bluuebunny/crossref_metadata_2025 huggingface dataset:
Size optimization of a stand-alone micro-grid integrated with flexible load and the complementary of solar and wind
Authors: Yang Lijun , Huang Kaiting , Kong Xiaolei , Luo Qiwu , Guo Haijun
Published: March 2019

With the development of micro-grids, the large-scale use of solar and wind energies, and the high growth of load demands, it is of great significance to improve the utilization ratio of renewable energy and economy for a micro-grid system. By making full use of the complementary of solar and wind energies or realizing the interaction between supply and demands, this situation can be effectively improved. Thus, regarding the ability of these two factors, this paper is devoted to analysing and modelling a stand-alone micro-grid with a hybrid PV/wind/battery power generation system. Also, an optimal energy management strategy, which emphasizes the coordination of sources/batteries/loads, is proposed based on the existing strategies. Furthermore, the effect of the complementary of solar and wind energies is studied. Aiming at minimizing the annualized cost of the system (fACS), flexible load dispatching cost (ffl), and unutilized renewable energy probability (fUREP), a multi-objective size optimization problem is efficiently solved using the particle swarm optimization algorithm. The simulation results depict the effectiveness of the proposed method.
Electrolyte-gated magnetoelectric actuation: Phenomenology, materials,
mechanisms, and prospective applications
Authors: Navarro-Senent Cristina , Quintana Alberto , Menéndez Enric , Pellicer Eva , Sort Jordi
Published: March 2019

Manipulation of the magnetic behavior of materials with voltage (i.e., magnetoelectric actuation) has become a topic of intense research during the last years. Apart from its obvious interest from a basic science standpoint, control and eventual switching of the magnetization without applying any external magnetic field (or spin polarized current) has the potential to drastically reduce the power consumption of magnetic devices due to the lack (or minimization) of Joule heating dissipation effects. Herein, an overview of the state-of-the-art of electrolyte-gated magnetoelectric actuation (where an electric field is applied using an electrolyte, either liquid or solid) is provided. The different types of mechanisms responsible for voltage-driven magnetic actuation (surface charging, ionic migration, also termed “magneto-ionics,” reduction/oxidation reactions, and ferroelectric/ferromagnetic coupling) are summarized. The various effects (changes in coercivity, anisotropy easy axis, exchange bias field, saturation magnetization, Curie temperature, etc.) observed in the different types of materials investigated so far (mainly metallic thin films and semiconductors, porous alloys, and nanocomposite structures) are described. The potential applications of electrolyte-gated magnetoelectric actuation in devices as well as the current challenges in the field are also reviewed with the aim of providing the basic ingredients for further prospects and technological advancements in this area.
Long Paddock: climate risk and grazing information for Australian rangelands and grazing communities
Authors: Stone G. , Pozza R. Dalla , Carter J. , McKeon G.
Published: March 2019

The Queensland Government’s Long Paddock website has been redeveloped on Amazon Web Services cloud computing platform, to provide Australian rangelands and grazing communities (i.e. rural landholders, managers, pastoralists (graziers), researchers, advisors, students, consultants and extension providers) with easier access to seasonal climate and pasture condition information. The website provides free, tailored information and services to support management decisions to maximise productivity, while maintaining the natural resource base. For example, historical rainfall and pasture analyses (i.e. maps, posters and data) have been developed to assist in communicating the risk of multi-year droughts that are a feature of Queensland’s highly variable climate.
PFG acted as an inducer of premature senescence in TIG-1 normal diploid fibroblast and an inhibitor of mitosis in the HeLa cells
Authors: Huang Ying , Ohno Osamu , Miyamoto Kenji
Published: March 2019

Our previous work has reported an anti-proliferative compound from moutan cortex, paeoniflorigenone which can induce cancer-selective apoptosis. However, its anti-proliferative mechanism is still unknown. According to morphology changes (hypertrophy and flattening), we hypothesized that PFG can induce senescence or inhibit cell mitosis. Here we show that PFG can induce cellular senescence, evidenced by the expression of senescence-associated β-galactosidase, G0/G1 cell cycle arrest and permanent loss of proliferative ability, in normal TIG-1 diploid fibroblast but not cancerous HeLa cells. In cancerous HeLa cells, PFG inhibited proliferation by inducing S and G2/M cell cycle arrest and mitosis inhibition. DNA damage response was activated by PFG, interestingly the reactive oxygen species level was suppressed instead of escalated. To sum up, we report 3 new roles of PFG as, 1. inducer of premature senescence in normal TIG-1 cells, 2. inhibitor of mitosis in cancerous HeLa cells, 3. ROS scavenger.

Abbreviations: PFG: Paeoniflorigenone; ROS: reactive oxygen species; ATM: ataxia telangiectasia mutated; t-BHP: tert-butyl hydroperoxide; SA-β-gal: senescence-associatedβ-galactosidase; DNA-PKcs: DNA-dependent protein kinase; γ-H2AX: H2AX phosphoryla-tion at Ser-139
Norlichexanthone produced by cultured endolichenic fungus induced from Pertusaria laeviganda and its antioxidant activity
Authors: Kawakami Hiroko , Suzuki Chihiro , Yamaguchi Haruka , Hara Kojiro , Komine Masashi , Yamamoto Yoshikazu
Published: March 2019

Endolichenic fungi, nonobligate microfungi that live in lichen, are promising as new bioresources of pharmacological compounds. We found that norlichexanthone isolated from the endolichenic fungus in Pertusaria laeviganda exhibited high antioxidant activity. Norlichexanthone produced by endolichenic fungus had the antioxidant activity with same level of ascorbic acid. This is the first report of high antioxidant activity of norlichexanthone.

Abbreviations: AAPH: 2,2ʹ-azobis (2-methylpropionamidine) dihydrochloride; DPPH: 2,2-diphenyl-1-picrylhydrazyl; FL: fluorescein sodium salt; HPLC-PDA: high-performance liquid chromatography with photodiode array; LC-ESI-MS: liquid chromatography with electrospray ionization mass spectrometry; ORAC: oxygen radical absorbance capacity; PB: phosphate buffer; ROS: reactive oxygen species; TLC: thin-layer chromatography
The Trail from Fukushima
Authors: Bernas Harry
Published: March 2019

In this reflection on the origin of the nuclear disaster at Fukushima, the author shows that it was not an “unexpected catastrophe” but the result of a historical process. Moreover, it had been predicted. The danger, publicized for years, was ignored or denied by the authorities and operator. Why was it allowed to occur? The focus is on human, rather than technical, reasons.
PyFeat: a Python-based effective feature generation tool for DNA, RNA and protein sequences
Authors: Muhammod Rafsanjani , Ahmed Sajid , Md Farid Dewan , Shatabda Swakkhar , Sharma Alok , Dehzangi Abdollah
Published: March 2019

Motivation

Extracting useful feature set which contains significant discriminatory information is a critical step in effectively presenting sequence data to predict structural, functional, interaction and expression of proteins, DNAs and RNAs. Also, being able to filter features with significant information and avoid sparsity in the extracted features require the employment of efficient feature selection techniques. Here we present PyFeat as a practical and easy to use toolkit implemented in Python for extracting various features from proteins, DNAs and RNAs. To build PyFeat we mainly focused on extracting features that capture information about the interaction of neighboring residues to be able to provide more local information. We then employ AdaBoost technique to select features with maximum discriminatory information. In this way, we can significantly reduce the number of extracted features and enable PyFeat to represent the combination of effective features from large neighboring residues. As a result, PyFeat is able to extract features from 13 different techniques and represent context free combination of effective features. The source code for PyFeat standalone toolkit and employed benchmarks with a comprehensive user manual explaining its system and workflow in a step by step manner are publicly available.

Results

https://github.com/mrzResearchArena/PyFeat/blob/master/RESULTS.md.

Availability and implementation

Toolkit, source code and manual to use PyFeat: https://github.com/mrzResearchArena/PyFeat/

Supplementary information

Supplementary data are available at Bioinformatics online.
Greening the common agricultural policy: a behavioural perspective and lab-in-the-field experiment in Germany
Authors: Thomas Fabian , Midler Estelle , Lefebvre Marianne , Engel Stefanie
Published: March 2019

This study investigates the behavioural economic underpinnings of current policy approaches to integrate environmental objectives into the Common Agricultural Policy. We conduct an economic lab-in-the-field experiment with farmers in Germany. We analyse the impact of the following policy design features on farmers’ decisions to adopt sustainable agricultural practices: (i) framing of the policy: whether farmers perceive themselves as being part of the problem or the solution, (ii) degree of control: mandatory vs. voluntary policy and (iii) framing of incentives as either losses or gains. All policy designs tested result in a significant increase in hectares conserved compared to a baseline scenario without policy. Also, behavioural factors do significantly affect farmers’ behaviour at the individual level. Only framing is found to significantly affect policy effectiveness.
Exhibitions, patents, and innovation in the early twentieth century: evidence from the Turin 1911 International Exhibition
Authors: Domini Giacomo
Published: March 2019

This paper investigates the relevance for innovation of international exhibitions. While the first of these events, i.e., London’s 1851 Great Exhibition, was an “exhibition of innovations,” many of the subsequent ones, following the model of industrial exhibitions developed in France, did not select exhibits based on novelty. In fact, they displayed a large spectrum of products, ranging from machines to primary products. Therefore, the suitability of data from their catalogs for proxying innovation, and their relationship to the traditional patent measure, should be better qualified. To do so, this paper performs an in-depth analysis of the Turin 1911 international exhibition, a medium-sized representative “French-model” exhibition. It matches a new database, built from the catalog of this event, with patents granted in Italy, revealing substantial differences. Furthermore, it evaluates how inventors could use the exhibition to promote their ideas, establish their reputation, and develop their career.
A new unbiased minimum variance observer for stochastic LTV systems with unknown inputs
Authors: Meyer Luc , Ichalal Dalil , Vigneron Vincent
Published: March 2019

This paper is devoted to the state and input estimation of a linear time varying system in the presence of an unknown input (UI) in both state and measurement equations, and affected by Gaussian noises. The classical rank condition used in this kind of approach is relaxed in order to be able to be used in a wider range of systems. A state observer, that is an unbiased estimator with minimum error variance, is proposed. Then a UI observer is constructed, in order to be a best linear unbiased estimator, it follows a unique construction whether the direct feedthrough matrix is null or not. In a sense the proposed approach, generalizes and unifies the existing ones. Besides, a stability result is given for linear time invariant systems, which is a novelty for unbiased minimum variance observers relaxing the classical rank condition.
Integrating Refugee Children and Youth: A Scoping Review of English and German Literature
Authors: Pritchard Paul , Maehler Débora B , Pötzschke Steffen , Ramos Howard
Published: March 2019

The United Nations High Commission for Refugees reports that more than half of the 65 million refugees and displaced people identified worldwide are under the age of 18. For this reason, researchers, practitioners and policymakers need to understand the consequences of forced migration on the integration of refugee children and youth in receiving countries. A first step to do that is to scope out the state of current research on these issues and identify possible gaps. To that end, the article offers a scoping review of peer-reviewed English and German academic articles on refugee children and youth’s integration over a 20-year period. The review finds: little consensus on the definitions of ‘children’ or ‘youth’; most studies focus on girls and boys that are between 12 and 19 years old; there is a focus on refugees landing in developed countries; and there is a lack of longitudinal and quantitative studies.
Genetic, Physiologic, and Behavioral Predictors of Cardiorespiratory Fitness in Specialized Military Men
Authors: Taylor Marcus K , Hernández Lisa M , Schoenherr Matthew R , Stump Jeremiah
Published: March 2019

Introduction

Cardiorespiratory fitness (CRF) is a crucial performance requirement of specialized military occupations. Age and physical activity are established predictors of CRF, but it is not clear how these predictors combine with each other and/or with genetic predisposition. The goal of this study was to derive inclusive explanatory models of CRF in US Navy Explosive Ordnance Disposal (EOD) operators, synthesizing conventional (e.g., age, body composition, and physical activity) and novel influences (e.g., genetic variance).

Materials and Methods

In this cross-sectional study, 40 male, active duty EOD operators completed a graded exercise test to assess maximal oxygen consumption and ventilatory threshold (VT) using the Bruce protocol. Aerobic performance was further quantified via time of test termination and time at which VT was achieved. Body composition was determined via dual x-ray absorptiometry, and physical activity was assessed by self-report. Genetic variants underlying human stress systems (5HTTLPR, BclI, −2 C/G, and COMT) were assayed. Descriptive analyses were conducted to summarize subject characteristics. Hypotheses were tested with linear regression models. Specifically, separate univariate regression models first determined associations between each of the independent and dependent variables. This protocol was approved by the Naval Health Research Center Institutional Review Board (NHRC.2015.0013).

Results

In univariate regression models, age, body composition, physical activity, and 5HTTLPR consistently predicted CRF and/or aerobic performance (R2 range 0.07–0.55). Multivariate regression models routinely outperformed the univariate models, explaining 36–62% of variance.

Conclusion

This study signifies a shift toward inclusive explanatory models of CRF and aerobic performance, accounting for combined roles of genetic, physiologic, and behavioral influences. Although we were able to quantify combined effects, we were unable to evaluate interaction effects (e.g., gene–gene, gene–behavior) due to limited statistical power. Other limitations are that this specialized military population may not readily generalize to broader populations, and the current sample was all male. Considering these limitations, we aim to replicate this study in various populations, both male and female. Despite its limitations, this study reflects a shift toward more comprehensive predictive models of CRF, explaining the unique and shared contributions of genetic predisposition, physiology, and behavior. These findings have implications for assessment, selection, and training of specialized military members, and may also impact mission success and survivability. Future studies are needed to better characterize additive, interactive, and mediated effects.
Effects of Early Altitude Exposure on the Open Abdomen After Laparotomy in Trauma
Authors: Martin Grace E , Johnson Mark , Veile Rose , Friend Lou Ann , Elterman Joel B , Johannigman Jay A , Pritts Timothy A , Goodman Michael D , Makley Amy T
Published: March 2019

Introduction

While damage control surgery and resuscitation techniques have revolutionized the care of injured service members who sustain severe traumatic hemorrhage, the physiologic and inflammatory consequences of hemostatic resuscitation and staged abdominal surgery in the face of early aeromedical evacuation (AE) have not been investigated. We hypothesized that post-injury AE with an open abdomen would have significant physiologic and inflammatory consequences compared to AE with a closed abdomen.

Materials and Methods

Evaluation of resuscitation and staged abdominal closure was performed using a murine model of hemorrhagic shock with laparotomy. Mice underwent controlled hemorrhage to a systolic blood pressure of 25 mmHg and received either no resuscitation, blood product resuscitation, or Hextend resuscitation to a systolic blood pressure of either 50 mmHg (partial resuscitation) or 80 mmHg (complete resuscitation). Laparotomies were either closed prior to AE (closed abdomens) or left open during AE (open abdomens) and subsequently closed. AE was simulated with a 1-hour exposure to a hypobaric hypoxic environment at 8,000 feet altitude. Mice were euthanized at 0, 4, or 24 hours following AE. Serum was collected and analyzed for physiologic variables and inflammatory cytokine levels. Samples of lung and small intestine were collected for tissue cytokine and myeloperoxidase analysis as indicators of intestinal inflammation. Survival curves were also performed.

Results

Unresuscitated mice sustained an 85% mortality rate from hemorrhage and laparotomy, limiting the assessment of the effect of simulated AE in these subgroups. Overall survival was similar among all resuscitated groups regardless of the presence of hypobaric hypoxia, type of resuscitation, or abdominal closure status. Simulated AE had no observed effects on acid/base imbalance or the inflammatory response as compared to ground level controls. All mice experienced both metabolic acidosis and an acute inflammatory response after hemorrhage and injury, represented by an initial increase in serum interleukin (IL)-6 levels. Furthermore, mice with open abdomens had an elevated inflammatory response with increased levels of serum IL-10, serum tumor necrosis factor alpha, intestinal IL-6, intestinal IL-10, and pulmonary myeloperoxidase.

Conclusion

These results demonstrate the complex interaction of AE and temporary or definitive abdominal closure after post-injury laparotomy. Contrary to our hypothesis, we found that AE in those animals with open abdomens is relatively safe with no difference in mortality compared to those with closed abdomens. However, given the physiologic and inflammatory changes observed in animals with open abdomens, further evaluation is necessary prior to definitive recommendations regarding the safety or downstream effects of exposure to AE prior to definitive abdominal closure.
Bioinspired polydopamine and polyphenol tannic acid functionalized titanium suppress osteoclast differentiation: a facile and efficient strategy to regulate osteoclast activity at bone–implant interface
Authors: Steffi Chris , Shi Zhilong , Kong Chee Hoe , Wang Wilson
Published: March 2019

Osseointegration of metallic implants in porous osteoporotic bone remains a challenge. Surface modification of implants to reduce peri-implant osteoclastic bone resorption was explored in the study. Bioinspired polydopamine (pDOP) and polyphenol tannic acid (pTAN) are nature-derived universal coating systems that have emerged either as a sole coating or ad-layer for biomolecular conjugation on different biomaterials. The effects pDOP and pTAN on osteoclast development have not been reported before. In this study, osteoclast development was investigated on titanium (Ti) substrates coated with pDOP (Ti-pDOP) and pTAN (Ti-pTAN). The results showed that Ti-pDOP and Ti-pTAN coating reduced tartrate-resistant acid phosphatase activity and osteoclast cell number as compared with pristine Ti. Intriguingly, the reduction was higher on Ti-pTAN than on Ti-pDOP. Economical and biocompatible tannic acid serves as a superior coating in decreasing osteoclast activity when compared with that of pDOP coating and could be used to modulate osteoclast activity at bone–implant interfaces.
PEEK surface modification by fast ambient-temperature sulfonation for bone implant applications
Authors: Wang Weigeng , Luo C. J. , Huang Jie , Edirisinghe Mohan
Published: March 2019

We develop a simple, fast and economical surface treatment under ambient temperature to improve the hydrophilicity and osteoconductivity of polyetheretherketone (PEEK) for bone implant applications. A major challenge in bone implants is the drastic difference in stiffness between traditional implant materials (such as titanium and stainless steel) and human bone. PEEK is biocompatible with an elastic modulus closely matching that of human bone, making it a highly attractive alternative. However, its bio-inert and poorly hydrophilic surface presents a serious challenge for osseointegration. Sulfonation can improve hydrophilicity and introduce bioactive sulfonate groups, but PEEK sulfonation has traditionally been applied for fuel cells, employing elevated temperatures and long reaction times to re-cast PEEK into sulfonated films. Little research has systematically studied PEEK surface modification by short reaction time (seconds) and ambient-temperature sulfonation for biomedical applications. Here, we investigate three ambient-temperature sulfonation treatments under varying reaction times (5–90 s) and evaluate the hydrophilicity and morphology of 15 modified PEEK surfaces. We establish an optimal treatment using 30 s H
2
SO
4
followed by 20 s rinsing, and then 20 s immersion in NaOH followed by 20 s rinsing. This 30 s ambient-temperature sulfonation is found to be more effective than conventional plasma treatments and reduced PEEK water contact angle from 78° to 37°.
Ancient Mesopotamian views on human skin and body: a cultural–historical analysis of dermatological data from cuneiform sources
Authors: Minen Francesca
Published: March 2019

Most recent advances in the study of ancient Mesopotamian medical texts have disclosed information pertaining to the fields of diagnosis, prognosis and therapy and are now available for a comparative study with other ancient medical systems. However, in the framework of Assyriological studies there are still methodological problems that need to be addressed. Disregarding a retrospective diagnostic approach, this paper aims at highlighting the cultural–historical relevance of the medical information reported in cuneiform texts, assuming data related to skin imperfections and ailments as a case study. After a brief overview of the sources from ancient Mediterranean and Near Eastern cultures that may be referred to the modern medical specialty of dermatology, the specificities of Mesopotamian medicine and dermatology will be presented. Two examples, dedicated to the reconstruction of the ancient Mesopotamian view on the skin and the body, will demonstrate how relevant sources may be fruitfully analysed in a cultural–historical context.
Schizophrenia risk and reproductive success: a Mendelian randomization study
Authors: Lawn Rebecca B. , Sallis Hannah M. , Taylor Amy E. , Wootton Robyn E. , Smith George Davey , Davies Neil M. , Hemani Gibran , Fraser Abigail , Penton-Voak Ian S. , Munafò Marcus R.
Published: March 2019

Schizophrenia is a debilitating and heritable mental disorder associated with lower reproductive success. However, the prevalence of schizophrenia is stable over populations and time, resulting in an evolutionary puzzle: how is schizophrenia maintained in the population, given its apparent fitness costs? One possibility is that increased genetic liability for schizophrenia, in the absence of the disorder itself, may confer some reproductive advantage. We assessed the correlation and causal effect of genetic liability for schizophrenia with number of children, age at first birth and number of sexual partners using data from the Psychiatric Genomics Consortium and UK Biobank. Linkage disequilibrium score regression showed little evidence of genetic correlation between genetic liability for schizophrenia and number of children (rg= 0.002,p= 0.84), age at first birth (rg= −0.007,p= 0.45) or number of sexual partners (rg= 0.007,p= 0.42). Mendelian randomization indicated no robust evidence of a causal effect of genetic liability for schizophrenia on number of children (mean difference: 0.003 increase in number of children per doubling in the natural log odds ratio of schizophrenia risk, 95% confidence interval (CI): −0.003 to 0.009,p= 0.39) or age at first birth (−0.004 years lower age at first birth, 95% CI: −0.043 to 0.034,p= 0.82). We find some evidence of a positive effect of genetic liability for schizophrenia on number of sexual partners (0.165 increase in the number of sexual partners, 95% CI: 0.117–0.212,p= 5.30×10−10). These results suggest that increased genetic liability for schizophrenia does not confer a fitness advantage but does increase mating success.
The influence of visual and haptic material information on early grasping force
Authors: Bergmann Tiest Wouter M. , Kappers Astrid M. L.
Published: March 2019

In this paper, we assess the importance of visual and haptic information about materials for scaling the grasping force when picking up an object. We asked 12 participants to pick up and lift objects with six different textures, either blindfolded or with visual information present. We measured the grip force and estimated the load force from the object’s weight and vertical acceleration. The coefficient of friction of the materials was measured separately. Already at an early phase in the grasp (before lift-off), the grip force correlated highly with the textures’ static coefficient of friction. However, no strong influence on the presence of visual information was found. We conclude that the main mechanism for modulation of grip force in the early phase of grasping is the real-time sensation of the texture’s friction.
Snap happy: camera traps are an effective sampling tool when compared with alternative methods
Authors: Wearn Oliver R. , Glover-Kapfer Paul
Published: March 2019

Camera traps have become a ubiquitous tool in ecology and conservation. They are routinely deployed in wildlife survey and monitoring work, and are being advocated as a tool for planetary-scale biodiversity monitoring. The camera trap's widespread adoption is predicated on the assumption of its effectiveness, but the evidence base for this is lacking. Using 104 past studies, we recorded the qualitative overall recommendations made by study authors (for or against camera traps, or ambiguous), together with quantitative data on the effectiveness of camera traps (e.g. number of species detected or detection probabilities) relative to 22 other methods. Most studies recommended the use of camera traps overall and they were 39% more effective based on the quantitative data. They were significantly more effective compared with live traps (88%) and were otherwise comparable in effectiveness to other methods. Camera traps were significantly more effective than other methods at detecting a large number of species (31% more) and for generating detections of species (91% more). This makes camera traps particularly suitable for broad-spectrum biodiversity surveys. Film camera traps were found to be far less effective than digital models, which has led to an increase in camera trap effectiveness over time. There was also evidence from the authors that the use of attractants with camera traps reduced their effectiveness (counter to their intended effect), while the quantitative data indicated that camera traps were more effective in closed than open habitats. Camera traps are a highly effective wildlife survey tool and their performance will only improve with future technological advances. The images they produce also have a range of other benefits, for example as digital voucher specimens and as visual aids for outreach. The evidence-base supports the increasing use of camera traps and underlines their suitability for meeting the challenges of global-scale biodiversity monitoring.
Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells
Authors: Kumar Banushree , Elsässer Simon J
Published: March 2019

To understand the epigenetic foundation of naïve pluripotent cells, we implement a quantitative multiplexed ChIP-Seq method (MINUTE-ChIP) comparing mouse ESC grown in 2i versus Serum conditions. Combined with quantitative western blot and mass spectrometry, we find compelling evidence for a broad H3K27me3 hypermethylation of the genome, concomitant with the widespread loss of DNA CpG methylation. We show that opposing action of EZH2 and JMJD3/UTX shape the H3K27me3 landscape, with almost all bivalent promoters stably retaining high H3K27me3 levels in 2i. In parallel, we show a mechanistically uncoupled, global decrease of H3K4me3 and strong reduction at bivalent promoters, suggesting that low H3K4me3 and high H3K27me3 levels at bivalent promoters safeguard naïve pluripotency.
Metabolic Cost of Rapid Adaptation of Single Yeast Cells
Authors: Woronoff Gabrielle , Nghe Philippe , Baudry Jean , Boitard Laurent , Braun Erez , Griffiths Andrew D. , Bibette Jérôme
Published: March 2019

Cells can rapidly adapt to changing environments through non-genetic processes; however, the metabolic cost of such adaptation has never been considered. Here we demonstrate metabolic coupling in a remarkable, rapid adaptation process (10-3cells/hour) by simultaneously measuring metabolism and division of thousands of individual Saccharomyces cerevisiae cells using a droplet microfluidic system. Following a severe challenge, most cells, while not dividing, continue to metabolize, displaying a remarkably wide diversity of metabolic trajectories from which adaptation events can be anticipated. Adaptation requires the consumption of a characteristic amount of energy, indicating that it is an active process. The demonstration that metabolic trajectories predict a priori adaptation events provides the first evidence of tight energetic coupling between metabolism and regulatory reorganization in adaptation.

One Sentence Summary

Demonstration of the tight coupling between metabolic activity and regulatory processes during rapid adaptation at the single-cell level.
Genomic architecture of phenotypic plasticity of complex traits in tetraploid wheat in response to water stress
Authors: Fatiukha Andrii , Deblieck Mathieu , Klymiuk Valentina , Merchuk-Ovnat Lianne , Peleg Zvi , Ordon Frank , Fahima Tzion , Korol Abraham B. , Saranga Yehoshua , Krugman Tamar
Published: March 2019

Phenotypic plasticity is one of the main mechanisms of adaptation to abiotic stresses via changes in critical developmental stages. Altering flowering phenology is a key evolutionary strategy of plant adaptation to abiotic stresses in order to achieve maximum possible reproduction. The current study is the first to apply the linear regression residuals as a drought plasticity scores, while taking into account the differences in flowering phenology and trait variation under non-stress conditions. We characterized the genomic architecture of 17 complex traits and their drought plasticity using a mapping population derived from a cross between durum wheat (Triticum durum) and wild emmer wheat (T. dicoccoides). We identified 79 QTLs, of which 33 were plastic in response to water stress and exhibited epistatic interactions and/or pleiotropy between the initial and plasticity traits.Vrn-B3 (TaTF1)residing within an interval of a major drought-escape QTL was proposed as a candidate gene. The favorable alleles for most of the plasticity QTLs were contributed by wild emmer, demonstrating the high potential of wild relatives for wheat improvement. Our study presents a new approach for quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.

Highlight

The study presents a new approach for quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.
Postural Representations of the Hand in Primate Sensorimotor Cortex
Authors: Goodman James M. , Tabot Gregg A. , Lee Alex S. , Suresh Aneesha K. , Rajan Alexander T. , Hatsopoulos Nicholas G. , Bensmaia Sliman J.
Published: March 2019

Dexterous hand control requires not only a sophisticated motor system but also a sensory system to provide tactile and proprioceptive feedback. To date, the study of the neural basis of proprioception in cortex has focused primarily on reaching movements, at the expense of hand-specific behaviors such as grasp. To fill this gap, we record both the time-varying hand kinematics and the neural activity evoked in somatosensory and motor cortices as monkeys grasp a variety of different objects. We find that neurons in somatosensory cortex, as well as in motor cortex, preferentially track postures of multi-joint combinations spanning the entire hand. This contrasts with neural responses during reaching movements, which preferentially track movement kinematics of the arm rather than its postural configuration. These results suggest different representations of arm and hand movements likely adapted to suit the different functional roles of these two effectors.
HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation
Authors: van Dierendonck Xanthe A.M.H. , de la Rosa Rodriguez Montserrat A. , Georgiadi Anastasia , Mattijssen Frits , Dijk Wieneke , van Weeghel Michel , Singh Rajat , Borst Jan Willem , Stienstra Rinke , Kersten Sander
Published: March 2019

Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.
The neurofunctional basis of affective startle modulation in humans – evidence from combined facial EMG-fMRI
Authors: Kuhn Manuel , Wendt Julia , Sjouwerman Rachel , Büchel Christian , Hamm Alfons , Lonsdorf Tina B.
Published: March 2019

The startle reflex, a protective response elicited by an immediate, unexpected sensory event, ispotentiatedwhen evoked during threat andinhibitedduring safety. In contrast to skin conductance responses or pupil dilation, modulation of the startle reflex is valence-specific and consideredthecross-species translational tool for defensive responding.

Rodent models implicate a modulatory pathway centering on the brainstem (i.e., nucleus reticularis pontis caudalis, PnC) and the centromedial amygdala (CeM) as key hubs for flexibly integrating valence information into differential startle magnitude.

We employed innovative combined EMG-fMRI measurements in two independent experiments and samples and provide converging evidence for the involvement of these key regions in the modulatory acoustic startle reflex pathway in humans. Furthermore, we provide the crucial direct link between EMG startle eye-blink magnitude and neural response strength.

We argue that startle-evoked amygdala responding and its affective modulation may hold promise as an important novel tool for affective neuroscience.
Translational products encoded by novel ORFs may form protein-like structures and have biological functions
Authors: Erady Chaitanya , Chong David , Meena Narendra , Puntambekar Shraddha , Chauhan Ruchi , Umrania Yagnesh , Andreani Adam , Nel Jean , Wayland Matthew T. , Pina Cristina , Lilley Kathryn S. , Prabakaran Sudhakaran
Published: March 2019

Translation products encoded by non canonical or novel open reading frame (ORF) genomic regions are generally considered too small to play any significant biological role, and dismissed as inconsequential. In this study, we show that mutations mapping to novel ORFs have significantly higher pathogenicity scores than mutations in protein-coding regions. Importantly, novel ORFs can translate into protein-like structures with putative independent biological functions that can be of relevance in disease states, including cancer. We thus provide strong evidence to support the systematic study of novel ORFs to gain new insights into normal biological and disease processes.

One Sentence Summary

Non coding regions may encode protein-like products that are important to understand diseases.
Dynamic neuronal activation of a distributed cortico-basal ganglia-thalamus loop in learning a delayed sensorimotor task
Authors: Gu Xiaowei , Li Chengyu T.
Published: March 2019

The cortico-basal ganglia-thalamus (CBT) loop is important for behavior. However, the activity and learning-related modulation within the loop in behavior remain unclear. To tackle this problem, we trained mice to perform a delayed sensorimotor-transformation task and recorded single-unit activity during learning simultaneously from four regions in a CBT loop: prelimbic area (PrL), posterior premotor cortex (pM2), dorsomedial caudate/putamen (dmCP), and mediodorsal thalamus (MD). Sensory and decision related information were encoded by the neurons within the loop, with weak interaction among neurons of different coding ability. The functional interaction among regions within the loop was dynamically routed in the loop during different behavioral phases and contributed to explain decision-related neuronal activity. The neurons of PrL and dmCP exhibited learning-related reorganization in neuronal activity and more persistent coding of sensory and decision-related information. Thus, both sensory- and decision-related information are processed in a functionally interacted CBT loop that is modulated by learning.
Mechanics of wood boring by beetle mandibles
Authors: Kundanati Lakshminath , Chahare Nimesh R. , Jaddivada Siddhartha , Karkisaval Abhijith G. , Pugno Nicola M. , Gundiah Namrata
Published: March 2019

Wood boring is a feature of several insect species and is a major cause of severe and irreparable damage to trees. Adult females typically deposit their eggs on the stem surface under bark scales. The emerging hatchlings live within hard wood during their larval phase, avoiding possible predation, whilst continually boring and tunneling through wood until pupation. A study of wood boring by insects offers unique insights into the bioengineering principles that drive evolutionary adaptations. We show that larval mandibles of the coffee wood stem borer beetle (Xylotrechus quadripes: Cerambycidae) have a highly sharp cusp edge to initiate fractures inArabicawood and a suitable shape to generate small wood chips that are suitable for digestion. Cuticle hardness at the tip is significantly enhanced through zinc-enrichment. Finite element model of the mandible, based on the differential material properties at the tip, intermediate and base regions of the mandible, showed highest stresses in the tip region; these decreased to significantly lower values at the start of the hollow section. A hollow architecture significantly reduces bending stresses at mandibular base without compromising the structural integrity. A scaling model based on a fracture mechanics framework shows the importance of the mandible shape in generating optimal chip sizes. These findings contain general principles in tool design and put in focus interactions of insects and their woody hosts.
Human liver organoids; a patient-derived primary model for HBV Infection and Related Hepatocellular Carcinoma
Authors: Crignis Elisa De , Romal Shahla , Carofiglio Fabrizia , Moulos Panagiotis , Verstegen Monique M.A. , Khalid Mir Mubashir , Pourfarzad Farzin , Rao Shringar , Bazrafshan Ameneh , Koutsothanassis Christina , Gehart Helmuth , Kan Tsung Wai , Palstra Robert-Jan , Boucher Charles , IJzermans Jan M.N. , Huch Meritxell , Boj Sylvia F. , Vries Robert , Clevers Hans , van der Laan Luc , Hatzis Pantelis , Mahmoudi Tokameh
Published: March 2019

The molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV infected organoids produced cccDNA, expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity as well as for drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor NTCP by lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for disease surveillance and development of HCC in HBV infected patients.
Single-Organelle Quantification Reveals Stoichiometric and Structural Variability of Carboxysomes Dependent on the Environment
Authors: Sun Yaqi , Wollman Adam J. M. , Huang Fang , Leake Mark C. , Liu Lu-Ning
Published: March 2019

The carboxysome is a complex, proteinaceous organelle that plays essential roles in carbon assimilation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble in space to form an icosahedral structure. Despite its significance in enhancing CO2fixation and potentials in bioengineering applications, the formation of carboxysomes and their structural composition, stoichiometry and adaptation to cope with environmental changes remain unclear. Here we use live-cell single-molecule fluorescence microscopy, coupled with confocal and electron microscopy, to decipher the absolute protein stoichiometry and organizational variability of single β-carboxysomes in the model cyanobacteriumSynechococcus elongatusPCC7942. We determine the physiological abundance of individual building blocks within the icosahedral carboxysome. We further find that the protein stoichiometry, diameter, localization and mobility patterns of carboxysomes in cells depend sensitively on the microenvironmental levels of CO2and light intensity during cell growth, revealing cellular strategies of dynamic regulation. These findings, also applicable to other bacterial microcompartments and macromolecular self-assembling systems, advance our knowledge of the principles that mediate carboxysome formation and structural modulation. It will empower rational design and construction of entire functional metabolic factories in heterologous organisms, for example crop plants, to boost photosynthesis and agricultural productivity.

One Sentence Summary

Determination of absolute protein stoichiometry reveals the organizational variability of carboxysomes in response to microenvironmental changes

The authors responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Author (www.plantcell.org) is: Lu-Ning Liu (luning.liu@liverpool.ac.uk).
The inflammasome of circulatory collapse: single cell analysis of survival on extracorporeal life support
Authors: Kort Eric J. , Weiland Matthew , Grins Edgars , Eugster Emily , Milliron Hsiao-yun , Kelty Catherine , Shrestha Nabin Manandhar , Timek Tomasz , Leacche Marzia , Fitch Stephen J , Boeve Theodore J , Marco Greg , Dickinson Michael , Wilton Penny , Jovinge Stefan
Published: March 2019

Background

Despite being a lifesaving intervention for the most critically ill and circulatory compromised patients, veno-arterial extra-corporeal life support (VA-ECLS) is associated with a mortality rate of nearly 60%. Understanding how the immune response to VA-ECLS either promotes or impedes survival would both enhance risk stratification and uncover new therapeutic strategies for these patients. However, conventional enumeration of peripheral blood mononuclear cells (PBMCs) and their subsets have failed to identify determinants of outcome among these cells.

Methods

Flow cytometry and plasma cytokine measurement was combined with single cell RNASeq analysis of PBMCs from patients in circulatory shock being started on VA-ECLS to identify clinical, laboratory, and cellular features associated with 72 hour survival.

Results

Non-surviving patients exhibited higher plasma levels of the tissue aggressive inflammatory cytokines IL-1, IL-6, IL-12 and TNF-α. Distribution of cells between conventional PBMC subtypes was not predictive of survival. Single cell RNASeq analysis of discriminatory markers within each PBMC subtype revealed that the proportion of CD8+ Natural Killer T-cells (NKT) that expressed CD52, a known immune-modulator, was associated with improved survival. This cell population correlated inversely with IL-6 production. CD8+/CD52+ NKT cells were quantified by flow cytometry in a second, validation cohort. Those patients with a high proportion of CD52+ cells among all CD8+ NKT cells had more severe disease relative to the low CD52+ group, but nevertheless were nearly 5 time less likely to die in the first 72 hours of VA-ECLS (p=0.043 by log rank test).

Conclusions

CD8+/CD52+ NKT cells are associated with survival in patients undergoing VA-ECLS. Fluidics based scRNASeq can reveal important aspects of pathophysiology in complex disease states such as circulatory collapse and VA-ECLS. Further studies in animal models will be required to determine if stimulation of CD8+/CD52+ NKT cell expansion may be an effective therapeutic strategy in this patient population.