bluuebunny/crossref_metadata_2025 huggingface dataset:
SimRare: a program to generate and analyze sequence-based data for association studies of quantitative and qualitative traits
Authors: Li Biao , Wang Gao , Leal Suzanne M.
Published: August 2012

Motivation: Currently, there is great interest in detecting complex trait rare variant associations using next-generation sequence data. On a monthly basis, new rare variant association methods are published. It is difficult to evaluate these methods because there is no standard to generate data and often comparisons are biased. In order to fairly compare rare variant association methods, it is necessary to generate data using realistic population demographic and phenotypic models.

Result: SimRare is an interactive program that integrates generation of rare variant genotype/phenotype data and evaluation of association methods using a unified platform. Variant data are generated for gene regions using forward-time simulation that incorporates realistic population demographic and evolutionary scenarios. Phenotype data can be obtained for both case–control and quantitative traits. SimRare has a user-friendly interface that allows for easy entry of genetic and phenotypic parameters. Novel rare variant association methods implemented in R can also be imported into SimRare, to evaluate their performance and compare results, e.g. power and Type I error, with other currently available methods both numerically and graphically.

Availability:  http://code.google.com/p/simrare/

Contact:  sleal@bcm.edu
An empirical Bayes mixture model for SNP detection in pooled sequencing data
Authors: Zhou Baiyu
Published: August 2012

Motivation: Detecting single-nucleotide polymorphism (SNP) in pooled sequencing data is more challenging than in individual sequencing because of sampling variations across pools. To effectively differentiate SNP signal from sequencing error, appropriate estimation of the sequencing error is necessary. In this article, we propose an empirical Bayes mixture (EBM) model for SNP detection and allele frequency estimation in pooled sequencing data.

Results: The proposed model reliably learns the error distribution by pooling information across pools and genomic positions. In addition, the proposed EBM model builds in characteristics unique to the pooled sequencing data, boosting the sensitivity of SNP detection. For large-scale inference in SNP detection, the EBM model provides a flexible and robust way for estimation and control of local false discovery rate. We demonstrate the performance of the proposed method through simulation studies and real data application.

Availability: Implementation of this method is available at https://sites.google.com/site/zhouby98

Contact:  baiyu.zhou@einstein.yu.edu
Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy
Authors: Franz Martin , Eiden Martin , Balkema-Buschmann Anne , Greenlee Justin , Schatzl Hermann , Fast Christine , Richt Jürgen , Hildebrandt Jan-Peter , Groschup Martin H.
Published: August 2012

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that mainly affects cattle. Transmission of BSE to humans caused a variant form of Creutzfeldt–Jakob disease. Following infection, the protease-resistant, disease-associated isoform of prion protein (PrPSc) accumulates in the central nervous system and in other tissues. Many countries have defined bovine tissues that may contain prions as specified risk materials, which must not enter the human or animal food chains and therefore must be discarded. Ultrasensitive techniques such as protein misfolding cyclic amplification (PMCA) have been developed to detect PrPSc when present in minuscule amounts that are not readily detected by other diagnostic methods such as immunohistochemistry or Western blotting. This study was conducted to determine when and where PrPSc can be found by PMCA in cattle orally challenged with BSE. A total of 48 different tissue samples from four cattle infected orally with BSE at various clinical stages of disease were examined using a standardized PMCA protocol. The protocol used brain homogenate from bovine PrP transgenic mice (Tgbov XV) as substrate and three consecutive rounds of PMCA. Using this protocol, PrPSc was found in the brain, spinal cord, nerve ganglia, optic nerve and Peyer’s patches. The presence of PrPSc was confirmed in adrenal glands, as well as in mesenteric lymph nodes – a finding that was reported recently by another group. Interestingly, additional positive results were obtained for the first time in the oesophagus, abomasum, rumen and rectum of clinically affected cattle.
Epidemiology and fitness effects of wood mouse herpesvirus in a natural host population
Authors: Knowles Sarah C. L. , Fenton Andy , Pedersen Amy B.
Published: August 2012

Rodent gammaherpesviruses have become important models for understanding human herpesvirus diseases. In particular, interactions between murid herpesvirus 4 and Mus musculus (a non-natural host species) have been extensively studied under controlled laboratory conditions. However, several fundamental aspects of murine gammaherpesvirus biology are not well understood, including how these viruses are transmitted from host to host, and their impacts on host fitness under natural conditions. Here, we investigate the epidemiology of a gammaherpesvirus in free-living wood mice (Apodemus sylvaticus) and bank voles (Myodes glareolus) in a 2-year longitudinal study. Wood mouse herpesvirus (WMHV) was the only herpesvirus detected and occurred frequently in wood mice and also less commonly in bank voles. Strikingly, WMHV infection probability was highest in reproductively active, heavy male mice. Infection risk also showed a repeatable seasonal pattern, peaking in spring and declining through the summer. We show that this seasonal decline can be at least partly attributed to reduced recapture of WMHV-infected adults. These results suggest that male reproductive behaviours could provide an important natural route of transmission for these viruses. They also suggest that gammaherpesvirus infection may have significant detrimental effects in wild hosts, questioning the view that these viruses have limited impacts in natural, co-evolved host species.
Evidence of bat origin for Menangle virus, a zoonotic paramyxovirus first isolated from diseased pigs
Authors: Barr Jennifer A. , Smith Craig , Marsh Glenn A. , Field Hume , Wang Lin-Fa
Published: August 2012

Menangle virus (MenPV) is a zoonotic paramyxovirus capable of causing disease in pigs and humans. It was first isolated in 1997 from stillborn piglets at a commercial piggery in New South Wales, Australia, where an outbreak of reproductive disease occurred. Neutralizing antibodies to MenPV were detected in various pteropid bat species in Australia and fruit bats were suspected to be the source of the virus responsible for the outbreak in pigs. However, previous attempts to isolate MenPV from various fruit bat species proved fruitless. Here, we report the isolation of MenPV from urine samples of the black flying fox, Pteropus alecto, using a combination of improved procedures and newly established bat cell lines. The nucleotide sequence of the bat isolate is 94 % identical to the pig isolate. This finding provides strong evidence supporting the hypothesis that the MenPV outbreak in pigs originated from viruses in bats roosting near the piggery.
A Bifunctional Enzyme That Has Both Monoacylglycerol Acyltransferase and Acyl Hydrolase Activities
Authors: Vijayaraj Panneerselvam , Jashal Charnitkaur B. , Vijayakumar Anitha , Rani Sapa Hima , Venkata Rao D.K. , Rajasekharan Ram
Published: August 2012

Monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of triacylglycerol biosynthesis and an important signaling molecule. Here, we describe the isolation and characterization of the peanut (Arachis hypogaea) MGAT gene. The soluble enzyme utilizes invariant histidine-62 and aspartate-67 residues of the acyltransferase motif for its MGAT activity. A sequence analysis revealed the presence of a hydrolase (GXSXG) motif, and enzyme assays revealed the presence of monoacylglycerol (MAG) and lysophosphatidylcholine (LPC) hydrolytic activities, indicating the bifunctional nature of the enzyme. The overexpression of the MGAT gene in yeast (Saccharomyces cerevisiae) caused an increase in triacylglycerol accumulation. Similar to the peanut MGAT, the Arabidopsis (Arabidopsis thaliana) homolog (At1g52760) also exhibited both acyltransferase and hydrolase activities. Interestingly, the yeast homolog lacks the conserved HX4D motif, and it is deficient in the acyltransferase function but exhibits MAG and LPC hydrolase activities. This study demonstrates the presence of a soluble MGAT/hydrolase in plants. The predicted three-dimensional homology modeling and substrate docking suggested the presence of two separate substrate (MAG and LPC)-binding sites in a single polypeptide. Our study describes a soluble bifunctional enzyme that has both MGAT and hydrolase functions.
Occupational disability in bipolar disorder: analysis of predictors of being on severe disablement benefit (PREBIS study data)
Authors: Grande I. , Goikolea J. M. , de Dios C. , González‐Pinto A. , Montes J. M. , Saiz‐Ruiz J. , Prieto E. , Vieta E. ,   for the PREBIS group
Published: August 2012

Grande I, Goikolea JM, de Dios C, González‐Pinto A, Montes JM, Saiz‐Ruiz J, Prieto E, Vieta E, for the PREBIS group. Occupational disability in bipolar disorder: analysis of predictors of being on severe disablement benefit PREBIS study data).

Objective:  Patients diagnosed with bipolar disorder (BD) are reported to have significant work impairment during interepisode intervals. This study was carried out to assess potential predictors of occupational disability in a longitudinal follow‐up of euthymic patients.

Method:  We included 327 euthymic patients diagnosed with BD type I or type II, 226 of whom were employed and 101 were receiving a severe disablement benefit (SDB). Sociodemographic data were studied and episode recurrence was assessed along a 1‐year follow‐up. Logistic regression analysis was applied to determine predictors of receiving SDB. Cox regression was built to study recurrences.

Results:  Predictors of receiving SDB were: axis II comorbidity [Odds Ratio (OR) = 2.94, CI: 1.26–6.86, P = 0.013], number of manic episodes (OR = 1.21, CI: 1.10–1.34, P < 0.001), being without stable partner (OR = 2.44, CI: 1.34–4.44, P = 0.004) and older age (OR = 1.08, CI: 1.05–1.12, P < 0.001). Bipolar patients receiving SDB presented more episodic recurrences regardless of polarity than employed bipolar patients (P = 0.002). The time until recurrence in 25% of the bipolar patients receiving SDB was 6.08 months (CI: 4.44–11.77) being 13.08 months (CI: 9.60 to –) in the employed group.

Conclusion:  Occupational disability in bipolar patients is associated with axis II comorbidity, more previous manic episodes, not having a stable relationship, older age, and more recurrences at 1‐year follow‐up.
Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin inhibitor, on food allergy in mice
Authors: Yamaki K. , Yoshino S.
Published: August 2012

Background

Because few curative treatments are available for food allergy, we investigated the therapeutic potential of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, on mouse food allergy.

Methods

The preventive and therapeutic effects of oral rapamycin on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in food allergy mice were investigated. Mast cell functions in response to rapamycin were also measured in the passive systemic anaphylaxis model and bone marrow–derived mast cells (BMMCs).

Results

Daily rapamycin from the first challenge (preventive protocol) attenuated food allergy symptoms including diarrhea, anaphylactic reactions, and hypothermia in mice. The treatment decreased the challenge‐induced increases in mouse mast cell protease‐1 in serum and mast cell numbers in the intestine. Notably, the mice that already showed food allergy symptoms by previous challenges recovered from the disease with daily administration of rapamycin (therapeutic protocol). Anti‐OVA IgG1 and IgE levels in serum, as well as IFN‐γ, IL‐4, IL‐13, IL‐9, IL‐10, and IL‐17 secretion from splenocytes, were decreased by the treatments. In contrast, a single dose of rapamycin failed to affect passive systemic anaphylaxis. Spontaneous and IL‐9‐dependent survival and IgE‐induced IL‐13 secretion, but not degranulation, of BMMCs were reduced by rapamycin.

Conclusion

Our data show that mouse food allergy was attenuated by rapamycin through an immunosuppressive effect and inhibition of intestinal mast cell hyperplasia. Inhibition of the IL‐9 production–mast cell survival axis is one of the mechanisms of the therapeutic effect of rapamycin. Rapamycin and other mTOR inhibitors might be good candidates for therapeutic drugs for food allergy.
Prevalence and clinical relevance of local allergic rhinitis
Authors: Rondón C. , Campo P. , Galindo L. , Blanca‐López N. , Cassinello M. S. , Rodriguez‐Bada J. L. , Torres M. J. , Blanca M.
Published: August 2012

Background

Evidence demonstrates the existence of local allergic rhinitis (LAR) in nonatopic patients, although its prevalence in the rhinitis population remains unknown. The aim, therefore, of this study was to evaluate the prevalence, clinical characteristics, and severity of LAR in a Spanish rhinitis population, compared with patients having classical allergic rhinitis (AR) with systemic atopy or nonallergic rhinitis (NAR).

Methods

A group of 452 adult rhinitis patients were randomly selected from a total of 3860 who attended our allergy service over 1 year. A clinical questionnaire, skin prick test (SPT), spirometry, and serum total and specific IgE (sIgE) were evaluated. A nasal allergen provocation test with multiple aeroallergens (NAPT‐M), including Dermatophagoides pteronyssinus, pollens, alternaria, and dog epithelia, was performed in patients with negative SPT and serum sIgE.

Results

A total of 428 patients completed the study; 24 were excluded because of nasal hyper‐reactivity. LAR was diagnosed in 25.7%, AR in 63.1%, and NAR in 11.2%. The LAR and AR patients had a similar clinical profile: a nonsmoking woman with severe, persistent perennial rhinitis frequently associated with conjunctivitis and asthma. More than 36% of LAR patients reported rhinitis onset in childhood. NAPT‐M detected aeroallergen polysensitization in 37.3% of the LAR patients. Dermatophagoides pteronyssinus was the main sensitizing aeroallergen in LAR and AR (60% vs 54%, P > 0.05).

Conclusions

Local allergic rhinitis is a prevalent entity in patients evaluated with rhinitis. Persistent and severe symptoms associated with conjunctivitis and/or asthma and polysensitization were likely to be detected in LAR and AR.
Interleukin‐33 in allergy
Authors: Ohno Tatsukuni , Morita Hideaki , Arae Ken , Matsumoto Kenji , Nakae Susumu
Published: August 2012

Interleukin‐33 (IL‐33) is a member of the IL‐1 cytokine family, which includes IL‐1 and IL‐18, and is considered to be important for host defense against nematodes by inducing Th2 cytokine production via the IL‐33 receptor. IL‐33 receptor is a heterodimer of IL‐1 receptor‐like 1 (IL‐1RL1; also called ST2, T1, Der4, and fit‐1) and IL‐1 receptor accessory protein (IL‐1RAcP). On the other hand, excessive and/or inappropriate production of IL‐33 is considered to be involved in the development of various disorders, such as allergic and autoimmune diseases. Unlike IL‐1β and IL‐18, IL‐33 does not seem to be secreted through the activation of inflammasomes in events such as apoptosis. However, IL‐33 is localized in the nucleus of cells and is released during tissue injury associated with necrosis. This suggests that it acts as an alarmin, like IL‐1α and high‐mobility group box chromosomal protein‐1 (HMGB‐1). This review summarizes current knowledge regarding the roles of IL‐33 in the functions of various cell types and the pathogenesis of allergy.
Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin‐stimulation test?
Authors: Pina Géraldine , Dubois Séverine , Murat Arnaud , Berger Nicole , Niccoli Patricia , Peix Jean‐Louis , Cohen Régis , Guillausseau Claudine , Charrie Anne , Chabre Olivier , Cornu Catherine , Borson‐Chazot Françoise , Rohmer Vincent ,   The Groupe des Tumeurs Endocrines
Published: August 2012

Objective

To evaluate a second‐generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin‐stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow‐up of patients withMTCafter surgery. Recent American Thyroid Association recommendations suggest the use of basalCTalone to diagnose and assess follow‐up ofMTCas the pentagastrin (Pg) test is unavailable in many countries.

Design

Multicentric prospective study.

Patients

A total of 162 patients with basalCT<10 ng/l were included: 54 asymptomatic patients harboured noncysteine ‘rearranged during transfection’ (RET) proto‐oncogene mutations and 108 patients had entered follow‐up ofMTCafter surgery.

Measurement

All patients underwent basal andPg‐stimulatedCTmeasurements using a second‐generation assay with 5‐ng/l functional sensitivity.

Results

Ninety‐five per cent of patients with basalCT≥5 ng/l and 25% of patients with basalCT<5 ng/l had a positivePg‐stimulation test (PgCT>10 ng/l). Compared with the referencePg test, basalCT≥5 ng/l had 99% specificity, a 95%‐positive predictive value but only 35% sensitivity (P < 0·0001). Overall, there were 31% less false‐negative results using a 5‐ng/l threshold for basalCTinstead of the previously used 10‐ng/l threshold.

Conclusion

The ultrasensitiveCTassay reduces the false‐negative rate of basalCTmeasurements when diagnosing familialMTCand in postoperative follow‐up compared with previously used assays. However, its sensitivity to detectC‐cell disease remains lower than that of thePg‐stimulation test.
Acitretin exerted a greater influence on T‐helper (Th)1 and Th17 than on Th2 cells in treatment of psoriasis vulgaris
Authors: NIU Xinwu , CAO Wei , MA Huiqun , FENG Jie , LI Ximei , ZHANG Xinhua
Published: August 2012

T‐helper (Th) cells, including Th1, Th2 and Th17 cells, may play an important role in the pathogenesis of psoriasis vulgaris (PV). Acitretin is an effective treatment for PV; however, its influence on Th cells during the treatment of PV is unclear. This study aimed to investigate the influence of acitretin on Th1, Th2 and Th17 cells in PV patients. PV patients (n = 30) received acitretin p.o. (20 mg/day) for 8 weeks. Sera and skin biopsies were obtained before and after treatment. Double‐labeled immunofluorescence was used to analyze T, Th1, Th2 and Th17 cells in skin lesions. Enzyme‐linked immunosorbent assay and western blot were used to analyze the expressions of interferon (IFN)‐γ, interleukin (IL)‐4 and IL‐17 in sera and skin lesions. The expressions of IFN‐γ mRNA, IL‐4 mRNA and IL‐17 mRNA in skin lesions were detected by in situ hybridization. Acitretin decreased the quantity of T, Th1 and Th17 cells in PV lesions, but had no significant influence on Th2 cells. Acitretin also decreased the expression of IFN‐γ and IL‐17 in serum and lesions. The expressions of IFN‐γ mRNA and IL‐17 mRNA decreased significantly after 8 weeks of therapy. However, acitretin had no significant influence on the expression of IL‐4 protein and mRNA. Acitretin can reverse Th1 and Th17 preponderance in PV patients to some degree. This may be due to the mechanism of acitretin on PV; however, Th2 cells were not affected by acitretin treatment.
A survey of the outcome of prophylaxis, on‐demand treatment or combined treatment in 18–35‐year old men with severe haemophilia in six countries
Authors: Noone D. , O'Mahony B. , van Dijk J. P. , Prihodova L.
Published: August 2012

A number of studies have been published on the benefits of prophylactic treatment in adults with haemophilia. However, in many countries, it is considered as optional due to financial constraints. This survey was carried out to examine the long‐term effects of prophylaxis and the continuing benefit of the treatment into adulthood. Self‐assessed health‐related data and the EQ‐5D questionnaire measuring health utility were collected from 124 men (26.9 ± 4.6 years) from Canada (N = 40), France (N = 14), Ireland (N = 17), the Netherlands (N = 16), Poland (N = 24) and the UK (N = 13). The respondents were split into four groups: On‐Demand, <50% life on prophylaxis, ≥50% life on prophylaxis, Prophylaxis. Overall, long‐term prophylaxis results in lower presence of target joints (P ≤ 0.001), occurrence of serious bleeding episodes (P ≤ 0.05), recurring bleeding episodes (P ≤ 0.01) and requirement for surgical procedures (P ≤ 0.05). Furthermore, health utility (P ≤ 0.01) in the On‐demand group was significantly lower (P ≤ 0.01) compared to the ≥50% life on prophylaxis and the Prophylaxis group. No significant differences between countries were found except between the Netherlands and Poland, with Poland showing the lowest health utility (P ≤ 0.01) and the most problems with mobility (P ≤ 0.05) and pain/discomfort (P ≤ 0.001). The Netherlands showed the highest health utility (0.915) followed by Canada (0.791), Ireland (0.786), UK (0.768), France (0.687) and Poland (0.629). The results demonstrate consistently higher quality of life of individuals who are on long‐term prophylactic treatment when compared to on‐demand treatment or intermittent prophylaxis and on ‐demand treatment.
Instructional design or school politics? A discussion of ‘orchestration' in TEL research
Authors: Perrotta C. , Evans M.A.
Published: August 2012

This paper argues that the emphasis on orchestration as a metaphor for teaching in technology‐enhanced learning (TEL) environments, featured in recent academic discussions, is an opportunity to broaden the scope of the inquiry into educational technology. Drawing on sociological literature and research that investigated the systemic factors that influence the uptake of information and communication technologies in formal and informal learning contexts, the paper contends that a focus on instructional design does insufficient justice to the complexities of actual technology use in classrooms and after‐school programs. It is suggested, instead, that orchestration might better be used as a heuristic device to deepen our understandings of the relationships between power, bestowed on teachers or claimed by them through a number of strategies, educational technology, and teaching practices. The paper concludes that to fully understand this relationship and to support teachers, concern should be given equally to the existing political and cultural dynamics of TEL environments. Examples of orchestration as a political, cultural process are provided, illustrating how teachers appropriate technology and ‘innovative’ pedagogies to negotiate power.
Endogenous Angiotensin II‐induced p44/42 Mitogen‐Activated Protein Kinase Activation Mediates Sodium Appetite but not Thirst or Neurohypophysial Secretion in Male Rats
Authors: Felgendreger L. A. , Fluharty S. J. , Yee D. K. , Flanagan‐Cato L. M.
Published: August 2012

The renin–angiotensin–aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen‐activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin‐converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap‐induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap‐ or exogenous AngII‐induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII‐induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed.
Developmental Changes in Desensitisation of c‐Fos Expression Induced by Repeated Maternal Separation in Pre‐Weaned Mice
Authors: Horii‐Hayashi N. , Sasagawa T. , Matsunaga W. , Matsusue Y. , Azuma C. , Nishi M.
Published: August 2012

Early‐life stress has long‐lasting effects on neuroendocrine and behaviour in adulthood. Maternal separation (MS) is used as a model of early‐life stress and daily repeated MS (RMS) for 3 h during the first two postnatal weeks is widely used in rodent studies. However, it is not fully understood whether early‐life animals desensitise/habituate to repeated stress. In the present study, we investigated the effects of daily RMS for 3 h and acute/single time MS (SMS) for 3 h on the plasma corticosterone level and c‐Fos expression in the brain in mice at different postnatal ages. Mice were subjected to: (i) RMS from postnatal day (PND) 1 to 14 (RMS14); (ii) RMS from PND14 to 21 (RMS21); (iii) SMS on PND14 (SMS14); and (iv) SMS on PND21 (SMS21). Plasma corticosterone and c‐Fos expression were examined on the final day in each experiment. The basal corticosterone levels in RMS14 and RMS21 were equal to those in respective age‐matched controls. After the final separation, the levels were significantly increased and were comparable with those after SMS14 and SMS21, respectively. Histological analysis indicated that c‐Fos expression significantly increased in many brain regions, including the paraventricular nucleus, prefrontal cortex, hippocampus, and basolateral and medial amygdale in both SMS14 and SMS21 mice. However, c‐Fos expression in RMS14 mice significantly increased in many regions, whereas such increases were hardly seen in RMS21 mice. These results indicate that repeated early‐life stress neither increases basal corticosterone, nor decreases the magnitude of the corticosterone response during the first three postnatal weeks, although desensitisation of c‐Fos expression induced by repeated stress is changed during postnatal development.
Scaling up: examining the macroecology of ectomycorrhizal fungi
Authors: KENNEDY PETER G. , MATHENY P. B. , RYBERG K. M. , HENKEL TERRY W. , UEHLING JESSIE K. , SMITH MATTHEW E.
Published: August 2012

Ectomycorrhizal (ECM) fungi play major ecological roles in temperate and tropical ecosystems. Although the richness of ECM fungal communities and the factors controlling their structure have been documented at local spatial scales, how they vary at larger spatial scales remains unclear. In this issue of Molecular Ecology, Tedersoo et al. (2012) present the results of a meta‐analysis of ECM fungal community structure that sheds important new light on global‐scale patterns. Using data from 69 study systems and 6021 fungal species, the researchers found that ECM fungal richness does not fit the classic latitudinal diversity gradient in which species richness peaks at lower latitudes. Instead, richness of ECM fungal communities has a unimodal relationship with latitude that peaks in temperate zones. Intriguingly, this conclusion suggests the mechanisms driving ECM fungal community richness may differ from those of many other organisms, including their plant hosts. Future research will be key to determine the robustness of this pattern and to examine the processes that generate and maintain global‐scale gradients of ECM fungal richness.
Dermatophytes from skin lesions of domestic animals in Nsukka, Enugu State, Nigeria
Authors: Chah Kennedy F. , Majiagbe Kehinde A. , Kazeem Haruna M. , Ezeanyika Ogechukwu , Agbo Ifeoma C.
Published: August 2012

Background –  Dermatophytes are well‐recognized cutaneous fungi with public health implications. In Nigeria, several studies have been carried out on dermatophytosis in humans; however, data on dermatophytes in animals are lacking.

Objectives –  This study was conducted to determine the occurrence and species of dermatophytes in skin lesions in domestic animals in Nsukka Agricultural Zone of Enugu State, Nigeria.

Animals –  Forty‐six domestic animals (dogs, goats, sheep and pigs) presented for sale in the local markets in the study area and with suspected lesions of dermatophytosis were used for the study.

Methods –  Plucked hairs and epidermal scales from the skin lesions of affected animals were inoculated on Sabouraud dextrose agar slants containing 0.05 mg/mL of chloramphenicol and 0.5 mg/mL of cycloheximide. Inoculated slants were incubated at room temperature (27°C) for up to 4 weeks and examined at 2–3 day intervals for fungal growth. Laboratory identification of the fungal isolates was based on their colonial, microscopic and biochemical characteristics.

Results –  Of the 46 animals with suspected lesions of dermatophytosis, six (13.0%) were positive for a dermatophyte, and the following dermatophytes were identified: Microsporum gypseum, two of 12 sheep; Microsporum audouinii, one of 16 dogs; Trichophyton mentagrophytes, one of 16 dogs and one of 12 sheep; and Trichophyton schoenleinii, one of 13 goats.

Conclusions and clinical importance –  Anthropophilic dermatophytes are among the fungal agents associated with dermatophytosis in animals in Nsukka Agricultural Zone. These dermatophytes could constitute health risks to humans in contact with the animals.
Dermal delivery by niosomes of black tea extract as a sunscreen agent
Authors: Yeh Meng‐I , Huang Hsiu‐Chin , Liaw Jia‐Horng , Huang Min‐Chuan , Huang Kuei‐Fen , Hsu Feng‐Lin
Published: August 2012

Objectives  The primary objective of this study was to investigate the feasibility of using niosomes as a delivery vehicle for the dermal administration in vitro of black tea extract (BTE) as a sunscreen.

Methods  Multi‐lamellar niosomes were obtained by means of a previously reported method of lipid hydration films. In vitro penetration experiments through nude mouse skin were carried out to evaluate the potential of niosomes as a dermal formulation. The nude mouse skin membrane allowed the effects of penetration with a niosome formulation to be evaluated. Penetration rates of caffeine‐ and gallic acid‐loaded niosomes in a steady state were higher than dispersion in aqueous solutions.

Results  For skin permeation, higher transdermal absorption rates were seen with solutions of caffeine and gallic acid.

Conclusions  In the near future, BTE as a sunscreen agent will be dermally delivered by niosomes.
Incidence of deep vein thrombosis in erysipelas or cellulitis of the lower extremities
Authors: Mortazavi Mohammadreza , Samiee Mitra M. , Spencer Frederick A.
Published: August 2012

The incidence of deep vein thrombosis (DVT) in patients with erysipelas and cellulitis of the lower extremities is unknown. As such, the indication and efficacy of prophylactic anticoagulation for prevention of DVT in these patients is unclear. The main goal of this review is to provide an estimate of the incidence of DVT in erysipelas and cellulitis based on existing literature.

A comprehensive search of the electronic sources: MEDLINE, EMBASE, CINAHL, LILAC and Cochrane without any language limitation was performed from 1950 to April 2011 for articles focused on the occurrence of DVT in cellulitis or erysipelas of the lower extremities.

The selected studies were divided into two groups according to presence or absence of systematic investigation for DVT. Those studies in which the patients received prophylactic or therapeutic anticoagulants before a diagnosis of DVT were excluded.

The reported incidence rate of DVT in patients with erysipelas or cellulitis of the lower extremities is highly variable, ranging from 0 to 15%. In this review, the overall incidence rates of DVT in studies with and without systematic investigation for thromboembolism were 2.72% (95% CI: 1.71–3.75%) and 0.68% (95% CI: 0.27–1.07%), respectively.

Given the low reported overall incidence of DVT, neither routine prophylactic anticoagulation nor systematic paraclinical investigation for DVT is indicated in low risk patients with erysipelas or cellulitis of the lower extremities. DVT should still be considered in patients with high pretest probability or other thromboembolic risk factors.
Transforming growth factor‐beta1 in inflammatory airway disease: a key for understanding inflammation and remodeling
Authors: Yang Y. C. , Zhang N. , Van Crombruggen K. , Hu G. H. , Hong S. L. , Bachert C.
Published: August 2012

Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix regulatory cytokines, transforming growth factor‐beta (TGF‐β) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF‐β1, from the view points of inflammation and remodeling, and discuss the role of TGF‐β in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF‐β1.
Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort
Authors: Lieberman J. A. , Morotti R. A. , Konstantinou G. N. , Yershov O. , Chehade M.
Published: August 2012

Background

Fibrosis of the esophageal lamina propria is a known complication of eosinophilic esophagitis (EoE). To date, therapy with topical corticosteroids has been shown to reverse esophageal fibrosis in some patients; however, there is little evidence to suggest that dietary therapy can also reverse it. Our aim was to examine whether dietary therapy alone can reverse esophageal fibrosis in children with EoE.

Methods

We performed a historical cohort study based on children with EoE who had esophageal fibrosis on pretreatment biopsies using trichrome staining. Post‐treatment biopsies were analyzed for fibrosis reversal, and results were compared between patients treated with dietary restriction and those that received topical steroids. Clinical characteristics (age, symptoms, duration of symptoms prior to therapy, treatment type, and duration of therapy) were recorded. Histological markers (eosinophil numbers and eosinophilic degranulation in both epithelium and lamina propria, basal zone hyperplasia, and the presence of eosinophilic microabscesses in the epithelium) were examined by reviewing hematoxylin and eosin‐stained biopsies and by immunohistochemical staining. These were examined as potential predictors for fibrosis reversal.

Results

Fibrosis resolved following both dietary restriction and topical steroids (3/17 and 5/9 patients respectively, P = 0.078). Post‐treatment symptom resolution and decreased intraepithelial eosinophil numbers were found to be the only significant predictors of fibrosis resolution.

Conclusions

Dietary restriction alone, similar to topical steroids, can reverse fibrosis in children with EoE.
Why is it so Difficult to Derive Pluripotent Stem Cells in Domestic Ungulates?
Authors: Gandolfi F , Pennarossa G , Maffei S , Brevini TAL
Published: August 2012

Content

Pluripotent stem cells are the focus of an extremely active field of investigation that is bringing new light on our understanding of the mechanisms that control pluripotency and differentiation. Rodent and primates are the only species where true, or bona fide, pluripotent stem cells have been derived. The attempts to derive pluripotent stem cells from domestic ungulates have been going on for more than 20 years with little progress. Cell lines from these species present a series of limitations that have precluded their use for both basic and clinically oriented studies. However, in the last 3 years, some substantial progress have been made making the currently available ungulate pluripotent stem cells closest than ever before to their human and mouse counterpart. This result has been achieved through both conceptual and technical progress that will be illustrated and discussed in this review.
Reproductive Issues Arising from Different Management Systems in the Dairy Industry
Authors: Mee JF
Published: August 2012

Contents

The objective of this review is to address the reproductive issues arising from different dairy management systems by describing divergent systems and comparing their reproductive outcomes. The increasing global demand for dairy products has led to the majority of the world’s milk being produced in intensive management systems. This intensification has occurred in both zero‐grazed (ZG) and in pasture‐based (PB) systems, and it has contributed directly to the current decline in dairy cow fertility globally. Given the heterogeneous nature of both ZG and PB systems, comparisons between them in dairy cow reproductive performance need to be treated with caution. In general, cows in ZG systems have higher milk production and better energy balance but more of some animal health problems, lower ovarian activity post‐partum, reduced oestrous expression, reduced conception success, and higher culling and mortality rates, than cows in PB systems. Key environmental descriptors affecting reproductive performance within management systems include the type and duration of housing and the pre‐ and post‐partum diet composition. Genetic by environment (GxE) interactions for dairy cow fertility have been detected for some, but not for other, management systems. Given the concerns of some consumers within the EU about the health, fertility and welfare of dairy cows in modern dairy herd management systems, there is a need to address these concerns with large‐scale experimental and epidemiological studies.
Reproductive Issues in Welfare‐Friendly Housing Systems in Pig Husbandry: A Review
Authors: Kemp B , Soede NM
Published: August 2012

Contents

In Europe, housing conditions of sows are currently changing, related with a larger emphasis on pig welfare. As a result, sows are and will be less kept in crates, but more so in loose housing systems (farrowing, lactation) and group housing systems (pregnancy, lactation, weaning‐to‐oestrus interval). These changes in housing conditions may affect reproductive functioning of the sows. Group housing of sows may decrease farrowing rate and litter size when stress levels rise or when feed intake in early pregnancy is not fully secured. Loose housing during farrowing results in an improved farrowing process, but may increase piglet mortality by crushing during early lactation. Further, group housing during lactation may increase the risk of lactational oestrus. Thus, new – welfare friendly – housing systems require increased attention to management to ensure optimal reproductive performance.
The Influencing Factor of In Vitro Fertilization and Embryonic Transfer in the Domestic Fowl (Gallus domesticus)
Authors: Li BC , Li W , Chen H , Zhang YN , Zhang ZT , Wang XY , Gao B , Dou TC , Wang KH
Published: August 2012

Contents

This study was conducted to explore the influencing factors of ova in vitro fertilization (IVF) and transfer of the fertilized ova into the oviduct of recipient hens. The efficiency of fertilization was compared using three aspects: (i) the different time of ova collection and transfer, (ii) egg‐laying period of recipient hen; and (iii) semen volume. The following results are observed: 72%, 40% and 0% of ova were found in ovarian sac in 30∼40 min, 50∼60 min and more than 90 min post‐oviposition, respectively; 20%, 18%, 14% and 5.8% of ova were fertilized with 0.1, 0.2, 0.5 and 1.0 ml semen, respectively; and 33% and 100% of healthy chickens were hatched from fertile ova with 0.1 and 0.5 ml of semen, respectively. All oocytes obtained from ovary and mid‐oviduct were unfertilized. Embryos were transferred into recipient hens 30 min ± 10 min post‐oviposition, and 70% of shelled eggs were produced. There were no eggs produced in the other transfer times. This demonstrated that live chicken can be obtained by IVF of ova collected shortly after oviposition. It was important that the ovum was transferred into the oviduct infundibulum of recipient hens immediately or shortly after oviposition.
Neurocognitive function in obstructive sleep apnoea: A meta‐review
Authors: BUCKS ROMOLA S. , OLAITHE MICHELLE , EASTWOOD PETER
Published: August 2012

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta‐analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand‐searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long‐term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short‐term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long‐term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests.
Nitric oxide as intracellular modulator: internal production of NO increases neuronal excitability via modulation of several ionic conductances
Authors: Artinian Liana , Zhong Lei , Yang Hansoo , Rehder Vincent
Published: August 2012

Nitric oxide (NO) has been shown to regulate neuronal excitability in the nervous system, but little is known as to whether NO, which is synthesized in certain neurons, also serves functional roles within NO‐producing neurons themselves. We investigated this possibility by using a nitric oxide synthase (NOS)‐expressing neuron, and studied the role of intrinsic NO production on neuronal firing properties in single‐cell culture. B5 neurons of the pond snail Helisoma trivolvis fire spontaneous action potentials (APs), but once the intrinsic activity of NOS was inhibited, neurons became hyperpolarized and were unable to fire evoked APs. These striking long‐term effects could be attributed to intrinsic NO acting on three types of conductances, a persistent sodium current (INaP), voltage‐gated Ca currents (ICa) and small‐conductance calcium‐activated potassium (SK) channels. We show that NOS inhibitors 7‐nitroindazole and S‐methyl‐l‐thiocitrulline resulted in a decrease in INaP, and that their hyperpolarizing and inhibiting effects on spontaneous spiking were mimicked by the inhibitor of INaP, riluzole. Moreover, inhibition of NOS, soluble guanylate cyclase (sGC) or protein kinase G (PKG) attenuated ICa, and blocked spontaneous and depolarization‐induced spiking, suggesting that intrinsic NO controlled ICa via the sGC/PKG pathway. The SK channel inhibitor apamin partially prevented the hyperpolarization observed after inhibition of NOS, suggesting a downregulation of SK channels by intrinsic NO. Taken together, we describe a novel mechanism by which neurons utilize their self‐produced NO as an intrinsic modulator of neuronal excitability. In B5 neurons, intrinsic NO production is necessary to maintain spontaneous tonic and evoked spiking activity.
Maximising return on conservation investment in the conterminous USA
Authors: Withey John C. , Lawler Joshua J. , Polasky Stephen , Plantinga Andrew J. , Nelson Erik J. , Kareiva Peter , Wilsey Chad B. , Schloss Carrie A. , Nogeire Theresa M. , Ruesch Aaron , Ramos Jorge , Reid Walter
Published: August 2012

Efficient conservation planning requires knowledge about conservation targets, threats to those targets, costs of conservation and the marginal return to additional conservation efforts. Systematic conservation planning typically only takes a small piece of this complex puzzle into account. Here, we use a return‐on‐investment (ROI) approach to prioritise lands for conservation at the county level in the conterminous USA. Our approach accounts for species richness, county area, the proportion of species' ranges already protected, the threat of land conversion and land costs. Areas selected by a complementarity‐based greedy heuristic using our full ROI approach provided greater averted species losses per dollar spent compared with areas selected by heuristics accounting for richness alone or richness and cost, and avoided acquiring lands not threatened with conversion. In contrast to traditional prioritisation approaches, our results highlight conservation bargains, opportunities to avert the threat of development and places where conservation efforts are currently lacking.