bluuebunny/crossref_metadata_2025 huggingface dataset:
Human biliary tree stem/progenitor cells immunomodulation: Role of hepatocyte growth factor
Authors: Maraldi Tullia , Guida Marianna , Beretti Francesca , Resca Elisa , Carpino Guido , Cardinale Vincenzo , Gentile Raffaele , Ardizzoni Andrea , Murgia Alba , Alvaro Domenico , Gaudio Eugenio , De Pol Anto
Published: July 2016

Aim

Human biliary tree stem/progenitor cells (hBTSC) are multipotent epithelial stem cells with the potential for allogenic transplant in liver, biliary tree, and pancreatic diseases. Human mesenchymal stem cells, but also epithelial stem cells, are able to modulate immune responses with different types of secretion molecules.

Methods

The initial aim of the present study was to develop for the first time a culture protocol in order to expand hBTSC in vitro through passages, allowing to maintain a similar stem cell and secretome profile. Furthermore, we investigated the secretome profile of the hBTSC to assess the production of molecules capable of affecting immune feedback.

Results

We found that hepatocyte growth factor produced by hBTSC exerts its cytoprotective role inducing apoptosis in human immune cells, such as lymphocytes.

Conclusions

The present study, therefore, supports the hypothesis that hBTSC can be useful for the purpose of regenerative medicine, as they can be banked and expanded, and they can secrete immunoregulatory factors.
HIV information needs of parents of young men who have sex with men
Authors: Rose India D. , Friedman Daniela B.
Published: July 2016

Objective

Young men who have sex with men (YMSM) have unique health concerns, including high rates of HIV infection. To prevent HIV, YMSM need credible information from trusted sources, specifically parents. Little is known about what health information resources parents of YMSM need to communicate with their child about HIV prevention. The primary objective of this study was to examine the proxy health information seeking behaviours of parents of YMSM and to identify information resources that parents need to communicate with their YMSM identified child about HIV prevention.

Methods

Qualitative findings were grouped into four categories: parents’ current health information sources; barriers to seeking health information; parents’ health information needs; and recommendations for delivery of health information for parents. Ten in‐depth interviews were conducted with parents of YMSM.

Results

Parents reported consulting physicians and the Internet for HIV/AIDS information. They reported finding limited information targeted towards parents of YMSM and provided suggestions for improving the delivery of health information including training, websites and the local news.

Conclusions

Delivery of tailored HIV prevention information to parents may be effective in helping combat HIV among YMSM. Given that YMSM bear the greatest burden for HIV, this study highlights the need to include parents of YMSM in future interventions aimed at reducing YMSM's risk of HIV/AIDS.
Atypical Ewing sarcoma breakpoint region 1 fluorescence in‐situ hybridization signal patterns in bone and soft tissue tumours: diagnostic experience with 135 cases
Authors: Vargas A Cristina , Selinger Christina I , Satgunaseelan Laveniya , Cooper Wendy A , Gupta Ruta , Stalley Paul , Brown Wendy , Soper Judy , Schatz Julie , Boyle Richard , Thomas David M , Tattersall Martin H N , Bhadri Vivek A , Maclean Fiona , Bonar S Fiona , Scolyer Richard A , Karim Rooshdiya Z , McCarthy Stanley W , Mahar Annabelle , O'Toole Sandra A
Published: July 2016

Aims

Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in‐situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5′ centromeric region or 3′ telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements.

Methods and results

Using an EWSR1 break‐apart probe, we performed FISH assays on formalin‐fixed paraffin‐embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work‐up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non‐rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1‐associated that were technically EWSR1‐rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10–30% of lesional cells) were present in an additional 17% of these cases.

Conclusions

While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1‐associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1‐associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings.
Species trait selection along a prescribed fire chronosequence
Authors: Bargmann Tessa , Heegaard Einar , Hatteland Bjørn Arild , Chipperfield Joseph Daniel , Grytnes John‐Arvid
Published: July 2016

Fire is a widespread management practice used in the maintenance of European heathland. Frequent prescribed burns in small patches have been shown to benefit carabid communities; however, how fire favours specific life‐history traits is poorly understood.

In this study, we identify characteristic species of the successional stages within heathlands, and find the traits which are characteristic of species in burnt areas versus areas dominated by older heath stands.

We identify 10 species as indicator species for heathland in the pioneer stage (0–5 years old); Amara lunicollis, Bembidion lampros, Calathus fuscipes, Carabus problematicus, Cicindela campestris, Nebria salina, Notiophilus aquaticus, Poecilus cupreus, P. lepidus and P. versicolor. Dyschirius globosus is identified as an indicator for the building stage (6–14 years old), and Carabus violaceus as an indicator for the mature stage (15–25 years old).

Moisture preference and diet are identified as traits that determine species response to prescribed fire. Collembolan specialists and species with no moisture preference are shown to be most abundant in burnt patches, whereas generalist predators and species with a high moisture preference are less tolerant of fire.

Knowledge of species sorting along a prescribed fire gradient can provide valuable information for heathland conservation.
Retrospective review of factors associated with severe hospitalised community‐acquired influenza in a tertiary paediatric hospital in South Australia
Authors: Lakhan Nerissa , Clarke Michelle , Mathew Suja M. , Marshall Helen
Published: July 2016

Background

Influenza infection can result in severe disease with debilitating complications. Young children have the highest rate of influenza hospitalisations with various factors influencing influenza susceptibility and severity.

Objectives

This study aimed to determine the disease burden and assess risk factors for severe hospitalised influenza in South Australian children under 5 years of age.

Methods

Influenza admissions to the tertiary paediatric hospital in South Australia from 2008 to 2012 were identified. Data from laboratory‐confirmed influenza cases were collected, including infecting influenza strain, co‐infections, prematurity, pre‐existing medical comorbidities and other potential risk factors. Predictors of high‐level care were assessed using logistic regression.

Results

A total of 267 children with laboratory‐confirmed influenza were hospitalised. Of these, 147 admissions (53%) occurred in children without underlying medical risk factors. Eighteen children (7%) required high‐level care, of which 11 (61%) had no underlying medical risk factors. No deaths were reported. The majority of children were unimmunised against influenza. Co‐infections were identified in 40% of children (n = 107). Influenza B was associated with a requirement for higher care (OR 3.7, CI 1.3–10.9, P = .02) as was a history of food allergies (OR 9.7, CI 1.5–61.4, P = .02) and iron deficiency anaemia (OR 4.8, CI 1.4–16.1, P = .01).

Conclusions

Influenza can be a severe illness, even in children without underlying medical conditions. The identification of Influenza B strain, history of food allergies and iron deficiency anaemia as predictors of severity in hospitalised cases warrants further investigation and may have important implications for preventative strategies to reduce the burden of childhood influenza.
Non‐moulted primary coverts correlate with rapid primary moulting
Authors: Kiat Yosef , Izhaki Ido
Published: July 2016

Time constraint is a main factor which affects the moult strategies in passerines, mainly during the first year of life. The variability of moult strategies between species is associated with the extent of the moult. In the first year of life, the extent of the moult is highly variable between species and individuals. In most passerine species, juveniles only renew some of their feathers, but the factors that govern which feathers are renewed and which are retained have been largely overlooked. Here we examine the common pattern of non‐moulted primary coverts (PC) in passerines during the first‐year moult cycle (post‐juvenile and first‐year pre‐breeding moults). On the interspecific level we found that among 63 species of passerines, PCs are the least commonly moulted feather tract. For five species (Hirundo rustica, Pycnonotus xanthopygos, Prinia gracilis, Acrocephalus stentoreus and Passer moabiticus) which perform a complete post‐juvenile moult, we found that the PC moult occurs over a longer period than greater coverts (GCs) and is sequential (non‐simultaneous). At the intraspecific level, we found that the main difference between a partial and complete moult in Prinia gracilis is the moulting or non‐moulting of the PCs. We also demonstrate that for Prinia gracilis 1) juveniles which do not moult their PCs, moult their primaries at a higher speed than those which moult their PCs and 2) area/mass ratio of PCs is lower than of GCs. These two findings may explain why many passerines skip PC renewal during the first year of life. Because the PC moult lasts a long time, forgoing this moult enables long term resource savings that allow for dealing with time constraints. Our results highlight the adaptive advantages of non‐moulted PCs in cases of time constraints.
Molecular changes in the postmortem parkinsonian brain
Authors: Toulorge Damien , Schapira Anthony H. V. , Hajj Rodolphe
Published: July 2016

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post‐mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post‐mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post‐mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post‐mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD.

image

Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's‐linked genes; Transition metals, calcium and calcium‐binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways.

This article is part of a special issue on Parkinson disease.
Clinical efficacy and safety of 20% glycolic peel, 15% lactic peel, and topical 20% vitamin C in constitutional type of periorbital melanosis: a comparative study
Authors: Dayal Surabhi , Sahu Priyadarshini , Jain Vijay Kumar , Khetri Sneh
Published: July 2016

Introduction

Periorbital Melanosis (POM) is a very common esthetic condition, yet there is no definite treatment modality. Topical therapy is the mainstay of treatment which includes chemical peels, vitamin C, and other depigmenting agents.

Objective

To compare clinical efficacy, safety, and tolerability of 20% glycolic acid peels, 15% lactic acid peels, and topical 20% vitamin C in treatment of constitutional type of POM in Indian patients.

Method

Ninety patients of constitutional POM were enrolled for 12 weeks. The patients were distributed into three groups. One‐third of patients underwent 3‐weekly GA peel, another one‐third underwent 3‐weekly lactic peel, and rest applied vitamin C daily. Clinical improvement was assessed objectively using POM grading. Patient's and physicians global assessment along with patient's global tolerance was also evaluated.

Results

More than 50% improvement in POM was observed in 73.34% of patients on GA peel, 56.67% on lactic peel, and 26.67% on vitamin C. On comparing improvement with respect to duration of therapy, GA peel was significantly more effective than lactic peel from 12 weeks onward, while it was more effective than vitamin C from 6 weeks onward. Lactic peel was more effective than vitamin C from 6 weeks onward. Physician and patient global assessment was excellent with glycolic peel followed by lactic peel and vitamin C. The incidence of adverse effect was maximum with GA peel followed by lactic peel and vitamin C.

Conclusion

Glycolic peel was best among the three modalities, although it was associated with increased rate of side effects.
Patterns of ‘at‐home’ alcohol‐related injury presentations to emergency departments
Authors: Bunker Naomi , Woods Cindy , Conway Jane , Barker Ruth , Usher Kim
Published: July 2016

Aims and objectives

This study aimed to establish the scale of alcohol‐related injuries originating in the home.

Background

Despite recent media and public attention on alcohol‐related injuries occurring at licensed venues, many occur in other locations including the home.

Design

A retrospective observational study.

Methods

Emergency department surveillance data sourced from the Queensland Injury Surveillance Unit were interrogated for alcohol‐related emergency department presentations from 2003–2012 (n = 12,296). Descriptive analysis was undertaken to assess alcohol involvement in injury, and analysis of variance was used to determine the differences among group means and their associated presentations. The relationship between demographic variables and injury location was assessed using p value of <0·05 as statistically significant.

Results

Of all injuries that were positively identified as being alcohol related, 41·07% occurred at the ‘other’ location, 36·14% ‘at home’, 13·00% on the street and 9·78% at licensed premises. Of these, males (n = 2635; 59%) represented a higher proportion than females (n = 1807; 41%). Of injuries identified as domestic violence by spouse or partner (n = 510), 59·5% occurred ‘at home’.

Conclusions

This is the first study to investigate alcohol‐related injuries occurring at home. The home accounts for a greater proportion of injuries than the frequently assessed licensed premises location. Further research is required to validate these findings in a wider setting.

Relevance to clinical practice

A public health campaign is required to minimise harm associated with alcohol‐related injuries in the home, and nurses are positioned to inform health policy makers around this issue. Furthermore, emergency department nurses are in a unique position to provide brief interventions around safe alcohol consumption and injury prevention.
Genetic profile of PTEN gene in Indian oral squamous cell carcinoma primary tumors
Authors: Shah Sejal , Jajal Dhara , Mishra Girish , Kalia Kiran
Published: July 2016

Background

Phosphatase and tensin homolog (PTEN) is the tumor suppressor gene located on chromosome10q23.3. Genetic variations in the PTEN gene have been found in various sporadic tumors. However, petite is known about the genetic profile of the PTEN gene in oral squamous cell carcinoma (OSCC), which is the eighth most common neoplasm worldwide and leading cancer in India. The purpose of the present study was to determine the frequency of genetic variations in the tyrosine phosphatase domain of the PTEN gene in an Indian OSCC subset.

Methods

We analyzed tyrosine phosphatase domain encoded by exon 5 of the PTEN gene in 59 OSCC primary tumors using PCR ‐ direct genomic sequencing.

Result

We observed one somatic deletion mutation, IVS4‐30delT in three OSCC patients; two of them were at an advanced stage of carcinoma. Moreover, we identified one SNP rs 35560700(C>T), in five OSCC patients with the late stage of oral carcinoma.

Conclusion

We identified 5% somatic mutational frequency in the intronic region of the tyrosine phosphatase domain of the PTEN gene; however, mutations were found absent in the coding region. Therefore, PTEN gene mutation is not a frequent event in the pathogenesis of OSCC in the targeted Indian cohort.
Expression of astrocyte elevated gene‐1 protein in ameloblastomas, keratocystic odontogenic tumors, and dentigerous cysts
Authors: Wu Yu‐Hsueh , Chang Julia Yu‐Fong , Tseng Chih‐Huang , Chiang Chun‐Pin , Wang Yi‐Ping
Published: July 2016

Background

Benign epithelial odontogenic tumors such as ameloblastoma and keratocystic odontogenic tumor (KCOT) may exhibit an aggressive clinical course reminiscent of malignancies. Recent studies have indicated that astrocyte elevated gene‐1 (AEG‐1) is highly expressed in a variety of malignant neoplasms and its overexpression is associated with tumor invasion, metastasis, and poor survival. However, the role of AEG‐1 in odontogenic tumors and cysts is still undiscovered.

Methods

Immunohistochemical staining of AEG‐1 was performed in 42 cases of ameloblastoma, 29 cases of KCOT, and 19 cases of dentigerous cyst. Correlations between AEG‐1 expression and clinical parameters of ameloblastomas or KCOTs were statistically analyzed.

Results

AEG‐1‐positive staining was found in 37 (88%) of 42 ameloblastomas and in 24 (83%) of 29 KCOTs. None of 19 dentigerous cysts were positive for AEG‐1 protein. For ameloblastomas, AEG‐1 protein expression was significantly higher in ameloblast‐like cells than in stellate reticulum‐like cells (P = 0.003). For KCOTs, AEG‐1 protein was diffusely expressed in all lining epithelial cells except the superficial parakeratinized cells. Moreover, the frequency of cortical plate perforation was significantly higher in ameloblastomas with high AEG‐1 expression than in ameloblastomas with low or negative AEG‐1 expression (P = 0.043).

Conclusion

Significantly higher expression of AEG‐1 protein in ameloblastomas and KCOTs than in dentigerous cysts and significantly greater frequency of cortical plate perforation in high AEG‐1‐expressed ameloblastomas than in low or negative AEG‐1‐expressed ameloblastomas may imply the high potential of AEG‐1 to serve as a locally invasive biomarker and a target for novel therapy.
Do We Have to Get Along to Innovate? The Influence of Multilevel Social Cohesion on New Product and New Service Development
Authors: Shaner Matthew B. , Beeler Lisa , Noble Charles H.
Published: July 2016

In this study, based on the Comparative Performance Assessment Study survey conducted by the Product Development Management Association, the authors develop and test a model which considers the antecedents and performance outcomes of social cohesion, a seemingly critical organizational factor in new product development (NPD). Using a sample of over 450 innovation and product development professionals from North America, Europe, and Asia, social cohesion is conceptualized and tested across three levels—within team cohesion, between team cohesion, and between firm cohesion. The results of a structural equation model indicate several differences between the antecedents of the varying forms of social cohesion. A post hoc exploration of the difference between goods‐ versus service‐dominant firms provides a clearer picture of cohesion's influence on innovation outcomes. Specifically, within team and between team cohesion are positively associated with new services performance, while for traditional goods‐based NPD, within team, between team, and between firm cohesion all appear to be positively related to performance. The findings suggest that high social cohesion is not always optimal and that managers should focus on specific types or levels of social cohesion as opposed to thinking about social cohesion as a one‐dimensional construct. The findings also suggest that goods‐ and service‐centric firms can use different tactics or strategies to drive social cohesion and, ultimately, new product performance, and that innovation managers may need to allocate resources differently depending on the nature of the market offering being developed. The paper also presents several implications for theory and practice, as well as future research directions related to the various levels of social cohesion and their influence on new product and new service performance.
From Reproductive Rights to Responsibilization: Fashioning Liberal Subjects in Mexico City's New Public Sector Abortion Program
Authors: Singer Elyse Ona
Published: July 2016

Building on medical anthropology literature that analyzes doctor–patient interactions as a charged site for the production of political subjectivities, I demonstrate how a central feature of Mexico City's new public sector abortion program involves “responsibilization.” In accordance with entrenched Ministry of Health objectives, providers transmit a suite of values about personal responsibility and self‐regulation through the use of birth control, hinging abortion rights to responsible reproductive subjectivity. Based on 18 months of ethnographic research across program clinics, including 75 interviews with patients and providers, I show how interrupción legal del embarazo protocols fashion “responsibilized” liberal subjects. I argue that the recent granting of abortion rights in Mexico City—ostensibly a new moment for the construction of women's citizenship—instead reflects and extends long‐standing state agendas of “reproductive governance.” My analysis of reproductive rights as the newest framing of ongoing population policies in Mexico adds to a critical anthropology of human rights and of liberal projects of governance.
GerM is required to assemble the basal platform of the SpoIIIA–SpoIIQ transenvelope complex during sporulation in Bacillus subtilis
Authors: Rodrigues Christopher D. A. , Ramírez‐Guadiana Fernando H. , Meeske Alexander J. , Wang Xindan , Rudner David Z.
Published: July 2016

Sporulating Bacillus subtilis cells assemble a multimeric membrane complex connecting the mother cell and developing spore that is required to maintain forespore differentiation. An early step in the assembly of this transenvelope complex (called the A–Q complex) is an interaction between the extracellular domains of the forespore membrane protein SpoIIQ and the mother cell membrane protein SpoIIIAH. This interaction provides a platform onto which the remaining components of the complex assemble and also functions as an anchor for cell–cell signalling and morphogenetic proteins involved in spore development. SpoIIQ is required to recruit SpoIIIAH to the sporulation septum on the mother cell side; however, the mechanism by which SpoIIQ specifically localizes to the septal membranes on the forespore side has remained enigmatic. Here, we identify GerM, a lipoprotein previously implicated in spore germination, as the missing factor required for SpoIIQ localization. Our data indicate that GerM and SpoIIIAH, derived from the mother cell, and SpoIIQ, from the forespore, have reciprocal localization dependencies suggesting they constitute a tripartite platform for the assembly of the A–Q complex and a hub for the localization of mother cell and forespore proteins.
Nesfatin‐1/NUCB2 in the amygdala influences visceral sensitivity via glucocorticoid and mineralocorticoid receptors in male maternal separation rats
Authors: Zhou X.‐P. , Sha J. , Huang L. , Li T.‐N. , Zhang R.‐R. , Tang M.‐D. , Lin L. , Li X.‐L.
Published: July 2016

Background

Nesfatin‐1, a recently identified satiety molecule derived from nucleobindin 2 (NUCB2), is associated with visceral hypersensitivity in rats and is expressed in the amygdala. We tested the hypothesis that nesfatin‐1 expression in the amygdala is involved in the pathogenesis of irritable bowel syndrome (IBS) visceral hypersensitivity.

Methods

An animal model of IBS‐like visceral hypersensitivity was established using maternal separation (MS) during postnatal days 2–16. The role of nesfatin‐1 in the amygdala on visceral sensitivity was evaluated.

Key Results

Rats subjected to MS showed a significantly increased mean abdominal withdrawal reflex (AWR) score and electromyographic (EMG) activity at 40, 60, and 80 mmHg colorectal distension. Plasma concentrations of nesfatin‐1 and corticosterone were significantly higher than in non‐handled (NH) rats. mRNA and protein expression of nesfatin‐1/NUCB2 in the amygdala were increased in MS rats, but not in NH rats. In MS rats, AWR scores and EMG activity were significantly decreased after anti‐nesfatin‐1/NUCB2 injection. In normal rats, mean AWR score, EMG activity, and corticosterone expression were significantly increased after nesfatin‐1 injection into the amygdala. Nesfatin‐1‐induced visceral hypersensitivity was abolished following application of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) antagonists.

Conclusions & Inferences

Elevated expression of nesfatin‐1/NUCB2 in the amygdala in MS rats suggests a potential role in the pathogenesis of visceral hypersensitivity, which could potentially take place via activation of GR and MR signaling pathways.
Convergence in relationships between leaf traits, spectra and age across diverse canopy environments and two contrasting tropical forests
Authors: Wu Jin , Chavana‐Bryant Cecilia , Prohaska Neill , Serbin Shawn P. , Guan Kaiyu , Albert Loren P. , Yang Xi , van Leeuwen Willem J. D. , Garnello Anthony John , Martins Giordane , Malhi Yadvinder , Gerard France , Oliviera Raimundo Cosme , Saleska Scott R.
Published: July 2016

Leaf age structures the phenology and development of plants, as well as the evolution of leaf traits over life histories. However, a general method for efficiently estimating leaf age across forests and canopy environments is lacking.

Here, we explored the potential for a statistical model, previously developed for Peruvian sunlit leaves, to consistently predict leaf ages from leaf reflectance spectra across two contrasting forests in Peru and Brazil and across diverse canopy environments.

The model performed well for independent Brazilian sunlit and shade canopy leaves (R2 = 0.75–0.78), suggesting that canopy leaves (and their associated spectra) follow constrained developmental trajectories even in contrasting forests. The model did not perform as well for mid‐canopy and understory leaves (R2 = 0.27–0.29), because leaves in different environments have distinct traits and trait developmental trajectories. When we accounted for distinct environment–trait linkages – either by explicitly including traits and environments in the model, or, even better, by re‐parameterizing the spectra‐only model to implicitly capture distinct trait‐trajectories in different environments – we achieved a more general model that well‐predicted leaf age across forests and environments (R2 = 0.79).

Fundamental rules, linked to leaf environments, constrain the development of leaf traits and allow for general prediction of leaf age from spectra across species, sites and canopy environments.
High‐resolution community profiling of arbuscular mycorrhizal fungi
Authors: Schlaeppi Klaus , Bender S. Franz , Mascher Fabio , Russo Giancarlo , Patrignani Andrea , Camenzind Tessa , Hempel Stefan , Rillig Matthias C. , van der Heijden Marcel G. A.
Published: July 2016

Community analyses of arbuscular mycorrhizal fungi (AMF) using ribosomal small subunit (SSU) or internal transcribed spacer (ITS) DNA sequences often suffer from low resolution or coverage. We developed a novel sequencing based approach for a highly resolving and specific profiling of AMF communities.

We took advantage of previously established AMF‐specific PCR primers that amplify a c. 1.5‐kb long fragment covering parts of SSU, ITS and parts of the large ribosomal subunit (LSU), and we sequenced the resulting amplicons with single molecule real‐time (SMRT) sequencing.

The method was applicable to soil and root samples, detected all major AMF families and successfully discriminated closely related AMF species, which would not be discernible using SSU sequences. In inoculation tests we could trace the introduced AMF inoculum at the molecular level. One of the introduced strains almost replaced the local strain(s), revealing that AMF inoculation can have a profound impact on the native community.

The methodology presented offers researchers a powerful new tool for AMF community analysis because it unifies improved specificity and enhanced resolution, whereas the drawback of medium sequencing throughput appears of lesser importance for low‐diversity groups such as AMF.
Sulfur mustard inhalation: mechanisms of injury, alteration of coagulation, and fibrinolytic therapy
Authors: White Carl W. , Rancourt Raymond C. , Veress Livia A.
Published: July 2016

Acute lung injury due to sulfur mustard (SM) inhalation causes the formation of airway fibrin casts that obstruct airways at multiple levels, leading to acute respiratory failure and death. These pathophysiological effects are seen in rodent models of acute SM vapor inhalation, as well as in human victims of acute SM inhalation. In rat models, the initial steps in activation of the coagulation system at extravascular sites depend on tissue factor (TF) expression by airway cells, especially in the microparticle fraction, and these effects can be inhibited by TF pathway inhibitor protein. Not only does the procoagulant environment of the acutely injured lung contribute to airway cast formation, but these lesions persist in airways because of the activation of multiple antifibrinolytic pathways, including plasminogen activator inhibitor‐1, thrombin‐activatable fibrinolysis inhibitor, and α2‐antiplasmin. Airway administration of tissue plasminogen activator can overwhelm these effects and save lives by preventing fibrin‐dependent airway obstruction, gas‐exchange abnormalities, and respiratory failure. In human survivors of SM inhalation, fibrotic processes, including bronchiolitis obliterans and interstitial fibrosis of the lung, are among the most disabling chronic lesions. Antifibrotic therapies may prove useful in preventing either or both of these forms of chronic lung damage.
The Credibility of Hong Kong's Currency Board System: Looking Through the Prism of MS‐VAR Models with Time‐Varying Transition Probabilities
Authors: Blagov Boris , Funke Michael
Published: July 2016

This paper employs a Markov regime‐switching VAR model to describe and analyse the time‐varying credibility of Hong Kong's currency board system. The endogenously estimated discrete regime shifts are made dependent on macroeconomic fundamentals. This enables us to determine which changes in macroeconomic variables can trigger switches between the low and high credibility regimes. We carry out extensive testing to search for the most appropriate specification of the Markov regime‐switching model. We find strong evidence of regime switching behaviour that portrays the time‐varying nature of credibility in the historical data.
Wood‐inhabiting fungi with tight associations with other species have declined as a response to forest management
Authors: Abrego Nerea , Dunson David , Halme Panu , Salcedo Isabel , Ovaskainen Otso
Published: July 2016

Research on mutualistic and antagonistic networks, such as plant–pollinator and host–parasite networks, has shown that species interactions can influence and be influenced by the responses of species to environmental perturbations. Here we examine whether results obtained for directly observable networks generalize to more complex networks in which species interactions cannot be observed directly. As a case study, we consider data on the occurrences of 98 wood‐inhabiting fungal species in managed and natural forests. We specifically ask if and how much the positions of wood‐inhabiting fungal species within the interaction networks influence their responses to forest management. For this, we utilize a joint species distribution model that partitions variation in species occurrences among environmental (i.e. resource availability) and biotic (i.e. species‐to‐species associations) predictors. Our results indicate that in addition to the direct loss of resource‐specialised species, forest management has indirect effects mediated through interactive associations. In particular, species with strong associative links to other species are especially sensitive to forest management.
Will Economic Partnership Agreements Increase Poverty? The Case of Uganda
Authors: Boysen Ole , Matthews Alan
Published: July 2016

Economic Partnership Agreements (EPAs) between the EU and African Caribbean and Pacific countries are frequently criticized because of fears about negative implications for economic development. Using Uganda as a case study, this paper employs an integrated computable general equilibrium‐microsimulation model framework rich in household‐level detail to assess the consequences of the East African Community EPA for economic output and poverty in Uganda. Simulations of the agreement's tariff liberalization provisions indicate a very small negative economic impact and ambiguous outcomes for poverty. The poverty results depend in size and sign on the poverty line, on the way the government addresses tariff revenue losses and on labor market assumptions.
Tuberculosis and non‐tuberculous mycobacteria among HIV‐infected individuals in Ghana
Authors: Bjerrum Stephanie , Oliver‐Commey Joseph , Kenu Ernest , Lartey Margaret , Newman Mercy Jemima , Addo Kennedy Kwasi , Hilleman Doris , Andersen Aase Bengaard , Johansen Isik Somuncu
Published: July 2016

Objectives

To assess the prevalence and clinical importance of previously unrecognised tuberculosis (TB) and isolation of non‐tuberculous mycobacteria (NTM) among HIV‐infected individuals in a teaching hospital in Ghana.

Methods

Intensified mycobacterial case finding was conducted among HIV‐positive individuals before initiation of antiretroviral therapy (ART). Data were collected on socio‐demographic characteristics, medical history and TB‐related signs and symptoms, and participants were followed for six months to determine treatment and vital status. Two sputum samples were obtained and examined for mycobacteria with smear microscopy, culture and Xpert MTB/RIF assay. NTM species were identified with the GenoType Mycobacterium CM/AS or sequence analysis of 16S rRNA gene.

Results

Of 473 participants, 60 (12.7%) had confirmed pulmonary TB, and 38 (8.0%) had positive cultures for NTM. Mycobacterium avium complex was identified in 9/38 (23.7%) of NTM isolates. Participants with NTM isolated were more likely to have CD4 cell count< 100 cells/μL (aOR 2.37; 95% CI: 1.10‐5.14), BMI<18.5kg/m2 (aOR 2.51; 95% CI: 1.15‐5.51) and fever ≥2 weeks (aOR 2.76; 95% CI: 1.27‐6.03) at baseline than participants with no mycobacteria. By six months, 76 (16.1%) participants had died; 20 (33.3%) with confirmed TB and 9 (23.7%) with NTM‐positive culture. Mortality at six months was independently associated with TB diagnosis at enrolment (aHR 1.97; 95% CI 1.09‐3.59), but not with NTM isolation after controlling for age, sex, CD4 cell count, BMI, prolonged fever and ART initiation.

Conclusions

Intensified mycobacterial screening of HIV‐infected individuals revealed a high burden of unrecognised pulmonary TB before ART initiation, which increased risk of death within six months. NTM were frequently isolated and associated with signs of poor clinical status but not with increased mortality.
Lower‐dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study
Authors: Kamphuis Marije , Paridaans Noortje , Winkelhorst Dian , Wikman Agneta , Tiblad Eleonor , Lopriore Enrico , Westgren Magnus , Oepkes Dick
Published: July 2016

BACKGROUND

Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose‐finding study. IVIG is an expensive multidonor human blood product with dose‐related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG.

STUDY DESIGN AND METHODS

We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed.

RESULTS

A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], −37.4 to 23.7]) and incidence of severe thrombocytopenia (<30 × 109/L; n = 7/46 vs. n = 7/63; odds ratio, 1.43 [CI, 0.46–4.42]). No ICH occurred.

CONCLUSION

In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia.
Lynxacarus radovskyimites in feral cats: a study of diagnostic methods, preferential body locations, co‐infestations and prevalence
Authors: Ketzis Jennifer K. , Dundas James , Shell Linda G.
Published: July 2016

Background

Lynxacarus radovskyi(fur mites) are ectoparasites found on the hair shafts of cats living in tropical environments. Diagnosis is via microscopic examination of hairs. Various anatomical areas have been reported to harbour these mites.

Objectives

To assess adhesive tape impressions and trichograms for detectingL. radovskyiand co‐infestations;to determine host body predilection sites and affected gender; to determine prevalence ofL. radovskyiin a feral cat population.

Animals

121 feral cats in a trap, neuter and release programme.

Methods

After cats were premedicated for surgical sterilization, hairs from seven to nine body sites were removed from each cat using adhesive tape impression and trichogram techniques. Samples were examined at 10–100× magnification using compound or stereo microscopes.

Results

The prevalence ofL. radovskyiwas 71% (86 of 121) within the feral cat population. Tape impressions identified 75 cats; trichograms identified 56 cats. There were fewer false negative results with tape impressions. Caudal body sites were more likely to be positive, with the perianal area being the most commonly affected. Males and females were infested equally. Tape impressions identified moreCheyletiella blakeiinfestations and both methods identified someFelicola felisinfestations.

Conclusions and clinical importance

Tape impressions were easier to perform and identified moreL. radovskyipositive cats and more co‐infestations. Hairs from the perianal area and other caudal body sites are most likely to harbourL. radovskyi. Within this feral cat population,L. radovskyiwas a common infestation.
Acute‐phase proteins as diagnostic markers in horses with colic
Authors: Pihl Tina H. , Scheepers Elrien , Sanz Macarena , Goddard Amelia , Page Patrick , Toft Nils , Kjelgaard‐Hansen Mads , Andersen Pia H. , Jacobsen Stine
Published: July 2016

Objective

To investigate the diagnostic potential of the concentrations of acute‐phase proteins serum amyloid A (SAA), haptoglobin (Hp), and fibrinogen in blood and peritoneal fluid (PF) for differentiating horses with inflammatory colic (entero‐colitis and peritonitis) from those with surgical colic.

Design

Prospective observational multicenter study.

Setting

Two university referral hospitals.

Animals

Horses referred for severe acute abdominal pain to Hospital 1 (n = 148) or Hospital 2 (n = 78).

Intervention

Blood and PF samples collected at admission were used for acute‐phase protein concentration measurement.

Measurements and Main Results

A multivariable logistic model including clinical parameters (lethargy, rectal temperature >38°C [100.4°F], normal rectal examination findings, and gastric reflux of 5–10 L) recorded at admission was constructed from Hospital 1 data. The ability of the model to correctly differentiate inflammatory from surgical colic was 86% determined as area under the receiver operating characteristic curve. Adding blood parameters (WBC, PCV, total plasma protein, lactate, SAA, Hp, and fibrinogen concentrations) to the logistic model based on clinical parameters revealed that only WBC and SAA and fibrinogen concentrations improved the model. With SAA included in the model no additional blood parameters improved the model, and the final model had an area under the curve of 90%. Addition of PF parameters (hemolysis, total protein concentration, WBC, SAA, or Hp concentrations) did not improve the model. When validated in Hospital 2 data, the models had good integrity and diagnostic performance.

Conclusions

Evaluation of SAA in serum improved the ability to differentiate horses with acute inflammatory colic requiring medical treatment from horses with colic requiring surgery, as it allowed an additional 4% of horses to be correctly classified into medical and surgical cases. Improved differentiation of these 2 groups of horses with colic may minimize the risk of unnecessary or delayed surgery.
Traumatic uterine rupture in three felids
Authors: Davies Rebecca , Rozanski Elizabeth , Tseng Florina , Jennings Samuel , Paul April
Published: July 2016

Objective

To describe 3 near‐full‐term, young‐adult felids (2 domestic shorthair cats, and 1 bobcat [Lynx rufus]) that experienced uterine rupture following trauma.

Series Summary

Two of the animals had motor vehicular trauma and 1 had abdominal bite wounds. The 2 domestic cats that were treated with surgical exploration and ovariohysterectomy recovered uneventfully. The bobcat died during hospitalization prior to surgical intervention, and necropsy identified uterine rupture and associated peritonitis.

Unique Information Provided

Traumatic uterine rupture should be considered in known or suspected pregnant animals that experience blunt or penetrating trauma, particularly if they are in late‐term pregnancy.
Has the tooth fairy entered the realm of science?
Authors: Peñagarikano Olga
Published: July 2016

Analysis of baby teeth links prenatal and infant exposure to metals with development of schizophrenia.
Structural and Mutagenic Analysis of Metallo-β-Lactamase IMP-18
Authors: Furuyama Takamitsu , Nonomura Haruka , Ishii Yoshikazu , Hanson Nancy D. , Shimizu-Ibuka Akiko
Published: July 2016

IMP-type metallo-β-lactamases (MBLs) are exogenous zinc metalloenzymes that hydrolyze a broad range of β-lactams, including carbapenems. Here we report the crystal structure of IMP-18, an MBL cloned from
Pseudomonas aeruginosa
, at 2.0-Å resolution. The overall structure of IMP-18 resembles that of IMP-1, with an αβ/βα “folded sandwich” configuration, but the loop that covers the active site has a distinct conformation. The relationship between IMP-18's loop conformation and its kinetic properties was investigated by replacing the amino acid residues that can affect the loop conformation (Lys44, Thr50, and Ile69) in IMP-18 with those occupying the corresponding positions in the well-described enzyme IMP-1. The replacement of Thr50 with Pro considerably modified IMP-18's kinetic properties, specifically those pertaining to meropenem, with the
k
cat
/

K
m

value increased by an order of magnitude. The results indicate that this is a key residue that defines the kinetic properties of IMP-type β-lactamases.
Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival
Authors: Lina Taslima T. , Dunphy Paige S. , Luo Tian , McBride Jere W.
Published: July 2016

Ehrlichia chaffeensis
preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown
E. chaffeensis
type 1 secreted tandem repeat protein (TRP) effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate
E. chaffeensis
, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD) occurs in response to
E. chaffeensis
or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes
notch1
,
adam17
,
hes
, and
hey
. Significant differences in canonical Notch signaling gene expression levels (>40%) were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs) against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that
E. chaffeensis
TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4) expression. This investigation reveals a novel mechanism whereby
E. chaffeensis
exploits the Notch pathway to evade the host innate immune response for intracellular survival.

IMPORTANCE
E. chaffeensis
is an obligately intracellular bacterium and the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. Mechanisms by which
E. chaffeensis
establishes intracellular infection and avoids innate host defenses are not understood, but functionally relevant host-pathogen interactions with type 1 secreted TRP effectors are essential for the ehrlichial cellular reprogramming strategy. This study provides further insight into the molecular strategies used by obligately intracellular pathogens such as
E. chaffeensis
, which have small genomes and a limited number of effector proteins and exploit evolutionarily conserved host cell programs such as Notch signaling to promote infection and intracellular survival.