bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychopathy from a Basic Trait Perspective: The Utility of a Five‐Factor Model Approach
Authors: Lynam Donald R. , Miller Joshua D.
Published: September 2014

The present article argues that psychopathy is best understood as a collection of traits from the Five‐Factor Model of personality (FFM). We demonstrate that specific FFM traits involved in psychopathy are well delineated; the same personality profile emerges across methods. We review research demonstrating that this FFM profile can be used to assess psychopathy, including the development of a psychopathy‐specific FFM assessment that appears to do an even better job of assessing psychopathy than the NEO PI‐R while remaining true to the basic structural model. We demonstrate the advantages to understanding psychopathy in this way. The FFM provides an assay of extant inventories, accounts for the epidemiology of psychopathy, and explains the factor structure of various inventories. The elemental view of psychopathy allows psychopathy to be built from the ground up, trait by trait. Perhaps most importantly, the FFM is unique in providing a connection to basic research in personality.
Hybrid speciation through sorting of parental incompatibilities in Italian sparrows
Authors: Hermansen Jo S. , Haas Fredrik , Trier Cassandra N. , Bailey Richard I. , Nederbragt Alexander J. , Marzal Alfonso , Sætre Glenn‐Peter
Published: September 2014

Speciation by hybridization is emerging as a significant contributor to biological diversification. Yet, little is known about the relative contributions of (i) evolutionary novelty and (ii) sorting of pre‐existing parental incompatibilities to the build‐up of reproductive isolation under this mode of speciation. Few studies have addressed empirically whether hybrid animal taxa are intrinsically isolated from their parents, and no study has so far investigated by which of the two aforementioned routes intrinsic barriers evolve. Here, we show that sorting of pre‐existing parental incompatibilities contributes to intrinsic isolation of a hybrid animal taxon. Using a genomic cline framework, we demonstrate that the sex‐linked and mitonuclear incompatibilities isolating the homoploid hybrid Italian sparrow at its two geographically separated hybrid–parent boundaries represent a subset of those contributing to reproductive isolation between its parent species, house and Spanish sparrows. Should such a sorting mechanism prove to be pervasive, the circumstances promoting homoploid hybrid speciation may be broader than currently thought, and indeed, there may be many cryptic hybrid taxa separated from their parent species by sorted, inherited incompatibilities.
Epigenetic variation predicts regional and local intraspecific functional diversity in a perennial herb
Authors: Medrano Mónica , Herrera Carlos M. , Bazaga Pilar
Published: September 2014

The ecological significance of epigenetic variation has been generally inferred from studies on model plants under artificial conditions, but the importance of epigenetic differences between individuals as a source of intraspecific diversity in natural plant populations remains essentially unknown. This study investigates the relationship between epigenetic variation and functional plant diversity by conducting epigenetic (methylation‐sensitive amplified fragment length polymorphisms, MSAP) and genetic (amplified fragment length polymorphisms, AFLP) marker–trait association analyses for 20 whole‐plant, leaf and regenerative functional traits in a large sample of wild‐growing plants of the perennial herb Helleborus foetidus from ten sampling sites in south‐eastern Spain. Plants differed widely in functional characteristics, and exhibited greater epigenetic than genetic diversity, as shown by per cent polymorphism of MSAP fragments (92%) or markers (69%) greatly exceeding that for AFLP ones (41%). After controlling for genetic structuring and possible cryptic relatedness, every functional trait considered exhibited a significant association with at least one AFLP or MSAP marker. A total of 27 MSAP (13.0% of total) and 12 AFLP (4.4%) markers were involved in significant associations, which explained on average 8.2% and 8.0% of trait variance, respectively. Individual MSAP markers were more likely to be associated with functional traits than AFLP markers. Between‐site differences in multivariate functional diversity were directly related to variation in multilocus epigenetic diversity after multilocus genetic diversity was statistically accounted for. Results suggest that epigenetic variation can be an important source of intraspecific functional diversity in H. foetidus, possibly endowing this species with the capacity to exploit a broad range of ecological conditions despite its modest genetic diversity.
Mobile Impact Testing for Structural Flexibility Identification with only a Single Reference
Authors: Zhang J. , Guo S.L. , Zhang Q.Q.
Published: September 2014

In contrast to the traditional impact test method requiring a number of sensors to measure the entire structure, a mobile impact test method sequentially measuring segments of the structure and the related data processing strategy is proposed. Especially, only a single reference node is required when integrating measurements of the segments to identify the flexibility characteristic of the entire structure. Equations are first derived to adjust the magnitudes of mode shapes of the substructure to a same scaling level. Then the phase angle concept is utilized to determine the coherent signs of mode shapes for structural flexibility identification. The advantage of the proposed method is that it outputs the same flexibility identification results as the traditional impact test method, whereas it only requires a single reference no matter how many segments of the structure are divided, thus it significantly speeds up the impact test and makes it be an ideal approach for rapid testing of short/middle span bridges. Numerical and experiment examples investigated successfully verify the effectiveness of the proposed method for structural flexibility identification.
Gymnosperms of Laos
Authors: Averyanov Leonid V. , Nguyen Tien Hiep , Sinh Khang Nguyen , Pham The Van , Lamxay Vichith , Bounphanmy Somchanh , Lorphengsy Shengvilai , Phan Loc Ke , Lanorsavanh Soulivanh , Chantthavongsa Khamfa
Published: September 2014

The present review includes keys for identification and summary data on the nomenclature, morphology, ecology and distribution for all 33 species of gymnosperms hitherto recorded in the flora of Laos. They belong to 8 families and 15 genera. Important additions to these data were obtained during fieldwork in 2009–2013, when 58 localities containing 25 species from 14 genera and 8 families were explored and initially studied. Two species, Cycas laotica and Pinus cernua, are described as new species for science. Seven species, Cycas dolichophylla, C. inermis, C. macrocarpa, C. micholitzii, C. nongnoochiae, C. petraea and Taxus wallichiana, are found in Laos and represent new records for the flora of the country. Maps of the distribution and illustrations for the newly discovered gymnosperm species are provided. All observations, records and discoveries are based on reliable scientific literature and collected voucher herbarium specimens housed in main regional herbaria.
High occurrence of rare inland halophytes on post‐mining sites in western Ukraine
Authors: Woch Marcin Wiktor , Trzcińska‐Tacik Helena
Published: September 2014

Rare inland halophytic vegetation including the associations Salicornietum prostratae, Spergulario marginatae‐Suaedetum prostratae, Puccinellietum limosae, com. Puccinellietum limosae – a variant of Aster tripolium subsp. pannonicus and Astero pannonici‐Bolboschoenetum compacti have been found on 3 localities in the Drohobych region of western Ukraine. These are isolated (‘island’) localities, almost unknown until today. Halophytes grew there on salted sites in the vicinity of the old salt industry. Species of halophytes previously not known from this region were discovered: Aster tripolium subsp. pannonicus, Bolboschoenus maritimus, Gypsophila paniculata, Limonium gmelinii, Lotus tenuis, Puccinellia distans, Sonchus palustris, Suaeda prostrata, Trifolium fragiferum var. bonannii, Triglochin maritima, Typha laxmannii and Zannichellia palustris subsp. pedicellata. The occurence of these plants strictly depends on the presence of salt in the soil and they are endangered by shrinkage of salted sites following the termination of the salt industry in Drohobych region.
Experiences from the Brazilian Atlantic Forest: ecological findings and conservation initiatives
Authors: Joly Carlos A. , Metzger Jean Paul , Tabarelli Marcelo
Published: September 2014

The Brazilian Atlantic Forest hosts one of the world's most diverse and threatened tropical forest biota. In many ways, its history of degradation describes the fate experienced by tropical forests around the world. After five centuries of human expansion, most Atlantic Forest landscapes are archipelagos of small forest fragments surrounded by open‐habitat matrices. This ‘natural laboratory’ has contributed to a better understanding of the evolutionary history and ecology of tropical forests and to determining the extent to which this irreplaceable biota is susceptible to major human disturbances. We share some of the major findings with respect to the responses of tropical forests to human disturbances across multiple biological levels and spatial scales and discuss some of the conservation initiatives adopted in the past decade. First, we provide a short description of the Atlantic Forest biota and its historical degradation. Secondly, we offer conceptual models describing major shifts experienced by tree assemblages at local scales and discuss landscape ecological processes that can help to maintain this biota at larger scales. We also examine potential plant responses to climate change. Finally, we propose a research agenda to improve the conservation value of human‐modified landscapes and safeguard the biological heritage of tropical forests.

Contents

Summary
459

I.
Introduction
459

II.
The Atlantic Forest: a highly diverse, relevant and threatened forest
460

III.
Biotic homogenization and forest secondarization
462

IV.
Species persistence at larger scales
464

V.
Future threats: climate change impacts
466

VI.
Atlantic Forest conservation: integrating basic and applied research agendas
467

VII.
Concluding remarks
469

Acknowledgements
469

References
469
The unseen iceberg: plant roots in arctic tundra
Authors: Iversen Colleen M. , Sloan Victoria L. , Sullivan Patrick F. , Euskirchen Eugenie S. , McGuire A. David , Norby Richard J. , Walker Anthony P. , Warren Jeffrey M. , Wullschleger Stan D.
Published: September 2014

Plant roots play a critical role in ecosystem function in arctic tundra, but root dynamics in these ecosystems are poorly understood. To address this knowledge gap, we synthesized available literature on tundra roots, including their distribution, dynamics and contribution to ecosystem carbon and nutrient fluxes, and highlighted key aspects of their representation in terrestrial biosphere models. Across all tundra ecosystems, belowground plant biomass exceeded aboveground biomass, with the exception of polar desert tundra. Roots were shallowly distributed in the thin layer of soil that thaws annually, and were often found in surface organic soil horizons. Root traits – including distribution, chemistry, anatomy and resource partitioning – play an important role in controlling plant species competition, and therefore ecosystem carbon and nutrient fluxes, under changing climatic conditions, but have only been quantified for a small fraction of tundra plants. Further, the annual production and mortality of fine roots are key components of ecosystem processes in tundra, but extant data are sparse. Tundra root traits and dynamics should be the focus of future research efforts. Better representation of the dynamics and characteristics of tundra roots will improve the utility of models for the evaluation of the responses of tundra ecosystems to changing environmental conditions.

Contents

Summary
34

I.
Arctic tundra and plant roots: an introduction
35

II.
A comprehensive literature review
35

III.
A brief history of fine‐root studies in tundra ecosystems
41

IV.
Distribution and dynamics of tundra plant roots: current knowledge and future directions
43

V.
Contribution of living plant roots to fluxes of CO2 and CH4 from tundra ecosystems to the atmosphere
49

VI.
The role of fine roots in tundra ecosystem nutrient cycling
50

VII.
Opportunities for improving the representation of root processes in arctic models
51

VIII.
Conclusions and priorities for future research
52

Acknowledgements
53

References
53
The Oral Surgery trainee perspective
Authors: Patel V. , Ormondroyd L.
Published: September 2014

Aim

This study aims to gather information about Oral Surgery training programmes by carrying out a survey of the trainees currently in post.

Materials and methods

A web‐based questionnaire was sent to current Oral Surgery trainees. Questions about training environment, clinical exposure, examinations and future career aspirations were included.

Results

Thirty of the 40 trainees contacted responded by part or fully completing the questionnaire. The mean time period of qualification from dental school to Oral Surgery training was 5.1 years. The majority, 80%, of trainees were on a 3‐year full‐time programme that entitled them to sit the Membership in Oral Surgery Examination (M Oral Surg) only. Four trainees who responded were eligible to sit both M Oral Surg and the Intercollegiate Specialty Fellowship Exam.

Conclusions

The questionnaire highlighted areas Oral Surgery trainees perceived to be important for their training and development. Identification of these issues will allow attention to be focused in addressing them.
Regression Analysis of Length‐biased and Right‐censored Failure Time Data with Missing Covariates
Authors: Hu Na , Chen Xuerong , Sun Jianguo
Published: September 2014

Length‐biased and right‐censored failure time data arise from many fields, and their analysis has recently attracted a great deal of attention. Two examples of the areas that often produce such data are epidemiological studies and cancer screening trials. In this paper, we discuss regression analysis of such data in the presence of missing covariates, for which no established inference procedure seems to exist. For the problem, we consider the data arising from the proportional hazards model and propose two inverse probability weighted estimation procedures. The asymptotic properties of the resulting estimators are established, and the extensive simulation study conducted for the evaluation of the proposed methods suggests that they work well for practical situations.
Comparison of equine endometrial cytology samples collected with uterine swab, uterine brush, and low‐volume lavage from healthy mares
Authors: Bohn Andrea A. , Ferris Ryan A. , McCue Patrick M.
Published: September 2014

Background

There have been no studies evaluating and comparing the quality of equine endometrial cytology samples obtained via the 3 most common sampling techniques from healthy mares.

Objectives

The objective was to compare the quality and contents of equine endometrial samples obtained by 3 different sampling techniques: double‐guarded uterine swab, double‐guarded uterine brush, and low‐volume lavage (LVL), all collected from clinically healthy mares.

Methods

Samples were collected from 24 healthy mares in early estrus. In 19 mares, samples were obtained in a sequential manner, first with the swab, then with the brush, followed by LVL. Cytologic evaluation included estimates of quality, cellularity, and presence of inflammatory cells. The clinical pathologist performing the evaluations was blinded to the collection technique. The Friedman test with Dunn's multiple comparisons was used to compare rankings of quality, cellularity, and the presence or absence of inflammatory cells. Observed cytologic differences were described.

Results

All techniques provided diagnostic samples, but swabs yielded the lowest quality sample. In our hands, the uterine brush provided the highest quality sample. Low‐volume lavage samples contained higher numbers of neutrophils, although, in general, < 1 neutrophil/400× field is expected for all endometrial sampling techniques in healthy mares.

Conclusions

All sampling techniques can be adequate methods for endometrial cytology, but the brush technique consistently provided the best sample. Sample contamination or poor slide quality can adversely affect interpretation. The most accurate criteria for determining what constitutes mild endometritis in mares have yet to be established.
Physiological links between circadian rhythms, metabolism and nutrition
Authors: Johnston Jonathan D.
Published: September 2014

New Findings

What is the topic of this review?

This review provides a discussion of the links between circadian, metabolic and nutritional physiology, with a particular focus on mouse and human studies.

What advances does it highlight?

Links between circadian biology and metabolism exist from the molecular level through to whole‐organism physiology. Advances highlighted include the following: interactions between circadian clock genes/proteins and intracellular metabolic pathways; identification of the function of clocks in specific peripheral tissues; effects of timed feeding; and the variable effect of obesity on rhythms.

Circadian rhythms, metabolism and nutrition are closely interlinked. A great deal of recent research has investigated not only how aspects of metabolic physiology are driven by circadian clocks, but also how these circadian clocks are themselves sensitive to metabolic change. At the cellular level, novel feedback loops have been identified that couple circadian ‘clock genes’ and their proteins to expression of nuclear receptors, regulation of redox state and other major pathways. Using targeted disruption of circadian clocks, mouse models are providing novel insight into the role of tissue‐specific clocks in glucose homeostasis and body weight regulation. The relationship between circadian rhythms and obesity appears complex, with variable alteration of rhythms in obese individuals. However, it is clear from animal studies that the timing and nutritional composition of meals can regulate circadian rhythms, particularly in peripheral tissues. Translation of these findings to human physiology now represents an important goal.
The role of gut endocrine cells in control of metabolism and appetite
Authors: Parker Helen E. , Gribble Fiona M. , Reimann Frank
Published: September 2014

New Findings

What is the topic of this review?

Gut hormones, especially glucagon‐like peptide‐1 (GLP‐1), have beneficial effects in diabetes and obesity. Recent research addresses the underlying mechanisms of the secretion and action of GLP‐1.

What advances does it highlight?

The development of transgenic reporter mice with fluorescently tagged GLP‐1‐secreting cells has helped to characterize the molecular mechanisms underlying hormone secretion and has challenged the traditional classification of enteroendocrine cells by hormone expression alone. Recent adoption of this strategy to label GLP‐1‐receptor‐positive cells has highlighted that peripheral and centrally released GLP‐1 acts on a number of different targets, including a variety of neurons. Evidence for their role in glucose homeostasis and appetite control is discussed.

After food is ingested, nutrients pass through the gastrointestinal tract, stimulating the release of a range of peptide hormones. Among their many local, central and peripheral actions, these hormones act to mediate glucose metabolism and satiety. Indeed, it is the modification of gut hormone secretion that is considered partly responsible for the normalization of glycaemic control and the reduction in appetite seen in many patients after certain forms of bariatric surgery. This review describes recent developments in our understanding of the secretion and action of anorexigenic gut hormones, primarily concentrating on glucagon‐like peptide‐1 (GLP‐1).
Role of nucleation layer morphology in determining the statistical roughness of CVD-grown thin films
Authors: Babar Shaista , Li Tian T. , Abelson John R.
Published: September 2014

During the chemical vapor deposition of thin films, a molecular inhibitor can be added to control the morphology during the nucleation stage and/or the conformal coating behavior during the growth stage. The authors use this control strategy to determine the separate influence of nucleation morphology and of conformal growth on the final surface roughness, evaluated through the power spectral density of AFM height data. The experimental system is HfB2 deposition from the precursor Hf(BH4)4 using NH3 as the inhibitor. For a nucleation layer consisting of mounds, the low frequency (long lateral range) roughness cannot be reduced by the overgrowth of film, even with the conformal growth conditions. Conversely, when the nucleation layer consists of a dense compact of islands, the low frequency roughness remains low throughout film growth, even when carried out in the nonconformal growth conditions. In all cases, the high frequency portion of the roughness decays in a similar manner, indicating that short-range smoothing mechanism is operative. The sensitivity of the final surface roughness to the morphology of the initial nucleation layer demonstrates that “shadowing” by peaks in the surface height is a strong kinetic driving force for roughening, consistent with previous theory. The use of an inhibitor molecule in CVD provides a means to obtain ultrasmooth films on relatively unreactive substrates, without the need for surface activation and without changing the film composition.
WHO for the 21st Century
Authors: Chan Margaret
Published: September 2014

WHO is leading the search for better ways to improve health in the face of new challenges to the well-being of individuals and populations.
The Unconscionable Gap Between What We Know and What We Do
Authors: Hyman Steven E.
Published: September 2014

Policy failures precipitate unacceptable treatment of mental illnesses worldwide.
Culture Shock! Brain-Like Tissue Grown in Vitro Has Potential
Authors: Spiller Kara L.
Published: September 2014

Careful biomaterial design supports generation of electrophysiologically relevant brain-like tissue in vitro.
Multifunctional Nutrient-Binding Proteins Adapt Human Symbiotic Bacteria for Glycan Competition in the Gut by Separately Promoting Enhanced Sensing and Catalysis
Authors: Cameron Elizabeth A. , Kwiatkowski Kurt J. , Lee Byung-Hoo , Hamaker Bruce R. , Koropatkin Nicole M. , Martens Eric C.
Published: September 2014

To compete for the dynamic stream of nutrients flowing into their ecosystem, colonic bacteria must respond rapidly to new resources and then catabolize them efficiently once they are detected. The
Bacteroides thetaiotaomicron
starch utilization system (Sus) is a model for nutrient acquisition by symbiotic gut bacteria, which harbor thousands of related Sus-like systems. Structural investigation of the four Sus outer membrane proteins (SusD, -E, -F, and -G) revealed that they contain a total of eight starch-binding sites that we demonstrated, using genetic and biochemical approaches, to play distinct roles in starch metabolism
in vitro
and
in vivo
in gnotobiotic mice. SusD, whose homologs are abundant in the human microbiome, is critical for the initial sensing of available starch, allowing
sus
transcriptional activation at much lower concentrations than without this function. In contrast, seven additional binding sites across SusE, -F, and -G are dispensable for
sus
activation. However, they optimize the rate of growth on starch in a manner dependent on the expression of the bacterial polysaccharide capsule, suggesting that they have evolved to offset the diffusion barrier created by this structure. These findings demonstrate how proteins with similar biochemical behavior can serve orthogonal functions during different stages of cellular adaptation to nutrients. Finally, we demonstrated in gnotobiotic mice fed a starch-rich diet that the Sus binding sites confer a competitive advantage to
B. thetaiotaomicron
in vivo
in a manner that is dependent on other colonizing microbes. This study reveals how numerically dominant families of carbohydrate-binding proteins in the human microbiome fulfill separate and sometimes cooperative roles to optimize gut commensal bacteria for nutrient acquisition.

IMPORTANCE
Our intestinal tract harbors trillions of symbiotic microbes. A critical function contributed by this microbial community is the ability to degrade most of the complex carbohydrates in our diet, which not only change from meal to meal but also cannot be digested by our own bodies. A numerically abundant group of gut bacteria called the
Bacteroidetes
plays a prominent role in carbohydrate digestion in humans and other animals. Currently, the mechanisms that allow this bacterial group to rapidly respond to available carbohydrates and then digest them efficiently are unclear. Here, we present novel functions for four carbohydrate-binding proteins present in one member of the
Bacteroidetes
, revealing that these proteins serve unique and separable roles in either initial nutrient sensing or subsequent digestion. Because the protein families investigated are numerous in other gut bacteria colonizing nearly all humans and animals, our findings are fundamentally important to understanding how symbiotic microbes assist human digestion.
Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in
Python regius
Authors: Stenglein Mark D. , Jacobson Elliott R. , Wozniak Edward J. , Wellehan James F. X. , Kincaid Anne , Gordon Marcus , Porter Brian F. , Baumgartner Wes , Stahl Scott , Kelley Karen , Towner Jonathan S. , DeRisi Joseph L.
Published: September 2014

A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (
Python regius
) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order
Nidovirales
. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (
n
= 8) but was not detected in healthy pythons or other snakes (
n
= 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in
Torovirinae
subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.

IMPORTANCE
Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order
Nidovirales
that was present in cases but not controls. While nidoviruses are known to infect a variety of animals, this is the first report of a nidovirus recovered from any reptile. This report will enable diagnostics that will assist in determining the role of this virus in the causation of disease, which would allow control of the disease in zoos and private collections. Given its evolutionary divergence from known nidoviruses and its unique host, the study of reptile nidoviruses may further our understanding of related diseases and the viruses that cause them in humans and other animals.
Critical Glycosylated Residues in Exon Three of Erythrocyte Glycophorin A Engage Plasmodium falciparum EBA-175 and Define Receptor Specificity
Authors: Salinas Nichole D. , Paing May M. , Tolia Niraj H.
Published: September 2014

Erythrocyte invasion is an essential step in the pathogenesis of malaria. The erythrocyte binding-like (EBL) family of
Plasmodium falciparum
proteins recognizes glycophorins (Gp) on erythrocytes and plays a critical role in attachment during invasion. However, the molecular basis for specific receptor recognition by each parasite ligand has remained elusive, as is the case with the ligand/receptor pair
P. falciparum
EBA-175 (PfEBA-175)/GpA. This is due largely to difficulties in producing properly glycosylated and functional receptors. Here, we developed an expression system to produce recombinant glycosylated and functional GpA, as well as mutations and truncations. We identified the essential binding region and determinants for PfEBA-175 engagement, demonstrated that these determinants are required for the inhibition of parasite growth, and identified the glycans important in mediating the PfEBA-175–GpA interaction. The results suggest that PfEBA-175 engages multiple glycans of GpA encoded by exon 3 and that the presentation of glycans is likely required for high-avidity binding. The absence of exon 3 in GpB and GpE due to a splice site mutation confers specific recognition of GpA by PfEBA-175. We speculate that GpB and GpE may have arisen due to selective pressure to lose the PfEBA-175 binding site in GpA. The expression system described here has wider application for examining other EBL members important in parasite invasion, as well as additional pathogens that recognize glycophorins. The ability to define critical binding determinants in receptor-ligand interactions, as well as a system to genetically manipulate glycosylated receptors, opens new avenues for the design of interventions that disrupt parasite invasion.

IMPORTANCE
Plasmodium falciparum
uses distinct ligands that bind host cell receptors for invasion of red blood cells (RBCs) during malaria infection. A key entry pathway involves
P. falciparum
EBA-175 (PfEBA-175) recognizing glycophorin A (GpA) on RBCs. Despite knowledge of this protein-protein interaction, the complete mechanism for specific receptor engagement is not known. PfEBA-175 recognizes GpA but is unable to engage the related RBC receptor GpB or GpE. Understanding the necessary elements that enable PfEBA-175 to specifically recognize GpA is critical in developing specific and potent inhibitors of PfEBA-175 that disrupt host cell invasion and aid in malaria control. Here, we describe a novel system to produce and manipulate the host receptor GpA. Using this system, we probed the elements in GpA necessary for engagement and thus for host cell invasion. These studies have important implications for understanding how ligands and receptors interact and for the future development of malaria interventions.
Outcomes of full-term infants with bilious vomiting: observational study of a retrieved cohort
Authors: Mohinuddin Syed , Sakhuja Pankaj , Bermundo Benjie , Ratnavel Nandiran , Kempley Stephen , Ward Harry C , Sinha Ajay
Published: September 2014

Bilious vomiting in a neonate may be a sign of intestinal obstruction often resulting in transfer requests to surgical centres. The aim of this study was to assess the use of clinical findings at referral in predicting outcomes and to determine how often such patients have a time-critical surgical condition (eg, volvulus, where a delay in treatment is likely to compromise gut viability).

Methods

4-year data and outcomes of all term newborns aged ≤7 days with bilious vomiting transferred by a regional transfer service were analysed. Specificity, sensitivity, likelihood ratios, correlations, prior and posterior probability of clinical findings in predicting newborns with surgical diagnosis were calculated.

Results

Of 163 neonates with bilious vomiting, 75 (46%) had a surgical diagnosis and 23 (14.1%) had a time-critical surgical condition. The diagnosis of a surgical condition in neonates with bilious vomiting was significantly associated with abdominal distension (χ2=5.17, p=0.023), abdominal tenderness (χ2=5.90, p=0.015) and abnormal abdominal X-ray findings (χ2=5.68, p=0.017) but not with palpation findings of a soft as compared with a tense abdomen (χ2=3.21, p=0.073). Abnormal abdominal X-ray, abdominal distension and tenderness had 97%, 74% and 62% sensitivity, respectively, with regard to association with an underlying surgical diagnosis. Normal abdominal X-ray reduced the posterior probability of surgical diagnosis from 50% to 16%. Overall, clinical findings at referral did not differentiate between infants with or without surgical or time-critical condition.

Conclusions

We recommend that term neonates with bilious vomiting referred for transfer are prioritised as time critical.
Lock and key cast metallic sectional denture: a revised approach for oral rehabilitation of a patient with microstomia
Authors: Baslas Varun , Agrawal Kaushal Kishor , Chand Pooran , Jurel Sunit Kumar
Published: September 2014

Microstomia is a common occurrence in clinical practice that may hinder the conventional prosthetic treatment of edentulous patients. Oral augmentation exercises to increase the vertical opening and sectional or collapsible dentures have been described in the past, which have their own drawbacks and limitations. The present article highlights a new approach for rehabilitation of a patient with microstomia with cast lock and key attachments leading to greater ease for both the patient and the clinician. The chief advantage of this technique is the simple fabrication procedure and the reduction in the denture base thickness, providing a larger intraoral space and thus better comfort to the patient, overcoming the shortcomings of previously described sectional denture bases.
Negative socioeconomic changes and mental disorders: a longitudinal study
Authors: Barbaglia María Gabriela , Have Margreet ten , Dorsselaer Saskia , Alonso Jordi , de Graaf Ron
Published: September 2014

Background

There is increasing interest on whether the current global economic uncertainties have an influence on the population's mental health. In this paper, we examined the association of negative socioeconomic changes, job loss and household income reductions with incident mental disorders. The moderating effect of gender was assessed.

Methods

Data come from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a representative population-based, longitudinal study. Individuals with a paid job and without a 12-month mental disorder at baseline were selected and reassessed 3 years later (2007–2009/2010–2012). Substantial household income reductions and not being at a paid job anymore were self-reported at follow-up. Multivariate logistic models were utilised to investigate the association between these negative socioeconomic changes and the incidence of mood, anxiety and substance use Diagnostic and Statistical Manual-IV disorders assessed by the Composite International Diagnostic Interview 3.0.

Results

After 3 years, 6% had lost their job, 11% had a substantial household income reduction and 12.2% had developed a mental disorder. Household income reductions increased the risk of any mental disorder (aOR=1.77), particularly the risk of mood (aOR=2.24). Job loss increased the risk of mood disorders (aOR=2.02). Gender modified the relationship: job loss increased the risk of any mental disorder among men (aOR=3.04) and household income reductions did so among women (aOR=2.32).

Conclusions

Negative socioeconomic changes occurring within a short time period significantly increased the risk of incident mental disorders, particularly of mood disorders. Effective interventions to alleviate the public mental health impact of negative socioeconomic changes on men and women are needed.
Eocene partial melting recorded in peritectic garnets from kyanite-gneiss, Greater Himalayan Sequence, central Nepal
Authors: Carosi Rodolfo , Montomoli Chiara , Langone Antonio , Turina Alice , Cesare Bernardo , Iaccarino Salvatore , Fascioli Luca , Visonà Dario , Ronchi Ausonio , Rai Santa Man
Published: September 2014

Anatectic melt inclusions (nanogranites and nanotonalites) have been found in garnet of kyanite-gneiss at the bottom of the Greater Himalayan Sequence (GHS) along the Kali Gandaki valley, central Nepal,
c.
1 km structurally above the Main Central Thrust (MCT).
In situ
U–Th–Pb dating of monazite included in garnets, in the same structural positions as melt inclusions, allowed us to constrain partial melting starting at
c.
41–36 Ma. Eocene partial melting occurred during prograde metamorphism in the kyanite stability field (Eo-Himalayan event). Sillimanite-bearing mylonitic foliation wraps around garnets showing a top-to-the-SW sense of shear linked to the MCT ductile activity and to the exhumation of the GHS. These findings highlight the occurrence of an older melting event in the GHS during prograde metamorphism in the kyanite stability field before the more diffuse Miocene melting event.

The growth of prograde garnet and kyanite at 41–6 Ma in the MCT zone, affecting the bottom of the GHS, suggests that inverted metamorphism in the MCT zone and folded isograds in the GHS should be carefully proved with the aid of geochronology, because not all Barrovian minerals grew during the same time span and they grew in different tectonic settings.
Petrological constraints of the ‘Channel Flow’ model in eastern Nepal
Authors: Rolfo F. , Groppo C. , Mosca P.
Published: September 2014

The metamorphic architecture of eastern Nepalese Himalaya is characterized by a well-documented inverted metamorphic field gradient, with metamorphic grade increasing northward from lower (LHS) to higher (HHC) structural levels across the north-dipping Main Central Thrust Zone (MCTZ). Peak metamorphic conditions experienced by units at different structural levels have been investigated extensively, but their
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) evolution could be constrained better.

A synthesis of our recent petrological studies in eastern Nepal is based on selected geotraverses across the Dudh–Kosi, Arun, and Tamur tectonic windows, where the LHS is exposed beneath MCTZ and HHC. To define the entire
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evolution experienced by lithotectonic units, detailed petrological investigations were focused on metapelites.
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trajectories were constrained combining microstructural observations and isochemical phase diagrams modelling. The uniformity of the approach applied is a robust method to quantitatively compare the resulting
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paths.

These
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paths are compared with the petrological constraints inferred from the ‘Channel Flow’ model, one of the most popular paradigms to explain the tectonometamorphic evolution and the first-order geological features of the Himalaya. The overall geometries of our
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paths match the results of the numerical model, suggesting that ‘Channel Flow’ is compatible, from a petrological viewpoint, as the main process operating during the exhumation of eastern Himalaya.
Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts
Authors: Motté Evi , Szepessy Edit , Suenens Krista , Stangé Geert , Bomans Myriam , Jacobs-Tulleneers-Thevissen Daniel , Ling Zhidong , Kroon Evert , Pipeleers Daniel ,   Beta Cell Therapy Consortium EU-FP7
Published: September 2014

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20–30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20–30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation.
Insulin secretion stimulated by l-arginine and its metabolite l-ornithine depends on Gαi2
Authors: Leiss Veronika , Flockerzie Katarina , Novakovic Ana , Rath Michaela , Schönsiegel Annika , Birnbaumer Lutz , Schürmann Annette , Harteneck Christian , Nürnberg Bernd
Published: September 2014

Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gαo proteins or from combined inactivation of Gαo, Gαi1, Gαi2, and Gαi3 isoforms. However, the specific role of Gαi2 in pancreatic β-cells still remains unknown. In global (Gαi2−/−) and β-cell-specific (Gαi2βcko) gene-targeted Gαi2 mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca2+ measurements were used to characterize Gαi2 function in vitro. Gαi2−/− and Gαi2βcko mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gαi2−/− and Gαi2βcko mice, whereas plasma glucose concentrations were unchanged in Gαi2−/− but significantly increased in Gαi2βcko mice. These findings indicate a novel albeit unexpected role for Gαi2 in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gαi2-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by l-arginine or l-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gαi2. In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid l-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gαi2 showing that amino acid-induced insulin-release depends on Gαi2.
Interleukin-6 amplifies glucagon secretion: coordinated control via the brain and pancreas
Authors: Barnes Tammy M. , Otero Yolanda F. , Elliott Amicia D. , Locke Alicia D. , Malabanan Carlo M. , Coldren Anastasia G. , Brissova Marcela , Piston David W. , McGuinness Owen P.
Published: September 2014

Inappropriate glucagon secretion contributes to hyperglycemia in inflammatory disease. Previous work implicates the proinflammatory cytokine interleukin-6 (IL-6) in glucagon secretion. IL-6-KO mice have a blunted glucagon response to lipopolysaccharide (LPS) that is restored by intravenous replacement of IL-6. Given that IL-6 has previously been demonstrated to have a transcriptional (i.e., slow) effect on glucagon secretion from islets, we hypothesized that the rapid increase in glucagon following LPS occurred by a faster mechanism, such as by action within the brain. Using chronically catheterized conscious mice, we have demonstrated that central IL-6 stimulates glucagon secretion uniquely in the presence of an accompanying stressor (hypoglycemia or LPS). Contrary to our hypothesis, however, we found that IL-6 amplifies glucagon secretion in two ways; IL-6 not only stimulates glucagon secretion via the brain but also by direct action on islets. Interestingly, IL-6 augments glucagon secretion from both sites only in the presence of an accompanying stressor (such as epinephrine). Given that both adrenergic tone and plasma IL-6 are elevated in multiple inflammatory diseases, the interactions of the IL-6 and catecholaminergic signaling pathways in regulating GCG secretion may contribute to our present understanding of these diseases.
Influence of serotonergic mechanisms on the urine flow rate in male rats
Authors: Fan Wen-Jia , Chen Shih-Ching , Hsieh Tsung-Hsun , Lai Chien-Hung , Lin You Shuei , Peng Chih-Wei , Kou Yu Ru
Published: September 2014

This study extensively examined the role of a 5-HT1A receptor in controlling voiding function in anesthetized male rats. A simultaneous recording of the intravesical pressure (IVP), external urethral sphincter (EUS)-electromyography (EMG), and urine flow rate (UFR) during continuous cystometry was used. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, significantly improved the voiding efficiency, as detected by increases in the evoked contraction amplitude, EUS burst period, and silent period, and decreases in the volume threshold, pressure threshold, and residual volume. Interestingly, the UFR during voiding was reduced by 8-OH-DPAT, as evidenced by decreases in the maximal UFR and mean UFRs of the voiding period, spike duration, and interspike interval. Conversely, treating rats with WAY-100635, a 5-HT1A antagonist, produced effects opposite to those produced by 8-OH-DPAT. These findings suggest that 8-OH-DPAT improved the voiding efficiency by enhancing the detrusor contractile ability and prolonging EUS burst period, which would compensate for the lower UFR, resulting from urethral smooth muscle contractions and longer EUS silent periods during voiding. The present study contributes to our understanding of the role of 5-HT1A receptors in controlling the urine flow rate in male rats.