bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut-Derived Lipopolysaccharide Promotes T-Cell–Mediated Hepatitis in Mice through Toll-Like Receptor 4
Authors: Lin Yan , Yu Le-Xing , Yan He-Xin , Yang Wen , Tang Liang , Zhang Hui-Lu , Liu Qiong , Zou Shan-Shan , He Ya-Qin , Wang Chao , Wu Meng-Chao , Wang Hong-Yang
Published: May 2012

Robust clinical and epidemiologic data support the role of inflammation as a key player in hepatocellular carcinoma (HCC) development. Our previous data showed that gut-derived lipopolysaccharide (LPS) promote HCC development by activating Toll-like receptor 4 (TLR4) expressed on myeloid-derived cells. However, the effects of gut-derived LPS on other types of liver injury models are yet to be studied. The purpose of this study was to determine the importance of gut-derived LPS and TLR4 signaling in a T-cell–mediated hepatitis—Con A–induced hepatitis model, which mimic the viral hepatitis. Reduction of endotoxin using antibiotics regimen or genetic ablation of TLR4 in mice significantly alleviate Con A–induced liver injury by inhibiting the infiltration of T lymphocytes into the liver and the activation of CD4+ T lymphocytes as well as the production of T helper 1 cytokines; in contrast, exogenous LPS can promote Con A–induced hepatitis and CD4+ T cells activation in vivo and in vitro. Reconstitution of TLR4–expressing myeloid cells in TLR4-deficient mice restored Con A–induced liver injury and inflammation, indicating the major cell target of LPS. In addition, TLR4 may positively regulate the target hepatocellular apoptosis via the perforin/granzyme B pathway. These data suggest that gut-derived LPS and TLR4 play important positive roles in Con A–induced hepatitis and modulation of the gut microbiotia may represent a new avenue for therapeutic intervention to treat acute hepatitis induced by hepatitis virus infection, thus to prevent hepatocellular carcinoma. Cancer Prev Res; 5(9); 1090–102. ©2012 AACR.
Ideal Cardiovascular Health Predicts Lower Risks of Myocardial Infarction, Stroke, and Vascular Death Across Whites, Blacks, and Hispanics
Authors: Dong Chuanhui , Rundek Tatjana , Wright Clinton B. , Anwar Zane , Elkind Mitchell S.V. , Sacco Ralph L.
Published: May 2012

Background—

Evidence of the relationship of cardiovascular health (CVH), defined by the American Heart Association, and specific cardiovascular outcomes is lacking, particularly among Hispanics. This study sought to evaluate the relationship between the number of ideal CVH metrics and cardiovascular risk, overall and by event subtype, in a multiethnic community-based prospective cohort.

Methods and Results—

A total of 2981 subjects (mean age, 69±10 years; 54% Caribbean Hispanic, 25% black, 21% white) free of myocardial infarction and stroke at baseline in the Northern Manhattan Study were prospectively followed up (median follow-up, 11 years). The relationship between the number of ideal CVH metrics and the risk of cardiovascular disease, including myocardial infarction, stroke, and vascular death, was investigated. Overall, a strong gradient relationship was observed between the adjusted hazard ratios for cardiovascular disease and the number of ideal CVH metrics: 0.73 (95% confidence interval, 0.60–0.89), 0.61 (95% confidence interval, 0.50–0.76), 0.49 (95% confidence interval, 0.38–0.63), and 0.41 (95% confidence interval, 0.26–0.63) for those having 2, 3, 4, and 5 to 6 ideal CVH metrics, respectively, compared with those having 0 to 1 ideal CVH metrics (
P
for trend <0.0001). Similar graded relationships were found between the number of ideal CVH metrics and the adjusted incidence rate for each specific outcome and among whites, blacks, and Caribbean Hispanics.

Conclusions—

Our findings demonstrated a steep gradient relationship between ideal CVH and individual cardiovascular disease end points, including stroke, that was similar for whites, blacks, and Caribbean Hispanics. This evidence supports the application of the AHA ideal cardiovascular health metrics for cardiovascular disease risk assessment and health promotion for all Americans regardless of race-ethnic background.
Both the Middle Temporal Gyrus and the Ventral Anterior Temporal Area Are Crucial for Multimodal Semantic Processing: Distortion-corrected fMRI Evidence for a Double Gradient of Information Convergence in the Temporal Lobes
Authors: Visser Maya , Jefferies Elizabeth , Embleton Karl V. , Lambon Ralph Matthew A.
Published: May 2012

Most contemporary theories of semantic memory assume that concepts are formed from the distillation of information arising in distinct sensory and verbal modalities. The neural basis of this distillation or convergence of information was the focus of this study. Specifically, we explored two commonly posed hypotheses: (a) that the human middle temporal gyrus (MTG) provides a crucial semantic interface given the fact that it interposes auditory and visual processing streams and (b) that the anterior temporal region—especially its ventral surface (vATL)—provides a critical region for the multimodal integration of information. By utilizing distortion-corrected fMRI and an established semantic association assessment (commonly used in neuropsychological investigations), we compared the activation patterns observed for both the verbal and nonverbal versions of the same task. The results are consistent with the two hypotheses simultaneously: Both MTG and vATL are activated in common for word and picture semantic processing. Additional planned, ROI analyses show that this result follows from two principal axes of convergence in the temporal lobe: both lateral (toward MTG) and longitudinal (toward the anterior temporal lobe).
Changes in state-society relations from the First World War to the National Independence Struggle (1914-1923)
Authors: Polat Gülsüm
Published: May 2012

This article compares and contrasts state-society relations during wartime, first under the Ottoman government during the First World War and, secondly, under the Ankara government during the National War of Liberation, and concludes that while the Ottoman government did attempt to address the great hardships faced by the population in this period, the Ankara government placed more emphasis both on the importance of the people, the halk, and on the development of a social state.
The Role of Oceanic Feedback in the Climate Response to Doubling CO2
Authors: Lu Jian , Zhao Bin
Published: May 2012

Two suites of partial coupling experiments are devised with the upper-ocean dynamics version (UOM) of the CCSM3 to isolate the effects of the feedbacks from the change of the wind-driven ocean circulation and air–sea heat flux in the global climate response to the forcing of doubling CO2. The partial coupling is achieved by implementing a so-called overriding technique, which helps quantitatively partition the total response in the fully coupled model to the feedback component in question and the response to external forcing in the absence of the former. By overriding the wind stress seen by the ocean and the wind speed through the bulk formula for evaporation, the experiments help to reveal that (i) the wind–evaporation–SST (WES) feedback is the main formation mechanism for the tropical SST pattern under the CO2 forcing, verifying the hypothesis proposed by Xie et al.; (ii) the weakened tropical Pacific wind is shown in this UOM model not to be the cause for the enhanced equatorial Pacific warming, as one might expect from the thermocline and Bjerknes feedbacks; (iii) WES is also the leading mechanism for shaping the tropical precipitation response in the ocean; and (iv) both the wind-driven ocean dynamical feedback and the WES feedback act to increase the persistence of the southern annular mode (SAM) and the increased time scale of the SAM due to these feedbacks manifests itself in the response of the jet shift to an identical CO2 forcing, in a manner conforming to the fluctuation–dissipation theorem.
Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from five European countries
Authors: Karampampa Korinna , Gustavsson Anders , Miltenburger Carolin , Eckert Benjamin
Published: May 2012

Background: Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The TRIBUNE study provides a detailed exploration of costs in relation to relapses and disease severity, and assesses the quality of life impact on MS patients in terms of utilities, fatigue and activities of daily living (ADL).

Methods: Patients in five European countries (France, Germany, Italy, Spain and the United Kingdom) completed a self-administered web-based questionnaire capturing information on demographics, disease characteristics and severity (EDSS), co-morbidities, relapses, resource consumption, utilities, fatigue, and activities of daily living.

Results: In total, 1261 MS patients completed the questionnaire. More than half of the patients (68%) had the relapsing–remitting form of the disease; 87% of the sample reported receiving MS treatments. Costs were higher with advancing disease severity; for mild patients (EDSS score ≤ 3) the costs ranged between €13,534 and €22,461 across countries; for moderate (EDSS score 4 – 6.5) between €28,524 and €43,948; for severe (EDSS ≥ 7) between €39,592 and €65,395. Relapses were also associated with increasing costs; the difference in the cost per patient per year for relapsing–remitting patients with EDSS score ≤ 5 that did experience at least one relapse during the past 12 months and those who did not ranged between €3321 and €9430. The quality of life of patients decreased with disease progression and existence of relapses.

Conclusion: The TRIBUNE study provides an important update on the economic burden of MS in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity, and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.
Raf-1, a Potential Therapeutic Target, Mediates Early Steps in Endometriosis Lesion Development by Endometrial Epithelial and Stromal Cells
Authors: De La Garza Elizabeth M. , Binkley Peter A. , Ganapathy Manonmani , Krishnegowda Naveen K. , Tekmal Rajeshwar R. , Schenken Robert S. , Kirma Nameer B.
Published: May 2012

Endometriosis is a hormone-sensitive gynecological disorder characterized by the benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic lesions composed of endometrial stromal cells (ESC) and glandular epithelial cells (EEC) are thought to arise from menstrual endometrial tissue reaching the pelvic cavity via retrograde menstruation. The cause of endometriotic lesion formation is still not clear. Recent evidence suggest that cytokines may play a role in the early development of endometriosis lesions. Because cytokines and growth factors signal via the v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase pathway, we have examined the role of Raf-1 in early steps of endometriosis lesion formation, specifically attachment of endometrial cells to peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated TGFβ-induced trans-mesothelial invasion by the established, low-invasive EEC line EM42. TGFβ treatment of EEC resulted in Raf-1 phosphorylation at S338 and phosphorylation of ERK, suggesting that TGFβ activates Raf-1 signaling in these cells. GW5074 had little effect on ESC proliferation but inhibited EEC growth significantly under reduced serum conditions. Antagonizing Raf-1 activity and expression via GW5074 and specific Raf-1 small interfering RNA, respectively, did not alter EEC resistance to growth inhibition by TGFβ. Raf-1 inhibition blocked induction of EEC growth by epidermal growth factor. Our data suggest that Raf-1 may mediate pathologic steps involved in early endometriosis lesion formation and may be a mediator of TGFβ and epidermal growth factor actions in endometriosis.
Birds achieve high robustness in uneven terrain through active control of landing conditions
Authors: Birn-Jeffery Aleksandra V. , Daley Monica A.
Published: May 2012

We understand little about how animals adjust locomotor behaviour to negotiate uneven terrain. The mechanical demands and constraints of such behaviours likely differ from uniform terrain locomotion. Here we investigated how common pheasants negotiate visible obstacles with heights from 10 to 50% of leg length. Our goal was to determine the neuro-mechanical strategies used to achieve robust stability, and address whether strategies vary with obstacle height. We found that control of landing conditions was crucial for minimising fluctuations in stance leg loading and work in uneven terrain. Variation in touchdown leg angle (θTD) was correlated with the orientation of ground force during stance, and the angle between the leg and body velocity vector at touchdown (βTD) was correlated with net limb work. Pheasants actively targeted obstacles to control body velocity and leg posture at touchdown to achieve nearly steady dynamics on the obstacle step. In the approach step to an obstacle, the birds produced net positive limb work to launch themselves upward. On the obstacle, body dynamics were similar to uniform terrain. Pheasants also increased swing leg retraction velocity during obstacle negotiation, which we suggest is an active strategy to minimise fluctuations in peak force and leg posture in uneven terrain. Thus, pheasants appear to achieve robustly stable locomotion through a combination of path planning using visual feedback and active adjustment of leg swing dynamics to control landing conditions. We suggest that strategies for robust stability are context specific, depending on the quality of sensory feedback available, especially visual input.
Hibernation energetics of free-ranging little brown bats
Authors: Jonasson Kristin A. , Willis Craig K. R.
Published: May 2012

Hibernation physiology and energy expenditure have been relatively well studied in large captive hibernators, especially rodents, but data from smaller, free-ranging hibernators are sparse. We examined variation in the hibernation patterns of free-ranging little brown bats (Myotis lucifugus) using temperature-sensitive radio-transmitters. First, we aimed to test the hypothesis that age, sex and body condition affect expression of torpor and energy expenditure during hibernation. Second, we examined skin temperature to assess whether qualitative differences in the thermal properties of the hibernacula of bats, compared with the burrows of hibernating rodents, might lead to different patterns of torpor and arousal for bats. We also evaluated the impact of carrying transmitters on body condition to help determine the potential impact of telemetry studies. We observed large variation in the duration of torpor bouts within and between individuals but detected no effect of age, sex or body condition on torpor expression or estimates of energy expenditure. We observed the use of shallow torpor in the midst of periodic arousals, which may represent a unique adaptation of bats for conservation of energy during the most costly phase of hibernation. There was no difference in the body condition of hibernating bats outfitted with transmitters compared with that of control bats captured from the same hibernaculum at the same time. This study provides new information on the energetics of hibernation in an under-represented taxon and baseline data important for understanding how white-nose syndrome, a new disease devastating populations of hibernating bats in North America, may alter the expression of hibernation in affected bats.
An unusual myosuppressin from the blood-feeding bugRhodnius prolixus
Authors: Lee Dohee , Taufique Hamza , da Silva Rosa , Lange Angela B.
Published: May 2012

The myosuppressin (MS) gene was cloned from a central nervous system (CNS) cDNA library of the hematophagous insect Rhodnius prolixus and is predicted to contain two introns and three exons. The mRNA transcribed from the myosuppressin gene encodes an 88 amino acid prepropeptide, which results in a mature decapeptide after post-translational modification. When compared with the myosuppressins isolated from other insects, the R. prolixus myosuppressin has a unique amino acid sequence (pQDIDHVFMRFamide), with isoleucine (I) in position 3 and methionine (M) in position 8. Reverse transcriptase (RT)-PCR shows that Rhopr-MS is expressed in the CNS and posterior midgut in R. prolixus and immunohistochemistry suggests that an RFamide-like peptide is present in endocrine-like cells in the midgut. Physiological assays using Rhopr-MS indicate that, despite the unusual M at position 8, it still retains myoinhibitory activity, inhibiting the frequency and reducing the amplitude of contractions in the anterior midgut and hindgut, and decreasing heart rate.
Targeting a neuropeptide to discrete regions of the motor arborizations of a single neuron
Authors: Kueh Daniel , Jellies John A.
Published: May 2012

The heart excitor (HE) motor neuron in the leech Hirudo releases acetylcholine (ACh) and a peptide, FMRFamide, to regulate the contractile activity of the heart tube and associated side vessels. Consistent with Dale's principle, it was assumed that both neurotransmitters were localized to all presynaptic varicosities. However, we found discrete peptide-positive and peptide-negative varicosities associated with particular sites of innervation on the heart tube. We produced dual-labeled HE neurons by pressure injecting Neurobiotin into single HE cell bodies and applied anti-FMRFamide antibodies on the same preparations. Consistent with initial expectations, peptide-labeled varicosities were numerous and widely distributed along the heart tube and at one of the three side vessels, the latero-abdominal vessel. Nevertheless, some Neurobiotin-labeled varicosities along the heart tube lacked peptide label entirely. Moreover, there were dense and distinct peptide-negative innervations at the valve junctions of the latero-dorsal and latero-lateral vessels at each segment. Nevertheless, the peptide label was found in HE axons and varicosities that projected distally along the side vessels. Therefore, the more proximal peptide-negative clusters cannot simply be the result of restricted transport or deficient staining of peptide. Rather, we infer that FMRFamide is transported to (or selectively excluded from) discrete locations and that ACh is present in varicosities that lacked peptide. Such targeting of neurotransmitters could be described using a discrete targeting model of synaptic transmission. Compared with Dale's principle, this model may provide a more complete perspective of chemical communication than previously understood.
A nicotinic acetylcholine receptor agonist affects honey bee sucrose responsiveness and decreases waggle dancing
Authors: Eiri Daren M. , Nieh James C.
Published: May 2012

A nicotinic acetylcholine receptor agonist, imidacloprid, impairs memory formation in honey bees and has general effects on foraging. However, little is known about how this agonist affects two specific aspects of foraging: sucrose responsiveness (SR) and waggle dancing (which recruits nestmates). Using lab and field experiments, we tested the effect of sublethal doses of imidacloprid on (1) bee SR with the proboscis extension response assay, and (2) free-flying foragers visiting and dancing for a sucrose feeder. Bees that ingested imidacloprid (0.21 or 2.16 ng bee–1) had higher sucrose response thresholds 1 h after treatment. Foragers that ingested imidacloprid also produced significantly fewer waggle dance circuits (10.5- and 4.5-fold fewer for 50% and 30% sucrose solutions, respectively) 24 h after treatment as compared with controls. However, there was no significant effect of imidacloprid on the sucrose concentrations that foragers collected at a feeder 24 h after treatment. Thus, imidacloprid temporarily increased the minimum sucrose concentration that foragers would accept (short time scale, 1 h after treatment) and reduced waggle dancing (longer time scale, 24 h after treatment). The effect of time suggests different neurological effects of imidacloprid resulting from the parent compound and its metabolites. Waggle dancing can significantly increase colony food intake, and thus a sublethal dose (0.21 ng bee–1, 24 p.p.b.) of this commonly used pesticide may impair colony fitness.
Correlations between ultrasonographic characteristics of corpora lutea and systemic concentrations of progesterone during the discrete stages of corpora lutea lifespan and secretory activity in cyclic ewes
Authors: Gallienne Jacqueline , Gregg Caroline , LeBlanc Evan , Yaakob Norazlin , Wu Di , Davies Kate , Rawlings Norman , Pierson Roger , Deardon Rob , Bartlewski Pawel
Published: May 2012

Associations between physical characteristics and functionality of corpora lutea (CL) have previously been reported in monovulatory species, albeit several studies in cattle and humans have refuted the existence of temporal relationships between CL size, echotexture and serum progesterone (P4) concentrations. The main objective of the present study was to examine whether or not there were correlations between ultrasonographic image attributes of CL and systemic concentrations of P4 during the discrete stages of the luteal phase in two breeds of sheep differing in ovulation rates (non-prolific Western White Face [WWF] ewes and prolific Finn [F] sheep). Transrectal ovarian ultrasonography utilized a 7.5-MHz linear-array transducer connected to a portable scanner (Aloka SSD-500) and the images were analyzed using commercially available image analytical software (Image ProPlus®) validated for the present application in sheep. The correlations were assessed using the Pearson's Product Moment (PPM) analysis and also, to increase the accuracy of statistical tests, the analysis of covariance (ANCOVA), with the number of CL as a co-factor. In WWF ewes, serum concentrations of P4 correlated significantly with the total luteal area (TLA) during the CL growth phase (days 3–6; day 0 = ovulation) and functional luteolysis (days 12–15), and with numerical pixel values (NPVs – pixel intensity) during luteolysis; the results obtained by using two different statistical methods were generally similar. In prolific F ewes, serum P4 concentrations were directly correlated with TLA during CL growth (days 3–6; ANCOVA), functional luteolysis (days 13–14; PPM), and structural CL regression (days 11–14; PPM and ANCOVA), and with NPVs during functional luteolysis (PPM and ANCOVA). We concluded that systemic P4 concentrations could only be accurately predicted from the changes in luteal area during CL growth and regression, and from NPVs during luteolysis, in both prolific and non-prolific ewes, but the changes in size and echotexture of the luteal glands at mid-cycle were not indicative of serum P4 concentrations in sheep.
Y-box binding protein-1 implicated in translational control of fetal myocardial gene expression after cardiac transplant
Authors: David Jason J , Subramanian Sukanya V , Zhang Aiwen , Willis William L , Kelm Robert J , Leier Carl V , Strauch Arthur R
Published: May 2012

Peri-transplant surgical trauma and ischemia/reperfusion injury in accepted murine heterotopic heart grafts has been associated with myofibroblast differentiation, cardiac fibrosis and biomechanical-stress activation of the fetal myocardial smooth muscle α-actin (SMαA) gene. The wound-healing agonists, transforming growth factor β1 and thrombin, are known to coordinate SMαA mRNA transcription and translation in activated myofibroblasts by altering the subcellular localization and mRNA-binding affinity of the Y-box binding protein-1 (YB-1) cold-shock domain (CSD) protein that governs a variety of cellular responses to metabolic stress. YB-1 accumulated in polyribosome-enriched regions of the sarcoplasm proximal to cardiac intercalated discs in accepted heart grafts. YB-1 binding to a purine-rich motif in exon 3 of SMαA mRNA that regulates translational efficiency increased substantially in perfusion-isolated, rod-shaped adult rat cardiomyocytes during phenotypic de-differentiation in the presence of serum-derived growth factors. Cardiomyocyte de-differentiation was accompanied by the loss of a 60 kDa YB-1 variant that was highly expressed in both adult myocardium and freshly isolated myocytes and replacement with the 50 kDa form of YB-1 (p50) typically expressed in myofibroblasts that demonstrated sequence-specific interaction with SMαA mRNA. Accumulation of p50 YB-1 in reprogrammed, de-differentiated myocytes was associated with a 10-fold increase in SMαA protein expression. Endomyocardial biopsies collected from patients up to 14 years after heart transplant showed variable yet coordinately elevated expression of SMαA and p50 YB-1 protein and demonstrable p50 YB-1:SMαA mRNA interaction. The p60 YB-1 variant in human heart graft samples, but neither mouse p60 nor mouse or human p50, reacted with an antibody specific for the phosphoserine 102 modification in the YB-1 CSD. Modulation of YB-1 subcellular compartmentalization and mRNA-binding activity may be linked with reprogramming of contractile protein gene expression in ventricular cardiomyocytes that could contribute to maladaptive remodeling in accepted, long-term heart grafts.
Proposed MHRA changes to UK children's paracetamol dosing recommendations: modelling study
Authors: Eyers Sally , Fingleton James , Perrin Kyle , Beasley Richard
Published: May 2012

Objectives

Paracetamol is the most commonly administered medicine to children. A recent study highlighted the risk of overdose of paracetamol using British National Formulary for Children (BNFC) age-based dosing guidelines. This current study assesses the safety of changes to the UK paracetamol product dosing system proposed by the Medicines and Healthcare products Regulatory Authority (MHRA) which include a larger number of narrower age bands and a single dose per age band.

Design

Theoretical comparison of the proposed MHRA dosing system with the product dosing instructions of a commonly prescribed form of paracetamol in the UK.

Setting

United Kingdom

Participants

Proposed MHRA dosing recommendations and current product dosing instructions were compared using a previously validated model.

Main outcome measures

For both dosing recommendations, single and cumulative daily doses of paracetamol for boys and girls at the 9th, 50th and 91st centiles for weight were calculated for 3 month, 1 year, 6 year and 12 year age groups.

Results

With the current product dosing instructions, underweight children are at risk of receiving approximately two times the recommended single and cumulative daily dose of paracetamol, particularly at age 1 year and 6 years. This risk is negligible when the same model is applied to the proposed MHRA dosing system, whereby underweight, average weight and overweight children at all ages receive doses marginally above or within the recommended dose range or limit.

Conclusion

The proposed MHRA dosing recommendations for paracetamol use in children are effective at reducing the risk of paracetamol overdose in children of all ages, when compared with current product dosing instructions.
Brain weight–body weight ratio in sudden infant death syndrome revisited
Authors: Elliott Jane A , Vink Robert , Jensen Lisbeth , Byard Roger W
Published: May 2012

Aims

To determine whether the brain–body weight ratio is increased in sudden infant death syndrome (SIDS).

Methods

Review of autopsy files from Forensic Science SA, South Australia was undertaken over an eight-year period from 1999 to 2006, with classification of cases according to the San Diego definition. Sudden and/or unexpected deaths in previously healthy infants due to asphyxia or infection were selected as controls.

Results

There were 42 SIDS cases and 25 controls. The SIDS cases were aged from 1 to 42 weeks (mean: 16.26 ± 1.5 weeks) with a male to female ratio of 26:16. The control infants were aged from 3 to 48 weeks (mean: 19.24 ± 2.9 weeks) ( P > 0.05) (M:F = 16:9) and included 13 cases of asphyxia and 12 cases of sepsis. Comparison of the brain–body weight ratios failed to demonstrate a significant difference: SIDS mean = 0.121 ± 0.003; control mean = 0.115 ± 0.003 ( P > 0.05).

Conclusion

Although, there was a trend towards higher brain–body weight ratios in SIDS infants, this did not reach significance. The role of brain weight in the aetiology of SIDS remains controversial.
Source of Job Satisfaction among South Korean Police Officers
Authors: Jo Youngoh , Hoover Larry T.
Published: May 2012

Studies of police job satisfaction show consistent findings that work-related variables have greater effects than personal demographic factors. Despite the cumulative knowledge about the sources of police officers' job satisfaction, there exist several limitations, including the applicability of the findings drawn from Western studies to the Asian context and differences in the determinants of job satisfaction across organisational subgroups. This study contributes to current literature by examining both phenomena: (1) whether work-related factors dominate for South Korean police officers, and (2) whether determinants of job satisfaction vary across type of duty. Using a sample of 341 Korean police officers, this study found that work-related variables indeed had stronger effects than demographic on job satisfaction in the sample. However, the determinants of job satisfaction differ between patrol officers and clerical officers. Although perceptions of pay and commitment have significant effects on job satisfaction for both groups, autonomy, job security and citizen feedback affect only clerical officers' job satisfaction, but not patrol officers'.
Physiological Measurement of Crime Scene Investigator Stress
Authors: Adderley Rick , Smith Lisa L. , Bond John W. , Smith Michelle
Published: May 2012

This study aims to identify quantitatively the level of increased stress in civilian crime scene investigators (CSIs) whilst they were performing a variety of tasks as part of their normal duties. Mean above-average resting heart rate was used as the quantitative measure of physiological changes, recorded once a second for 12 CSIs during a working shift of 8 hours over a period of 7 days. Each CSI maintained an activity log of their work which enabled the physiological readings to be aligned to tasks undertaken. As well as physical stress, results show that CSIs undergo psychosocial stress during the examination of routine crime scenes such as domestic burglary and vehicle examination. Increased levels of stress diminished between scene visits. Reasons for increased stress reactivity at routine crime scenes are considered and opportunities for further work discussed. This study demonstrates quantitatively the stress undergone by civilian CSIs and questions the effect this might have on the effective recovery of forensic material from the crime scene as well as the welfare of the CSI.
The County Sheriff's Leadership and Management Decisions in the Local Budget Process Revisited
Authors: LaFrance T. Casey
Published: May 2012

LaFrance and Placide found that a substantial majority of county sheriffs (10/12, or 83 per cent) are likely to cooperate with the county legislative body during a budget crisis (LaFrance, T. C., & Placide, M. (2010). Sheriffs' and police chiefs' leadership and management decisions in the local law enforcement budgetary process: an exploration. International Journal of Police Science and Management, 12(2), 238–255). However, their study is plagued by a small sample size that does not allow for generalisability of their findings. Describing these limitations, the researchers ask for subsequent research with a larger number of cases. In this paper, this call is answered by proposing an identical scenario to a sample of 107 sheriffs in three states.
In VivoVisualization of Delta Opioid Receptors upon Physiological Activation Uncovers a Distinct Internalization Profile
Authors: Faget Lauren , Erbs Eric , Le Merrer Julie , Scherrer Gregory , Matifas Audrey , Benturquia Nadia , Noble Florence , Decossas Marion , Koch Marc , Kessler Pascal , Vonesch Jean-Luc , Schwab Yannick , Kieffer Brigitte L. , Massotte Dominique
Published: May 2012

G-protein-coupled receptors (GPCRs) mediate numerous physiological functions and represent prime therapeutic targets. Receptor trafficking upon agonist stimulation is critical for GPCR function, but examining this processin vivoremains a true challenge. Using knock-in mice expressing functional fluorescent delta opioid receptors under the control of the endogenous promoter, we visualizedin vivointernalization of this native GPCR upon physiological stimulation. We developed a paradigm in which animals were made dependent on morphine in a drug-paired context. When re-exposed to this context in a drug-free state, mice showed context-dependent withdrawal signs and activation of the hippocampus. Receptor internalization was transiently detected in a subset of CA1 neurons, uncovering regionally restricted opioid peptide release. Importantly, a pool of surface receptors always remained, which contrasts with thein vivoprofile previously established for exogenous drug-induced internalization. Therefore, a distinct response is observed at the receptor level upon a physiological or pharmacological stimulation. Altogether, directin vivoGPCR visualization enables mapping receptor stimulation promoted by a behavioral challenge and represents a powerful approach to study endogenous GPCR physiology.
Initial Neighborhood Biases and the Quality of Motion Stimulation Jointly Influence the Rapid Emergence of Direction Preference in Visual Cortex
Authors: Van Hooser Stephen D. , Li Ye , Christensson Maria , Smith Gordon B. , White Leonard E. , Fitzpatrick David
Published: May 2012

Visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. In visually naive animals, presentation of a bidirectional “training” stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. In this study we usedin vivotwo-photon imaging of calcium signals to further explore the contribution of visual experience to the emergence of direction- selective responses in ferret visual cortex. The first set of experiments was designed to determine whether visual experience is required for the development of the initial neighborhood bias. In animals that were dark-reared until the time of eye opening, we found that individual neurons exhibited weak direction-selective responses accompanied by a reduced but statistically significant neighborhood bias, indicating that both features arise without the need for visual experience. The second set of experiments used a unidirectional training stimulus to assess the relative roles of the neighborhood bias and visual experience in determining the direction preference that cortical neurons acquire during direction training. We found that neurons became more responsive to the trained direction even when they were located in regions of the cortex with an initial neighborhood bias for the direction opposite the training stimulus. Together, these results suggest an adaptive developmental strategy for the elaboration of direction-selective responses, one in which experience-independent mechanisms provide a symmetry-breaking seed for the instructive effects of visual experience.
Palmitoylation of A-Kinase Anchoring Protein 79/150 Regulates Dendritic Endosomal Targeting and Synaptic Plasticity Mechanisms
Authors: Keith Dove J. , Sanderson Jennifer L. , Gibson Emily S. , Woolfrey Kevin M. , Robertson Holly R. , Olszewski Kyle , Kang Rujun , El-Husseini Alaa , Dell'Acqua Mark L.
Published: May 2012

NMDA receptor-dependent long-term potentiation (LTP) and depression (LTD) are forms of synaptic plasticity underlying learning and memory that are expressed through increases and decreases, respectively, in dendritic spine size and AMPA receptor (AMPAR) phosphorylation and postsynaptic localization. The A-kinase anchoring protein 79/150 (AKAP79/150) signaling scaffold regulates AMPAR phosphorylation, channel activity, and endosomal trafficking associated with LTP and LTD. AKAP79/150 is targeted to dendritic spine plasma membranes by an N-terminal polybasic domain that binds phosphoinositide lipids, F-actin, and cadherin cell adhesion molecules. However, we do not understand how regulation of AKAP targeting controls AMPAR endosomal trafficking. Here, we report that palmitoylation of the AKAP N-terminal polybasic domain targets it to postsynaptic lipid rafts and dendritic recycling endosomes. AKAP palmitoylation was regulated by seizure activityin vivoand LTP/LTD plasticity-inducing stimuli in cultured rat hippocampal neurons. With chemical LTP induction, we observed AKAP79 dendritic spine recruitment that required palmityolation and Rab11-regulated endosome recycling coincident with spine enlargement and AMPAR surface delivery. Importantly, a palmitoylation-deficient AKAP79 mutant impaired regulation of spine size, endosome recycling, AMPAR trafficking, and synaptic potentiation. These findings emphasize the emerging importance of palmitoylation in controlling synaptic function and reveal novel roles for the AKAP79/150 signaling complex in dendritic endosomes.
Selectively Silencing GSK-3 Isoforms Reduces Plaques and Tangles in Mouse Models of Alzheimer's Disease
Authors: Hurtado David E. , Molina-Porcel Laura , Carroll Jenna C. , MacDonald Caryn , Aboagye Awo K. , Trojanowski John Q. , Lee Virginia M.-Y.
Published: May 2012

Glycogen synthase kinase-3 (GSK-3) is linked to the pathogenesis of Alzheimer's disease (AD), senile plaques (SPs), and neurofibrillary tangles (NFTs), but the specific contributions of each of the GSK-3 α and β isoforms to mechanisms of AD have not been clarified. In this study, we sought to elucidate the role of each GSK-3α and GSK-3β using novel viral and genetic approaches. First, we developed recombinant adeno-associated virus 2/1 short hairpin RNA constructs which specifically reduced expression and activity of GSK-3α or GSK-3β. These constructs were injected intraventricularly in newborn AD transgenic (tg) mouse models of SPs (PDAPP+/−), both SPs and NFTs (PDAPP+/−;PS19+/−), or wild-type controls. We found that knockdown (KD) of GSK-3α, but not GSK-3β, reduced SP formation in PDAPP+/−and PS19+/−;PDAPP+/−tg mice. Moreover, both GSK-3α and GSK-3β KD reduced tau phosphorylation and tau misfolding in PS19+/−;PDAPP+/−mice. Next, we generated triple tg mice using the CaMKIIα-Cre (α-calcium/calmodulin-dependent protein kinase II-Cre) system to KDGSK-3α in PDAPP+/−mice for further study of the effects of GSK-3α reduction on SP formation. GSK-3α KD showed a significant effect on reducing SPs and ameliorating memory deficits in PDAPP+/−mice. Together, the data from both approaches suggest that GSK-3α contributes to both SP and NFT pathogenesis while GSK-3β only modulates NFT formation, suggesting common but also different targets for both isoforms. These findings highlight the potential importance of GSK-3α as a possible therapeutic target for ameliorating behavioral impairments linked to AD SPs and NFTs.
Scene Representations in Parahippocampal Cortex Depend on Temporal Context
Authors: Turk-Browne Nicholas B. , Simon Mason G. , Sederberg Per B.
Published: May 2012

Human perception is supported by regions of ventral visual cortex that become active when specific types of information appear in the environment. This coupling has led to a common assumption in cognitive neuroscience that stimulus-evoked activity in these regions only reflects information about the current stimulus. Here we challenge this assumption for how scenes are represented in a scene-selective region of parahippocampal cortex. This region treated two identical scenes as more similar when they were preceded in time by the same stimuli compared to when they were preceded by different stimuli. These findings suggest that parahippocampal cortex embeds scenes in their temporal context to determine what they represent. By integrating the past and present, such representations may support the encoding and navigation of complex environments.
Striatal Dopamine D2/D3Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans
Authors: Ghahremani Dara G. , Lee Buyean , Robertson Chelsea L. , Tabibnia Golnaz , Morgan Andrew T. , De Shetler Natalie , Brown Amira K. , Monterosso John R. , Aron Adam R. , Mandelkern Mark A. , Poldrack Russell A. , London Edythe D.
Published: May 2012

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D2-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D2-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D2/D3dopamine receptor ligand [18F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D2/D3receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D2/D3receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D2-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.
Running Speed Alters the Frequency of Hippocampal Gamma Oscillations
Authors: Ahmed Omar J. , Mehta Mayank R.
Published: May 2012

Successful spatial navigation is thought to employ a combination of at least two strategies: the following of landmark cues and path integration. Path integration requires that the brain use the speed and direction of movement in a meaningful way to continuously compute the position of the animal. Indeed, the running speed of rats modulates both the firing rate of neurons and the spectral properties of low frequency, theta oscillations seen in the local field potential (LFP) of the hippocampus, a region important for spatial memory formation. Higher frequency, gamma-band LFP oscillations are usually associated with decision-making, increased attention, and improved reaction times. Here, we show that increased running speed is accompanied by large, systematic increases in the frequency of hippocampal CA1 network oscillations spanning the entire gamma range (30–120 Hz) and beyond. These speed-dependent changes in frequency are seen on both linear tracks and two-dimensional platforms, and are thus independent of the behavioral task. Synchrony between anatomically distant CA1 regions also shifts to higher gamma frequencies as running speed increases. The changes in frequency are strongly correlated with changes in the firing rates of individual interneurons, consistent with models of gamma generation. Our results suggest that as a rat runs faster, there are faster gamma frequency transitions between sequential place cell-assemblies. This may help to preserve the spatial specificity of place cells and spatial memories at vastly different running speeds.
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Authors: Gasser Andreas , Ho Tammy Szu-Yu , Cheng Xiaoyang , Chang Kae-Jiun , Waxman Stephen G. , Rasband Matthew N. , Dib-Hajj Sulayman D.
Published: May 2012

Neurons are highly polarized cells with functionally distinct axonal and somatodendritic compartments. Voltage-gated sodium channels Nav1.2 and Nav1.6 are highly enriched at axon initial segments (AISs) and nodes of Ranvier, where they are necessary for generation and propagation of action potentials. Previous studies using reporter proteins in unmyelinated cultured neurons suggest that an ankyrinG-binding motif within intracellular loop 2 (L2) of sodium channels is sufficient for targeting these channels to the AIS, but mechanisms of channel targeting to nodes remain poorly understood. Using a CD4-Nav1.2/L2 reporter protein in rat dorsal root ganglion neuron–Schwann cell myelinating cocultures, we show that the ankyrinG-binding motif is sufficient for protein targeting to nodes of Ranvier. However, reporter proteins cannot capture the complexity of full-length channels. To determine how native, full-length sodium channels are clustered in axons, and to show the feasibility of studying these channelsin vivo, we constructed fluorescently tagged and functional mouse Nav1.6 channels forin vivoanalysis usingin uterobrain electroporation. We show here that wild-type tagged-Nav1.6 channels are efficiently clustered at nodes and AISsin vivo. Furthermore, we show that mutation of a single invariant glutamic acid residue (E1100) within the ankyrinG-binding motif blocked Nav1.6 targeting in neurons bothin vitroandin vivo. Additionally, we show that caseine kinase phosphorylation sites within this motif, while not essential for targeting, can modulate clustering at the AIS. Thus, the ankyrinG-binding motif is both necessary and sufficient for the clustering of sodium channels at nodes of Ranvier and the AIS.
p38 MAPK Activation Promotes Denervated Schwann Cell Phenotype and Functions as a Negative Regulator of Schwann Cell Differentiation and Myelination
Authors: Yang David P. , Kim Jihyun , Syed Neeraja , Tung Young-john , Bhaskaran Ambily , Mindos Thomas , Mirsky Rhona , Jessen Kristjan R. , Maurel Patrice , Parkinson David B. , Kim Haesun A.
Published: May 2012

Physical damage to the peripheral nerves triggers Schwann cell injury response in the distal nerves in an event termed Wallerian degeneration: the Schwann cells degrade their myelin sheaths and dedifferentiate, reverting to a phenotype that supports axon regeneration and nerve repair. The molecular mechanisms regulating Schwann cell plasticity in the PNS remain to be elucidated. Using bothin vivoandin vitromodels for peripheral nerve injury, here we show that inhibition of p38 mitogen-activated protein kinase (MAPK) activity in mice blocks Schwann cell demyelination and dedifferentiation following nerve injury, suggesting that the kinase mediates the injury signal that triggers distal Schwann cell injury response. In myelinating cocultures, p38 MAPK also mediates myelin breakdown induced by Schwann cell growth factors, such as neuregulin and FGF-2. Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin breakdown and drives differentiated Schwann cells to acquire phenotypic features of immature Schwann cells. We also show that p38 MAPK concomitantly functions as a negative regulator of Schwann cell differentiation: enforced p38 MAPK activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but induces expression of c-Jun. As expected of its role as a negative signal for myelination, inhibition of p38 MAPK in cocultures promotes myelin formation by increasing the number as well as the length of individual myelin segments. Altogether, our data identify p38 MAPK as an important regulator of Schwann cell plasticity and differentiation.