bluuebunny/crossref_metadata_2025 huggingface dataset:
rpoS
-Regulated Core Genes Involved in the Competitive Fitness of Salmonella enterica Serovar Kentucky in the Intestines of Chickens
Authors: Cheng Ying , Pedroso Adriana Ayres , Porwollik Steffen , McClelland Michael , Lee Margie D. , Kwan Tiffany , Zamperini Katherine , Soni Vivek , Sellers Holly S. , Russell Scott M. , Maurer John J.
Published: November 2014

Salmonella enterica
serovar Kentucky has become the most frequently isolated serovar from poultry in the United States over the past decade. Despite its prevalence in poultry, it causes few human illnesses in the United States. The dominance of
S
. Kentucky in poultry does not appear to be due to single introduction of a clonal strain, and its reduced virulence appears to correlate with the absence of virulence genes
grvA
,
sseI
,
sopE
, and
sodC1. S
. Kentucky's prevalence in poultry is possibly attributable to its metabolic adaptation to the chicken cecum. While there were no difference in the growth rate of
S
. Kentucky and
S
. Typhimurium grown microaerophilically in cecal contents,
S
. Kentucky persisted longer when chickens were coinfected with
S
. Typhimurium. The
in vivo
advantage that
S
. Kentucky has over
S
. Typhimurium appears to be due to differential regulation of core
Salmonella
genes via the stationary-phase sigma factor
rpoS
. Microarray analysis of
Salmonella
grown in cecal contents
in vitro
identified several metabolic genes and motility and adherence genes that are differentially activated in
S
. Kentucky. The contributions of four of these operons (
mgl
,
prp
,
nar
, and
csg
) to
Salmonella
colonization in chickens were assessed. Deletion of
mgl
and
csg
reduced
S
. Kentucky persistence in competition studies in chickens infected with wild-type or mutant strains. Subtle mutations affecting differential regulation of core
Salmonella
genes appear to be important in
Salmonella
's adaptation to its animal host and especially for
S
. Kentucky's emergence as the dominant serovar in poultry.
The Cullin-4 Complex DCDC Does Not Require E3 Ubiquitin Ligase Elements To Control Heterochromatin in Neurospora crassa
Authors: Adhvaryu Keyur K. , Gessaman Jordan D. , Honda Shinji , Lewis Zachary A. , Grisafi Paula L. , Selker Eric U.
Published: November 2014

The cullin-4 (CUL4) complex DCDC (
D
IM-5/-7/-9/
C
UL4/
D
DB1
c
omplex) is essential for DNA methylation and heterochromatin formation in
Neurospora crassa
. Cullins form the scaffold of cullin-RING E3 ubiquitin ligases (CRLs) and are modified by the covalent attachment of NEDD8, a ubiquitin-like protein that regulates the stability and activity of CRLs. We report that neddylation is not required for CUL4-dependent DNA methylation or heterochromatin formation but is required for the DNA repair functions. Moreover, the RING domain protein RBX1 and a segment of the CUL4 C terminus that normally interacts with RBX1, the E2 ligase, CAND1, and CSN are dispensable for DNA methylation and heterochromatin formation by DCDC. Our study provides evidence for the noncanonical functions of core CRL components.
BiobankConnect: software to rapidly connect data elements for pooled analysis across biobanks using ontological and lexical indexing
Authors: Pang Chao , Hendriksen Dennis , Dijkstra Martijn , van der Velde K Joeri , Kuiper Joel , Hillege Hans L , Swertz Morris A
Published: November 2014

Objective Pooling data across biobanks is necessary to increase statistical power, reveal more subtle associations, and synergize the value of data sources. However, searching for desired data elements among the thousands of available elements and harmonizing differences in terminology, data collection, and structure, is arduous and time consuming.

Materials and methods To speed up biobank data pooling we developed BiobankConnect, a system to semi-automatically match desired data elements to available elements by: (1) annotating the desired elements with ontology terms using BioPortal; (2) automatically expanding the query for these elements with synonyms and subclass information using OntoCAT; (3) automatically searching available elements for these expanded terms using Lucene lexical matching; and (4) shortlisting relevant matches sorted by matching score.

Results We evaluated BiobankConnect using human curated matches from EU-BioSHaRE, searching for 32 desired data elements in 7461 available elements from six biobanks. We found 0.75 precision at rank 1 and 0.74 recall at rank 10 compared to a manually curated set of relevant matches. In addition, best matches chosen by BioSHaRE experts ranked first in 63.0% and in the top 10 in 98.4% of cases, indicating that our system has the potential to significantly reduce manual matching work.

Conclusions BiobankConnect provides an easy user interface to significantly speed up the biobank harmonization process. It may also prove useful for other forms of biomedical data integration. All the software can be downloaded as a MOLGENIS open source app from http://www.github.com/molgenis, with a demo available at http://www.biobankconnect.org.
American Medical Society for Sports Medicine recommended sports ultrasound curriculum for sports medicine fellowships
Authors: Finnoff Jonathan T , Berkoff David , Brennan Fred , DiFiori John , Hall Mederic M , Harmon Kimberly , Lavallee Mark , Martin Sean , Smith Jay , Stovak Mark
Published: November 2014

The American Medical Society for Sports Medicine (AMSSM) developed a musculoskeletal ultrasound curriculum for sports medicine fellowships in 2010. As the use of diagnostic and interventional ultrasound in sports medicine has evolved, it became clear that the curriculum needed to be updated. Furthermore, the name ‘musculoskeletal ultrasound’ was changed to ‘sports ultrasound’ (SPORTS US) to reflect the broad range of diagnostic and interventional applications of ultrasound in sports medicine.

This document was created to outline the core competencies of SPORTS US and to provide sports medicine fellowship directors and others interested in SPORTS US education with a guide to create a SPORTS US curriculum. By completing this SPORTS US curriculum, sports medicine fellows and physicians can attain proficiency in the core competencies of SPORTS US required for the practice of sports medicine.
Results from a dietary survey in an Indian T2DM population: a STARCH study
Authors: Joshi Shashank R , Bhansali Anil , Bajaj Sarita , Banzal Subodh S , Dharmalingam Mala , Gupta Shachin , Mukhopadhyay Satinath , Shah Parag R , Sahay Rakesh , Sarkar Swapan , Manjrekar Pravin V , Rathod Rahul T , Joshi Shilpa S
Published: November 2014

Objective

To assess the dietary total and complex carbohydrate (CHO) contents in type-2 diabetes mellitus (T2DM) participants in India.

Setting

We enrolled 796 participants in this cross-sectional, single-visit, multicentre, two-arm, single-country survey. Participants were enrolled from 10 specialty endocrinology/dialectology centres from five regions of India.

Participants

A total of 796 participants (Asian) were enrolled in this study (385, T2DM and 409, non-T2DM). Key inclusion criteria—male or female ≥18 years, diagnosed with T2DM ≥12 months (T2DM), and not on any diet plan (non-T2DM).

Study outcome

Primary outcome was to find out the percentage of total energy intake as simple and complex CHO from total CHO. Secondary outcomes were to find the differences in percentage of total energy intake as simple CHO, complex CHO, proteins and fats between T2DM and non-T2DM groups. The percentage of T2DM participants adhering to diet plan and showing glycaemic controls were also examined.

Results

The mean (SD) of total calorie intake per day (Kcal) was 1547 (610, 95% CI 1486 to 1608) and 2132 (1892, 95% CI 1948 to 2316), respectively, for T2DM and non-T2DM groups. In the T2DM group (n=385), the mean (SD) percentage of total energy intake as total CHO, complex CHO and simple CHO was 64.1±8.3 (95% CI 63.3 to 64.9), 57.0±11.0 (95% CI 55.9 to 58.1) and 7.1±10.8 (95% CI 6.0 to 8.2), respectively. The mean (SD) percentage of complex CHO intake from total CHO was 89.5±15.3 (95% CI 88.0 to 91.1). The mean (SD) total protein/fat intake per day (g) was 57.1 (74.0)/37.2 (18.6) and 57.9 (27.2)/55.3 (98.2) in T2DM and non-T2DM groups, respectively.

Conclusions

Our study shows that CHO constitutes 64.1% of total energy from diet in T2DM participants, higher than that recommended in India. However, our findings need to be confirmed in a larger epidemiological survey.

Trial registration number

NCT01450592 & Clinical Trial Registry of India: CTRI/2012/02/002398.
Individualising dual antiplatelet therapy after percutaneous coronary intervention: the IDEAL-PCI registry
Authors: Christ Günter , Siller-Matula Jolanta M , Francesconi Marcel , Dechant Cornelia , Grohs Katharina , Podczeck-Schweighofer Andrea
Published: November 2014

Objective

To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.

Setting

Tertiary care single centre registry.

Participants

1008 consecutive PCI patients with stent implantation, without exclusion criteria.

Intervention

Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U).

Outcome measures

The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE).

Results

53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both).

Conclusions

Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted.

Trial registration number

http://www.clinicaltrials.gov;NCT01515345.
Evaluating Midwifery Units (EMU): a prospective cohort study of freestanding midwifery units in New South Wales, Australia
Authors: Monk Amy , Tracy Mark , Foureur Maralyn , Grigg Celia , Tracy Sally
Published: November 2014

Objective

To compare maternal and neonatal birth outcomes and morbidities associated with the intention to give birth in two freestanding midwifery units and two tertiary-level maternity units in New South Wales, Australia.

Design

Prospective cohort study.

Participants

494 women who intended to give birth at freestanding midwifery units and 3157 women who intended to give birth at tertiary-level maternity units. Participants had low risk, singleton pregnancies and were at less than 28+0weeks gestation at the time of booking.

Primary and secondary outcome measures

Primary outcomes were mode of birth, Apgar score of less than 7 at 5 min and admission to the neonatal intensive care unit or special care nursery. Secondary outcomes were onset of labour, analgesia, blood loss, management of third stage of labour, perineal trauma, transfer, neonatal resuscitation, breastfeeding, gestational age at birth, birth weight, severe morbidity and mortality.

Results

Women who planned to give birth at a freestanding midwifery unit were significantly more likely to have a spontaneous vaginal birth (AOR 1.57; 95% CI 1.20 to 2.06) and significantly less likely to have a caesarean section (AOR 0.65; 95% CI 0.48 to 0.88). There was no significant difference in the AOR of 5 min Apgar scores, however, babies from the freestanding midwifery unit group were significantly less likely to be admitted to neonatal intensive care or special care nursery (AOR 0.60; 95% CI 0.39 to 0.91). Analysis of secondary outcomes indicated that planning to give birth in a freestanding midwifery unit was associated with similar or reduced odds of intrapartum interventions and similar or improved odds of indicators of neonatal well-being.

Conclusions

The results of this study support the provision of care in freestanding midwifery units as an alternative to tertiary-level maternity units for women with low risk pregnancies at the time of booking.
Computerised cognitive behaviour therapy for depression in adolescents: study protocol for a feasibility randomised controlled trial
Authors: Wright Barry , Tindall Lucy , Littlewood Elizabeth , Adamson Joy , Allgar Victoria , Bennett Sophie , Gilbody Simon , Verduyn Chrissie , Alderson-Day Ben , Dyson Lisa , Trépel Dominic , Ali Shehzad
Published: November 2014

Introduction

The 1 year prevalence of depression in adolescents is about 2%. Treatment with antidepressant medication is not recommended for initial treatment in young people due to concerns over high side effects, poor efficacy and addictive potential. Evidence suggests that cognitive behaviour therapy (CBT) is an effective treatment for depression and is currently one of the main treatment options recommended in adolescents. Given the affinity young people have with information technology they may be treated effectively, more widely and earlier in their illness evolution using computer-administered CBT (CCBT). Currently little is known about the clinical and resource implications of implementing CCBT within the National Health Service for adolescents with low mood/depression. We aim to establish the feasibility of running a fully powered randomised controlled trial (RCT).

Methods and analysis

Adolescents aged 12–18 with low mood/depression, (scoring ≥20 on the Mood and Feelings Questionnaire (MFQ)), will be approached to participate. Consenting participants will be randomised to either a CCBT programme (Stressbusters) or accessing selected websites providing information about low mood/depression. The primary outcome measure will be the Beck Depression Inventory (BDI). Participants will also complete generic health measures (EQ5D-Y, HUI2) and resource use questionnaires to examine the feasibility of cost-effectiveness analysis. Questionnaires will be completed at baseline, 4 and 12-month follow-ups. Progress and risk will be monitored via the MFQ administered at each treatment session. The acceptability of a CCBT programme to adolescents; and the willingness of clinicians to recruit participants and of participants to be randomised, recruitment rates, attrition rates and questionnaire completion rates will be collected for feasibility analysis. We will estimate ‘numbers needed’ to plan a fully powered RCT of clinical and cost-effectiveness.

Ethics and dissemination

The current trial protocol received a favourable ethical opinion from Leeds (West) Research and Ethics Committee. (Reference: 10/H1307/137).

Trial registration number

ISRCTN31219579.
Abdominal ultrasound features and reference values in 21 healthy rabbits
Authors: Banzato T. , Bellini L. , Contiero B. , Selleri P. , Zotti A.
Published: November 2014

This study aimed to determine the ultrasonographic features and reference values of the abdominal anatomy in mixed‐breed dwarf rabbits. Complete abdominal ultrasonographic examination was performed in 21 mixed‐breed rabbits (12 males and 9 females) referred for examination to the Department of Animal Medicine, Production and Health, University of Padua, Italy. All animals were sedated during the procedure. The ultrasonographic anatomy of the abdomen was determined, including measurement (mean±SD) of the right kidney (length 2.87±0.34 mm; width 1.62±0.17 mm; height 1.66±0.14 mm) and left kidney (length 2.86±0.33 mm; width 1.72±0.19; height 1.58±0.15 mm), left adrenal gland (width 0.38±0.11 mm; length 0.71±0.14), right adrenal gland (width 0.34±0.08 mm; length 0.73±0.15 mm) and thickness of the walls of the stomach (0.10±0.01 mm), pylorus (0.28±0.04 mm), duodenum (0.19±0.04 mm), sacculus rotundus (0.22±0.06 mm), caecum (0.08±0.01 mm), appendix (0.19±0.04 mm), spiral loop of the ascending colon (0.14±0.04 mm) and distal colon (0.10±0.02 mm). A significant positive correlation between bodyweight and kidney size, adrenal gland length, stomach wall and sacculus rotundus wall was detected.
Persistence of ovine scrapie infectivity in a farm environment following cleaning and decontamination
Authors: Hawkins Steve A. C. , Simmons Hugh A. , Gough Kevin C. , Maddison Ben C.
Published: November 2014

Scrapie of sheep/goats and chronic wasting disease of deer/elk are contagious prion diseases where environmental reservoirs are directly implicated in the transmission of disease. In this study, the effectiveness of recommended scrapie farm decontamination regimens was evaluated by a sheep bioassay using buildings naturally contaminated with scrapie. Pens within a farm building were treated with either 20,000 parts per million free chorine solution for one hour or were treated with the same but were followed by painting and full re‐galvanisation or replacement of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype VRQ/VRQ were reared within these pens and their scrapie status was monitored by recto‐anal mucosa‐associated lymphoid tissue. All animals became infected over an 18‐month period, even in the pen that had been subject to the most stringent decontamination process. These data suggest that recommended current guidelines for the decontamination of farm buildings following outbreaks of scrapie do little to reduce the titre of infectious scrapie material and that environmental recontamination could also be an issue associated with these premises.
Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates
Authors: Kulshrestha Mudit , Sola-Visner Martha , Widness John A. , Veng-Pedersen Peter , Mager Donald E.
Published: November 2014

Neonatal thrombocytopenia affects 22–35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates.
Age-related changes in rat dermal extracellular matrix composition affect the distribution of plasma proteins as a function of size and charge
Authors: Sagstad Solfrid J. , Oveland Eystein , Karlsen Tine V. , Haslene-Hox Hanne , Tenstad Olav , Wiig Helge
Published: November 2014

Collagen and glycosaminoglycans (GAGs) constituting the ECM may limit the space available and thus exclude macromolecules from a fraction of the interstitial fluid (IF) phase. This exclusion phenomenon is of importance for transcapillary fluid and solute exchange. The purpose of the study was to examine the range of interstitial exclusion in rat skin by using probes within a span of molecular weights and electrical charge and also to test if a change in interstitial composition, occurring as a consequence of aging, affected exclusion. To this end, we used a novel approach, involving the exact determination of albumin concentration and mass in IF and tissue eluate by HPLC and thereafter, expressing the corresponding numbers relative to albumin for a set of probe proteins assessed by quantitative proteomics. Albumin was excluded from 55 ± 4% ( n = 8) of the extracellular fluid phase. There was a highly significant, positive correlation between probe Stokes-Einstein (SE) radius and fractional excluded volume (VEF), described by VEF = 0.078·SE radius + 0.269 ( P < 0.001), and oppositely, a negative correlation between probe isoelectric point (pI) and exclusion for proteins with comparable size, VEF = −0.036·pI + 0.719 ( P = 0.04). Aging resulted in a significant reduction in skin hydration and sulfated GAGs, a moderate increase in hyaluronan, and a corresponding, reduced VEF for albumin and the other macromolecular probes. Our findings suggest that the changes in the ECM in aged skin may result in delayed adjustments of fluid perturbations and reduced ability for salt storage.
Suppression of influenza A virus replication in human lung epithelial cells by noncytotoxic concentrations bafilomycin A1
Authors: Yeganeh Behzad , Ghavami Saeid , Kroeker Andrea L. , Mahood Thomas H. , Stelmack Gerald L. , Klonisch Thomas , Coombs Kevin M. , Halayko Andrew J.
Published: November 2014

Subcellular trafficking within host cells plays a critical role in viral life cycles, including influenza A virus (IAV). Thus targeting relevant subcellular compartments holds promise for effective intervention to control the impact of influenza infection. Bafilomycin A1(Baf-A1), when used at relative high concentrations (≥10 nM), inhibits vacuolar ATPase (V-ATPase) and reduces endosome acidification and lysosome number, thus inhibiting IAV replication but promoting host cell cytotoxicity. We tested the hypothesis that much lower doses of Baf-A1also have anti-IAV activity, but without toxic effects. Thus we assessed the antiviral activity of Baf-A1at different concentrations (0.1–100 nM) in human alveolar epithelial cells (A549) infected with IAV strain A/PR/8/34 virus (H1N1). Infected and mock-infected cells pre- and cotreated with Baf-A1were harvested 0–24 h postinfection and analyzed by immunoblotting, immunofluorescence, and confocal and electron microscopy. We found that Baf-A1had disparate concentration-dependent effects on subcellular organelles and suppressed affected IAV replication. At concentrations ≥10 nM Baf-A1inhibited acid lysosome formation, which resulted in greatly reduced IAV replication and release. Notably, at a very low concentration of 0.1 nM that is insufficient to reduce lysosome number, Baf-A1retained the capacity to significantly impair IAV nuclear accumulation as well as IAV replication and release. In contrast to the effects of high concentrations of Baf-A1, very low concentrations did not exhibit cytotoxic effects or induce apoptotic cell death, based on morphological and FACS analyses. In conclusion, our results reveal that low-concentration Baf-A1is an effective inhibitor of IAV replication, without impacting host cell viability.
The Genetic Basis of Chronic Mountain Sickness
Authors: Ronen Roy , Zhou Dan , Bafna Vineet , Haddad Gabriel G.
Published: November 2014

Chronic mountain sickness (CMS) is a disease that affects many high-altitude dwellers, particularly in the Andean Mountains in South America. The hallmark symptom of CMS is polycythemia, which causes increased risk of pulmonary hypertension and stroke (among other symptoms). A prevailing hypothesis in high-altitude medicine is that CMS results from a population-specific “maladaptation” to the hypoxic conditions at high altitude. In contrast, the prevalence of CMS is very low in other high-altitude populations (e.g., Tibetans and Ethiopians), which are seemingly well adapted to hypoxia. In recent years, concurrent with the advent of genomic technologies, several studies have investigated the genetic basis of adaptation to altitude. These studies have identified several candidate genes that may underlie the adaptation, or maladaptation. Interestingly, some of these genes are targeted by known drugs, raising the possibility of new treatments for CMS and other ischemic diseases. We review recent discoveries, alongside the methodologies used to obtain them, and outline some of the challenges remaining in the field.
Making Microvascular Networks Work: Angiogenesis, Remodeling, and Pruning
Authors: Pries Axel R. , Secomb Timothy W.
Published: November 2014

The adequate and efficient functioning of the microcirculation requires not only numerous vessels providing a large surface area for transport but also a structure that provides short diffusion distances from capillaries to tissue and efficient distribution of convective blood flow. Theoretical models show how a combination of angiogenesis, remodeling, and pruning in response to hemodynamic and metabolic stimuli, termed “angioadaptation,” generates well organized, functional networks.
Exercise, Neurotrophins, and Axon Regeneration in the PNS
Authors: English Arthur W. , Wilhelm Jennifer C. , Ward Patricia J.
Published: November 2014

Electrical stimulation and exercise are treatments to enhance recovery from peripheral nerve injuries. Brain-derived neurotrophic factor and androgen receptor signaling are requirements for the effectiveness of these treatments. Increased neuronal activity is adequate to promote regeneration in injured nerves, but the dosing of activity and its relationship to neurotrophins and sex steroid hormones is less clear. Translation of these therapies will require principles associated with their cellular mechanisms.
Translating Animal Model Research: Does It Matter That Our Rodents Are Cold?
Authors: Maloney Shane K. , Fuller Andrea , Mitchell Duncan , Gordon Christopher , Overton J. Michael
Published: November 2014

Does it matter that rodents used as preclinical models of human biology are routinely housed below their thermoneutral zone? We compile evidence showing that such rodents are cold-stressed, hypermetabolic, hypertensive, sleep-deprived, obesity-resistant, fever-resistant, aging-resistant, and tumor-prone compared with mice housed at thermoneutrality. The same genotype of mouse has a very different phenotype and response to physiological or pharmacological intervention when raised below or at thermoneutrality.
Organ-Specific Physiological Responses to Acute Physical Exercise and Long-Term Training in Humans
Authors: Heinonen Ilkka , Kalliokoski Kari K. , Hannukainen Jarna C. , Duncker Dirk J. , Nuutila Pirjo , Knuuti Juhani
Published: November 2014

Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review.
Mutant KRAS–Induced Expression of ICAM-1 in Pancreatic Acinar Cells Causes Attraction of Macrophages to Expedite the Formation of Precancerous Lesions
Authors: Liou Geou-Yarh , Döppler Heike , Necela Brian , Edenfield Brandy , Zhang Lizhi , Dawson David W. , Storz Peter
Published: November 2014

Desmoplasia and an inflammatory environment are defining features of pancreatic cancer. Unclear is how pancreatic cells that undergo oncogenic transformation can cross-talk with immune cells and how this contributes to the development of pancreatic lesions. Here, we demonstrate that pancreatic acinar cells expressing mutant KRAS can expedite their transformation to a duct-like phenotype by inducing local inflammation. Specifically, we show that KRASG12D induces the expression of intercellular adhesion molecule-1 (ICAM-1), which serves as chemoattractant for macrophages. Infiltrating macrophages amplify the formation of KRASG12D-caused abnormal pancreatic structures by remodeling the extracellular matrix and providing cytokines such as TNF. Depletion of macrophages or treatment with a neutralizing antibody for ICAM-1 in mice expressing oncogenic Kras under an acinar cell–specific promoter resulted in both a decreased formation of abnormal structures and decreased progression of acinar-to-ductal metaplasia to pancreatic intraepithelial neoplastic lesions.

Significance: We here show that oncogenic KRAS in pancreatic acinar cells upregulates the expression of ICAM-1 to attract macrophages. Hence, our results reveal a direct cooperative mechanism between oncogenic Kras mutations and the inflammatory environment to drive the initiation of pancreatic cancer. Cancer Discov; 5(1); 52–63. ©2014 AACR.

This article is highlighted in the In This Issue feature, p. 1
MicroRNA-451 Exacerbates Lipotoxicity in Cardiac Myocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway
Authors: Kuwabara Yasuhide , Horie Takahiro , Baba Osamu , Watanabe Shin , Nishiga Masataka , Usami Shunsuke , Izuhara Masayasu , Nakao Tetsushi , Nishino Tomohiro , Otsu Kinya , Kita Toru , Kimura Takeshi , Ono Koh
Published: November 2014

Rationale:

In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated.

Objective:

To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM.

Methods and Results:

C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in neonatal rat cardiac myocytes and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cardiomyocyte-specific miR-451 knockout mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in cardiomyocyte-specific miR-451 knockout mouse hearts compared with control mouse hearts.

Conclusions:

Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway.
Ischemic Stroke Activates Hematopoietic Bone Marrow Stem Cells
Authors: Courties Gabriel , Herisson Fanny , Sager Hendrik B. , Heidt Timo , Ye Yuxiang , Wei Ying , Sun Yuan , Severe Nicolas , Dutta Partha , Scharff Jennifer , Scadden David T. , Weissleder Ralph , Swirski Filip K. , Moskowitz Michael A. , Nahrendorf Matthias
Published: November 2014

Rationale:

The mechanisms leading to an expanded neutrophil and monocyte supply after stroke are incompletely understood.

Objective:

To test the hypothesis that transient middle cerebral artery occlusion (tMCAO) in mice leads to activation of hematopoietic bone marrow stem cells.

Methods and Results:

Serial in vivo bioluminescence reporter gene imaging in mice with tMCAO revealed that bone marrow cell cycling peaked 4 days after stroke (
P
<0.05 versus pre tMCAO). Flow cytometry and cell cycle analysis showed activation of the entire hematopoietic tree, including myeloid progenitors. The cycling fraction of the most upstream hematopoietic stem cells increased from 3.34%±0.19% to 7.32%±0.52% after tMCAO (
P
<0.05). In vivo microscopy corroborated proliferation of adoptively transferred hematopoietic progenitors in the bone marrow of mice with stroke. The hematopoietic system’s myeloid bias was reflected by increased expression of myeloid transcription factors, including PU.1 (
P
<0.05), and by a decline in lymphocyte precursors. In mice after tMCAO, tyrosine hydroxylase levels in sympathetic fibers and bone marrow noradrenaline levels rose (
P
<0.05, respectively), associated with a decrease of hematopoietic niche factors that promote stem cell quiescence. In mice with genetic deficiency of the β
3
adrenergic receptor, hematopoietic stem cells did not enter the cell cycle in increased numbers after tMCAO (naive control, 3.23±0.22; tMCAO, 3.74±0.33,
P
=0.51).

Conclusions:

Ischemic stroke activates hematopoietic stem cells via increased sympathetic tone, leading to a myeloid bias of hematopoiesis and higher bone marrow output of inflammatory Ly6C
high
monocytes and neutrophils.
Familial Clustering of Mitral Valve Prolapse in the Community
Authors: Delling Francesca N. , Rong Jian , Larson Martin G. , Lehman Birgitta , Osypiuk Ewa , Stantchev Plamen , Slaugenhaupt Susan A. , Benjamin Emelia J. , Levine Robert A. , Vasan Ramachandran S.
Published: November 2014

Background—

Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP.

Methods and Results—

Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus ≤2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40±9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13–9.54;
P
<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25–5.10;
P
=0.01).

Conclusions—

Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community.
Political Polarization as a Social Movement Outcome
Authors: McVeigh Rory , Cunningham David , Farrell Justin
Published: November 2014

Radical social movements can exacerbate tensions in local settings while drawing attention to how movement goals align with political party agendas. Short-term movement influence on voting outcomes can endure when orientations toward the movement disrupt social ties, embedding individuals within new discussion networks that reinforce new partisan loyalties. To demonstrate this dynamic, we employ longitudinal data to show that increases in Republican voting, across several different time intervals, were most pronounced in southern counties where the Ku Klux Klan had been active in the 1960s. In an individual-level analysis of voting intent, we show that decades after the Klan declined, racial attitudes map onto party voting among southern voters, but only in counties where the Klan had been active.
Modular Open-Source Software for Item Factor Analysis
Authors: Pritikin Joshua N. , Hunter Micheal D. , Boker Steven M.
Published: November 2014

This article introduces an item factor analysis (IFA) module for OpenMx, a free, open-source, and modular statistical modeling package that runs within the R programming environment on GNU/Linux, Mac OS X, and Microsoft Windows. The IFA module offers a novel model specification language that is well suited to programmatic generation and manipulation of models. Modular organization of the source code facilitates the easy addition of item models, item parameter estimation algorithms, optimizers, test scoring algorithms, and fit diagnostics all within an integrated framework. Three short example scripts are presented for fitting item parameters, latent distribution parameters, and a multiple group model. The availability of both IFA and structural equation modeling in the same software is a step toward the unification of these two methodologies.
Unsettled Landscapes: Czech and German Conceptions of Social and Ecological Decline in the Postwar Czechoslovak Borderlands
Authors: Glassheim Eagle
Published: November 2014

After the Second World War, Czechoslovakia expelled around three million Germans from the border region known as the Sudetenland. Close to two million Czechs and Slovaks moved from the country's interior to settle the region. Though cut off from their former homes by international borders soon hardened by the Cold War, expelled Germans vigorously engaged their homelands. They wrote odes to their lost Heimats, travelogues of trips through ‘Sudeten’ landscapes, critical essays on Czech management of the borderlands, and demands for restitution or return. For Czechoslovak settlers and communist officials, the specters of Germans past and present were persistent reminders of the shortcomings of resettlement and the need to consolidate conditions in the borderlands. This article traces an ongoing conversation from the 1940s to the 1980s among communist officials, Sudeten German expellees, communist reformers, and dissidents about the Czechoslovak borderlands. By the 1980s, most parties to the conversation had come to understand the borderlands in ecological terms, stressing the inter-relationship of mental, social, and physical geographies. Though communist officials and critics largely shared a diagnosis of borderland decline, there was a wide range of prescriptions for how to restore the region to ecological and social health.
Temporal artery biopsies: do they make the cut?
Authors: McMurran AEL , Boom SJ
Published: November 2014

Background and Aims

Temporal artery biopsy is the gold standard investigation for giant cell arteritis. Guidelines recommend that specimens should measure no less than 1 cm and ideally more than 2 cm in length, as this influences the likelihood of biopsy positivity. This audit investigates the extent to which temporal artery biopsies acquired in our hospital meet these guidelines.

Methods

Histopathology reports for all temporal artery biopsies performed at University Hospital Ayr between January 2011 and June 2013 were examined.

Results

Fifty-six temporal artery biopsy specimens showed a range in length from 0.5 cm to 3.1 cm, with a mean of 1.4 cm. Thirty-seven biopsies measured ≥1 cm (66%) and 13 were ≥2 cm (23%). Therefore, 19 samples (34%) did not meet the recommended standard. Just seven biopsies showed features of giant cell arteritis, with six of these measuring ≥1 cm in length (86%).

Conclusion

The guidelines for temporal artery specimens are not being met at our centre. Furthermore, biopsies measuring ≥1 cm are much more common in the small group of positive results. This validates the minimum recommended biopsy length and displays the importance of achieving this standard. We suggest changes to increase the number of biopsies meeting these guidelines, improving the accuracy of this invasive test.
Post-communist state measures to thwart organized labor: The case of Romania
Authors: Varga Mihai , Freyberg-Inan Annette
Published: November 2014

This article supplements the literature on post-communist trade unions with an account of how state measures can affect union strength in post-communist Europe. The authors focus on the case of Romanian trade unions, which is exceptional in post-communist Europe in that it is possible to rule out lack of protest capacity as a cause for weakness of policy influence: Romanian unions have maintained a high protest capacity throughout the transition. However, this protest capacity has translated into influence over national economic policy and labor-relevant legislation only throughout the 1990s, and much less so in the 2000s and beyond. The authors examine the reasons for the trade unions’ diminishing influence over national policies and observe a refinement of government measures to render protest ineffective. Key measures include a reduction of the unionized labor force, especially in protest-prone sectors, the de-coupling of plant-level protests from national mobilizations, the granting of selective concessions dividing organized labor, and, more recently, efforts to employ legal changes and state agencies to apply pressure on union leaders.
Intra-European labour migration and deteriorating employment relations in Danish cleaning and agriculture: Industrial relations under pressure from EU8/2 labour inflows?
Authors: Refslund Bjarke
Published: November 2014

Eastern and Central European labour migration following the EU enlargement has significant impact on the Nordic labour markets. This article demonstrates, through sector-based case studies in Denmark, how labour migration influences working condition and wages in two sectors that have so far only been sparsely studied: the agriculture and cleaning industries. The high inflow of labour migrants is used by some employers to bypass and undermine the institutionalized class compromise, by employing EU8/2-workers at lower wages and often without collective agreements coverage frequently combined with below average working conditions. This put strains on the Danish agreement-based model of industrial relations, potentially leading to a more segmented labour market as well as replacement of native, mainly low-skilled workers with EU8/2-workers.
Immigrants and job satisfaction: Do high performance work systems play a role?
Authors: Chowhan James , Zeytinoglu Isik U , Cooke Gordon B
Published: November 2014

This study focuses on immigrants in Canada and examines their job satisfaction as compared to Canadian-born employees. The authors explore whether high performance work systems (HPWS) affect immigrant employees’ job satisfaction differently than Canadian-born, where HPWS include empowerment, motivation and skill enhancing sub-bundles of practices. The study uses Statistics Canada’s Workplace and Employee Survey, a longitudinal dataset consisting of six years of data from 1999 to 2004 and 49,344 employees. Ordered logistic regression analyses are used to explore causal relationships. The moderation results show that increases in the motivation sub-bundle and increases in overall experience of HPWS practices are related to increases in job satisfaction among immigrants when compared to Canadian-born employees. Immigrants are a segment of the workforce that is understudied in management. This study identifies HPWS bundles that positively affect immigrants’ job satisfaction, suggesting a role for managers to capitalize on job satisfaction improvements ultimately contributing to organizational success.
The economic effects of works councils: channels and conditions. Using secondary data to test a new theoretical model
Authors: Wigboldus Jan Ekke , Grift Yolanda , van den Berg Annette , Looise Jan Kees
Published: November 2014

German studies already have supported the existing positive economic effects of works councils, but failed to explain how these effects are produced. New case study based research from the Netherlands has provided a theory consisting of three channels to create economic impact, also including a set of necessary conditions. This article presents a secondary analysis of this theory with the use of a large data set. This quantitative analysis further supports the theory and contains interesting nuances about how the channels work, in particular about the role of the availability of sufficient works council candidates at elections.
Analysis of Italian medium-sized enterprises’ collective bargaining from an international perspective: Evidence from the manufacturing sector
Authors: Signoretti Andrea
Published: November 2014

The article analyses local collective bargaining in seven medium-sized manufacturing firms operating in Northern Italy. The goals are to understand, within an international perspective, the degree of development of Italian MEs’ collective bargaining, and its outcomes in the construction of participative industrial relations and innovative forms of work organisation. The analysis highlights a ‘low-decentralised collective bargaining system’, where the concrete regulatory space exerted by company collective contracts is usually limited. Then, industrial relations turn out to be characterised neither by participation nor by conflict, from which come forms of work organisation based on a good quantitative mutual availability, like overtime and related payments, among social actors, but with poor results in terms of more qualitative aspects. Institutions and the prevailing culture of industrial relations turn out to be the main explanatory factors, requiring a more profound reflection on the Italian system of industrial relations.