bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Old West” in the Middle East: U.S. Military Metaphors in Real and Imagined Indian Country
Authors: SILLIMAN STEPHEN W.
Published: December 2008

ABSTRACT In this article, I examine the role of the “Indian Country” heritage metaphor in U.S. military activities in the Middle East from a critical anthropological perspective. Research has revealed the proliferation of such discourse among soldiers, military strategists, reporters, and World Wide Web users to refer to hostile, unsecured, and dangerous territory in Iraq and Afghanistan. The salience of this symbol in 21st‐century U.S. armed conflicts attests to its staying power in national narratives of colonialism at home and abroad. Summoning the “Indian wars” of the 19th century in the U.S. West as malleable symbolic parallels to the current war in Iraq serves to offer combat lessons in guerilla warfare while reinscribing epic stories of U.S. military imperialism and renarrating uncritically the struggles and conflicts of Native Americans, past and present, through the lens of contemporary perspectives on terrorism.
A Review of Hu Tai‐li's Documentary Educational Resources Series
Authors: MOSKOWITZ MARC L.
Published: December 2008

ABSTRACT  This review addresses six films made by Taiwan's most well respected ethnographic filmmaker, Hu Tai‐li. The films were recently released as part of the Documentary Educational Resources series and cover Hu's most well‐known works. The films in the series span two decades, beginning with her first film in 1985. Hu's films capture the everyday lives of the disenfranchised in Taiwan, ranging from aboriginal groups to working‐class Taiwanese who have been displaced by shifting economic structures. Her films are especially important for Taiwan Studies, for they capture fading traditions as well as continued ethnic and class tensions within Taiwan. As such, the films are important for anyone who wants to come to a better understanding of Taiwan's past and present.
Kurdish Refugee Reception Centers in Greece: Home Displaced
Authors: SMITH BARBARA
Published: December 2008

Refugee campsites in Greece have provided temporary relief for hundreds of asylum seekers. At their peak, camp populations have exceeded over a thousand people, mainly Kurdish people seeking refugee status. In search of a better life, the people arrive in Greece by way of a smuggler's speedboat, a dilapidated ship, or crossing minefields. People often create functioning villages within the confines of the most difficult living situations. Their life there becomes a small mirror of the country and the life that they left behind. When the people are finally ready to leave the camps, it is simply the start of another chapter in their complicated journey to the golden land.
The Obama Victory, Asset‐Based Development and the Re‐Politicization of Community Organizing
Authors: Hyatt Susan B.
Published: December 2008

Abstract: In this commentary, I argue that Obama's victory in the recent Democratic primary was largely a consequence of his early experiences as an Alinsky‐style community organizer in Chicago. I compare the nature of the broad‐based organizing that Obama was trained in to a newer model of “community building” called Asset‐Based Community Development (ABCD). ABCD promotes the belief that communities suffering the effects of economic restructuring, such as abandoned housing, crime, and deindustrialization among others, can “heal themselves” by looking within for resources—or “assets”—rather than by making demands on the state, a stance its proponents stigmatize as evidence of a “client” mentality. I argue that however chimerical its promises of redemption are, ABCD illustrates an important shift in contemporary understandings of citizenship, away from the possibilities for collective action that characterize Alinsky‐style organizing and toward a view that is both radically neoliberal and potentially totalitarian in its homogenizing notions of its two key concepts—”community” and “assets.” I suggest that the grassroots nature of the Obama campaign may have the potential to reanimate an interest in broad‐based organizing toward the end of creating a more just distribution of resources.
Undifferentiated carcinoma of the jejunum with extensive rhabdoid features . Case report and review of the literature
Authors: SALAMANCA JAVIER , NEVADO MANUEL , MARTÍNEZ‐GONZÁLEZ MIGUEL ÁNGEL , PÉREZ‐ESPEJO GUSTAVO , PINEDO FERNANDO
Published: December 2008

Malignant rhabdoid tumor, first described in the kidney of young infants, is a rare and highly aggressive neoplasm of controversial histogenesis that has been reported at many other sites, including the gastrointestinal tract. However, malignant rhabdoid tumor of the small intestine is very rare, with only seven cases published to date. We report a 70‐year‐old man who presented with abdominal pain and weight loss, and showed a perforated jejunal mass with disseminated metastases by imaging. The patient underwent partial jejunectomy and biopsy of a liver metastasis. Microscopically, the tumor was characterized by neoplastic cells with vesicular nuclei, large nucleoli and abundant eccentric cytoplasm with hyaline globular intracytoplasmic inclusions. Immunohistochemically, the neoplasm coexpressed vimentin and epithelial antigens (AE1/AE3, Cam 5.2, CK34βE12, CK19 and EMA), most of them showing a peculiar immunostaining pattern in relation to the globular inclusions. Ultrastructurally, the inclusions corresponded to paranuclear whorls of intermediate filaments. The patient received postoperative chemotherapy but died 9 months after surgery. In summary, we report the exceptional case of an undifferentiated carcinoma of the jejunum with rhabdoid phenotype. As with tumors at other sites, recognition of rhabdoid morphology in small intestine neoplasms is of significance because the prognosis is extremely poor.
First diagnosis of Martin‐Albright syndrome in a 58‐year‐old patient
Authors: Quist Sven R. , Franke Ingolf , Hiort Olaf , Gollnick Harald P. , Leverkus Martin
Published: December 2008

Albright hereditary osteodystrophy (AHO), also known as Martin‐Albright syndrome (MAS), is a rare autosomal dominantly transmitted disease characterized by short stature, obesity, mental retardation, a round facies, and brachymetacarpia and ‐tarsia, as well as cutaneous calcification. The disease is caused by mutations in the GNAS gene localized on chromosome 20q13.2 encoding for an adenyl‐cyclase‐stimulating protein (Gsα). A 58‐year‐old patient presented with small stature since childhood, moderate mental retardation, round facies and soft tissue masses on the thighs. A biopsy of the latter showed subcutaneous ossification. Laboratory results showed hypocalcemia, as well as increased plasma levels of PTH and calcitonin. The clinical diagnosis was confirmed by detection of reduced activity of Gsα. In patients with cutaneous calcification and disturbed calcium metabolism, AHO is an important differential diagnostic consideration.
Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling
Authors: Laure Lydie , Suel Laurence , Roudaut Carinne , Bourg Nathalie , Ouali Ahmed , Bartoli Marc , Richard Isabelle , Danièle Nathalie
Published: December 2008

In an attempt to identify potential therapeutic targets for the correction of muscle wasting, the gene expression of several pivotal proteins involved in protein metabolism was investigated in experimental atrophy induced by transient or definitive denervation, as well as in four animal models of muscular dystrophies (deficient for calpain 3, dysferlin, α‐sarcoglycan and dystrophin, respectively). The results showed that: (a) the components of the ubiquitin–proteasome pathway are upregulated during the very early phases of atrophy but do not greatly increase in the muscular dystrophy models; (b) forkhead box protein O1 mRNA expression is augmented in the muscles of a limb girdle muscular dystrophy 2A murine model; and (c) the expression of cardiac ankyrin repeat protein (CARP), a regulator of transcription factors, appears to be persistently upregulated in every condition, suggesting that CARP could be a hub protein participating in common pathological molecular pathway(s). Interestingly, the mRNA level of a cell cycle inhibitor known to be upregulated by CARP in other tissues, p21WAF1/CIP1, is consistently increased whenever CARP is upregulated. CARP overexpression in muscle fibres fails to affect their calibre, indicating that CARP per se cannot initiate atrophy. However, a switch towards fast‐twitch fibres is observed, suggesting that CARP plays a role in skeletal muscle plasticity. The observation that p21WAF1/CIP1 is upregulated, put in perspective with the effects of CARP on the fibre type, fits well with the idea that the mechanisms at stake might be required to oppose muscle remodelling in skeletal muscle.
Autocatalytic processing of procathepsin B is triggered by proenzyme activity
Authors: Pungerčar Jerica Rozman , Caglič Dejan , Sajid Mohammed , Dolinar Marko , Vasiljeva Olga , Požgan Urška , Turk Dušan , Bogyo Matthew , Turk Vito , Turk Boris
Published: December 2008

Cathepsin B (EC 3.4.22.1) and other cysteine proteases are synthesized as zymogens, which are processed to their mature forms autocatalytically or by other proteases. Autocatalytic processing was suggested to be a bimolecular process, whereas initiation of the processing has not yet been clarified. Procathepsin B was shown by zymography to hydrolyze the synthetic substrate 7‐N‐benzyloxycarbonyl‐l‐arginyl‐l‐arginylamide‐4‐methylcoumarin (Z‐Arg‐Arg‐NH‐MEC), suggesting that procathepsin B is catalytically active. The activity‐based probe DCG‐04, which is an E‐64‐type inhibitor, was found to label both mature cathepsin B and its zymogen, confirming the zymography data. Mutation analyses in the linker region between the propeptide and the mature part revealed that autocatalytic processing of procathepsin B is largely unaffected by mutations in this region, including mutations to prolines. On the basis of these results, a model for autocatalytic activation of cysteine cathepsins is proposed, involving propeptide dissociation from the active‐site cleft as the first step during zymogen activation. This unimolecular conformational change is followed by a bimolecular proteolytic removal of the propeptide, which can be accomplished in one or more steps. Such activation, which can be also facilitated by glycosaminoglycans or by binding to negatively charged surfaces, may have important physiological consequences because cathepsin zymogens were often found secreted in various pathological states.
Long‐term monitoring of endoparasites in birds‐of‐paradise at Al Wabra Wildlife Preservation, Doha
Authors: ZERBE P. , SCHWARZ C. , DEB A. , BORJAL R. J. , ARIF A. , TAHA A. S. , STREICH W. J. , CLAUSS M. , HAMMER S.
Published: December 2008

We evaluated results of over 4400 documented faecal parasitological examinations between 2000 and 2007 in more than 90 individuals of six species of birds of paradise (BoP). Between 2000 and 2007, 83·2% of investigated samples were negative for parasites, and the number of negative samples increased consistently over the years; in positive samples, the proportion of Capillaria sp decreased (from 100 to 4·8%) and that of Coccidia sp increased (from 0 to 67·5%). Differences in the prevalence of endoparasites between species, epidemiological units (houses) and sexes were found. The Twelve‐wired bird‐of‐paradise Seleucidis melanoleuca, which has the highest reported proportion of insects in its natural diet, had the highest prevalence of tapeworms, indicating a high propensity to ingest intermediate hosts. Coccidia sp were particularly prevalent in an epidemiological unit with high exposure to free‐ranging birds. The number of offspring per female and year correlated with the percentage of negative samples taken in the according year and species. The results indicate that (1) consistent antiparasitic management leads to a reduction of parasite species, (2) parasites with intermediate hosts are more difficult to control, (3) exposure to free‐ranging birds should be minimized and (4) a tight antiparasitic management potentially contributes to the improved breeding success in bird species.
Measuring performance: environmental management systems
Authors: TURNER I.
Published: December 2008

Climate change will have an impact on biodiversity; most modern zoos are concerned with the conservation of biodiversity and therefore have an obligation to minimize their impact on the environment, particularly their contribution to factors causing climate change. An environmental management system (EMS) is a tool to identify, measure and reduce an organization's impacts on the environment in a systematic way and to continually improve environmental performance through a four‐stage cyclical method, Plan–Do–Check–Act. Paignton Zoo Environmental Park began to implement an EMS in 2003 and achieved the international standard ISO14001 for environmental management in 2005. In addition to improving environmental performance and legal compliance, and reducing environmental risk, the main advantages of the EMS have been costs savings on utilities, improved credibility and media coverage, and improved access to grant funding for ‘green’ initiatives. However, there have also been cost implications in terms of staff time, administration, financial costs in setting up the system, capital costs in investment in processes and equipment with the best environmental ratings, and additional constraints on development because environmental issues can no longer be conveniently ignored. Despite these disadvantages, the EMS has been a very effective tool for Paignton Zoo Environmental Park, enabling it to become a recognized leader in this field and truthfully to live up to its name.
The role of zoos and aquariums in research into the effects of climate change on animal health
Authors: BARBOSA A.
Published: December 2008

The role that the zoos and aquariums can play in the study into the effects of global climate change, particularly on animal health, is discussed and examples of how this could be achieved are presented. Animals in zoos and aquariums often live under environmentally controlled conditions and may not be subject to the effects of climate change or exposed to the increased numbers of parasites or pathogens that might conceivably be a product of climate change. However, climate‐change effects have been reported in both humans and livestock and so it is likely that some animals in zoos and aquariums will also be affected. In 2004, there was a report of 118 transmissible diseases affecting animals in zoos and aquariums, and 29 (25%) of these can be identified as likely to be affected by climate change. Because it is possible to simulate different environmental conditions in zoos and aquariums, and many such institutions have valuable data on animal health that have been collected historically, they may be particularly appropriate places to carry out climate‐change studies.
Managing low‐skill workers: a study of small UK food manufacturing firms
Authors: Edwards Paul , Sengupta Sukanya , Tsai Chin‐Ju
Published: December 2008

Low‐wage work is of growing significance in the UK. This article tests the model of the low‐skills equilibrium (LSE) through a study of 27 small firms in a sector, food manufacturing, widely identified as being in an LSE. Three hypotheses are tested. (1) There will be a single, fixed equilibrium. We find more variety, reflecting the specific circumstances of firms. (2) An equilibrium is sustained by weak support institutions and a product market dominated by low value‐added goods. The expectation about institutions is supported, but the product market permitted some, albeit weak, opportunities to escape the LSE. (3) Skills will be low, and workplace regimes will be characterised by work intensification. Some firms were developing employee skills. Work intensification was rare, reflecting the absence of Taylorisation and the importance of face‐to‐face relationships. Overall, some firms had the will to escape the LSE, but weak institutional support and a ready supply of labour substantially reduced the incentives to do so.
Regulation of P2X2 Receptors by the Neuronal Calcium Sensor VILIP1
Authors: Chaumont Severine , Compan Vincent , Toulme Estelle , Richler Esther , Housley Gary D. , Rassendren Francois , Khakh Baljit S.
Published: December 2008

Optics and electrophysiology reveal the dynamics of an ATP-gated ion channel signaling complex.
BDNF Selectively Regulates GABA
A
Receptor Transcription by Activation of the JAK/STAT Pathway
Authors: Lund Ingrid V. , Hu Yinghui , Raol YogendraSinh H. , Benham Rebecca S. , Faris Ramona , Russek Shelley J. , Brooks-Kayal Amy R.
Published: December 2008

BDNF regulates a GABA receptor subunit through the repressor ICER.
β-Blockers: Both Antagonist and Agonist
Authors: Gough Nancy R.
Published: December 2008

Select drugs that inhibit β-adrenergic receptor-mediated activation of G proteins stimulate signaling through β-arrestin.
Converging on β-Catenin
Authors: Adler Elizabeth M.
Published: December 2008

Studies by two groups converge to implicate the cyclin-dependent kinase CDK8 in the pathogenesis of colorectal cancer.
Cystic Fibrosis Remodeled
Authors: Kiberstis Paula A.
Published: December 2008

Newborn pigs carrying a mutated copy of the gene defective in cystic fibrosis exhibit many features of the human disease and may provide fresh insights for therapy.
Why Albinism Impairs Eyesight
Authors: Gough Nancy R.
Published: December 2008

L-DOPA, an intermediate in melanin synthesis, stimulates an orphan G protein-coupled receptor to trigger release of a trophic factor from the retinal pigmented epithelia.
Apoptosis by Another Route
Authors: Ray L. Bryan
Published: December 2008

In worms, lipid signaling at the mitochondria is necessary for the germ-cell death that follows radiation damage but not for normal developmental cell death.
Science Signaling
Podcast: 07 October 2008
Authors: Gough Nancy R. , Foley John F.
Published: December 2008

The bacteria that cause periodontitis evade destruction by promoting crosstalk between two receptors that regulate the immune response.
Sugar Sensor
Authors: Ray L. Bryan
Published: December 2008

A receptor senses glucose and contributes to metabolic regulation in the fruit fly.
More Light, Less Disease
Authors: Gough Nancy R.
Published: December 2008

Excess light changes the redox status of the chloroplast plastoquinone pool, which triggers both responses involved in acclimation to the light and pathogen defense.
Taking It Slow
Authors: Foley John F.
Published: December 2008

By increasing the half-lives of peptide-MHC complexes on dendritic cells, TLR ligands lead to increased T cell receptor activation in CD8
+
T cells.
Hindering Herpes
Authors: Hurtley Stella M.
Published: December 2008

Herpes virus in neurons can be kept in a latent state by T cells, which release granzyme B, an inhibitor of a protein necessary for viral gene expression.
T Regulation of Dendritic Cells
Authors: Kelner Katrina L.
Published: December 2008

A protein in T regulatory cells controls their ability to dampen activation of the immune system by antigen-presenting cells, preventing autoimmune disease.
Acetylation of MKP-1 and the Control of Inflammation
Authors: Chi Hongbo , Flavell Richard A.
Published: December 2008

Toll-like receptor signaling is inhibited by acetylated MKP-1, a mitogen-activated protein kinase phosphatase.
MLK3 as a RhoGEF Partner
Authors: Gough Nancy R.
Published: December 2008

The MAPKKK MLK3 appears to interact with a Rho guanine nucleotide exchange factor to dampen Gα
q
signaling.
Allosteric Networks on Demand
Authors: Vinson Valda J.
Published: December 2008

Two allosterically regulated proteins can be engineered to interact so that when light activates one it triggers the enzymatic output (dihydrofolate reductase) of the other.
Going Multicellular with a Beefed-Up Kinome
Authors: Ray L. Bryan
Published: December 2008

Bacteria that act together like a multicellular organism have a diverse set of kinases like those of eukaryotic organisms.
Systems- and Molecular-Level Elucidation of Signaling Processes Through Chemistry
Authors: Chiang Kyle P. , Muir Tom W.
Published: December 2008

New techniques take advantage of chemistry to investigate signal transduction mechanisms in the cell.
Lateral Root Regulation
Authors: Hines Pamela J.
Published: December 2008

A membrane kinase regulates the number of stem cells in the main tip of the root as well as the de novo generation of stem cells in new laterally projecting roots.
Signaling Networks and Mathematics
Authors: Yaffe Michael B.
Published: December 2008

Biologists discover that mathematics can reveal the complexity of cellular signaling networks.
Sensing When Happy Days Are Here Again
Authors: Adler Elizabeth M.
Published: December 2008

Peptidoglycan fragments released from growing bacteria trigger germination of dormant spores.
Induced Pore Formation by Tetramerization
Authors: Gough Nancy R.
Published: December 2008

Stim appears to trigger calcium-induced calcium release by inducing tetramerization of the pore-forming Orai subunits.
Inducing Endocycling
Authors: VanHook Annalisa M.
Published: December 2008

Selective inhibition of CDK1 is sufficient to induce endoreduplication in mammalian trophoblast giant cells.
Stress and the RACK
Authors: Ray L. Bryan
Published: December 2008

Too much stress is bad, particularly when one stress pathway inhibits function of another.
Brain Repair
Authors: Hines Pamela J.
Published: December 2008

Regeneration in the central nervous system is impeded by inhibitory receptors that recognize myelin-embedded proteins.
Science Signaling
Podcast: 11 November 2008
Authors: Major Michael B. , Moon Randall T. , VanHook Annalisa M.
Published: December 2008

Ben Major and Randall Moon discuss their screen for cell type-specific modifiers of Wnt signaling.
Under Cover
Authors: Foley John F.
Published: December 2008

Binding of CD3ε subunits to the plasma membrane shields critical residues from tyrosine kinases, thus preventing inadvertent T cell activation.
Surviving Lean Times
Authors: Gough Nancy R.
Published: December 2008

An acetylation switch controls the activity of CRTC2 in regulating the hepatic gluconeogenic program in response to fasting.
Meaningful Fluctuations
Authors: Wong Wei
Published: December 2008

Oscillations in MAPK activity in pheromone-stimulated yeast are linked to the formation of multiple mating projections.
Holding Their Own: The Noncanonical Roles of Smad Proteins
Authors: Hoover Loretta L. , Kubalak Steven W.
Published: December 2008

There are TGF-β–independent regulatory mechanisms and functions of Smads.
Making a Tight Seal
Authors: VanHook Annalisa M.
Published: December 2008

Wnt signaling is required for early stages of blood-brain barrier formation in mice.
Suppressing Chemotaxis
Authors: Adler Elizabeth M.
Published: December 2008

Oleic acid in plasma inhibits neutrophil chemotaxis.
Modeling Subcellular Morphogenesis
Authors: Hurtley Stella M.
Published: December 2008

A reaction-diffusion model involving regulatory molecules and a microtubule-stabilizing phosphoprotein predicts the spatial distribution of microtubules during cell division.
GPCR Structural Diversity
Authors: Vinson Valda J.
Published: December 2008

The ligand binding pocket of the caffeine-binding human adenosine receptor has a position and orientation different from that of other G protein–linked receptors.
How to “Cell” a Genomic or Proteomic Screen
Authors: Yaffe Michael B.
Published: December 2008

With the amount of data from screens increasing, researchers need better ways to make the information most useful.
An All-Purpose Tool for Axon Guidance
Authors: Schecterson Leslayann C. , Bothwell Mark
Published: December 2008

The p75 neurotrophin receptor functions as a co-receptor in three distinct systems that mediate repellant signals.
An Unexpected Partner
Authors: Adler Elizabeth M.
Published: December 2008

FGF and adenosine synergistically activate ERK, an interaction mediated through the physical association of their receptors.
It’s a Knock Out
Authors: Ray L. Bryan
Published: December 2008

In mice, a coactivator binds to a nuclear orphan receptor and regulates glucose-6-phosphatase transcription and thus glucose homeostasis.
Two Inhibitors in One
Authors: VanHook Annalisa M.
Published: December 2008

The amino-terminal domain of Wnt antagonist Dickkopf-1 functions independently of the canonical Wnt signaling pathway.
New Tricks for the Old PH Domain
Authors: Ray L. Bryan
Published: December 2008

The pleckstrin homology domain forms a molecular switch that regulates association of an adaptor protein with the cytoskeleton.
From Gut to Bone
Authors: Gough Nancy R.
Published: December 2008

Serotonin produced by the gut reduces bone mass.
Turning On TRPM3
Authors: Adler Elizabeth M.
Published: December 2008

Pregnenolone sulphate, an endogenous steroid, directly activates the TRPM3 cation channel.
Toward Normalizing Metabolic Regulation
Authors: Ray L. Bryan
Published: December 2008

In mice, some detrimental effects of a diet high in fat—insulin resistance, for example—result from hormonal signals sent from fat cells to the liver.
Geometry Influences Polarity
Authors: VanHook Annalisa M.
Published: December 2008

Local propagation of polarity can occur in the absence of global cues provided the cells are regularly packed.
Follow the Leader
Authors: Wong Wei
Published: December 2008

One set of signaling proteins directs migration at the edge of a sheet of endothelial cells, whereas a distinct set coordinates cell movements within the sheet.
GSK-3, Jack of All Trades
Authors: Ray L. Bryan
Published: December 2008

Cross-talk between signaling pathways alters transcriptional regulatory activity of the glucocorticoid nuclear receptor.
What Is Behind the Secondary Inward Current?
Authors: Stern Peter
Published: December 2008

Activation of a glutamate receptor in hippocampal cells leads to secondary opening of a gap junction–like channel that can contribute to seizure-like bursting.
Focus Issue: Organ Development from Beginning to End
Authors: VanHook Annalisa M.
Published: December 2008

Cell signaling events play a key role in the induction, regulation, and maintenance of organ development.
Intercellular Peptide Signals Regulate Plant Meristematic Cell Fate Decisions
Authors: Gray Julie E. , Casson Stuart , Hunt Lee
Published: December 2008

By controlling stem cell fate, secreted peptides control the formation of many plant cell types.
Luminal Sensors from the Basal Side
Authors: Gough Nancy R.
Published: December 2008

Basal cells extend projections that reach the luminal surface and respond to luminal hormones.
Invariant Chain Migration Control
Authors: Hurtley Stella M.
Published: December 2008

By binding to a myosin, an immune-specific protein known to control antigen processing also regulates the migration of dendritic cells, possibly coordinating the two functions.
Sensitive Fluorescence
Authors: Foley John F.
Published: December 2008

A FRET-based sensor enables the live monitoring of the temporal and spatial dynamics of ERK activity in cells and intact tissues.
Global Influence
Authors: VanHook Annalisa M.
Published: December 2008

FGF signaling initiates planar cell polarity during convergent extension.
Meiosis in the Making
Authors: Riddihough Guy
Published: December 2008

Mouse germ cells begin meiosis for sperm or egg production only when they both are stimulated by the hormone retinoic acid and express a particular RNA-binding protein.
Food for Thought
Authors: Ray L. Bryan
Published: December 2008

Brain cells monitor metabolism to appropriately control blood flow according to neuronal activity and oxygen supply.
Science Signaling
Podcast: 16 December 2008
Authors: Foley John F. , VanHook Annalisa M.
Published: December 2008

Binding of CD3ε subunits to plasma membrane lipids blocks T cell receptor signaling.
Gender Bias
Authors: Wong Wei
Published: December 2008

Testosterone affects ERK2 activity, which in turn regulates the subcellular localization and activity of a lipoxygenase involved in inflammation.
More Estrogen, More Active
Authors: Ray L. Bryan
Published: December 2008

The gonadotropin follicle-stimulating hormone both promotes production of estrogen and enhances its transcriptional activity at the ovary.
Beyond Microarrays
Authors: Yaffe Michael B.
Published: December 2008

Studies of global changes in mRNA abundance may be less than insightful.
Regulatory T Cells: The Cunning Fox and Its Clinical ApplicationSelected highlights from the International Conference on Regulatory T Cells and Clinical Application in Human Diseases: “China Tregs 2008,” Beijing, China, 25 to 27 October 2008.
Authors: Game David S. , Cao Xuetao , Jiang Shuiping
Published: December 2008

A conference in Beijing, China, focused on the biology of regulatory T cells and their potential uses in treating various diseases.
mAKAP Compartmentalizes Oxygen-Dependent Control of HIF-1α
Authors: Wong Wei , Goehring April S. , Kapiloff Michael S. , Langeberg Lorene K. , Scott John D.
Published: December 2008

The scaffold protein muscle A kinase–anchoring protein (mAKAP) regulates the stability and localization of the transcription factor HIF-1α.
New Regulators of Wnt/β-Catenin Signaling Revealed by Integrative Molecular Screening
Authors: Major Michael B. , Roberts Brian S. , Berndt Jason D. , Marine Shane , Anastas Jamie , Chung Namjin , Ferrer Marc , Yi XianHua , Stoick-Cooper Cristi L. , von Haller Priska D. , Kategaya Lorna , Chien Andy , Angers Stephane , MacCoss Michael , Cleary Michele A. , Arthur William T. , Moon Randall T.
Published: December 2008

Integration of protein-protein interaction networks and human genome-wide RNAi screens produces mechanistic insight into Wnt/β-catenin signaling.
Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects
Authors: Salgin B. , Marcovecchio M. L. , Humphreys S. M. , Hill N. , Chassin L. J. , Lunn D. J. , Hovorka R. , Dunger D. B.
Published: December 2008

Normal β-cells adjust their function to compensate for any decrease in insulin sensitivity. Our aim was to explore whether a prolonged fast would allow a study of the effects of changes in circulating free fatty acid (FFA) levels on insulin secretion and insulin sensitivity and whether any potential effects could be reversed by the antilipolytic agent acipimox. Fourteen (8 female, 6 male) healthy young adults (aged 22.8–26.9 yr) without a family history of diabetes and a body mass index of 22.6 ± 3.2 kg/m2 were studied on three occasions in random order. Growth hormone and FFA levels were regularly measured overnight (2200-0759), and subjects underwent an intravenous glucose tolerance test in the morning (0800-1100) on each visit. Treatment A was an overnight fast, treatment B was a 24-h fast with regular administrations of a placebo, and treatment C was a 24-h fast with regular ingestions of 250 mg of acipimox. The 24-h fast increased overnight FFA levels (as measured by the area under the curve) 2.8-fold [51.3 (45.6–56.9) vs. 18.4 (14.4–22.5) *104 μmol/l*min, P < 0.0001], and it led to decreases in insulin sensitivity [5.7 (3.6–8.9) vs. 2.6 (1.3–4.7) *10−4 min−1 per mU/l, P < 0.0001] and the acute insulin response [16.3 (10.9–21.6) vs. 12.7 (8.7–16.6) *102 pmol/l*min, P = 0.02], and therefore a reduction in the disposition index [93.1 (64.8–121.4) vs. 35.5 (21.6–49.4) *102 pmol/mU, P < 0.0001]. Administration of acipimox during the 24-h fast lowered FFA levels by an average of 20% (range: −62 to +49%; P = 0.03), resulting in a mean increase in the disposition index of 31% ( P = 0.03). In conclusion, the 24-h fast was accompanied by substantial increases in fasting FFA levels and induced reductions in the acute glucose-simulated insulin response and insulin sensitivity. The use of acipimox during the prolonged fast increased the disposition index, suggesting a partial reversal of the effects of fasting on the acute insulin response and insulin sensitivity.
Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo
Authors: Fujita Yukihiro , Wideman Rhonda D. , Speck Madeleine , Asadi Ali , King David S. , Webber Travis D. , Haneda Masakazu , Kieffer Timothy J.
Published: December 2008

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released during meals from endocrine cells located in the gut mucosa and stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar sensing and its downstream events coupled to the release of the incretin hormones are not clearly elucidated. Recently, it was reported that sucralose, a sweetener that activates the sweet receptors of taste buds, triggers incretin release from a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity of α-gustducin, a key G-coupled protein involved in taste sensing, is sometimes colocalized with GIP in rat duodenum. We investigated whether secretion of incretins in response to carbohydrates is mediated via taste receptors by feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d-tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce the blood glucose excursion to a subsequent intraperitoneal glucose tolerance test. Neither oral sucralose nor oral stevia reduced blood glucose levels in Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP levels ∼4-fold and GLP-1 levels ∼2.5-fold postadministration, none of the sweeteners tested significantly increased levels of these incretins. Collectively, our findings do not support the concept that release of incretins from enteroendocrine cells is triggered by carbohydrates via a pathway identical to the sensation of “sweet taste” in the tongue.
Nonlinear properties of vagal and sympathetic modulations of heart rate variability in ovine fetus near term
Authors: Frasch Martin G. , Müller Thomas , Hoyer Dirk , Weiss Christian , Schubert Harald , Schwab Matthias
Published: December 2008

Fetal heart rate (FHR) monitoring is commonly used although clinical studies questioned its diagnostic value. Sophisticated FHR variability (fHRV) measures such as fHRV complexity may improve the sensitivity and specificity of FHR monitoring. A more detailed understanding of the physiology underlying fHRV complexity is essential to harness its use for monitoring fetal health. To examine the specific effects of vagal and sympathetic modulations on fHRV complexity, we blocked vagal activity with atropine and sympathetic activity with propranolol in near-term fetal sheep ( n = 7, 0.85 gestation). Under these conditions, we analyzed the linear and nonlinear parts of fHRV complexity from autonomic information flow. Overall fHRV complexity decreased with both drugs compared with nonrapid eye movement sleep baseline ( P < 0.05). With atropine, this was because of a decrease of the linear part of fHRV complexity on the long-term time scale ( P < 0.05), suggesting that vagal modulation of fHRV is adequately described by linear fHRV measures. With propranolol, the nonlinear part of fHRV complexity decreased on the short-term time scale ( P < 0.05), suggesting that sympathetic influences on fHRV can be detected by the nonlinear part of fHRV complexity. Thus the complex interplay of vagal and sympathetic modulations of fHRV is reflected differently and specifically in the linear and nonlinear properties of fHRV complexity, and on different time scales. Analysis of linear and nonlinear properties of fHRV may improve sensitivity and specificity of FHR monitoring.
Using a Common Average Reference to Improve Cortical Neuron Recordings From Microelectrode Arrays
Authors: Ludwig Kip A. , Miriani Rachel M. , Langhals Nicholas B. , Joseph Michael D. , Anderson David J. , Kipke Daryl R.
Published: December 2008

In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.
Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver
Authors: Nelson Clark J. , Otis Jessica P. , Martin Sandra L. , Carey Hannah V.
Published: December 2008

A hallmark of hibernation in mammals is metabolic flexibility, which is typified by reversible bouts of metabolic depression (torpor) and the seasonal shift from predominantly carbohydrate to lipid metabolism from summer to winter. To provide new insight into the control and consequences of hibernation, we used LC/MS-based metabolomics to measure differences in small molecules in ground squirrel liver in five activity states: summer, entering torpor, late torpor, arousing from torpor, and interbout arousal. There were significant alterations both seasonally and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid catabolism, and purine and pyrimidine metabolism, with observed metabolites reduced during torpor and increased upon arousal. Multiple lipids also changed, including 1-oleoyllysophosphatidylcholine, cholesterol sulfate, and sphingosine, which tended to be lowest during torpor, and hexadecanedioic acid, which accumulated during a torpor bout. The results reveal the dramatic alterations that occur in several classes of metabolites, highlighting the value of metabolomic analyses in deciphering the hibernation phenotype.
Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle
Authors: Saleem Ayesha , Adhihetty Peter J. , Hood David A.
Published: December 2008

p53 is a tumor suppressor protein that also plays a role in regulating aerobic metabolism. Since skeletal muscle is a major source of whole body aerobic respiration, it is important to delineate the effects of p53 on muscle metabolism. In p53 knockout (KO) mice, we observed diminished mitochondrial content in mixed muscle and lowered peroxisome proliferator-activated receptor-γ (PPARγ) coactivator (PGC)-1α protein levels in gastrocnemius muscle. In intermyofibrillar (IMF) mitochondria, lack of p53 was associated with reduced respiration and elevated reactive oxygen species production. Permeability transition pore kinetics remained unchanged; however, IMF mitochondrial cytochrome c release was reduced and DNA fragmentation was lowered, illustrating a resistance to mitochondrially driven apoptosis in muscle of KO mice. p53-null animals displayed similar muscle strength but greater fatigability and less locomotory endurance than wild-type (WT) animals. Surprisingly, the adaptive responses in mitochondrial content to running were similar in WT and KO mice. Thus p53 may be important, but not necessary, for exercise-induced mitochondrial biogenesis. In WT animals, acute muscle contractions induced the phosphorylation of p53 in concert with increased activation of upstream kinases AMP-activated protein kinase and p38, indicating a pathway through which p53 may initiate mitochondrial biogenesis in response to contractile activity. These data illustrate a novel role for p53 in maintaining mitochondrial biogenesis, apoptosis, and performance in skeletal muscle.
Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice
Authors: Motoyama Keiko , Nakai Yuji , Miyashita Tomoya , Fukui Yuichiro , Morita Maki , Sanmiya Kazutsuka , Sakakibara Hiroyuki , Matsumoto Ichiro , Abe Keiko , Yakabe Takafumi , Yajima Nobuhiro , Shimoi Kayoko
Published: December 2008

To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate). Gene Ontology analysis of these differentially expressed genes indicated that the stress remarkably downregulated the lipid metabolism-related pathway through peroxisome proliferator-activated receptor-α, while the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1, Golgi vesicle transport, and secretory pathway-related genes were significantly upregulated. These results suggest that isolation for 30 days with a mild and consecutive social stress regulates the systems for lipid metabolism and also causes endoplasmic reticulum stress in mouse liver.
Impact des vaccins dans les pays à bas et hauts revenus
Authors: Gothefors Leif
Published: December 2008

La vaccination est devenue la mesure de santé publique la plus efficace pour le contrôle des maladies infectieuses, après l’accès à de l’eau potable non contaminée. L’histoire de la vaccination est marquée par de grands espoirs et quelques déceptions. La seconde moitié du 20ème siècle a été notamment témoin du développement de remarquables projets de vaccination. Il sera possible d’éradiquer la poliomyélite et la rougeole dans quelques années, mais près de 3 millions de personnes, habituellement des enfants âgés de moins de 5 ans, décèdent chaque année de maladies pouvant être prévenues par des vaccins. Les pays en développement luttent pour obtenir les vaccins dont leurs enfants ont désespérément besoin. Pourtant, en Europe et en Amérique du Nord, des personnes ont fait preuve d’une certaine inconscience à propos des vaccins: «ces maladies ne sont plus une menace, les vaccins sont plus dangereux que ces maladies». Ces conceptions erronées ont été à l’origine d’épidémies de rougeole, de diphtérie et de coqueluche. La communauté internationale doit continuer à consacrer les ressources nécessaires, le financement et le travail humain afin d’exploiter totalement les promesses de soulagement de la misère humaine qu‘offrent les vaccins.
Recherches traductionnelles pour obtenir l’introduction rationnelle et efficace de nouveaux vaccins dans les pays en développement: l’expérience de l’International Vaccine Institute
Authors: Clemens John
Published: December 2008

L’introduction de nouveaux vaccins dans les pays à hauts revenus s’est effectuée à un rythme accéléré ces dernières années. Par comparaison, peu de vaccins de nouvelle génération ont été introduits dans les programmes de santé publique destinés aux populations pauvres des pays en développement et, pour ceux qui l’ont été, l’introduction a été malheureusement lente en raison des limitations des ressources financières. Cette lenteur a été cependant également due à une pénurie des données nécessaires pour la prise de décisions politiques rationnelles. Le soutien insuffisant pour la conduite d’études de phase I de vaccins candidats ciblant des maladies affectant des pays en développement est un obstacle bien connu. De plus, d’autres types de recherches traductionnelles sont nécessaires afin d’obtenir les données nécessaires pour cette politique. Des études ont montré que les performances de nombreux vaccins étaient inférieures dans les populations défavorisées des pays en développement par rapport à celles observées chez des personnes résidant dans des pays à plus hauts revenus. En conséquence, les essais de phases II et III représentent un second type essentiel de recherches traductionnelles nécessaires pour l’introduction de vaccins dans des pays en développement. De plus, même dans le cas de vaccins ayant obtenu une autorisation de mise sur le marché par l’intermédiaire d’essais cliniques dans des pays en développement, des doutes peuvent persister quant à savoir si la charge de la maladie justifie l’introduction du vaccin, et si l’administration du vaccin dans le cadre de programmes de santé publique sera économique, réalisable et acceptable sur le plan de la programmation et financièrement abordable. Un troisième type de recherches traductionnelles est nécessaire afin de répondre à ces doutes résiduels. Depuis sa fondation en 1987, l’International Vaccine Institute, organisme international à but non lucratif de recherche et développement situé à Séoul, Corée, mène des recherches traductionnelles sur l’introduction de nouveaux vaccins contre diverses maladies dans 22 pays d’Asie, d’Afrique et d’Amérique latine. Dans le présent article, nous décrivons des projets de recherches traductionnelles entrepris par l’International Vaccine Institute et les leçons acquises quant aux stratégies d’augmentation de l’impact des recherches de ce type sur la politique vaccinale pour les pays en développement.