bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new method to evaluate the effects of shear on the skin
Authors: de Wert Luuk A. , Bader Dan L. , Oomens Cees W. J. , Schoonhoven Lisette , Poeze Martijn , Bouvy Nicole D. 
Published: October 2015

AbstractCurrently, pressure ulcer preventive strategies focus mainly on pressure redistribution. Little attention is paid to reduce the harmful effects of shear‐force, because little is known about pathophysiological aspects of shear‐force. Even today, no method to measure the effects of shear‐force on the skin is available. Therefore, the aim of this study was to investigate the response to shear‐forces in terms of analyzing a noninvasive biomarker and reactive hyperemic parameter measured at the skin of healthy participants. A physical model was developed to produce a combination of pressure and shear or pressure alone on the skin. Ten healthy male participants were included and pressure (3.9 kPa) and a combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to collect IL‐1α and total protein (TP) noninvasively. The reactive hyperemic parameter was derived from a laser Doppler flowmeter. The increase in IL‐1α/TP‐ratio after a combined loading of pressure and shear for 30 minutes of 6.2 ± 2.5 was significantly higher compared with all other test conditions (p < 0.05). The increase in cutaneous blood cell flux was already significantly higher when a combined loading of pressure and shear was applied for 15 minutes compared with pressure alone. These results shows that the IL‐1α/TP‐ratio and cutaneous blood cell flux can be used as robust measures of the effect of shear‐force on skin in humans. Therefore, this model can be used to evaluate materials aimed at the reduction of shear.
Community stability and selective extinction during the Permian-Triassic mass extinction
Authors: Roopnarine Peter D. , Angielczyk Kenneth D. 
Published: October 2015

No precedent
Human activities are creating a mass extinction event. The intensity of this event is unprecedented during human times, but there have been several comparable events during Earth's history. Roopnarine and Angielczyk examined one of the largest, the Permian-Triassic Extinction (see the Perspective by Marshall). The structure and diversity of communities were key predictors of stability through the event. Furthermore, extinctions were not random, with smaller-bodied species being more prone to extinction. This pattern is in direct contradiction to the patterns seen in our current extinction. Thus, the current anthropogenically driven extinction is fundamentally different from previous catastrophic extinctions.

Science
, this issue p.
90
; see also p.
38
Somatic mutation in single human neurons tracks developmental and transcriptional history
Authors: Lodato Michael A. , Woodworth Mollie B. , Lee Semin , Evrony Gilad D. , Mehta Bhaven K. , Karger Amir , Lee Soohyun , Chittenden Thomas W. , D’Gama Alissa M. , Cai Xuyu , Luquette Lovelace J. , Lee Eunjung , Park Peter J. , Walsh Christopher A. 
Published: October 2015

Individualized neuronal mutations in the human brainThe neurons of the human brain can last for decades, carrying out computational and signaling functions. Lodatoet al.analyzed the DNA of individual neurons sampled from postmortem human brains and found that individual neurons acquired somatic mutations (see the Perspective by Linnarsson). The mechanism of mutation involved gene transcription rather than DNA replication. Thus, postmitotic neurons would seem to be their own worst enemy: Genes used for neuronal function are the very genes put most at risk of somatic mutation.Science, this issue p.94; see also p.37
The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain
Authors: Tsurudome Masato , Ito Morihiro , Ohtsuka Junpei , Hara Kenichiro , Komada Hiroshi , Nishio Machiko , Nosaka Tetsuya 
Published: October 2015

ABSTRACT
Virus-specific interaction between the attachment protein (HN) and the fusion protein (F) is prerequisite for the induction of membrane fusion by parainfluenza viruses. This HN-F interaction presumably is mediated by particular amino acids in the HN stalk domain and those in the F head domain. We found in the present study, however, that a simian virus 41 (SV41) F-specific chimeric HPIV2 HN protein, SCA, whose cytoplasmic, transmembrane, and stalk domains were derived from the SV41 HN protein, could not induce cell-cell fusion of BHK-21 cells when coexpressed with an SV41 HN-specific chimeric PIV5 F protein, no. 36. Similarly, a headless form of the SV41 HN protein failed to induce fusion with chimera no. 36, whereas it was able to induce fusion with the SV41 F protein. Interestingly, replacement of 13 amino acids of the SCA head domain, which are located at or around the dimer interface of the head domain, with SV41 HN counterparts resulted in a chimeric HN protein, SCA-RII, which induced fusion with chimera no. 36 but not with the SV41 F protein. More interestingly, retroreplacement of 11 out of the 13 amino acids of SCA-RII with the SCA counterparts resulted in another chimeric HN protein, IM18, which induced fusion either with chimera no. 36 or with the SV41 F protein, similar to the SV41 HN protein. Thus, we conclude that the F protein specificity of the HN protein that is observed in the fusion event is not solely defined by the primary structure of the HN stalk domain.

IMPORTANCE
It is appreciated that the HN head domain initially conceals the HN stalk domain but exposes it after the head domain has bound to the receptors, which allows particular amino acids in the stalk domain to interact with the F protein and trigger it to induce fusion. However, other regulatory roles of the HN head domain in the fusion event have been ill defined. We have shown in the current study that removal of the head domain or amino acid substitutions in a particular region of the head domain drastically change the F protein specificity of the HN protein, suggesting that the ability of a given HN protein to interact with an F protein is defined not only by the primary structure of the HN stalk domain but also by its conformation. This notion seems to account for the unidirectional substitutability among rubulavirus HN proteins in triggering noncognate F proteins.
Contribution of Epidemiological Predictors in Unraveling the Phylogeographic History of HIV-1 Subtype C in Brazil
Authors: Gräf Tiago , Vrancken Bram , Maletich Junqueira Dennis , de Medeiros Rúbia Marília , Suchard Marc A. , Lemey Philippe , Esteves de Matos Almeida Sabrina , Pinto Aguinaldo Roberto 
Published: October 2015

ABSTRACT
The phylogeographic history of the Brazilian HIV-1 subtype C (HIV-1C) epidemic is still unclear. Previous studies have mainly focused on the capital cities of Brazilian federal states, and the fact that HIV-1C infections increase at a higher rate than subtype B infections in Brazil calls for a better understanding of the process of spatial spread. A comprehensive sequence data set sampled across 22 Brazilian locations was assembled and analyzed. A Bayesian phylogeographic generalized linear model approach was used to reconstruct the spatiotemporal history of HIV-1C in Brazil, considering several potential explanatory predictors of the viral diffusion process. Analyses were performed on several subsampled data sets in order to mitigate potential sample biases. We reveal a central role for the city of Porto Alegre, the capital of the southernmost state, in the Brazilian HIV-1C epidemic (HIV-1C_BR), and the northward expansion of HIV-1C_BR could be linked to source populations with higher HIV-1 burdens and larger proportions of HIV-1C infections. The results presented here bring new insights to the continuing discussion about the HIV-1C epidemic in Brazil and raise an alternative hypothesis for its spatiotemporal history. The current work also highlights how sampling bias can confound phylogeographic analyses and demonstrates the importance of incorporating external information to protect against this.

IMPORTANCE
Subtype C is responsible for the largest HIV infection burden worldwide, but our understanding of its transmission dynamics remains incomplete. Brazil witnessed a relatively recent introduction of HIV-1C compared to HIV-1B, but it swiftly spread throughout the south, where it now circulates as the dominant variant. The northward spread has been comparatively slow, and HIV-1B still prevails in that region. While epidemiological data and viral genetic analyses have both independently shed light on the dynamics of spread in isolation, their combination has not yet been explored. Here, we complement publically available sequences and new genetic data from 13 cities with epidemiological data to reconstruct the history of HIV-1C spread in Brazil. The combined approach results in more robust reconstructions and can protect against sampling bias. We found evidence for an alternative view of the HIV-1C spatiotemporal history in Brazil that, contrary to previous explanations, integrates seamlessly with other observational data.
An RNA Domain Imparts Specificity and Selectivity to a Viral DNA Packaging Motor
Authors: Zhao Wei , Jardine Paul J. , Grimes Shelley 
Published: October 2015

ABSTRACT

During assembly, double-stranded DNA viruses, including bacteriophages and herpesviruses, utilize a powerful molecular motor to package their genomic DNA into a preformed viral capsid. An integral component of the packaging motor in the
Bacillus subtilis
bacteriophage ϕ29 is a viral genome-encoded pentameric ring of RNA (prohead RNA [pRNA]). pRNA is a 174-base transcript comprised of two domains, domains I and II. Early studies initially isolated a 120-base form (domain I only) that retains high biological activity
in vitro
; hence, no function could be assigned to domain II. Here we define a role for this domain in the packaging process. DNA packaging using restriction digests of ϕ29 DNA showed that motors with the 174-base pRNA supported the correct polarity of DNA packaging, selectively packaging the DNA left end. In contrast, motors containing the 120-base pRNA had compromised specificity, packaging both left- and right-end fragments. The presence of domain II also provides selectivity in competition assays with genomes from related phages. Furthermore, motors with the 174-base pRNA were restrictive, in that they packaged only one DNA fragment into the head, whereas motors with the 120-base pRNA packaged several fragments into the head, indicating multiple initiation events. These results show that domain II imparts specificity and stringency to the motor during the packaging initiation events that precede DNA translocation. Heteromeric rings of pRNA demonstrated that one or two copies of domain II were sufficient to impart this selectivity/stringency. Although ϕ29 differs from other double-stranded DNA phages in having an RNA motor component, the function provided by pRNA is carried on the motor protein components in other phages.

IMPORTANCE
During virus assembly, genome packaging involves the delivery of newly synthesized viral nucleic acid into a protein shell. In the double-stranded DNA phages and herpesviruses, this is accomplished by a powerful molecular motor that translocates the viral DNA into a preformed viral shell. A key event in DNA packaging is recognition of the viral DNA among other nucleic acids in the host cell. Commonly, a DNA-binding protein mediates the interaction of viral DNA with the motor/head shell. Here we show that for the bacteriophage ϕ29, this essential step of genome recognition is mediated by a viral genome-encoded RNA rather than a protein. A domain of the prohead RNA (pRNA) imparts specificity and stringency to the motor by ensuring the correct orientation of DNA packaging and restricting initiation to a single event. Since this assembly step is unique to the virus, DNA packaging is a novel target for the development of antiviral drugs.
A Unique 5′ Translation Element Discovered in Triticum Mosaic Virus
Authors: Roberts Robyn , Zhang Jincan , Mayberry Laura K. , Tatineni Satyanarayana , Browning Karen S. , Rakotondrafara Aurélie M. 
Published: October 2015

ABSTRACT

Several plant viruses encode elements at the 5′ end of their RNAs, which, unlike most cellular mRNAs, can initiate translation in the absence of a 5′ m7GpppG cap. Here, we describe an exceptionally long (739-nucleotide [nt]) leader sequence in triticum mosaic virus (TriMV), a recently emerged wheat pathogen that belongs to the
Potyviridae
family of positive-strand RNA viruses. We demonstrate that the TriMV 5′ leader drives strong cap-independent translation in both wheat germ extract and oat protoplasts through a novel, noncanonical translation mechanism. Translation preferentially initiates at the 13th start codon within the leader sequence independently of eIF4E but involves eIF4G. We truncated the 5′ leader to a 300-nucleotide sequence that drives cap-independent translation from the 5′ end. We show that within this sequence, translation activity relies on a stem-loop structure identified at nucleotide positions 469 to 490. The disruption of the stem significantly impairs the function of the 5′ untranslated region (UTR) in driving translation and competing against a capped RNA. Additionally, the TriMV 5′ UTR can direct translation from an internal position of a bicistronic mRNA, and unlike cap-driven translation, it is unimpaired when the 5′ end is blocked by a strong hairpin in a monocistronic reporter. However, the disruption of the identified stem structure eliminates such a translational advantage. Our results reveal a potent and uniquely controlled translation enhancer that may provide new insights into mechanisms of plant virus translational regulation.

IMPORTANCE
Many members of the
Potyviridae
family rely on their 5′ end for translation. Here, we show that the 739-nucleotide-long triticum mosaic virus 5′ leader bears a powerful translation element with features distinct from those described for other plant viruses. Despite the presence of 12 AUG start codons within the TriMV 5′ UTR, translation initiates primarily at the 13th AUG codon. The TriMV 5′ UTR is capable of driving cap-independent translation
in vitro
and
in vivo
, is independent of eIF4E, and can drive internal translation initiation. A hairpin structure at nucleotide positions 469 to 490 is required for the cap-independent translation and internal translation initiation abilities of the element and plays a role in the ability of the TriMV UTR to compete against a capped RNA
in vitro
. Our results reveal a novel translation enhancer that may provide new insights into the large diversity of plant virus translation mechanisms.
Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from Falling Precursor Levels and Increased Levels of Oligomeric PrP
Sc
Species
Authors: Mays Charles E. , van der Merwe Jacques , Kim Chae , Haldiman Tracy , McKenzie Debbie , Safar Jiri G. , Westaway David 
Published: October 2015

ABSTRACT

In lethal prion neurodegenerative diseases, misfolded prion proteins (PrP
Sc
) replicate by redirecting the folding of the cellular prion glycoprotein (PrP
C
). Infections of different durations can have a subclinical phase with constant levels of infectious particles, but the mechanisms underlying this plateau and a subsequent exit to overt clinical disease are unknown. Using tandem biophysical techniques, we show that attenuated accumulation of infectious particles in presymptomatic disease is preceded by a progressive fall in PrP
C
level, which constricts replication rate and thereby causes the plateau effect. Furthermore, disease symptoms occurred at the threshold associated with increasing levels of small, relatively less protease-resistant oligomeric prion particles (oPrP
Sc
). Although a hypothetical lethal isoform of PrP cannot be excluded, our data argue that diminishing residual PrP
C
levels and continuously increasing levels of oPrP
Sc
are crucial determinants in the transition from presymptomatic to symptomatic prion disease.

IMPORTANCE
Prions are infectious agents that cause lethal brain diseases; they arise from misfolding of a cell surface protein, PrP
C
to a form called PrP
Sc
. Prion infections can have long latencies even though there is no protective immune response. Accumulation of infectious prion particles has been suggested to always reach the same plateau in the brain during latent periods, with clinical disease only occurring when hypothetical toxic forms (called PrP
L
or TPrP) begin to accumulate. We show here that infectivity plateaus arise because PrP
C
precursor levels become downregulated and that the duration of latent periods can be accounted for by the level of residual PrP
C
, which transduces a toxic effect, along with the amount of oligomeric forms of PrP
Sc
.
Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study
Authors: Lally Peter J , Pauliah Shreela , Montaldo Paolo , Chaban Badr , Oliveira Vania , Bainbridge Alan , Soe Aung , Pattnayak Santosh , Clarke Paul , Satodia Prakash , Harigopal Sundeep , Abernethy Laurence J , Turner Mark A , Huertas-Ceballos Angela , Shankaran Seetha , Thayyil Sudhin 
Published: October 2015

IntroductionDespite cooling, adverse outcomes are seen in up to half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Rigorous evaluation of these therapies in phase II trials using surrogate MR biomarkers may speed up their bench to bedside translation. A recent systematic review of single-centre studies has suggested that MR spectroscopy biomarkers offer the best promise; however, the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makers is not known.Methods and analysisThe MR scanners (3 T; Philips, Siemens, GE) in all the participating sites will be harmonised using phantom experiments and healthy adult volunteers before the start of the study. We will then recruit 180 encephalopathic infants treated with whole body cooling from the participating centres. MRI and spectroscopy will be performed within 2 weeks of birth. Neurodevelopmental outcomes will be assessed at 18–24 months of age. Agreement between MR cerebral biomarkers and neurodevelopmental outcome will be reported. The sample size is calculated using the ‘rule of 10’, generally used to calculate the sample size requirements for developing prognostic models. Considering 9 parameters, we require 9×10 adverse events, which suggest that a total sample size of 180 is required.Ethics and disseminationHuman Research Ethics Committee approvals have been received from Brent Research Ethics Committee (London), and from Imperial College London (Sponsor). We will submit the results of the study to relevant journals and offer national and international presentations.Trial registration numberClinical Trials.gov Number:NCT01309711.
Observation for assessment of clinician performance: a narrative review
Authors: Yanes Arianna F , McElroy Lisa M , Abecassis Zachary A , Holl Jane , Woods Donna , Ladner Daniela P 
Published: October 2015

BackgroundVideo recorded and in-person observations are methods of quality assessment and monitoring that have been employed in high risk industries. In the medical field, observations have been used to evaluate the quality and safety of various clinical processes. This review summarises studies utilising video recorded or in-person observations for assessing clinician performance in medicine and surgery.MethodsA search of MEDLINE (PubMed) was conducted using a combination of medical subject headings (MeSH) terms. Articles were included if they described the use of in-person or video recorded observations to assess clinician practices in three categories: (1) teamwork and communication between clinicians; (2) errors and weaknesses in practice; and (3) compliance and adherence to interventions or guidelines.ResultsThe initial search criteria returned 3215 studies, 223 of which were identified for full text review. A total of 69 studies were included in the final set of literature. Observations were most commonly used in data dense and high risk environments, such as the emergency department or operating room. The most common use was for assessing teamwork and communication factors.ConclusionsObservations are useful for the improvement of healthcare delivery through the identification of clinician lapses and weaknesses that affect quality and safety. Limitations of observations include the Hawthorne effect and the necessity of trained observers to capture and analyse the notes or videos. The comprehensive, subtle and sensitive information observations provided can supplement traditional quality assessment methods and inform targeted interventions to improve patient safety and the quality of care.
Accounting for a lame cow
Authors: Brown Richard 
Published: October 2015

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Accounting for a lame cow’, was submitted and is discussed by Richard Brown. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘“Off colour” alpaca’, which was published in the September issue of In Practice, appears on page 487.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Enhanced thermoelectric properties of the hole-doped Bi2−xKxSr2Co2Oy ceramics
Authors: Gao Feng , He Qinglin , Cao Ruijuan , Wu Fang , Hu Xing , Song Hongzhang 
Published: October 2015

In this paper, the influence of K element doping on the thermoelectric properties of the [Formula: see text] (x = 0.00, 0.05, 0.10, 0.15, and 0.20) samples prepared by the solid-state reaction method were investigated from 333 K to 973 K. It was shown that due to the p-type K doping the electrical resistivity of the doped sample can be reduced remarkably as compared with the undoped sample, especially for the optimum doped sample [Formula: see text]. The Seebeck coefficients of the K doped samples have only a slight decrease as compared with the undoped sample. As a result of the remarkable reduction of the electrical resistivity the power factor of the doped sample have a significant improvement. The thermal conductivity of the samples is depressed due to the defects caused by K doping. As an overall result, the dimensionless figure of merit (ZT) of the [Formula: see text] sample reaches a maximum value of 0.3 at 973 K, being 93% higher than that of the undoped sample.