bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and assembly of an inner membrane platform for initiation of type IV pilus biogenesis
Authors: Karuppiah Vijaykumar , Collins Richard F. , Thistlethwaite Angela , Gao Ya , Derrick Jeremy P. 
Published: November 2013

Significance
Type IV pili are long, thin fibers, formed mainly of polymers of a single pilin protein, which are displayed on the surfaces of many bacteria, including several human pathogens. Here, we report three-dimensional reconstructions of the PilMNO inner membrane complex, alone and in complex with pilin protein, through a combination of X-ray crystallography and electron microscopy. PilMNO forms a dimeric T-shaped structure, binding two copies of the pilin protein at its extremities. The results provide a structural model for the way in which pilin is harvested from the inner membrane and made available to other components of the type IV pilus biogenesis machinery.
A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions
Authors: Windheim Mark , Southcombe Jennifer H. , Kremmer Elisabeth , Chaplin Lucy , Urlaub Doris , Falk Christine S. , Claus Maren , Mihm Janine , Braithwaite Myles , Dennehy Kevin , Renz Harald , Sester Martina , Watzl Carsten , Burgert Hans-Gerhard 
Published: November 2013

SignificanceHuman adenoviruses encode Early region 3 (E3) proteins that manipulate the host immune response to establish an infection or to persist longer. To date, only a few E3 functions from a single adenovirus species (C) have been characterized, all of which act directly on infected cells. Here we describe a secreted E3 protein that is uniquely expressed by species D adenoviruses. This protein targets noninfected leukocytes using a cell surface phosphatase as a receptor. We provide evidence that this interaction suppresses leukocyte activation and effector functions, implying that species D adenoviruses can affect the host distant from the site of infection.
Dynamic faces speed up the onset of auditory cortical spiking responses during vocal detection
Authors: Chandrasekaran Chandramouli , Lemus Luis , Ghazanfar Asif A. 
Published: November 2013

SignificanceWe combine facial motion with voices to help us hear better, but the role that low-level sensory areas such as the auditory cortex may play in this process is unclear. We combined a vocalization detection task with auditory cortical physiology in monkeys to bridge this epistemic gap. Surprisingly, and contrary to previous assumptions and hypotheses, changes in firing rate had no clear relationship to the detection advantage that dynamic faces provided when listening for vocalizations. Instead, dynamic faces uniformly sped up the onset of spiking activity in the auditory cortex, and this faster onset partially explains the behavioral benefits of combining faces and voices.
Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways
Authors: Hines Elizabeth A. , Jones Mary-Kayt N. , Verheyden Jamie M. , Harvey Julie F. , Sun Xin 
Published: November 2013

Significance
A balance of airway rigidity and elasticity is critical for uninterrupted airflow to and from the lungs. In the trachea and bronchi, this balance is achieved by the precise juxtaposition of smooth muscle (SM) and cartilage that together encircle the airway. We investigate how this juxtaposition is established during embryogenesis by using mouse mutants that lack either SM or cartilage in the developing lung. We demonstrate the nature of the antagonism between the nascent SM and cartilage lineages. Our results also reveal a role for cartilage in the proper differentiation of tracheal epithelium. Together these findings elucidate unique mechanisms of how airway SM or cartilage malformation may impact airway function.
Revised standards for statistical evidence
Authors: Johnson Valen E. 
Published: November 2013

Significance
The lack of reproducibility of scientific research undermines public confidence in science and leads to the misuse of resources when researchers attempt to replicate and extend fallacious research findings. Using recent developments in Bayesian hypothesis testing, a root cause of nonreproducibility is traced to the conduct of significance tests at inappropriately high levels of significance. Modifications of common standards of evidence are proposed to reduce the rate of nonreproducibility of scientific research by a factor of 5 or greater.
Structural and genetic analyses reveal the protein SepF as a new membrane anchor for the Z ring
Authors: Duman Ramona , Ishikawa Shu , Celik Ilkay , Strahl Henrik , Ogasawara Naotake , Troc Paulina , Löwe Jan , Hamoen Leendert W. 
Published: November 2013

Significance
A key step in bacterial cell division is the polymerization of FtsZ at midcell into a ring-like structure. This so-called Z ring forms a scaffold for the other cell division proteins. FtsA anchors the Z ring to the cell membrane; however, many bacterial species do not have FtsA. Here, we show that the conserved protein SepF, which forms large protein rings, also functions as a membrane anchor for the Z ring. We determined the molecular structure of the FtsZ-binding and ring-forming domain of SepF and show that the membrane-binding domain is located at the very beginning of the protein. These results explain why FtsA and SepF can fulfill similar functions in bacterial cell division.
Crystal structure of the human eIF4AIII–CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain
Authors: Buchwald Gretel , Schüssler Steffen , Basquin Claire , Le Hir Hervé , Conti Elena 
Published: November 2013

Significance
The fate of eukaryotic mRNAs is intimately linked to the complement of proteins that associate with them to form mRNA—protein complexes, the so-called messenger ribonucleoprotein particles (mRNPs). Transitions in the architecture of an mRNP lead to specific functional consequences. DEAD-box proteins are key players in orchestrating these structural rearrangements: They associate with RNA in response to ATP binding and dissociate from it upon ATP hydrolysis. In this paper, we have elucidated the molecular mechanisms by which a DEAD-box protein, which in human cells marks spliced mRNPs for a specialized surveillance pathway, is recognized by the MIF4G domain of a splicing factor. This structure shows how a MIF4G domain can act as a negative regulator of DEAD-box ATPase activity.
Growth hormone prevents the development of autoimmune diabetes
Authors: Villares Ricardo , Kakabadse Dimitri , Juarranz Yasmina , Gomariz Rosa P. , Martínez-A Carlos , Mellado Mario 
Published: November 2013

SignificanceAlthough the relationship between endocrine and immune systems is well documented, few studies have been performed on autoimmune disorders other than those that are sex hormone-related. We studied a murine model of autoimmune diabetes, showing that growth hormone (GH) modifies the immune response to render diabetic mice resistant to disease development. The mechanism involves a GH-mediated effect on β-cell survival and/or proliferation and a direct effect on immune cells. GH triggers a cytokine environment that promotes anti-inflammatory macrophage polarization, maintains the activity of the suppressor T cells, and limits Th17 cell plasticity. This study provides evidence of the importance of endocrine control of immune functions and indicates that therapies based on GH analogs should be considered for treatment of autoimmune diabetes.
Transmission of multiple system atrophy prions to transgenic mice
Authors: Watts Joel C. , Giles Kurt , Oehler Abby , Middleton Lefkos , Dexter David T. , Gentleman Steve M. , DeArmond Stephen J. , Prusiner Stanley B. 
Published: November 2013

Significance
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by the accumulation of misfolded α-synuclein protein in glial cells within the brain. Transgenic mice expressing mutant α-synuclein that were inoculated with brain homogenate from MSA patients developed clinical, biochemical, and pathological signs of a neurodegenerative disease, indicating that MSA is transmissible under certain conditions. This transmissibility is reminiscent of the human prion disorders, such as Creutzfeldt–Jakob disease, and suggests that MSA is caused by the accumulation of toxic α-synuclein prions in the brain.
Bioavailable copper modulates oxidative phosphorylation and growth of tumors
Authors: Ishida Seiko , Andreux Pénélope , Poitry-Yamate Carole , Auwerx Johan , Hanahan Douglas 
Published: November 2013

Significance
This paper describes the mechanism by which copper mediates the interplay between the two energy-producing pathways, respiration and glycolysis. Many tumors produce increased levels of lactate, even when oxygen abounds, reflecting aerobic glycolysis (“Warburg effect”), whereas most normal tissues solely use respiration. We demonstrate that reducing systemic copper with a chelating drug impaired mitochondrial energy metabolism and decreased ATP levels despite induction of glycolysis. We propose that the metabolic phenotype of tumors is modulated in part by variable levels of copper in tumor microenvironment. Our work identifies copper as a tumor promoter by demonstrating that chronic exposure to elevated levels of copper in drinking water—to the maximum allowed in public water supplies—accelerates tumor growth in mice.
High-affinity olfactory receptor for the death-associated odor cadaverine
Authors: Hussain Ashiq , Saraiva Luis R. , Ferrero David M. , Ahuja Gaurav , Krishna Venkatesh S. , Liberles Stephen D. , Korsching Sigrun I. 
Published: November 2013

Significance
Cadaverine and putrescine, two diamines emanating from decaying flesh, are strongly repulsive odors to humans but serve as innate attractive or social cues in other species. Here we show that zebrafish, a vertebrate model system, exhibit powerful and innate avoidance behavior to both diamines, and identify a high-affinity olfactory receptor for cadaverine.
Obesity and Self‐control: Food Consumption, Physical Activity, and Weight‐loss Intention
Authors: Fan Maoyong , Jin Yanhong 
Published: November 2013

AbstractWe find that despite a stronger intention to lose weight, overweight and obese individuals in the United States are less likely to meet the federal recommendations for fruit and vegetable consumption, energy and nutrient intakes, and physical activity than are normal‐weight individuals. By utilizing the Rotter score that measures self‐control capability, we find that obese individuals exhibit a lower degree of self‐control than normal‐weight individuals, and that this lack of self‐control is associated with poor eating and exercise behaviors, as well as increased Body Mass Index and obesity risk. We discuss three mechanisms that are regularly employed to overcome self‐control problems: physician advice, improvement in the built environment, and commitment devices. Our results suggest that knowledge‐based anti‐obesity intervention policies are likely to have limited effects.
In vitro susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytes
Authors: Tamura Takashi , Asahara Miwa , Yamamoto Mikachi , Yamaura Mariko , Matsumura Mitsuru , Goto Kazuo , Rezaei‐Matehkolaei Ali , Mirhendi Hossein , Makimura Miho , Makimura Koichi 
Published: November 2013

ABSTRACTTo investigate the antifungal drug susceptibility of fungi responsible for dermatomycoses, minimum inhibition concentration (MIC) tests were performed in 44 strains of dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum and Epidermophyton floccosum, with six antifungal drugs (amorolfine, terbinafine, butenafine, ketoconazole, itraconazole and bifonazole) by broth microdilution assay according to Clinical Laboratory Standard Institute protocols. Six possible dermatomycosis‐causing non‐dermatophytic fungi were also tested. The two major causes of tinea, T. rubrum and T. mentagrophytes, showed significantly different sensitivities to ketoconazole and bifonazole. Clinically derived dermatophytes were sensitive to the six antifungal drugs tested. However, non‐dermatophytes, especially Fusarium spp., tended to be resistant to these antifungal drugs. In Trichophyton spp., the MICs of non‐azole drugs had narrower distributions than those of azoles. To evaluate the effects of antifungal drug combinations, the fractional inhibitory concentration index was calculated for the combination of amorolfine and itraconazole as representative external and internal drugs for dermatophytes. It was found that this combination had synergistic or additive effects on most dermatophytes, and had no antagonistic effects. The variation in susceptibility of clinically derived fungal isolates indicates that identification of causative fungi is indispensable for appropriately choosing effective antifungal drugs in the early stages of infection. The results of combination assay suggest that multiple drugs with different antifungal mechanisms against growth of dermatophytes should be used to treat refractory dermatomycoses, especially onychomycosis.
The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation
Authors: Ishibashi Kei , Tokumoto Tadahiko , Shirakawa Hiroki , Oguro Toshiki , Yanagida Tomohiko , Takahashi Norio , Nomiya Masanori , Haga Nobuhiro , Aikawa Ken , Tanabe Kazunari , Inoue Naoki , Kojima Yoshiyuki , Suzutani Tatsuo 
Published: November 2013

ABSTRACTThe aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy‐seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy‐proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.
Specialization and phenological synchrony of plant–pollinator interactions along an altitudinal gradient
Authors: Benadi Gita , Hovestadt Thomas , Poethke Hans‐Joachim , Blüthgen Nico 
Published: November 2013

Summary

One of the most noticeable effects of anthropogenic climate change is the shift in timing of seasonal events towards earlier occurrence. The high degree of variation in species' phenological shifts has raised concerns about the temporal decoupling of interspecific interactions, but the extent and implications of this effect are largely unknown. In the case of plant–pollinator systems, more specialized species are predicted to be particularly threatened by phenological decoupling, since they are assumed to be less flexible in the choice of interaction partners, but until now this hypothesis has not been tested.

In this paper, we studied phenology and interactions of plant and pollinator communities along an altitudinal gradient in the Alps as a model for the possible effects of climate change in time.

Our results show that even relatively specialized pollinators were much more flexible in their use of plant species as floral resources than their local flower visitation suggested. We found no relationship between local specialization of pollinators and the consistency of their visitation patterns across sites, and also no relationship between specialization and phenological synchrony of pollinators with particular plants.

Thus, in contrast to the conclusions of a recent simulation study, our results suggest that most pollinator species included in this study are not threatened by phenological decoupling from specific flowering plants. However, the flexibility of many rarely observed pollinator species remains unknown. Moreover, our results suggest that specialized flower visitors select plant species based on certain floral traits such as the length of the nectar holder tube. If that is the case, the observed flexibility of plant–pollinator interactions likely depends on a high degree of functional redundancy in the plant community, which may not exist in less diverse systems.
Building integral projection models: a user's guide
Authors: Rees Mark , Childs Dylan Z. , Ellner Stephen P. 
Published: November 2013

Summary

In order to understand how changes in individual performance (growth, survival or reproduction) influence population dynamics and evolution, ecologists are increasingly using parameterized mathematical models.

For continuously structured populations, where some continuous measure of individual state influences growth, survival or reproduction, integral projection models (IPMs) are commonly used.

We provide a detailed description of the steps involved in constructing an IPM, explaining how to: (i) translate your study system into an IPM; (ii) implement your IPM; and (iii) diagnose potential problems with your IPM. We emphasize how the study organism's life cycle, and the timing of censuses, together determine the structure of the IPM kernel and important aspects of the statistical analysis used to parameterize an IPM using data on marked individuals.

An IPM based on population studies of Soay sheep is used to illustrate the complete process of constructing, implementing and evaluating an IPM fitted to sample data.

We then look at very general approaches to parameterizing an IPM, using a wide range of statistical techniques (e.g. maximum likelihood methods, generalized additive models, nonparametric kernel density estimators). Methods for selecting models for parameterizing IPMs are briefly discussed.

We conclude with key recommendations and a brief overview of applications that extend the basic model. The online Supporting Information provides commented R code for all our analyses.
Warmer temperatures increase disease transmission and outbreak intensity in a host–pathogen system
Authors: Elderd Bret D. , Reilly James R. 
Published: November 2013

SummaryWhile rising global temperatures are increasingly affecting both species and their biotic interactions, the debate about whether global warming will increase or decrease disease transmission between individuals remains far from resolved. This may stem from the lack of empirical data.Using a tractable and easily manipulated insect host–pathogen system, we conducted a series of field and laboratory experiments to examine how increased temperatures affect disease transmission using the crop‐defoliating pest, the fall armyworm (Spodoptera frugiperda) and its species‐specific baculovirus, which causes a fatal infection.To examine the effects of temperature on disease transmission in the field, we manipulated baculovirus density and temperature. As infection occurs when a host consumes leaf tissue on which the pathogen resides, baculovirus density was controlled by placing varying numbers of infected neonate larvae on experimental plants. Temperature was manipulated by using open‐top chambers (OTCs). The laboratory experiments examined how increased temperatures affect fall armyworm feeding and development rates, which provide insight into how host feeding behaviour and physiology may affect transmission.Disease transmission and outbreak intensity, measured as the cumulative fraction infected during an epizootic, increased at higher temperatures. However, there was no appreciable change in the mean transmission rate of the disease, which is often the focus of empirical and theoretical research. Instead, the coefficient of variation (CV) associated with the transmission rate shrunk. As theCVdecreased, heterogeneity in disease risk across individuals declined, which resulted in an increase in outbreak intensity.In the laboratory, increased temperatures increased feeding rates and decreased developmental times. As the host consumes the virus along with the leaf tissue on which it resides, increased feeding rate is likely to increase the probability of an individual consuming virus‐infected leaf tissue. On the other hand, decreased developmental time increases the sloughing of midgut cells, which is predicted to hinder viral infection.Increases in outbreak intensity or epizootic severity, as the climate warms, may lead to changes in the long‐term dynamics of pests whose populations are strongly affected by host–pathogen interactions. Overall, this work demonstrates that the usual assumptions governing these effects, via changes in the mean transmission rate alone, may not be correct.
The Renewed Hope of Multilateralism in South Asia: Applying the MFN Principle to Pakistan–India Trade
Authors: Gopalan Sasidaran , Malik Ammar A. , Reinert Kenneth A. 
Published: November 2013

AbstractThe multilateral trading principle of nondiscrimination and the World Trade Organization commitment of most‐favoured nation (MFN) treatment have been missing in the Pakistan–India trading relationship. This practitioner commentary addresses recent moves toward multilateral principles between these two countries, namely Pakistan's decision to grant MFN status to India. It considers the political economy of Pakistan's ‘negative list’ in addressing ‘sensitive sectors’ in Pakistan and provides partial equilibrium estimates of the domestic output, consumer welfare and net welfare impacts in Pakistan of liberalizing trade in this negative list.
Wild Animal Welfare in International Law: The Present Position and the Scope for Development
Authors: Harrop Stuart R. 
Published: November 2013

AbstractWild animal welfare is a global subject and yet international regulation and policy dealing with welfare is sparse and in places idiosyncratic. Nevertheless, there is potential to develop a comprehensive and coherent international wild animal welfare regime in law and policy derived from the propositions in the World Charter for Nature that life has intrinsic value and deserves ‘respect’. Beyond that, the Convention in International Trade in Endangered Species establishes a principle – in the context of international trade but with potential for wider application – that welfare protection should be extended to wild animals under human control. However, further development is more problematic. Although the International Whaling Commission to a minor extent regulates the welfare of hunted whales, there is no universal approach to extending welfare to freely living animals in international law and policy. This article analyses this background and goes on to recommend a way in which international policy may overcome the challenges of polarised debate and the gulf between moral relativism and moral universalism to develop the foundations of a comprehensive welfare regime at the international level.