustrated by Sharon Kane
Written by Patrick NessIllustrated by Jim Kay
Written by Jennifer Richard Jacobson
Written by RaffiIllustrated by Nadine Bernard Westcott
Written by Jez AlboroughIllustrated by Jez Alborough
Written by Martin WaddellIllustrated by Patrick Benson
Written by Karen KatzIllustrated by Karen Katz
Written by Janet FrankIllustrated by Tibor Gergely
Written by Deborah UnderwoodIllustrated by Stephen Gilpin
Written by Luciana Navarro Powell
Written by Katrina GermeinIllustrated by Tom Jellett
Use of this site indicates your consent to the Terms of Use. Copyright © 1995-2014 Random House LLC. All rights reserved.


text:
Explain how a figure can be a rectangle, a rhombus, and a square.
Quadrilateral AnswersMost Active Answered Newest Most Votes
what type of quadrilaterals has perpendicular sides.
Prove: if a quadrilateral has one pair of sides both parallel and congruent then the quadrilateral is a parallelogram.
I think I have to prove that the other opposite sides are also parallel, but I am not sure how to do it. It is given that the other opposite sides are congruent and parallel.
ABCD is a rectangle in which diagonals AC bisects angle A as well as angle C. Show that ABCD is a squre.
give it to me now please please..................
does a quadrilateral have to have four congruent sides
Show me a shape quadrilateral


text:
Related quotes
"I was eating burritos with this girl and she asked me to be her prom date. How could I say no? We went and had a great time."
"They originally talked about moving the prom to the night before either graduation or graduation practice, ... because if you don't show up to practice, you're not allowed to walk, which I thought was understandable. We'd have our prom, the next day show up to practice."


text:
Freezin' for a reason! Plunge into the Atlantic to help children!
Walk or Roll on Saturday May 17th in beautiful Johnson Park. Bring the whole family for the FREE carnival to follow!
Limited spots available for the 25th Annual Golf Classic at Fairmount Country Club.
Check out our new location this year at the beautiful Pine Barrens Golf Club in Jackson, NJ.
Night at the Casino! Saturday, April 12, at the Plainfield Country Club.


text:
Home Accounting for Android and Windows
Tired of not controlling your expenses? Thanks to this application of personal and household finances is now possible. Condra Home Accounting makes your life easier
Record at the time the expenditure and income you make, and keep a virtual balance of your own home accounting.
Always at hand, it will be very easy to know the money you have at all times.
Control your expenses easy and fast with Condra Home Accounting!
You can make report of your data and export it to PDF.
Buy the android app in Google Play for only 1,15$ and use it in several devices along with the Desktop version


text:
Births- Jan. 15
Lakewood Health System, Staples
Michelle and Jonathan Nevala, Sebeka, a boy, Ian David, 6 pounds, 9 ounces, Dec. 23, 2011.
Nicole and Thomas Petroske, a girl, Lynsie Emma, 7 pounds, 9 ounces, Dec. 24, 2011.
Amanda Plattner and Jason Denniston, Aldrich, a boy, Gabriel Schey, 8 pounds, 13 ounces, Dec. 26, 2011.
Nanette and Mackenzie Nelson, Wadena, a boy, Declan Mackenzie, 8 pounds, 13 ounces, Dec. 27, 2011.
Are you a newspaper subscriber but you don't have a Digital Access account yet? https://secure.forumcomm.com/?publisher_ID=40&event=subscriber/lookup.
You will need your subscription account number and phone number. Not sure if you have an account? Email us at email@example.com and we can help you.


text:
Part of the flowerbox group established in 1975.
We bring 37 years of experienced floristry to our customers, no matter what your requirements our team of qualified florists will always create a unique floral gift.
Not only will your floral gift be unique, but why not make it extra special by adding chocolates, balloons, wine, champagne or even a cute teddy bear.
All our flowers are bought each day direct from the leading flower auctions in Holland this method not only guarantees freshness, but also cuts out any middle men which in turn adds
extra flower value to you our customer.
The Flower Box is part of Interflora, therefore any orders placed before 2pm, can be with you that very same day for just a £8.99 delivery charge. However if you do not need them
that same day you can order for FREE next day delivery or a date of your choice.
Sign up to the Flower Box newsletter to receive all of our latest offers, info and deals straight to your email inbox!


text:
Welcome To Spirit HalloweenX
Thank you for signing up to receive Spirit Halloween emails!
You will now be eligible to receive special email offers and discounts.
So Much Fun It's Scary! - Only Days Until HALLOWEEN!
Cookie Monster Hat
1 - 2 of 2
Sort by:
1 of 1
Sort by:
1 of 1
Cookie Monster Flatbill Hat
A tip of the hat to this easy costume - party like a monster when you sport the officially licensed Cookie Monster flatbill hat! Wear it any way you want and get all the treats, and the cookies.
Cookie Monster Bib Hat Set
Your baby's first words will be "Me want cookie" on Halloween when you dress your little on in this officially licensed Cookie Monster Bib Hat Set. Blue cap with signature character googly eyes and green bib with furry body print holding a cookie included.
Sort by:
1 of 1


text:
The Christmas story will come to life at Redeemer Lutheran Church in Marana's Continental Ranch community this weekend, and you don't even have to get out of your car to participate.
The 70-year-old-plus church is holding a drive-through Live Nativity, with volunteers from the congregation assuming the roles of Mary and Joseph, shepherds and Roman soldiers.
Visitors will drive through the church's parking lot and wind their way through several stations, where they will hear children and adults sing and hear Redeemer Pastor Adam Mueller tell the story of Christ's birth. Participants will listen to Mueller through their car radios.
In addition to the volunteers, the cast will include a trio of sheep.
The drive-through Live Nativity, spearheaded by congregation member Tawnya Caldwell, is modeled after a similar event held at Word of Life Lutheran Church in Surprise. It will be held from 6 to 9 p.m. Friday and Saturday at Redeemer, 8845 N. Silverbell Road, in Continental Ranch.
Admission is free. For details go to redeemertucson.com online or call 572-8136.


text:
Where Mandela Kept Hope, Guide Tells Their Shared Sagatags: NYT, South Africa, Nelson Mandela, apartheid
CAPE TOWN, South Africa — As Ahmed Kathrada led President Obama and his family recently through the prison on Robben Island where Mr. Kathrada had spent much of his life, he explained how the rules of apartheid had granted him, because of his Indian ancestry, long pants and socks. One of his fellow inmates, Nelson Mandela, as a black man, received short pants and no socks.
Mr. Kathrada, 83, also showed the Obamas the sign listing the different amounts of sugar, coffee, soup and other foods that South Africa's prison system had apportioned to blacks; mixed-race inmates, who were known as coloreds; Indians; and whites.
"In everything there was apartheid," he said in an interview on Thursday in his small apartment here in the shadow of Table Mountain....
comments powered by Disqus
- WWII Atomic Bomb Project Had More Than 1,500 "Leaks"
- Neanderthal 'Art' Found In Cave Sheds Surprising New Light On Ancient Intelligence
- Midterm Election Mind-Reading: The Market Tends to Win
- Proof surfaces for affair between Queen Victoria and her male assistant
- Could humans cause another Paleocene-Eocene Thermal Maximum?
- Marcus Rediker says it was pirates, slaves, and motley crews who shaped the modern world, not the big heroes we hear so much about
- Pro-Israel website chides Middle East Studies professors, claiming they're apologists for Hamas
- UCLA Economist, Known as Railroad Historian, Dies at 89
- David Rosand, an Art History Scholar Whose Heart Was in Venice, Dies at 75
- NYT interviews Rick Perlstein about his book


text:
All HCPL branches will be closed on Monday, September 1. We will reopen on Tuesday, September 2 for regular hours.
Lone Star College - Cy-Fair Library will close at 4:30 PM on Friday, August 29 and be closed Saturday, August 30 - Monday, September 1.
Lone Star College - Cy-Fair Library will close at 4:30 PM on Friday, August 29 and be closed Saturday, August 30 - Monday, September 1.
ADA Info
Value Line recently debuted a new and improved interface. We have developed a PDF with information on where to find your favorite reports. In addition, there is also a video from Value Line that explains the changes.
Have you noticed that you can now access Value Line from you home computer? If you are researching stocks you can go into the the databases from the HCPL home page and then into business section. There you can find Value Line and access it by using your library card. Tracking your investments has never been easier.
Harris County Texas
Mobile Site
About the Library
Locations & Hours
Holiday Closings
Library Cards
Military Library Cards
HCPL Digital Media Catalog
Interlibrary Loan
Meeting Rooms
Purchase Suggestion
Library Jobs
Job Search Guide
Frequently Asked Questions
Ask a Librarian
Staff List
Connect with HCPL
Staff Login
Information for Persons with Disabilities: Harris County Public Library will make reasonable accommodations for persons with disabilities who are interested in attending library programs. To make a request for yourself or someone you know, please notify the Branch Librarian two working days in advance of the program.
The Harris County Public Library Website by Harris County Public Library is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 United States License. It is designed for 1024x768 resolution and Internet Explorer 7+, Firefox 3+, and Safari 3+ browsers. For additional information, see our Credits page.


text:
A United Kingdom man, Eamonn Kilbride, died from a heart attack at his job's Christmas party after dancing to the widely popular "Gangnam Style."
Kilbride, 46, had been doing the fast-paced dance moves to Psy's "Gangnam Style" with his co-workers when he suddenly collapsed,
The dance includes motions similar to riding a horse while spinning an imaginary rope over ones head.
The incident occurred at an office party for the Thwaites brewery, where Kilbride worked as an IT manager.
Kilbride leaves behind a wife and three children.
(Photo Credit: AP)
Also On Black America Web:
AUGUST: This Month in Black History
http://ioneblackamericaweb.files.wordpress.com/2013/08/1-aug1st-ronbrown.jpg?w=180&h=180&crop=1 http://ioneblackamericaweb.files.wordpress.com/2013/08/2-aug-2nd-philippaschuyler.jpg?w=180&h=180&crop=1 http://ioneblackamericaweb.files.wordpress.com/2013/08/3-aug-3rd-syreeta-wright.jpg?w=180&h=180&crop=1 http://ioneblackamericaweb.files.wordpress.com/2013/08/4-aug-4th-presidentobama.jpg?w=180&h=180&crop=1 http://ioneblackamericaweb.files.wordpress.com/2013/08/5-aug5th-naomisims.jpg?w=180&h=180&crop=1


text:
RHIANNA REB'L FLEUR for Woman EAU DE TOILETTE Spray 3.4 Oz (100ml) Is An Intense And Glamorous Fragrance Introduced In 2010. This Perfume Is A Creation By Caroline Sabas And Marypierre Julien From The House Of Givaudan. Women Will Be Intrigued By The Sophisticated And Daring Qualities Of This Fragrance. It Expresses The Wearer's True Self And Confidence. The Top Notes Burst Open With Tuberose, Violet, And Hibiscus. The Heart Notes Brim With Refreshing Coconut Water. These Notes Are Masterfully Balanced On A Smooth Base. The Perfume Is Contained Within An Elegantly Designed Bottle In The Shape Of A High Heel. It Is Decorated With Silk Ribbons And Has A Golden Ring Stopper. RHIANNA REB'L FLEUR Perfume is recommended for casual occasions
When applying any fragrance please consider that there are several factors which can affect the natural smell of your skin and, in turn, the way a scent smells on you. For instance, your mood, stress level, age, body chemistry, diet, and current medications may all alter the scents you wear. Similarly, factor such as dry or oily skin can even affect the amount of time a fragrance will last after being applied.
For external use only. Avoid contact with eyes. Keep away from naked flame or direct heat sources. Do not apply to sensitive skin. Do not apply to broken or inflamed skin. If irritation develops, reduce frequency or discontinue use.
Buy Perfumes Online. 100% Genuine Fragrances. Guaranteed. Brand Name Perfumes!
Free Shipping ONLY for USA Customers
List price: $59.00
You save: 55%
An an valley indeed so no wonder future nature vanity. Debating all she mistaken indulged believed provided declared. He many kept on draw lain song as same. Whether at dearest certain spirits is entered in to. Rich fine bred real use too many good. She compliment unaffected expression favourable any. Unknown chiefly showing to conduct no. Hung as love evil able to post at as.
Guest it he tears aware as. Make my no cold of need. He been past in by my hard. Warmly thrown oh he common future. Otherwise concealed favourite frankness on be at dashwoods defective at. Sympathize interested simplicity at do projecting increasing terminated. As edward settle limits at in.
And produce say the ten moments parties. Simple innate summer fat appear basket his desire joy. Outward clothes promise at gravity do excited. Sufficient particular impossible by reasonable oh expression is. Yet preference connection unpleasant yet melancholy but end appearance. And excellence partiality estimating terminated day everything.
Surprise steepest recurred landlord mr wandered amounted of. Continuing devonshire but considered its. Rose past oh shew roof is song neat. Do depend better praise do friend garden an wonder to. Intention age nay otherwise but breakfast. Around garden beyond to extent by.


text:
Serving your area
Serving your area
1020 12th St, Erie, IL 61250
Serving your area
LET OUR FAMILY MOVE YOUR FAMILY. All My Sons Moving and Storage is family owned and operated with over four generations of moving experience.
Serving your area
Full Service Pick Up & Deliveries. Great Prices From Excellent BBB Pro...
Serving your area
Prescreened and Rated with HomeAdvisor. Hire with Confidence Today!
Serving your area
Let HomeAdvisor Match you to Full Service Moving and Storage Pros
Serving your area
User Reviews & Service Guarantee. Find a Prescreened Shed Contractor!
14.1 Miles
(563) 726-3337
2103 Buffalo Ave, Davenport, IA 52804
Latest review: "Clean, Brand New and secure. Add that to pleasent, honest owners who actuallly care about y..."
3.0 Miles
(309) 496-9145
1414 179th Street North, East Moline, IL 61244
3.8 Miles
(563) 332-8875
7185 State St, Bettendorf, IA 52722
Visit our other local sites: Daily-Journal.com | MyWebTimes.com | PostBulletin.com
Copyright 2014 QCOnline All Rights Reserved
Copyright 2014 Local Corporation - US Patent Number 7,231,405. - Privacy Policy - Terms of Service
Some data provided by Acxiom.


text:
In Stock
Expected to ship by .
Place your mouse over large image above to zoom.
Click to view enlarged image.
To view an item in an alternate color, place your mouse over a swatch above.
To view item in an alternate color, click on a swatch above.
Item #: 0538-03024-1265
has a broad-based heel for added sure footing.
Full and half sizes:
(based on 147 reviews)
of respondents would recommend this to a friend.
Best Uses
Feels full size too small
Feels half size too small
Feels true to size
86% (126 reviews)
(126 reviews)
Feels half size too big
Feels full size too big
Feels too narrow
Feels true to width
92% (130 reviews)
(130 reviews)
Feels too wide
Reviewed by 147 customers
Sort by
Displaying reviews 1-10
Back to top
Previous | Next »
I would and will be buying this product
By Smileysgypsy
from Rogersville, TN
About Me Comfort-oriented, Disabled, Needs To Exercise Walkin, With Back And Neck Issues
Comments about Jessica London Propet® Stability leather walking sneaker:
If you choose the right size, it's like your foot is being hugged by cusions all around it. Provides support where needed. Comfortable to walk in. Great ankle support. My go to shoes now.
Was this review helpful? Yes / No
- You may also flag this review
I will buy again
By Tricia
from Ridgeland
About Me Comfort-oriented
Bottom Line Yes, I would recommend this to a friend
(1 of 1 customers found this review helpful)
Great shoe
By Lynn
from Milwaukee, WI
I am mobility challenged and have been wearing these shoes for years, only tennis shoes that work for me.The wide based heel provides great stability & support. Reduced my knee & back pain.
I would buy this product again
By Grandmom
from Philadelphia, PA
About Me Comfort-oriented, Practical
I have a hard time finding a shoe wide enough for my feet. So far this one is just what I need.
Just as descrbed!
By Old Gal
from Chicago
About Me Practical
first new pair of shoes in two years! Comfortable and help my bad ankles keep me up right!
Great walking shoe
By Barb
from St.Paul, MN
I have been purchasing this brand walking shoe for about 10 years. Always great fit and wearablity as well as affordable.
Walking feels better with Propet!
By Josie
from Chaska,Mn
I love a great shoe and it beats the over $100 ones I used to buy!
not good
By none
from Crystal River, Fl
Not the right one
Bottom Line No, I would not recommend this to a friend
good support
By momma D
from Corning,NY
Propet Stability leather Walking Sneaker
By sweetspirit
from Jackson Ga
About Me Practical, Stylish
These were purchased for my daughter who needs exta wide shoes and has suffered from swollen ankles, the fit great! Using a coupon helped with the price..../
Our goal is your complete satisfaction! If we have not delighted you, all unworn, unwashed or defective merchandise may be returned within 90 days. We are happy to send you a new size, color or style or issue a refund for the purchase price (excluding shipping and handling charges). For returns made after 90 days we will issue a gift card equal to the purchase price (less shipping and handling charges) that can be used toward a future purchase.


text:
iPad Air 2 Rumoured To Be Launching October 21August 12, 2014 | William Jackson+
Apple's iPad Air 2 is rumoured to be launching on October 21′st and will feature some very interesting additions to the screen.
Apple Gears Up For Healthkit RolloutAugust 12, 2014 | William Jackson+
Apple are preparing to launch their new service called Healthkit and they have been discussing the ideas and features and what will be launching soon.
What Apple Product You Should Choose This Year?August 11, 2014 | AppleFanSite+
With Apple introducing more and more products on to the market giving customers more and more choice it is becoming harder and harder to choose what you want this year
New Lets Fly Application Designed By Mathew MartinoAugust 11, 2014 | William Jackson+
The lets fly app contains vital information for aviation enthusiasts and PPL students and is based on the books by Matthew Martino
Uswitch, BuyMobiles.net and 3 Offering iPhone 5s For FreeAugust 11, 2014 | William Jackson+
Three major UK mobile giants are offering a free iPhone 5s deal to their customers ahead of the rumoured iPhone 6 launch.
Gliph Private Messaging App Supports Bitcoin AgainAugust 10, 2014 | William Jackson+
The makers behind the Gliph private messaging app have once again allowed Bitcoin's to be sent using the application.
Apple Donates $1.6 Million To China Earthquake Relief EffortsAugust 10, 2014 | William Jackson+
Apple have announced they made a donation of $1.6 Million to help with the relief effort after the Chinese earthquake last month.
AppleFanSite Predicts Features Of The iPhone 6August 10, 2014 | William Jackson+
With the iPhone 6 predicted to hit the shelves within a month, we predict exactly what we think will feature in the new iPhone
Apple iTunes Update Brings With It Podcast FixAugust 9, 2014 | William Jackson+
Apples latest iTunes Update brings in some major updates for its Podcast application solving a continuing problem for podcast listeners where subscribed podcast's stop updating with new episodes.
$324.5 Million Settlement Rejected By California JudgeAugust 9, 2014 | William Jackson+
Some 4 California companies including Apple and Google have failed to convince a US judge to sign off on a $324.5 million settlement to resolve a lawsuit by tech workers.
Sam Sung Apple Worker eBay's Name CardAugust 9, 2014 | William Jackson+
Sam Sung, from Vancouver, Canada, worked at the city's Apple store and is selling his staff lanyard and business card for charity.
iPhone 6 Expected To Get Three More Major UpgradesAugust 8, 2014 | William Jackson+
Apple could be pulling out all the stops for the iPhone 6 launch next month and now there is even more features expected to hit this much anticipated device.


text:
Find records of Sarah Briscoe
Find birth, death, marriage, military, and other records of Sarah Briscoe at Ancestry.com.Search for records
Biography & Family History Add details
Sarah Briscoe (1680 - 1718) was born in 1680. She was born into the Briscoe family.
There are no known marriages or children on record for Sarah. Sarah died in 1718 at age 38.
This genealogy of Sarah Briscoe's life was created by AncientFaces members Share any information you have to connect to the people who know her. Some common things we would like to know about Sarah's genealogy:
- Where was Sarah born?
- Where did Sarah die?
- Who was Sarahs family?
- What did Sarah look like? Add some photos of their life.
Family Tree & Genealogy Add / Edit People
You can add or remove people from this genealogy by clicking here.
History of Sarah Briscoe Add details
- Given name
- Sarah
- Surnames
- Briscoe family history
- Born
- Death
- Gender
- Female
Do you know more about Sarah Briscoe?
You can add details to this page and share Sarah's story.
Obituary Add details
We don't have information about the obituary records of Sarah Briscoe. You can add obituary information about Sarah Briscoe by clicking "Add Details".
Discuss Sarah
Share your memories below with the rest of Sarah's family. We'll notify anyone else who is searching for Sarah of your message.
Find records of Sarah Briscoe
Find birth, death, marriage, military, and other records of Sarah Briscoe at Ancestry.com.Search for records


text:
Posts tagged Ministry of Posts and Telecommunications
Orascom has $422 million in cash in North Korea
Dec 16th
Posted by Martyn Williams in Business
Orascom Telecom Media and Technology (OTMT), the Egyptian company that owns a 75 percent stake in North Korea's on 3G cellular network operator, has apparently been doing very well in the North Korean market.
A recent audit report by Deloitte says the company's assets in North Korea stand at US$512 million, of which $422 million is sitting in cash. The figures were obtained using the official exchange rate on September 30. Due to currency controls imposed by the government, that cash isn't readily available to OTMT to withdraw from the country.
"North Korea has implemented currency control restrictions and, in particular, rules More >
Ham radio operators to refine DPRK plans
Jul 2nd
Posted by Martyn Williams in Media
Two ham radio operators hoping to get permission to set up a temporary amateur radio station in North Korea have returned from a trip to the country and have plans to visit again.
Paul Ewing (N6PSE) and David Flack (AH6HY) of the "Intrepid DX" group wrote that they will refine their proposal and "continue to communicate with the Ministry of Foreign Affairs and the Ministry of Posts and Telecommunications."
The two want permission to lead two groups of twelve people each on a More >
Ham radio operators hope to put North Korea on the air
Jun 11th
Posted by Martyn Williams in Media
A group of amateur radio operators are hoping to get permission from the North Korean government for a month-long trip to the country during which they'll set up a ham radio operation.
If they manage to pull off the plan, they'll have succeeded where few have before.
North Korea has no amateur radio operators and government-sanctioned transmissions by foreigners in the country are extremely rare. This makes North Korea the rarest country for contacts in the amateur radio world.
The project is still in the planning phase but is being led by operators with experience of both North Korea and operating in usually closed countries. More >
Koryolink hits 2 million subscribers
Jun 2nd
Posted by Martyn Williams in Cellular
North Korea's Koryolink cellular network has hit the 2 million subscriber mark, majority owner Orascom Telecom said this week.
The landmark was reached in late May, 15 months after it surpassed the million subscriber mark.
Koryolink launched its 3G cellular service in the final days of December 2008 and in the last four years has expanded service to cover all major towns, highways and railways in North Korea.
"When we first acquired the license in North Korea, people thought the service will only be provided to a few privileged individuals," said Naguib Sawiris, Executive Chairman of Orascom Telecom Media and Technology in a statement. "We are More >
Pyongyang denies GPS jamming
May 19th
Posted by Martyn Williams in Electronic warfare
North Korea denied on Friday that it played any part in a two and a half week long jamming of Global Positioning System (GPS) signals in the border area between North and South Korea.
The denial was carried in several state media outlets and said allegations that the DPRK was behind the jamming were part of "a new farce and smear campaign."
The jamming took place between April 28 and May 14 and resulted in several hundred civilian aircraft and ships experiencing disruption to their navigation systems, according to reports. It made GPS signals unavailable or unreliable but didn't result in any serious accidents. South Korean More >
DPRK radio transmitters a national secret
Apr 25th
Posted by Martyn Williams in Media
When North Korea launched a modernization of its broadcasting network in 2011, the Chinese company chosen to supply new TV and radio transmitters to the country faced a problem.
The location of broadcast towers in North Korea is so much of a state secret that engineers from the company weren't permitted to travel to the DPRK to help install the transmitters, the company, Beijing BBEF Science and Technology, said on its website.
Instead, eight North Korean engineers spent a month in China being trained on how to install and operate the devices, which included a medium-power TV transmitter, several shortwave radio transmitters and a powerful More >
Koryolink hits a million subscribers
Feb 3rd
Posted by Martyn Williams in Cellular
Koryolink, North Korea's only commercial 3G cell phone network, has signed up its millionth subscriber. The landmark was reached just over three years since service was launched.
Koryolink has been adding more than 100,000 new subscribers for each of the last five quarters and was expected to hit the million mark in early 2012.
The company is operated by Cheo Technology, which is a joint venture between Egypt's Orascom Telecom Media And Technology Holding (OTMT) and North Korea's Ministry of Posts and Telecommunications. OTMT holds a 75 percent stake and the North Korean government owns the remaining 25 percent.
Koryolink's service has popularized cell More >
Koryolink surpasses 800,000 3G subscriptions
Nov 18th
Posted by Martyn Williams in Cellular
North Korea's nationwide 3G cellular network could miss an end-of-year target to have a million subscribers despite two successive quarters of record subscriber growth.
Koryolink added 142,000 subscriptions in the third quarter, beating the 131,000 subscriptions added in the previous three months, to end September with 809,000 users. That leaves it 191,000 subscribers short of hitting a million users — a 2011 target that had been talked about at the beginning of the year. Based on current subscriber growth it appears that Koryolink will come close to the million mark but — barring a surge of new sign-ups in the current quarter — More >
AP expands KRT video deal to high-def
Sep 30th
Posted by Martyn Williams in Media
The Associated Press has signed a deal with North Korean state television that gives it exclusive rights to high-definition video of major news events in the country.
The deal comes as AP and its biggest competitor, Reuters, race to expand their access to North Korea ahead of the 100th anniversary of Kim Il Sung's birth — an event that is expected to see large scale celebrations and events in Pyongyang around April 15.
The new deal lasts three years and makes London-based APTN (Associated Press Television News) "the only agency to transmit broadcast-quality HD pictures of key news events in North Korea," More >
More details on Star Joint Venture
May 19th
Posted by Martyn Williams in Business
A couple of new details about Star JV, the company now responsible for North Korea's connection to the global Internet, came to light this week.
They were included in a report from the Internet Assigned Numbers Authority (IANA) about the reassignment of the country's dot-kp domain to Star JV.
The report reveals the mission of the company and its president:
Proposed Sponsoring Organisation and Contacts
The proposed sponsoring organisation is Star Joint Venture Company, based in Pyongyang, Democratic People's Republic of Korea. The company is a joint venture between the Korean Post and Telecommunications Corporation, a governmental enterprise; and Loxley Pacific Company Limited. The More >


text:
Reporter: Inmate Took About 640 Gasps Of Air During Execution That Lasted Nearly 2 Hours
Arizona officials say a murderer who was sentenced to death has died nearly two hours after his execution started.
Inmate Facing 15 Years For Escaping Hospital, Assaulting Officer
Washoe County jail inmate who escaped from a Reno hospital room and assaulted an officer before he was shot in the leg has been convicted of several felony charges.
Powder Sent To Nevada Court Came From Inmate
The suspicious powder labeled as anthrax that prompted the evacuation of the Nevada Supreme Court was sent by an inmate at a southern Nevada prison, authorities said Friday.
Inmate Who Walked Away From Work In Reno Captured
Authorities say they have captured an inmate who walked away from his work assignment in Reno.
Inmate Dies In Medical Facility At Nevada Prison
Nevada prison officials say an autopsy will be conducted on the body of a 60-year-old inmate from Virginia who died last week.
Inmate Found Dead In Prison Cell
Authorities say a 62-year-old inmate was found dead in his cell in Ely State Prison this week.
State May Settle With Shackled Pregnant Inmate
The state Board of Examiners is scheduled to consider settling a lawsuit with a former Nevada inmate who was shackled while in labor.
Washoe County Jail Inmate Death Investigated
Washoe County sheriff's deputies are investigating the death of an inmate at the county jail in Reno.
Ex-Inmate Claims Department Of Corrections Shackled Legs During Labor
A former inmate is suing the Nevada Department of Corrections, claiming staff members imposed cruel and unusual punishment by shackling her legs while she was in labor.
Utah Prison Balks At Mental Tests For Inmate
Prison authorities say an inmate charged with killing a guard is so dangerous they can't accommodate a mental evaluation for the man.


text:
Play for life….join a sporting club is the philosophy of the Active After-school Communities (AASC) program.
This philosophy is based on the internationally recognised game sense approach to coaching. The AASC program has adopted this philosophy as it creates a fun and inclusive environment for the introduction of sport and other structured physical activities to primary-school aged children. This approach ensures children of all abilities are engaged in the activities and have a positive and successful experience.
The program introduces up to 70 different sports, as well as 20 other structured physical activities to primary school students across Australia with the aim of inspiring children to join a local sporting club and make sport a regular part of their lives.
Parents can use the AASC club finder to help connect with sporting clubs in their area. Simply select your state and the sport you are interested in and then click Search. Links to relevant websites will appear on your screen.
For more information about the AASC program visit ausport.gov.au/aasc or find your nearest sporting club visit ausport.gov.au/findaclub. To find out more visit the Play for Life...join a sporting club Australian Government, Australian Sports Commission website (new window).
5 Ways to a Healthy Lifestyle
Sporting Clubs and Healthy Kids fact sheet (PDF 359KB)
Dehydration can cause headaches, crankiness and fatigue. Find out how much water you should be drinking every day.
Drinks for Hydration
Find out how much moderate and vigorous activity you should be doing every day.
Get Active Each Day
An initiative of NSW Ministry of Health, NSW Department of Education and Communities and the Heart Foundation.