bluuebunny/crossref_metadata_2025 huggingface dataset:
Motherese, affect, and vocabulary development: dyadic communicative interactions in infants and toddlers
Authors: DAVE Shruti , MASTERGEORGE Ann M. , OLSWANG Lesley B.
Published: February 2018

Responsive parental communication during an infant's first year has been positively associated with later language outcomes. This study explores responsivity in mother–infant communication by modeling how change in guiding language between 7 and 11 months influences toddler vocabulary development. In a group of 32 mother–child dyads, change in early maternal guiding language positively predicted child language outcomes measured at 18 and 24 months. In contrast, a number of other linguistic variables – including total utterances and non-guiding language – did not correlate with toddler vocabulary development, suggesting a critical role of responsive change in infant-directed communication. We further assessed whether maternal affect during early communication influenced toddler vocabulary outcomes, finding that dominant affect during early mother–infant communications correlated to lower child language outcomes. These findings provide evidence that responsive parenting should not only be assessed longitudinally, but unique contributions of language and affect should also be concurrently considered in future study.
Hypoalbuminaemia as a marker of trans-capillary leakage in community-acquired bacteraemia patients
Authors: Gradel K. O. , Vinholt P. J. , Magnussen B. , Pedersen C. , Jensen T. G. , Kolmos H. J. , Lassen A. T.
Published: February 2018

Community-acquired bacteraemia patients (n = 2472), Denmark, 2000–2008. Albumin, C-reactive protein (CRP) and haemoglobin (Hb) measured 2000–2010. We assessed daily mean levels of albumin, CRP and Hb from 30 days before to 30 days after bacteraemia and correlations between albumin vs. CRP and albumin vs. Hb. In linear regression models, we evaluated the contribution of CRP, Hb, chronic and acute variables to the albumin level variations. The mean albumin level (33.6 g/l) was steady before day 1, declined to 29.3 g/l on day 1 with little increase afterward. The mean CRP increased from day −5, peaked on day 1 and declined thereafter. The mean Hb level was fairly constant during days −30/30. Albumin was inversely (R range, − 0.18/–0.47, P < 10−4) correlated with the CRP level and positively (R = 0.17–0.46, P < 10−4) correlated with the HB level. In most models, CRP was the first variable that contributed to the albumin variations, 34–70% of the full model. The sudden decrease of albumin levels, without sudden fluctuations of CRP or Hb, indicated that hypoalbuminaemia was a marker of trans-capillary leakage.
Usefulness and safety of anakinra in refractory Kawasaki disease complicated by coronary artery aneurysm
Authors: Guillaume Marie-Paule , Reumaux Héloïse , Dubos François
Published: February 2018

Kawasaki disease is an acute self-limited vasculitis of unknown aetiology. The prognosis depends mainly on coronary damage. There is no consensus regarding optimal adjunctive therapeutics for refractory forms to treatment by intravenous immunoglobulins and corticosteroids. We report the case of an 18-month-old infant with refractory Kawasaki disease complicated by diffuse aneurysms of coronary arteries and successfully treated by anakinra with partial regression of coronary aneurysms
Characterization of Interventional Studies of the Cholera Epidemic in Haiti
Authors: Miller Jessica , Birnbaum Marvin L.
Published: February 2018

In October 2010, the Haitian Ministry of Public Health and Population (MSPP; Port au Prince, Haiti) reported a cholera epidemic caused by contamination of the Artibonite River by a United Nation Stabilization Mission camp. Interventional studies of the subsequent responses, including a descriptive Methods section and systematic approach, may be useful in facilitating comparisons and applying lessons learned to future outbreaks. The purpose of this study was to examine publicly available documents relating to the 2010 cholera outbreak to answer: (1) What information is publicly available on interventional studies conducted during the epidemic, and what was/were the impact(s)? and (2) Can the interventions be compared, and what lessons can be learned from their comparison?

A PubMed (National Center for Biotechnology Information, National Institutes of Health; Bethesda, Maryland USA) search was conducted using the parameters “Haiti” and “cholera.” Studies were categorized as “interventional research,” “epidemiological research,” or “other.” A distinction was made between studies and narrative reports. The PubMed search yielded 171 papers, 59 (34.0%) of which were epidemiological and 12 (7.0%) were interventional studies. The remaining 100 papers (59.0%) comprised largely of narrative, anecdotal descriptions. An expanded examination of publications by the World Health Organization (WHO; Geneva, Switzerland), the Center for Research in the Epidemiology of Disasters (CRED; Brussels, Belgium), United States Agency for International Development (USAID; Washington, DC USA)-Development Experience Clearinghouse (DEC), and US National Library of Medicine’s (NLM; Bethesda, Maryland USA) Disaster Literature databases yielded no additional interventional studies. The unstructured formats and differing levels of detail prohibited comparisons between interventions, even between those with a similar approach. Only two (17.0%) interventional studies included any impact data, although neither commented whether the intervention improved health or reduced incidence or mortality related to cholera. Agreed frameworks for guiding responses and subsequent reporting are needed to ensure reports contain sufficient detail to draw conclusions for the definition of best practices and for the design of future interventions.

MillerJ, BirnbaumML. Characterization of interventional studies of the cholera epidemic in Haiti. Prehosp Disaster Med. 2018;33(2):176–181.
Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons’ Willingness to Respond During a Traumatic Medical Emergency
Authors: Ross Elliot M. , Redman Theodore T. , Mapp Julian G. , Brown Derek J. , Tanaka Kaori , Cooley Craig W. , Kharod Chetan U. , Wampler David A.
Published: February 2018

Background

The “Stop the Bleed” campaign advocates for non-medical personnel to be trained in basic hemorrhage control. However, it is not clear what type of education or the duration of instruction needed to meet that requirement. The objective of this study was to determine the impact of a brief hemorrhage control educational curriculum on the willingness of laypersons to respond during a traumatic emergency.

Methods

This “Stop the Bleed” education initiative was conducted by the University of Texas Health San Antonio Office of the Medical Director (San Antonio, Texas USA) between September 2016 and March 2017. Individuals with formal medical certification were excluded from this analysis. Trainers used a pre-event questionnaire to assess participants knowledge and attitudes about tourniquets and responding to traumatic emergencies. Each training course included an individual evaluation of tourniquet placement, 20 minutes of didactic instruction on hemorrhage control techniques, and hands-on instruction with tourniquet application on both adult and child mannequins. The primary outcome in this study was the willingness to use a tourniquet in response to a traumatic medical emergency.

Results

Of 236 participants, 218 met the eligibility criteria. When initially asked if they would use a tourniquet in real life, 64.2% (140/218) responded “Yes.” Following training, 95.6% (194/203) of participants responded that they would use a tourniquet in real life. When participants were asked about their comfort level with using a tourniquet in real life, there was a statistically significant improvement between their initial response and their response post training (2.5 versus 4.0, based on 5-point Likert scale; P<.001).

Conclusion

In this hemorrhage control education study, it was found that a short educational intervention can improve laypersons’ self-efficacy and reported willingness to use a tourniquet in an emergency. Identified barriers to act should be addressed when designing future hemorrhage control public health education campaigns. Community education should continue to be a priority of the “Stop the Bleed” campaign.

RossEM, RedmanTT, MappJG, BrownDJ, TanakaK, CooleyCW, KharodCU, WamplerDA. Stop the bleed: the effect of hemorrhage control education on laypersons’ willingness to respond during a traumatic medical emergency. Prehosp Disaster Med. 2018;33(2):127–132.
Emergency Medical Service (EMS) Utilization by Syrian Refugees Residing in Ankara, Turkey
Authors: Altıner Ali Osman , Yeşil Sıdıka Tekeli
Published: February 2018

Introduction

Many Syrians have left their country and migrated to other countries since March 2011, due to the civil war. As of March 2016, a total of 2,747,946 Syrian refugees had immigrated to Turkey. Some Syrian refugees have been living in camps, while 2,475,134 have been living in metropolitan areas, such as Ankara.

Study Objective

This study investigated Emergency Medical Service (EMS) utilization among Syrian refugees residing in Ankara.

Methods

This study was a descriptive, cross-sectional database analysis using data obtained from the Department of EMS of the Ankara Provincial Health Directorate.

Conclusion

Five stations in the Altındağ region of Ankara responded to 42% of all calls from Syrian refugees. Prehospital EMS in Ankara have been used mostly by Syrian refugees younger than 18-years-old. Study findings also suggest that medical staff in regions where Syrian refugees are likely to be treated should be supported and provided with the ability to overcome language barriers and cultural differences.

AltınerAO, Tekeli YeşilS. Emergency Medical Service (EMS) utilization by Syrian refugees residing in Ankara, Turkey. Prehosp Disaster Med. 2018;33(2):160–164.
SaferDrive: An NLG-based behaviour change support system for drivers
Authors: BRAUN DANIEL , REITER EHUD , SIDDHARTHAN ADVAITH
Published: February 2018

Despite the long history of Natural Language Generation (NLG) research, the potential for influencing real world behaviour through automatically generated texts has not received much attention. In this paper, we presentSaferDrive, a behaviour change support system that uses NLG and telematic data in order to create weekly textual feedback for automobile drivers, which is delivered through a smartphone application. Usage-based car insurances use sensors to track driver behaviour. Although the data collected by such insurances could provide detailed feedback about the driving style, they are typically withheld from the driver and used only to calculate insurance premiums.SaferDriveinstead provides detailed textual feedback about the driving style, with the intent to help drivers improve their driving habits. We evaluate the system with real drivers and report that the textual feedback generated by our system does have a positive influence on driving habits, especially with regard to speeding.
Barriers to fruit and vegetable consumption among farmers’ market incentive programme users in Illinois, USA
Authors: Singleton Chelsea R , Fouché Sydney , Deshpande Rucha , Odoms-Young Angela , Chatman Corey , Spreen Connie
Published: February 2018

Objective

Previous research indicates that low-income individuals often struggle to consume the recommended amount of fruits and vegetables (F&V). LINK Up Illinois is a farmers’ market incentive programme that aims to increase F&V consumption among Supplemental Nutrition Assistance Program (SNAP) recipients by improving access to and affordability of locally grown foods. The present research aimed to identify barriers to F&V consumption that exist among users of the LINK Up Illinois programme.

Design

Cross-sectional.

Setting

Farmers’ markets in Chicago, Springfield, Northbrook, Woodstock, Aurora and Urbana, IL.

Subjects

In 2016, a volunteer sample of 140 LINK Up Illinois users (mean age 42·5 years; 81·7 % female; 28·7 % African American; 44·0 % obese) completed a survey at participating farmers’ markets across the state. Information on demographics, food shopping behaviours, programme satisfaction, barriers to F&V consumption and frequency of F&V consumption was collected and examined.

Results

Approximately 23 % of survey participants reported consuming F&V ≥3 times/d. The barriers to F&V consumption most often reported by survey participants were the cost of F&V (29·5 %), spoilage (18·6 %), knowing how to cook F&V (8·7 %) and not thinking about F&V when hungry (8·6 %). Results from multivariable-adjusted logistic regression models suggested that reporting one or more barriers was associated with reduced odds of consuming vegetables ≥3 times/d, but not fruits.

Conclusions

Cost, spoilage and knowledge of cooking are key barriers to F&V consumption that exist among LINK Up Illinois users. Strategies are needed to mitigate these barriers and increase F&V consumption in this population.
Space, place and (waiting) time: reflections on health policy and politics
Authors: Sheard Sally
Published: February 2018

Health systems have repeatedly addressed concerns about efficiency and equity by employing trans-national comparisons to draw out the strengths and weaknesses of specific policy initiatives. This paper demonstrates the potential for explicit historical analysis of waiting times for hospital treatment to add value to spatial comparative methodologies. Waiting times and the size of the lists of waiting patients have become key operational indicators. In the United Kingdom, as National Health Service (NHS) financial pressures intensified from the 1970s, waiting times have become a topic for regular public and political debate. Various explanations for waiting times include the following: hospital consultants manipulate NHS waiting lists to maintain their private practice; there is under-investment in the NHS; and available (and adequate) resources are being used inefficiently. Other countries have also experienced ongoing tensions between the public and private delivery of universal health care in which national and trans-national comparisons of waiting times have been regularly used. The paper discusses the development of key UK policies, and provides a limited Canadian comparative perspective, to explore wider issues, including whether ‘waiting crises’ were consciously used by policymakers, especially those brought into government to implement new economic and managerial strategies, to diminish the autonomy and authority of the medical professional in the hospital environment.
Proteorhodopsin variability and distribution in the North Pacific Subtropical Gyre
Authors: Olson Daniel K , Yoshizawa Susumu , Boeuf Dominique , Iwasaki Wataru , DeLong Edward F
Published: February 2018

Proteorhodopsin is a light-activated retinal-containing proton pump found in many marine bacteria. These photoproteins are globally distributed in the ocean’s photic zone and are capable of generating a proton motive force across the cell membrane. We investigated the phylogenetic diversity, distribution, and abundance of proteorhodopsin encoding genes in free-living bacterioplankton in the North Pacific Subtropical Gyre, leveraging a gene catalog derived from metagenomic samples from the ocean’s surface to 1000 m depth. Proteorhodopsin genes were identified at all depths sampled, but were most abundant at depths shallower than 200 m. The majority of proteorhodopsin gene sequences (60.9%) belonged to members of the SAR11 lineage, with remaining sequences distributed among other diverse taxa. We observed variations in the conserved residues involved in ion pumping and spectral tuning, and biochemically confirmed four different proton pumping proteorhodopsin motifs, including one unique to deep-water SAR11. We also identified a new group of putative proteorhodopsins having unknown function. Our results reveal a broad organismal and unexpected depth distribution for different proteorhodopsin types, as well as substantial within-taxon variability. These data provide a framework for exploring the ecological relevance of proteorhodopsins and their spatiotemporal variation and function in heterotrophic bacteria in the open ocean.
PeatlandAcidobacteriawith a dissimilatory sulfur metabolism
Authors: Hausmann Bela , Pelikan Claus , Herbold Craig W , Köstlbacher Stephan , Albertsen Mads , Eichorst Stephanie A , Glavina del Rio Tijana , Huemer Martin , Nielsen Per H , Rattei Thomas , Stingl Ulrich , Tringe Susannah G , Trojan Daniela , Wentrup Cecilia , Woebken Dagmar , Pester Michael , Loy Alexander
Published: February 2018

Sulfur-cycling microorganisms impact organic matter decomposition in wetlands and consequently greenhouse gas emissions from these globally relevant environments. However, their identities and physiological properties are largely unknown. By applying a functional metagenomics approach to an acidic peatland, we recovered draft genomes of seven novel Acidobacteria species with the potential for dissimilatory sulfite (dsrAB, dsrC, dsrD, dsrN, dsrT, dsrMKJOP) or sulfate respiration (sat, aprBA, qmoABC plus dsr genes). Surprisingly, the genomes also encoded DsrL, which so far was only found in sulfur-oxidizing microorganisms. Metatranscriptome analysis demonstrated expression of acidobacterial sulfur-metabolism genes in native peat soil and their upregulation in diverse anoxic microcosms. This indicated an active sulfate respiration pathway, which, however, might also operate in reverse for dissimilatory sulfur oxidation or disproportionation as proposed for the sulfur-oxidizing Desulfurivibrio alkaliphilus. Acidobacteria that only harbored genes for sulfite reduction additionally encoded enzymes that liberate sulfite from organosulfonates, which suggested organic sulfur compounds as complementary energy sources. Further metabolic potentials included polysaccharide hydrolysis and sugar utilization, aerobic respiration, several fermentative capabilities, and hydrogen oxidation. Our findings extend both, the known physiological and genetic properties of Acidobacteria and the known taxonomic diversity of microorganisms with a DsrAB-based sulfur metabolism, and highlight new fundamental niches for facultative anaerobic Acidobacteria in wetlands based on exploitation of inorganic and organic sulfur molecules for energy conservation.
Genome-resolved metagenomics identifies genetic mobility, metabolic interactions, and unexpected diversity in perchlorate-reducing communities
Authors: Barnum Tyler P , Figueroa Israel A , Carlström Charlotte I , Lucas Lauren N , Engelbrektson Anna L , Coates John D
Published: February 2018

Dissimilatory perchlorate reduction is an anaerobic respiratory pathway that in communities might be influenced by metabolic interactions. Because the genes for perchlorate reduction are horizontally transferred, previous studies have been unable to identify uncultivated perchlorate-reducing populations. Here we recovered metagenome-assembled genomes from perchlorate-reducing sediment enrichments and employed a manual scaffolding approach to reconstruct gene clusters for perchlorate reduction found within mobile genetic elements. De novo assembly and binning of four enriched communities yielded 48 total draft genomes. In addition to canonical perchlorate reduction gene clusters and taxa, a new type of gene cluster with an alternative perchlorate reductase was identified. Phylogenetic analysis indicated past exchange between these gene clusters, and the presence of plasmids with either gene cluster shows that the potential for gene transfer via plasmid persisted throughout enrichment. However, a majority of genomes in each community lacked perchlorate reduction genes. Putative chlorate-reducing or sulfur-reducing populations were dominant in most communities, supporting the hypothesis that metabolic interactions might result from perchlorate reduction intermediates and byproducts. Other populations included a novel phylum-level lineage (Ca. Muirbacteria) and epibiotic prokaryotes with no known role in perchlorate reduction. These results reveal unexpected genetic diversity, suggest that perchlorate-reducing communities involve substantial metabolic interactions, and encourage expanded strategies to further understand the evolution and ecology of this metabolism.
miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)
Authors: Lu Yunjie , Gao Ji , Zhang Shaopeng , Gu Jian , Lu Hao , Xia Yongxiang , Zhu Qin , Qian Xiaofeng , Zhang Feng , Zhang Chuanyong , shen Hongbing , Hippen Keli L. , Blazar Bruce R. , Lu Ling , Wang Xuehao
Published: February 2018

Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise in the prevention of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation patients. However, strategies are needed to improve tTreg proliferative ability and survival as a means to improve tTreg therapy and reduce the requirement for producing large numbers of Treg cells for adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic components, which is involved in cells death, differentiation, lymphocyte homeostasis, and tTreg function. Studies have shown that mice with tTreg cells that have a disrupted autophagy process have defective tTreg cell generation and function, resulting in autoimmune disease and failed GVHD prevention by adoptively transferred tTreg cells. We found the attenuated autophagy status during ex vivo expansion, which leads us to determine whether tTreg cell survival could be augmented by miR-142-3p, the miRNA which is highly expressed in tTreg cells and potentially targets autophagy-related protein (ATG)-1, ATG16L1. We demonstrate that miR-142-3p downregulates ATG16L1 mRNA and production of ATG16L1, that has been linked to autoimmune diseases. Conversely, miR-142-3p knock-down improved tTreg cell expansion, survival and function in vitro and vivo. In aggregate, these studies provide a new approach that uses miR-142-3p knockdown to increase tTreg cell efficacy by increasing ATG16L1 mRNA and protein and the autophagy process.
Long noncoding RNA Gomafu upregulates Foxo1 expression to promote hepatic insulin resistance by sponging miR-139-5p
Authors: Yan Caifeng , Li Jin , Feng Shangyong , Li Ying , Tan Lu
Published: February 2018

Long non-coding RNA Gomafu is involved in diabetes-related diseases. However, its role in insulin resistance (IR) remains unclear. Our objective is to explore the role of Gomafu in hepatic IR and glucose intolerance. Gomafu expression was determined in livers of ob/ob mice and high-fat diet (HFD) mice. The binding activity of NF-κB on the Gomafu promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assays. Increased Gomafu expression was observed in the livers of obese mice. Besides, the binding of NF-κB on the Gomafu promoter was also observed in hepatocytes from ob/ob mice. Further study showed that knockdown of NF-κB p65 alleviated the increase in hepatic Gomafu expression in vivo and in vitro. Knockdown of hepatic Gomafu inhibited hepatic glucose production (HGP) and improved insulin sensitivity in obese mice, whereas, overexpression of hepatic Gomafu resulted in an increase in random and fasting blood glucose levels in lean mice. In addition, we demonstrated that Gomafu functioned as miR-139 sponge and led to the de-repression of its target gene Foxo1, which played an important role in gluconeogenesis and HGP in hepatocytes. Finally, silenced Foxo1 expression abolished the effect of Gomafu overexpression on gluconeogenesis and glucose production in hepatocytes. Taken together, our data suggested that the increase in Gomafu expression contributed to hepatic IR in obese mice.
The binding of DCC-P3 motif and FAK-FAT domain mediates the initial step of netrin-1/DCC signaling for axon attraction
Authors: Xu Shutong , Liu Yiqiong , Li Xiaolong , Liu Ying , Meijers Rob , Zhang Yan , Wang Jia-huai
Published: February 2018

Netrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution. Axon guidance assays confirm that the DCC/FAK complex is essential for netrin-1-induced chemoattraction. We propose that netrin-1/DCC engagement creates a small cluster of P3/FAT for FAK recruitment close to the cell membrane, which exerts a concerted effect with PIP2 for FAK signaling. We also compare P3/FAT binding with paxillin/FAT binding and discuss their distinct recognition specificity on a common FAT domain for axon attraction versus integrin signaling, respectively.
Increasing temperature of cooling granular gases
Authors: Brilliantov Nikolai V. , Formella Arno , Pöschel Thorsten
Published: February 2018

The kinetic energy of a force-free granular gas decays monotonously due to inelastic collisions of the particles. For a homogeneous granular gas of identical particles, the corresponding decay of granular temperature is quantified by Haff’s law. Here, we report that for a granular gas of aggregating particles, the granular temperature does not necessarily decay but may even increase. Surprisingly, the increase of temperature is accompanied by the continuous loss of total gas energy. This stunning effect arises from a subtle interplay between decaying kinetic energy and gradual reduction of the number of degrees of freedom associated with the particles’ dynamics. We derive a set of kinetic equations of Smoluchowski type for the concentrations of aggregates of different sizes and their energies. We find scaling solutions to these equations and a condition for the aggregation mechanism predicting growth of temperature. Numerical direct simulation Monte Carlo results confirm the theoretical predictions.
A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle
Authors: Goode Benjamin , Mondal Gourish , Hyun Michael , Ruiz Diego Garrido , Lin Yu-Hsiu , Van Ziffle Jessica , Joseph Nancy M. , Onodera Courtney , Talevich Eric , Grenert James P. , Hewedi Iman H. , Snuderl Matija , Brat Daniel J. , Kleinschmidt-DeMasters Bette K. , Rodriguez Fausto J. , Louis David N. , Yong William H. , Lopes M. Beatriz , Rosenblum Marc K. , Butowski Nicholas , Tihan Tarik , Bollen Andrew W. , Phillips Joanna J. , Wiita Arun P. , Yeh Iwei , Jacobson Matthew P. , Bastian Boris C. , Perry Arie , Solomon David A.
Published: February 2018

Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina terminalis along the anterior wall of the third ventricle. Despite being histologically low-grade, chordoid gliomas are often associated with poor outcome, as their stereotypic location in the third ventricle makes resection challenging and efficacious adjuvant therapies have not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutation in PRKCA in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα). Expression of mutant PRKCA in immortalized human astrocytes led to increased phospho-ERK and anchorage-independent growth that could be blocked by MEK inhibition. These studies define PRKCA as a recurrently mutated oncogene in human cancer and identify a potential therapeutic vulnerability in this uncommon brain tumor.
Zebrafish and medaka offer insights into the neurobehavioral correlates of vertebrate magnetoreception
Authors: Myklatun Ahne , Lauri Antonella , Eder Stephan H. K. , Cappetta Michele , Shcherbakov Denis , Wurst Wolfgang , Winklhofer Michael , Westmeyer Gil G.
Published: February 2018

An impediment to a mechanistic understanding of how some species sense the geomagnetic field (“magnetoreception”) is the lack of vertebrate genetic models that exhibit well-characterized magnetoreceptive behavior and are amenable to whole-brain analysis. We investigated the genetic model organisms zebrafish and medaka, whose young stages are transparent and optically accessible. In an unfamiliar environment, adult fish orient according to the directional change of a magnetic field even in darkness. To enable experiments also in juveniles, we applied slowly oscillating magnetic fields, aimed at generating conflicting sensory inputs during exploratory behavior. Medaka (but not zebrafish) increase their locomotor activity in this assay. Complementary brain  activity mapping reveals neuronal activation in the lateral hindbrain during magnetic stimulation. These comparative data support magnetoreception in teleosts, provide evidence for a light-independent mechanism, and demonstrate the usefulness of zebrafish and medaka as genetic vertebrate models for studying the biophysical and neuronal mechanisms underlying magnetoreception.
Membrane cholesterol mediates the cellular effects of monolayer graphene substrates
Authors: Kitko Kristina E. , Hong Tu , Lazarenko Roman M. , Ying Da , Xu Ya-Qiong , Zhang Qi
Published: February 2018

Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene’s cellular effects, providing insight into the biological impact of graphene.
Membrane sculpting by curved DNA origami scaffolds
Authors: Franquelim Henri G. , Khmelinskaia Alena , Sobczak Jean-Philippe , Dietz Hendrik , Schwille Petra
Published: February 2018

Membrane sculpting and transformation is essential for many cellular functions, thus being largely regulated by self-assembling and self-organizing protein coats. Their functionality is often encoded by particular spatial structures. Prominent examples are BAR domain proteins, the ‘banana-like’ shapes of which are thought to aid scaffolding and membrane tubulation. To elucidate whether 3D structure can be uncoupled from other functional features of complex scaffolding proteins, we hereby develop curved DNA origami in various shapes and stacking features, following the presumable design features of BAR proteins, and characterize their ability for membrane binding and transformation. We show that dependent on curvature, membrane affinity and surface density, DNA origami coats can indeed reproduce the activity of membrane-sculpting proteins such as BAR, suggesting exciting perspectives for using them in bottom-up approaches towards minimal biomimetic cellular machineries.
Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells
Authors: Kirkin Alexei F. , Dzhandzhugazyan Karine N. , Guldberg Per , Fang Johnny Jon , Andersen Rikke S. , Dahl Christina , Mortensen Jann , Lundby Tim , Wagner Aase , Law Ian , Broholm Helle , Madsen Line , Lundell-Ek Christer , Gjerstorff Morten F. , Ditzel Henrik J. , Jensen Martin R. , Fischer Walter
Published: February 2018

In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25 patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can be generated ex vivo by exposure to antigens induced by DNA demethylation, providing a novel, minimally invasive therapeutic strategy for treating cancer.
Molecular demultiplexer as a terminator automaton
Authors: Turan Ilke S. , Gunaydin Gurcan , Ayan Seylan , Akkaya Engin U.
Published: February 2018

Molecular logic gates are expected to play an important role on the way to information processing therapeutic agents, especially considering the wide variety of physical and chemical responses that they can elicit in response to the inputs applied. Here, we show that a 1:2 demultiplexer based on a Zn2+-terpyridine-Bodipy conjugate with a quenched fluorescent emission, is efficient in photosensitized singlet oxygen generation as inferred from trap compound experiments and cell culture data. However, once the singlet oxygen generated by photosensitization triggers apoptotic response, the Zn2+ complex then interacts with the exposed phosphatidylserine lipids in the external leaflet of the membrane bilayer, autonomously switching off singlet oxygen generation, and simultaneously switching on a bright emission response. This is the confirmatory signal of the cancer cell death by the action of molecular automaton and the confinement of unintended damage by excessive singlet oxygen production.
Anaesthesia in austere environments: literature review and considerations for future space exploration missions
Authors: Komorowski Matthieu , Fleming Sarah , Mawkin Mala , Hinkelbein Jochen
Published: February 2018

Future space exploration missions will take humans far beyond low Earth orbit and require complete crew autonomy. The ability to provide anaesthesia will be important given the expected risk of severe medical events requiring surgery. Knowledge and experience of such procedures during space missions is currently extremely limited. Austere and isolated environments (such as polar bases or submarines) have been used extensively as test beds for spaceflight to probe hazards, train crews, develop clinical protocols and countermeasures for prospective space missions. We have conducted a literature review on anaesthesia in austere environments relevant to distant space missions. In each setting, we assessed how the problems related to the provision of anaesthesia (e.g., medical kit and skills) are dealt with or prepared for. We analysed how these factors could be applied to the unique environment of a space exploration mission. The delivery of anaesthesia will be complicated by many factors including space-induced physiological changes and limitations in skills and equipment. The basic principles of a safe anaesthesia in an austere environment (appropriate training, presence of minimal safety and monitoring equipment, etc.) can be extended to the context of a space exploration mission. Skills redundancy is an important safety factor, and basic competency in anaesthesia should be part of the skillset of several crewmembers. The literature suggests that safe and effective anaesthesia could be achieved by a physician during future space exploration missions. In a life-or-limb situation, non-physicians may be able to conduct anaesthetic procedures, including simplified general anaesthesia.
Longitudinal change in the serology of antibodies to Chlamydia trachomatis pgp3 in children residing in a trachoma area
Authors: West Sheila K. , Munoz Beatriz , Kaur Hemjot , Dize Laura , Mkocha Harran , Gaydos Charlotte A. , Quinn Thomas C.
Published: February 2018

A serologic test for antibodies to chlamydial antigen pgp3 may be a useful tool for trachoma surveillance. However, little is known about the stability of antibody status over time, or factors associated with seroreversion/conversion. A cohort of 2,111 children ages 1–9 years in Tanzania were followed for one year in the absence of mass azithromycin. At baseline and follow-up, they were evaluated for trachoma, chlamydial infection, and antibodies to chlamydial antigen pgp3. At baseline, 31% of children were seropositive for pgp3 antibodies and 6.4% seroreverted to negative over one year. Of those seronegative, 9.8% seroconverted over the year. The seroreverters had lower baseline mean fluorescence intensity (MFI-BG) values compared to the seropositives who remained positive (Odds Ratio = 0.04 for every unit increase in log10MFI-BG, 95% CI = 0.02–0.09), and were more likely to live in communities with trachoma <5% (p < 0.008). While seroconversion was expected, seroreversion was unexpected. The low seroprevalence rate reported from low endemic areas may be due to seroreversion as well as lack of exposure.
Snap-through transition of buckled graphene membranes for memcapacitor applications
Authors: Yamaletdinov Ruslan D. , Ivakhnenko Oleg V. , Sedelnikova Olga V. , Shevchenko Sergey N. , Pershin Yuriy V.
Published: February 2018

Using computational and theoretical approaches, we investigate the snap-through transition of buckled graphene membranes. Our main interest is related to the possibility of using the buckled membrane as a plate of capacitor with memory (memcapacitor). For this purpose, we performed molecular-dynamics (MD) simulations and elasticity theory calculations of the up-to-down and down-to-up snap-through transitions for membranes of several sizes. We have obtained expressions for the threshold switching forces for both up-to-down and down-to-up transitions. Moreover, the up-to-down threshold switching force was calculated using the density functional theory (DFT). Our DFT results are in general agreement with MD and analytical theory findings. Our systematic approach can be used for the description of other structures, including nanomechanical and biological ones, experiencing the snap-through transition.
Changes in Ugandan Climate Rainfall at the Village and Forest Level
Authors: Ssentongo Paddy , Muwanguzi Abraham J. B. , Eden Uri , Sauer Timothy , Bwanga George , Kateregga Geoffrey , Aribo Lawrence , Ojara Moses , Mugerwa Wilberforce Kisamba , Schiff Steven J.
Published: February 2018

In 2013, the US National Oceanographic and Atmospheric Administration (NOAA) refined the historical rainfall estimates over the African Continent and produced the African Rainfall Climate version 2.0 (ARC2) estimator. ARC2 offers a nearly complete record of daily rainfall estimates since 1983 at 0.1° × 0.1° resolution. Despite short-term anomalies, we identify an overall decrease in average rainfall of about 12% during the past 34 years in Uganda. Spatiotemporally, these decreases are greatest in agricultural regions of central and western Uganda, but similar rainfall decreases are also reflected in the gorilla habitat within the Bwindi Forest in Southwest Uganda. The findings carry significant implications for agriculture production, food security, wildlife habitat, and economic impact at the community and societal level.
Identification and characterization of the BRI2 interactome in the brain
Authors: Martins Filipa , Marafona Ana M. , Pereira Cátia D. , Müller Thorsten , Loosse Christina , Kolbe Katharina , da Cruz e Silva Odete A. B. , Rebelo Sandra
Published: February 2018

BRI family proteins are ubiquitous type II transmembrane proteins but BRI2 is highly expressed in some neuronal tissues. Possible BRI2 functions include neuronal maturation and differentiation. Protein complexes appear to be important in mediating its functions. Previously described BRI2 interactors include the Alzheimer’s amyloid precursor protein and protein phosphatase 1, but clearly the identification of novel interactors provides an important tool to understand the role and function of BRI2. To this end three rat brain regions (cerebellum, hippocampus, and cerebral cortex) were processed by BRI2 immunoprecipitation; co-precipitating proteins were identified by Nano-HPLC-MS/MS. The pool of the brain regions resulted in 511 BRI2 interacting proteins (BRI2 brain interactome) of which 120 were brain specific and 49 involved in neuronal differentiation. Brain region-specific analyses were also carried out for cerebellum, hippocampus, and cerebral cortex. Several novel BRI2 interactors were identified among them DLG4/PSD-95, which is singularly important as it places BRI2 in the postsynaptic compartment. This interaction was validated as well as the interaction with GAP-43 and synaptophysin. In essence, the resulting BRI2 brain interactome, associates this protein with neurite outgrowth and neuronal differentiation, as well as synaptic signalling and plasticity. It follows that further studies should address BRI2 particularly given its relevance to neuropathological conditions.
Allopurinol partially prevents disuse muscle atrophy in mice and humans
Authors: Ferrando Beatriz , Gomez-Cabrera Mari Carmen , Salvador-Pascual Andrea , Puchades Carlos , Derbré Frederic , Gratas-Delamarche Arlette , Laparre Ludovic , Olaso-Gonzalez Gloria , Cerda Miguel , Viosca Enrique , Alabajos Ana , Sebastiá Vicente , Alberich-Bayarri Angel , García-Castro Fabio , Viña Jose
Published: February 2018

Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.
Role of the Metal-Oxide Work Function on Photocurrent Generation in Hybrid Solar Cells
Authors: Thu Chawloon , Ehrenreich Philipp , Wong Ka Kan , Zimmermann Eugen , Dorman James , Wang Wei , Fakharuddin Azhar , Putnik Martin , Drivas Charalampos , Koutsoubelitis Aimilios , Vasilopoulou Maria , Palilis Leonidas C. , Kennou Stella , Kalb Julian , Pfadler Thomas , Schmidt-Mende Lukas
Published: February 2018

ZnO is a widely used metal-oxide semiconductor for photovoltaic application. In solar cell heterostructures they not only serve as a charge selective contact, but also act as electron acceptor. Although ZnO offers a suitable interface for exciton dissociation, charge separation efficiencies have stayed rather poor and conceptual differences to organic acceptors are rarely investigated. In this work, we employ Sn doping to ZnO nanowires in order to understand the role of defect and surface states in the charge separation process. Upon doping we are able to modify the metal-oxide work function and we show its direct correlation with the charge separation efficiency. For this purpose, we use the polymer poly(3-hexylthiophene) as donor and the squaraine dye SQ2 as interlayer. Interestingly, neither mobilities nor defects are prime performance limiting factor, but rather the density of available states around the conduction band is of crucial importance for hybrid interfaces. This work highlights crucial aspects to improve the charge generation process of metal-oxide based solar cells and reveals new strategies to improve the power conversion efficiency of hybrid solar cells.
Distribution of metals and metalloids in dried seaweeds and health risk to population in southeastern China
Authors: Chen Qing , Pan Xiao-Dong , Huang Bai-Fen , Han Jian-Long
Published: February 2018

Concern about metals and metalloids, especially heavy metals in seaweeds has risen due to potential health risk. This study investigated the distribution of 10 metals and metalloids in 295 dried seaweeds (brown and red) and estimated the possible health risk via hazard index (HI). Elements in seaweeds can be sequenced in descending order by mean values: Al > Mn > As > Cu > Cr > Ni > Cd > Se > Pb > Hg. The levels of Cd, Cu, Mn and Ni in red seaweeds were significantly higher than those in brown seaweeds (P < 0.01). Correlation analysis showed contents of Ni-Cr (r = 0.59, P < 0.01) in seaweeds had moderate positive correlations. Seaweeds from different geographical origins had diverse element distribution. Risk assessment showed that HI at mean level was less than the threshold of 1. It indicates that for the general people there is low health risk to these elements by the intake of seaweeds. Furthermore, in terms of the confirmative toxicity of some metals, such as Cd, Pb and Hg, surveillance of metals in seaweeds should be performed continuously.
Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia
Authors: Chen Yuan-Yuei , Kao Tung-Wei , Chou Cheng-Wai , Wu Chen-Jung , Yang Hui-Fang , Lai Ching-Huang , Wu Li-Wei , Chen Wei-Liang
Published: February 2018

Emerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20–65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.