bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics Analysis of Skeletal Muscle from Leptin‐Deficient ob/ob Mice Reveals Adaptive Remodeling of Metabolic Characteristics and Fiber Type Composition
Authors: Schönke Milena , Björnholm Marie , Chibalin Alexander V. , Zierath Juleen R. , Deshmukh Atul S.
Published: January 2018

Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes (T2D), may be a cause or consequence of altered protein expression profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using state‐of‐the‐art multienzyme digestion and filter‐aided sample preparation (MED‐FASP) and a mass spectrometry (MS)‐based workflow, we performed a global proteomics analysis of skeletal muscle from leptin‐deficient, obese, insulin resistant (ob/ob) and lean mice in mere two fractions in a short time (8 h per sample). We identified more than 6000 proteins with 118 proteins differentially regulated in obesity. This included protein kinases, phosphatases, and secreted and fiber type associated proteins. Enzymes involved in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing evidence against reduced fatty acid oxidation in lipid‐induced insulin resistance. Mitochondrial and peroxisomal proteins, as well as components of pyruvate and lactate metabolism, were increased. Finally, the skeletal muscle proteome from ob/ob mice displayed a shift toward the “slow fiber type.” This detailed characterization of an obese rodent model of T2D demonstrates an efficient workflow for skeletal muscle proteomics, which may easily be adapted to other complex tissues.
Accurate understanding of infertility risk among families of adolescent males newly diagnosed with cancer
Authors: Lehmann Vicky , Flynn Jessica S. , Foster Rebecca H. , Russell Kathryn M. , Klosky James L.
Published: January 2018

Objective

To examine patient and parent understanding of infertility risk (relative to oncologists' risk ratings) among adolescents newly diagnosed with cancer, and to identify background factors related to inaccurate reporting/estimating.

Methods

Male patients (N = 137; aged 13‐21) and their parents completed self‐report questionnaires. Those who reported a fertility‐related conversation with their provider (N = 102 adolescents, N = 74 parents) reported their infertility risk (ie, what oncologist had communicated) and all participants' estimated risk (ie, personal belief). Reports/estimates were compared with oncologists' ratings to assess relative accuracy, and regression analyses assessed potentially related background factors.

Results

Participants' agreement of their risk reports with the oncologist was poor (κ = .079/.122 for adolescents/parents), resulting in most adolescents (59.8%) and parents (58.7%) inaccurately reporting risk. Older adolescents were less likely to overreport risk (OR = 0.69; 95% CI, 0.49‐0.97) and parents of sons with the highest Tanner stage were less likely to underreport (OR = 0.28; 95% CI, 0.08‐0.92). Risk estimates were also in poor agreement with oncologists' ratings among adolescents (κ = .040) and parents (κ = .088). Accordingly, incongruent estimates occurred in most adolescents (63.7%) and parents (62.2%), although all reported fertility‐related conversations with their providers.

Conclusions

Most adolescents and parents inaccurately reported infertility risk, and more poorly estimated risk. Research is needed to identify additional factors associated with accurate understanding of cancer‐related infertility risk. Providers should be supported with user‐friendly educational tools to promote awareness of infertility risk.
Distal amyloid β‐protein fragments template amyloid assembly
Authors: Do Thanh D. , Sangwan Smriti , de Almeida Natália E. C. , Ilitchev Alexandre I. , Giammona Maxwell , Sawaya Michael R. , Buratto Steven K. , Eisenberg David S. , Bowers Michael T.
Published: January 2018

Amyloid formation is associated with devastating diseases such as Alzheimer's, Parkinson's and Type‐2 diabetes. The large amyloid deposits found in patients suffering from these diseases have remained difficult to probe by structural means. Recent NMR models also predict heterotypic interactions from distinct peptide fragments but limited evidence of heterotypic packed sheets is observed in solution. Here we characterize two segments of the protein amyloid β (Aβ) known to form fibrils in Alzheimer's disease patients. We designed two variants of Aβ(19–24) and Aβ(27–32), IFAEDV (I6V) and NKGAIF (N6F) to lower the aggregation propensity of individual peptides while maintaining the similar interactions between the two segments in their native forms. We found that the variants do not form significant amyloid fibrils individually but a 1:1 mixture forms abundant fibrils. Using ion mobility‐mass spectrometry (IM‐MS), hetero‐oligomers up to decamers were found in the mixture while the individual peptides formed primarily dimers and some tetramers consistent with a strong heterotypic interaction between the two segments. We showed by X‐ray crystallography that I6V formed a Class 7 zipper with a weakly packed pair of β‐sheets and no segregated dry interface, while N6F formed a more stable Class 1 zipper. In a mixture of equimolar N6F:I6V, I6V forms a more stable zipper than in I6V alone while no N6F or hetero‐typic zippers are observed. These data are consistent with a mechanism where N6F catalyzes assembly of I6V into a stable zipper and perhaps into stable, pure I6V fibrils that are observed in AFM measurements.
Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti‐diabetic agents
Authors: Musale Vishal , Casciaro Bruno , Mangoni Maria Luisa , Abdel‐Wahab Yasser H.A. , Flatt Peter R. , Conlon J. Michael
Published: January 2018

Temporin A (FLPLIGRVLSGIL‐NH2), temporin F (FLPLIGKVLSGIL‐NH2), and temporin G (FFPVIGRILNGIL‐NH2), first identified in skin secretions of the frog Rana temporaria, produced concentration‐dependent stimulation of insulin release from BRIN‐BD11 rat clonal β‐cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active. Temporins A, F, and G also produced a concentration‐dependent stimulation of insulin release from 1.1B4 human‐derived pancreatic β‐cells, with temporin G being the most potent and effective, and from isolated mouse islets. The data indicate that cationicity, hydrophobicity, and the angle subtended by the charged residues in the temporin molecule are important determinants for in vitro insulinotropic activity. Temporin A and F (1 μM), but not temporin G, protected BRIN‐BD11 cells against cytokine‐induced apoptosis (P < 0.001) and augmented (P < 0.001) proliferation of the cells to a similar extent as glucagon‐like peptide‐1. Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion whereas temporin A and F administration was without significant effect on plasma glucose levels. The study suggests that combination therapy involving agents developed from the temporin A and G sequences may find application in Type 2 diabetes treatment.
Robust adaptive fixed‐time tracking control of 6‐DOF spacecraft fly‐around mission for noncooperative target
Authors: Huang Yi , Jia Yingmin
Published: January 2018

The fixed‐time relative position tracking and attitude synchronization control problem of a spacecraft fly‐around mission for a noncooperative target in the presence of parameter uncertainties and external disturbances is investigated. Firstly, a novel and coupled relative position and attitude motion model for a noncooperative fly‐around mission is established. Subsequently, a novel nonsingular fast terminal sliding mode (NFTSM) surface is developed, and the explicit estimation of the convergence time independent of initial states is provided. Fair and systematic comparisons among several typical terminal sliding modes show that the designed NFTSM has faster convergence performance than the fast terminal sliding mode. Then, a robust integrated adaptive fixed‐time NFTSM control law with no precise knowledge of the mass and inertia matrix and disturbances by combining the nonsingular terminal sliding mode technique with an adaptive methodology is proposed, which can eliminate the chattering phenomenon and guarantee that the relative position and attitude tracking errors can converge into the small regions containing the origin in fixed time. Finally, numerical simulations are performed to demonstrate the effectiveness of the proposed control schemes.
Nature‐like fishways as compensatory lotic habitats
Authors: Tamario C. , Degerman E. , Donadi S. , Spjut D. , Sandin L.
Published: January 2018

Damming of rivers disrupts migration of fish and results in lotic habitats being both scarcer and spaced further apart, ultimately affecting riverine fish communities. Nature‐like fishways are often designed as bypass channels, constructed with natural materials that reroute part of the water around weirs and dams, restoring longitudinal connectivity as well as forming nature‐mimicking habitats. We evaluated the potential of such bypasses to function as compensatory lotic habitats by comparing fish fauna in 23 bypasses to adjacent lotic stream habitats in a same‐river pairwise design. Bypasses were narrower, shallower, and less shaded than adjacent stream habitats, but very few significant differences could be detected in the fish communities, indicating the potential of such nature‐like fishways to constitute compensatory lotic habitats for fish. Analyses also indicated how bypass design may be altered to favour or disfavour certain target species. Generally, narrower and shallower bypasses with high gradient favoured brown trout (Salmo trutta), whereas European eel (Anguilla anguilla) were more abundant at sites with lower gradient. Finally, to increase the impact of these compensatory habitats on running water ecosystems, we suggest that the size of bypasses should be maximized in areas where natural stream habitats have been lost.
Meta‐analysis of Gaussian individual patient data: Two‐stage or not two‐stage?
Authors: Morris Tim P. , Fisher David J. , Kenward Michael G. , Carpenter James R.
Published: January 2018

Quantitative evidence synthesis through meta‐analysis is central to evidence‐based medicine. For well‐documented reasons, the meta‐analysis of individual patient data is held in higher regard than aggregate data. With access to individual patient data, the analysis is not restricted to a “two‐stage” approach (combining estimates and standard errors) but can estimate parameters of interest by fitting a single model to all of the data, a so‐called “one‐stage” analysis. There has been debate about the merits of one‐ and two‐stage analysis. Arguments for one‐stage analysis have typically noted that a wider range of models can be fitted and overall estimates may be more precise. The two‐stage side has emphasised that the models that can be fitted in two stages are sufficient to answer the relevant questions, with less scope for mistakes because there are fewer modelling choices to be made in the two‐stage approach. For Gaussian data, we consider the statistical arguments for flexibility and precision in small‐sample settings. Regarding flexibility, several of the models that can be fitted only in one stage may not be of serious interest to most meta‐analysis practitioners. Regarding precision, we consider fixed‐ and random‐effects meta‐analysis and see that, for a model making certain assumptions, the number of stages used to fit this model is irrelevant; the precision will be approximately equal. Meta‐analysts should choose modelling assumptions carefully. Sometimes relevant models can only be fitted in one stage. Otherwise, meta‐analysts are free to use whichever procedure is most convenient to fit the identified model.
Fault diagnosis model based on Bayesian network considering information uncertainty and its application in traction power supply system
Authors: Lin Sheng , Chen Xiyang , Wang Qi
Published: January 2018

Fault diagnosis is of great significance in maintaining the safe and stable operation of a system. Fast and precise location of faults is important for restoring power supply systems. In this paper, considering the interference of information uncertainty to fault diagnosis under different weather conditions, a fault diagnosis model based on Bayesian network is proposed. The model inherits the capability of processing uncertain information of a Bayesian network and divides the information into historical information and evidence information. The uncertainty of historical information is reduced by modifying the parameters through improving parameter learning formulas, while that of evidence information can be reduced by logical judgment. A fault simulation model based on Monte Carlo method is used to generate simulation data for parameter learning, and a case study confirms the correctness of the proposed fault diagnosis and fault simulation models. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Study on windage yaw calculation and real‐time warning method of Shanxi power grid considering microclimate and micro‐terrain factors
Authors: Shao Jianwei , Wang Junhua , Long Mengjiao , Wang Jingjing , Tang Yake , Sun Mingui
Published: January 2018

An improved computational model and real‐time warning method for windage yaw is proposed based on dynamic air density theory to solve the current problem in Shanxi power grid, whereas the traditional method excludes considerations of microclimate and micro‐terrain effects. The standard value of the air density is replaced by dynamic air density, which takes microclimate factors such as temperature, humidity, and pressure into account. Aiming at the cat‐head type tower, which is most prone to windage yaw in Shanxi province, this paper proposes a method to calculate the minimum air gap. Based on the statistical analysis of meteorological data of Shanxi Province, it is concluded that the microclimate and micro‐terrain factors greatly influence the windage yaw calculation. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Low-energy effective field theory below the electroweak scale: anomalous dimensions
Authors: Jenkins Elizabeth E. , Manohar Aneesh V. , Stoffer Peter
Published: January 2018

Abstract

We compute the one-loop anomalous dimensions of the low-energy effective Lagrangian below the electroweak scale, up to terms of dimension six. The theory has 70 dimension-five and 3631 dimension-six Hermitian operators that preserve baryon and lepton number, as well as additional operators that violate baryon number and lepton number. The renormalization group equations for the quark and lepton masses and the QCD and QED gauge couplings are modified by dimension-five and dimension-six operator contributions. We compute the renormalization group equations from one insertion of dimension-five and dimension-six operators, as well as two insertions of dimension-five operators, to all terms of dimension less than or equal to six. The use of the equations of motion to eliminate operators can be ambiguous, and we show how to resolve this ambiguity by a careful use of field redefinitions.
xylA and xylB overexpression as a successful strategy for improving xylose utilization and poly-3-hydroxybutyrate production in Burkholderia sacchari
Authors: Guamán Linda P , Oliveira-Filho Edmar R , Barba-Ostria Carlos , Gomez José G C , Taciro Marilda K , da Silva Luiziana Ferreira
Published: January 2018

Despite the versatility and many advantages of polyhydroxyalkanoates as petroleum-based plastic substitutes, their higher production cost compared to petroleum-based polymers has historically limited their large-scale production. One appealing approach to reducing production costs is to employ less expensive, renewable feedstocks. Xylose, for example is an abundant and inexpensive carbon source derived from hemicellulosic residues abundant in agro-industrial waste (sugarcane bagasse hemicellulosic hydrolysates). In this work, the production of poly-3-hydroxybutyrate P(3HB) from xylose was studied to develop technologies for conversion of agro-industrial waste into high-value chemicals and biopolymers. Specifically, this work elucidates the organization of the xylose assimilation operon of Burkholderia sacchari, a non-model bacterium with high capacity for P(3HB) accumulation. Overexpression of endogenous xylose isomerase and xylulokinase genes was successfully assessed, improving both specific growth rate and P(3HB) production. Compared to control strain (harboring pBBR1MCS-2), xylose utilization in the engineered strain was substantially improved with 25% increase in specific growth rate, 34% increase in P(3HB) production, and the highest P(3HB) yield from xylose reported to date for B. sacchari (Y  P3HB/Xil = 0.35 g/g). This study highlights that xylA and xylB overexpression is an effective strategy to improve xylose utilization and P(3HB) production in B. sacchari.
The Importance of the Left Occipitotemporal Cortex in Developmental Dyslexia
Authors: Kronbichler Lisa , Kronbichler Martin
Published: January 2018

Purpose of Review

Developmental dyslexia is characterized by an impaired acquisition of fluent and skilled reading ability. Numerous studies have explored the neural correlates of this neurodevelopmental disorder, with most classic accounts strongly focussing on left temporoparietal regions. We will review recent findings from structural and functional MRI studies that suggest a more important role of occipitotemporal cortex abnormalities in dyslexia.

Recent Findings

Recent findings highlight the role of the occipitotemporal cortex which exhibits functional as well as structural abnormalities in dyslexic readers and in children at risk for dyslexia and suggest a more central role for the occipitotemporal cortex in the pathophysiology of dyslexia.

We demonstrate the importance of the occipitotemporal cortex in for understanding impaired reading acquisition and point out how future research might enhance our understanding of functional and structural impairments in the reading network via large-scale data analysis approaches.
STOCHASTIC DIFFERENTIAL GAMES BETWEEN TWO INSURERS WITH GENERALIZED MEAN-VARIANCE PREMIUM PRINCIPLE
Authors: Chen Shumin , Yang Hailiang , Zeng Yan
Published: January 2018

We study a stochastic differential game problem between two insurers, who invest in a financial market and adopt reinsurance to manage their claim risks. Supposing that their reinsurance premium rates are calculated according to the generalized mean-variance principle, we consider the competition between the two insurers as a non-zero sum stochastic differential game. Using dynamic programming technique, we derive a system of coupled Hamilton–Jacobi–Bellman equations and show the existence of equilibrium strategies. For an exponential utility maximizing game and a probability maximizing game, we obtain semi-explicit solutions for the equilibrium strategies and the equilibrium value functions, respectively. Finally, we provide some detailed comparative-static analyses on the equilibrium strategies and illustrate some economic insights.
Managing a “People Business” in Times of Uncertainty: Human Resources Strategy at Ocean Transport & Trading in the 1970s
Authors: PETERSSON NIELS P.
Published: January 2018

This article examines the role of human resources in the business strategy of Ocean Steam Ship Company (later Ocean Transport & Trading), one of the United Kingdom’s leading shipping firms. The time under review is the 1970s, a period of rapid and disruptive change for the shipping industry and of considerable difficulties for the UK economy. As a result of uncertainty over the development of the shipping industry in general, and Ocean’s business in particular, managing staff numbers and career opportunities became key elements of the company’s overall business strategy during these years. The article also examines the changing objectives of that strategy, the means by which these objectives were pursued, and the external constraints under which these objectives had to take place. It argues that Ocean found itself privileging the requirements of running a “people business” over other strategic concerns and that external constraints prevented the firm from pursuing theoretically more appropriate strategies, such as increased use of outsourcing and extricating itself from its UK-based, human resource intensive business.
Formal and Informal Long-Term Care in the Community: Interlocking or Incoherent Systems?
Authors: BURCHARDT TANIA , JONES EMILY , OBOLENSKAYA POLINA
Published: January 2018

Help with activities of daily living for people in the community is provided through formal services (public and private) and informal (often unpaid) care. This paper investigates how these systems interlock and who is at risk of unmet need. It begins by mapping differences between OECD countries in the balance between formal and informal care, before giving a detailed breakdown for the UK. New analysis of UK Family Resources Survey data for 2012/13 and 2013/14 suggests high levels of unmet need. We investigate who receives formal and informal care, and who receives neither, among the working-age and older populations. We find that while informal care fills some gaps left by the lack of availability of formal services (and vice versa), not all older or working-age disabled people are protected in these ways. Adults living alone and those with high but not the highest levels of difficulty are most likely to have unmet need. Means-tested public entitlements ameliorate but do not remove the increased risk among people in low-income households. The paper concludes that public policy needs to integrate its support for formal and informal modes of care, with particular attention to those groups most at risk of unmet need.
Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?
Authors: Villemain Olivier , Malekzadeh-Milani Sophie , Sitefane Fidelio , Mostefa-Kara Meriem , Boudjemline Younes
Published: January 2018

Objectives

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure.

Background

Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers.

Methods

We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time.

Results

A total of 324 patients were included (median age=1.51 [Q1–Q3: 0.62–4.23] years; weight=10.3 [6.7–17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5–49.3) mGy; dose area product: 1.01 (0.56–2.24) Gy.cm2; dose area product/kg: 0.106 (0.061–0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2–4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure.

Conclusion

Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.
A review of the neurobiology of obesity and the available pharmacotherapies
Authors: Subramaniapillai Mehala , McIntyre Roger S.
Published: January 2018

Obesity is becoming an increasing problem worldwide. In addition to causing many physical health consequences, there is increasing evidence demonstrating that obesity is toxic to the brain and, as such, can be considered a disease of the central nervous system. Peripheral level regulators of appetite, such as leptin, insulin, ghrelin, and cholecystokinin, feed into the appetite center of the brain, which is controlled by the hypothalamus, to maintain homeostasis and energy balance. However, food consumption is not solely mediated by energy balance, but is also regulated by the mesolimbic reward system, where motivation, reward, and reinforcement factors influence obesity. The purpose of this review is to highlight the neurobiology of eating behavior and obesity and to describe various neurobiological treatment mechanisms to treat obesity.
Converting oral to long-acting injectable antipsychotics: a guide for the perplexed
Authors: Meyer Jonathan M.
Published: January 2018

There has been increasing recognition that antipsychotic nonadherence is common across all stages of schizophrenia, starting from the first episode. Moreover, numerous meta-analyses of the existing literature indicate superiority of long-acting injectable (LAI) over oral antipsychotics when one adjusts for the greater illness severity and duration among patients in LAI antipsychotic trials. The increasing availability of LAI antipsychotic options has raised interest in converting patients from oral medication; however, the successful transition from oral to the comparable LAI antipsychotic requires an understanding of the current extent of antipsychotic exposure, the kinetics of the LAI preparation, and the expected plasma levels achieved by the LAI formulation. The purpose of this article is to provide, in a concise format, the essential information for converting patients to the LAI forms of haloperidol, fluphenazine, risperidone, paliperidone, olanzapine, and aripiprazole from the comparable oral medication, and how the use of plasma antipsychotic levels can be invaluable for this process.
Between a rock-a-bye and a hard place: mood disorders during the peripartum period
Authors: Thomson Michael , Sharma Verinder
Published: January 2018

Mood disorders including major depressive disorder and bipolar disorder are common during and after pregnancy. Timely identification and appropriate management of mood episodes is essential to maximize maternal well-being and minimize adverse outcomes. Failure to do so results in maternal suffering and impaired child bonding, and has the potential for devastating outcomes including suicide and infanticide. Women are routinely screened for unipolar depression during or after pregnancy but not for bipolar disorder, in spite of the fact that childbirth is associated with a major risk for onset or exacerbation of bipolar disorder. Delays in detection as well as misdiagnosis of bipolar disorder as major depressive disorder may put women at risk of many adverse consequences, including symptom exacerbation, psychiatric hospitalization, and suicide. A thorough psychiatric assessment is necessary to establish diagnosis, to address safety issues, and to formulate a treatment plan. Treatment of mood disorders during pregnancy is complicated by the potential risks of fetal exposure to psychotropic medications, and the use of these medications during the postpartum period may result in infant medication exposure through breastmilk. These risks of psychotropic medication exposure must be weighed against the risk of untreated mood disorders. This review will discuss the pathophysiology, epidemiology, diagnosis, and treatment of mood disorders during pregnancy and the postpartum period. Screening tools that can be used in the primary care and obstetrics settings to assist in identifying women with peripartum mood disorders will also be discussed.
The effect of task complexity on linguistic and non-linguistic control mechanisms in bilingual aphasia
Authors: GRAY TERESA , KIRAN SWATHI
Published: January 2018

In this study we examined linguistic and non-linguistic control mechanisms in 20 Spanish–English neurologically healthy bilingual adults and 13 Spanish–English bilingual adults with aphasia. Participants completed two linguistic and two non-linguistic control tasks accounting for low and high complexity. Healthy bilingual results were indicative of domain general cognitive control, whereas patient results were indicative of domain specific cognitive control. The magnitude of conflict required to complete the tasks was also examined. Healthy bilinguals exhibited significant amounts of conflict on all tasks and linguistic and non-linguistic conflict ratios were correlated; whereas patient results revealed significant conflict only on non-linguistic tasks and those conflict ratios were not correlated with linguistic conflict ratios, indicating a dissociation between how patients are controlling information in these two domains. Finally, a relationship between language impairment and language control was identified and brain damage was associated with linguistic and non-linguistic task performance.
Phage or foe: an insight into the impact of viral predation on microbial communities
Authors: Fernández Lucía , Rodríguez Ana , García Pilar
Published: January 2018

Since their discovery, bacteriophages have been traditionally regarded as the natural enemies of bacteria. However, recent advances in molecular biology techniques, especially data from “omics” analyses, have revealed that the interplay between bacterial viruses and their hosts is far more intricate than initially thought. On the one hand, we have become more aware of the impact of viral predation on the composition and genetic makeup of microbial communities thanks to genomic and metagenomic approaches. Moreover, data obtained from transcriptomic, proteomic, and metabolomic studies have shown that responses to phage predation are complex and diverse, varying greatly depending on the bacterial host, phage, and multiplicity of infection. Interestingly, phage exposure may alter different phenotypes, including virulence and biofilm formation. The complexity of the interactions between microbes and their viral predators is also evidenced by the link between quorum-sensing signaling pathways and bacteriophage resistance. Overall, new data increasingly suggests that both temperate and virulent phages have a positive effect on the evolution and adaptation of microbial populations. From this perspective, further research is still necessary to fully understand the interactions between phage and host under conditions that allow co-existence of both populations, reflecting more accurately the dynamics in natural microbial communities.
Dandelions, tulips and orchids: evidence for the existence of low-sensitive, medium-sensitive and high-sensitive individuals
Authors: Lionetti Francesca , Aron Arthur , Aron Elaine N. , Burns G. Leonard , Jagiellowicz Jadzia , Pluess Michael
Published: January 2018

According to empirical studies and recent theories, people differ substantially in their reactivity or sensitivity to environmental influences with some being generally more affected than others. More sensitive individuals have been described as orchids and less-sensitive ones as dandelions. Applying a data-driven approach, we explored the existence of sensitivity groups in a sample of 906 adults who completed the highly sensitive person (HSP) scale. According to factor analyses, the HSP scale reflects a bifactor model with a general sensitivity factor. In contrast to prevailing theories, latent class analyses consistently suggested the existence of three rather than two groups. While we were able to identify a highly sensitive (orchids, 31%) and a low-sensitive group (dandelions, 29%), we also detected a third group (40%) characterised by medium sensitivity, which we refer to as tulips in keeping with the flower metaphor. Preliminary cut-off scores for all three groups are provided. In order to characterise the different sensitivity groups, we investigated group differences regarding the Big Five personality traits, as well as experimentally assessed emotional reactivity in an additional independent sample. According to these follow-up analyses, the three groups differed in neuroticism, extraversion and emotional reactivity to positive mood induction with orchids scoring significantly higher in neuroticism and emotional reactivity and lower in extraversion than the other two groups (dandelions also differed significantly from tulips). Findings suggest that environmental sensitivity is a continuous and normally distributed trait but that people fall into three distinct sensitive groups along a sensitivity continuum.
Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells
Authors: Lucantoni Federico , Lindner Andreas U. , O’Donovan Norma , Düssmann Heiko , Prehn Jochen H. M.
Published: January 2018

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15–20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells by BCL2 inhibitors. Using absolute protein levels of BAX, BAK, BCL2, BCL(X)L and MCL1 as input for DR_MOMP, we found a strong correlation between model predictions and responses of a panel of TNBC cells to 24 and 48 h cisplatin (R2 = 0.96 and 0.95, respectively) and paclitaxel treatments (R2 = 0.94 and 0.95, respectively). This outperformed single protein correlations (best performer BCL(X)L with R2 of 0.69 and 0.50 for cisplatin and paclitaxel treatments, respectively) and BCL2 proteins ratio (R2 of 0.50 for cisplatin and 0.49 for paclitaxel). Next we performed synergy studies using the BCL2 selective antagonist Venetoclax /ABT199, the BCL(X)L selective antagonist WEHI-539, or the MCL1 selective antagonist A-1210477 in combination with cisplatin. In silico predictions by DR_MOMP revealed substantial differences in treatment responses of BCL(X)L, BCL2 or MCL1 inhibitors combinations with cisplatin that were successfully validated in cell lines. Our findings provide evidence that DR_MOMP predicts responses of TNBC cells to genotoxic therapy, and can aid in the choice of the optimal BCL2 protein antagonist for combination treatments of resistant cells.
Ethanol sensitizes hepatocytes for TGF-β-triggered apoptosis
Authors: Gaitantzi Haristi , Meyer Christoph , Rakoczy Pia , Thomas Maria , Wahl Kristin , Wandrer Franziska , Bantel Heike , Alborzinia Hamed , Wölfl Stefan , Ehnert Sabrina , Nüssler Andreas , Bergheim Ina , Ciuclan Loredana , Ebert Matthias , Breitkopf-Heinlein Katja , Dooley Steven
Published: January 2018

Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β—a potent pro-fibrogenic cytokine—leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels. To substantiate findings, animal model specimens and human liver tissue cultures were investigated. Results: On its own, ethanol had no effect on hepatocyte apoptosis, whereas TGF-β increased cell death. Combined treatment led to massive hepatocyte apoptosis, which could also be recapitulated in human HCC liver tissue treated ex vivo. Alcohol boosted the TGF-β pro-apoptotic gene signature. The underlying mechanism of pathway crosstalk involves SMAD and non-SMAD/AKT signaling. Blunting CYP2E1 and ADH activities did not prevent this effect, implying that it was not a consequence of alcohol metabolism. In line with this, the ethanol metabolite acetaldehyde did not mimic the effect and glutathione supplementation did not prevent the super-induction of cell death. In contrast, blocking GSK-3β activity, a downstream mediator of AKT signaling, rescued the strong apoptotic response triggered by ethanol and TGF-β. This study provides novel information on the crosstalk between ethanol and TGF-β. We give evidence that ethanol directly leads to a boost of TGF-β’s pro-apoptotic function in hepatocytes, which may have implications for patients with chronic alcoholic liver disease.
Streamlined asymmetric α-difunctionalization of ynones
Authors: Peng Siyu , Wang Zhaofeng , Zhang Linxing , Zhang Xinhao , Huang Yong
Published: January 2018

Ynones are a unique class of structural motifs that show remarkable chemical versatility. Chiral ynones, particularly those possessing an α-stereogenic center, are highly attractive templates for structural diversification. So far, only very limited examples have been reported for asymmetric α-functionalization of ynones. Asymmetric double α-functionalization of ynones remains elusive. Here we describe a streamlined strategy for asymmetric α-difunctionalization of ynones. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an α-quaternary carbon and containing a fluorine and an alkyne can be synthesized in high yield and high ee. The synthetic utility of this method is demonstrated by the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.
Integrated computational materials engineering of corrosion resistant alloys
Authors: Taylor Christopher D. , Lu Pin , Saal James , Frankel G. S. , Scully J. R.
Published: January 2018

Structure, composition and surface properties dictate corrosion resistance in any given environment. The degrees of freedom in alloy design are too numerous in emerging materials such as high entropy alloys and bulk metallic glasses for the use of high-throughput methods or trial and error. We review three domains of knowledge that can be applied towards the goal of corrosion resistant alloy (CRA) design: (a) the aggregation of knowledge gained through experience in developing CRAs empirically, (b) data-driven approaches that use descriptive metrics for alloy composition optimization, and (c) first-principles models of elementary processes that regulate corrosion informed by theory and inspired by phenomenological models in the literature. A path forward for integrated computational materials engineering (ICME) of CRAs that unites these three knowledge domains is introduced.
Risks, Release and Concentrations of Engineered Nanomaterial in the Environment
Authors: Giese Bernd , Klaessig Fred , Park Barry , Kaegi Ralf , Steinfeldt Michael , Wigger Henning , von Gleich Arnim , Gottschalk Fadri
Published: January 2018

For frequently used engineered nanomaterials (ENMs) CeO2-, SiO2-, and Ag, past, current, and future use and environmental release are investigated. Considering an extended period (1950 to 2050), we assess ENMs released through commercial activity as well as found in natural and technical settings. Temporal dynamics, including shifts in release due to ENM product application, stock (delayed use), and subsequent end-of-life product treatment were taken into account. We distinguish predicted concentrations originating in ENM use phase and those originating from end-of-life release. Furthermore, we compare Ag- and CeO2-ENM predictions with existing measurements. The correlations and limitations of the model, and the analytic validity of our approach are discussed in the context of massive use of assumptive model data and high uncertainty on the colloidal material captured by the measurements. Predictions for freshwater CeO2-ENMs range from 1 pg/l (2017) to a few hundred ng/l (2050). Relative to CeO2, the SiO2-ENMs estimates are approximately 1,000 times higher, and those for Ag-ENMs 10 times lower. For most environmental compartments, ENM pose relatively low risk; however, organisms residing near ENM ‘point sources’ (e.g., production plant outfalls and waste treatment plants), which are not considered in the present work, may be at increased risk.
Starfish Apaf-1 activates effector caspase-3/9 upon apoptosis of aged eggs
Authors: Tamura Ritsuko , Takada Mariko , Sakaue Miki , Yoshida Ayaka , Ohi Shirabe , Hirano Kaoru , Hayakawa Tomoyo , Hirohashi Noritaka , Yura Kei , Chiba Kazuyoshi
Published: January 2018

Caspase-3-related DEVDase activity is initiated upon apoptosis in unfertilized starfish eggs. In this study, we cloned a starfish procaspase-3 corresponding to mammalian effector caspase containing a CARD that is similar to the amino terminal CARD of mammalian capsase-9, and we named it procaspase-3/9. Recombinant procaspase-3/9 expressed at 15 °C was cleaved to form active caspase-3/9 which has DEVDase activity. Microinjection of the active caspase-3/9 into starfish oocytes/eggs induced apoptosis. An antibody against the recombinant protein recognized endogenous procaspase-3/9 in starfish oocytes, which was cleaved upon apoptosis in aged unfertilized eggs. These results indicate that caspase-3/9 is an effector caspase in starfish. To verify the mechanism of caspase-3/9 activation, we cloned starfish Apaf-1 containing a CARD, a NOD, and 11 WD40 repeat regions, and we named it sfApaf-1. Recombinant sfApaf-1 CARD interacts with recombinant caspase-3/9 CARD and with endogenous procaspase-3/9 in cell-free preparations made from starfish oocytes, causing the formation of active caspase-3/9. When the cell-free preparation without mitochondria was incubated with inactive recombinant procaspase-3/9 expressed at 37 °C, DEVDase activity increased and apoptosome-like complexes were formed in the high molecular weight fractions containing both sfApaf-1 and cleaved caspase-3/9. These results suggest that sfApaf-1 activation is not dependent on cytochrome c.
Global Quantitative Proteomics reveal Deregulation of Cytoskeletal and Apoptotic Signalling Proteins in Oral Tongue Squamous Cell Carcinoma
Authors: Ananthi Sivagnanam , Lakshmi Ch Naga Padma , Atmika Paul , Anbarasu Kumaraswamy , Mahalingam Sundarasamy
Published: January 2018

Oral malignancies remain to have higher morbidity and mortality rates owing to the poor understanding of the carcinogenesis and the lack of early detection and diagnosis. The lack of established biomarkers for oral tongue squamous cell carcinoma (OTSCC) resulted in aggressive multi-modality management less effective. Here, we report for the first time that a panel of potential markers identified from tongue tumor samples using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE). Our approach of combining 2D-DIGE with tandem mass spectrometry identified 24 candidate proteins including cofilins, myosin light chain family members, annexins, serpins, HSPs and tropomyosins, with significant differential expression in tongue carcinomas as compared with their matched adjacent normal tissues. The expression levels of the identified proteins were further validated in larger cohort of Indian samples using qPCR. Most of the differentially regulated proteins are involved in actin cytoskeletal dynamics, drug resistance, immune system, inflammation and apoptotic signalling pathways and are known to play critical role in oral tumorigenesis. Taken together, the results from present investigation provide a valuable base for understanding the development and progression of OTSCC. The validated panel of proteins may be used as potential biomarkers for early detection as well as in predicting therapeutic outcome of OTSCC.
Alterations of oral microbiota distinguish children with autism spectrum disorders from healthy controls
Authors: Qiao Yanan , Wu Mingtao , Feng Yanhuizhi , Zhou Zhichong , Chen Lei , Chen Fengshan
Published: January 2018

Altered gut microbiota is associated with autism spectrum disorders (ASD), a group of complex, fast growing but difficult-to-diagnose neurodevelopmental disorders worldwide. However, the role of the oral microbiota in ASD remains unexplored. Via high-throughput sequencing of 111 oral samples in 32 children with ASD and 27 healthy controls, we demonstrated that the salivary and dental microbiota of ASD patients were highly distinct from those of healthy individuals. Lower bacterial diversity was observed in ASD children compared to controls, especially in dental samples. Also, principal coordinate analysis revealed divergences between ASD patients and controls. Moreover, pathogens such as Haemophilus in saliva and Streptococcus in plaques showed significantly higher abundance in ASD patients, whereas commensals such as Prevotella, Selenomonas, Actinomyces, Porphyromonas, and Fusobacterium were reduced. Specifically, an overt depletion of Prevotellaceae co-occurrence network in ASD patients was obtained in dental plaques. The distinguishable bacteria were also correlated with clinical indices, reflecting disease severity and the oral health status (i.e. dental caries). Finally, diagnostic models based on key microbes were constructed, with 96.3% accuracy in saliva. Taken together, this study characterized the habitat-specific profile of the oral microbiota in ASD patients, which might help develop novel strategies for the diagnosis of ASD.
Topological Valley Transport in Two-dimensional Honeycomb Photonic Crystals
Authors: Yang Yuting , Jiang Hua , Hang Zhi Hong
Published: January 2018

Two-dimensional photonic crystals, in analogy to AB/BA stacking bilayer graphene in electronic system, are studied. Inequivalent valleys in the momentum space for photons can be manipulated by simply engineering diameters of cylinders in a honeycomb lattice. The inequivalent valleys in photonic crystal are selectively excited by a designed optical chiral source and bulk valley polarizations are visualized. Unidirectional valley interface states are proved to exist on a domain wall connecting two photonic crystals with different valley Chern numbers. With the similar optical vortex index, interface states can couple with bulk valley polarizations and thus valley filter and valley coupler can be designed. Our simple dielectric PC scheme can help to exploit the valley degree of freedom for future optical devices.