bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective risk aversion in thin risk‐sharing markets
Authors: Anthropelos Michail , Kardaras Constantinos , Vichos Georgios
Published: April 2020

We consider thin incomplete financial markets, where traders with heterogeneous preferences and risk exposures have motive to behave strategically regarding the demand schedules they submit, thereby impacting prices and allocations. We argue that traders relatively more exposed to the market portfolio tend to behave in a more risk tolerant manner. Noncompetitive equilibrium prices and allocations result as an outcome of a game among traders. General sufficient conditions for existence and uniqueness of such equilibrium are provided, with extensive analysis of two‐trader transactions. Even though strategic behavior causes inefficient social allocations, traders with sufficiently high risk tolerance and/or high initial exposure to tradable securities obtain more utility gain in the noncompetitive equilibrium, when compared to the competitive one.
Microbiome maturation during a unique developmental window
Authors: Videvall Elin
Published: April 2020

Shortly after birth, mammals are colonized by a multitude of microbes derived from the mother and the environment. Studies in model organisms have demonstrated that the structure and composition of the gut microbiome of offspring steadily mature with increasing diversity during nursing and weaning (Sommer & Bäckhed, 2013). This period of microbiome assembly is critical for young mammals because the gut microbes they acquire will help train their immune system (Lathrop et al., 2011) with potential long‐lasting effects on their health (Cox et al., 2014). In an article in this issue of Molecular Ecology, Stoffel et al. (2020) investigated the gut microbiota of northern elephant seals (Mirounga angustirostris) during a key developmental window. A month after giving birth, elephant seal mothers stop nursing their pups and return to the sea. As a consequence, their pups go from a diet of milk rich in fat to abruptly enter a post weaning fasting period which lasts for about two months while they remain with the colony. This particular life‐history trait therefore offered the authors a unique and exciting opportunity to evaluate intrinsic factors contributing to gut microbiota development in a wild marine mammal.
Plasma proteomic profiles differ between European and North American myotid bats colonized by Pseudogymnoascus destructans
Authors: Hecht‐Höger Alexander M. , Braun Beate C. , Krause Eberhard , Meschede Angelika , Krahe Rüdiger , Voigt Christian C. , Greenwood Alex D. , Czirják Gábor Á.
Published: April 2020

Emerging fungal diseases have become challenges for wildlife health and conservation. North American hibernating bat species are threatened by the psychrophilic fungus Pseudogymnoascus destructans (Pd) causing the disease called white‐nose syndrome (WNS) with unprecedented mortality rates. The fungus is widespread in North America and Europe, however, disease is not manifested in European bats. Differences in epidemiology and pathology indicate an evolution of resistance or tolerance mechanisms towards Pd in European bats. We compared the proteomic profile of blood plasma in healthy and Pd‐colonized European Myotis myotis and North American Myotis lucifugus in order to identify pathophysiological changes associated with Pd colonization, which might also explain the differences in bat survival. Expression analyses of plasma proteins revealed differences in healthy and Pd‐colonized M. lucifugus, but not in M. myotis. We identified differentially expressed proteins for acute phase response, constitutive and adaptive immunity, oxidative stress defence, metabolism and structural proteins of exosomes and desmosomes, suggesting a systemic response against Pd in North American M. lucifugus but not European M. myotis. The differences in plasma proteomic profiles between European and North American bat species colonized by Pd suggest European bats have evolved tolerance mechanisms towards Pd infection.
A type VI secretion system delivers a cell wall amidase to target bacterial competitors
Authors: Wang Tietao , Hu Zhaoyu , Du Xiao , Shi Yue , Dang Jing , Lee Mijoon , Hesek Dusan , Mobashery Shahriar , Wu Min , Liang Haihua
Published: April 2020

The human pathogen Pseudomonas aeruginosa harbors three paralogous zinc proteases annotated as AmpD, AmpDh2, and AmpDh3, which turn over the cell wall and cell wall‐derived muropeptides. AmpD is cytoplasmic and plays a role in the recycling of cell wall muropeptides, with a link to antibiotic resistance. AmpDh2 is a periplasmic soluble enzyme with the former anchored to the inner leaflet of the outer membrane. We document, herein, that the type VI secretion system locus II (H2‐T6SS) of P. aeruginosa delivers AmpDh3 (but not AmpD or AmpDh2) to the periplasm of a prey bacterium upon contact. AmpDh3 hydrolyzes the cell wall peptidoglycan of the prey bacterium, which leads to its killing, thereby providing a growth advantage for P. aeruginosa in bacterial competition. We also document that the periplasmic protein PA0808, heretofore of unknown function, affords self‐protection from lysis by AmpDh3. Cognates of the AmpDh3‐PA0808 pair are widely distributed across Gram‐negative bacteria. Taken together, these findings underscore the importance of their function as an evolutionary advantage and that of the H2‐T6SS as the means for the manifestation of the effect.
Plant nutrient‐acquisition strategies drive topsoil microbiome structure and function
Authors: Bahram Mohammad , Netherway Tarquin , Hildebrand Falk , Pritsch Karin , Drenkhan Rein , Loit Kaire , Anslan Sten , Bork Peer , Tedersoo Leho
Published: April 2020

Plant nutrient‐acquisition strategies drive soil processes and vegetation performance, but their effect on the soil microbiome remains poorly understood. This knowledge is important to predict the shifts in microbial diversity and functions due to increasing changes in vegetation traits under global change.

Here we documented the topsoil microbiomes of 145 boreal and temperate terrestrial sites in the Baltic region that broadly differed in vegetation type and nutritional traits, such as mycorrhizal types and symbiotic nitrogen‐fixation.

We found that sites dominated by arbuscular mycorrhizal (AM) vegetation harbor relatively more AM fungi, bacteria, fungal saprotrophs, and pathogens in the topsoil compared with sites dominated by ectomycorrhizal (EM) plants. These differences in microbiome composition reflect the rapid nutrient cycling and negative plant–soil feedback in AM soils. Lower fungal diversity and bacteria : fungi ratios in EM‐dominated habitats are driven by monodominance of woody vegetation as well as soil acidification by EM fungi, which are associated with greater diversity and relative abundance of carbohydrate‐active enzymes.

Our study suggests that shifts in vegetation related to global change and land use may strongly alter the topsoil microbiome structure and function.
Cherry picking by pseudomonads: After a century of research on canker, genomics provides insights into the evolution of pathogenicity towards stone fruits
Authors: Hulin Michelle T. , Jackson Robert W. , Harrison Richard J. , Mansfield John W.
Published: April 2020

Bacterial canker disease is a major limiting factor in the growing of cherry and otherPrunusspecies worldwide. At least five distinct clades within the bacterial species complexPseudomonas syringaeare known to be causal agents of the disease. The different pathogens commonly coexist in the field. Reducing canker is a challenging prospect as the efficacy of chemical controls and host resistance may vary against each of the diverse clades involved. Genomic analysis has revealed that the pathogens use a variable repertoire of virulence factors to cause the disease. Significantly, strains ofP.syringaepv.syringaepossess more genes for toxin biosynthesis and fewer encoding type III effector proteins. There is also a shared pool of key effector genes present on mobile elements such as plasmids and prophages that may have roles in virulence. By contrast, there is evidence that absence or truncation of certain effector genes, such ashopAB, is characteristic of cherry pathogens. Here we highlight how recent research, underpinned by the earlier epidemiological studies, is allowing significant progress in our understanding of the canker pathogens. This fundamental knowledge, combined with emerging insights into host genetics, provides the groundwork for development of precise control measures and informed approaches to breed for disease resistance.
Anti‐Mullerian hormone and its relationship to ovulation response and fertility in timed AI Bos indicus heifers
Authors: Batista Emiliana O. S. , Vieira Lais M. , Freitas Bruno G. , Guerreiro Bruna M. , Carvalho J. G. S. , Mingoti Rodolfo D. , Vasconcellos Guilherme , Souza Alexandre H. , Bento Sterman Ferraz Jose , Sampaio Baruselli Pietro
Published: April 2020

This study evaluated the association between plasma anti‐Mullerian hormone (AMH) concentration and fertility in Nelore (Bos indicus) heifers submitted to timed artificial insemination (TAI). At the onset of the synchronization protocol, heifers (n = 289) received a subcutaneous P4 ear implant (3 mg) and 2 mg of oestradiol benzoate. Eight days later, the P4 implant was removed and 0.5 mg of oestradiol cypionate, prostaglandin (0.265 mg, i.m.) and equine chorionic gonadotropin (300 UI, i.m.) was administered, and TAI was performed 48 hr after ear implant removal. Ovarian ultrasound evaluations were performed to measure number of ovarian follicles, dominant follicle size and ovulation response. Pregnancy diagnosis was performed by ultrasound 30 days after AI. Heifers with greater circulating AMH had more antral follicles, a smaller dominant follicle near timed ovulation and lower ovulation response to the timed AI protocol compared to heifers with lower circulating AMH. Although AMH and pregnancy outcome had a quadratic‐shaped pattern, AMH was not significantly associated with fertility. In conclusion, heifers with lower AMH had larger follicles towards the end of the synchronization protocol and greater ovulation responses, whereas greater circulating AMH was unrelated to conception success.
Individualistic and Collectivistic Orientations: Examining the Relationship between Ethnicity and National Attachment in Ghana
Authors: Asante Kofi Takyi
Published: April 2020

Ethnicity is regarded as the greatest threat to national attachment by both politicians and scholars. However, ethnicity is only one of the many forms of identification which could potentially clash with national attachment. This study therefore examines the relationship between ethnicity and national attachment by asking a general question: what is the impact of alternative group loyalties on national attachment? To answer this question, I develop a measure of national attachment drawing on several sentiments oriented towards the state. Using a survey of 996 university students, I find varying degrees of intensity of the selected identities. Specifically, while descriptive analysis supports recent reports of the declining salience of ethnicity in Ghana, inferential analysis contradicts theoretical expectations that the increasing salience of ethnicity would negatively affect national attachment. Conceptually, it is possible to map the various identities onto a collectivistic‐individualistic scale. Individualistic orientations undermine national attachment, while collectivistic orientations boost it. I argue that rather than being contradictory impulses, ethnicity and national attachment are both underlain by the same collectivistic orientation, pointing to the importance of social rootedness. I deploy qualitative and historical data to give substance and texture to these findings.
On T cell development, T cell signals, T cell specificity and sensitivity, and the autoimmunity facilitated by lymphopenia
Authors: Bretscher Peter A. , Al‐Yassin Ghassan , Anderson Colin C.
Published: April 2020

We propose a framework to explain how T cells achieve specificity and sensitivity, how the affinity of the TcR peptide/MHC interaction controls positive and negative thymic selection and mature T cell survival, and whether antigen‐dependent activation and inactivation takes place. Two distinct types of signalling can lead to mature T cell multiplication. One requires the TcR to recognize with a certain affinity an antigen‐derived peptide, an agonist peptide, bound to an MHC molecule. The other, the tonic signal, leads to naïve T cell survival and modest proliferation if the T cell successfully competes for endogenous, self‐peptide/MHC ligands, involving lower affinity TCR/ligand interactions. Many suggest lymphopenia contributes to autoimmunity by increasing the strength of TcR‐tonic signalling, and so activation of anti‐self T cells. We suggest T cell activation requires antigen‐mediated cooperation between T cells. Increased tonic signalling under lymphopenic conditions facilitates T cell proliferation and so antigen‐dependent cooperation and activation of anti‐self T cells.
Is there rationale for the cuff pressures prescribed for blood flow restriction exercise? A systematic review
Authors: Clarkson Matthew J. , May Anthony K. , Warmington Stuart A.
Published: April 2020

Background

Blood flow restriction exercise has increasingly broad applications among healthy and clinical populations. Ensuring the technique is applied in a safe, controlled, and beneficial way for target populations is essential. Individualized cuff pressures are a favored method for achieving this. However, there remains marked inconsistency in how individualized cuff pressures are applied.

Objectives

To quantify the cuff pressures used in the broader blood flow restriction exercise literature, and determine whether there is clear justification for the choice of pressure prescribed.

Methods

Studies were included in this review from database searches if they employed an experimental design using original data, involved either acute or chronic exercise using blood flow restriction, and they assessed limb or arterial occlusion pressure to determine an individualized cuff pressure. Methodologies of the studies were evaluated using a bespoke quality assessment tool.

Results

Fifty‐one studies met the inclusion criteria. Individualized cuff pressures ranged from 30% to 100% arterial occlusion pressure. Only 7 out of 52 studies attempted to justify the individualized cuff pressure applied during exercise. The mean quality rating for all studies was 11.1 ± 1.2 out of 13.

Conclusions

The broader blood flow restriction exercise literature uses markedly heterogeneous prescription variables despite using individualized cuff pressures. This is problematic in the absence of any clear justification for the individualized cuff pressures selected. Systematically measuring and reporting all relevant acute responses and training adaptations to the full spectrum of BFR pressures alongside increased clarity around the methodology used during blood flow restriction exercise is paramount.
Different eplet software programs give discordant and incorrect results: An analysis of HLAMatchmaker vs Fusion Matchmaker Eplet calling software
Authors: Tassone Gabriella , De Santis Dianne , Vukovic Irena , Downing Jonathan , Martinez Olga Patricia , D'Orsogna Lloyd J.
Published: April 2020

HLA eplet matching is a novel approach to define acceptable HLA mismatches for transplant recipients. We performed an eplet analysis of three different transplant case‐series to determine if the available software programs gave accurate results. Eplet analysis was performed for three different transplant case‐series typed by NGS for all HLA class I and II loci. The three different HLA datasets were entered into both the HLAMatchmaker program (v2.1) and OLI Fusion MatchMaker (v4.2) software tools. Eplet results which were discordant were cross referenced against eplet registry and published HLA allele sequence data to determine the correct assignments. The comparison reveals that there was poor concordance between the two eplet programs. Analysis of the same donor/recipient pair often gave rise to different total eplet scores, incorrect eplet mismatches and antibody verification status, and both programs have eplets assigned to incorrect HLA alleles. Overall, the OLI Fusion MatchMaker eplet tool gave more accurate and useful eplet results. Eplet matching is still primarily a research tool. Before eplet matching can enter routine clinical practice further work is required to validate the accuracy of available eplet software programs. Incorrect eplet assignment could have serious adverse consequences in the clinical transplant setting.
Threatening drug‐drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID‐19)
Authors: Bartiromo Marilù , Borchi Beatrice , Botta Annarita , Bagalà Alfredo , Lugli Gianmarco , Tilli Marta , Cavallo Annalisa , Xhaferi Brunilda , Cutruzzulà Roberta , Vaglio Augusto , Bresci Silvia , Larti Aida , Bartoloni Alessandro , Cirami Calogero
Published: April 2020

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long‐term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36‐year‐old kidney‐transplanted woman affected by Senior‐Loken syndrome diagnosed with COVID‐19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID‐19 infection with particular regard to the management of therapy.
The Arabidopsis transcription factor AINTEGUMENTA orchestrates patterning genes and auxin signaling in the establishment of floral growth and form
Authors: Krizek Beth A. , Blakley Ivory C. , Ho Yen‐Yi , Freese Nowlan , Loraine Ann E.
Published: April 2020

Understanding how flowers form is an important problem in plant biology, as human food supply depends on flower and seed production. Flower development also provides an excellent model for understanding how cell division, expansion and differentiation are coordinated during organogenesis. In the model plant Arabidopsis thaliana, floral organogenesis requires AINTEGUMENTA (ANT) and AINTEGUMENTA‐LIKE 6 (AIL6)/PLETHORA 3 (PLT3), two members of the Arabidopsis AINTEGUMENTA‐LIKE/PLETHORA (AIL/PLT) transcription factor family. Together, ANT and AIL6/PLT3 regulate aspects of floral organogenesis, including floral organ initiation, growth, identity specification and patterning. Previously, we used RNA‐Seq to identify thousands of genes with disrupted expression in ant ail6 mutant flowers, indicating that ANT and AIL6/PLT3 influence a vast transcriptional network. The immediate downstream targets of ANT and AIL6/PLT3 in flowers are unknown, however. To identify direct targets of ANT regulation, we performed an RNA‐Seq time‐course experiment in which we induced ANT activity in transgenic plants bearing an ANT‐glucocorticoid receptor fusion construct. In addition, we performed a ChIP‐Seq experiment that identified ANT binding sites in developing flowers. These experiments identified 200 potential ANT target genes based on their proximity to ANT binding sites and differential expression in response to ANT. These 200 candidate target genes were involved in functions such as polarity specification, floral organ development, meristem development and auxin signaling. In addition, we identified several genes associated with lateral organ growth that may mediate the role of ANT in organ size control. These results reveal new features of the ANT transcriptional network by linking ANT to previously unknown regulatory targets.
Optimization of Fin Parameters to Reduce Entropy Generation and Melting Time of a Latent Heat Storage Unit
Authors: Kalapala Lokesh , Devanuri Jaya Krishna
Published: April 2020

One of the challenges in the design and development of a latent heat storage unit (LHSU) is to increase the charging and discharging rates which are inherently low because of low thermal conductivity of phase change materials (PCM). Out of various heat transfer enhancement techniques, employing annular fins is very simple, efficient and no fabrication complexity is involved. Fin parameters (fin size and number of fins) significantly influence the enhancement in heat transfer rate. Hence, optimization of fin parameters is necessary for the efficient design of an LHSU. While designing an LHSU along with heat transfer rate, entropy generation should also be considered in order to make it exergetically efficient. Therefore, the present study is aimed at multi-objective optimization of annular fin parameters to minimize the melting time and entropy generation. Fin diameter and the number of fins are taken as the variables. The influence of these two variables on the melting time, average Nusselt number, energy stored, and distribution of entropy is presented. The melting rate is increased, and global entropy generation decreased by increasing the number of fins up to 15. An increase in the fin diameter reduced the melting time while entropy generation got increased. For the multi-objective optimization, the multi-objective optimization based on ratio analysis (MOORA) technique is chosen and the optimized values of fin diameter and number of fins are observed to be 80 mm and 15 respectively. Finally, optimized parameters are represented in non-dimensional form to make them applicable for any size of the LHSU.
Low Intensity Ultrasound Induces Epithelial Cell Adhesion Responses
Authors: Lim Jormay , Chu Yeh-Shiu , Chu Ya-Cherng , Lo Chun-Min , Wang Jaw-Lin
Published: April 2020

In this study, we investigated the cellular mechanosensitive responses to a low intensity ultrasound (LIUS) stimulation (ISATA = 1 mW/cm2, pressure = 10 kPa). The dose and temporal effects at cell–substrate adhesion (CSA) at the basal level and cell–cell adhesion (CCA) at the apical level are reported in detail. A model of mouse mammary gland epithelial cells (EpH4) and the phosphorylation of mechanosensitive 130 kDa Crk-associated substrate (p130CAS) as an indicator for cellular responses were used. The intensity of phospho-p130CAS was found to be dependent on LIUS stress level, and the p130CAS was phosphorylated after 1 min stimulation at CSA. The phospho-p130CAS was also found to increase significantly at CCA upon LIUS stimulation. We confirmed that the cellular responses to ultrasound are immediate and dose dependent. Ultrasound affects not only CSA but also CCA. An E-cadherin knockout (EpH4ECad−/−) model also confirmed that phosphorylation of p130CAS at CCA is related to E-cadherins.
Estimation of Minimum Design Metal Temperature by MDMT Curve and Correlations of Charpy Impact and Fracture Toughness
Authors: Zhou Zhongqiang , Huang Song , Hui Hu , Zhang Yalin
Published: April 2020

Charpy impact specimens are preferred to characterize the deterioration of steel in irradiation surveillance program in nuclear industry. But the fracture toughness cannot be acquired by the Charpy impact experiment directly. In this paper, the reference temperature T0MC of Q345R and A508-3 are determined by experiment and empirical formulas between Charpy impact energy (CVN) and fracture toughness. The measured values of T0MC are compared with predicted values. Empirical formulas combined with minimum design metal temperature (MDMT) curve is put forward to determine the minimum design metal temperature of ferritic steel conservatively.
Identification of a Cytopathogenic Toxin from Sneathia amnii
Authors: Gentile Gabriella L. , Rupert Amy Sanford , Carrasco Lizette I. , Garcia Erin M. , Kumar Naren Gajenthra , Walsh Scott W. , Jefferson Kimberly K.
Published: April 2020

Sneathia amnii is a poorly characterized emerging pathogen that has been implicated in amnionitis and urethritis. We found that S. amnii damages fetal membranes, and we identified and purified a cytotoxic exotoxin that lyses human red blood cells and damages cells from fetal membranes. The gene appears to be cotranscribed with a second gene that encodes a protein with identity to two-partner system transporters, suggesting that it is the “A,” or secreted component of a type Vb system. The toxin is 1,881 amino acids with a molecular weight of approximately 200 kDa. It binds to red blood cell membranes and forms pores with a diameter of 2.0 to 3.0 nm, resulting in osmolysis. Because it appears to be the “A” or passenger component of a two-partner system, we propose to name this novel cytotoxin/hemolysin CptA for cytopathogenic toxin component A.

IMPORTANCE Sneathia amnii is a very poorly characterized emerging pathogen that can affect pregnancy outcome and cause urethritis and other infections. To date, nothing is known about its virulence factors or pathogenesis. We have identified and isolated a cytotoxin, named CptA for cytopathogenic toxin, component A, that is produced by S. amnii. CptA is capable of permeabilizing chorionic trophoblasts and lysing human red blood cells and, thus, may play a role in virulence. Except for small domains conserved among two-partner secretion system passenger proteins, the cytotoxin exhibits little amino acid sequence homology to known toxins. In this study, we demonstrate the pore-forming activity of this novel toxin.
Francisella novicida CRISPR-Cas Systems Can Functionally Complement Each Other in DNA Defense while Providing Target Flexibility
Authors: Ratner Hannah K. , Weiss David S.
Published: April 2020

CRISPR-Cas systems are prokaryotic adaptive immune systems that facilitate protection of bacteria and archaea against infection by external mobile genetic elements. The model pathogen Francisella novicida encodes a CRISPR-Cas12a (FnoCas12a) system and a CRISPR-Cas9 (FnoCas9) system, the latter of which has an additional and noncanonical function in bacterial virulence. Here, we investigated and compared the functional roles of the FnoCas12a and FnoCas9 systems in transformation inhibition and bacterial virulence. Unlike FnoCas9, FnoCas12a was not required for F. novicida virulence. However, both systems were highly effective at plasmid restriction and acted independently of each other. We further identified a critical protospacer-adjacent motif (PAM) necessary for transformation inhibition by FnoCas12a, demonstrating a greater flexibility for target identification by FnoCas12a than previously appreciated and a specificity that is distinct from that of FnoCas9. The effectors of the two systems exhibited different patterns of expression at the mRNA level, suggesting that they may confer distinct benefits to the bacterium in diverse environments. These data suggest that due to the differences between the two CRISPR-Cas systems, together they may provide F. novicida with a more comprehensive defense against foreign nucleic acids. Finally, we demonstrated that the FnoCas12a and FnoCas9 machineries could be simultaneously engineered to restrict the same nonnative target, thereby expanding the toolset for prokaryotic genome manipulation.

IMPORTANCE CRISPR-Cas9 and CRISPR-Cas12a systems have been widely commandeered for genome engineering. However, they originate in prokaryotes, where they function as adaptive immune systems. The details of this activity and relationship between these systems within native host organisms have been minimally explored. The human pathogen Francisella novicida contains both of these systems, with the Cas9 system also exhibiting a second activity, modulating virulence through transcriptional regulation. We compared and contrasted the ability of these two systems to control virulence and restrict DNA within their native host bacterium, highlighting differences and similarities in these two functions. Collectively, our results indicate that these two distinct and reprogrammable endogenous systems provide F. novicida with a more comprehensive defense against mobile genetic elements.
Global Regulatory Roles of the Histidine-Responsive Transcriptional Repressor HutC in Pseudomonas fluorescens SBW25
Authors: Naren Naran , Zhang Xue-Xian
Published: April 2020

HutC is known as a transcriptional repressor specific for histidine utilization (hut) genes in Gram-negative bacteria, including Pseudomonas fluorescens SBW25. However, its precise mode of protein-DNA interactions hasn’t been examined with purified HutC proteins. Here, we performed electrophoretic mobility shift assay (EMSA) and DNase I footprinting using His6-tagged HutC and biotin-labeled probe of the hut promoter (PhutU). Results revealed a complex pattern of HutC oligomerization, and the specific protein-DNA interaction is disrupted by urocanate, a histidine derivative, in a concentration-dependent manner. Next, we searched for putative HutC-binding sites in the SBW25 genome. This led to the identification of 143 candidate targets with a P value less than 10−4. HutC interaction with eight selected candidate sites was subsequently confirmed by EMSA analysis, including the type IV pilus assembly protein PilZ, phospholipase C (PlcC) for phosphatidylcholine hydrolyzation, and key regulators of cellular nitrogen metabolism (NtrBC and GlnE). Finally, an isogenic hutC deletion mutant was subjected to transcriptome sequencing (RNA-seq) analysis and phenotypic characterization. When bacteria were grown on succinate and histidine, hutC deletion caused upregulation of 794 genes and downregulation of 525 genes at a P value of <0.05 with a fold change cutoff of 2.0. The hutC mutant displayed an enhanced spreading motility and pyoverdine production in laboratory media, in addition to the previously reported growth defect on the surfaces of plants. Together, our data indicate that HutC plays global regulatory roles beyond histidine catabolism through low-affinity binding with operator sites located outside the hut locus.

IMPORTANCE HutC in Pseudomonas is a representative member of the GntR/HutC family of transcriptional regulators, which possess a N-terminal winged helix-turn-helix (wHTH) DNA-binding domain and a C-terminal substrate-binding domain. HutC is generally known to repress expression of histidine utilization (hut) genes through binding to the PhutU promoter with urocanate (the first intermediate of the histidine degradation pathway) as the direct inducer. Here, we first describe the detailed molecular interactions between HutC and its PhutU target site in a plant growth-promoting bacterium, P. fluorescens SBW25, and further show that HutC possesses specific DNA-binding activities with many targets in the SBW25 genome. Subsequent RNA-seq analysis and phenotypic assays revealed an unexpected global regulatory role of HutC for successful bacterial colonization in planta.
Varicella-Zoster Virus (VZV) Small Noncoding RNAs Antisense to the VZV Latency-Encoded Transcript VLT Enhance Viral Replication
Authors: Bisht Punam , Das Biswajit , Kinchington Paul R. , Goldstein Ronald S.
Published: April 2020

Varicella-zoster virus (VZV) causes herpes zoster, a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNA) are recognized as important actors in modulating gene expression. This study extends our previous work and shows that four VZVsncRNA clustering in and near ORF61 and antisense to the latency-associated transcript of VZV can positively influence productive VZV infection. The ability of multiple exogenous small oligonucleotides targeting VZVsncRNA to inhibit VZV replication strengthens the possibility that they may inform development of novel treatments for painful herpes zoster.
Energetic Basis of Microbial Growth and Persistence in Desert Ecosystems
Authors: Leung Pok Man , Bay Sean K. , Meier Dimitri V. , Chiri Eleonora , Cowan Don A. , Gillor Osnat , Woebken Dagmar , Greening Chris
Published: April 2020

Microbial life is surprisingly abundant and diverse in global desert ecosystems. In these environments, microorganisms endure a multitude of physicochemical stresses, including low water potential, carbon and nitrogen starvation, and extreme temperatures. In this review, we summarize our current understanding of the energetic mechanisms and trophic dynamics that underpin microbial function in desert ecosystems. Accumulating evidence suggests that dormancy is a common strategy that facilitates microbial survival in response to water and carbon limitation.
The exhumation detachment factory
Authors: Peron-Pinvidic Gwenn , Naliboff John
Published: April 2020

Rifted margins include series of tectonic structures and basement geometries that record the thinning of continental crust and the birth of oceanic spreading centers. A consensus has been reached on the fact that the evolution is composite, including a phase of basement exhumation during which detachment faults play a major role. Rolling-hinge–type models are often advocated as the driving mechanism for basement exhumation, although the structural complexity of the exhumed regions frequently prohibits detailed analysis of the ways in which the faults form and evolve through time. Here, we place constraints on this process through an analysis of continental rifting numerical simulations, which we used to map fault network activity. The high-resolution models and mapping reveal a specific weak surface where detachments initiate at depth and terminate while migrating upward to the seafloor. This “detachment factory” model provides constraints on where, when, and how detachment faults originate in an exhumation system. Our model also predicts how abandoned detachments migrate off-axis with time, within the footwall and hanging wall, generating specific signals in geophysical data sets.
The origin of neotectonics on the lunar nearside
Authors: Valantinas A. , Schultz P.H.
Published: April 2020

New observations of wrinkle ridges on the nearside maria of the Moon display signs of ongoing ridge modification. In association with the wrinkle ridges, we observed an absence of superposed craters, narrow (<30 m) lobate scarps and graben, and thermal anomalies related to exposures of meter-size blocks. Many of these active wrinkle ridge systems are well beyond the influence of mascon basins and unrelated to any global tectonic pattern. Nevertheless, they spatially correlate with ancient deep-seated dike intrusions on the lunar nearside revealed by gravity data analysis. We propose that this active nearside tectonic system (ANTS) reflects ongoing reactivation of an ancient system related to offset antipodal effects from the South Pole–Aitken basin.
Hepatitis C elimination in the Netherlands (CELINE): study protocol for nationwide retrieval of lost to follow-up patients with chronic hepatitis C
Authors: Isfordink Cas J , Brakenhoff Sylvia M , van Dijk Marleen , van der Valk Marc , de Knegt Rob J , Arends Joop E , Drenth Joost PH
Published: April 2020

Background

The Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval.

Methods

Laboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who are eligible for retrieval. These patients will be invited for outpatient clinic care. The primary outcome of the study is the total number of LTFU patients who have been successfully linked to care.

Discussion

Hepatitis C ELimination In the NEtherlands (CELINE) is within the remit of WHO elimination targets and the Dutch National Hepatitis Plan. The methodology of CELINE is based on previously conducted regional retrieval projects and is designed to overcome some of their limitations. After ethical approval was obtained in 2018, the first centre initiated retrieval in 2018 and the project is expected to finish in 2021.

Trial registration number

NCT04208035.
Impact of ‘HIV-related stigma-reduction workshops’ on knowledge and attitude of healthcare providers and students in Central India: a pre-test and post-test intervention study
Authors: Machowska Anna , Bamboria Babu Lal , Bercan Courtney , Sharma Megha
Published: April 2020

Introduction

People living with HIV and AIDS (PLWHA) experience stigma and discrimination throughout their life. The consequences of stigma and discrimination are severe when enacted by healthcare providers (HCPs), and result in a delay in or poor adherence to treatment. Studies have demonstrated the presence of stigmatising behaviours among HCPs, yet only a few have presented the impact of interventions on the knowledge and attitude of practising (clinicians and nurses) and future (students) HCPs.

Objectives

To evaluate knowledge, attitudes and infection risk perceptions related to HIV/AIDS among practising and future HCPs in central India. In addition, the impact of the ‘HIV-related stigma-reduction workshop’ using a pre-intervention and post-intervention study design was evaluated.

Settings and participants

The study was conducted in 2016 at two tertiary-care hospitals and three healthcare colleges in central India. Overall, 650 HCPs (75 clinicians and 211 nurses) and students (205 medical, 123 nursing and 36 Diploma in Medical and Laboratory Technology (DMLT)) voluntarily participated in the study.

Intervention

The educational intervention comprised of training in epidemiology, the transmission and treatment of the HIV infection, the rights of PLWHA, the duties of HCPs and the use of standard precautions.

Results

At pre-intervention, DMLT students had the lowest and clinicians the highest knowledge scores (24% and 45%, respectively). The stigmatised attitude was reflected in all groups, the lowest among clinicians (21%) and the highest among DMLT students (34%). Improvement in the post-intervention knowledge scores was the highest in medical students (36%) and the lowest among clinicians (16%). The participants’ attitudes improved between 3% and 17% across all groups.

Conclusions

Significant post-intervention improvements were seen in both knowledge and attitudes in all groups. Students had a higher tendency to improve than HCPs. Further long-term studies are needed to evaluate the sustainability of the improvements in knowledge and attitudes of the participants.
Definitions of blinding in randomised controlled trials of interventions published in high-impact anaesthesiology journals: a methodological study and survey of authors
Authors: Penić Antonija , Begić Dinka , Balajić Karolina , Kowalski Martin , Marušić Ana , Puljak Livia
Published: April 2020

Objectives

To analyse the completeness of reporting of blinding in randomised controlled trials (RCTs) of interventions in anaesthesiology, the actual blinding status of various persons associated with an RCT and trial authors’ interpretation of blinding terminology related to RCTs.

Methods

This was a methodological study and a cross-sectional survey. We analysed reporting related to blinding in published RCTs of interventions published in seven highly cited anaesthesiology journals from 2014 to 2016 and registered protocols in ClinicalTrials.gov. We surveyed corresponding authors of included RCTs about their definitions of blinding. The primary outcome was the number of RCTs that explicitly described who was blinded in a trial. Secondary outcomes were definitions of blinding terminology in the trials; trial authors’ interpretation of blinding terminology; discrepancies in the blinding description within registered protocols and between registered protocols and publications.

Results

Out of 622 analysed RCTs, 38% were not explicitly described as either open label or blinded studies and 10% did not report any information about blinding or lack of blinding. Only one manuscript fully reported the status of blinding for various individuals that may be involved with a trial. The most common descriptor was that a trial was double-blind. We found discrepant information regarding blinding in the majority of registered protocols. Even when there were no discrepancies in the registration, we found discrepancies in the reporting of blinding between the majority of registered protocols and published manuscripts. The survey of authors (40 responses from 231 eligible authors; 17% response rate) of analysed RCTs showed that they differed in how they defined different levels of blinding in trials.

Conclusions

Reporting of the blinding status of key individuals involved in analysed anaesthesiology RCTs was insufficient. For reporting guidelines, peer reviewers and editors should insist on clear information on who was blinded in a trial instead of using the term ‘double-blind’ for different blinding practices.
The association between dementia severity and hospitalisation profile in a newly assessed clinical cohort: the South London and Maudsley case register
Authors: Gungabissoon Usha , Perera Gayan , Galwey Nicholas W , Stewart Robert
Published: April 2020

Objectives

To evaluate the risk and common causes of hospitalisation in patients with newly diagnosed dementia and variation by severity of cognitive impairment.

Setting

We used data from a large London mental healthcare case register linked to a national hospitalisation database.

Participants

Individuals aged ≥65 years with newly diagnosed dementia with recorded cognitive function and the catchment population within the same geography.

Outcome measures

We evaluated the risk and duration of hospitalisation in the year following a dementia diagnosis. In addition we identified the most common causes of hospitalisation and calculated age-standardised and gender-standardised admission ratios by dementia severity (mild/moderate/severe) relative to the catchment population.

Results

Of the 5218 patients with dementia, 2596 (49.8%) were hospitalised in the year following diagnosis. The proportion of individuals with mild, moderate and severe dementia who had a hospital admission was 47.9%, 50.8% and 51.7%, respectively (p= 0.097). Duration of hospital stay increased with dementia severity (median 2 days in mild to 4 days in severe dementia, p 0.0001). After excluding readmissions for the same cause, the most common primary hospitalisation discharge diagnoses among patients with dementia were urinary system disorders, pneumonia and fracture of femur, accounting for 15%, 10% and 6% of admissions, respectively. Overall, patients with dementia were hospitalised 30% more than the catchment population, and this trend was observed for most of the discharge diagnoses evaluated. Standardised admission ratios for urinary and respiratory disorders were higher in those with more severe dementia at diagnosis.

Conclusions

Individuals with a dementia diagnosis were more likely to be hospitalised than individuals in the catchment population. The length of hospital stay increased with dementia severity. Most of the common causes of hospitalisation were more common than expected relative to the catchment population, but standardised admission ratios only varied by dementia stage for certain groups of conditions.
Salvage harvest planning for spruce budworm outbreak using multistage stochastic programming
Authors: Mushakhian Siamak , Ouhimmou Mustapha , Rönnqvist Mikael
Published: April 2020

Forest supply chain planning must deal with many natural disturbance uncertainties such as fires, insects, and windthrow. One important consideration is wood infestation by invasive insects, as it causes environmental and economic harm. An example of invasive insects in Eastern Canada is the spruce budworm (Choristoneura fumiferana (Clemens)), which is the most destructive insect in North America’s conifer stands. In 2017, more than 5 million ha of forest were defoliated by spruce budworm in Quebec. Repeated defoliation causes tree mortality, reduction of growth rates, and reduced lumber quality. Consequently, different wood qualities with greatly varied values are found in the forest. Changes in the outbreak intensity impact wood values throughout the forest. One of the common actions to mitigate the economic and environmental damages is salvage harvesting. However, because of the large uncertainties and lack of detailed information, it is a difficult problem to model. We propose a multistage stochastic mixed-integer programming model for harvest scheduling under various outbreak intensities. The objective is to maximize revenues of wood value minus logistic costs while satisfying demand for wood in the industry. The results show that when there is an outbreak throughout the forest, the priority for salvage harvesting is to focus on forest areas with the lowest level of infestation.
Analytic derivation of the photon structure function $$F^{\gamma }_{2} (x,Q^{2})$$ at the leading order and the next-to-leading order approximations based on the Laplace transform method
Authors: Dadfar S. , Zarrin S.
Published: April 2020

In this paper, we present the analytical solutions, based on the Laplace transform method, for the Dokshitzer–Gribov–Lipatov–Altarelli–Parisi evolution equations of the photon at the leading order (LO) and next-to-leading order (NLO) approximations in perturbative QCD. Using these solutions, we derive the singlet, non-singlet, gluon, and photon distribution functions of the photon and also the photon structure function$$F^{\gamma }_{2} (x,Q^{2})$$F2γ(x,Q2)at the LO and NLO approximations. We show that the resulting distribution functions are in agreement with the results of the parameterization model formulated by Gluck, Reya, and Vogt (GRV) (Phys Rev D 46(5):1973, 1992). Moreover, our numerical results of$$F^{\gamma }_{2} (x,Q^{2})$$F2γ(x,Q2)are comparable with the results achieved by Aurenche, Fontannaz, and Guillet (AFG) (Eur Phys J C Part Fields 44(3):395–409, 2005) and also with the experimental data released by the L3, DELPHI, OPAL, ALEPH and PLUTO collaborations.
Bulk-boundary correspondence in non-Hermitian systems: stability analysis for generalized boundary conditions
Authors: Koch Rebekka , Budich Jan Carl
Published: April 2020

The bulk-boundary correspondence (BBC), i.e. the direct relation between bulk topological invariants defined for infinite periodic systems and the occurrence of protected zero-energy surface states in finite samples, is a ubiquitous and widely observed phenomenon in topological matter. In non-Hermitian generalizations of topological systems, however, this fundamental correspondence has recently been found to be qualitatively altered, largely owing to the sensitivity of non-Hermitian eigenspectra to changing the boundary conditions. In this work, we report on two contributions towards comprehensively explaining this remarkable behavior unique to non-Hermitian systems with theory. First, we analytically solve paradigmatic non-Hermitian topological models for their zero-energy modes in the presence of generalized boundary conditions interpolating between open and periodic boundary conditions, thus explicitly following the breakdown of the conventional BBC. Second, addressing the aforementioned spectral fragility of non-Hermitian matrices, we investigate as to what extent the modified non-Hermitian BBC represents a robust and generically observable phenomenon.

Graphical abstract