bluuebunny/crossref_metadata_2025 huggingface dataset:
The need for richness‐independent measures of turnover when delineating biogeographical regions
Authors: Leprieur Fabien , Oikonomou Anthi
Published: January 2014

Delineating biogeographical regions is one of the primary steps when analysing biogeographical patterns. In their proposed quantitative framework, Kreft & Jetz (2010, Journal of Biogeography, 37, 2029–2053) recommended the use of the βsim index to delineate biogeographical regions because this turnover measure is weakly affected by differences in species richness between localities. A recent study by Carvalho et al. (2012, Global Ecology and Biogeography, 21, 760–771) critiziced the use of βsim in ecological and biogeographical studies, and proposed the β‐3 index. Here we used simple numerical examples and an empirical case study (European freshwater fishes) to highlight potential pitfalls associated with the use of β‐3 for bioregionalization. We show that β‐3 is not a richness‐independent measure of species turnover. We also show that this index violates the ‘complementarity’ property, namely that localities without species in common have the largest dissimilarity, which is an essential prerequisite for beta diversity studies.
Crosstalk between AMPK activation and angiotensin II‐induced hypertrophy in cardiomyocytes: the role of mitochondria
Authors: Hernández Jessica Soto , Barreto‐Torres Giselle , Kuznetsov Andrey V. , Khuchua Zaza , Javadov Sabzali
Published: January 2014

AMP‐kinase (AMPK) activation reduces cardiac hypertrophy, although underlying molecular mechanisms remain unclear. In this study, we elucidated the anti‐hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53 pathway. H9c2 rat cardiomyocytes were treated with angiotensin II (AngII) for 24 hrs in the presence or absence of metformin (AMPK agonist), losartan [AngII type 1 receptor (AT1R) blocker], Nω‐nitro‐L‐arginine methyl ester (L‐NAME, pan‐NOS inhibitor), splitomicin (SIRT1 inhibitor) or pifithrin‐α (p53 inhibitor). Results showed that treatment with metformin significantly attenuated AngII‐induced cell hypertrophy and death. Metformin attenuated AngII‐induced activation (cleavage) of caspase 3, Bcl‐2 down‐regulation and p53 up‐regulation. It also reduced AngII‐induced AT1R up‐regulation by 30% (P < 0.05) and enhanced AMPK phosphorylation by 99% (P < 0.01) and P‐eNOS levels by 3.3‐fold (P < 0.01). Likewise, losartan reduced AT1R up‐regulation and enhanced AMPK phosphorylation by 54% (P < 0.05). The AMPK inhibitor, compound C, prevented AT1R down‐regulation, indicating that metformin mediated its effects via AMPK activation. Beneficial effects of metformin and losartan converged on mitochondria that demonstrated high membrane potential (Δψm) and low permeability transition pore opening. Thus, this study demonstrates that the anti‐hypertrophic effects of metformin are associated with AMPK‐induced AT1R down‐regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.
Nonlinear effects of temperature on body form and developmental canalization in the threespine stickleback
Authors: Ramler D. , Mitteroecker P. , Shama L. N. S. , Wegner K. M. , Ahnelt H.
Published: January 2014

Theoretical models predict that nonlinear environmental effects on the phenotype also affect developmental canalization, which in turn can influence the tempo and course of organismal evolution. Here, we used an oceanic population of threespine stickleback (Gasterosteus aculeatus) to investigate temperature‐induced phenotypic plasticity of body size and shape using a paternal half‐sibling, split‐clutch experimental design and rearing offspring under three different temperature regimes (13, 17 and 21 °C). Body size and shape of 466 stickleback individuals were assessed by a set of 53 landmarks and analysed using geometric morphometric methods. At approximately 100 days, individuals differed significantly in both size and shape across the temperature groups. However, the temperature‐induced differences between 13 and 17 °C (mainly comprising relative head and eye size) deviated considerably from those between 17 and 21 °C (involving the relative size of the ectocoracoid, the operculum and the ventral process of the pelvic girdle). Body size was largest at 17 °C. For both size and shape, phenotypic variance was significantly smaller at 17 °C than at 13 and 21 °C, indicating that development is most stable at the intermediate temperature matching the conditions encountered in the wild. Higher additive genetic variance at 13 and 21 °C indicates that the plastic response to temperature had a heritable basis. Understanding nonlinear effects of temperature on development and the underlying genetics are important for modelling evolution and for predicting outcomes of global warming, which can lead not only to shifts in average morphology but also to destabilization of development.
Validation of the Charlson Comorbidity Index in Acutely Hospitalized Elderly Adults: A Prospective Cohort Study
Authors: Frenkel Wijnanda J. , Jongerius Erika J. , Mandjes‐van Uitert Miranda J. , van Munster Barbara C. , de Rooij Sophia E.
Published: January 2014

Objectives

To determine whether the Charlson Comorbidity Index (CCI) predicts short‐ and long‐term mortality.

Design

Prospective cohort study.

Setting

The medical department of two university hospitals and one community‐based hospital.

Participants

Acutely hospitalized individuals aged 65 and older with a mean age of 77.8 ± 7.9, 45.8% male (n = 1,313).

Measurements

In eligible persons, information on demographic characteristics, activities of daily living (modified Katz ADL Index score), and disease‐related measures was collected within 48 hours after admission. Follow‐up using self‐reporting questionnaires was performed at 3 months and 1 year. Functional decline was defined as a decline of at least 1 point on the modified Katz ADL Index score at 12 months from baseline. Mortality data at 3 months and 1 and 5 years were collected from the municipal database.

Results

Logistic regression analysis, adjusted for age and sex, showed that participants with a CCI of 5 or more had higher 3‐month (odds ratio (OR) = 3.6, 95% confidence interval (CI) = 2.1–6.4), 1‐year (OR = 7.1, 95% CI = 4.2–11.9), and 5‐year (OR = 52.4, 95% CI = 13.3–206.4) mortality than those with a CCI of 0. Participants with CCI scores between 1 and 4 also had greater mortality risk at 3 months and 1 and 5 years.

Conclusion

The CCI independently predicts short‐ and long‐term mortality in acutely ill hospitalized elderly adults.
Executive Function Processes Predict Mobility Outcomes in Older Adults
Authors: Gothe Neha P. , Fanning Jason , Awick Elizabeth , Chung David , Wójcicki Thomas R. , Olson Erin A. , Mullen Sean P. , Voss Michelle , Erickson Kirk I. , Kramer Arthur F. , McAuley Edward
Published: January 2014

Objectives

To examine the relationship between performance on executive function measures and subsequent mobility outcomes in community‐dwelling older adults.

Design

Randomized controlled clinical trial.

Setting

Champaign‐Urbana, Illinois.

Participants

Community‐dwelling older adults (N = 179; mean age 66.4).

Intervention

A 12‐month exercise trial with two arms: an aerobic exercise group and a stretching and strengthening group.

Measurements

Established cognitive tests of executive function (flanker task, task switching, and a dual‐task paradigm) and the Wisconsin card sort test. Mobility was assessed using the timed 8‐foot up and go test and times to climb up and down a flight of stairs.

Methods

Participants completed the cognitive tests at baseline and the mobility measures at baseline and after 12 months of the intervention. Multiple regression analyses were conducted to determine whether baseline executive function predicted postintervention functional performance after controlling for age, sex, education, cardiorespiratory fitness, and baseline mobility levels.

Results

Selective baseline executive function measurements, particularly performance on the flanker task (β = 0.15–0.17) and the Wisconsin card sort test (β = 0.11–0.16) consistently predicted mobility outcomes at 12 months. The estimates were in the expected direction, such that better baseline performance on the executive function measures predicted better performance on the timed mobility tests independent of intervention.

Conclusion

Executive functions of inhibitory control, mental set shifting, and attentional flexibility were predictive of functional mobility. Given the literature associating mobility limitations with disability, morbidity, and mortality, these results are important for understanding the antecedents to poor mobility function that well‐designed interventions to improve cognitive performance can attenuate.
Radiographic thoracic anatomy of the ring‐tailed lemur (Lemur catta)
Authors: Makungu Modesta , du Plessis Wencke M. , Barrows Michelle , Groenewald Hermanus B. , Koeppel Katja N.
Published: January 2014

Background

The ring‐tailed lemur (Lemur catta) is a quadruped arboreal primate primarily distributed in south and south‐westernMadagascar. This study was carried out to describe the normal radiographic thoracic anatomy of the ring‐tailed lemur as a reference for clinical use.

Methods

Radiography of the thorax was performed in 15 captive ring‐tailed lemurs during their annual health examinations.

Results

Normal radiographic reference ranges for thoracic structures were established and ratios were calculated, such as the vertebral heart score (VHS). The meanVHSon the right lateral and dorsoventral views was 8.92 ± 0.47 and 9.42 ± 0.52, respectively.

Conclusions

Differences exist in the normal radiographic thoracic anatomy of primates. Knowledge of the normal radiographic thoracic anatomy of individual species is important and fundamental to assist in clinical cases and for accurate diagnosis of diseases.
Tnfaip8 l1/Oxi‐β binds to FBXW5, increasing autophagy through activation of TSC2 in a Parkinson's disease model
Authors: Ha Ji‐Young , Kim Ji‐Soo , Kang Young‐Hee , Bok Eugene , Kim Yoon‐Seong , Son Jin H.
Published: January 2014

Abnormal autophagy may contribute to neurodegeneration in Parkinson's disease (PD). However, it is largely unknown how autophagy is dysregulated by oxidative stress (OS), one of major pathogenic causes of PD. We recently discovered the potential autophagy regulator gene family including Tnfaip8/Oxi‐α, which is a mammalian target of rapamycin (mTOR) activator down‐regulated by OS in dopaminergic neurons (J. Neurochem., 112, 2010, 366). Here, we demonstrate that the OS‐induced Tnfaip8 l1/Oxi‐β could increase autophagy by a unique mechanism that increases the stability of tuberous sclerosis complex 2 (TSC2), a critical negative regulator of mTOR. Tnfaip8 l1/Oxi‐β and Tnfaip8/Oxi‐α are the novel regulators of mTOR acting in opposition in dopaminergic (DA) neurons. Specifically, 6‐hydroxydopamine (6‐OHDA) treatment up‐regulated Tnfaip8 l1/Oxi‐β in DA neurons, thus inducing autophagy, while knockdown of Tnfaip8 l1/Oxi‐β prevented significantly activation of autophagic markers by 6‐OHDA. FBXW5 was identified as a novel binding protein for Tnfaip8 l1/Oxi‐β. FBXW5 is a TSC2 binding receptor within CUL4 E3 ligase complex, and it promotes proteasomal degradation of TSC2. Thus, Tnfaip8 l1/Oxi‐β competes with TSC2 to bind FBXW5, increasing TSC2 stability by preventing its ubiquitination. Our data show that the OS‐induced Tnfaip8 l1/Oxi‐β stabilizes TSC2 protein, decreases mTOR phosphorylation, and enhances autophagy. Therefore, altered regulation of Tnfaip8 l1/Oxi‐β may contribute significantly to dysregulated autophagy observed in dopaminergic neurons under pathogenic OS condition.

image

Dysfunctional autophagy is frequently observed in post‐mortem brains of patients and animal models of Parkinson's disease. In dopaminergic neurons of the 6‐hydroxydopamine (6‐OHDA) model, oxidative stress induces Tnfaip8 l1/Oxi‐β, which results in increased autophagy by its exclusive binding with FBXW5 to stabilize TSC2. Thus, altered regulation of Tnfaip8 l1/Oxi‐β may contribute to dysregulated autophagy in dopaminergic neurons under pathogenic oxidative stress, implicating both Oxi‐β and FBXW5 as potential intervention targets for dysfunctional autophagy in dopaminergic neurons under oxidative stress.
Human body preservation – old and new techniques
Authors: Brenner Erich
Published: January 2014

This review deals with the art of (anatomical) embalming. The first part contains a brief historical review of the history of embalming, starting with ancient cultures such as the Egyptians and the lesser known Chinchorro culture, then going down the centuries and describing the anatomical techniques developed over the last two centuries. The second part deals in detail with the chemicals used for embalming purposes. The third part deals with several approaches to evaluating embalming methods, their suitability for biomechanical testing, antimicrobial properties, histological appearance, and usability. The fourth and final part analyze the European Biocidal Products Directive (98/8/EC) in the light of embalming.
A moderated mediation analysis of job demands, presenteeism, and absenteeism
Authors: Deery Stephen , Walsh Janet , Zatzick Christopher D.
Published: January 2014

Presenteeism or attending work while ill is a growing organizational problem. This study examined the association between job demands, presenteeism, and absenteeism. We tested a moderated mediation model of the effects of job demands on absenteeism with the key objective of exploring the mediation effects of presenteeism and the moderating effects of organizational justice on this relationship. Based on a sample of emergency services call centre workers (N = 227), the research revealed that high job demands were associated with presenteeism, which in turn predicted longer absence spells. Furthermore, employee perceptions of distributive justice acted as an important mechanism through which presenteeism mediated the relationship between job demands and absenteeism.

Practitioner points

Organizations should be aware that work overload and strict attendance management practices can stimulate presenteeism.

Managers should recognize that presenteeism can subsequently lead to longer spells of absence.

Employee perceptions of fair outcomes minimize the deleterious effects of presenteeism on absenteeism.
Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders
Authors: Peck C. C. , Goulet J‐P. , Lobbezoo F. , Schiffman E. L. , Alstergren P. , Anderson G. C. , de Leeuw R. , Jensen R. , Michelotti A. , Ohrbach R. , Petersson A. , List T.
Published: January 2014

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus‐based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long‐term aim was to establish a foundation, vis‐à‐vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.
SYMPTOM CLUSTERS IN PATIENTS ON DIALYSIS AND THEIR ASSOCIATION WITH QUALITY‐OF‐LIFE OUTCOMES
Authors: Amro Amin , Waldum Bård , Dammen Toril , Miaskowski Christine , Os Ingrid
Published: January 2014

Background

Patients who are on dialysis report multiple symptoms. The aim of the study was to explore and identify symptom clusters (co‐occurring symptoms) in patients on dialysis and their possible associations with depressive symptoms and health‐related quality‐of‐life (HRQOL) outcomes.

Methods

In a cross‐sectional study of 301 prevalent patients on dialysis, physical symptoms, depressive symptoms and HRQOL were assessed using the Beck Depression Inventory (BDI) and the Kidney Disease and Quality‐of‐Life‐Short Form version 1.3 (KDQOL‐SF36) questionnaires. Symptom clusters were identified using principal component analysis with varimax rotation. Multivariate linear regression analyses were carried out to evaluate the relationships between symptom clusters and depressive symptoms and HRQOL outcomes.

Results

The majority of patients (63.5%) rated their symptoms in the ‘very much’ to ‘extremely bothersome’ range, and 29.4% had significant depressive symptoms. Three symptom clusters were identified and were named uraemic (nausea, lack of appetite, dizziness/faintness, feeling squeezed out, shortness of breath, chest pain), neuromuscular (numbness in extremities, sore muscles, cramps) and skin (itching, dry skin) clusters. The three clusters were associated with BDI, physical component summary (PCS) and mental component summary (MCS) scores. After multiple adjustments, the uraemic and neuromuscular clusters remained independently associated with BDI and PCS scores and the uraemic and skin clusters with MCS scores.

Conclusion

The strong associations between symptom clusters and depressive symptoms and the physical and mental domains of HRQOL should lead to an increased focus on symptom‐alleviating interventions. Additional research is warranted to determine whether treatment of symptom clusters rather than single symptoms will improve HRQOL.
Medications at School: Disposing of Pharmaceutical Waste
Authors: Taras Howard , Haste Nina M. , Berry Angela T. , Tran Jennifer , Singh Renu F.
Published: January 2014

BACKGROUND

This project quantified and categorized medications left unclaimed by students at the end of the school year. It determined the feasibility of a model medication disposal program and assessed school nurses' perceptions of environmentally responsible medication disposal.

METHODS

At a large urban school district all unclaimed medications were collected at the end of a school year to determine the extent and nature of this problem. Nurses documented unclaimed medications and transported them to a central district location. An environmentally responsible medication disposal program, consisting of sealed containers bound for a local hospital's disposal system, was implemented.

RESULTS

In a school district of approximately 133,000 students, there were 926 different medications abandoned at the end of a school year brought to a central disposal area. Nurses complied with the newly implemented protocol. Information collected from nurses indicates acceptance of the program. Disposal of unclaimed medications at a central location, use of secured containers, and transportation to a hospital for environmentally responsible disposal proved to be feasible and acceptable to the staff.

CONCLUSIONS

Unclaimed medications at school each year pose a potentially huge environmental risk when disposed of improperly. It is feasible to implement an environmentally responsible medication disposal protocol at schools.
Sugar‐Sweetened Beverage Consumption Among a Subset of Canadian Youth
Authors: Vanderlee Lana , Manske Steve , Murnaghan Donna , Hanning Rhona , Hammond David
Published: January 2014

BACKGROUND

Sugar‐sweetened beverages (SSBs) may play a role in increased rates of obesity. This study examined patterns and frequencies of beverage consumption among youth in 3 distinct regions in Canada, and examined associations between beverage consumption and age, sex, body mass index (BMI), physical activity and dieting behavior, as well as beverage displacement.

METHODS

The study included data from 10,188 youth (ages 13‐18) from Hamilton and Thunder Bay, Ontario, and Prince Edward Island (PEI) in 2009 to 2010. The study used in‐school self‐reported surveys with 12 questions regarding beverage consumption during the previous day, along with self‐reported height, weight, physical activity levels, and demographic information. Logistic regression analyses were conducted to examine variables associated with SSB intake.

RESULTS

Overall, 80% of youth consumed at least 1 SSB in the previous day, with 44% consuming 3 or more SSBs. Youth in Thunder Bay consumed significantly more SSBs than Hamilton and PEI, and youth in Hamilton consumed more SSBs than PEI. Boys consumed significantly more SSBs than girls. Older and more physically active youth consumed significantly fewer SSBs. No significant association between BMI and SSB consumption was observed in any model. A modest positive correlation was identified between SSB consumption and milk (r = .06, p < .001) and 100% fruit juice (r = .10, p < .001).

CONCLUSIONS

A large proportion of youth consumed SSBs, many at high levels. Research evaluating SSB policy and interventions should be considered a priority.
Mitochondria as promising targets for nutritional interventions aiming to improve performance and longevity of sows
Authors: Lapointe J.
Published: January 2014

Genetic selection and management changes during the last decades have significantly increased the average litter size of sows. However, this recent success has not correlated with an extension of longevity and reduction in replacement rate. Longevity or lifetime production of sows is determined by a combination of environmental and genetic factors. Nutrition is an environmental factor of importance, and it has long been appreciated that animals fed with specific diets may perform differently. The advent of modern science revealed that this is partly due to the ability of nutrients to act as signalling molecules that, through appropriate intracellular sensing mechanisms, can control gene expression and modulate cell functions. Based on this concept, nutrigenomics studies now aim to show that not only are certain nutrients essential for general health, but also that specific quantities of precise nutrients are necessary during critical periods of energy deficiency and oxidative stress such as gestation and lactation to ensure long‐term productivity. The toxic molecules at the origin of oxidative stress, free radicals, are mainly generated as normal by‐products of aerobic energy production by mitochondria. In all cells, mitochondria are dynamic organelles that are mainly known as the primary energy‐generating system. Thus, when metabolic demands are elevated as it is for hyperprolific sows, mitochondria are heavily solicited for answering all energetic needs, and substantive amounts of free radicals are generated. As a result, optimal conditions in term of antioxidant protection and metabolic substrates availability are required to support mitochondrial function in these animals. This article discusses how performance and longevity of sows are linked to mitochondrial function and oxidative stress and reviews the major natural nutrients known for their antioxidant and/or energetic properties that are susceptible to impact mitochondria and likely improved sows productivity.
Assessment of Ospemifene or Lubricants on Clinical Signs of VVA
Authors: Constantine Ginger , Graham Shelli , Koltun William D. , Kingsberg Sheryl A.
Published: January 2014

Introduction

Ospemifene is a new oral estrogen receptor agonist/antagonist with tissue-selective effects approved for the treatment of moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy (VVA).

Aim

The aim of the study is to assess ospemifene or lubricant use on the clinical signs of VVA.

Methods

Subjects in three double-blind, placebo-controlled clinical trials were randomized to ospemifene or placebo. In two of the trials, women were provided nonhormonal lubricants for use as needed, and a preplanned evaluation of the frequency of lubricant use was performed. Additionally, a post hoc placebo group analysis for impact of lubricant use or nonuse on physiologic effects of the percentage of superficial and parabasal cells (maturation index) and vaginal pH was conducted. A secondary preplanned end point included visual examination of the vagina (clinical signs of vaginal dryness, petechiae, pallor, friability, and redness of the mucosa) comparing change from baseline to end of treatment for the ospemifene 60-mg/day group and vs. placebo.

Main Outcome Measures

The primary end points in the phase 3 clinical trials included the percentage of superficial cells, parabasal cells, vaginal pH, and most bothersome symptoms compared with placebo.

Results

There was no significant difference in physiologic effects between placebo lubricant users vs. nonusers in either 12-week study. Compared with baseline, substantially more subjects receiving ospemifene 60 mg/day than placebo showed complete resolution of clinical signs of VVA after 12 and 52 weeks of treatment.

Conclusions

Ospemifene substantially improved clinical signs of VVA. Within the placebo group, there was no difference in physiologic effects in lubricant users vs. nonusers. Based on gynecologic evaluation of the vagina, benefits were apparent at 12 weeks and sustained for 52 weeks in the ospemifene-treated subjects with significant improvement over placebo. In these three clinical trials, in contrast to ospemifene-treated women, placebo subjects who utilized lubricants had no improvement in their underlying vaginal physiology.
Testosterone Replacement Therapy Following the Diagnosis of Prostate Cancer: Outcomes and Utilization Trends
Authors: Kaplan Alan L. , Trinh Quoc-Dien , Sun Maxine , Carter Stacey C. , Nguyen Paul L. , Shih Ya-Chen Tina , Marks Leonard S. , Hu Jim C.
Published: January 2014

Introduction

Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population.

Aim

The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer.

Methods

Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1,181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality.

Main Outcome Measures

We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy.

Results

Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy.

Conclusions

In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed.
A touch of glue to complete bacteriophage assembly: the tail‐to‐head joining protein (THJP) family
Authors: Auzat Isabelle , Petitpas Isabelle , Lurz Rudi , Weise Frank , Tavares Paulo
Published: January 2014

Bacteriophage SPP1 is a nanomachine built to infect the bacterium Bacillus subtilis. The phage particle is composed of an icosahedric capsid, which contains the viral DNA, and a long non‐contractile tail. Capsids and tails are produced in infected cells by two distinct morphogenetic pathways. Characterization of the suppressor‐sensitive mutant SPP1sus82 showed that it produces DNA‐filled capsids and tails but is unable to assemble complete virions. Its purified tails have a normal length but lack a narrow ring that tapers the tail end found at the tail‐to‐head interface. The mutant is defective in production of gp17. The gp17 ring is exposed in free tails competent for viral assembly but becomes shielded in the final virion structure. Recombinant gp17 is active in an in vitro assay to stick together capsids and tails present in extracts of SPP1sus82‐infected cells, leading to formation of infectious particles. Gp17 thus plays a fundamental role in the tail‐to‐head joining reaction, the ultimate step of virus particle assembly. This is the conserved function of gp17 and its structurally related proteins like lambda gpU. This family of proteins can also provide fidelity to termination of the tail tube elongation reaction in a subset of phages including coliphage lambda.
Environment sensing in spring‐dispersed seeds of a winter annual Arabidopsis influences the regulation of dormancy to align germination potential with seasonal changes
Authors: Footitt Steven , Clay Heather A. , Dent Katherine , Finch‐Savage William E.
Published: January 2014

Seed dormancy cycling plays a crucial role in the lifecycle timing of many plants. Little is known of how the seeds respond to the soil seed bank environment following dispersal in spring into the short‐term seed bank before seedling emergence in autumn.

Seeds of the winter annual Arabidopsis ecotype Cvi were buried in field soils in spring and recovered monthly until autumn and their molecular eco‐physiological responses were recorded.

DOG1 expression is initially low and then increases as dormancy increases. MFT expression is negatively correlated with germination potential. Abscisic acid (ABA) and gibberellin (GA) signalling responds rapidly following burial and adjusts to the seasonal change in soil temperature. Collectively these changes align germination potential with the optimum climate space for seedling emergence.

Seeds naturally dispersed to the soil in spring enter a shallow dormancy cycle dominated by spatial sensing that adjusts germination potential to the maximum when soil environment is most favourable for germination and seedling emergence upon soil disturbance. This behaviour differs subtly from that of seeds overwintered in the soil seed bank to spread the period of potential germination in the seed population (existing seed bank and newly dispersed). As soil temperature declines in autumn, deep dormancy is re‐imposed as seeds become part of the persistent seed bank.
Type I interferon signature in the initiation of the immune response in vitiligo
Authors: Bertolotti Antoine , Boniface Katia , Vergier Beatrice , Mossalayi Djavad , Taieb Alain , Ezzedine Khaled , Seneschal Julien
Published: January 2014

Immune‐mediated responses are consistently observed in progressing vitiligo at the edge of depigmenting patches. Besides the role of the adaptive immune system, the profile of the innate immune response is now at the center of the stage. We report that plasmacytoid dendritic cells (pDC), which are the major interferon (IFN)‐alpha‐producing cells, are part of the infiltrate of progressive vitiligo with local production of MxA (a protein induced by IFNα). MxA was associated with expression of the type I IFN‐inducible ligand CXCL9 and correlated with the recruitment of CXCR3+ immune cells. Interestingly, strong MxA expression was observed in perilesional skin in close apposition to remaining melanocytes, surrounded by a prominent T‐cell infiltrate. In contrast, MxA was not detectable in lesional skin, suggesting that IFN‐α production is an early event in the progression of the disease. Our data highlight a new innate immune pathway leading to progression of vitiligo.
Differential patterns of neuropsychological performance in the euthymic and depressive phases of bipolar disorders
Authors: Ha Tae Hyon , Chang Jae Seung , Oh Sung Hee , Kim Ji Sun , Cho Hyun Sang , Ha Kyooseob
Published: January 2014

Aims

Patients with bipolar disorders (BD) show a broad range of neurocognitive impairments. We compared the patterns of neuropsychological performance in depressed and euthymic patients with BD, and explored the state‐dependent cognitive markers of bipolar depression.

Methods

The study participants included 32 BD patients (15 depressed and 17 euthymic) and 42 healthy controls. All of the subjects completed tests that assessed attention, psychomotor speed, verbal and visual memory, and executive functions. Between‐group neuropsychological performance differences were examined. Multidimensional scaling (MDS) was used to compare the patterns of cognitive variables in euthymic and depressed BD patients.

Results

Compared to the euthymic BD patients and healthy controls, the depressed BD patients performed lower in verbal memory and executive functions. No significant differences were found between the three groups in attention, psychomotor speed, and visual memory. The depressed BD patients showed a lower level of association between psychomotor speed and the time to initial concept formation than the healthy controls and euthymic BD patients. In contrast, the correlation between word association and verbal memory was stronger in the depressed group than either the control or euthymic groups.

Conclusion

The depressed BD patients showed greater impairments in verbal memory and executive functions than the euthymic BD patients. In addition, our study identified a differential pattern of correlations between the cognitive domains of euthymic and depressed BD patients, which suggests the potential role of verbal memory and executive functions as cognitive markers of BD.
Ovarian development and modes of apoptosis during oogenesis in various castes of the termite Reticulitermes aculabialis
Authors: SU XIAO‐HONG , WEI YAN‐HONG , LIU MING‐HUA
Published: January 2014

Reproductive division in termites is the most significant biological process that leads to the formation of caste‐specific differences in tasks and status. However, little is known about the mechanism of reproductive division that underlies caste differentiation. In the present study, ovarian development and stage‐specific apoptotic patterns are investigated during oogenesis in reproductive, worker and soldier termites Reticulitermes aculabialis Tsai & Hwang. The results show that the mean lengths of the ovaries of reproductives are two‐fold longer compared with those of workers and six‐fold longer compared with soldiers. By contrast to the reproductives, the process of oogenesis in the workers includes only the oogonium differentiation stage (stage I) and oocyte growth stage (stage II), and oogenesis in the soldiers stops at stage I. Vitelogenic oocytes (stage III) are absent from workers and soldiers. During stage II in the reproductives and workers, the layer of follicle cells has a thickness of 7.56 ± 0.52 and 2.81 ± 0.34 µm, respectively. In addition, there are significant differences in the number and size of the germ cells at the same stage in the various castes. The existence of two apoptotic patterns during oogenesis is demonstrated by the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) assay. First, the majority of the cells showing apoptosis occur at stage I of oogenesis in reproductives, workers and soldiers. Second, DNA fragmentation is demonstrated by TUNEL staining of the follicle cell layers and oocytes at stage II in reproductives. Finally, the proliferation activity of follicle cells in the reproductives is observed by 5‐bromo‐2′‐deoxy‐uridine labelling. The level of oogenesis may explain the significant discrepancies in the reproductive capacity among the reproductives, soldiers and workers. These large discrepancies are controlled by apoptosis during early oogenesis.
Effect of Light on Expression of Clock Genes in Xenopus laevis Melanophores
Authors: Magalhães Moraes Maria Nathália de Carvalho , de Oliveira Poletini Maristela , Ribeiro Ramos Bruno Cesar , de Lima Leonardo Henrique Ribeiro Graciani , de Lauro Castrucci Ana Maria
Published: January 2014

Light–dark cycles are considered important cues to entrain biological clocks. A feedback loop of clock gene transcription and translation is the molecular basis underlying the mechanism of both central and peripheral clocks. Xenopus laevis embryonic melanophores respond to light with melanin granule dispersion, response possibly mediated by the photopigment melanopsin. To test whether light modulates clock gene expression in Xenopus melanophores, we used qPCR to evaluate the relative mRNA levels of Per1, Per2, Clock and Bmal1 in cultured melanophores exposed to light–dark (LD) cycle or constant darkness (DD). LD cycles elicited temporal changes in the expression of Per1, Per2 and Bmal1. A 10‐min pulse of blue light was able to increases the expression of Per1 and Per2. Red light had no effect on the expression of these clock genes. These data suggest the participation of a blue‐wavelength sensitive pigment in the light–dark cycle‐mediated oscillation of the endogenous clock. Our results add an important contribution to the emerging field of peripheral clocks, which in nonmammalian vertebrates have been mostly studied in Drosophila and Danio rerio. Within this context, we show that X. laevis melanophores, which have already led to melanopsin discovery, represent an ideal model to understanding circadian rhythms.
Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia
Authors: Shortt Christine M. , Fredsted Anne , Chow Han Bing , Williams Robert , Skelly J. Richard , Edge Deirdre , Bradford Aidan , O'Halloran Ken D.
Published: January 2014

New Findings

What is the central question of this study?

The effects of chronic intermittent hypoxia (CIH) on respiratory muscles are relatively underexplored. It is speculated that muscle dysfunction and other key morbidities associated with sleep apnoea are the result of CIH‐induced oxidative stress. We sought to investigate the putative role of CIH‐induced reactive oxygen species in the development of respiratory muscle dysfunction.

What is the main finding and its importance?

The CIH‐induced diaphragm muscle fatigue is time and intensity dependent and is associated with a modest oxidative stress. Supplementation with N‐acetyl cysteine prevents CIH‐induced diaphragm muscle dysfunction, suggesting that antioxidant supplementation may have therapeutic value in respiratory muscle disorders characterized by CIH, such as obstructive sleep apnoea.

Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to explore the effects of different CIH protocols on respiratory muscle form and function in a rodent model. Adult male Wistar rats were exposed to CIH (n = 32) consisting of 90 s normoxia–90 s hypoxia (either 10 or 5% oxygen at the nadir; arterial O2 saturation ∼90 or 80%, respectively] for 8 h per day or to sham treatment (air–air, n = 32) for 1 or 2 weeks. Three additional groups of CIH‐treated rats (5% O2 for 2 weeks) had free access to water containing N‐acetyl cysteine (1% NAC, n = 8), tempol (1 mm, n = 8) or apocynin (2 mm, n = 8). Functional properties of the diaphragm muscle were examined ex vivo at 35°C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca2+‐ATPase isoform distribution, succinate dehydrogenase and glyercol phosphate dehydrogenase enzyme activities, Na+–K+‐ATPase pump content, concentration of thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2 weeks) decreased diaphragm muscle force and endurance. All three drugs reversed the deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH‐induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm muscle myosin heavy chain 2B areal density and oxidized glutathione/reduced glutathione (GSSG/GSH) ratio. We conclude that CIH‐induced diaphragm dysfunction is reactive oxygen species dependent. N‐Acetyl cysteine was most effective in reversing CIH‐induced effects on diaphragm. Our results suggest that respiratory muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as such, antioxidant treatment could prove a useful adjunctive therapy for the disorder.
A plasminogen activator inhibitor type 1 mutant retards diabetic nephropathy in db/db mice by protecting podocytes
Authors: Zhang Jiandong , Gu Chunyan , Lawrence Daniel A. , Cheung Alfred K. , Huang Yufeng
Published: January 2014

New Findings

What is the central question of this study?

The mechanism by which PAI‐1R reduces proteinuria has not been previously explored.

What is the main finding and its importance?

Using cultured podocytes and diabetic db/db mice, we show that, similar to the effects of transforming growth factor‐β1, PAI‐1 directly injures podocytes. Reducing the increased PAI‐1 activity by PAI‐1R in diabetic db/db mice, in fact, reduces podocyte injury, thereby reducing albuminuria. Therefore, PAI‐1R may provide an additional therapeutic effect in slowing progression of diabetic nephropathy by maintaining podocyte integrity.

A mutant non‐inhibiting plasminogen activator inhibitor type 1 (PAI‐1), termed PAI‐1R, which reduces endogenous PAI‐1 activity, has been shown to inhibit albuminuria and reduce glomerulosclerosis in experimental diabetes. The mechanism of the reduction of albuminuria is unclear. This study sought to determine whether the administration of PAI‐1R protected podocytes from injury directly, thereby reducing albuminuria in the db/db mouse, a model of type 2 diabetes. Untreated uninephrectomized db/db mice developed significant mesangial matrix expansion and albuminuria at week 22 of age, associated with segmental podocyte foot‐process effacement, reduction of renal nephrin, podocin and zonula occludin‐1 production and induction of renal desmin and B7‐1 generation. In contrast, treatment with PAI‐1R at 0.5 mg (kg body weight)−1 i.p., twice daily from week 20 to 22, reduced glomerular matrix accumulation, fibronectin and collagen production and albuminuria by 36, 62, 65 and 31%, respectively (P < 0.05), without affecting blood glucose level or body weight. Podocyte morphology and protein markers were also significantly attenuated by PAI‐1R administration. Importantly, recombinant PAI‐1 downregulated nephrin and zonula occludin‐1 but increased desmin and B7‐1 mRNA expression and protein production by podocytes in vitro, similar to the effects of transforming growth factor‐β1. These observations provide evidence that PAI‐1, in a manner similar to transforming growth factor‐β1, directly induces podocyte injury, particularly in the setting of diabetes, where elevated PAI‐1 may contribute to the progression of albuminuria. Reducing the increased PAI‐1 activity by administration of PAI‐1R, in fact, reduces podocyte injury, thereby reducing albuminuria. Therefore, PAI‐1R provides an additional therapeutic effect in slowing the progression of diabetic nephropathy via the protection of podocytes.
Gaussian and Gabor Filter Approach for Object Segmentation
Authors: Thilagamani S. , Shanthi N.
Published: January 2014

The problem of segmenting the object from the background is addressed in the proposed Gaussian and Gabor Filter Approach (GGFA) for object segmentation. An improved and efficient approach based on Gaussian and Gabor Filter reads the given input image and performs filtering and smoothing operation. The region occupied by the object is extracted from the image by performing various operations like bilateral filtering, Edge detection, Clustering, and Region growing. The proposed approach experimented on standard images taken from Caltech datasets, Corel Photo CDs, and Weizmann horse datasets show significantly improved results.
Comparison of Models Correlating Cumulative Oil Production and Water Cut
Authors: Cheng Changhui , Li Kewen
Published: January 2014

There have been many models to estimate reserves and predict oil production performance using the relationship between water cut, fw, (or water-oil ratio, WOR) and cumulative oil production (Np) in the literature. However, it is difficult to choose the suitable models for specific reservoirs. On the other hand, consistency and accuracy are yet to be improved. In this study, several frequently used models for predicting cumulative oil production using water cut have been compared using production data from low permeability reservoirs. These models include the conventional model, the Ershaghi–Omoregie model, the Purvis model, the Arps model, the Bondar–Blasingame model, and the Warren model. All of the models were applied to production data, respectively, and then compared in one single figure, that is, fw versus Np, for one set of production data from both reservoirs and the core sample. To do so, it facilitated the comparison of different models. Otherwise, it may be difficult to make the comparison for all of the models because the models have different dependent variables. The analysis and discussion to the results have been conducted. The results have demonstrated that no model could fit all of the cases studied. Each model has the advantages and limitations. However, the Warren model is better than the other five models statistically. It fits most of the cases studied satisfactorily.
Interpretation of Hydraulic Fracturing Pressure in Tight Gas Formations1
Authors: Kim Gun-Ho , Yilin Wang John
Published: January 2014

The interpretation of hydraulic fracturing pressure was initiated by Nolte and Smith in the 1980s. An accurate interpretation of hydraulic fracturing pressures is critical to understand and improve the fracture treatment in tight gas formations. In this paper, accurate calculation of bottomhole treating pressure was achieved by incorporating hydrostatic pressure, fluid friction pressure, fracture fluid property changes along the wellbore, friction due to proppant, perforation friction, tortuosity, casing roughness, rock toughness, and thermal and pore pressure effects on in-situ stress. New methods were then developed for more accurate interpretation of the net pressure and fracture propagation. Our results were validated with field data from tight gas formations.