bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender Inequality Across the Academic Life Course
Authors: Winslow Sarah , Davis Shannon N.
Published: May 2016

Recent decades have witnessed increasing scholarly and public attention to the status of women in academia. Although women are now the majority of degree recipients and their share of initial academic appointments approximates their representation among degree recipients, substantial gender inequality persists. In this article, we review existing research on this topic, focusing on how gender inequality manifests and unfolds throughout the academic career life course, from graduate school experiences, through initial academic appointments, into the associate professor years, and, finally, to women's experiences as full professors and administrators. Throughout, we emphasize how institutionalized policies and subtle biases, rather than overt discrimination, perpetuate gender inequality. We conclude with suggested areas for future research.
Volk oder Parlament: Wer entscheidet nachhaltiger? Eine vergleichende Untersuchung von Nachhaltigkeitsabstimmungen in der Schweiz
Authors: Rohm Christian , Wurster Stefan
Published: May 2016

Dieser Artikel beschäftigt sich am Beispiel der halbdirekten Demokratie der Schweiz mit der Frage, wie sehr Stimmbevölkerung und Parlament dazu neigen, sich bei Abstimmungen über inter‐ und intragenerationelle Nachhaltigkeitsbelange für die zukunftsverantwortlichere Variante zu entscheiden. Die vergleichende empirische Analyse von 109 nachhaltigkeitsrelevanten Abstimmungsvorlagen, die gleichermaßen der Schweizer Stimmbevölkerung und dem Schweizer Nationalrat in den Jahren 1980 bis 2014 vorgelegt wurden, fördert dabei drei Hauptbefunde zutage. Erstens: Entgegen der theoretischen Erwartung votierte sowohl das Schweizer Volk als auch das Schweizer Parlament bei der Mehrzahl der Nachhaltigkeitsabstimmungen für die „nachhaltigere” Alternative. Zweitens: Im direkten Vergleich der beiden Entscheidungsebenen zeigte das Parlament eine deutlich höhere Bereitschaft, im Sinne der Nachhaltigkeit abzustimmen. Drittens: Das Parlament stimmte insbesondere bei Abstimmungen über intragenerationelle Nachhaltigkeitsaspekte – und hier wiederum besonders bei Abstimmungen über die Rechte von Fremdgruppen (Ausländer, Asylsuchende) – nachhaltigkeitsaffiner ab als die Stimmbevölkerung. Eine nähere Analyse der jüngsten Nachhaltigkeitsabstimmungen unter Berücksichtigung kantonaler Unterschiede macht darüber hinaus darauf aufmerksam, dass seitens der Stimmbevölkerung neben dem ökonomischen Entwicklungsstand auch die Altersstruktur des Wohnkantons einen bedeutenden Einfluss auf das Abstimmungsergebnis ausübte.
The evolutionary history of Biston suppressaria (Guenée) (Lepidoptera: Geometridae) related to complex topography and geological history
Authors: CHENG RUI , JIANG NAN , XUE DAYONG , LI XINXIN , BAN XIAOSHUANG , HAN HONGXIANG
Published: May 2016

The Mountains of Southwest China (MSC) – the most important mountain system in East Asia – creates physical barriers to migration and isolates organisms in different regions. In this study, we explored the genetic structure and phylogeography of Biston suppressaria, a moth species widely distributed in MSC and south China, based on three mtDNA and three ncDNA loci. MtDNA revealed high genetic differentiation among the geographical populations and divided B. suppressaria into five phylogroups (A–E). With the exception of phylogroups B and E which are sympatric, the other three phylogroups have their own distinct distribution areas. Four population differentiations occurred, and the divergence time was consistent with the three phases of the Qinghai–Tibet Movement and Kunhuang Movement, respectively. In contrast, ncDNA did not reveal any phylogeographical structure. Incomplete lineage sorting is considered the most plausible cause of the discordance between mtDNA and ncDNA genes, after excluding secondary admixture and Wolbachia infection. A complex combination of topography and geological movements of south China and MSC contributes to the complex evolutionary history of B. suppressaria.
Mapping‐by‐sequencing in complex polyploid genomes using genic sequence capture: a case study to map yellow rust resistance in hexaploid wheat
Authors: Gardiner Laura‐Jayne , Bansept‐Basler Pauline , Olohan Lisa , Joynson Ryan , Brenchley Rachel , Hall Neil , O'Sullivan Donal M. , Hall Anthony
Published: May 2016

Previously we extended the utility of mapping‐by‐sequencing by combining it with sequence capture and mapping sequence data to pseudo‐chromosomes that were organized using wheat–Brachypodium synteny. This, with a bespoke haplotyping algorithm, enabled us to map the flowering time locus in the diploid wheat Triticum monococcum L. identifying a set of deleted genes (Gardiner et al., 2014). Here, we develop this combination of gene enrichment and sliding window mapping‐by‐synteny analysis to map the Yr6 locus for yellow stripe rust resistance in hexaploid wheat. A 110 MB NimbleGen capture probe set was used to enrich and sequence a doubled haploid mapping population of hexaploid wheat derived from an Avalon and Cadenza cross. The Yr6 locus was identified by mapping to the POPSEQ chromosomal pseudomolecules using a bespoke pipeline and algorithm (Chapman et al., 2015). Furthermore the same locus was identified using newly developed pseudo‐chromosome sequences as a mapping reference that are based on the genic sequence used for sequence enrichment. The pseudo‐chromosomes allow us to demonstrate the application of mapping‐by‐sequencing to even poorly defined polyploidy genomes where chromosomes are incomplete and sub‐genome assemblies are collapsed. This analysis uniquely enabled us to: compare wheat genome annotations; identify the Yr6 locus – defining a smaller genic region than was previously possible; associate the interval with one wheat sub‐genome and increase the density of SNP markers associated. Finally, we built the pipeline in iPlant, making it a user‐friendly community resource for phenotype mapping.
Attenuation of PAMP‐triggered immunity in maize requires down‐regulation of the key β‐1,6‐glucan synthesis genes KRE5 and KRE6 in biotrophic hyphae of Colletotrichum graminicola
Authors: Oliveira‐Garcia Ely , Deising Holger B.
Published: May 2016

In plants, pathogen defense is initiated by recognition of pathogen‐associated molecular patterns (PAMPs) via plasma membrane‐localized pattern‐recognition receptors (PRRs). Fungal structural cell wall polymers such as branched β‐glucans are essential for infection structure rigidity and pathogenicity, but at the same time represent PAMPs. Kre5 and Kre6 are key enzymes in β‐1,6‐glucan synthesis and formation of branch points of the β‐glucan network. In spite of the importance of branched β‐glucan for hyphal rigidity and plant–fungus interactions, neither the role of KRE5 and KRE6 in pathogenesis nor mechanisms allowing circumventing branched β‐glucan‐triggered immune responses are known. We functionally characterized KRE5 and KRE6 of the ascomycete Colletotrichum graminicola, a hemibiotroph that infects maize (Zea mays). After appressorial plant invasion, this fungus sequentially differentiates biotrophic and highly destructive necrotrophic hyphae. RNAi‐mediated reduction of KRE5 and KRE6 transcript abundance caused appressoria to burst and swelling of necrotrophic hyphae, indicating that β‐1,6‐glucosidic bonds are essential in these cells. Live cell imaging employing KRE5:mCherry and KRE6:mCherry knock‐in strains and probing of infection structures with a YFP‐conjugated β‐1,6‐glucan‐binding protein showed expression of these genes and exposure of β‐1,6‐glucan in conidia, appressoria and necrotrophic, but not in biotrophic hyphae. Overexpression of KRE5 and KRE6 in biotrophic hyphae led to activation of broad‐spectrum plant defense responses, including papilla and H2O2 formation, as well as transcriptional activation of several defense‐related genes. Collectively, our results strongly suggest that down‐regulation of synthesis and avoidance of exposure of branched β‐1,3‐β‐1,6‐glucan in biotrophic hyphae is required for attenuation of plant immune responses.
The role of arabinokinase in arabinose toxicity in plants
Authors: Behmüller Robert , Kavkova Eva , Düh Stefanie , Huber Christian G. , Tenhaken Raimund
Published: May 2016

Plant cell wall polymers are synthesized by glycosyltransferases using nucleotide sugars as substrates. Most UDP‐sugars are synthesized from UDP‐glucose via de novo pathways but salvage pathways work in parallel to recycle sugars, which have been released during cell wall polymer and glycoprotein turnover. Here we report on the cloning and biochemical analysis of two arabinokinases in Arabidopsis. Arabinokinase is a 100 kDa protein located in the cytosol with a putative N‐terminal glycosyltransferase domain and a C‐terminal sugar‐1‐kinase domain. This unique structure is highly conserved in the plant kingdom. Arabinokinase has a high affinity for l‐arabinose, which is the only sugar substrate of this GHMP (galactose; homoserine; mevalonate; phosphomevalonate) kinase. Plants that were knocked‐out for arabinokinase and the previously described ara1‐1 mutant were characterized. The ARA1‐1 mutant form of the enzyme carries a point mutation in an α‐helix. The mutation is close to the substrate binding site and changes the Km value for arabinose from 80 μm in the wild type to 17 000 μm in ARA1‐1. The previous arabinose toxicity explanation is challenged by knockout plants in arabinokinase that accumulate higher levels of arabinose but do not show signs of arabinose toxicity. Analysis of marker genes from sugar signalling pathways (SnRK1 and Tor) suggest that ara1‐1 misinterprets its carbon energy status. Although glucose is present in ara1‐1 similar to wild type levels, it constitutively changes gene expression as typically found in wild type plants only under starvation conditions. Furthermore, ara1‐1 shows increased expression of marker genes for programmed cell death as found in other lesion mimic mutants.
The walnut (Juglans regia) genome sequence reveals diversity in genes coding for the biosynthesis of non‐structural polyphenols
Authors: Martínez‐García Pedro J. , Crepeau Marc W. , Puiu Daniela , Gonzalez‐Ibeas Daniel , Whalen Jeanne , Stevens Kristian A. , Paul Robin , Butterfield Timothy S. , Britton Monica T. , Reagan Russell L. , Chakraborty Sandeep , Walawage Sriema L. , Vasquez‐Gross Hans A. , Cardeno Charis , Famula Randi A. , Pratt Kevin , Kuruganti Sowmya , Aradhya Mallikarjuna K. , Leslie Charles A. , Dandekar Abhaya M. , Salzberg Steven L. , Wegrzyn Jill L. , Langley Charles H. , Neale David B.
Published: May 2016

The Persian walnut (Juglans regia L.), a diploid species native to the mountainous regions of Central Asia, is the major walnut species cultivated for nut production and is one of the most widespread tree nut species in the world. The high nutritional value of J. regia nuts is associated with a rich array of polyphenolic compounds, whose complete biosynthetic pathways are still unknown. A J. regia genome sequence was obtained from the cultivar ‘Chandler’ to discover target genes and additional unknown genes. The 667‐Mbp genome was assembled using two different methods (SOAPdenovo2 and MaSuRCA), with an N50 scaffold size of 464 955 bp (based on a genome size of 606 Mbp), 221 640 contigs and a GC content of 37%. Annotation with MAKER‐P and other genomic resources yielded 32 498 gene models. Previous studies in walnut relying on tissue‐specific methods have only identified a single polyphenol oxidase (PPO) gene (JrPPO1). Enabled by the J. regia genome sequence, a second homolog of PPO (JrPPO2) was discovered. In addition, about 130 genes in the large gallate 1‐β‐glucosyltransferase (GGT) superfamily were detected. Specifically, two genes, JrGGT1 and JrGGT2, were significantly homologous to the GGT from Quercus robur (QrGGT), which is involved in the synthesis of 1‐O‐galloyl‐β‐d‐glucose, a precursor for the synthesis of hydrolysable tannins. The reference genome for J. regia provides meaningful insight into the complex pathways required for the synthesis of polyphenols. The walnut genome sequence provides important tools and methods to accelerate breeding and to facilitate the genetic dissection of complex traits.
An evaluation of overall effectiveness and treatment satisfaction with intravenous immunoglobulin among patients with immune thrombocytopenia
Authors: Sholapur Naushin S. , Hamilton Korinne , Butler Lianna , Heddle Nancy M. , Arnold Donald M.
Published: May 2016

BACKGROUND

A global assessment of patient satisfaction that considers therapeutic effect, toxicities, and convenience is needed to evaluate the acceptability of intravenous immunoglobulin (IVIG) as a treatment for patients with immune thrombocytopenia (ITP).

STUDY DESIGN AND METHODS

We performed a cross‐sectional pilot study to assess the feasibility and usefulness of a treatment satisfaction questionnaire for adult patients with ITP receiving IVIG in an academic hematology clinic. Treatment satisfaction was evaluated by administration of a validated survey‐based tool 7 days after IVIG administration. The tool assessed treatment satisfaction across four domains (effectiveness, toxicity, convenience, and global satisfaction); results were summarized with mean scores.

RESULTS

Twelve patients were enrolled (nine females; median age, 44 years; interquartile range, 35‐69 years). Mean platelet increment after infusion was 54.2 × 109/L (SD, 47.6 × 109/L). Treatment satisfaction scores were highest in the side effect burden domain (88.2/100; SD, 19.3; higher scores indicate a lower burden of side effects). Six participants reported IVIG‐associated toxicities; most were “slightly” or “not at all” dissatisfied by the impact of side effects. The domain with the lowest score was convenience (62.0/100; SD, 24.7).

CONCLUSION

The assessment of treatment satisfaction using a survey‐based assessment tool was feasible for patients receiving IVIG and provided meaningful results that discriminated between domains. Patients found IVIG treatment to be inconvenient, but were satisfied with its tolerability as an ITP treatment. Larger studies are needed to determine the precise impact on each domain and the reproducibility of study results. Patient satisfaction scores can be used to compare different ITP treatments.
Barcode error leading to sample misidentification during blood grouping
Authors: Shastry Shamee , Sreelekshmi Sreedevi , Raturi Manish , Baliga Poornima
Published: May 2016

View Supplementary Video
MAGNETIC RESONANCE IMAGING OF INTRACRANIAL INFLAMMATORY CONDITIONS IN DOGS: SENSITIVITY OF SUBTRACTION IMAGES VERSUS PRE‐ AND POST‐GADOLINIUM T1‐WEIGHTED IMAGE PAIRS
Authors: Dirrig Helen , Lamb Christopher R.
Published: May 2016

Ante mortem diagnosis of canine meningoencephalitis is usually based on the results of neurologic examination, cerebrospinal fluid analysis and magnetic resonance (MR) imaging. It has been hypothesized that subtraction MR imaging may increase the sensitivity of MR for intracranial inflammatory lesions compared to conventional post‐gadolinium T1‐weighted imaging. Sensitivity of pre‐ and post‐gadolinium (C‐/C+) image pairs and dynamic subtraction (DS) images was compared in a retrospective diagnostic accuracy study of 52 dogs with inflammatory cerebrospinal fluid and 67 dogs with idiopathic epilepsy. Series of transverse C‐/C+ and DS images were reviewed independently for signs of abnormal enhancement affecting the pachymeninges, leptomeninges or intra‐axial structures. Sensitivity of C‐/C+ image pairs and DS images was 48% (95% CI: 35–61%) and 65% (95% CI: 52–77%), respectively (P = 0.01). Intra‐axial lesions were observed more frequently than meningeal lesions in both C‐/C+ (43% vs. 31%) and DS images (61% vs. 22%). The difference in sensitivities of C‐/C+ and DS series was entirely due to increased sensitivity of DS images for intra‐axial lesions. Eight (12%) dogs with epilepsy had evidence of intra‐axial gadolinium accumulation affecting the cerebral cortex in DS images. This finding may represent a false‐positive result or a true sign of pathology, possibly associated with a leaky blood–brain barrier in areas of the brain affected by neovascularization secondary to repeated seizures. Results suggest that DS imaging has higher sensitivity than comparison of pre‐ and post‐gadolinium image pairs for inflammatory intra‐axial lesions.
IMAGING DIAGNOSIS—MAGNETIC RESONANCE IMAGING AND HISTOPATHOLOGICAL FEATURES OF A SKULL BASE CHORDOMA IN A CAT
Authors: Brocal Josep , Gamino Virginia , Guevar Julien , Gutierrez‐Quintana Rodrigo , Marchesi Francesco , Hammond Gawain , Stalin Catherine
Published: May 2016

An 8‐year‐old domestic short‐haired cat was presented with anorexia, lethargy, ataxia and one episode of consciousness loss. A midline vertically orientated, biconcave, extra‐axial mass originating from the basioccipital bone was detected on magnetic resonance images of the head. The mass was T1W iso‐ to hypointense when compared with normal grey matter, T2W hyperintense with small areas of isointensity and heterogeneously enhanced with contrast. Multiple signal voids were observed on T2*images. Histopathological evaluation confirmed a chordoma. To the authors’ knowledge this is the first report of the imaging characteristics of a chordoma affecting the skull base in a cat.
Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care
Authors: Remington Austin C. , Hernandez‐Boussard Tina , Warstadt Nicholus M. , Finnegan Micaela A. , Shaffer Robyn , Kwong Jereen Z. , Curtin Catherine
Published: May 2016

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.
Electrochemical Property Assessment of Pr2CuO4 Submicrofiber Cathode for Intermediate-Temperature Solid Oxide Fuel Cells
Authors: Zhao Ting , Sun Li-Ping , Li Qiang , Huo Li-Hua , Zhao Hui , Bassat Jean-Marc , Rougier Aline , Fourcade Sébastien , Grenier Jean-Claude
Published: May 2016

The Pr2CuO4 (PCO) submicrofiber precursors are prepared by electrospinning technique and the thermo-decomposition procedures are characterized by thermal gravity (TG), X-ray diffraction (XRD), Fourier transform infrared spectoscopy (FT-IR), and scanning electron microscopy (SEM), respectively. The fibrous PCO material was formed by sintering the precursors at 900 °C for 5 hrs. The highly porous PCO submicrofiber cathode forms good contact with the Ce0.9Gd0.1O1.95 (CGO) electrolyte after heat-treated at 900 °C for 2 hrs. The performance of PCO submicrofiber cathode is comparably studied with the powder counterpart at various temperatures. The porous microstructure of the submicrofiber cathode effectively increases the three-phase boundary (TPB), which promotes the surface oxygen diffusion and/or adsorption process on the cathode. The PCO submicrofiber cathode exhibits an area specific resistance (ASR) of 0.38 Ω cm2 at 700 °C in air, which is 30% less than the PCO powder cathode. The charge transfer process is the rate limiting step of the oxygen reduction reaction (ORR) on the submicrofiber cathode. The maximum power densities of the electrolyte-support single cell PCO|CGO|NiO-CGO reach 149 and 74.5 mW cm−2 at 800 and 700 °C, respectively. The preliminary results indicate that the PCO submicrofiber can be considered as potential cathode for intermediate temperature solid fuel cells (IT-SOFCs).
Suppression of bending waves in a beam using resonators with different separation lengths
Authors: Yang Cheng , Cheng Li
Published: May 2016

This work is concerned with the suppression of a bending wave in a beam using resonators. Particular focus is put on the separation length between resonators. It is demonstrated that, for a beam with identical resonators attached at equal intervals, the bending wave transmission efficiency varies with respect to the separation length. The phenomena and the underlying physics are investigated by resorting to a simple beam model having two resonators resting on it. The two resonators are coupled over the segment through various bending wave components, comprising both propagating waves and evanescent waves, generated at the resonator locations where the beam encounters impedance discontinuities. The separation length, specifying the phase change of the propagating waves and the amplitude decay of the evanescent waves travelling from one resonator to the other, is thereby the parameter determining the extent to which the resonators would be coupled and the degree of the power that is transmitted. Results show, qualitatively, the difference in the working mechanism of the resonators in different separation length regions, with criteria being defined to distinguish those regions. Particularly, in the intermediate separation region, the evanescent waves are shown to play an important role in the coupling and are responsible for transmitting power, comparable with that transmitted by propagating waves, to the far field.
Changes in Leisure-Time Physical Activity and Subsequent Sickness Absence Due to Any Cause, Musculoskeletal, and Mental Causes
Authors: Holstila Ansku , Rahkonen Ossi , Lahelma Eero , Lahti Jouni
Published: May 2016

Background:

The association between changes in physical activity and sickness absence is poorly understood. The aim of this study was to examine the association between changes in leisure-time physical activity and long-term sickness absence due to any cause and musculoskeletal and mental causes.

Methods:

We measured physical activity at baseline in 2000–2002 (response rate 67%) and at follow-up in 2007 (response rate 83%) among middle-aged employees of the City of Helsinki, Finland. The survey data were linked to the Finnish Social Insurance Institute’s register data on sickness benefit periods > 9 days, including diagnoses (ICD-10; International Statistical Classification of Diseases and Related Health Problems, 10th revision) (mean follow-up 2.3 years). We used a negative binomial model to calculate rate ratios. The analyses included 4010 respondents (81% women).

Results:

Those who were persistently vigorously active and those whose physical activity level changed from low to moderate or vigorous, from moderate to vigorous, or from vigorous to moderate were at lower risk for sickness absence than were the persistently low-activity group. For sickness absence due to musculoskeletal causes, vigorous activity showed stronger associations, whereas mental causes showed no such associations.

Conclusions:

To reduce sickness absence due to both musculoskeletal and mental causes, middle-aged and aging employees should be encouraged to engage in physical activity.
Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system
Authors: Montgomery Kate L. , Iyer Shrivats M. , Christensen Amelia J. , Deisseroth Karl , Delp Scott L.
Published: May 2016

This Review discusses the use of optogenetics in the spinal cord and peripheral nervous system, distills the key results achieved thus far, and discusses the translational potential.
Supervised autonomous robotic soft tissue surgery
Authors: Shademan Azad , Decker Ryan S. , Opfermann Justin D. , Leonard Simon , Krieger Axel , Kim Peter C. W.
Published: May 2016

Supervised autonomous in vivo robotic surgery is possible on soft tissues and outperforms standard clinical techniques in a dynamic preclinical environment.
Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine–driven inflammation and fibrosis
Authors: Vannella Kevin M. , Ramalingam Thirumalai R. , Borthwick Lee A. , Barron Luke , Hart Kevin M. , Thompson Robert W. , Kindrachuk Kristen N. , Cheever Allen W. , White Sandra , Budelsky Alison L. , Comeau Michael R. , Smith Dirk E. , Wynn Thomas A.
Published: May 2016

Combined blockade of TSLP, IL-25, and IL-33 may be needed to treat some forms of progressive inflammation and fibrosis.
Development of a bile acid–based newborn screen for Niemann-Pick disease type C
Authors: Jiang Xuntian , Sidhu Rohini , Mydock-McGrane Laurel , Hsu Fong-Fu , Covey Douglas F. , Scherrer David E. , Earley Brian , Gale Sarah E. , Farhat Nicole Y. , Porter Forbes D. , Dietzen Dennis J. , Orsini Joseph J. , Berry-Kravis Elizabeth , Zhang Xiaokui , Reunert Janice , Marquardt Thorsten , Runz Heiko , Giugliani Roberto , Schaffer Jean E. , Ory Daniel S.
Published: May 2016

A newborn screen for Niemann-Pick disease type C was developed on the basis of discovery of a bile acid marker.
Sex (steroids) is in the AIRE
Authors: Moore Daniel J.
Published: May 2016

Male and female hormones regulate autoimmunity by controlling T cell tolerance mechanisms.
Extra! Extra! Microfluidic chips go to print
Authors: Castro Cesar M.
Published: May 2016

Roll-to-roll manufacturing and inertial focusing principles are combined to achieve scalable yet low-cost microfluidic chips for cellular analyses.
Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals
Authors: Stegemann-Koniszewski S. , Jeron Andreas , Gereke Marcus , Geffers Robert , Kröger Andrea , Gunzer Matthias , Bruder Dunja
Published: May 2016

Influenza A virus (IAV) periodically causes substantial morbidity and mortality in the human population. In the lower lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. So far, little is known about their reaction to IAV and their contribution to respiratory antiviral immunity
in vivo
. Therefore, we characterized the AECII response during early IAV infection by analyzing transcriptional regulation in cells sorted from the lungs of infected mice. We detected rapid and extensive regulation of gene expression in AECII following
in vivo
IAV infection. The comparison to transcriptional regulation in lung tissue revealed a strong contribution of AECII to the respiratory response. IAV infection triggered the expression of a plethora of antiviral factors and immune mediators in AECII with a high prevalence for interferon-stimulated genes. Functional pathway analyses revealed high activity in pathogen recognition, immune cell recruitment, and antigen presentation. Ultimately, our analyses of transcriptional regulation in AECII and lung tissue as well as interferon I/III levels and cell recruitment indicated AECII to integrate signals provided by direct pathogen recognition and surrounding cells.
Ex vivo
analysis of AECII proved a powerful tool to increase our understanding of their role in respiratory immune responses, and our results clearly show that AECII need to be considered a part of the surveillance and effector system of the lower respiratory tract.

IMPORTANCE
In order to confront the health hazard posed by IAV, we need to complete our understanding of its pathogenesis. AECII are primary targets for IAV replication in the lung, and while we are beginning to understand their importance for respiratory immunity, the
in vivo
AECII response during IAV infection has not been analyzed. In contrast to studies addressing the response of AECII infected with IAV
ex vivo
, we have performed detailed gene transcriptional profiling of AECII isolated from the lungs of infected mice. Thereby, we have identified an exceptionally rapid and versatile response to IAV infection that is shaped by pathogen-derived as well as microenvironment-derived signals and aims at the induction of antiviral measures and the recruitment and activation of immune cells. In conclusion, our study presents AECII as active players in antiviral defense
in vivo
that need to be considered part of the sentinel and effector immune system of the lung.
Genome-Wide Mapping of Binding Sites Reveals Multiple Biological Functions of the Transcription Factor Cst6p in Saccharomyces cerevisiae
Authors: Liu Guodong , Bergenholm David , Nielsen Jens
Published: May 2016

In the model eukaryote
Saccharomyces cerevisiae
, the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the
CST6
deletion mutant on ethanol is attributed to the markedly decreased expression of
NCE103
, encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a
CST6
deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in
S. cerevisiae
.

IMPORTANCE
Transcription factors regulate the activity of various biological processes through binding to specific DNA sequences. Therefore, the determination of binding positions is important for the understanding of the regulatory effects of transcription factors. In the model eukaryote
Saccharomyces cerevisiae
, the transcription factor Cst6p has been reported to regulate several biological processes, while its genome-wide targets remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. We show that the binding of Cst6p to its target promoters is condition dependent and explain the mechanism for the retarded growth of the
CST6
deletion mutant on ethanol. Furthermore, we demonstrate that Cst6p is a new member of a stress-responsive transcriptional regulatory network. These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in
S. cerevisiae
.
The ABC of Ribosome-Related Antibiotic Resistance
Authors: Wilson Daniel N.
Published: May 2016

The increase in multidrug-resistant pathogenic bacteria is limiting the utility of our current arsenal of antimicrobial agents. Mechanistically understanding how bacteria obtain antibiotic resistance is a critical first step to the development of improved inhibitors. One common mechanism for bacteria to obtain antibiotic resistance is by employing ATP-binding cassette (ABC) transporters to actively pump the drug from the cell. The ABC-F family includes proteins conferring resistance to a variety of clinically important ribosome-targeting antibiotics; however, controversy remains as to whether resistance is conferred via efflux like other ABC transporters or whether another mechanism, such as ribosome protection, is at play. A recent study by Sharkey and coworkers (L. K. Sharkey, T. A. Edwards, and A. J. O’Neill, mBio 7:e01975-15, 2016,
http://dx.doi.org/10.1128/mBio.01975-15
) provides strong evidence that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosome and displacing the drug from its binding site, thus revealing a novel role for ABC-F proteins in antibiotic resistance.
An Integrated Metabolomic and Genomic Mining Workflow To Uncover the Biosynthetic Potential of Bacteria
Authors: Maansson Maria , Vynne Nikolaj G. , Klitgaard Andreas , Nybo Jane L. , Melchiorsen Jette , Nguyen Don D. , Sanchez Laura M. , Ziemert Nadine , Dorrestein Pieter C. , Andersen Mikael R. , Gram Lone
Published: May 2016

We here combine chemical analysis and genomics to probe for new bioactive secondary metabolites based on their pattern of distribution within bacterial species. We demonstrate the usefulness of this combined approach in a group of marine Gram-negative bacteria closely related to
Pseudoalteromonas luteoviolacea
, which is a species known to produce a broad spectrum of chemicals. The approach allowed us to identify new antibiotics and their associated biosynthetic pathways. Combining chemical analysis and genetics is an efficient “mining” workflow for identifying diverse pharmaceutical candidates in a broad range of microorganisms and therefore of great use in bioprospecting.
Unusual case of respiratory embarrassment secondary to tracheal compression by a dilated oesophagus in a patient with recurrent achalasia
Authors: Brodie Andrew , Okeahialam Nicola , Farinella Eriberto
Published: May 2016

We present the case of a 79-year-old woman with recurrent achalasia following a laparoscopic Heller's cardiomyotomy. The patient presented to the emergency department, with epigastric pain, severe dyspnoea and profound respiratory acidosis. She required intubation and ventilation followed by gastric decompression with nasogastric tube and the administration of intravenous antibiotics for a lower respiratory tract infection. Once stable, she underwent a CT scan revealing a massively dilated oesophagus causing marked tracheal compression. She received a period of continuous positive airway pressure ventilation while on the intensive care unit, for persistent low saturations, however, this was promptly ceased due to exacerbation of gastric dilation and fears over perforation. The patient responded well to conservative measures and was discharged home 18 days later awaiting follow-up with operating consultant surgeon.
Profound opiate toxicity in gastroparesis following therapeutic dose
Authors: Craven Henry , Iftikhar Hina , Bhatnagar Pallav
Published: May 2016

Gastroparesis is defined by the presence of delayed gastric emptying without mechanical obstruction. Patients may present with severe discomfort that can mimic an acute abdomen including abdominal pain, vomiting, nausea, bloating, fullness and early satiety. The prevalence of gastroparesis is estimated at 24 per 100 000 and women are more commonly affected than men. It is associated with a number of conditions including diabetes, Parkinson's disease, multiple sclerosis, previous abdominal surgeries and connective tissue disorders, including scleroderma and Ehlers-Danlos syndrome. Drugs known to prolong gastric transit time, such as opiates, have been shown to exacerbate symptoms. We report a case of a 20-year-old woman with Ehlers-Danlos syndrome who developed respiratory depression after being administered a therapeutic dose of morphine. This occurred due to opiate toxicity confounded by gastroparesis. The patient required further support from intensive care until she recovered, and eventually underwent a gastric pacing procedure for symptomatic relief.
Socioeconomic disadvantage and its implications for population health planning of obesity and overweight, using cross-sectional data from general practices from a regional catchment in Australia
Authors: Ghosh Abhijeet , Charlton Karen E , Batterham Marijka J
Published: May 2016

Objectives

To identify smaller geographic and region-specific evidence to inform population health planning for overweight and obesity.

Design

Cross-sectional secondary analysis of data.

Setting

Primary healthcare—17 general practices located in the Illawarra-Shoalhaven region of New South Wales (NSW).

Participants

A subset (n=36 674) of the Sentinel Practices Data Sourcing project adult persons data set (n=118 794) that included information on disease status of all adult patients who had height and weight measurements recorded in their electronic health records and had visited the included general practices within the Illawarra-Shoalhaven region of NSW between September 2011 and September 2013.

Main outcome measures

Age-adjusted odds ratio (aOR) of overweight and obesity was determined for high and low levels of socioeconomic disadvantage based on Socio-Economic Indexes for Areas (SEIFA)—Index of Relative Socio-Economic Disadvantage (IRSD) scores of patients' residential statistical local area.

Results

In men, overweight was lowest in areas of highest socioeconomic disadvantage (aOR=0.910; 95% CI 0.830 to 0.998; p<0.001); but no statistically significant association with socioeconomic score was found for women. Overall obesity was associated with high socioeconomic disadvantage (aOR=1.292; 95% CI 1.210 to 1.379; p<0.001).

Conclusions

This type of data analysis reveals multiple layers of evidence that should be assessed for population health approaches to curb the epidemic of obesity and overweight. It strongly highlights the need for preventive health initiatives to be specific to gender and socioeconomic attributes of the target population.
Leprosy in England and Wales 1953–2012: surveillance and challenges in low incidence countries
Authors: Fulton Nicholas , Anderson Laura F , Watson John M , Abubakar Ibrahim
Published: May 2016

Objective

To review all notified cases of leprosy in England and Wales between 1953 and 2012.

Design

National surveillance study of all reported cases.

Setting

England and Wales.

Outcome

Number and characteristics of reported cases.

Results

During this period, a total of 1449 leprosy cases were notified. The incidence fell from 356 new cases notified between 1953 and 1962 to 139 new cases between 2003 and 2012. Where data were available, leprosy was more common in men, 15–45 year olds and those from the Indian subcontinent. There was considerable undernotification in 2001–2012.

Conclusions

The high level of under-reporting indicates a need for improved surveillance in the UK. Public Health England, in collaboration with the UK Panel of Leprosy opinion, has revised the UK Memorandum on Leprosy in order to provide updated guidance on diagnostic procedures, treatment, case management, contact tracing and notification.
Modified international e-Delphi survey to define healthcare professional competencies for working with teenagers and young adults with cancer
Authors: Taylor Rachel M , Feltbower Richard G , Aslam Natasha , Raine Rosalind , Whelan Jeremy S , Gibson Faith
Published: May 2016

Objectives

To provide international consensus on the competencies required by healthcare professionals in order to provide specialist care for teenagers and young adults (TYA) with cancer.

Design

Modified e-Delphi survey.

Setting

International, multicentre study.

Participants

Experts were defined as professionals having worked in TYA cancer care for more than 12 months. They were identified through publications and professional organisations.

Methods

Round 1, developed from a previous qualitative study, included 87 closed-ended questions with responses on a nine-point Likert scale and further open-ended responses to identify other skills, knowledge and attitudes. Round 2 contained only items with no consensus in round 1 and suggestions of additional items of competency. Consensus was defined as a median score ranging from 7 to 9 and strength of agreement using mean absolute deviation of the median.

Results

A total of 179 registered to be members of the expert panel; valid responses were available from 158 (88%) in round 1 and 136/158 (86%) in round 2. The majority of participants were nurses (35%) or doctors (39%) from Europe (55%) or North America (35%). All 87 items in round 1 reached consensus with an additional 15 items identified for round 2, which also reached consensus. The strength of agreement was mostly high for statements. The areas of competence rated most important were agreed to be: ‘Identify the impact of disease on young people's life’ (skill), ‘Know about side effects of treatment and how this might be different to those experienced by children or older adults’ (knowledge), ‘Honesty’ (attitude) and ‘Listen to young people's concerns’ (aspect of communication).

Conclusions

Given the high degree of consensus, this list of competencies should influence education curriculum, professional development and inform workforce planning. Variation in strength of agreement for some competencies between professional groups should be explored further in pursuit of effective multidisciplinary team working.
A Gender Gap in the Next Generation of Physician-Scientists: Medical Student Interest and Participation in Research
Authors: Guelich Jill M. , Singer Burton H. , Castro Marcia C. , Rosenberg Leon E.
Published: May 2016

Background

For 2 decades, the number of physician-scientists has not kept pace with the overall growth of the medical research community. Concomitantly, the number of women entering medical schools has increased markedly. We have explored the effect of the changing gender composition of medical schools on the present and future pipeline of young physician-scientists.

Methods

We analyzed data obtained from the Association of American Medical Colleges, the National Institutes of Health, and the Howard Hughes Medical Institute pertaining to the expressed research intentions or research participation of male and female medical students in the United States.

Results

A statistically significant decline in the percentage of matriculating and graduating medical students\Mboth men and women\Mwho expressed strong research career intentions occurred during the decade between 1987 and 1997. Moreover, matriculating and graduating women were significantly less likely than men to indicate strong research career intentions. Each of these trends has been observed for medical schools overall and for research-intensive ones. Cohort data obtained by tracking individuals from matriculation to graduation revealed that women who expressed strong research career intentions upon matriculation were more likely than men to decrease their research career intentions during medical school. Medical student participation in research supported the gender gap identified by assessing research intentions. Female medical student participation in the Medical Scientist Training Program and the Howard Hughes Medical Institute/National Institutes of Health-sponsored Cloisters Program has increased but lags far behind the growth in the female population in medical schools.

Conclusion

Three worrisome trends in the research career intentions and participation of the nation\'s medical students (a decade-long decline for both men and women, a large and persistent gender gap, and a negative effect of the medical school experience for women) presage a further decline in the physician-scientist pipeline unless they are reversed promptly and decisively.
Morphine Enhances HIV Infection of Human Blood Mononuclear Phagocytes through Modulation of β-Chemokines and CCR5 Receptor
Authors: Guo Chang-Jiang , Li Yuan , Tian Sha , Wang Xu , Douglas Steven D. , Ho Wen-Zhe
Published: May 2016

Background

Injection drug use remains a significant risk for acquiring HIV infection. The mechanisms by which morphine enhances HIV infection of human immune cells are largely unknown.

Objective

In this study, we sought to determine the possible mechanisms by which morphine upregulates HIV infection of human blood monocyte-derived macrophages (MDM).

Methods

In this study, MDM were infected with the R5, X4, and R5X4 HIV strains. HIV replication was determined by performing reverse transcriptase activity assays. HIV receptors were determined by performing reverse transcriptase polymerase chain reactions and flow cytometry assays. β-chemokines were analyzed by performing enzyme-linked immunosorbent assays. In addition, HIV R5 strain and murine leukemia virus envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level.

Results

Morphine significantly enhanced HIV R5 strain infection of MDM but had little effect on X4 strain infection. The macrophage-tropic R5 strain envelope-pseudotyped HIV infection was markedly increased by morphine, whereas murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly upregulated CCR5 receptor expression and inhibited the endogenous production of β-chemokines in MDM. The opioid receptor antagonist naltrexone blocked the effects of morphine on the production of β-chemokines.

Conclusion

Opiates enhance HIV R5 strain infection of macrophages through the downregulation of β-chemokine production and upregulation of CCR5 receptor expression and may have an important role in HIV immunopathogenesis.
Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage
Authors: Garg Pankaj , Kidambi Ananth , Foley James R J , Musa Tarique Al , Ripley David P , Swoboda Peter P , Erhayiem Bara , Dobson Laura E , McDiarmid Adam K , Greenwood John P , Plein Sven
Published: May 2016

Background

Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography.

Objective

We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling.

Methods

54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging.

Results

44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=−0.655, p<0.001) and MVO (β=−0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22).

Conclusions

Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH.