bluuebunny/crossref_metadata_2025 huggingface dataset:
Nineteenth Century Black and Mixed-Race Physical Activity, Calories, and Life Expectancy: Nutrition, Sanitation, or Medical Intervention?
Authors: Carson Scott Alan
Published: December 2016

Using data from late 19th and early twentieth century US prisons, this study considers how black and mixed-race basal metabolic rates and calories varied with economic development. During the nineteenth century, African-American physical activity and net nutrition decreased across their BMR and calorie distributions, and increasing black life expectancy indicates that decreasing mortality was not likely due to improved nutrition. Physically active farmers had greater BMRs and required more calories per day than workers in other occupations. Black diets, nutrition, and calories varied by residence, and rural blacks in the Deep South required the most calories per day, while their Northeastern urban counterparts required the least. Policy implications are that public sanitation facilities may be of greater import than nutrition during economic development.
The role of assessment in supporting the movement toward patient-centred care
Authors: Norcini John J.
Published: December 2016

None
Seclusion and enforced medication in dealing with aggression: A prospective dynamic cohort study
Authors: Verlinde A.A. , Noorthoorn E.O. , Snelleman W. , van den Berg H. , Snelleman – van der Plas M. , Lepping P.
Published: December 2016

Background

In the Netherlands, seclusion is historically the measure of first choice in dealing with aggressive incidents. In 2010, the Mediant Mental Health Trust in Eastern Netherlands introduced a policy prioritising the use of enforced medication to manage aggressive incidents over seclusion. The main goal of the study was to investigate whether prioritising enforced medication over seclusion leads to a change of aggressive incidents and coercive measures.

Methods

The study was carried out with data from 2764 patients admitted between 2007 and 2013 to the hospital locations of the Mediant Mental Health Trust in Eastern Netherlands, with a catchment area of 500,000 inhabitants. Seclusion, restraint and enforced medications as well as other coercive measures were gathered systematically. Aggressive incidents were assessed with the SOAS-R. An event sequence analysis was preformed, to assess the whether seclusion, restraint or enforced medication were used or not before or after aggressive incidents.

Results

Enforced medication use went up by 363% from a very low baseline. There was a marked reduction of overall coercive measures by 44%. Seclusion hours went down by 62%. Aggression against staff or patients was reduced by 40%.

Conclusions

When dealing with aggression, prioritising medication significantly reduces other coercive measures and aggression against staff, while within principles of subsidiarity, proportionality and expediency.
Latent classes in diagnoses among psychiatric inpatients predicting mortality and imprisonment – a nationwide cohort study
Authors: Carlsen H.K. , Steingrimsson S. , Sigurdsson M.I. , Sigfússon S. , Magnússon A.
Published: December 2016

Purpose

Identify risk factors of death or imprisonment within classes defined by demographic factors and diagnoses within one year of first psychiatric admission.

Methods

Nationwide data was obtained from hospital registers from psychiatric hospitals in Iceland 1983–2007. Mortality and cause of death as well as information about imprisonments during the study period, and discharge diagnoses for the first year after initial admission were obtained for each individual. Individuals aged 18 during the study period with at least one year of follow-up were included. Latent Class Analysis was used to identify groups with distinguishable risk of either being alive, dead or having been imprisoned at the end of follow-up.

Results

Among psychiatric patients, 4677 were included, average age was 27 years (range 18–43). Four latent classes were identified with different risks of adverse outcomes. Class B (16%), predominantly males with substance use disorder (SUD) diagnoses, had highly increased risk of imprisonment and death accounting for 85 and 34% of these outcomes, respectively. Class A (12%), all with alcohol use disorder, had similar mortality rate as the general population and no imprisonments. Class C (23%) were younger at first admission with some SUD and increased risk of mortality. Class D (46%) had increased mortality rate, SUDs were rare but depression common.

Conclusions

Risk of mortality and criminal trends among psychiatric inpatients can be described as distinct clusters of risk factors present at first admission to a psychiatric hospital. Treatment and interventions to reduce mortality and criminality should take these risk differences into account.
Which DSM validated tools for diagnosing depression are usable in primary care research? A systematic literature review
Authors: Nabbe P. , Le Reste J.Y. , Guillou-Landreat M. , Munoz Perez M.A. , Argyriadou S. , Claveria A. , Fernández San Martín M.I. , Czachowski S. , Lingner H. , Lygidakis C. , Sowinska A. , Chiron B. , Derriennic J. , Le Prielec A. , Le Floch B. , Montier T. , Van Marwijk H. , Van Royen P.
Published: December 2016

Introduction

Depression occurs frequently in primary care. Its broad clinical variability makes it difficult to diagnose. This makes it essential that family practitioner (FP) researchers have validated tools to minimize bias in studies of everyday practice. Which tools validated against psychiatric examination, according to the major depression criteria of DSM-IV or 5, can be used for research purposes?

Method

An international FP team conducted a systematic review using the following databases: Pubmed, Cochrane and Embase, from 2000/01/01 to 2015/10/01.

Results

The three databases search identified 770 abstracts: 546 abstracts were analyzed after duplicates had been removed (224 duplicates); 50 of the validity studies were eligible and 4 studies were included. In 4 studies, the following tools were found: GDS-5, GDS-15, GDS-30, CESD-R, HADS, PSC-51 and HSCL-25. Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value were collected. The Youden index was calculated.

Discussion

Using efficiency data alone to compare these studies could be misleading. Additional reliability, reproducibility and ergonomic data will be essential for making comparisons.

Conclusion

This study selected seven tools, usable in primary care research, for the diagnosis of depression. In order to define the best tools in terms of efficiency, reproducibility, reliability and ergonomics for research in primary care, and for care itself, further research will be essential.
The complexity of interpreting genomic data in patients with acute myeloid leukemia
Authors: Nazha A , Zarzour A , Al-Issa K , Radivoyevitch T , Carraway H E , Hirsch C M , Przychodzen B , Patel B J , Clemente M , Sanikommu S R , Kalaycio M , Maciejewski J P , Sekeres M A
Published: December 2016

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.
Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era
Authors: Chakraborty R , Muchtar E , Kumar S K , Jevremovic D , Buadi F K , Dingli D , Dispenzieri A , Hayman S R , Hogan W J , Kapoor P , Lacy M Q , Leung N , Gertz M A
Published: December 2016

The impact of circulating plasma cells (CPCs) prior to autologous stem cell transplantation (ASCT) for multiple myeloma has not been defined in the novel agent era. We evaluated the impact of pre-transplant CPCs, detected by six-color flow cytometry in patients undergoing early ASCT on post-transplant response, progression-free survival (PFS) and overall survival (OS). CPCs were detected in 162 out of 840 (19.3%) patients, with the median number of CPCs being 58 per 150 000 events. Ninety-nine percent of patients had received proteasome inhibitor and/or immunomodulator-based induction. The incidence of post-transplant stringent complete response (sCR) in the subgroups with and without CPCs was 15% and 38%, respectively, (P<0.001). The median PFS in the subgroups with and without CPCs was 15.1 (95% confidence interval (CI), 12.5–17.8) and 29.6 months (95% CI, 26.2–32.8), respectively, and the median OS was 41.0 months (95% CI, 32.6–58.2) and not reached (NR) (95% CI, 99.1-NR), respectively, (P<0.001 for both). On multivariate analysis for OS, factors independently predictive of mortality were the presence of CPCs (hazard ratio (HR) 2.5; 95% CI, 1.8–3.6;P<0.001) and sCR post transplant (HR 0.4; 95% CI, 0.2–0.6;P<0.001). Presence of CPCs prior to transplant has a high prognostic impact and should be prospectively validated in clinical trials.
Fungal–bacterial dynamics and their contribution to terrigenous carbon turnover in relation to organic matter quality
Authors: Fabian Jenny , Zlatanovic Sanja , Mutz Michael , Premke Katrin
Published: December 2016

Ecological functions of fungal and bacterial decomposers vary with environmental conditions. However, the response of these decomposers to particulate organic matter (POM) quality, which varies widely in aquatic ecosystems, remains poorly understood. Here we investigated how POM pools of substrates of different qualities determine the relative contributions of aquatic fungi and bacteria to terrigenous carbon (C) turnover. To this end, surface sediments were incubated with different POM pools of algae and/or leaf litter. 13C stable-isotope measurements of C mineralization were combined with phospholipid analysis to link the metabolic activities and substrate preferences of fungal and bacterial heterotrophs to dynamics in their abundance. We found that the presence of labile POM greatly affected the dominance of bacteria over fungi within the degrader communities and stimulated the decomposition of beech litter primarily through an increase in metabolic activity. Our data indicated that fungi primarily contribute to terrigenous C turnover by providing litter C for the microbial loop, whereas bacteria determine whether the supplied C substrate is assimilated into biomass or recycled back into the atmosphere in relation to phosphate availability. Thus, this study provides a better understanding of the role of fungi and bacteria in terrestrial–aquatic C cycling in relation to environmental conditions.
Convergent patterns in the evolution of mealybug symbioses involving different intrabacterial symbionts
Authors: Szabó Gitta , Schulz Frederik , Toenshoff Elena R , Volland Jean-Marie , Finkel Omri M , Belkin Shimshon , Horn Matthias
Published: December 2016

Mealybugs (Insecta: Hemiptera: Pseudococcidae) maintain obligatory relationships with bacterial symbionts, which provide essential nutrients to their insect hosts. Most pseudococcinae mealybugs harbor a unique symbiosis setup with enlarged betaproteobacterial symbionts (‘Candidatus Tremblaya princeps’), which themselves contain gammaproteobacterial symbionts. Here we investigated the symbiosis of the manna mealybug, Trabutina mannipara, using a metagenomic approach. Phylogenetic analyses revealed that the intrabacterial symbiont of T. mannipara represents a novel lineage within the Gammaproteobacteria, for which we propose the tentative name ‘Candidatus Trabutinella endobia’. Combining our results with previous data available for the nested symbiosis of the citrus mealybug Planococcus citri, we show that synthesis of essential amino acids and vitamins and translation-related functions partition between the symbiotic partners in a highly similar manner in the two systems, despite the distinct evolutionary origin of the intrabacterial symbionts. Bacterial genes found in both mealybug genomes and complementing missing functions in both symbioses were likely integrated in ancestral mealybugs before T. mannipara and P. citri diversified. The high level of correspondence between the two mealybug systems and their highly intertwined metabolic pathways are unprecedented. Our work contributes to a better understanding of the only known intracellular symbiosis between two bacteria and suggests that the evolution of this unique symbiosis included the replacement of intrabacterial symbionts in ancestral mealybugs.
Helminth burden and ecological factors associated with alterations in wild host gastrointestinal microbiota
Authors: Newbold Lindsay K , Burthe Sarah J , Oliver Anna E , Gweon Hyun S , Barnes Christopher J , Daunt Francis , van der Gast Christopher J
Published: December 2016

Infection by gastrointestinal helminths of humans, livestock and wild animals is common, but the impact of such endoparasites on wild hosts and their gut microbiota represents an important overlooked component of population dynamics. Wild host gut microbiota and endoparasites occupy the same physical niche spaces with both affecting host nutrition and health. However, associations between the two are poorly understood. Here we used the commonly parasitized European shag (Phalacrocorax aristotelis) as a model wild host. Forty live adults from the same colony were sampled. Endoscopy was employed to quantify helminth infection in situ. Microbiota from the significantly distinct proventriculus (site of infection), cloacal and faecal gastrointestinal tract microbiomes were characterised using 16S rRNA gene-targeted high-throughput sequencing. We found increasingly strong associations between helminth infection and microbiota composition progressing away from the site of infection, observing a pronounced dysbiosis in microbiota when samples were partitioned into high- and low-burden groups. We posit this dysbiosis is predominately explained by helminths inducing an anti-inflammatory environment in the proventriculus, diverting host immune responses away from themselves. This study, within live wild animals, provides a vital foundation to better understand the mechanisms that underpin the three-way relationship between helminths, microbiota and hosts.
Photosynthetic temperature adaptation during niche diversification of the thermophilic cyanobacterium Synechococcus A/B clade
Authors: Pedersen Deana , Miller Scott R
Published: December 2016

We take an in vivo fluorescence approach to investigate photosynthetic adaptation by ecologically divergent members of the A/B clade of the hot spring cyanobacterium Synechococcus, the most thermotolerant of which defines the upper thermal limit for photosynthesis. During Synechococcus diversification, both photosystem II and the light-harvesting phycobilisome have evolved greater thermostability as the group has invaded higher temperature habitats, particularly for the most thermotolerant lineage. This enhanced function at higher temperatures has come at the cost of reduced performance at lower temperatures, and these trade-offs contribute to niche specialization in the clade. Molecular evolutionary analyses revealed specific adaptive protein changes in the most thermotolerant lineage. Our study advances our understanding of the origins of Synechococcus diversity.
Viruses and the origin of microbiome selection and immunity
Authors: Quistad Steven D , Grasis Juris A , Barr Jeremy J , Rohwer Forest L
Published: December 2016

The last common metazoan ancestor (LCMA) emerged over half a billion years ago. These complex metazoans provided newly available niche space for viruses and microbes. Modern day contemporaries, such as cnidarians, suggest that the LCMA consisted of two cell layers: a basal endoderm and a mucus-secreting ectoderm, which formed a surface mucus layer (SML). Here we propose a model for the origin of metazoan immunity based on external and internal microbial selection mechanisms. In this model, the SML concentrated bacteria and their associated viruses (phage) through physical dynamics (that is, the slower flow fields near a diffusive boundary layer), which selected for mucin-binding capabilities. The concentration of phage within the SML provided the LCMA with an external microbial selective described by the bacteriophage adherence to mucus (BAM) model. In the BAM model, phage adhere to mucus protecting the metazoan host against invading, potentially pathogenic bacteria. The same fluid dynamics that concentrated phage and bacteria in the SML also concentrated eukaryotic viruses. As eukaryotic viruses competed for host intracellular niche space, those viruses that provided the LCMA with immune protection were maintained. If a resident virus became pathogenic or if a non-beneficial infection occurred, we propose that tumor necrosis factor (TNF)-mediated programmed cell death, as well as other apoptosis mechanisms, were utilized to remove virally infected cells. The ubiquity of the mucosal environment across metazoan phyla suggest that both BAM and TNF-induced apoptosis emerged during the Precambrian era and continue to drive the evolution of metazoan immunity.
Concepts of ferrovalley material and anomalous valley Hall effect
Authors: Tong Wen-Yi , Gong Shi-Jing , Wan Xiangang , Duan Chun-Gang
Published: December 2016

Valleytronics rooted in the valley degree of freedom is of both theoretical and technological importance as it offers additional opportunities for information storage, as well as electronic, magnetic and optical switches. In analogy to ferroelectric materials with spontaneous charge polarization, or ferromagnetic materials with spontaneous spin polarization, here we introduce a new member of ferroic family, that is, a ferrovalley material with spontaneous valley polarization. Combining a two-band k·p model with first-principles calculations, we show that 2H-VSe2 monolayer, where the spin–orbit coupling coexists with the intrinsic exchange interaction of transition-metal d electrons, is such a room-temperature ferrovalley material. We further predict that such system could demonstrate many distinctive properties, for example, chirality-dependent optical band gap and, more interestingly, anomalous valley Hall effect. On account of the latter, functional devices based on ferrovalley materials, such as valley-based nonvolatile random access memory and valley filter, are contemplated for valleytronic applications.
A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice
Authors: Sibilano Riccardo , Gaudenzio Nicolas , DeGorter Marianne K. , Reber Laurent L. , Hernandez Joseph D. , Starkl Philipp M. , Zurek Oliwia W. , Tsai Mindy , Zahner Sonja , Montgomery Stephen B. , Roers Axel , Kronenberg Mitchell , Yu Mang , Galli Stephen J.
Published: December 2016

Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1 and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.
Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis
Authors: Ohs Isabel , van den Broek Maries , Nussbaum Kathrin , Münz Christian , Arnold Sebastian J. , Quezada Sergio A. , Tugues Sonia , Becher Burkhard
Published: December 2016

Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122+CD49b+ cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM). We confirm the NK-cell identity of these cells by transcriptome-wide analyses and their ability to eliminate tumour cells. Rather than using the conventional pathway of NK-cell development, IL-12-driven CD122+CD49b+ cells remain confined to a NK1.1lowNKp46low stage, but differentiate into NK1.1+NKp46+ cells in the presence of γc-cytokines. Our data reveal an IL-12-driven hard-wired pathway of emergency NK-cell lymphopoiesis bypassing steady-state γc-signalling.
Evolution of multiple cell clones over a 29-year period of a CLL patient
Authors: Zhao Zhikun , Goldin Lynn , Liu Shiping , Wu Liang , Zhou Weiyin , Lou Hong , Yu Qichao , Tsang Shirley X. , Jiang Miaomiao , Li Fuqiang , McMaster MaryLou , Li Yang , Lin Xinxin , Wang Zhifeng , Xu Liqin , Marti Gerald , Li Guibo , Wu Kui , Yeager Meredith , Yang Huanming , Xu Xun , Chanock Stephen J. , Li Bo , Hou Yong , Caporaso Neil , Dean Michael
Published: December 2016

Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14−, 6q− and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death. Serial single-cell RNA sequencing reveals an expression pattern with high FOS, JUN and KLF4 at disease acceleration, which resolves following therapy, but reoccurs following relapse and death. Transcriptome evolution indicates complex changes in expression occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.
Erratum: Molecular basis of cooperativity in pH-triggered supramolecular self-assembly
Authors: Li Yang , Zhao Tian , Wang Chensu , Lin Zhiqiang , Huang Gang , Sumer Baran D. , Gao Jinming
Published: December 2016

Nature Communications 7: Article number: 13214 (2016); Published: 27 October 2016; Updated: 16 December 2016 Figure 5 of this article contained errors introduced during the production process. In Fig. 5c, the minimum value of the x axis (left hand side) should be −1.0 and not 1.0. Additionally, the maximum value of the y axis in Fig.
Cooperative redox activation for carbon dioxide conversion
Authors: Lian Zhong , Nielsen Dennis U. , Lindhardt Anders T. , Daasbjerg Kim , Skrydstrup Troels
Published: December 2016

A longstanding challenge in production chemistry is the development of catalytic methods for the transformation of carbon dioxide into useful chemicals. Silane and borane promoted reductions can be fined-tuned to provide a number of C1-building blocks under mild conditions, but these approaches are limited because of the production of stoichiometric waste compounds. Here we report on the conversion of CO2with diaryldisilanes, which through cooperative redox activation generate carbon monoxide and a diaryldisiloxane that actively participate in a palladium-catalysed carbonylative Hiyama-Denmark coupling for the synthesis of an array of pharmaceutically relevant diarylketones. Thus the disilane reagent not only serves as the oxygen abstracting agent from CO2, but the silicon-containing ‘waste’, produced through oxygen insertion into the Si–Si bond, participates as a reagent for the transmetalation step in the carbonylative coupling. Hence this concept of cooperative redox activation opens up for new avenues in the conversion of CO2.
Global repositioning of transcription start sites in a plant-fermenting bacterium
Authors: Boutard Magali , Ettwiller Laurence , Cerisy Tristan , Alberti Adriana , Labadie Karine , Salanoubat Marcel , Schildkraut Ira , Tolonen Andrew C.
Published: December 2016

Bacteria respond to their environment by regulating mRNA synthesis, often by altering the genomic sites at which RNA polymerase initiates transcription. Here, we investigate genome-wide changes in transcription start site (TSS) usage by Clostridium phytofermentans, a model bacterium for fermentation of lignocellulosic biomass. We quantify expression of nearly 10,000 TSS at single base resolution by Capp-Switch sequencing, which combines capture of synthetically capped 5′ mRNA fragments with template-switching reverse transcription. We find the locations and expression levels of TSS for hundreds of genes change during metabolism of different plant substrates. We show that TSS reveals riboswitches, non-coding RNA and novel transcription units. We identify sequence motifs associated with carbon source-specific TSS and use them for regulon discovery, implicating a LacI/GalR protein in control of pectin metabolism. We discuss how the high resolution and specificity of Capp-Switch enables study of condition-specific changes in transcription initiation in bacteria.
Zinc isotope evidence for sulfate-rich fluid transfer across subduction zones
Authors: Pons Marie-Laure , Debret Baptiste , Bouilhol Pierre , Delacour Adélie , Williams Helen
Published: December 2016

Subduction zones modulate the chemical evolution of the Earth’s mantle. Water and volatile elements in the slab are released as fluids into the mantle wedge and this process is widely considered to result in the oxidation of the sub-arc mantle. However, the chemical composition and speciation of these fluids, which is critical for the mobility of economically important elements, remain poorly constrained. Sulfur has the potential to act both as oxidizing agent and transport medium. Here we use zinc stable isotopes (δ66Zn) in subducted Alpine serpentinites to decipher the chemical properties of slab-derived fluids. We show that the progressive decrease in δ66Zn with metamorphic grade is correlated with a decrease in sulfur content. As existing theoretical work predicts that Zn-SO42− complexes preferentially incorporate heavy δ66Zn, our results provide strong evidence for the release of oxidized, sulfate-rich, slab serpentinite-derived fluids to the mantle wedge.
A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice
Authors: Tripathi Deepak , Venkatasubramanian Sambasivan , Cheekatla Satyanarayana S. , Paidipally Padmaja , Welch Elwyn , Tvinnereim Amy R. , Vankayalapati Ramakrishna
Published: December 2016

Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1+ cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1+ cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1+ cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1+ cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1+ cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma.
Contactless processing of SiGe-melts in EML under reduced gravity
Authors: Luo Yuansu , Damaschke Bernd , Schneider Stephan , Lohöfer Georg , Abrosimov Nikolay , Czupalla Matthias , Samwer Konrad
Published: December 2016

The processing of semiconductors based on electromagnetic levitation is a challenge, because this kind of materials shows a poor electrical conductivity. Here, we report the results of measurements of the thermophysical properties obtained recently from highly doped semiconductors Si1−x
Ge
x
under microgravity conditions in the framework of parabola flight campaigns. Due to the limited time of about 20 s of microgravity especially Ge-rich samples with low melting temperatures were investigated. The measurements were performed contactlessly by video techniques with subsequent digital image processing. Linear and volume thermal expansion coefficients were measured hereby from image data. An anomaly of volume changes near the solidus temperature is visible. Viscosity and surface tension were determined by the oscillating drop technique using optic and electronic data. It was observed that the alloying of Si into Ge increases the surface tension of the melts. The viscosity is following an Arrhenius equation and shows a crossover temperature which separates simple liquid at high temperatures from cooperative liquid at low temperatures.
Impact of pneumonia and lung cancer on mortality of women with hypertension
Authors: Shen Yuechun , Tian Zuojun , Lu Dongfeng , Huang Junyao , Zhang Zuopeng , Li Xinchun , Li Jun
Published: December 2016

Essential hypertension is one of the most severe women’s health problems. Modern life brings more chances of pulmonary diseases to human. The purpose of the study is to investigate weather pneumonia and lung cancer are associated with the mortality of women with hypertension in different age. A cross-sectional retrospective study was conducted in women with hypertension, who were admitted into our hospital in 2004–2013. 14219 women were enrolled and 68.8 ± 12.2 year old (y). Isolated hypertension was 14.7%. The age of death was 78.1 ± 9.8 y. The mortality was 4.4% for average and 0.2%, 1.1%, 2.4%, 4.8%, 10.4% and 15.8% in group age ≦49, 50–59, 60–69, 70–79, 80–89 and ≧90 y separately. This mortality increased with age was positively significantly correlated with the increased incidences of pneumonia (P < 0.05, r = 0.77). Pneumonia was a significant risk associated with the mortality in age 55–89 y (OR = 6.4–22.5; 95% CI = 3.06–51.12). While, lung cancer was the significant risk in 70–79 y. These observations indicate that pneumonia and lung cancer are significant risk factors associated with the mortality of certain age women with hypertension, and bring an alert that pneumonia and lung cancer should be prevented and treated intensively in modern life in order to reduce the mortality.
A molecular and neuronal basis for amino acid sensing in the Drosophila larva
Authors: Croset Vincent , Schleyer Michael , Arguello J. Roman , Gerber Bertram , Benton Richard
Published: December 2016

Amino acids are important nutrients for animals, reflected in conserved internal pathways in vertebrates and invertebrates for monitoring cellular levels of these compounds. In mammals, sensory cells and metabotropic glutamate receptor-related taste receptors that detect environmental sources of amino acids in food are also well-characterised. By contrast, it is unclear how insects perceive this class of molecules through peripheral chemosensory mechanisms. Here we investigate amino acid sensing in Drosophila melanogaster larvae, which feed ravenously to support their rapid growth. We show that larvae display diverse behaviours (attraction, aversion, neutral) towards different amino acids, which depend upon stimulus concentration. Some of these behaviours require IR76b, a member of the variant ionotropic glutamate receptor repertoire of invertebrate chemoreceptors. IR76b is broadly expressed in larval taste neurons, suggesting a role as a co-receptor. We identify a subpopulation of these neurons that displays physiological activation by some, but not all, amino acids, and which mediate suppression of feeding by high concentrations of at least a subset of these compounds. Our data reveal the first elements of a sophisticated neuronal and molecular substrate by which these animals detect and behave towards external sources of amino acids.
Harnessing the natural inhibitory domain to control TNFα Converting Enzyme (TACE) activity in vivo
Authors: Wong Eitan , Cohen Tal , Romi Erez , Levin Maxim , Peleg Yoav , Arad Uri , Yaron Avraham , Milla Marcos E. , Sagi Irit
Published: December 2016

Dysregulated activity of A Disintegrin And Metalloproteinase 17 (ADAM17)/TNFα Converting Enzyme (TACE) is associated with inflammatory disorders and cancer progression by releasing regulatory membrane-tethered proteins like TNFα, IL6R and EGFR ligands. Although specific inhibition of TACE is thought to be a viable strategy for inflammatory disorders and for malignancies treatment, the generation of effective inhibitors in vivo has been proven to be challenging. Here we report on the development of a protein inhibitor that leverages the endogenous modulator of TACE. We have generated a stable form of the auto-inhibitory TACE prodomain (TPD), which specifically inhibits in vitro and cell-surface TACE, but not the related ADAM10, and effectively modulated TNFα secretion in cells. TPD significantly attenuated TACE-mediated disease models of sepsis, rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and reduced TNFα in synovial fluids from RA patients. Our results demonstrate that intervening with endogenous ADAM sheddase modulatory mechanisms holds potential as a general strategy for the design of ADAM inhibitors.
Time Series miRNA-mRNA integrated analysis reveals critical miRNAs and targets in macrophage polarization
Authors: Lu Liangqun , McCurdy Sara , Huang Sijia , Zhu Xun , Peplowska Karolina , Tiirikainen Maarit , Boisvert William A. , Garmire Lana X.
Published: December 2016

Polarization of macrophages is regulated through complex signaling networks. Correlating miRNA and mRNA expression over time after macrophage polarization has not yet been investigated. We used paired RNA-Seq and miRNA-Seq experiments to measure the mRNA and miRNA expression in bone marrow-derived macrophages over a time-series of 8 hours. Bioinformatics analysis identified 31 differentially expressed miRNAs between M1 and M2 polarized macrophages. The top 4 M1 miRNAs (miR-155-3p, miR-155-5p, miR-147-3p and miR-9-5p) and top 4 M2 miRNAs (miR-27a-5p, let-7c-1-3p, miR-23a-5p and miR-23b-5p) were validated by qPCR. Interestingly, M1 specific miRNAs could be categorized to early- and late-response groups, in which three new miRNAs miR-1931, miR-3473e and miR-5128 were validated as early-response miRNAs. M1 polarization led to the enrichment of genes involved in immune responses and signal transduction, whereas M2 polarization enriched genes involved in cell cycle and metabolic processes. C2H2 zinc-finger family members are key targets of DE miRNAs. The integrative analysis between miRNAs and mRNAs demonstrates the regulations of miRNAs on nearly four thousand differentially expressed genes and most of the biological pathways enriched in macrophage polarization. In summary, this study elucidates the expression profiles of miRNAs and their potential targetomes during macrophage polarization.
Longitudinal metagenomic profiling of bovine milk to assess the impact of intramammary treatment using a third-generation cephalosporin
Authors: Ganda Erika K. , Bisinotto Rafael S. , Lima Svetlana F. , Kronauer Kristina , Decter Dean H. , Oikonomou Georgios , Schukken Ynte H. , Bicalho Rodrigo C.
Published: December 2016

Antimicrobial usage in food animals has a direct impact on human health, and approximately 80% of the antibiotics prescribed in the dairy industry are used to treat bovine mastitis. Here we provide a longitudinal description of the changes in the microbiome of milk that are associated with mastitis and antimicrobial therapy. Next-generation sequencing, 16 S rRNA gene quantitative real-time PCR, and aerobic culturing were applied to assess the effect of disease and antibiotic therapy on the milk microbiome. Cows diagnosed with clinical mastitis associated with Gram-negative pathogens or negative aerobic culture were randomly allocated into 5 days of Ceftiofur intramammary treatment or remained as untreated controls. Serial milk samples were collected from the affected quarter and the ipsilateral healthy quarter of the same animal. Milk from the mastitic quarter had a higher bacterial load and reduced microbial diversity compared to healthy milk. Resolution of the disease was accompanied by increases in diversity indexes and a decrease in pathogen relative abundance.Escherichia coli-associated mastitic milk samples had a remarkably distinct bacterial profile, dominated by Enterobacteriaceae, when compared to healthy milk. However, no differences were observed in culture-negative mastitis samples when compared to healthy milk. Antimicrobial treatment had no significant effect on clinical cure, bacteriological cure, pathogen clearance rate or bacterial load.
How types of premises modulate the typicality effect in category-based induction: diverging evidence from the P2, P3, and LPC effects
Authors: Liang Xiuling , Chen Qingfei , Lei Yi , Li Hong
Published: December 2016

Behavioural studies have indicated that semantic typicality influences processing time and accuracy during the performance of inductive reasoning (i.e., the typicality effect). The present study examines this effect by manipulating the types of premises and conclusions (i.e., general, typical, or atypical) at an electrophysiological level using a semantic category-based induction task. With regard to behavioural results, higher inductive strength was found in typical conclusions in all premise conditions, whereas a longer response time for atypical conclusions was only found in general and typical premise conditions. The ERP results had different response patterns: in the general premise condition, a larger P2, as well as a smaller P3 and LPC (500–600 ms), were elicited by atypical conclusions relative to typical ones; in the typical premise condition, a larger P2 and LPC (600–700 ms) were found for atypical conclusions; in the atypical premise condition, however, only a larger P2 was found for atypical conclusions. The divergent evidence for the typicality effect indicated that the processing of the typicality effect in general, and specific premise conditions, might involve different cognitive processes, such as resource allocation and inference violation, which yielded new insights into the neural underpinnings of the typicality effect in a category-based induction.
The nature of photoinduced phase transition and metastable states in vanadium dioxide
Authors: Tao Zhensheng , Zhou Faran , Han Tzong-Ru T. , Torres David , Wang Tongyu , Sepulveda Nelson , Chang Kiseok , Young Margaret , Lunt Richard R. , Ruan Chong-Yu
Published: December 2016

Photoinduced threshold switching processes that lead to bistability and the formation of metastable phases in photoinduced phase transition of VO2 are elucidated through ultrafast electron diffraction and diffusive scattering techniques with varying excitation wavelengths. We uncover two distinct regimes of the dynamical phase change: a nearly instantaneous crossover into an intermediate state and its decay led by lattice instabilities over 10 ps timescales. The structure of this intermediate state is identified to be monoclinic, but more akin to M2 rather than M1 based on structure refinements. The extinction of all major monoclinic features within just a few picoseconds at the above-threshold-level (~20%) photoexcitations and the distinct dynamics in diffusive scattering that represents medium-range atomic fluctuations at two photon wavelengths strongly suggest a density-driven and nonthermal pathway for the initial process of the photoinduced phase transition. These results highlight the critical roles of electron correlations and lattice instabilities in driving and controlling phase transformations far from equilibrium.
Acute kidney injury as a risk factor for diagnostic discrepancy among geriatric patients: a pilot study
Authors: Chao Chia-Ter , Tsai Hung-Bin , Chiang Chih-Kang , Huang Jenq-Wen , Hung Kuan-Yu ,   COGENT study group, Shih Chih-Yuan , Hsu Su-Hsuan , Hung Yu-Chien , Lai Chun-Fu , Chan Derrick Ding-Cheng , Yen Chung-Jen , Chu Tzong-Shinn
Published: December 2016

Diagnostic discrepancy, defined as different admission and discharge diagnoses, could be a potential source of diagnostic error. We evaluated whether acute kidney injury (AKI) in the elderly affected their risk for diagnostic discrepancy. Patients aged ≥60 years from the general medical wards were prospectively enrolled and divided according to AKI status upon admission, using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We compared their discharge and admission diagnoses and identified patients with a diagnostic discrepancy, using multiple logistic regression analysis to evaluate the relationship between initial AKI and the presence of a diagnostic discrepancy. A total of 188 participants (mean age, 77.9 years) were recruited. Regression analysis showed that initial AKI on admission was associated with a higher risk of diagnostic discrepancy upon discharge (odds ratio [OR] 3.3; p < 0.01). In contrast, higher AKI severity was also associated with an increased risk of diagnostic discrepancy (for KDIGO grade 1, 2, and 3; OR 2.92, 3.91, and 4.32; p = 0.04, 0.03, and 0.02, respectively), suggesting that initial AKI upon admission could be an important risk factor for diagnostic discrepancy. Consequently, reducing geriatric AKI might have the potential to reduce diagnostic discrepancy among these patients.
Recent breeding programs enhanced genetic diversity in both desi and kabuli varieties of chickpea (Cicer arietinum L.)
Authors: Thudi Mahendar , Chitikineni Annapurna , Liu Xin , He Weiming , Roorkiwal Manish , Yang Wei , Jian Jianbo , Doddamani Dadakhalandar , Gaur Pooran M. , Rathore Abhishek , Samineni Srinivasan , Saxena Rachit K. , Xu Dawen , Singh Narendra P. , Chaturvedi Sushil K. , Zhang Gengyun , Wang Jun , Datta Swapan K. , Xu Xun , Varshney Rajeev K.
Published: December 2016

In order to understand the impact of breeding on genetic diversity and gain insights into temporal trends in diversity in chickpea, a set of 100 chickpea varieties released in 14 countries between 1948 and 2012 were re-sequenced. For analysis, the re-sequencing data for 29 varieties available from an earlier study was also included. Copy number variations and presence absence variations identified in the present study have potential to drive phenotypic variations for trait improvement. Re-sequencing of a large number of varieties has provided opportunities to inspect the genetic and genomic changes reflecting the history of breeding, which we consider as breeding signatures and the selected loci may provide targets for crop improvement. Our study also reports enhanced diversity in both desi and kabuli varieties as a result of recent chickpea breeding efforts. The current study will aid the explicit efforts to breed for local adaptation in the context of anticipated climate changes.
Lipidomic analysis enables prediction of clinical outcomes in burn patients
Authors: Qi Peter , Abdullahi Abdikarim , Stanojcic Mile , Patsouris David , Jeschke Marc G.
Published: December 2016

Recent discoveries have highlighted the novel metabolic functions of adipose tissue in enhancing hypermetabolism after trauma. As the exact function and expression profiles of serum lipids and free fatty acids (FFA) are essentially unknown, we determined the lipidomic expression profile after burn in correlation to clinical outcomes to identify important lipid mediators affecting post-burn outcomes. We conducted a prospective cohort study with 46 adult burn patients and 5 healthy controls at the Ross Tilley Burn Center in Toronto, Canada. Patients were stratified based on major demographic and clinical variables, including age, burn severity, mortality, and sepsis. Serum FFAs and inflammatory markers were measured during acute hospital stay. We found that FFAs were acutely elevated post-burn and returned to baseline over time. Greater burn severity and age were associated with an impaired acute response in unsaturated FFAs and pro-inflammatory cytokines. Elevations in saturated and mono-unsaturated FFAs correlated significantly to increased mortality. In summary, persistent elevation of unsaturated lipids was associated with a functionally altered inflammatory-immunological milieu and worse clinical outcomes. The present lipidomic analysis indicates profound alterations in the lipid profile after burn by characterizing key lipids as potential diagnostic and outcome indicators in critically injured patients.
A Clickable Analogue of Ketamine Retains NMDA Receptor Activity, Psychoactivity, and Accumulates in Neurons
Authors: Emnett Christine , Li Hairong , Jiang Xiaoping , Benz Ann , Boggiano Joseph , Conyers Sara , Wozniak David F. , Zorumski Charles F. , Reichert David E. , Mennerick Steven
Published: December 2016

Ketamine is a psychotomimetic and antidepressant drug. Although antagonism of cell-surface NMDA receptors (NMDARs) may trigger ketamine’s psychoactive effects, ketamine or its major metabolite norketamine could act intracellularly to produce some behavioral effects. To explore the viability of this latter hypothesis, we examined intracellular accumulation of novel visualizable analogues of ketamine/norketamine. We introduced an alkyne “click” handle into norketamine (alkyne-norketamine, A-NK) at the key nitrogen atom. Ketamine, norketamine, and A-NK, but not A-NK-amide, showed acute and persisting psychoactive effects in mice. This psychoactivity profile paralleled activity of the compounds as NMDAR channel blockers; A-NK-amide was inactive at NMDARs, and norketamine and A-NK were active but ~4-fold less potent than ketamine. We incubated rat hippocampal cells with 10 μM A-NK or A-NK-amide then performed Cu2+ catalyzed cycloaddition of azide-Alexa Fluor 488, which covalently attaches the fluorophore to the alkyne moiety in the compounds. Fluorescent imaging revealed intracellular localization of A-NK but weak A-NK-amide labeling. Accumulation was not dependent on membrane potential, NMDAR expression, or NMDAR activity. Overall, the approach revealed a correlation among NMDAR activity, intracellular accumulation/retention, and behavioral effects. Thus, we advance first generation chemical biology tools to aid in the identification of ketamine targets.