bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of rotavirus transmission dynamics and impact of vaccination in Ghana
Authors: Asare Ernest O. , Al-Mamun Mohammad A. , Armah George E. , Lopman Benjamin A. , Parashar Umesh D. , Binka Fred , Pitzer Virginia E.
Published: March 2020

Background

Rotavirus incidence remains relatively high in low-income countries (LICs) compared to high-income countries (HICs) after vaccine introduction. Ghana introduced monovalent rotavirus vaccine in April 2012 and despite the high coverage, vaccine performance has been modest compared to developed countries. The predictors of low vaccine effectiveness in LICs are poorly understood, and the drivers of subnational heterogeneity in rotavirus vaccine impact are unknown.

Methods

We used mathematical models to investigate variations in rotavirus incidence in children <5 years old in Ghana. We fit models to surveillance and case-control data from three different hospitals: Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and War Memorial Hospital in Navrongo. The models were fitted to both pre- and post-vaccine data to estimate parameters describing the transmission rate, waning of maternal immunity, and vaccine response rate.

Results

The seasonal pattern and age distribution of rotavirus cases varied among the three study sites in Ghana. Our model was able to capture the spatio-temporal variations in rotavirus incidence across the three sites and showed good agreement with the age distribution of observed cases. The rotavirus transmission rate was highest in Accra and lowest in Navrongo, while the estimated duration of maternal immunity was longer (∼5 months) in Accra and Kumasi and shorter (∼3 months) in Navrongo. The proportion of infants who responded to the vaccine was estimated to be high in Accra and Kumasi and low in Navrongo.

Conclusions

Rotavirus vaccine impact varies within Ghana. A low vaccine response rate was estimated for Navrongo, where rotavirus is highly seasonal and incidence limited to a few months of the year. Our findings highlight the need to further explore the relationship between rotavirus seasonality, maternal immunity, and vaccine response rate to determine how they influence vaccine effectiveness and to develop strategies to improve vaccine impact.

Highlights

Marked variations in rotavirus incidence and vaccine impact within Ghana

Similar rotavirus seasonality before and after vaccine introduction

A shift in age distribution occurred following vaccine introduction

The models provide satisfactory predictions of rotavirus outbreaks and vaccine impact
Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes
Authors: Mangiameli Elisabeth , Cecchele Anna , Morena Francesco , Sanvito Francesca , Matafora Vittoria , Cattaneo Angela , Della Volpe Lucrezia , Gnani Daniela , Paulis Marianna , Susani Lucia , Martino Sabata , Di Micco Raffaella , Bachi Angela , Gritti Angela
Published: March 2020

Globoid Cell Leukodystrophy (GLD, or Krabbe disease) is a rare lysosomal storage disease caused by inherited deficiency of β-galactocerebrosidase (GALC). The build-up of galactosylsphingosine (psychosine) and other undegraded galactosylsphingolipids in the nervous system causes severe demyelination and neurodegeneration. The molecular mechanisms of GLD are poorly elucidated in neural cells and whether murine systems recapitulate critical aspects of the human disease is still to be defined.

Here, we established a collection of GLD patient-specific induced pluripotent stem cell (iPSC) lines. We differentiated iPSCs from two patients (bearing different disease-causing mutations) into neural progenitors cells (NPCs) and their neuronal/glial progeny, assessing the impact of GALC deficiency and lentiviral vector-mediated GALC rescue/overexpression by means of phenotypic, biochemical, molecular, and lipidomic analysis. We show a progressive increase of psychosine during the differentiation of GLD NPCs to neurons and glia. We report an early and persistent impairment of oligodendroglial and neuronal differentiation in GLD cultures, with peculiar differences observed in the two GLD lines. GLD cells display a global unbalance of lipid composition during the iPSC to neural differentiation and early activation of cellular senescence, depending on the disease-causing mutation. Restoration of GALC activity normalizes the primary pathological hallmarks and partially rescues the differentiation program of GLD NPCs.

Our results suggest that multiple mechanisms besides psychosine toxicity concur to CNS pathology in GLD and highlight the need of a timely regulated GALC expression for proper lineage commitment and differentiation of human NPCs. These findings have important implications for establishing tailored gene therapy strategies to enhance disease correction in GLD.
Fast eco-evolutionary changes in bacterial genomes after anthropogenic perturbation
Authors: García-Ulloa Manuel , Escalante Ana Elena , Letelier Alejandra Moreno , Eguiarte Luis Enrique , Souza Valeria
Published: March 2020

Anthropogenic perturbations such as water overexploitation introduce novel selective pressures to the natural environments, impacting on the genomic variability of organisms and thus altering the evolutionary trajectory of its populations. Bad agricultural practices and defective policies in Cuatro Cienegas, Coahuila, Mexico, have strongly impacted its water reservoir, pushing entire hydrological systems to the brink of extinction together with their native populations. Here, we studied the effects of continuous water overexploitation on an environmental aquatic lineage ofPseudomonas otitidis, inhabitant to a particularly affected lagoon of an exhaustively studied system in the middle of the desert, over a 13 year period which encompasses three desiccation events. By comparing the genomes of a population sample from 2003 (original state) and 2015 (perturbed state), we analyzed the demographic history and evolutionary response of this bacterial lineage to the perturbation. Through coalescent simulations, we obtained a demographic model of contraction-expansion-contraction which, alongside an increment in mean Tajima’sDand recombination rate, loss of genetic and nucleotidic variation and a single amino acid under positive selection, points the occurrence of an evolutionary rescue event, possibly potentiated by horizontal gene transfer, where the population nearly went extinct during the first desiccation event but sharply recovered in the second and adapted to its new environment. Furthermore, the gain of phosphorylation, DNA recombination and small-molecule metabolism and loss of biosynthetic and regulation genes on the exclusive accessory genome suggest a functional shift to a more generalist scavenger lifestyle in an environment that went from oligotrophic to nutrient-rich.
100,000 years of gene flow between Neandertals and Denisovans in the Altai mountains
Authors: Peter Benjamin M
Published: March 2020

Summary paragraph

The Siberian Altai mountains have been intermittently occupied by both Neandertals and Denisovans, two extinct hominin groups1,2. While they diverged at least 390,000 years ago3,4, later contacts lead to gene flow from Neandertals into Denisovans5,6. Using a new population genetic method that is capable of inferring signatures of admixture from highly degraded genetic data, I show that this gene flow was much more widespread than previously thought. While the two earliest Denisovans both have substantial and recent Neandertal ancestry, I find signatures of admixture in all archaic genomes from the Altai, demonstrating that gene flow also occurred from Denisovans into Neandertals. This suggests that a contact zone between Neandertals and Denisovan populations persisted in the Altai region throughout much of the Middle Paleolithic. In contrast, Western Eurasian Neandertals have little to no Denisovan ancestry. As I find no evidence of natural selection against gene flow, this suggests that neutral demographic processes and geographic isolation were likely major drivers of human differentiation.
A review of models of natural pest control: toward predictions across agricultural landscapes
Authors: Alexandridis Nikolaos , Marion Glenn , Chaplin-Kramer Rebecca , Dainese Matteo , Ekroos Johan , Grab Heather , Jonsson Mattias , Karp Daniel S. , Meyer Carsten , O’Rourke Megan E. , Pontarp Mikael , Poveda Katja , Seppelt Ralf , Smith Henrik G. , Martin Emily A. , Clough Yann
Published: March 2020

Natural control of crop pests has the potential to complement or replace intensive agricultural practices, but its mainstream application requires reliable predictions in diverse socioecological settings. In lack of a widely accepted model of natural pest control, we review existing modelling approaches and critically examine their potential to provide understanding and predictions across agricultural landscapes. Models that explicitly represent the underlying mechanisms are better positioned to represent the diversity and context sensitivity of natural pest control than correlative models. Such mechanistic models have used diverse techniques to represent crop-pest-enemy combinations at various spatiotemporal scales. However, certain regions of the world and socioeconomic aspects of natural pest control are underrepresented, while modelling approaches are restricted by a fundamental trade-off between generality and realism. We propose that modelling natural pest control across agroecosystems requires a framework of context-specific generalizations, based on empirical evidence and theoretical expectations. Reviewed models of natural pest control indicate potential attributes of such a general predictive framework.
Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family
Authors: Walker Mark C. , Mitchell Douglas A. , van der Donk Wilfred A.
Published: March 2020

Background

Lanthipeptides belong to the ribosomally synthesized and post-translationally modified peptide group of natural products and have a variety of biological activities ranging from antibiotics to antinociceptives. These peptides are cyclized through thioether crosslinks and can bear other secondary post-translational modifications. While lanthipeptide biosynthetic gene clusters can be identified by the presence of characteristic enzymes involved in the post-translational modification of these peptides, locating the precursor peptides encoded within these clusters is challenging due to their short length and high sequence variability, which limits the high-throughput exploration of lanthipeptide precursor peptides. To address this challenge, we enhanced the predictive capabilities of Rapid ORF Description & Evaluation Online (RODEO) to identify all known classes of lanthipeptides.

Results

Using RODEO, we mined over 100,000 bacterial and archaeal genomes in the RefSeq database. We identified nearly 8,500 lanthipeptide precursor peptides. These precursor peptides were identified in a broad range of bacterial phyla as well as the Euryarchaeota phylum of archaea. Bacteroidetes were found to encode a large number of these biosynthetic gene clusters, despite making up a relatively small portion of the genomes in this dataset. While a number of these precursor peptides are similar to those of previously characterized lanthipeptides, even more were not, including potential antibiotics. Additionally, examination of the biosynthetic gene clusters revealed enzymes that install secondary post-translational modifications are more widespread than initially thought.

Conclusion

Lanthipeptide biosynthetic gene clusters are more widely distributed and the precursor peptides encoded within these clusters are more diverse than previously appreciated, demonstrating that the lanthipeptide sequence-function space remains largely underexplored.
Functional Changes Induced by Short Term Caloric Restriction in Cardiac and Skeletal Muscle Mitochondria
Authors: Serna Julian David C. , Caldeira da Silva Camille C. , Kowaltowski Alicia J.
Published: March 2020

Caloric restriction (CR) is widely known to increase life span and resistance against different types of injuries in several organisms. We have previously shown that mitochondria from livers or brains of CR animals exhibit higher calcium uptake rates and lower sensitivity to calcium-induced mitochondrial permeability transition (mPT), an event related to the resilient phenotype exhibited by these organs. Given the importance of calcium in metabolic control and cell homeostasis, we aimed here to uncover possible changes in mitochondrial calcium handling, redox balance and bioenergetics in cardiac and skeletal muscle mitochondria. Unexpectedly, we found that CR does not alter the susceptibility to mPT in muscle (cardiac or skeletal), nor calcium uptake rates. Despite the lack in changes in calcium transport properties, CR consistently decreased respiration in the presence of ATP synthesis in heart and soleus muscle. In heart, such changes were accompanied by a decrease in respiration in the absence of ATP synthesis, lower maximal respiratory rates and a reduced rate of hydrogen peroxide release. Hydrogen peroxide release was unaltered by CR in skeletal muscle. No changes were observed in inner membrane potentials and respiratory control ratios. Together, these results highlight the tissue-specific bioenergetic and ion transport effects induced by CR, demonstrating that resilience against calcium-induced mPT is not present in all tissues.
AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination
Authors: Peyrégne Stéphane , Peter Benjamin M.
Published: March 2020

Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses. We present AuthentiCT, a command-line tool to estimate the proportion of present-day DNA contamination in ancient DNA datasets generated from single-stranded DNA libraries. The prediction is based solely on the patterns of post-mortem damage observed on ancient DNA sequences. The method has the power to quantify contamination from as few as 10,000 mapped sequences, making it particularly useful for analysing specimens that are poorly preserved or for which little data is available.

Contact

stephane.peyregne@gmail.com
Identifying priority connectivity in a tropical forest hotspot severely affected by land use changes
Authors: de Oliveira-Junior Neil Damas , Heringer Gustavo , Bueno Marcelo Leandro , Pontara Vanessa , Meira-Neto João Augusto Alves
Published: March 2020

The probability that a propagule reaches a certain location where it can establish and persist is affected by the distance from the source. Fragmented landscapes often promote the isolation of habitats that hinder or impede the movement of species that affect their range distribution, even when environmental conditions are adequate. Studies that assess the connectivity of the landscape are essential to ensure that ecological conservation planning covers all vital processes that occur on a landscape scale. Based on the classification of land cover in the Rio Doce Basin - RDB, we used a habitat / non-habitat approach to assess RDB connectivity for tree species. Based on circuit theory, we built 6 surface models of resistance based on habitat and non-habitat areas. We performed the analysis using the GIS plug-in and Linkage Mapper to generate lest cost path maps. The RDB is very fragmented, but still has functionally connected regions. The west to nothwestern and southeastern portions of the basin are well-connected and demand conservation practices, while the center-north of the basin and the far southwest are regions with greater resistance to connectivity as a result of strong anthropic pressures that reduce forests, requiring intervention through restoration projects avoiding loss due to lack of connectivity. In addition, land reclamation projects in degraded areas must also be organized in the Linhares region, as it is inserted in a region of very high biodiversity with a high level of endemism and a high number of threatened species.
A novel HER2-targeted antibody-drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels
Authors: Barfield Robyn M. , Kim Yun Cheol , Chuprakov Stepan , Zhang Fangjiu , Bauzon Maxine , Ogunkoya Ayodele O. , Yeo Dominick , Hickle Colin , Pegram Mark D. , Rabuka David , Drake Penelope M.
Published: March 2020

Trastuzumab and the related antibody-drug conjugate (ADC), ado-trastuzumab emtansine (T-DM1), both target HER2-overexpressing cells. Together, these drugs have treatment indications in both early-stage and metastatic settings for HER2+ breast cancer. T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. Interestingly, in the clinic, T-DM1 cannot always replace the use of trastuzumab plus chemotherapy administered together as single agents. We hypothesize that this failure may be due in part to the limited systemic exposure achieved by T-DM1 relative to trastuzumab because of toxicity-related dosing constraints on the ADC. We have developed a trastuzumab-based ADC site-specifically conjugated to maytansine through a noncleavable linker. This construct, termed CAT-01-106, has a drug-to-antibody ratio (DAR) of 1.8, approximately half the average DAR of T-DM1, which comprises a mixture of antibodies variously conjugated with DARs ranging from 0-8. The high DAR species present in T-DM1 contribute to its toxicity and limit its clinical dose. CAT-01-106 showed superior in vivo efficacy compared to T-DM1 at equal payload dosing and was equally or better tolerated compared to T-DM1 at equal payload dosing up to 120 mg/kg in Sprague-Dawley rats and 60 mg/kg in cynomolgus monkeys. CAT-01-106 also showed improved pharmacokinetics in rats relative to T-DM1, with 40% higher ADC exposure levels. Together, the data suggest that CAT-01-106 may be sufficiently tolerable to enable clinical dosing at trastuzumab-equivalent exposure levels, combining the functions of both the antibody and the payload in one drug and potentially improving patient outcomes.
Menthol in Electronic Cigarettes: A Contributor to Respiratory Disease?
Authors: Nair Vijayalekshmi , Tran Malcolm , Behar Rachel Z. , Zhai Song , Cui Xinping , Phandthong Rattapol , Wang Yuhuan , Pan Songqin , Luo Wentai , Pankow James F. , Volz David C. , Talbot Prue
Published: March 2020

Menthol is widely used in tobacco products. This study compared the effects of menthol on human bronchial epithelium using submerged cultures, a VITROCELL® cloud chamber that provides air liquid interface (ALI) exposure without solvents or heating, and a Cultex ALI system that delivers aerosol equivalent to that inhaled during vaping. In submerged culture, menthol significantly increased calcium influx and mitochondrial reactive oxygen species (ROS) via the TRPM8 receptor, responses that were inhibited by a TRPM8 antagonist. VITROCELL® cloud chamber exposure of BEAS-2B monolayers increased mitochondrial protein oxidation, expression of the antioxidant enzyme SOD2, activation of NF-κB, and secretion of inflammatory cytokines (IL-6 and IL-8). Proteomics data collected following ALI exposure of 3D EpiAirway tissue in the Cultex showed upregulation of NRF-2-mediated oxidative stress, oxidative phosphorylation, and IL-8 signaling. Across the three platforms, menthol adversely effected human bronchial epithelium in a manner that could lead to respiratory disease.

Graphical Abstract. Mechanism of action of menthol on human bronchial epithelium.

Threein vitroplatforms were used to study the effect of menthol on bronchial epithelium. In submerged culture (using BEAS-2B cells), menthol produced rapid calcium influx followed by an increase in oxidative stress and inflammatory cytokines. ALI exposure of BEAS-2B cells to unheated menthol in a cloud chamber caused activation of an inflammatory transcription factor (NF-κB) and oxidative stress. Proteomics analysis of human EpiAirway tissues exposed at the ALI to heated menthol EC aerosols identified changes in the expression of proteins involved in oxidative stress and in an inflammatory response.
JNK signaling regulates oviposition in the malaria vectorAnopheles gambiae
Authors: Peirce Matthew J. , Mitchell Sara N. , Kakani Evdoxia G. , Scarpelli Paolo , South Adam , Shaw W. Robert , Werling Kristine L. , Gabrieli Paolo , Marcenac Perrine , Bordoni Martina , Talesa Vincenzo , Catteruccia Flaminia
Published: March 2020

The reproductive fitness of theAnopheles gambiaemosquito represents a promising target to prevent malaria transmission. The ecdysteroid hormone 20-hydroxyecdysone (20E), transferred from male to female during copulation, is key toAn. gambiaereproductive success as it licenses females to oviposit eggs developed after blood feeding. Here we show that 20E-triggered oviposition in these mosquitoes is regulated by the stress- and immune-responsive c-Jun N-terminal kinase (JNK). The heads of mated females exhibit a transcriptional signature reminiscent of a JNK-dependent wounding response while mating — or injection of virgins with exogenous 20E — selectively activates JNK in the same tissue. RNAi-mediated depletion of JNK pathway components inhibits oviposition in mated females, whereas JNK activation by silencing the JNK phosphatasepuckeredinduces egg laying in virgins. Together, these data identify JNK as a potential conduit linking stress responses and reproductive success in the most important vector of malaria.
Sex determining gene transposition as an evolutionary platform for chromosome turnover
Authors: Ayllon Fernando , Favnebøe Solberg Monica , Besnier François , Fjelldal Per Gunnar , Hansen Tom Johnny , Wargelius Anna , Edvardsen Rolf Brudvik , Glover Kevin Alan
Published: March 2020

Despite the key role that sex-determination plays in evolutionary processes, it is still poorly understood in many species. In salmonids, which are the best studied family of fishes, the master sex-determining gene sexually dimorphic on the Y-chromosome (sdY) has been identified. However,sdYdisplays unexplained discordance to the phenotypic sex, with a variable frequency of phenotypic females being reported as genetic males. Multiple sex determining loci in Atlantic salmon have also been reported, possibly as a result of transposition, suggesting a recent and non-random sex chromosome turnover in this species. We hypothesized the existence of an autosomic pseudocopy ofsdYthat is transmitted in accordance with Mendelian inheritance. To test this we developed a qPCR methodology to detect the number ofsdYcopies present in the genome. Based on the observed phenotype/genotype frequencies and linkage analysis among 2025 offspring from 64 pedigree-controlled families of accurately phenotyped Atlantic salmon, we identified both males and females carrying one or two autosomic copies in addition to the Y-specific copy present in males. Copy number frequencies were consistent with Mendelian inheritance. Pseudocopy loci were mapped to different chromosomes evidencing non-random transitions of the sex determining gene in Atlantic salmon and the existence of functional constraints for chromosome turnover.
Effect of egg cannibalism on mating preferences and reproductive fitness ofMenochilus sexmaculatusFabricius (Coleoptera: Coccinellidae)
Authors: Yadav Tripti , Omkar  , Mishra Geetanjali
Published: March 2020

Cannibalism has been reported in a large proportion of coccinellids in fields as well as in laboratories but studies involving mate preferences and potential benefits of cannibalism on reproduction inMenochilus sexmaculatusFabricius (Coleoptera: Coccinellidae)have yet not been done. Thus, we assessed the effect of conspecific egg cannibalism on mate preferences and reproductive outputs including offspring development. Higher mate preferences were recorded for non-cannibal mates (fed onA. craccivora) than cannibal ones (fed on conspecific eggs). Mating parameters significantly influenced by cannibalism. Time to commence mating lasted less for homogeneous diet pairs than heterogeneous diet pairs. Longer copulation duration and higher fecundity were recorded when one of the individuals in mating pair or both was a non-cannibal. Egg viability did not differed significantly in all reciprocal crosses. Total developmental durations of offspring were similar for all mating pairs.
Cellular-resolution mapping uncovers spatial adaptive filtering at the cerebellum input stage
Authors: Stefano Casali , Marialuisa Tognolina , Egidio D’Angelo
Published: March 2020

Long-term synaptic plasticity, in the form of either potentiation or depression (LTP or LTD), is thought to provide the substrate for adaptive computations in brain circuits. Although molecular and cellular processes of plasticity have been clarified to a considerable extent at individual synapses, very little is known about the spatiotemporal organization of LTP and LTD in local microcircuits. Here, we have combined multi-spot two-photon laser microscopy and realistic modeling to map the distribution of plasticity in multi-neuronal units of the cerebellar granular layer activated by stimulating an afferent mossy fiber bundle. The units, composed by ~300 active neurons connected to ~50 glomeruli, showed potentiation concentrated in the core and depression in the periphery. This plasticity was effectively accounted for by an NMDA receptor and calcium-dependent induction rule and was regulated by local microcircuit mechanisms in the inhibitory Golgi cell loops. The organization of LTP and LTD created effective spatial filters tuning the time-delay and gain of spike retransmission at the cerebellum input stage and provided a plausible basis for the spatiotemporal recoding of input spike patterns anticipated by the motor learning theory.
Edge-Gated CNNs for Volumetric Semantic Segmentation of Medical Images
Authors: Hatamizadeh Ali , Terzopoulos Demetri , Myronenko Andriy
Published: March 2020

Textures and edges contribute different information to image recognition. Edges and boundaries encode shape information, while textures manifest the appearance of regions. Despite the success of Convolutional Neural Networks (CNNs) in computer vision and medical image analysis applications, predominantly only texture abstractions are learned, which often leads to imprecise boundary delineations. In medical imaging, expert manual segmentation often relies on organ boundaries; for example, to manually segment a liver, a medical practitioner usually identifies edges first and subsequently fills in the segmentation mask. Motivated by these observations, we propose a plug-and-play module, dubbed Edge-Gated CNNs (EG-CNNs), that can be used with existing encoder-decoder architectures to process both edge and texture information. The EG-CNN learns to emphasize the edges in the encoder, to predict crisp boundaries by an auxiliary edge supervision, and to fuse its output with the original CNN output. We evaluate the effectiveness of the EG-CNN with various mainstream CNNs on two publicly available datasets, BraTS 19 and KiTS 19 for brain tumor and kidney semantic segmentation. We demonstrate how the addition of EG-CNN consistently improves segmentation accuracy and generalization performance.
Oxytocin differentially modulates amygdala responses during top-down and bottom-up aversive anticipation
Authors: Xin Fei , Zhou Xinqi , Dong Debo , Zhao Zhongbo , Yang Xi , Wang Qianqian , Gu Yan , Kendrick Keith M. , Chen Antao , Becker Benjamin
Published: March 2020

The ability to successfully regulate negative emotions such as fear and anxiety is vital for mental health. The neuropeptide oxytocin (OXT) acts as important modulator of emotion regulation, as reflected by reduced amygdala responses but increased amygdala–prefrontal cortex (PFC) functional connectivity in response to threatening stimuli. The present randomized, between-subject, placebo (PLC)-controlled pharmacological study combined intranasal administration of OXT with functional MRI during an explicit (cognitive) emotion regulation (i.e. distancing reappraisal) paradigm in 65 healthy male participants to investigate the modulatory effects of OXT on both bottom-up and top-down emotion regulation. OXT attenuated the activation in posterior insular cortex and amygdala during anticipation of top-down regulation of predictable threat stimuli in participants with high trait anxiety, providing evidence to support the anxiolytic action of OXT. In contrast, OXT enhanced amygdala activity during bottom-up anticipation of an unpredictable threat stimulus in participants with low trait anxiety. OXT may thus facilitate top-down goal-directed attention by attenuating amygdala activity in high anxiety individuals, while promote bottom-up attention/vigilance to unexpected threat by enhancing anticipatory amygdala activity in low anxiety individuals. The opposite effects of OXT on anticipatory amygdala activation in high versus low anxiety individuals may suggest a baseline anxiety level dependent mechanism via which OXT promotes optimal levels of amygdala activation during the anticipation of an imminent threat. OXT may thus have the potential to promote an adaptive balance between bottom-up and top-down attention systems depending on individual levels of pre-treatment trait anxiety levels.
A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly
Authors: Antón Zuriñe , Betin Virginie M.S. , Simonetti Boris , Traer Colin J. , Attar Naomi , Cullen Peter J. , Lane Jon D.
Published: March 2020

Efficient mammalian autophagosome biogenesis requires coordinated input from other cellular endomembrane compartments. Such coordination includes the stimulated trafficking to autophagosome assembly sites of the essential autophagy proteins, ATG9 and ATG16L1, via distinct endosomal compartments. Protein trafficking within the endocytic network is directed by a conserved family of sorting nexins (SNXs), with previous studies implicating SNX18 (an SH3 domain-type SNX-BAR protein) in the mobilisation of ATG9A and ATG16L1 from recycling endosomes during autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that a second mammalian SNX-BAR, SNX4, is needed for efficient LC3 lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and heterodimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30, and that these associate with tubulovesicular endocytic membranes at steady state. Detailed image-based analysis during the early stages of autophagosome assembly reveal that SNX4:SNX7 is the autophagy-specific heterodimeric SNX-BAR complex, required for efficient recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localises with juxtanuclear ATG9A-positive membranes, with our data linking the SNX4 autophagy defect to the mis-trafficking and/or retention of ATG9A in the Golgi region. Together, our findings show that the SNX4:SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites.

SUMMARY STATEMENT

A heterodimeric SNX4:SNX7 SNX-BAR complex regulates mammalian autophagosome assembly through the control of ATG9 trafficking.
Differentiation of human intestinal organoids with endogenous vascular endothelial cells
Authors: Holloway Emily M. , Wu Joshua H. , Czerwinkski Michael , Sweet Caden W. , Wu Angeline , Tsai Yu-Hwai , Huang Sha , Stoddard Amy E. , Capeling Meghan M. , Glass Ian , Spence Jason R.
Published: March 2020

Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) generated using directed differentiation lack some cellular populations found in the native organ, including vasculature. Using single cell RNA sequencing (scRNAseq), we have identified a transient population of endothelial cells (ECs) present early in HIO differentiation that are lost over time in culture. Here, we have developed a method to enhance co-differentiation and maintenance of ECs within HIOs (vHIOs). Given that ECs are known to possess organ specific gene expression, morphology and function, we used bulk RNAseq and scRNAseq to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC-gene signatures in these organ systems. By comparing organ-specific gene signatures along with markers validated by fluorescentin situhybridization to HIO ECs, we find that HIO ECs grownin vitroshare the highest similarity with native intestinal ECs relative to kidney and lung. Together, these data show that HIOs can co-differentiate a native EC population that are properly patterned with an intestine-specific EC transcriptional signaturein vitro.
A ComRS competence pathway in the oral pathogen Streptococcus sobrinus
Authors: Li Walden , Wyllie Ryan M. , Jensen Paul A.
Published: March 2020

Streptococcus sobrinus is one of two species of bacteria that cause dental caries (tooth decay) in humans. Our knowledge of S. sobrinus is limited despite the organism's important role in oral health. It is widely believed that S. sobrinus lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. The lack of natural competence has also prevented genetic manipulation of S. sobrinus, limiting our knowledge of its pathogenicity. We discovered a functional ComRS competence system in S. sobrinus. The ComRS pathway in S. sobrinus has a unique structure, including two copies of the transcriptional regulator ComR and a peptide pheromone (XIP) that lacks aromatic amino acids. We show that synthetic XIP allows transformation of S. sobrinus with plasmid or linear DNA, and we leverage this newfound genetic tractability to confirm that only one of the ComR homologs is required for induced competence. Although S. sobrinus is typically placed among the mutans group streptococci, the S. sobrinus ComRS system is structurally and functionally similar to the competence pathways in the salivarius group. Like S. salivarius, the ComRS gene cluster in S. sobrinus includes a peptide cleavage/export gene, and the ComRS system appears coupled to a bacteriocin response system. These findings raise questions about the true phylogenetic placement of S. sobrinus. Finally, we identified two strains of S. sobrinus appear to be "cheaters" by either not responding to or not producing XIP. While the mechanisms of cheating could be independent, we show how a recombination event in the non-responsive strain would restore function of the ComRS pathway but delete the gene encoding XIP. Thus the S. sobrinus ComRS pathway provides a lens into the evolution of ecological cheaters.
A Rapid Screening of Resistant Tomato Cultivars in Early Seedling Stage AgainstRalstonia solanacearumBacterial Wilt Under Soil and Nutrients Free Conditions
Authors: Singh Niraj
Published: March 2020

This work reports a rapid screening study of tomato(Solanum lycopersicum)cultivars resistant toR. solanacearum(F1C1) bacterial wilt in early seedling stage (6-7 days old, cotyledon leaf stage) under soil and nutrients free condition. This study was performed in 1.5-2.0 ml microfuge tube where root inoculation approach has been used during infection under gnotobiotic condition and got completed within 2 weeks. After continuous post inoculation observation of disease progression in all nine recruited tomato cultivar, Ayush was found to be the most resistant (~15% wilting) while the Ruby tomato cultivar was found to be the most susceptible (~95% wilting) againstR. solanacearumbacterial wilt. This comparative wilting and survivability study among nine different tomato cultivar under same conditions indicated that early seedling stage of tomato may be a potent and helpful tool for an easy and rapid screening of resistant tomato cultivar againstR. solanacearumbacterial wilt disease at large scale level in a very economical way in terms of time, space, labor and cost. Over and above The soil and nutrients free approach presented here may be helpful for the rapid selection and development of resistant tomato cultivar and new plant protection strategies againstR. solanacearumbacterial wilt disease.
Bacterial filament division dynamics allows rapid post-stress cell proliferation
Authors: Cayron Julien , Dedieu Annick , Lesterlin Christian
Published: March 2020

Many bacterial species grow into filaments under stress conditions. Initially regarded as an indicator of cell death, filamentation is now proposed to be a transient morphological change that improves bacterial survival in hostile environments. However, the mechanism of filament recovery remains poorly characterized. Using real-time microscopy in live-cells, we analysed the fate of filamentousEscherichia coliinduced by antibiotic-mediated specific inhibition of cell division, or by UV-induced DNA-damage that additionally perturbs chromosome segregation. Both filament types recover by successive and accelerated rounds of divisions, which are preferentially positioned asymmetrically at the tip of the cell by the Min system. Such division dynamics allows the rapid production of daughter cells with normal size, which DNA content depends on the progression of chromosome segregation prior to division. In most filaments, nucleoid segregation precedes tip-division, which produces nucleated daughter cells that resume normal growth. However, when segregation is deficient, tip-division occurs in the absence of DNA and produces anucleated cells. These findings uncover the mechanism by which bacterial filamentation allows efficient post-stress cell proliferation.

One Sentence Summary

Bacterial filaments recover by successive, frequent and Min-dependent asymmetric tip-divisions that rapidly produce multiple daughter cells with normal size and viability
Fast continuous measurement of synchrotron powder diffraction synchronized with controlling gas and vapour pressures at beamline BL02B2 of SPring-8
Authors: Kawaguchi Shogo , Takemoto Michitaka , Tanaka Hideki , Hiraide Shotaro , Sugimoto Kunihisa , Kubota Yoshiki
Published: March 2020

A gas- and vapour-pressure control system synchronized with the continuous data acquisition of millisecond high-resolution powder diffraction measurements was developed to study structural change processes in gas storage and reaction materials such as metal organic framework compounds, zeolite and layered double hydroxide. The apparatus, which can be set up on beamline BL02B2 at SPring-8, mainly comprises a pressure control system of gases and vapour, a gas cell for a capillary sample, and six one-dimensional solid-state (MYTHEN) detectors. The pressure control system can be remotely controlled via developed software connected to a diffraction measurement system and can be operated in the closed gas and vapour line system. By using the temperature-control system on the sample, high-resolution powder diffraction data can be obtained under gas and vapour pressures ranging from 1 Pa to 130 kPa in temperatures ranging from 30 to 1473 K. This system enables one to perform automatic and high-throughputin situX-ray powder diffraction experiments even at extremely low pressures. Furthermore, this developed system is useful for studying crystal structures during the adsorption/desorption processes, as acquired by millisecond and continuous powder diffraction measurements. The acquisition of diffraction data can be synchronized with the control of the pressure with a high frame rate of up to 100 Hz.In situand time-resolved powder diffraction measurements are demonstrated for nanoporous Cu coordination polymer in various gas and vapour atmospheres.
Soft X-ray diffraction patterns measured by a LiF detector with sub-micrometre resolution and an ultimate dynamic range
Authors: Makarov Sergey , Pikuz Sergey , Ryazantsev Sergey , Pikuz Tatiana , Buzmakov Alexey , Rose Max , Lazarev Sergey , Senkbeil Tobias , von Gundlach Andreas , Stuhr Susan , Rumancev Christoph , Dzhigaev Dmitry , Skopintsev Petr , Zaluzhnyy Ivan , Viefhaus Jens , Rosenhahn Axel , Kodama Ryosuke , Vartanyants Ivan A.
Published: March 2020

The unique diagnostic possibilities of X-ray diffraction, small X-ray scattering and phase-contrast imaging techniques applied with high-intensity coherent X-ray synchrotron and X-ray free-electron laser radiation can only be fully realized if a sufficient dynamic range and/or spatial resolution of the detector is available. In this work, it is demonstrated that the use of lithium fluoride (LiF) as a photoluminescence (PL) imaging detector allows measuring of an X-ray diffraction image with a dynamic range of ∼107 within the sub-micrometre spatial resolution. At the PETRA III facility, the diffraction pattern created behind a circular aperture with a diameter of 5 µm irradiated by a beam with a photon energy of 500 eV was recorded on a LiF crystal. In the diffraction pattern, the accumulated dose was varied from 1.7 × 105 J cm−3 in the central maximum to 2 × 10−2 J cm−3 in the 16th maximum of diffraction fringes. The period of the last fringe was measured with 0.8 µm width. The PL response of the LiF crystal being used as a detector on the irradiation dose of 500 eV photons was evaluated. For the particular model of laser-scanning confocal microscope Carl Zeiss LSM700, used for the readout of the PL signal, the calibration dependencies on the intensity of photopumping (excitation) radiation (λ = 488 nm) and the gain have been obtained.
The importance of relationship characteristics in the export performance of food firms
Authors: Karipidis Philippos , Chrysochou Polymeros , Karypidou Ioanna
Published: March 2020

Purpose

The purpose of this study is to explore how food-exporting firms assess the importance of relationship characteristics of the supply chain that impact their performance as well as how it relates to export performance indicators.

Design/methodology/approach

An online survey was administered across 83 food firms in Greece, assessing the importance of relationship characteristics of the supply chain by using the best–worst scaling technique.

Findings

The most important characteristics relate to the quality of the primary material and the procurement costs and producer prices; these are considered more important by export-oriented food firms compared to non–export-oriented food firms. Characteristics that relate to the relationship between members of the agri-food supply chain and the interorganizational business systems and governance mechanisms are also considered of average importance. Characteristics related to the adoption of differentiation strategies are considered least important.

Practical implications

Producers should emphasize the quality and prices of their product as well as establish collaborations with food firms. Food firms need to emphasize interorganizational business systems and governance mechanisms that reduce procurement costs, instead of trying to reduce producer prices. Public authorities should engage stakeholders of the agri-food supply chain in relationships that will enable food firms to deliver on their quality and price demands.

Originality/value

Primary production and collaborations of it with food firms have not been studied in regards to what extent they relate to food firms' export performance.
University-led internships for innovative thinking: a theoretical framework
Authors: Ranabahu Nadeera , Almeida Shamika , Kyriazis Elias
Published: March 2020

Purpose

This article explains how business internships can be used to develop innovation skills in undergraduates.

Design/methodology/approach

Using work-integrated learning and current literature on innovation, this article proposes a theoretical framework to design, implement, and measure outcomes of Innovation-Focused Internships (IFIs). The article also uses an illustrative case study from an Australian university to discuss practical use of this framework.

Findings

The theoretical framework illustrates that stakeholders (i.e., students, industry, and university) need a common goal. Factors associated with managing innovation and student placements are key features of the framework. The illustrative case study demonstrates ways in which students gather both professional work experience and innovative skills.

Practical implications

The illustrative case study outlines practical strategies and challenges in IFI programs. Managing innovation-related challenges requires adjustments from all the stakeholders.

Originality/value

This article modifies the existing stakeholder interdependency model of work-integrated learning by combining it with innovation-related literature. The novel insights from the IFI program demonstrate how factors associated with students, industry, and university, and associations between these key stakeholders shape and determine IFI success.
Mapping the antecedents and consequences of thriving at work
Authors: Shahid Sehrish , Muchiri Michael K. , Walumbwa Fred O.
Published: March 2020

Purpose

This paper aims to explore the antecedents and consequences of thriving at work, identifies existing gaps in the literature and proposes a framework, which encapsulates potential pathways for future research on thriving.

Design/methodology/approach

This paper follows a rigorous review of the extant literature on thriving mainly based on journal articles published between 2005 and 2020.

Findings

The paper proposes a feasible conceptual framework highlighting the antecedents and outcomes of thriving. Specifically, the review illustrates how contextual factors, represented by transformational leadership and organisational virtuousness (OV), act as antecedents of thriving and then proposes potential research direction where thriving is associated with psychological empowerment, psychological capital and innovative work behaviour.

Practical implications

Understanding how and when contextual factors such as transformational leadership and OV promote thriving is important for organisations and leaders who wish to know how and when they can shape resources and organisational features to enable thriving.

Originality/value

This unique review is one of a few studies adding to the growing research on positive psychology at the workplace. The proposed framework and future research directions have the potential to help unpack the unique relationship between work-related contextual factors and thriving.
Foreign ownership and investment efficiency: new evidence from an emerging market
Authors: Tran Quoc Trung
Published: March 2020

Purpose

This paper investigates the effect of foreign ownership on corporate investment efficiency in an emerging market.

Design/methodology/approach

This paper employs the investment-investment opportunities sensitivity to proxy for investment efficiency. Corporate investment and investment opportunities are measured by capital expenditure and Tobin's Q respectively. Control variables include state ownership, firm profitability, cash flow, financial leverage, firm size, bank debt, asset tangibility and financial distress. The research sample includes 5,502 firm-years from 621 firms listed in Vietnamese stock market from 2007 to 2017.

Findings

We find that foreign ownership negatively affects corporate investment efficiency. Furthermore, we continue to examine the effects of foreign ownership with financially unconstrained and constrained firms that are classified based on the annual medians of Kaplan and Zingales (1997) score, firm size and dividend payout ratio. We find that the negative relationship between foreign ownership and investment efficiency is stronger in financially unconstrained.

Originality/value

Prior research shows that foreign ownership is positively related to corporate investment efficiency. However, in Vietnamese stock market, foreign investors may prefer safe business activities as a response to uncertainty in the business environment, ineffective legislations on corporate governance and their informational disadvantage. Therefore, in this paper, we argue that foreign ownership negatively affects Vietnamese firms' investment efficiency. Risk-adverse foreign investors make firms lose some profitable investment opportunities and thus decrease their investment efficiency.