text:
Documentary Movies
The Academy of Motion Picture Arts and Sciences will soon be giving a gold-plated Oscar for the Best Documentary film. Documentaries have come a long, long way since Robert Flaherty's silent Nanook of the North back in 1922. Here are this year's nominated films:
5 Broken Cameras is a first-hand account of some Palestinians' non-violent resistance to the encroaching Israeli settlements that threatens their village. The Gatekeepers is about the Shin Bet from people on the inside, namely six former heads of Israel's secret security service. How to Survive a Plague is about the early years of AIDS. The Invisible War is about sexual assault in the United States military. The first two are especially recommended.
That's only four of the five nominated. They are informative and engaging and certainly worth seeing. And, of course, that's why you watch a documentary, to be engaged while being informed, usually about something depressingly important. But you probably won't come away feeling exhilarated, filled with a sense of lucky triumph, delighted that you've witnessed a real-world happy ending fairy tale.
Yet you might if you watch the fifth movie, Searching for Sugar Man. The movie is about the search by two Cape Town men who decide to find out whatever happened to the American singer/songwriter Rodriguez who was wildly popular in South Africa, especially among the rebellious young during the oppressive apartheid years. In fact, he was bigger than Elvis. When the search begins there are a couple of rumors about Rodriguez's death, but nothing is certain. The first thing they learn is that the man known to everyone in South Africa is virtually unknown in the United States where, as one man in the music business says, Rodriguez sold maybe six records. How it ends is almost miraculous.
OK — if you must be fussy fussy and picky picky — there are some inaccuracies in the film, but see it anyway. We think you'll feel better.
February 14th is Valentine's Day
Today, being the 14th of February, is secular Valentine's Day, which is a wholly different matter from St. Valentine's Day in the liturgical calendar. We had a nice post about both secular and liturgical Valentines last year, and it's still in our archive for the curious or the bored and lonely. (We hope you're not lonely today, but there's nothing we can do about that. We're sorry.) In any case, unless you've stumbled onto this site by accident you're probably fond of books and reading, and as we've come across a couple of photographs of books, reading and Valentine romance we've posted them for you.
You never know what you might find when you venture deep into the stacks at Harvard's Widener Library. Of course, not just anyone can get into that particular collection of books. But you might have luck at your local library. The lighting isn't too bright in the narrow aisles between bookcases, so make sure you have the right book and be very sure you have the right person.Here's another pair of intellectuals reading in bed. He's the kind of intellectual who gets tattooed, and she's the kind who smokes in bed. The like to live dangerously. Or carelessly. Anyway, it's a good bet he's not going to finish reading that paperback of Hemingway's A Farewell To Arms. But we don't care if they don't care. And we're pretty sure they don't care.We can't help it. We know we posted this same image exactly a year ago, but we like it. We admire the young gentleman helping the young lady across the street in a snowstorm, and we admire the young lady who wears a short dress and those high-heel shoes in a blizzard.
Dress Goes Transparent If You're Aroused
It's here — a dress that becomes transparent when you're in the mood. (And you thought only Steve Jobs had cool ideas.) Advanced tech artist Daan Roosegaarde and fashion designer Anouk Wipprecht produced the dress. It's called Intimacy 2.0 — the name doesn't sound like haute couture, but it does suggest the high degree of science and technology that went into the garment.
The dress is made of leather and — here's the good part — conductive e-foils that become transparent when exposed to electricity. It's possible to design a circuit that is activated by an accelerated heart beat or an increase in body heat. And the subsequent flow of electricity will cause the e-foils to become transparent.
According to Studio Roosegaarde's web site, "Studio Roosegaarde creates interactive designs that explore the dynamic relation between space, people, and technology." And "By creating interactive designs that instinctively respond to sound and movement, Roosegaarde explores the dawn of a new nature that is evolving from technological innovations." (more…)
The Sex Life Of Oranges
Here's something to brighten your gray wintry day — a Cara Cara orange. The Cara Cara has an unknown parentage. It's a kind of bastard orange. It's believed to have sprung from a mating of the Brazilian Bahia navel and the Washington navel. The orange was found in 1976, growing shamefully on a tree that regularly bore Washington navel oranges at the Hacienda de Cara Cara in Valencia, Venezuela. It could be a mutation. But that kind of immaculate conception excuse doesn't convince us. We're not naive. We think this is what happens when young and foolish oranges fool around. (By the way, this is a true story. You can look it up on Wikipedia. Go ahead. We'll wait here.)
As for the taste of the Cara Cara, it's been described as having a bit of cherry flavor, but some tasters add that it also has a bit of rose petal and blackberry. We at Critical Pages haven't eaten any rose petal, but we've dined on Cara Cara oranges. In fact, you might say we've binged on them. To our jaded palates they taste mostly like oranges. As our high-school teacher liked to say, "De gustibus, non disputandem est." That's Latin for "Don't tell me what it tastes like, I'll taste it for myself." You can get into trouble that way, too.
Richard III, Slaughtered In Battle
The recent unearthing of the skeletal remains of England's Richard III reminds us again that there was a time when leaders who ordered up a battle actually got into the bloody slaughter themselves. Richard, with his crooked back, one shoulder forever higher than the other, was in there hacking his way toward Henry Tudor when he was himself cut down.
The skeletal evidence dug up at Leicester fits with historical accounts and vividly suggests King Richard's final moments. The Royal Armouries' Bob Woosnam-Savage has provided a possible scenario based on that evidence. Richard either dismounted or his horse had been cut from under him—all we know for certain is that on horseback he had driven toward Henry in an attempt to kill him and was now on foot, covered in armor and fighting it out because there was nothing else to do. He was surrounded. At some point his armor was pierced, his helmet was torn away and he began to receive blows to his head. If you've seen videos of Muammar Gaddafi's last minute, you have a good picture of what was going on. Richard was cut and battered by pikes, swords and knives. Finally, according to Woosnam-Savage, he was stripped of his armor and repeatedly bashed, including a stab to the buttocks of his now lifeless body. "This last, insulting blow could easily have been delivered to king's body by an infantryman with a bladed weapon after it had been slung over the back of a horse, 'with the armes and legges hanging down on both sides', as he was borne to Leicester."
Our leaders don't join their soldiers in battle any more. And it probably wouldn't reduce the number of wars if they did. But there would be a certain satisfaction in knowing that the person who had ordered the bloody carnage was down there, risking his life, just like the rest.
Assessing Chuck Hegel
Chuck Hegel was interrogated by the Senate Armed Services Committee prior to their deciding whether or not to confirm him as Secretary of Defense. Now we have some idea as to what it was like to be questioned by the Inquisition.
Hegel is the first cabinet nominee in history to have his confirmation hearing preceded by smear and attack ads on television, ads paid for by anonymous donors. The New York Times has said that Sheldon Adelson, the pro-Israel billionaire, is invested in the fight against Hegel, but it's impossible to say that he has financed the ads.
During the hearing Republican members of the committee badgered Hegel — beat up on him verbally might be a more accurate description. John McCain hammered his former friend because Hegel, though a Republican Senator at the time, had said that the Iraq "surge" was a foreign policy disaster. McCain asked Hegel if he had been wrong and heatedly pursued Hegel for a yes or no answer. Hegel said he'd leave the judgement up to history.
Hegel was pounded for remarks he made about lobbyists for Israel, referring to them as "the Jewish lobby." (Just in passing, it might be noted that in a letter to the New York Times, Henry Siegman, who worked for the American Israel Public Affairs Committee, this country's biggest pro-Israel lobby, reported that "the organization was referred to by everyone in the Jewish community as 'the Jewish lobby for Israel.'" ) Senator Lindsey Graham, the Republican from South Carolina, was furious that Hegel had said lawmakers had been intimidated into doing "dumb things" on behalf of the lobby. You might wonder why Graham got so very, very worked up about that. Americans routinely say that Congress is intimidated by lobbyists and does dumb things. (more…)
The Monster That Ate The House
Sometimes you just can't win. And sometimes even winning doesn't work the way you want it to. Pity the Republicans. Currently, Republicans control most governorships and most state legislatures. And their success in the states over the years put them in the position of being able to redraw the boundaries of certain congressional districts. These victories have made it impossible for the Republican Speaker of the House to do politics — which is to say, make deals.
Maybe you've seen this political carton before. It's been around — it was first printed in 1812. Back then, Massachusetts' Governor Gerry and his allies redrew the lines of the state's electoral districts to give his party safe-and-sure voting districts. One of the districts was so contorted that on a map it looked like a salamander. And since it was the handiwork of Governor Gerry, it became known as a gerrymander. This is the monster that dined on the House of Representatives the last two years.
Sometimes the people drawing political maps want to break up an area where the opponent has a sure win, other times they may want to draw a district that snakes this way and that in order to gather like-minded voters into a safe-for-our-party haven. But there's a dangerous downside for a political party that gerrymanders too well.
When a party has redrawn congressional districts so it will surely win, the real contest becomes the primary vote. Then the only question is who the sure-to-win party will run in the upcoming congressional election. But the only people who turn out to vote in the party's primary are the most zealous members of the party — a relative minority. And that minority of zealots tends to be further to the left or further to the right of the national party. This is particularly true for Republicans. (Think Tea Party.)
Fortunately, politicians can't redraw state boundaries. Senators have to seek votes across an entire state, not a rigged congressional district. There are some no-compromise senators, but on the whole the Senate is more temperate and more moderate than the House — which is what the founders planned. Now a bipartisan group of eight senators has come up with an outline for immigration reform. After the presidential election, the Republican party realized that it would go on losing national elections unless it took a position on immigration that was within at least a few hundred miles of the Democratic party. (more…)
Far Away Planets Just Like Ours! Sort of… Maybe.
Maybe you've seen the curious painting just above here. It was released on January 7, 2013, by the Harvard-Smithsonian Center for Astrophysics. According to the caption that usually accompanies the painting, it shows the different types of planets in our Milky Way galaxy detected by NASA's Kepler spacecraft. The caption also says that a new analysis of Kepler data found there are at least 17 billion planets the size of Earth in the Milky Way.
New stories about the Kepler data are happy to suggest there's a possibility, a strong possibility — there must be !—-other worlds just like ours out there. I mean, out of 17 billion there must be at least one beautiful blue-and-white planet like our earth, right? Old TV viewers may remember Carl Sagan, the brilliant Cornell astrophysicist and his award winning TV series, Cosmos: A Personal Voyage. Sagan often spoke of the billions and billions of stars in the cosmos, and if there were "billions and billions" of stars, then there must be only a few billion fewer planets to orbit those suns, and if there are billions of planets then surely there's one, probably many, like our own.
Popular commentary on the recent Kepler data relies on the same statistical hope that there must be some, surely a few, certainly at least one, just like our own. And if it's just like our own, then it must have life, like our Earth does, and — oh, hell, let's go all the way — there must be somebody on some earth-like planet out there looking at a computer screen, reading a post just like you are now!
The people who gather and present the Kepler data don't make such claims. As a matter of fact, a visit to the Kepler web site will be a cold shower for anyone hoping to discover there's a world like ours out there. In dull fact, the Kepler site counts 105 confirmed planets and 2740 candidates that might get confirmed someday. Where did the news about 17 billion planets come from? It came from a press conference, January 7, 2013, at the American Astronomical Society Meeting in Long Beach, California. The first two panelists at the press conference spoke about Kepler:
- Planet Candidates Observed by Kepler: Two Years of Precision Photometry – Christopher Burke (SETI Institute)
- At Least One in Six Stars Has an Earth-size Planet – Francois Fressin (Harvard-Smithsonian Center for Astrophysics)
And why now? Maybe — is it possible? — because there are going to be severe cuts to budgets in all sectors of the United States government and even NASA will be on the chopping block. People, tax payers in particular, aren't especially interested in paying for a space program that scans a bit of the Milky Way looking for a transient dip in starlight, which dip might indicate a planet coming between us and that star, and that's what Kepler does. But even tax payers are curious about extra terrestial life. So now is a good time to hold a press conference and let the media do the rest.
The Flexible Flyer
We thought the Flexible Flyer sled was gone forever. True, it remained in memory, but we thought the Flexible Flyer was a victim of indifferent history, tossed on the pyre of worthless junk like the Rosebud sled that closes "Citizen Kane." But fortunately we were wrong! The Flexible Flyer in the cellar is no longer lonely — Flexible Flyers are being made and sold today
The S.L. Allen Company of Philadelphia patented the Flexible Flyer in 1889. It was revolutionary, because you could actually steer the sled. Prior to that, sleds were built like small sleighs — they had immovable runners. But the Flexible Flyer was flexible; the front section of each runner could be aimed left or right by pulling on a wood crosspiece that was pivoted at its center and attached to the front part of the runners. Soon the Flexible Flyer was the most popular sled in the United States. The next improvement came in the late thirties or forties when the straight back end of each runner was twisted up and around until it faced forward and was bolted safely to the underside of a wooden rail. Prior to that improvement, the back end of the sled was simply lethal. Fortunately, thick winter clothing prevented most kids from getting impaled.
The Flexible Flyer sled gradually disappeared from sight in the 1960s when the S. L. Allen Company was sold. Just about then the two-steel-runner sled began to be replaced, first by aluminum saucers, which were lighter and maybe safer than sleds though they had no steering ability, and then by sheets of sturdy, bright colored plastic that were much cheaper and even safer than metal saucers — and they went down a snowy slope faster. That's pretty much what you'll find on the snowy slopes today. Sure, kids fall off and even when they don't they bump into each other, but the chances of their getting badly hurt are minimal compared to what it used to be like on those old fashioned sleds.
Today we learned from NPR's "Only A Game" that the Flexible Flyer is back. The company that ended up owning S. L. Allen Company's patent went bust and sold the Flexible Flyer rights to an old, old sled making rival of the S. L. Allen Company, namely the Paris Manufacturing Company, now known as Paricon. (The business started in South Paris, Maine – not France.) The excellent and informative Flexible Flyer article at "Only A Game" is by Doug Tribou. The Flexible Flyer sled in the photo above comes from our childhood, which was a long, long time ago.


text:
Most Cited Molecular and Cellular Neuroscience Articles
The most cited articles published since 2011, extracted from Scopus.
Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activityGaelle Lachenal | Karin Pernet-Gallay | Mathilde Chivet | Fiona J. Hemming | Agnès Belly | Gilles Bodon | Béatrice Blot | Georg Haase | Yves Goldberg | Rémy Sadoul
Volume 46, Issue 2, February 2011, Pages 409-418
Exosomes are microvesicles released into the extracellular medium upon fusion to the plasma membrane of endosomal intermediates called multivesicular bodies. They represent ways for discarding proteins and metabolites and also for intercellular transfer of proteins and RNAs. In the nervous system, it has been hypothesized that exosomes might be involved in the normal physiology of the synapse and possibly allow the trans-synaptic propagation of pathogenic proteins throughout the tissue. As a first step to validate this concept, we used biochemical and morphological approaches to demonstrate that mature cortical neurons in culture do indeed secrete exosomes. Using electron microscopy, we observed exosomes being released from somato-dendritic compartments. The endosomal origin of exosomes was demonstrated by showing that the C-terminal domain of tetanus toxin specifically endocytosed by neurons and accumulating inside multivesicular bodies, is released in the extracellular medium in association with exosomes. Finally, we found that exosomal release is modulated by glutamatergic synaptic activity, suggesting that this process might be part of normal synaptic physiology. Thus, our study paves the way towards the demonstration that exosomes take part in the physiology of the normal and pathological nervous system. © 2010 Elsevier Inc.
The dendritic tree and brain disordersVaishali A. Kulkarni | Bonnie L. Firestein
Volume 50, Issue 1, May 2012, Pages 10-20
Dendrite morphogenesis is a complex but well-orchestrated process and includes the development of dendritic branches, forming characteristic dendrite arbors, and dendritic spines, allowing neurons to communicate with each other. Various studies report that many neuropsychiatric disorders are characterized by dendritic and synaptic pathology, including abnormal spine density and morphology, synapse loss, and aberrant synaptic signaling and plasticity. In this review, we discuss dendrite development and branching, and in specific, morphology, cytoskeletal architecture, and how the complexity of the dendrite tree and its functional capabilities are altered in various brain disorders. Identifying and understanding these changes in dendrite morphology are essential for understanding brain function in normal and disease states. © 2012 Elsevier Inc.
Which way to go? Cytoskeletal organization and polarized transport in neuronsLukas C. Kapitein | Casper C. Hoogenraad
Volume 46, Issue 1, January 2011, Pages 9-20
To establish and maintain their polarized morphology, neurons employ active transport driven by cytoskeletal motor proteins to sort cargo between axons and dendrites. These motors can move in a specific direction over either microtubules (kinesins, dynein) or actin filaments (myosins). The basic traffic rules governing polarized transport on the neuronal cytoskeleton have long remained unclear, but recent work has revealed several fundamental sorting principles based on differences in the cytoskeletal organization in axons versus dendrites. We will highlight the basic characteristics of the neuronal cytoskeleton and review existing evidence for microtubule and actin based traffic rules in polarized neuronal transport. We will propose a model in which polarized sorting of cargo is established by recruiting or activating the proper subset of motor proteins, which are subsequently guided to specific directions by the polarized organization of the neuronal cytoskeleton. © 2010 Elsevier Inc.
The role of the innate immune system in psychiatric disordersKenneth A. Jones | Christian Thomsen
Volume 53, Issue , March 2013, Pages 52-62
There is by now substantial clinical evidence for an association between specific mood disorders and altered immune function. More recently, a number of hypotheses have been forwarded to explain how components of the innate immune system can regulate brain function at the cellular and systems levels and how these may underlie the pathology of disorders such as depression, PTSD and bipolar disorder. In this review we draw reference to biochemical, cellular and animal disease models, as well as clinical observations to elucidate the role of the innate immune system in psychiatric disorders. Proinflammatory cytokines, such as IL-1β IL-6 and TNFα, which feature prominently in the immune response to pathogen in the periphery, have unique and specific actions on neurons and circuits within the central nervous system. Effects of these signaling molecules on neurotransmission, memory, and glucocorticoid function, as well as animal behaviors such as social withdrawal and fear conditioning relevant to psychiatric disorders are elucidated. Finally, we highlight future directions for studies, including the use of peripheral biomarkers, relevant for developing new therapeutic approaches for treating psychiatric illnesses. This article is part of Special Issue entitled 'neuroinflammation in neurodegeneration and neurodysfunction'. © 2012 Elsevier Inc.
Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and functionClare M. Gladding | Lynn A. Raymond
Volume 48, Issue 4, December 2011, Pages 308-320
Research over the last few decades has shaped our understanding of the crucial involvement of the N-methyl-d-aspartate receptor (NMDAR) in mediating excitatory synaptic neurotransmission, neuronal development and learning and memory. The complexity of NMDAR modulation has escalated with the knowledge that receptors can traffic between synaptic and extrasynaptic sites, and that location on the plasma membrane profoundly affects the physiological function of NMDARs. Moreover, mechanisms that regulate NMDAR subcellular localization and function, such as protein-protein interactions, phosphorylation, palmitoylation, ubiquitination and receptor proteolytic cleavage, may differ for synaptic and extrasynaptic NMDARs. Recent studies suggest that NMDAR mislocalization is a dominant contributing factor to glutamatergic dysfunction and pathogenesis in neurological disorders such as Huntington's disease, Alzheimer's disease and ischemia. Therapeutic approaches that specifically rectify receptor mislocalization or target resulting downstream apoptotic signaling could be beneficial for preventing disease onset or progression across many disorders that are commonly caused by NMDAR dysfunction. This review will summarize the molecular mechanisms that regulate synaptic and extrasynaptic NMDAR localization in both physiologic and pathogenic states. © 2011 Elsevier Inc.
A three-step model for the synaptic recruitment of AMPA receptorsPatricio Opazo | Daniel Choquet
Volume 46, Issue 1, January 2011, Pages 1-8
The amount of AMPARs at synapses is not a fixed number but varies according to different factors including synaptic development, activity and disease. Because the number of AMPARs sets the strength of synaptic transmission, their trafficking is subject to fine and tight regulation. In this review, we will describe the different steps taken by AMPARs in order to reach the synapse. We propose a three-step mechanism involving exocytosis at extra/perisynaptic sites, lateral diffusion to synapses and a subsequent rate-limiting diffusional trapping step. We will describe how the different trafficking steps are regulated during synaptic plasticity or altered during neurodegenerative diseases such as Alzheimer's. © 2010 Elsevier Inc.
A cellular model for sporadic ALS using patient-derived induced pluripotent stem cellsMatthew F. Burkhardt | Fernando J. Martinez | Sarah Wright | Carla Ramos | Dmitri Volfson | Michael Mason | Jeff Garnes | Vu Dang | Jeffery Lievers | Uzma Shoukat-Mumtaz | Rita Martinez | Hui Gai | Robert Blake | Eugeni Vaisberg | Marica Grskovic | Charles Johnson | Stefan Irion | Jessica Bright | Bonnie Cooper | Leane Nguyen | Irene Griswold-Prenner | Ashkan Javaherian
Volume 56, Issue , September 2013, Pages 355-364
Development of therapeutics for genetically complex neurodegenerative diseases such as sporadic amyotrophic lateral sclerosis (ALS) has largely been hampered by lack of relevant disease models. Reprogramming of sporadic ALS patients' fibroblasts into induced pluripotent stem cells (iPSC) and differentiation into affected neurons that show a disease phenotype could provide a cellular model for disease mechanism studies and drug discovery. Here we report the reprogramming to pluripotency of fibroblasts from a large cohort of healthy controls and ALS patients and their differentiation into motor neurons. We demonstrate that motor neurons derived from three sALS patients show de novo TDP-43 aggregation and that the aggregates recapitulate pathology in postmortem tissue from one of the same patients from which the iPSC were derived. We configured a high-content chemical screen using the TDP-43 aggregate endpoint both in lower motor neurons and upper motor neuron like cells and identified FDA-approved small molecule modulators including Digoxin demonstrating the feasibility of patient-derived iPSC-based disease modeling for drug screening. © 2013 Elsevier Inc.
Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stressGaelle Naert | Guy Ixart | Tangui Maurice | Lucia Tapia-Arancibia | Laurent Givalois
Volume 46, Issue 1, January 2011, Pages 55-66
Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3. h/day for 3. weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. © 2010 Elsevier Inc.
Inflammation and neurovascular changes in amyotrophic lateral sclerosisM. C. Evans | Y. Couch | N. Sibson | M. R. Turner
Volume 53, Issue , March 2013, Pages 34-41
Neuroinflammation in now established as an important factor in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). At various time points, astrocytes and microglia are markedly activated, either producing neuroprotective or pro-inflammatory molecules, which can decrease or increase the rate of primary motor neuron degeneration respectively. Recent research has shown that this neuroinflammatory component is affected by the peripheral immune system; T lymphocytes in particular are able to cross into the brain and spinal cord parenchyma, where they interact with resident microglia, either inducing them to adopt an M1 (cytotoxic) or M2 (protective) phenotype, depending on the stage of disease. Clearly understanding the changes that occur to allow the interaction between peripheral and central immune responses will be essential in any attempt to manipulate the disease process via neuroinflammatory mechanisms. However, our understanding of the endothelial changes, which facilitate the infiltration of peripheral immune cells into the brain and spinal cord, is still in its infancy. There are suggestions, though, of up-regulation of cellular adhesion molecules, which are able to arrest circulating leukocytes and facilitate diapedesis into the brain parenchyma. In addition, tight junction proteins appear to be down-regulated, leading to an increase in vascular permeability, an effect that is amplified by vascular damage late in the disease process. This review summarises our current knowledge regarding neuroinflammation, peripheral immune involvement, and endothelial changes in ALS. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. © 2012.
RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALSShangxi Xiao | Teresa Sanelli | Samar Dib | David Sheps | Joseph Findlater | Juan Bilbao | Julia Keith | Lorne Zinman | Ekaterina Rogaeva | Janice Robertson
Volume 47, Issue 3, July 2011, Pages 167-180
TDP-43 is a predominantly nuclear DNA/RNA binding protein involved in transcriptional regulation and RNA processing. TDP-43 is also a component of the cytoplasmic inclusion bodies characteristic of amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). We have investigated the premise that abnormalities of TDP-43 in disease would be reflected by changes in processing of its target RNAs. To this end, we have firstly identified RNA targets of TDP-43 using UV-Cross-Linking and Immunoprecipitation (UV-CLIP) of SHSY5Y cells, a human neuroblastoma cell line. We used conventional cloning strategies to identify, after quality control steps, 127 targets. Results show that TDP-43 binds mainly to introns at UG/TG repeat motifs (49%) and polypyrimidine rich sequences (17.65%). To determine if the identified RNA targets of TDP-43 were abnormally processed in ALS versus control lumbar spinal cord RNA, we performed RT-PCR using primers designed according to the location of TDP-43 binding within the gene, and prior evidence of alternative splicing of exons adjacent to this site. Of eight genes meeting these criteria, five were differentially spliced in ALS versus control. This supports the premise that abnormalities of TDP-43 in ALS are reflected in changes of RNA processing. © 2011 Elsevier Inc.
Single-cell analysis of sodium channel expression in dorsal root ganglion neuronsCojen Ho | Michael E. O'Leary
Volume 46, Issue 1, January 2011, Pages 159-166
Sensory neurons of the dorsal root ganglia (DRG) express multiple voltage-gated sodium (Na) channels that substantially differ in gating kinetics and pharmacology. Small-diameter (< 25 μm) neurons isolated from the rat DRG express a combination of fast tetrodotoxin-sensitive (TTX-S) and slow TTX-resistant (TTX-R) Na currents while large-diameter neurons (>30μm) predominately express fast TTX-S Na current. Na channel expression was further investigated using single-cell RT-PCR to measure the transcripts present in individually harvested DRG neurons. Consistent with cellular electrophysiology, the small neurons expressed transcripts encoding for both TTX-S (Nav1.1, Nav1.2, Nav1.6, and Nav1.7) and TTX-R (Nav1.8 and Nav1.9) Na channels. Nav1.7, Nav1.8 and Nav1.9 were the predominant Na channels expressed in the small neurons. The large neurons highly expressed TTX-S isoforms (Nav1.1, Nav1.6, and Nav1.7) while TTX-R channels were present at comparatively low levels. A unique subpopulation of the large neurons was identified that expressed TTX-R Na current and high levels of Nav1.8 transcript. DRG neurons also displayed substantial differences in the expression of neurofilaments (NF200, peripherin) and Necl-1, a neuronal adhesion molecule involved in myelination. The preferential expression of NF200 and Necl-1 suggests that large-diameter neurons give rise to thick myelinated axons. Small-diameter neurons expressed peripherin, but reduced levels of NF200 and Necl-1, a pattern more consistent with thin unmyelinated axons. Single-cell analysis of Na channel transcripts indicates that TTX-S and TTX-R Na channels are differentially expressed in large myelinated (Nav1.1, Nav1.6, and Nav1.7) and small unmyelinated (Nav1.7, Nav1.8, and Nav1.9) sensory neurons. © 2010 Elsevier Inc.
Centrosomes, microtubules and neuronal developmentMarijn Kuijpers | Casper C. Hoogenraad
Volume 48, Issue 4, December 2011, Pages 349-358
The formation of complex nervous systems requires processes that coordinate proliferation, migration and differentiation of neuronal cells. The remarkable morphological transformations of neurons as they migrate, extend axons and dendrites and establish synaptic connections, imply a strictly regulated process of structural organization and dynamic remodeling of the cytoskeleton. The centrosome serves as the main cytoskeleton-organizing center in the cell and is the classical site of microtubule nucleation and anchoring. Mutations in genes encoding centrosomal proteins cause severe neurodevelopmental disorders that lead to several neuropsychiatric diseases, such as lissencephaly, microcephaly and schizophrenia. While the centrosome has been considered crucial for coordinating neuronal migration and polarization, accumulating experimental findings seems to rule out a central role for the centrosome at later stages of neuronal development. Here, we will review these observations and discuss the importance of centrosomal and acentrosomal microtubule organization for neuronal development. This article is part of a Special Issue entitled 'Neuronal Function'. © 2011 Elsevier Inc.
Ephrin regulation of synapse formation, function and plasticityMartin Hruska | Matthew B. Dalva
Volume 50, Issue 1, May 2012, Pages 35-44
Synapses enable the transmission of information within neural circuits and allow the brain to change in response to experience. During the last decade numerous proteins that can induce synapse formation have been identified. Many of these synaptic inducers rely on trans-synaptic cell-cell interactions to generate functional contacts. Moreover, evidence now suggests that the same proteins that function early in development to regulate synapse formation may help to maintain and/or regulate the function and plasticity of mature synapses. One set of receptors and ligands that appear to impact both the development and the mature function of synapses are Eph receptors (erythropoietin-producing human hepatocellular carcinoma cell line) and their surface associated ligands, ephrins (Eph family receptor interacting proteins). Ephs can initiate new synaptic contacts, recruit and stabilize glutamate receptors at nascent synapses and regulate dendritic spine morphology. Recent evidence demonstrates that ephrin ligands also play major roles at synapses. Activation of ephrins by Eph receptors can induce synapse formation and spine morphogenesis, whereas in the mature nervous system ephrin signaling modulates synaptic function and long-term changes in synaptic strength. In this review we will summarize the recent progress in understanding the role of ephrins in presynaptic and postsynaptic differentiation, and synapse development, function and plasticity. © 2012 Elsevier Inc.
Mitochondria-associated ER membranes in Alzheimer diseaseEric A. Schon | Estela Area-Gomez
Volume 55, Issue , July 2013, Pages 26-36
Alzheimer disease (AD) is associated with the accumulation in the brain of extracellular neuritic plaques composed mainly of β-amyloid (Aβ) and of intracellular neurofibrillary tangles composed of hyperphosphorylated forms of the microtubule-associated protein tau. It is also associated with other features that have received less attention, including aberrant phospholipid, cholesterol, and calcium metabolism, and altered mitochondrial function and dynamics. The underlying mechanism(s) that might explain these observations are currently unknown. We recently showed that presenilin-1 (PS1), presenilin-2 (PS2), and γ-secretase activity, which processes the amyloid precursor protein (APP) to generate Aβ, are located predominantly in a specialized subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM). MAM is an intracellular lipid raft-like structure intimately involved in cholesterol and phospholipid lipid metabolism, in calcium homeostasis, and in mitochondrial function and dynamics. The coincidence of the functions associated with MAM with the symptomatology of AD led us to speculate that presenilins play a role in maintaining MAM function. We found that, consistent with this supposition, both MAM function and ER-mitochondrial connectivity are increased significantly in AD, which may help explain many of the biochemical and morphological features of the disease. Based on these findings, we propose that AD is fundamentally a disorder of ER-mitochondrial communication (the "MAM hypothesis"). This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. © 2012 Elsevier Inc.
Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: Protection by caffeineIbrahim A. Alhaider | Abdulaziz M. Aleisa | Trinh T. Tran | Karim A. Alkadhi
Volume 46, Issue 4, April 2011, Pages 742-751
It is well known that caffeine and sleep deprivation have opposing effects on learning and memory; therefore, this study was undertaken to determine the effects of chronic (4. wks) caffeine treatment (0.3. g/l in drinking water) on long-term memory deficit associated with 24. h sleep deprivation. Animals were sleep deprived using the modified multiple platform method. The results showed that chronic caffeine treatment prevented the impairment of long-term memory as measured by performance in the radial arm water maze task and normalized L-LTP in area CA1 of the hippocampi of sleep-deprived anesthetized rats. Sleep deprivation prevents the high frequency stimulation-induced increases in the levels of phosphorylated-cAMP response element binding protein (P-CREB) and brain-derived neurotrophic factor (BDNF) seen during the expression of late phase long-term potentiation (L-LTP). However, chronic caffeine treatment prevented the effect of sleep-deprivation on the stimulated levels of P-CREB and BDNF. The results suggest that chronic caffeine treatment may protect the sleep-deprived brain probably by preserving the levels of P-CREB and BDNF. © 2011 Elsevier Inc.
Peripheral and central inflammation in autism spectrum disordersAmaicha Mara Depino
Volume 53, Issue , March 2013, Pages 69-76
Recent reports have given a central role to environmental factors in the etiology of autism spectrum disorders (ASD). However, most proposed perinatal factors seem to converge into the activation of the immune system, suggesting that an early inflammatory response could be a unifying factor in the etiology ASD. Here I review the evidence of early immune activation in individuals with ASD, and the chronic peripheral and central alterations observed in the inflammatory response in ASD. This evidence shows that ASD is associated with altered neuroinflammatory processes and abnormal immune responses in adulthood. How these immune alterations can affect developmental programming of adult behavior or directly affect behavior later in life is discussed in the context of both clinical and animal models of research. Recent studies in rodents clearly support a role of elevated cytokines in the behavioral symptoms of ASD, both during development and in adulthood. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. © 2012 Elsevier Inc.
Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephalyTsuyoshi Fukuda | Akinori Tokunaga | Reiko Sakamoto | Nobuaki Yoshida
Volume 46, Issue 3, March 2011, Pages 614-624
Histone methylation is the important transcription regulatory system that affects mammalian development and cell differentiation. Alterations in epigenetic gene regulation are associated with disease. Fbxl10 (F-box and leucine-rich repeat protein 10) is a JmjC domain-containing histone demethylase. Although Fbxl10 has been implicated in cell cycle regulation, cell death, senescence, and tumorigenesis, these functions are controversial and its physiological function is unclear. To determine the in vivo function of Fbxl10, in this study, we generated a homozygous mutation in the mouse Fbxl10 gene. About half of Fbxl10-deficient mice exhibit failure of neural tube closure, resulting in exencephaly and die shortly after birth. Fbxl10 deficiency also causes retinal coloboma and a curled tail with low penetrances. Fbxl10 mRNA is specifically expressed in the cranial neural folds at E8.5 embryos, and apoptosis increased in the neuroepithelium and mesenchyme of Fbxl10-deficient E9.5 embryos, consistent with neural tube defects found in Fbxl10-deficient mice. Depletion of Fbxl10 induced the increased expression of p19ARF, an inducer of apoptosis, in E8.5 embryos and mouse embryonic fibroblast cells. In addition, the number of mitotic neural progenitor cells is significantly increased in the mutant E14.5 brain. Our findings suggest that the Fbxl10 gene makes important contributions to embryonic neural development by regulating cell proliferation and cell death in mice. © 2011 Elsevier Inc.
Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseasesRajnish K. Chaturvedi | M. Flint Beal
Volume 55, Issue , July 2013, Pages 101-114
Substantial evidence from both genetic and toxin induced animal and cellular models and postmortem human brain tissue indicates that mitochondrial dysfunction plays a central role in pathophysiology of the neurodegenerative disorders including Parkinson's disease (PD), and Huntington's disease (HD). This review discusses the emerging understanding of the role of mitochondrial dysfunction including bioenergetics defects, mitochondrial DNA mutations, familial nuclear DNA mutations, altered mitochondrial fusion/fission and morphology, mitochondrial transport/trafficking, altered transcription and increased interaction of pathogenic proteins with mitochondria in the pathogenesis of PD and HD. This review recapitulates some of the key therapeutic strategies applied to surmount mitochondrial dysfunction in these debilitating disorders. We discuss the therapeutic role of mitochondrial bioenergetic agents such as creatine, Coenzyme-Q10, mitochondrial targeted antioxidants and peptides, the SIRT1 activator resveratrol, and the pan-PPAR agonist bezafibrate in toxin and genetic cellular and animal models of PD and HD. We also summarize the phase II-III clinical trials conducted using some of these agents. Lastly, we discuss PGC-1α, TORC and Sirtuins as potential therapeutic targets for mitochondrial dysfunction in neurodegenerative disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. © 2012 Elsevier Inc.
CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventricular zone neurogenesisS. Herold | R. Jagasia | K. Merz | K. Wassmer | D. C. Lie
Volume 46, Issue 1, January 2011, Pages 79-88
Neural stem cells in the subventricular zone (SVZ) of the lateral ventricles give rise to new interneurons of the olfactory bulb (OB) throughout life. SVZ/OB neurogenesis is influenced by olfactory network activity, which modulates the survival of new neurons during their integration into the OB network. Previous work suggested that such activity-dependent survival is regulated via the CREB signalling pathway. Curiously, CREB signalling is already active during the early developmental stages of adult SVZ/OB neurogenesis. To investigate the role of cell autonomous CREB signalling during early stages of adult SVZ/OB neurogenesis, we ablated CREB-pathway activity in the SVZ/OB neurogenic lineage using a retroviral strategy. Surprisingly, loss of CREB signalling resulted in increased cell death and loss of expression of the neurogenic transcription factor Pax 6, and of a subset of neuronal proteins in migrating neurons of the RMS. Moreover, post-migratory neurons in the OB displayed impaired dendritic development. These results demonstrate an essential role for CREB signalling in maturation of newborn neurons in the OB and uncover a novel role for CREB signalling in the survival and maintenance of neuronal gene expression during the early stages of SVZ/OB neurogenesis. © 2010 Elsevier Inc.
Mechanisms of polarized membrane trafficking in neurons - Focusing in on endosomesZofia M. Lasiecka | Bettina Winckler
Volume 48, Issue 4, December 2011, Pages 278-287
Neurons are polarized cells that have a complex and unique morphology: long processes (axons and dendrites) extending far from the cell body. In addition, the somatodendritic and axonal domains are further divided into specific subdomains, such as synapses (pre- and postsynaptic specializations), proximal and distal dendrites, axon initial segments, nodes of Ranvier, and axon growth cones. The striking asymmetry and complexity of neuronal cells are necessary for their function in receiving, processing and transferring electrical signals, with each domain playing a precise function in these processes. In order to establish and maintain distinct neuronal domains, mechanisms must exist for protein delivery to specific neuronal compartments, such that each compartment has the correct functional molecular composition. How polarized membrane domains are established and maintained is a long-standing question. Transmembrane proteins, such as receptors and adhesion molecules, can be transported to their proper membrane domains by several pathways. The biosynthetic secretory system delivers newly synthesized transmembrane proteins from the ER via the Golgi and trans-Golgi-network (TGN) to the plasma membrane. In addition, the endosomal system is critically involved in many instances in ensuring proper (re)targeting of membrane components because it can internalize and degrade mislocalized proteins, or recycle proteins from one domain to another. The endosomal system is thus crucial for establishing and maintaining neuronal polarity. In this review, we focus mainly on the intracellular compartments that serve as sorting stations for polarized transport, with particular emphasis on the emerging roles of endosomes. © 2011 Elsevier Inc.
TNF-α potentiates glutamate-induced spinal cord motoneuron death via NF-κBLaia Tolosa | Víctor Caraballo-Miralles | Gabriel Olmos | Jerònia Lladó
Volume 46, Issue 1, January 2011, Pages 176-186
Besides glutamate excitotoxicity, the neuroinflammatory response is emerging as a relevant contributor to motoneuron loss in amyotrophic lateral sclerosis (ALS). In this regard, high levels of circulating proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) have been shown both in human patients and in animal models of ALS. The aim of this work was to study the effects of TNF-α on glutamate-induced excitotoxicity in spinal cord motoneurons. In rat spinal cord organotypic cultures chronic glutamate excitotoxicity, induced by the glutamate-uptake inhibitor threohydroxyaspartate (THA), resulted in motoneuron loss that was associated with a neuroinflammatory response. In the presence of TNF-α, THA-induced excitotoxic motoneuron death was potentiated. Co-exposure to TNF-α and THA also resulted in down-regulation of the astroglial glutamate transporter 1 (GLT-1) and in increased extracellular glutamate levels, which were prevented by nuclear factor-kappaB (NF-κB) inhibition. Furthermore, TNF-α and THA also cooperated in the induction of oxidative stress in a mechanism involving the NF-κB signalling pathway as well. The inhibition of this pathway abrogated the exacerbation of glutamate-mediated motoneuron death induced by TNF-α. These data link two important pathogenic mechanisms, excitotoxicity and neuroinflammation, suggested to play a role in ALS and, to our knowledge, this is the first time that TNF-α-induced NF-κB activation has been reported to potentiate glutamate excitotoxicity on motononeurons. © 2010 Elsevier Inc.
Raised calcium promotes α-synuclein aggregate formationS. Nath | J. Goodwin | Y. Engelborghs | D. L. Pountney
Volume 46, Issue 2, February 2011, Pages 516-526
Parkinson's and Parkinson's-plus diseases are associated with abnormal, aggregated forms of the protein, α-synuclein. We have investigated the effects of calcium on α-synuclein aggregation in vitro and in vivo. We treated monomeric α-synuclein with calcium in vitro and used fluorescence imaging, fluorescence correlation and scanning electron microscopy to investigate protein aggregation. Incubation of fluorescent-labelled monomeric α-synuclein (24h) at low concentration (10μM) with calcium resulted in surface aggregates (1.5±0.7μm2) detected by fluorescence microscopy saturating at a half-maximum calcium concentration of 80μM, whilst incubations without calcium showed few protein aggregates. Scanning electron microscopy revealed that α-synuclein surface plaques (0.5-1μm) form in the presence of calcium and comprise 10-20nm globular particles. Incubation of α-synuclein at high concentration (75μM; 6h) resulted in soluble oligomeric aggregates detected by fluorescence correlation spectroscopy in a calcium dependent process, saturating at a half maximum calcium concentration of 180μM. In cell culture experiments, we used thapsigargin or calcium ionophore A23187 to induce transient increases of intracellular free calcium in human 1321N1 cells expressing an α-synuclein-GFP construct and observed calcium flux and α-synuclein aggregation by fluorescence microscopy. The cell culture data shows that a transient increase in intracellular free calcium significantly increased the proportion of cells bearing cytoplasmic α-synuclein aggregates 6 and 12h post-treatment (P, 0.01). Our data indicates that calcium accelerates α-synuclein aggregation on surfaces, in free solution and in cultured cells and suggests that surface adsorption may play an important role in the calcium-dependent aggregation mechanism. © 2010 Elsevier Inc.
Glutamate receptor dynamics and protein interaction: Lessons from the NMDA receptorLucie Bard | Laurent Groc
Volume 48, Issue 4, December 2011, Pages 298-307
The plasticity of excitatory glutamate synapses emerged over the last decades as a core cellular mechanism for the encoding and processing of various cognitive functions. This property relies in part on the ability to dynamically adjust the content of glutamate receptors in the postsynaptic membrane. Among these receptors, NMDA receptors (NMDAR), which are composed of two obligatory GluN1 and two regulatory GluN2/3 subunits, play a key role in the induction of many forms of plasticity processes. Understanding how NMDAR subtypes are trafficked and regulated in the synapse has thus captured considerable attention. It has emerged that NMDAR synaptic content relies on an equilibrium between intracellular trafficking and rapid lateral diffusion of the receptor within the synaptic area. Here, we review our current understanding of NMDAR trafficking, mostly the ones at the surface membrane, with a specific focus on the role of interacting PDZ-containing proteins during the journey of NMDAR to and around the synaptic area. The cellular and molecular lessons obtained from examining NMDAR dynamics and regulation by interacting proteins appear to apply to other ionotropic neurotransmitter receptors, and thus shed new light on the modulation of excitatory, inhibitory, and modulatory transmission. This article is part of a Special Issue entitled 'Neuronal Function'. © 2011 Elsevier Inc.
Leak K + channel mRNAs in dorsal root ganglia: Relation to inflammation and spontaneous pain behaviourBarnaby Marsh | Cristian Acosta | Laiche Djouhri | Sally N. Lawson
Volume 49, Issue 3, March 2012, Pages 375-386
Two pore domain potassium (K2P) channels (KCNKx.x) cause K + leak currents and are major contributors to resting membrane potential. Their roles in dorsal root ganglion (DRG) neurons normally, and in pathological pain models, are poorly understood. Therefore, we examined mRNA levels for 10 K2P channels in L4 and L5 rat DRGs normally, and 1. day and 4. days after unilateral cutaneous inflammation, induced by intradermal complete Freund's adjuvant (CFA) injections. Spontaneous foot lifting (SFL) duration (spontaneous pain behaviour) was measured in 1 day and 4 day rats < 1. h before DRG harvest. mRNA levels for KCNK channels and Kv1.4 relative to GAPDH (n = 4-6 rats/group) were determined with real-time RT-PCR. This study is the first to demonstrate expression of THIK1, THIK2 and TWIK2 mRNA in DRGs. Abundance in normal DRGs was, in descending order: Kv1.4 > TRESK(KCNK18) > TRAAK(KCNK4) > TREK2(KCNK10) = TWIK2(KCNK6) > TREK1 (KCNK2) = THIK2(KCNK12) > TASK1(KCNK3) > TASK2(KCNK5) > THIK1(KCNK13) = TASK3(KCNK9).During inflammation, the main differences from normal in DRG mRNA levels were bilateral, suggesting systemic regulation, although some channels showed evidence of ipsilateral modulation. By 1. day, bilateral K2P mRNA levels had decreased (THIK1) or increased (TASK1, THIK2) but by 4. days they were consistently decreased (TASK2, TASK3) or tended to decrease (excluding TRAAK). The decreased TASK2 mRNA was mirrored by decreased protein (TASK2-immunoreactivity) at 4. days. Ipsilateral mRNA levels at 4. days compared with 1. day were lower (TRESK, TASK1, TASK3, TASK2 and THIK2) or higher (THIK1). Ipsilateral SFL duration during inflammation was positively correlated with ipsilateral TASK1 and TASK3 mRNAs, and contralateral TASK1, TRESK and TASK2 mRNAs. Thus changes in K2P mRNA levels occurred during inflammation and for 4 K2P channels were associated with spontaneous pain behaviour (SFL). K2P channels and their altered expression are therefore associated with inflammation-induced pain. © 2012 Elsevier Inc.
Mitochondria and ALS: Implications from novel genes and pathwaysMauro Cozzolino | Alberto Ferri | Cristiana Valle | Maria Teresa Carrì
Volume 55, Issue , July 2013, Pages 44-49
Evidence from patients with sporadic and familiar amyotrophic lateral sclerosis (ALS) and from models based on the overexpression of mutant SOD1 found in a small subset of patients, clearly point to mitochondrial damage as a relevant facet of this neurodegenerative condition. In this mini-review we provide a brief update on the subject in the light of newly discovered genes (such as TDP-43 and FUS/TLS) associated to familial ALS and of a deeper knowledge of the mechanisms of derangement of mitochondria. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. © 2012 Elsevier Inc.

subset: commoncrawl


text:
Top Contributors
Add to this Profile
- Investments
- 6 Investments in 6 Companies
- Headquarters:
- Taoyüan, T'ai-wan
- Description:
- Quanta Computer is a provider of design and manufacturing services in hi-tech markets.
- Categories:
- Computer, Information Technology
- Website:
- http://www.quantatw.com/Quanta/english
Company DetailsUpdate
Established in 1988, Quanta Computer is the largest notebook computer ODM company in the world.
With leading technology and strong R&D capability, Quanta has become a leader in hi-tech markets and the best partner providing quality design and manufacturing services to top-notched brands worldwide for technology products. Besides continuous high growth, high quality and high value creation in notebook computers, Quanta has extended its businesses into enterprise network systems, home entertainment, mobile communication, automotive electronics and digital home markets. With revealing "Cloud Computing" as the center of business innovation and development, Quanta has been integrating resources and redefining business model to capture emerging growth opportunities.
"Rooted in Taiwan with broad vision and aggressive expansion in the global market" is Quanta's strategy for long-term growth development. With "Quanta R&D Complex" (QRDC) as our global headquarters and the center of dynamics, we integrated worldwide resources in technology to ensure that Quanta Computer Inc. has technological advantages to design, develop, and manufacture high value-added products and solutions for customers. In addition, we have established operation centers across Asia, America, and Europe to manufacture, configure, and service products as well as to provide logistic supports to deliver products and services competitively everywhere in the world.
Quanta has over 70,000 employees worldwide, of which around 5,000 people are located in headquarters with the majority working in R&D and engineering development. QRDC, inaugurated in late 2005, is a symbol of Quanta's long-term deep-rooted investment in Taiwan. As an intelligent building, QRDC has three major functions, including R&D, humanity and arts, as well as educational and leisure activities. The facility is also equipped with laboratories, stadium seating art performance hall—"Quanta Hall", library, art gallery, gym and swimming pool. The construction of QRDC with advanced facility meets our goal to harmonize humanity and technology. Capable of accommodating up to 7,000 employees, QRDC is unprecedented in the information industry in Taiwan in terms of architectural designs, space planning, intelligent functions and size.
Investments (6)
Current Team (3)Update
C. C. Leung
General Manager
Barry Lam
Elton Lang
News (458)Update
|Aug 9, 2016
|PRNewswire All - BFSI Dominates Cloud Infrastructure Market - 12.9% CAGR to 2022
|Jul 13, 2016
|Business Wire - Nexenta 'Future Proofs' Storage for Northern Arizona University Researchers
|Jul 5, 2016
|Business Wire - Global Data Center Microserver Market 2016-2020 - Increased Construction of Green Data Centers - Key Vendors are Dell, HP & Fujitsu - Research and Markets
|Jun 20, 2016
|PRWeb Sitemap - QCT Introduces Industry Leading Hardware Platform to Support Deep Learning Applications
|Jun 16, 2016
|MacRumors - Hardware-Free WWDC Sets Stage for Busy Second Half of 2016
|Jun 6, 2016
|BetaKit - W
|Jun 2, 2016
|Times of India - Sitemap - This is world's first 360-degree VR streaming camera
|Jun 1, 2016
|Silicon India - World's First 360-Degree Live Smartphone VR Camera Unveiled
Offices/Locations (1)Update
211, Wen Hwa 2nd Road
Guishan District
Taoyüan, T'ai-wan 33377
Past Team (2)Update
Americo Lemos
VP, Platform Engineering Group & Director, Strategy & Product Planning @ Intel
Chris Terman
Director of Academics @ edX


text:
Eating healthily doesn't have to be complicated — especially when you learn to slim down recipes and prepare foods that take advantage of the season, says Canadian chef Corbin Tomaszeski.
Chef Corbin Tomaszeski cooks alongside Rozanne Persad, owner of Curry & Roti Restaurant in Scarborough, Ont., in the "Restaurant Takeover" studio kitchen. Tomaszeski has some tips for slimming down iconic Canadian recipes and turning them into healthy and delicious options. — Photo by The Canadian Press
The Food Network Canada star has teamed up with Weight Watchers Canada to help dispel the myth that food that's good for you has to be challenging to make.
"As a trained chef, you know the foundation is French cuisine. We're talking fat and cream and butter, duck fat, all that good stuff, which I still enjoy," says Tomaszeski, host of "Restaurant Takeover" and "Dinner Party Wars."
"I can still satisfy my palate with a little less fat," he adds. "It's not about depriving yourself. It's just heightening flavours in another way."
To help better understand Weight Watchers — which recently marked its 50-year milestone — and to develop healthy recipes, Tomaszeski recently tried the program. In the process, he became more aware of what he was eating and lost more than 18 pounds.
"Initially, I was a little reluctant because I thought, 'No. 1, I don't need to lose weight' because that's how I associated it, and No. 2, I thought I was going to have to starve myself to do it. Both are wrong.
"I think that's probably one of the biggest kind of hurdles people face when they look at a program like this, is that it's not a diet. That's the bad word because diet means starve yourself, deprive yourself. Eventually you lose the weight, but then you fall off the wagon and gain it back plus tenfold. This is a program that suits your life, allows you to eat everyday foods, allows you to enjoy food for what it is and you lose weight along the way."
Tomaszeski says he hears from many people who think it's difficult to cook and time-consuming to eat healthily at home.
"Untrue. Follow the rule 'less is more, keep it simple' (and) you'll be successful every time."
Tomaszeski recommends making food from scratch to be in control of the ingredients. Then assess how much oil or butter is needed in the recipe — that is, if any is needed at all.
"When you buy everything out of a box and you buy stuff that is pre-prepared and prefabricated you don't have that control. You may feel good when you eat it, but what does it do for you in the long run?" he says.
Another misconception is that cooking healthily is expensive. Tomaszeski says by cooking foods that are in season and planning ahead, individuals can stay within budget — probably even below.
The chef says there are also tricks to ensure you leave the table full, without suffering hunger pangs and cravings shortly afterward.
He has revamped four iconic Canadian dishes for Weight Watchers, including the classic burger, pulled pork sandwich, ginger beef and the Nanaimo bar.
For the sandwich, he swaps lean chicken for pork.
He uses spices for flavour, adds sweetness to the ginger beef with honey and nixes frying. For the sweet treat from the West Coast, his tricks are egg whites to incorporate volume to the Nanaimo bar's batter along with cocoa, while unsweetened applesauce provides moisture.
When it comes to burgers, those keeping an eye on their waistline might do well to forgo the condiments that add extra calories, fat and sodium to prepare a healthy simple dish that will satisfy the taste buds.
"The burger is all about the right toppings and I find that too many people put the wrong toppings on the burger.
"For example, cheese, bacon, condiments, sauces. You don't need it. If you have a burger with blue cheese, what happens? All you taste is the blue cheese. I want to taste the beef."
He heightens the beef's flavour with just a touch of homemade barbecue sauce and tops the burgers with black bean hummus, which is "really easy, super healthy and high in fibre."
Instead of filling up on a bun, he suggests using half a bun, preferably whole wheat as the additional fibre helps individuals stay fuller longer between meals. Alternatively, they can use a lettuce wrap or whole-wheat pita.
See page B2 for Tomaszeski's recipes


text:
Bob Scott
Bob Scott has been specializing in new boat sales and yacht brokerage for over 28 years. He has earned numerous sales achievement awards representing the finest yachts and boats in the industry. He offers a wealth of product knowledge while enjoying the fine art of matching the right boat to each individual needs. Bob is Oyster Harbors Marine's senior broker, joining Vice President and General Manager, Peter Maryott in 1991. His passion for boating began at a young age and has continued to grow throughout his career. A long time resident of Cape Cod, Bob and his family enjoy sharing time on the water.


text:
My first wedding cake ever, and the bride (my friend) wanted rolled fondant.
It was far from perfect but everybody liked the peach flavor that she's had chosen.
very pretty!
A very simple but classy cake, nice work!
Thank you very much! I was lucky she just wanted it simple.
CakeCentral.com is the world's largest cake community for cake decorating professionals and enthusiasts.
(if this is a private computer)
Yes please, register now!


text:
realmagick.com The shrine of knowledge.
Bethel Connecticut History
A selection of articles related to bethel connecticut history.
Original articles from our library related to the Bethel Connecticut History. See Table of Contents for further available material (downloadable resources) on Bethel Connecticut History.
- Indian History Rewritten
- The Indian civilisation, considered to be the product of clash and subsequent inter mixture of the white-skinned civilised invaders and the dark savages native to India, has been rightly questioned in recent years, and the mischievously fabricated history of...
History & Anthropology >> Indic / Vedic
- The Truth Behind the History of the Necronomicon
- I don't think there are many people out there who haven't heard of the Necronomicon and the dreadful things connected with it. We've all heard the theories about how it is a Satanist tool; actual copies of the book are bound in human skin and how you risk...
Deities & Heros >> Chthulu
- History of the Egyptian Religion, part I: Early Dynastic Period
- I - Predynastic - Early Dynastic Period. The temples were in essence the *Home of the God* and thus a place where only Pharaoh as the Son of God and those he appointed as his deputies, could meet with the god. This goes all the way back to Archaic and...
Religions >> Egyptian
- History of Egyptian Medicine and Philosophy
- When medical knowledge past is considered, lack of aseptic technique, pain-killing drugs and antibiotics are an accepted part of our modern legend of these ancient healing practices. You will find that none of this is true when it comes to Ancient Egypt....
Religions >> Egyptian
- History of the Egyptian Religion, part II: The Old Kingdom
- II - The Old Kingdom ca 2686-2181 BC During the Old Kingdom the Egyptian society moved from tribal communities to a fully developed theocratic system, where the power of the king was absolute. The great pyramids of Dynasty 4 was made possible by technological...
Religions >> Egyptian
Bethel Connecticut History is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Bethel Connecticut History books and related discussion.
Suggested News Resources
- Tennessee Tourism Round Up For March 11-April 2
- Brownsville – Trials, Triumphs and Lessons: Phenomenal Women Speak is the theme of the Women's History Month program 2 p.m. CT at the West Tennessee Delta Heritage Center.
- Daylight Saving Time 2016: When Does it Begin?
- David Prerau, recognized as one of the country's leading experts on our human quest for saving time, has devoted much of his life to chronicling the history and science of DST. He served as a consultant to the U.S.
- Westport gets a new town planner
- WESTPORT — Steven Palmer, the town planner in Bethel, will be returning to Westport to become the new Planning and Zoning Director. Palmer, who had been a zoning enforcement officer here between 1990 through 2002, replaces Larry Bradley, who ...
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
Bethel Connecticut History Topics
Related searchesindian gods
dream symbol black widow
mnemonic visual mnemonics
bhopal sites of interest
sertraline side effects
dart missile kestrosphendone
About - Contact - Advertising
© 2000 - 2016 Realmagick.com, All Rights Reserved.
© 2000 - 2016 Realmagick.com, All Rights Reserved.


text:
Skip to comments.Joel Osteen and Pope Francis
Posted on 08/28/2013 11:39:15 AM PDT by Brian Kopp DPM
click here to read article
A lot of money to be made in Amway. That's all this grinning buck tooth creep is. A fast-talking, grinning hyena, trying to swindle money off gullible old people.
Facts are funny sometimes, aren't they?
You're in for a big surprise.
"You're in for a big surprise."
That salvation isn't really through grace without the working of the law, but that I really needed to live in slavish fear to the Roman Catholic Church?
Somehow I doubt this will ever happen.
Not really fair to lump all protestants in with Blinky Osteen. His is only one if many different protestant viewpoints.
Please do not think that I thought that you were... my post was against osteen and not you. My apologies my friend.
Did I get that right? After all, isn't that the underlying point of Longnecker's article? That Joel Osteen is part of the eeeeevillllll 1%, and the [current] Pope is really one of the 99%?
Related threads:
March participants say Occupy movements concerns aligned with Catholic social teaching
US bishops call for continued unemployment benefits
Catholics 'more likely to back state economic intervention' [European Central Bank study]
CARA suggests polls on creation of a third party: Christian Democrats
Time for True Democrats to Start Their Own Party [or, why Catholics can't vote Democrat any more]
Pope Francis's Economics: Yes, He Has A Leftist View Of Free Markets
What a show of grace.
The vatican and the churches, two different things. Perhaps you are to focused on throwing insults to think before you make an ass of yourself.
Did I say anything about selling? Nope, bzzzzt try again.
I was replying to someone who said the value in monetary terms of the vatican was $1B. Now that you have the context you didn't bother to read before you can apply your vast learning and take another shot.
On the contrary, I think it was just to point out the hypocrisy/stupidity of all the anti-Catholic "the Vatican is too rich" bigots. At least that's how I read it :0)
That said, I have no real problem with the new and present "pope". But to me, in one sense, he's just another guy.
We recommend you remove your nose, then.
I don't fault any Christian for living in nice surroundings. However, poor doctrine and teaching is another matter. Both Osteen and the Pope are simply false teachers of scripture. I suppose in that sense that makes them equals.
"Very few protestant leaders live in 10m mansions."
How many protestant leaders are there? And how do you know which ones are correct in their preaching?
LOL! So saith a follower of false teachers of scriptures...
"How many protestant leaders are there? And how do you know which ones are correct in their preaching?"
There are many but not enough.
How to tell? Well usually I use the Bible as a guidepost. How do you tell?
"Well usually I use the Bible as a guidepost."
Puts you back at square one.
How do you know which denomination or Protestant leader, among thousands, has the correct interpretation of Scripture?
35,000 a recent study showed. 35,000 little napoleons, or should I say martin luthers?
No actually it doesn't put me at square one. It puts me in sync with God.
How do you know your priest has the right interpretation of the man made catholic doctrine?
"No actually it doesnt put me at square one. It puts me in sync with God."
In sync as much as the other 1,000s of denominations and leaders, with their different interpretations.
Unless you have a uniquely revealed ability to interpret Scripture better than those mentioned above.
keep trying, its really not that hard
Thanks. I will have to watch it from work tomorrow as this dsl line is creeping tonight. Gamers probably sucking up bandwidth.
"Well usually I use the Bible as a guidepost."
Only "usually"? What are some of your exceptions?
"Only usually? What are some of your exceptions?"
Thats between God and I. I guess you're the second perfect person to be born on the earth.
Actually, the Catholic Churches in the United States are not owned by the Vatican.
Has a court decided if the Catholic church owns it's churches, or does someone else.
It's the way they are set up legally. Each diocese is an independent unit and the parish properties are owned by the diocese, specifically the bishop.
I believe that in some dioceses, the ownership of the individual parishes have recently gone to the parishes.
I have no use for any televangelists.
Osteen, Hinn, whoever.
Charlatans, all.
Billy Graham is the only one who has any credibility.
longer than the President has lived in the White House, Queen Elizabeth in Buckingham Palace, your Governor in his state mansion.....but none of these people OWN the property....they just live there while they hold office....big difference
you must be a very lonely person....how sad....no sinners near you!!!
if you were the caretaker at the Smithsonian and they gave you an apartment there to live in.....would all that stuff be yours????
the Pope owns virtually NOTHING
Oh my - a 5,000 increase since the thread was posted this morning!
Just as Protestant leaders don't own their churches. Perhaps your issue is with personal wealth then?
Did I saw they were?
I prefer my spiritual leaders to be against sin instead of condoning it.
I thought that's what you meant. My apologies.
I have no isues with anything...true, the minister does not USUALLY own the church (sometimes does)....but he does own his ten million dollar mansion, and his plane, and his yacht, and his whatever.....the Pope owns virtually NOTHING.
Yeah ok, every single minister has a 10 million dollar mansion, a plane, a yacht. yep every single one
or you're a liar.
not every one of course....what an asinine thing to say.....but far more ministers own ten million dollar mansions, of five million dollar mansions, or $250,000 houses, or $10,000 houses, than Popes own anything of consequence. and that's what the discussion was about....the opulance of the Pope.....sad
Look out, another 'devotional' Joel Osteen thread has just been posted. Remember - no discussion of any kind is allowed. You gotta be 'devoted' to Joel!
Which one has a toilet with a gold flusher?
oh yeah the pope
"I guess youre the second perfect person to be born on the earth."
Nope; the best I could be is third. There's already been two: Jesus Christ and His Mother.
who is the more opulent....a person who OWNS a stainless steel toilet flusher or a person who merely uses someone elses gold toilet flusher???????
Jesus mother was not sinless and neither are you or I.
So you have more respect for people who takes money from the poor to buy a gold toilet then someone who purchased a regular old crapper with their own money?
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.


text:
Every month when the full moon rises, Mauna Lani gets ready for an evening of storytelling and entertainment at the oceanfront Eva Parker Woods Cottage. "Twilight at Kalahuipua'a" was designed to perpetuate the traditional folk art of storytelling. Everyone is invited to share stories, family histories, songs, and dance. It gives hotel guests a chance to experience the true aloha spirit, and residents the opportunity to meet and share stories with people from around the world. Join us from 5:30 pm - 8:30 pm. READ MORE for upcoming dates
Twilight Video
Upcoming Twilight Dates
There's always something happening at Mauna Lani. To learn about upcoming events at the resort and around the island please visit our Calendar of Events. If you'd like to know about Scheduled Hotel Activities during your visit please email email@example.com
Mauna Lani celebrates the 28th Annual Turtle Independence Day on Tuesday, July 4th in the morning. The honu will be gathered from the Honu Ponds and will be paraded to the beachfront for the release. A welcome ceremony will kick-off the event followed by the release. This annual celebration honors the honu and helps educate the public about the Hawaiian green sea turtle. Families are invited to join the celebration!
Mauna Lani welcomes Shiono Japanese Restaurant to the Golf Club House. Now open for lunch daily and dinner Tuesday through Sunday. Call 808-881-1111 Hours and Menu Sample
Mauna Lani has become hometo to a pair of Nene geese that have been spotted on the North Course. The Nene Goose is Hawaii's State Bird and is endemic to the Hawaiian Islands. It's one of the world's rarest geese and they are protected by the Federal Endangered Species Act. Please enjoy their beauty from a distance. It's a wonderful experience to see these graceful Nene as they explore the tranquil ambiance of Mauna Lani Resort.
Mason captures his second title in five hole play-off at the Mauna Lani Resort - Hawaii State Open.
DECEMBER 13, 2015 – A legendary Sunday finish on the Kohala Coast at Mauna Lani Resort as Nick Mason captures his second Hawaii State Open title at Mauna Lani Resort.
As round three got under way this morning Nick Mason was one shot off the lead as he teed it up with Parker McLachlin and Jake Grodzinsky. McLachlin would make bogey on the final hole falling back a stroke to tie Mason at 203 forcing a five hole sudden death play-off. Mason would sunk his final putt for birdie to end the play off earning a $10,000 payout. Kyle Suppa shot 68 today to finish at 208 as the low amateur and win the Championship flight.
It was a legendary finish in the Senior Open between Jeff Coston, Dave Eichelberger, Scott Simpson and David Ishii. With over 250 years of golfing experience between the four of them, Coston would claim the first place prize of $5,000 for the second time at Mauna Lani shooting a three day total 209. Eichelberger fell one shot short of Coston while Ishii and Simpson tied for 3rd place at 213. In the Senior Amateur flight, Clayton Amuro captured the low Senior Amateur title earning a $750 gift certificate from the golf shop at Mauna Lani for shooting 223.
After posting the women's course record of 65 during round two professional Britney Yada fired a final round score of 73 today. Yada's three day seven under total 209 earned her an $800 paycheck and the Women's Open. Kristen Peterson of Portland, Oregon finished as the low female amateur at 224. Playing in her very first Hawaii State Open, Peterson earn a $200 gift certificate from Mauna Lani. Pat McGinness held on to his three day lead of A-Flight posting a 231 to finish six shots ahead of Warren Doenz.
About Mauna Lani Resort: The famous golf courses, the Francis H. I'i Brown North & South are named in honor of the former Mauna Lani landowner and champion Hawaii golfer. The courses offer breathtaking scenery, unforgettable signature holes and cutting-edge course design built around ancient Hawaiian petroglyphs, trails and fishponds. Mauna Lani Resort is home to the annual Hawaii State Open played in December.
About the Aloha Section PGA: The Aloha Section PGA was established in 1976, and today is comprised of over 230 golf Professionals working at over 90 facilities within the Section. The mission of the Aloha Section (ASPGA) is that Purpose of the PGA of America, to promote the enjoyment and involvement in the game of golf and to contribute to its growth by providing services to golf professionals and the golf industry. The ASPGA provides competitive playing opportunities, educational seminars, and growth of the game initiatives, within the state of Hawaii.


text: Cole Haan Village Handbag It features supple pebbled leather, a lined interior, several pockets, and a top zip closure. It comes in 6 colors as well. Flag this deal What's the matter? Choose a reason Dead deal Duplicate Bad link Spam Inaccurate No value Alive again Edit deal MdavidK30 Jan 09, 2013 Very nice handbag... good price drop! Reply Load More Comments


text:
and Publications
and Events
Conferences & Events
Annual Conference
EDUCAUSE Connect Events
EDUCAUSE Institute Programs
ELI Annual Meeting
ECAR Annual Meeting
NERCOMP Annual Conference
Security Professionals Conference
Enterprise IT Summit
Online Events
Webinars/Online Events Calendar
Event Resources
Fellowship/Scholarship Program
Presenter Concierge
EDUCAUSE On Campus
Other Higher Ed Event Calendar
Events for all Levels and Interests
Whether you're looking for a conference to attend face-to-face to connect with peers, or for an online event for team professional development, see what's upcoming.Stay
Career Center
EDUCAUSE Institute
Leadership and Management Programs
Project Management
Fellowships and Awards
Getting Involved
Jump Start Your Career Growth
Explore EDUCAUSE professional development opportunities that match your career aspirations and desired level of time investment through our interactive online guide.Stay
Focus Areas
and Initiatives
EDUCAUSE organizes its efforts around three IT Focus Areas
Join These Programs If Your Focus IsStay
and Contribute
Find Others
Get on the Higher Ed IT Map
Employees of EDUCAUSE member institutions and organizations are invited to create individual profiles.
Uncommon Thinking for the Common Good™
EDUCAUSE is the foremost community of higher education IT leaders and professionals.
NIST Announces Cybersecurity Framework Workshop
NIST Announces Cybersecurity Framework Workshop
The National Institute for Standards in Technology (NIST) has announced a Cybersecurity Framework Workshop to be held on April 3rd at its headquarters in Gaithersburg, Maryland. According to the announcement, "NIST is interested in collecting information about current risk management practices; use of frameworks, standards, guidelines and best practices; and specific industry practices." The workshop is being held in response to a directive from the recent Cybersecurity Executive Order issued by President Obama that charges NIST to work with the public and private sectors to develop a framework for securing critical infrastructures. NIST has also issued a Request for Information (RFI) on Developing a Framework To Improve Critical Infrastructure Security. Comments are due on April 8th.
EDUCAUSE and Internet2 are working with the Higher Education Information Security Council to review the Questions in the RFI to develop a higher education response.


text: ENJOY, RESPECT ACHIEVE. We are committed to all our children being happy, confident and valued so they can grow, thrive and achieve success. The Grove Primary School is part of The Kite Academy Trust, a charitable company limited by guarantee and registered in England and Wales with company number 09785186. The registered address is The Grove Primary School, Chobham Road, Camberley, Surrey GU16 8PG.


text:
Bluffton is poised to move forward with as much as $3.5 million in renovations and an expansion of the Theodore Washington Municipal Building, where most of the town's government services are provided.
With the town of Bluffton preparing to take over operations and maintenance of Oyster Factory Park, staff is trying to make renting out space simpler and even cheaper for some organizations.
The owner of the golf course at Daufuskie Island's Bloody Point Golf Club & Resort has plans to redevelop the course into a hospitality and residential district that would include an inn, single-family homes, condos and commercial space.
Local youth on Monday called for more proactive leadership from their peers and the community to honor the legacy of Martin Luther King Jr.
After a month of discussion and four meetings, a trio of Beaufort County Council members and the family that owns the Pepper Hall tract aren't much closer to a development agreement for the property off U.S. 278 in Bluffton.
Plans to build a new RV park in Pritchardville have drawn the ire of some residents, including a Beaufort County school board member, who believe such a development poses both traffic and safety issues.
A month after he was removed from a Bluffton Town Council meeting, Skip Hoagland finished his speech this time — but not before a testy exchange with Mayor Lisa Sulka and town attorney Terry Finger.
Hargray Communications will bring gigabit Internet service to Haig Point on Daufuskie Island this year.
A Beaufort County Councilman's attempt to have council choose its economic development direction by next month failed Monday.
Bluffton Town Council will get its first look Wednesday at design recommendations from the Calhoun Street and Adjacent Area Study.
Subscriber Services:
Digital Network:
Social Networking:
Bluffton Today ©2016. All Rights Reserved.


text:
Free Civil Legal Services
Do you need help with family or housing problems? Are you having trouble getting or keeping public benefits? Do you have other problems that prevent you from finding or keeping a job? We may be able to help.
Who We Are:
Neighborhood Legal Services Program is a nonprofit law firm that provides free legal information, advice and representation to low-income District of Columbia residents. We are committed to equal access to justice for all members of our community.
Intake Hours for New Cases:
Monday, Wednesday, and Friday 10:00 am- 3:00 pm
Call 202-832-NLSP (6577) or come to one of our three neighborhood offices for assistance.
October 25, 2016
NLSP was awarded the Pro Bono Innovation Fund Grant to support our Barriers to Employment programming.read more
August 30, 2016
NLSP's Intake will be closed from 9/12/16 through 9/16/16 and will resume on Monday, 9/19/16. Intakes are available Monday, Wednesday and Friday from 10:00AM to 3:00PMread more
More news
Come to these free clinics at Benning Library to meet with an attorney about criminal records and Ban the Box.read more
Come to these free clinics at Benning Library to meet with an attorney about criminal records and Ban the Box.read more
More Events


text:
Train Chalon sur Saone → MaconFrom AU$ 17
Find a Train Ticket
Overview The average travel time between Chalon sur Saone and Macon is 1h47 minutes. The quickest route is 31 minutes. The first train leaving Chalon sur Saone is at 06:17, the last at 21:23. There is an average of 33 trains a day between Chalon sur Saone and Macon, leaving approximately every 30 minutes.
- Arrival station : Macon ville ( )
Why choose us?
3 million travellers in 2014
15,000 destinations
Rail Europe Travel+
Secured payment
Need assistance?
Travel forum
Travel resources
Contact Us
Main stations in Chalon sur Saone and Macon
Arrival station
Travel inspiration in Chalon sur Saone and Macon
Chalon sur Saone