bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Herpes Simplex Virus-1 on Nitric Oxide Synthase in the Rat Brain: The Role of Glucocorticoids
Authors: Hasson Joseph , Weidenfeld Joseph , Mizrachi-Kol Rachel , Ben-Hur Tamir , Ovadia Haim
Published: November 2010

Objective: Herpes simplex virus-1 (HSV-1) is a common cause of viral encephalitis manifested by activation of the adrenocortical axis, fever and behavioral changes. We investigated the early effects of HSV-1 on constitutive (c) and inducible (i) nitric oxide synthase (NOS) activity in rat brain and in mixed glial cell culture. The effect of glucocorticoids (GCs) on NOS responses to HSV-1 was also determined. Methods: NOS activity was evaluated by the conversion of 3H-arginine to 3H-citrulline. Nitrites were measured in supernatants of activated glial cells. Results: Under basal conditions, the highest cNOS activity was found in the cerebellum, while activity was much lower in the pons and negligible in the hypothalamus and hippocampus. Forty-eight hours after intracerebral injection of HSV-1, serum corticosterone was increased and NOS activity in the cerebellum and pons was inhibited. Adrenalectomy had no effect on the basal NOS activity but completely abrogated the inhibitory effect of HSV-1. Administration of the iNOS inhibitor aminoguanidine did not significantly change NOS activity, suggesting that the activity found in the cerebellum and pons can be attributed to the cNOS isoform. In mixed glial cell culture infected with HSV-1 and then activated with lipopolysaccharide, NOS activity and nitrite production were inhibited by 77 and 53%, respectively. Conclusions: These results suggest that brain NOS activity is inhibited in the early stages of HSV-1 infection and requires the presence of circulating GCs. HSV-1-induced brain NOS inhibition may play a role in neuronal viral invasion and in the activation of the adrenocortical axis.
Genome-Wide Linkage Scan of Bipolar Disorder in a Colombian Population Isolate Replicates Loci on Chromosomes 7p21–22, 1p31, 16p12 and 21q21–22 and Identifies a Novel Locus on Chromosome 12q
Authors: Kremeyer B. , García J. , Müller H. , Burley M.W. , Herzberg I. , Parra M.V. , Duque C. , Vega J. , Montoya P. , López M.C. , Bedoya G. , Reus V. , Palacio C. , López C. , Ospina-Duque J. , Freimer N.B. , Ruiz-Linares A.
Published: November 2010

Background/Aims: Bipolar disorder (BP) is a severe psychiatric illness, characterised by alternating episodes of depression and mania, which ranks among the top ten causes of morbidity and life-long disability world-wide. We have previously performed a whole-genome linkage scan on 6 pedigrees segregating severe BP from the well-characterised population isolate of Antioquia, Colombia. We recently collected genotypes for the same set of 382 autosomal microsatellite markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of the combined pedigree set. Methods: Linkage analysis using both parametric and nonparametric approaches was conducted for 3 different diagnostic models: severe BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis (operationally defined by the occurrence of at least 1 episode of hallucinations and/or delusions). Results and Conclusion: For BPI only, the most interesting result was obtained for chromosome 7p21.1–p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct–q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22–31 (mood disorders) and 21q21–22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24–31 and 16p12–q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP.
Incidence and Management of CoreValve Dislocation During Transcatheter Aortic Valve Implantation
Authors: Geisbüsch Sarah , Bleiziffer Sabine , Mazzitelli Domenico , Ruge Hendrik , Bauernschmitt Robert , Lange Rüdiger
Published: November 2010

Background—

Transcatheter aortic valve implantation is a highly specialized technique offering a new therapeutic option to patients at high risk for conventional surgery. Complications associated with this catheter procedure differ from complications after surgical aortic valve replacement. This is to report incidence, management, and impact on morbidity and mortality of CoreValve dislocation during catheter valve implantation.

Methods and Results—

Between June 2007 and September 2009, the self-expandable CoreValve prosthesis (Medtronic Inc, Minneapolis, Minn) was implanted in 212 patients through a transarterial (femoral or subclavian) access. Patients with severe aortic stenosis who were at high risk for conventional surgery were included. We observed dislocation of the prosthesis during CoreValve implantation in 21 patients. In 16 cases, the CoreValve could be implanted in the correct annular position after retrieving it and reloading the catheter. In 4 patients, the completely deployed prosthesis had to be placed in the ascending or abdominal aorta before implanting a second one. One patient underwent open surgery. Overall 30-day mortality was 11.0%, 21.5% in the dislocation group and 9.9% in patients without dislocation (
P
=0.024). Coronary ischemia, stroke, and renal failure occurred more frequently in patients with dislocation, whereas pacemaker dependency did not differ significantly between the groups.

Conclusions—

CoreValve dislocation during transcatheter aortic valve implantation occurred in 10% of the cases and significantly increases perioperative risk for severe complications or death. It requires individual specific management and can be managed either interventionally or, rarely, results in open surgery.
Reference and Accessibility from a Givenness Hierarchy Perspective
Authors: Gundel Jeanette
Published: November 2010

Most work on reference and discourse structure appeals, in some sense, to the notion of accessibility. While the term "accessibility" itself is rarely mentioned in research within Gundel, Hedberg and Zacharski's Givenness Hierarchy (GH) framework, the GH has often been interpreted by others as an accessibility hierarchy. This paper aims to clarify the major claims and predictions of the GH theory, showing how it is fundamentally diff erent from other referential hierarchies in a number of ways, most importantly because cognitive statuses on the hierarchy are assumed to encode manner of accessibility, not degree of accessibility. The GH thus differs from the other referential hierarchies, not only in the kinds of facts it aims to predict and explain, but in the specific empirical predictions that can plausibly be derived from it regarding degree of accessibility, as measured by ease of processing.
An Experimental Study on the Scope of (Un)modified Indefinites
Authors: Ionin Tania
Published: November 2010

This paper reports on three experiments which investigate the availability of long-distance scope for different types of indefinite expressions, in order to test the predictions of different semantic theories of indefinite scope. The main findings of the experiments are: (i) local, narrow-scope readings are preferred for a indefinites, whereas long-distance scope is preferred for a certain indefinites; and (ii) long-distance scope is more readily available to bare one indefinites than to modified at least/exactly one indefinites, but modified numeral indefinites nevertheless allow long-distance scope more readily than universal quantifiers. While the first finding is consistent with theories that link scope and epistemic specificity (since a certain indefinites are often analyzed as markers of specificity), the second finding suggests that long-distance scope is also available to non-specific, quantificational indefinites. It is shown that the findings are problematic for choice-function theories of indefinite scope, and are more consistent with long-distance scopeshifting, or with accounts that link scope and topicality.
State-Level Autonomy and Municipal Government Structure
Authors: Nelson Kimberly
Published: November 2010

A number of recent studies have argued that municipal governments have so significantly modified elements of their form of government that it is now difficult to distinguish form. However, none of these studies considers the influence of state government on these choices. This study uses a comprehensive data set of U.S. municipal governments with populations of at least 10,000 and a data set of state legislative provisions related to form of government to investigate the influence of state law on municipal form of government choices. The findings demonstrate that state law is associated with some choices of government form and that structures that hybridize the council-manager and mayor-council forms of government are still relatively uncommon.
Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia
Authors: Fiedler Katja , Sindrilaru Anca , Terszowski Grzegorz , Kokai Enikö , Feyerabend Thorsten B. , Bullinger Lars , Rodewald Hans-Reimer , Brunner Cornelia
Published: November 2010

Bruton tyrosine kinase (Btk) is essential for B cell development and function and also appears to be important for myeloid cells. The bone marrow of Btk-deficient mice shows enhanced granulopoiesis compared with that of wild-type mice. In purified granulocyte-monocyte-progenitors (GMP) from Btk-deficient mice, the development of granulocytes is favored at the expense of monocytes. However, Btk-deficient neutrophils are impaired in maturation and function. Using bone marrow chimeras, we show that this defect is cell-intrinsic to neutrophils. In GMP and neutrophils, Btk plays a role in GM-CSF– and Toll-like receptor–induced differentiation. Molecular analyses revealed that expression of the lineage-determining transcription factors C/EBPα, C/EBPβ, and PU.1, depends on Btk. In addition, expression of several granule proteins, including myeloperoxidase, neutrophilic granule protein, gelatinase and neutrophil elastase, is Btk-dependent. In the Arthus reaction, an acute inflammatory response, neutrophil migration into tissues, edema formation, and hemorrhage are significantly reduced in Btk-deficient animals. Together, our findings implicate Btk as an important regulator of neutrophilic granulocyte maturation and function in vivo.
Origin and evolution of a placental-specific microRNA family in the human genome
Authors: Yuan Zhidong , Sun Xiao , Jiang Dongke , Ding Yan , Lu Zhiyuan , Gong Lejun , Liu Hongde , Xie Jianming
Published: November 2010

Background

MicroRNAs (miRNAs) are a class of short regulatory RNAs encoded in the genome of DNA viruses, some single cell organisms, plants and animals. With the rapid development of technology, more and more miRNAs are being discovered. However, the origin and evolution of most miRNAs remain obscure. Here we report the origin and evolution dynamics of a human miRNA family.

Results

We have shown that all members of the miR-1302 family are derived from MER53 elements. Although the conservation scores of the MER53-derived pre-miRNA sequences are low, we have identified 36 potential paralogs of MER53-derived miR-1302 genes in the human genome and 58 potential orthologs of the human miR-1302 family in placental mammals. We suggest that in placental species, this miRNA family has evolved following the birth-and-death model of evolution. Three possible mechanisms that can mediate miRNA duplication in evolutionary history have been proposed: the transposition of the MER53 element, segmental duplications and Alu-mediated recombination. Finally, we have found that the target genes of miR-1302 are over-represented in transportation, localization, and system development processes and in the positive regulation of cellular processes. Many of them are predicted to function in binding and transcription regulation.

Conclusions

The members of miR-1302 family that are derived from MER53 elements are placental-specific miRNAs. They emerged at the early stage of the recent 180 million years since eutherian mammals diverged from marsupials. Under the birth-and-death model, the miR-1302 genes have experienced a complex expansion with some members evolving by segmental duplications and some by Alu-mediated recombination events.
SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in african-americans of the GENOA study
Authors: Meyers Kristin J , Chu Jian , Mosley Thomas H , Kardia Sharon LR
Published: November 2010

Background

Left ventricular mass (LVM) is a strong, independent predictor of heart disease incidence and mortality. LVM is a complex, quantitative trait with genetic and environmental risk factors. This research characterizes the genetic architecture of LVM in an African-American population by examining the main and interactive effects of individual candidate gene single nucleotide polymorphisms (SNPs) and conventional risk factors for increased LVM.

Methods

We used least-squares linear regression to investigate 1,878 SNPs from 234 candidate genes for SNP main effects, SNP-risk factor interactions, or SNP-SNP interactions associated with LVM in 1,328 African-Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We reduced the probability of false positive results by implementing three analytic criteria: 1) the false discovery rate, 2) cross-validation, and 3) testing for internal replication of results.

Results

We identified 409 SNP-SNP interactions passing all three criteria, while no SNP main effects or SNP-risk factor interactions passed all three. A multivariable model including four SNP-SNP interactions explained 11.3% of the variation in LVM in the full GENOA sample and 5.6% of LVM variation in independent test sets.

Conclusions

The results of this research underscore that context dependent effects, specifically SNP-SNP interactions, may dominate genetic contributions to variation in complex traits such as LVM.
Hospitalisation for rotavirus gastroenteritis in the paediatric population in the Veneto Region, Italy
Authors: Saia Mario , Giliberti Aurore , Callegaro Giampietro , Baldovin Tatjana , Busana Marta Cecilia , Pietrobon Francesco , Bertoncello Chiara , Baldo Vincenzo
Published: November 2010

Background

This study evaluates the epidemiological impact of RVGE hospitalisation in the Veneto Region during the period spanning from 2000-2007 along with the associated costs. The analysis was conducted in an area where rotavirus vaccination is not included into immunization programmes and is an attempt to assess the potential benefits of such introduction.

Methods

To update the estimates of acute RVGE hospitalisation rates in children ≤5 years in the Veneto Region, we conducted an 8 year retrospective observational population-based analysis (2000-2007).

Results

Over the study period, a total of 4,119 admissions for RVGE were reported, with a mean hospital stay of 3.5 days. The population-based hospitalisation RVGE incidence rate was 195.8 per 100,000 children aged ≤5 years (lower than other European countries).

Conclusions

RVGE is an important cause of paediatric hospitalisation in the Veneto Region. The data reaffirm the substantial burden of rotavirus hospitalisations in children and the potential health benefits of the vaccination as well as the possibility of adding rotavirus vaccination to the current schedule.
Identification of a stem-like cell population by exposing metastatic breast cancer cell lines to repetitive cycles of hypoxia and reoxygenation
Authors: Louie Elizabeth , Nik Sara , Chen Juei-suei , Schmidt Marlies , Song Bo , Pacson Christine , Chen Xiu Fang , Park Seonhye , Ju Jingfang , Chen Emily I
Published: November 2010

Introduction

The irregular vasculature of solid tumors creates hypoxic regions, which are characterized by cyclic periods of hypoxia and reoxygenation. Accumulated evidence suggests that chronic and repetitive exposure to hypoxia and reoxygenation seem to provide an advantage to tumor growth. Although the development of hypoxia tolerance in tumors predicts poor prognosis, mechanisms contributing to hypoxia tolerance remain to be elucidated. Recent studies have described a subpopulation of cancer stem cells (CSC) within tumors, which have stem-like properties such as self-renewal and the ability to differentiate into multiple cell types. The cancer stem cell theory suggests CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Since hypoxia is considered to be one of the critical niche factors to promote invasive growth of tumors, we hypothesize that repetitive cycles of hypoxia/reoxygenation also play a role in the enrichment of breast CSCs.

Methods

Two metastatic human breast cancer cell lines (MDA-MB 231 and BCM2) were used to optimize the conditions of hypoxia and reoxygenation cycles. The percentage of CSCs in the cycling hypoxia selected subpopulation was analyzed based on the CD44, CD24, ESA, and E-cadherin expression by three-color flow cytometry. Colony formation assays were used to assess the ability of this subpopulation to self-renew. Limiting dilution assays were performed to evaluate the tumor-initiating and metastatic ability of this subpopulation. Induction of EMT was examined by the expression of EMT-associated markers and EMT-associated microRNAs.

Results

Using an optimized hypoxia and reoxygenation regimen, we identified a novel cycling hypoxia-selected subpopulation from human breast cancer cell lines and demonstrated that a stem-like breast cancer cell subpopulation could be expanded through repetitive hypoxia/reoxygenation cycles without genetic manipulation. We also found that cells derived from this novel subpopulation form colonies readily, are highly tumorigenic in immune-deficient mice, and exhibit both stem-like and EMT phenotypes.

Conclusions

These results provide the validity to the newly developed hypoxia/reoxygenation culture system for examining the regulation of CSCs in breast cancer cell lines by niche factors in the tumor microenvironment and developing differential targeting strategies to eradicate breast CSCs.
Shifts in subjectivity during the therapy for psychosis
Authors: Karatza Harikleia , Avdi Evrinomy
Published: November 2010

Objectives. This paper examines the process of therapy with families in which a member has a diagnosis of psychosis. On a methodological level, the study aims to demonstrate the usefulness of discourse analysis as a method for analysing texts produced in therapy in the context of process research. On a clinical and theoretical level, it aims to contribute to the literature that approaches psychosis and its treatment from the viewpoint of narrative and discourse.

Design. Several contemporary conceptualizations emphasize the role of discursive processes, such as a collapse of meaning and narrative and an alienation from shared communicative practices, in psychosis. Drawing from this perspective, discourse analysis was used on family therapy session transcripts to empirically examine these processes. Moreover, given that in different conceptualizations psychosis is seen to entail a profound disturbance to the person's sense of self, the analysis focuses more specifically on the identified patients' subjectivity.

Methods. Seven sessions were analysed, drawn from the beginning, middle, and end phases of two therapies with families with a member with a diagnosis of psychosis. Discourse analysis was used and the analysis focused on the transformation of meaning and more specifically on shifts in the subject positions occupied by the identified patient in the clinical dialogue.

Results. With regards to the identified patients' subjectivity, the analysis suggests that (a) psychosis was associated with the ‘patient’ being rigidly positioned exclusively through the psychiatric discourse in the first case and the lack of a voice in the second, and (b) that therapeutic change was associated with increased flexibility in the subject positions that the identified patient occupied in the first case and with the emergence of a personal and reflective voice in the second.

Conclusions. The findings in this study suggest that an important aspect in clinical work with families with a member with a diagnosis of psychosis relates to de‐centring the dominant, pathology maintaining accounts and to the emergence of a wider range of less problematic explanatory frames.
Synthetic biodegradable elastomers for drug delivery and tissue engineering
Authors: Bettinger Christopher J.
Published: November 2010

Synthetic biodegradable elastomers are an emerging class of materials with many potential clinical applications including drug delivery and tissue engineering. Biodegradable elastomers offer advantages of structure diversity, tunable properties, and a wide range of processing capabilities. This review highlights some recent developments in various aspects of biodegradable materials synthesis, characterization, and processing with a specific focus on structure-processing–property relationships. Biodegradation mechanisms and issues regarding tissue biocompatibility of these materials are discussed. Applications of synthetic biodegradable elastomers, including use as a materials platform for controlled release systems, tissue engineering scaffolds, and engineered substrates for in vitro cell–biomaterials interactions will also be presented.
Valentim Fernandes' Five Maps and the Early History and Geography of São Tomé
Authors: Massing Andreas
Published: November 2010

Maps may be important historical documents, reflecting the situation of a given place at a given time, and comparing several maps from different periods of the same area can inform us of changes in social and human geography. For some distant parts of the world they may be the only sources for a past that provides us with few if any sources. Thus Valentim Fernandes' five maps of São Tomé are a unique source for the slow and gradual growth of the first settlements. The maps are complemented by Fernandes' 1506 description of the island.

Valentim Fernandes, a German printer who worked in Lisbon from 1495 to 1513, compiled several works on Africa and published them in 1506. Apparently he sent a copy to his friend Conrad Peutinger in Augsburg, whose book collection came into possession of the Bayerische Staatsbibliothek, where they survive in the Codex Hispanicus 27 (now available online. The compilation contains several texts and a map collection with description of the Atlantic islands. While Fernandes' description of Africa, as the sole copy of Diogo Gomes' account, has received wide attention as an important source for early African history, the five maps of São Tomé inserted at various places in the Codex have hardly received any attention at all.
Early Life Stress Enhances Behavioral Vulnerability to Stress through the Activation of REST4-Mediated Gene Transcription in the Medial Prefrontal Cortex of Rodents
Authors: Uchida Shusaku , Hara Kumiko , Kobayashi Ayumi , Funato Hiromasa , Hobara Teruyuki , Otsuki Koji , Yamagata Hirotaka , McEwen Bruce S. , Watanabe Yoshifumi
Published: November 2010

There is growing evidence suggesting that early life events have long-term effects on the neuroendocrine and behavioral developments of rodents. However, little is known about the involvement of early life events in the susceptibility to subsequent stress exposure during adulthood. The present study characterized the effect of maternal separation, an animal model of early life adversity, on the behavioral response to repeated restraint stress in adult rats and investigated the molecular mechanism underlying behavioral vulnerability to chronic stress induced by the maternal separation. Rat pups were separated from the dams for 180 min per day from postnatal day 2 through 14 (HMS180 rats). We found that, as young adults, HMS180 rats showed a greater hypothalamic-pituitary-adrenal axis response to acute restraint stress than nonseparated control rats. In addition, repeatedly restrained HMS180 rats showed increased depression-like behavior and an anhedonic response compared with nonrestrained HMS180 rats. Furthermore, HMS180 rats showed increased expression of REST4, a neuron-specific splicing variant of the transcriptional repressor REST (repressor element-1 silencing transcription factor), and a variety of REST target gene mRNAs and microRNAs in the medial prefrontal cortex (mPFC). Finally, REST4 overexpression in the mPFC of neonatal mice via polyethyleneimine-mediated gene transfer enhanced the expression of its target genes as well as behavioral vulnerability to repeated restraint stress. In contrast, REST4 overexpression in the mPFC of adult mice did not affect depression-like behaviors after repeated stress exposure. These results suggest that the activation of REST4-mediated gene regulation in the mPFC during postnatal development is involved in stress vulnerability.
Cortical GABAergic Interneurons Transiently Assume a Sea Urchin-Like Nonpolarized Shape before Axon Initiation
Authors: Yamasaki Emi , Tanaka Daisuke H. , Yanagawa Yuchio , Murakami Fujio
Published: November 2010

Mature neurons polarize by extending an axon and dendrites.In vitrostudies of dissociated neurons have demonstrated that axons are initiated from a nonpolarized stage. Dissociated hippocampal neurons form four to five minor neurites shortly after plating but then one of them starts to elongate rapidly to become the future axon, whereas the rest constitutes the dendrites at later stages. However, neuroepithelial cells as well as migrating neuronsin vivoare already polarized, raising the possibility that mature neurons inherit the polarities of immature neurons of neuroepithelial or migrating neurons. Here we show that the axon of interneurons in mouse cortical explant emerges from a morphologically nonpolarized shape. The morphological maturation of cortical interneurons labeled by electroporation at an embryonic stage was analyzed by time-lapse imaging during the perinatal stage. In contrast to earlier stages, most interneurons at this stage show sea urchin-like nonpolarized shapes with alternately extending and retracting short processes. Abruptly, one of these processes extends to give rise to an outstandingly long axon-like process. Given that the interneurons exhibit typical polarized shapes during embryonic development, the present results suggest that axon–dendrite polarity develops from a nonpolarized intermediate stage.
The Influence of Language on Perception: Listening to Sentences about Faces Affects the Perception of Faces
Authors: Landau Ayelet N. , Aziz-Zadeh Lisa , Ivry Richard B.
Published: November 2010

We examined the effect of linguistic comprehension on early perceptual encoding in a series of electrophysiological and behavioral studies on humans. Using the fact that pictures of faces elicit a robust and reliable evoked response that peaks at ∼170 ms after stimulus onset (N170), we measured the N170 to faces that were preceded by primes that referred to either faces or scenes. When the primes were auditory sentences, the magnitude of the N170 was larger when the face stimuli were preceded by sentences describing faces compared to sentences describing scenes. In contrast, when the primes were visual, the N170 was smaller after visual primes of faces compared to visual primes of scenes. Similar opposing effects of linguistic and visual primes were also observed in a reaction time experiment in which participants judged the gender of faces. These results provide novel evidence of the influence of language on early perceptual processes and suggest a surprising mechanistic description of this interaction: linguistic primes produce content-specific interference on subsequent visual processing. This interference may be a consequence of the natural statistics of language and vision given that linguistic content is generally uncorrelated with the contents of perception.
TRPA1 Contributes to Cold Hypersensitivity
Authors: del Camino Donato , Murphy Sarah , Heiry Melissa , Barrett Lee B. , Earley Taryn J. , Cook Colby A. , Petrus Matt J. , Zhao Michael , D'Amours Marc , Deering Nate , Brenner Gary J. , Costigan Michael , Hayward Neil J. , Chong Jayhong A. , Fanger Christopher M. , Woolf Clifford J. , Patapoutian Ardem , Moran Magdalene M.
Published: November 2010

TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but notTrpa1−/−mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.
Assessing Neuronal MetabolismIn Vivoby Modeling Imaging Measures
Authors: Ciccarelli Olga , Toosy Ahmed T. , De Stefano Nicola , Wheeler-Kingshott Claudia A.M. , Miller David H. , Thompson Alan J.
Published: November 2010

Mitochondrial dysfunction contributes to the pathogenesis of many neurological diseases, including multiple sclerosis (MS), but is not directly measurablein vivo. We modeledN-acetyl-aspartate (NAA), which reflects axonal structural integrity and mitochondrial metabolism, with imaging measures of axonal structural integrity (axial diffusivity and cord cross-sectional area) to extract its mitochondrial metabolic contribution. Lower residual variance in NAA, reflecting reduced mitochondrial metabolism, was associated with greater clinical disability in MS, independent of structural damage.
Activation of Microglia Depends on Na+/H+Exchange-Mediated H+Homeostasis
Authors: Liu Yan , Kintner Douglas B. , Chanana Vishal , Algharabli Jehad , Chen Xinzhi , Gao Yanqin , Chen Jun , Ferrazzano Peter , Olson Julie K. , Sun Dandan
Published: November 2010

H+extrusion is important for sustained NADPH oxidase activation after “respiratory” burst in macrophage/microglia activation. In this study, we investigated the role of Na+/H+exchanger isoform 1 (NHE-1) in activation of microglia after lipopolysaccharide (LPS) or oxygen and glucose deprivation and reoxygenation (OGD/REOX) exposure. NHE-1 functioned in maintaining basal pHiof immortalized M4T.4 microglia or mouse primary microglia. Pharmacological inhibition of NHE-1 activity with the potent inhibitor cariporide [HOE 642 (4-isopropyl-3-methylsulfonyl-benzoyl-guanidine-methanesulfonate)] abolished pHiregulation in microglia under basal conditions. Activation of microglia either by LPS, phorbol myristate acetate, or OGD/REOX accelerated pHiregulation and caused pHielevation, which was accompanied with an increase in [Na+]iand [Ca2+]ias well as production of superoxide anion and cytokines. Interestingly, inhibition of NHE-1 not only abolished pHiregulation but also reduced production of superoxide anion as well as expression of cytokines and inducible nitric oxide synthase. Together, these results reveal that there was a concurrent activation of NHE-1 in microglia in response to proinflammatory stimuli. The study suggests that NHE-1 functions to maintain microglial pHihomeostasis allowing for sustained NADPH oxidase function and “respiratory” burst.
Erasing Fear Memories with Extinction Training: Figure 1.
Authors: Quirk Gregory J. , Paré Denis , Richardson Rick , Herry Cyril , Monfils Marie H. , Schiller Daniela , Vicentic Aleksandra
Published: November 2010

Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new developments, which involve the timing of extinction training. Extinction-induced erasure of fear occurs in very young rats, but is lost with the development of perineuronal nets in the amygdala that render fear memories impervious to extinction. Moreover, extinction administered during the reconsolidation phase, when fear memory is destabilized, updates the fear association as safe, thereby preventing the return of fear, in both rats and humans. The use of modified extinction protocols to eliminate fear memories complements existing pharmacological strategies for strengthening extinction.
Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis
Authors: Pimplikar Sanjay W. , Nixon Ralph A. , Robakis Nikolaos K. , Shen Jie , Tsai Li-Huei
Published: November 2010

Despite the progress of the past two decades, the cause of Alzheimer's disease (AD) and effective treatments against it remain elusive. The hypothesis that amyloid-β (Aβ) peptides are the primary causative agents of AD retains significant support among researchers. Nonetheless, a growing body of evidence shows that Aβ peptides are unlikely to be the sole factor in AD etiology. Evidence that Aβ/amyloid-independent factors, including the actions of AD-related genes, also contribute significantly to AD pathogenesis was presented in a symposium at the 2010 Annual Meeting of the Society for Neuroscience. Here we summarize the studies showing how amyloid-independent mechanisms cause defective endo-lysosomal trafficking, altered intracellular signaling cascades, or impaired neurotransmitter release and contribute to synaptic dysfunction and/or neurodegeneration, leading to dementia in AD. A view of AD pathogenesis that encompasses both the amyloid-dependent and -independent mechanisms will help fill the gaps in our knowledge and reconcile the findings that cannot be explained solely by the amyloid hypothesis.
Removing Brakes on Adult Brain Plasticity: From Molecular to Behavioral Interventions
Authors: Bavelier Daphne , Levi Dennis M. , Li Roger W. , Dan Yang , Hensch Takao K.
Published: November 2010

Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.
Osteosclerosis in two brothers with autosomal dominant pseudohypoparathyroidism type 1b: bone histomorphometric analysis
Authors: Sbrocchi Anne Marie , Rauch Frank , Lawson Margaret L , Hadjiyannakis Stasia , Lawrence Sarah , Bastepe Murat , Jüppner Harald , Ward Leanne Marie
Published: November 2010

Objective

Pseudohypoparathyroidism (PHP) is a heterogeneous disorder characterized by hypocalcemia and hyperphosphatemia resulting from selective renal resistance to parathyroid hormone (PTH). One autosomal dominant form of PHP type 1b (PHP-Ib) is most frequently caused by a maternally inherited 3-kb deletion within STX16, the gene encoding syntaxin 16. To date, increased bone mineral density (BMD) has been described only in PHP type 1a, and there is a lack of detailed information on bone histomorphometry in PHP-Ib. The objective of this report was to present trans-iliac static and dynamic histomorphometry in two brothers with the 3-kb deletion in the STX16 region and elevated BMD.

Design

Observational study of two brothers (age 18.0 and 22.7 years) with the 3-kb STX16 deletion and increased BMD.

Results

The brothers had elevated PTH (146 pg/ml (15.6 pmol/l) and 102 pg/ml (10.9 pmol/l); normal: 10–64 pg/ml (1.1–6.8 pmol/l)) and striking osteosclerosis (lumbar spine areal BMD Z-scores: +5.4 and +4.9). Bone histomorphometry showed marked elevations in cortical width for both brothers (241 and 209% of the mean result expected for age), with elevations in the bone formation rate on the endocortical (119 and 260% of the healthy mean) and trabecular (220 and 190% of mean) surfaces.

Conclusion

Our findings suggest that PTH in this PHP-Ib genotype can increase cortical thickness due to its anabolic effect on endocortical bone, and underscore the heterogeneity in the skeletal phenotype among patients with PHP-Ib.
A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development
Authors: Kawai Yasuhiro , Noguchi Junko , Akiyama Kouyou , Takeno Yuriko , Fujiwara Yasuhiro , Kajita Shimpei , Tsuji Takehito , Kikuchi Kazuhiro , Kaneko Hiroyuki , Kunieda Tetsuo
Published: November 2010

Development of the male gonads is a complex process with interaction of various cells in the gonads including germ, Sertoli, Leydig, and myoid cells. TF is a mutant rat strain showing male pseudohermaphroditism, with agenesis of Leydig cells and androgen deficiency controlled by an autosomal single recessive gene (mp). Themplocus was mapped on the distal region of rat chromosome 7 by linkage analysis, but the gene responsible for thempmutation has not been identified. In this study, we performed fine linkage mapping and sequence analysis to determine the causative gene of thempmutation, and performed an immunohistochemical study using a Leydig cell-specific marker to investigate detailed phenotypes of the mutant rats during the testicular development. As a result, we found a missense mutation of the gene encoding Desert hedgehog (Dhh) in the mutant rat, which could result in loss of function of the DHH signaling pathway. Histochemical examination revealed remarkably reduced number of fetal Leydig cells and lack of typical spindle-shaped adult Leydig cell in themp/mprats. These phenotypes resembled those of theDhh-null mice. Additionally, testosterone levels were significantly lower in themp/mpfetus, indicating androgen deficiency during embryonic development. These results indicate that the mutation of theDhhgene may be responsible for the pseudohermaphrodite phenotypes of the mutant rat, and that theDhhgene is probably essential for the development of Leydig cells.
Development of an Evidence‐based Guideline for Supervisor Training in Promoting Mental Health: Literature Review
Authors: Tsutsumi Akizumi
Published: November 2010

Development of an Evidence‐based Guideline for Supervisor Training in Promoting Mental Health: Literature Review: Akizumi Tsutsumi, Occupational Health Training Center, University of Occupational and Environmental Health—

Objective

To review published studies to assess the effects of supervisor training on the mental health of subordinate workers, and thereby develop an evidence‐based guideline for supervisor training in promoting workers' mental health.

Method

Seven studies that assessed the effect of supervisor training, whose outcomes included psychological stress responses of (subordinate) employees, were retrieved for assessment from PubMed, the Cochrane Library, MEDLINE, the Web of Science, and Ichushi‐Web. An additional ive studies were also reviewed for discussion on the content and types of training.

Results

Providing supervisors with necessary skills and information on mental health, including relevant occupational stressors, has a favorable effect on workers' mental health, at least in the short term. The subject populations had a background of requiring mental health measures. The effect of the training varied depending on the participation rate of supervisors, suggesting that the overall effect on an organization may be limited without a certain extent of participation by supervisors. There is no evidence of a long‐term (over 1 yr) effect of supervisor training, and the effect of education on the supervisors' knowledge and behavior tends to be lost after 6 mo.

Conclusion

The current evidence indicates that the following items should be taken into consideration for the development of a guideline for supervisor training: identification of high‐priority populations requiring education, development of a strategy to improve the participation rate in education, inclusion of occupational stressors as well as basic information in workplace mental health teaching materials, and regular repetition of the program.
New Strategies for Acute Liver Failure: Focus on Xenotransplantation Therapy
Authors: Alves Luiz Anastácio , Bonavita André , Quaresma Kátia , Torres Elenilde , Pacheco Paulo Anastácio Furtado , Cotta-De-Almeida Vinícius , Saraiva Roberto Magalhães
Published: November 2010

Acute liver failure (ALF) has a poor prognosis and, despite intensive care support, reported average survival is only 10–40%. The most common causes responsible for ALF are viral hepatitis (mainly hepatitis A and B) and acetaminophen poisoning. Hepatic transplantation is the only appropriate treatment for patients with unlikely survival with supportive care alone. Survival rates after transplantation can be as high as 80–90% at the end of the first year. However, there is a shortage of donors and is not uncommon that no appropriate donor matches with the patient in time to avoid death. Therefore, new technologies are in constant development, including blood purification therapies as plasmapheresis, hemodiafiltration, and bioartificial liver support. However, they are still of limited efficacy or at an experimental level, and new strategies are welcome. Accordingly, cell transplantation has been developed to serve as a possible bridge to spontaneous recovery or liver transplantation. Xenotransplant of adult hepatocytes offers an interesting alternative. Moreover, the development of transgenic pigs with less immunogenic cells associated with new immunosuppressor strategies has allowed the development of this area. This article reviews some of the newly developed techniques, with focus on xenotransplant of adult hepatocytes, which might have clinical benefits as future treatment for ALF.
Concurrent observations of atomic iodine, molecular iodine and ultrafine particles in a coastal environment
Authors: Mahajan A. S. , Sorribas M. , Gómez Martín J. C. , MacDonald S. M. , Gil M. , Plane J. M. C. , Saiz-Lopez A.
Published: November 2010

Abstract. Simultaneous measurements of atomic iodine (I), molecular iodine (I2) and ultrafine particles were made at O Grove, Galicia (42.50° N, 8.87° W), on the northwest coast of Spain. The observations show a strong tidal signature, and indicate that the most probable sources of reactive iodine species are the exposed macroalgae during low tide. For the first time, I2 and I were concurrently measured revealing a high average I2/I ratio of ~32, which is higher than previously inferred by modelling studies. A 1-dimensional photochemical model is employed to simulate the observations showing that the high I2/I ratio can be reproduced in the presence of fast vertical mixing close to the surface, or using an extra chemical loss for I atoms with an unknown species. There is a lack of strong correlation between the I2/I and ultrafine particles, indicating that although they both have macroalgal sources, these were not at the same location. The model simulations also suggest that the source of the observed ultrafine particles is likely not very close to the measurement site, in order for the particles to form and grow, but the source for I and I2 must be local. Finally, the effect of NOx levels on iodine oxides, and the conditions under which iodine particle bursts will be suppressed, are explored.
A comparison of OEM CO retrievals from the IASI and MOPITT instruments
Authors: Illingworth S. M. , Remedios J. J. , Boesch H. , Ho S.-P. , Edwards D. P. , Palmer P. I. , Gonzi S.
Published: November 2010

Abstract. Observations of atmospheric CO can only be made on global and regional scales by remote sensing instruments situated in space. One such instrument is the Infrared Atmospheric Sounding Interferometer (IASI), producing spectrally resolved, top-of-atmosphere radiance measurements from which CO vertical layers and total columns can be retrieved. This paper presents the first intercomparison between an IASI CO data set, in this case that produced by the University of Leicester IASI Retrieval Scheme (ULIRS), and the V3 and V4 operationally retrieved CO products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument. The comparison is performed for a localised region of Africa. By comparing both the standard data and a special version of MOPITT data retrieved using the ULIRS a priori for CO, it is shown that standard intercomparisons of CO are strongly affected by the differing a priori data of the retrievals, and by the differing sensitivities of the two instruments. In particular, the differing a priori profiles for MOPITT V3 and V4 data result in systematic retrieved profile changes as expected. Application of averaging kernels is used to derive a difference quantity which is much less affected by smoothing error and hence more sensitive to systematic error. This technique is used to show that the systematic bias between MOPITT V4 and ULIRS IASI data, at MOPITT vertical resolution, is less than 7%. These conclusions are confirmed by simulations with model profiles for the same region.
Hydrological real-time modeling using remote sensing data
Authors: Meier P. , Frömelt A. , Kinzelbach W.
Published: November 2010

Abstract. Reliable real-time forecasts of the discharge can provide valuable information for the management of a river basin system. Sequential data assimilation using the Ensemble Kalman Filter provides a both efficient and robust tool for a real-time modeling framework. One key parameter in a hydrological system is the soil moisture which recently can be characterized by satellite based measurements. A forecasting framework for the prediction of discharges is developed and applied to three different sub-basins of the Zambezi River Basin. The model is solely based on remote sensing data providing soil moisture and rainfall estimates. The soil moisture product used is based on the back-scattering intensity of a radar signal measured by the radar scatterometer on board the ERS satellite. These soil moisture data correlate well with the measured discharge of the corresponding watershed if the data are shifted by a time lag which is dependent on the size and the dominant runoff process in the catchment. This time lag is the basis for the applicability of the soil moisture data for hydrological forecasts. The conceptual model developed is based on two storage compartments. The processes modeled include evaporation losses, infiltration and percolation. The application of this model in a real-time modeling framework yields good results in watersheds where the soil storage is an important factor. For the largest watershed a forecast over almost six weeks can be provided. However, the quality of the forecast increases significantly with decreasing prediction time. In watersheds with little soil storage and a quick response to rainfall events the performance is relatively poor.