bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Influences on Learning Walks in Desert Ants (Cataglyphis fortis)
Authors: Vermehren Jose Adrian Vega , Buehlmann Cornelia , Fernandes Ana Sofia David , Graham Paul
Published: April 2020

Ants are excellent navigators taking into account multimodal sensory information as they move through the world. To be able to accurately localise the nest at the end of a foraging journey, visual cues, wind direction and also olfactory cues need to be learnt. Learning walks are performed at the start of an ant’s foraging career or when the appearance of the nest surrounding has changed. We investigated here whether the structure of such learning walks in the desert antCataglyphis fortistakes into account wind direction in conjunction with the learning of new visual information. Ants learnt to travel back and forth between their nest and a feeder, and we then introduced a black cylinder near their nest to induce learning walks in regular foragers. By doing this across days with different prevailing wind directions, we were able to probe how ants balance the influence of different sensory modalities. We found that (i) the ants’ outwards headings are influenced by the direction of the wind with their routes deflected in such a way that they will arrive downwind of their nest when homing, (ii) a novel object along the route induces learning walks in experienced ants and (iii) the structure of learning walks is shaped by the wind direction rather than the position of the visual cue.
Learning precise spatiotemporal sequences via biophysically realistic circuits with modular structure
Authors: Cone I. , Shouval H. Z.
Published: April 2020

The ability to express and learn temporal sequences is an essential part of learning and memory. Learned temporal sequences are expressed in multiple brain regions and as such there may be common design in the circuits that mediate it. This work proposes a substrate for such representations, via a biophysically realistic network model that can robustly learn and recall discrete sequences of variable order and duration. The model consists of a network of spiking leaky-integrate-and-fire model neurons placed in a modular architecture designed to resemble cortical microcolumns. Learning is performed via a learning rule with “eligibility traces”, which hold a history of synaptic activity before being converted into changes in synaptic strength upon neuromodulator activation. Before training, the network responds to incoming stimuli, and contains no memory of any particular sequence. After training, presentation of only the first element in that sequence is sufficient for the network to recall an entire learned representation of the sequence. An extended version of the model also demonstrates the ability to successfully learn and recall non-Markovian sequences. This model provides a possible framework for biologically realistic sequence learning and memory, and is in agreement with recent experimental results, which have shown sequence dependent plasticity in sensory cortex.
“TMEM16K is an interorganelle regulator of endosomal sorting”
Authors: Petkovic Maja , Oses-Prieto Juan , Burlingame Alma , Jan Lily Yeh , Jan Yuh Nung
Published: April 2020

Communication between organelles is essential for their cellular homeostasis. Neurodegeneration reflects the declining ability of neurons to maintain cellular homeostasis over a lifetime1. The endolysosomal pathway plays a prominent role in this process by regulating protein and lipid sorting and degradation2. Here, we report that TMEM16K, an endoplasmic reticulum lipid scramblase3causative for spinocerebellar ataxia (SCAR10), is an interorganelle regulator of the endolysosomal pathway. We identify endosomal transport as a major functional cluster of TMEM16K in proximity biotinylation proteomics analyses. TMEM16K forms contact sites with endosomes, reconstituting split-GFP with small GTPase RAB7. Our study further implicates TMEM16K lipid scrambling activity in endosomal sorting at these sites. Loss of TMEM16K function led to impaired endosomal retrograde transport and neuromuscular function, one of the symptoms of SCAR10. Thus, TMEM16K-containing ER-endosome contact sites represent clinically relevant platforms for regulating endosomal sorting.
Terraces in Gene Tree Reconciliation-Based Species Tree Inference
Authors: Sanderson Michael J. , McMahon Michelle M. , Steel Mike
Published: April 2020

Abstract

Terraces in phylogenetic tree space are sets of trees with identical optimality scores for a given data set, arising from missing data. These were first described for multilocus phylogenetic data sets in the context of maximum parsimony inference and maximum likelihood inference under certain model assumptions. Here we show how the mathematical properties that lead to terraces extend to gene tree - species tree problems in which the gene trees are incomplete. Inference of species trees from either sets of gene family trees subject to duplication and loss, or allele trees subject to incomplete lineage sorting, can exhibit terraces in their solution space. First, we show conditions that lead to a new kind of terrace, which stems from subtree operations that appear in reconciliation problems for incomplete trees. Then we characterize when terraces of both types can occur when the optimality criterion for tree search is based on duplication, loss or deep coalescence scores. Finally, we examine the impact of assumptions about the causes of losses: whether they are due to imperfect sampling or true evolutionary deletion.
Locus coeruleus patterns differentially modulate learning and valence in ratviathe ventral tegmental area and basolateral amygdala respectively
Authors: Ghosh Abhinaba , Massaeli Faghihe , Power Kyron D. , Omoluabi Tamunotonye , Torraville Sarah E. , Pritchett Julia B. , Sepahvand Tayebeh , Strong Vanessa M. , Reinhardt Camila , Chen Xihua , Martin Gerard M. , Harley Carolyn W. , Yuan Qi
Published: April 2020

The locus coeruleus (LC), the main source of forebrain norepinephrine, produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence coding of sensory information are unknown. Here bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 msec or 10 sec accelerates acquisition of a food-rewarded similar odor discrimination, but not a dissimilar odor discrimination, consistent with LC-supported enhanced pattern separation and plasticity. Similar odor discrimination learning is impaired by noradrenergic blockade in the piriform cortex (PC). However, here 10-Hz LC phasic light-mediated learning facilitation is prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting an LC-VTA-PC dopamine circuitry mediates 10-Hz phasic learning facilitation. Tonic stimulation at 10 Hz did not alter odor discrimination acquisition, and was less effective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced freezing, anxiety and conditioned odor aversion, while 10-Hz phasic stimulation produced an odor preference consistent with positive valence. Noradrenergic blockade in the basolateral amygdala (BLA) prevented conditioned odor preference and aversion induced by 10-Hz phasic and 25-Hz tonic light respectively. CTB retro-labeling showed relatively larger engagement of nucleus accumbens projecting neurons over central amygdala projecting neurons in the BLA with 10-Hz LC phasic activation, compared to 25-Hz tonic. These outcomes argue that LC pauses, as well as LC firing frequencies, differentially influence both target networks and behaviour.
What makesHemidactylusinvasions successful? A case study on the island of Curaçao
Authors: Lamb April D. , Lippi Catherine A. , Watkins-Colwell Gregory J. , Jones Andrew , Warren Dan , Iglesias Teresa L. , Brandley Matt , Neagle Connor , Dornburg Alex
Published: April 2020

Hemidactylusspp. (House geckos) rank among the most successful invasive reptile species worldwide.Hemidactylus mabouiain particular has become ubiquitous across tropical urban settings in the Western Hemisphere.H. mabouia’sability to thrive in close proximity to humans has led to the rapid displacement of native geckos in urban areas, however the mechanisms driving this displacement remain understudied. Here we combine data from nitrogen and carbon stable isotopes, stomach contents, and morphometric analyses of traits associated with feeding and locomotion to test alternate hypotheses of displacement betweenH. mabouiaand a native gecko,Phyllodactylus martini, on the island of Curaçao. Consistent with expectations of direct food resource competition, we demonstrate substantial overlap of invertebrate prey resources between the species. Additionally, we found strong evidence from both diet content and stable isotope analyses thatH. mabouiaacts as a vertebrate predator, preying uponP. martinias well as other native and non-native reptiles. Finally, we show thatH. mabouiapossesses several morphological advantages, including larger sizes in feeding-associated traits and limb proportions that could offer a propulsive locomotor advantage on vertical surfaces. Together, these findings suggest the successful establishment ofH. mabouialikely involves a combination of both exploitative interspecific competition and predation. Given the ubiquity ofH. mabouia, illuminating the role of this species as both a competitor and a predator casts new concerns on the ecological and demographic impacts of this widespread urban invader.
Transfer learning improves antibiotic resistance class prediction
Authors: Hamid Md-Nafiz , Friedberg Iddo
Published: April 2020

Motivation

Antibiotic resistance is a growing public health problem, which affects millions of people worldwide, and if left unchecked is expected to upend many aspects of healthcare as it is practiced today. Identifying the type of antibiotic resistant genes in genome and metagenomic sample is of utmost importance in the prevention, diagnosis, and treatment of infections. Today there are multiple tools available that predict antibiotic resistance class from DNA and protein sequences, yet there is a lack of benchmarks on the performances of these tools.

Results

We have developed a dataset that is curated from 15 available databases, and annotated with their antibiotic class labels. We also developed a transfer learning approach with neural networks, TRAC, that outperforms existing antiobiotic resistance prediction tools. While TRAC provides the current state-of-the-art performance, we hope our newly developed dataset will also provide the community with a much needed standardized dataset to develop novel methods that can predict antibiotic resistance class with superior prediction performance.

Availability

TRAC is available at github (https://github.com/nafizh/TRAC) and the datasets are available at figshare (https://doi.org/10.6084/m9.figshare.11413302).

Contact

mhamid@mgh.harvard.edu,idoerg@iastate.edu
Behavioral and Neural Variability of Naturalistic Arm Movements
Authors: Peterson Steven M. , Singh Satpreet H. , Wang Nancy X. R. , Rao Rajesh P. N. , Brunton Bingni W.
Published: April 2020

Abstract

Motor behaviors are central to many functions and dysfunctions of the brain, and understanding their neural basis has consequently been a major focus in neuroscience. However, most studies of motor behaviors have been restricted to artificial, repetitive paradigms, far removed from natural movements performed “in the wild.” Here, we leveraged recent advances in machine learning and computer vision to analyze intracranial recordings from 12 human subjects during thousands of spontaneous, unstructured arm reach movements, observed over several days for each subject. These naturalistic movements elicited cortical spectral power patterns consistent with findings from controlled paradigms, but with considerable neural variability across subjects and events. We modeled inter-event variability using ten behavioral and environmental features; the most important features explaining this variability were reach angle and day of recording. Our work is among the first studies connecting behavioral and neural variability across cortex in humans during unstructured movements and contributes to our understanding of long-term naturalistic behavior.
The high-energy transition state of a membrane transporter
Authors: Huysmans Gerard H. M. , Ciftci Didar , Wang Xiaoyu , Blanchard Scott C. , Boudker Olga
Published: April 2020

Membrane transporters mediate cellular uptake of nutrients, signaling molecules and drugs. Their overall mechanisms are often well understood, but the structural features setting their rates are mostly unknown. Earlier single-molecule fluorescence imaging of a model glutamate transporter homologue suggested that the slow conformational transition from the outward- to the inward-facing state, when the bound substrate is translocated from the extracellular to the cytoplasmic side of the membrane, is rate-limiting to transport. Here, we aim to gain insight into the structure of the high-energy transition state that limits the rate of this critical isomerization reaction. Using bioinformatics, we identify gain-of-function mutants of the transporter and apply linear free energy relationship analysis to infer that the transition state structurally resembles the inward-facing conformation. Based on these analyses, we propose an approach for allosteric modulation of these transporters.
Network-principled deep generative models for designing drug combinations as graph sets
Authors: Karimi Mostafa , Hasanzadeh Arman , shen Yang
Published: April 2020

Motivation

Combination therapy has shown to improve therapeutic efficacy while reducing side effects. Importantly, it has become an indispensable strategy to overcome resistance in antibiotics, anti-microbials, and anti-cancer drugs. Facing enormous chemical space and unclear design principles for small-molecule combinations, computational drug-combination design has not seen generative models to meet its potential to accelerate resistance-overcoming drug combination discovery.

Results

We have developed the first deep generative model for drug combination design, by jointly embedding graph-structured domain knowledge and iteratively training a reinforcement learning-based chemical graph-set designer. First, we have developed Hierarchical Variational Graph Auto-Encoders (HVGAE) trained end-to-end to jointly embed gene-gene, gene-disease, and disease-disease networks. Novel attentional pooling is introduced here for learning disease-representations from associated genes’ representations. Second, targeting diseases in learned representations, we have recast the drug-combination design problem as graph-set generation and developed a deep learning-based model with novel rewards. Specifically, besides chemical validity rewards, we have introduced novel generative adversarial award, being generalized sliced Wasserstein, for chemically diverse molecules with distributions similar to known drugs. We have also designed a network principle-based reward for drug combinations. Numerical results indicate that, compared to state-of-the-art graph embedding methods, HVGAE learns more informative and generalizable disease representations. Results also show that the deep generative models generate drug combinations following the principle across diseases. Case studies on four diseases show that network-principled drug combinations tend to have low toxicity. The generated drug combinations collectively cover the disease module similar to FDA-approved drug combinations and could potentially suggest novel systems-pharmacology strategies. Our method allows for examining and following network-based principle or hypothesis to efficiently generate disease-specific drug combinations in a vast chemical combinatorial space.

Availability

https://github.com/Shen-Lab/Drug-Combo-Generator
Topsentinol L Trisulfate, a new Marine Natural Product, that Targets Basal-like and Claudin-low Breast Cancers
Authors: El-Chaar Nader N. , Smith Thomas E. , Shrestha Gajendra , Piccolo Stephen R. , Harper Mary Kay , Van Wagoner Ryan M. , Lu Zhenyu , Venancio Ashlee R. , Ireland Chris M. , Bild Andrea H. , Moos Philip J.
Published: April 2020

Background

Breast cancer is a heterogeneous disease. Genomic studies have revealed five different intrinsic subtypes - Luminal A, Luminal B, HER2-enriched, Claudin-low, and Basal-like. Patients diagnosed with Basal-like or Claudin-low breast cancer (BL-CL) suffer from poor prognosis and limited treatment options. Hence, there is an urgent need to identify a new therapeutic lead that can benefit patients with BL-CL breast cancer.

Methods

We used a step-wise screening approach to screen 2778 HP20 fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancer. We also performed biochemical investigations to study the effect of the compound in the signaling pathway. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound.

Results

We identified a previously unreported trisulfated sterol, topsentinol L trisulfate (TLT) that exhibits increased efficacy against BL-CL relative to Luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL revealed its ability to inhibit activation of AMPK and CHK1 and promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (Dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL compared to Luminal/HER2+ breast cancer. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT while glioblastoma multiforme as least sensitive.

Conclusions

Our study identified TLT, a previously uncharacterized trisulfated sterol, as a potential therapeutic selective against BL-CL. Our results also showed that inhibition of AMPK and/or CHK1 might be an effective therapy in BL-CL.
Inhibition of Striatal-Enriched Protein Tyrosine Phosphatase (STEP) Activity Reverses Behavioral Deficits in a Rodent Model of Autism
Authors: Chatterjee Manavi , Singh Priya , Xu Jian , Lombroso Paul J. , Kurup Pradeep K.
Published: April 2020

Autism spectrum disorders (ASDs) are highly prevalent childhood illnesses characterized by impairments in communication, social behavior, and repetitive behaviors. Studies have found aberrant synaptic plasticity and neuronal connectivity during the early stages of brain development and have suggested that these contribute to an increased risk for ASD. STEP is a protein tyrosine phosphatase that regulates synaptic plasticity and is implicated in several cognitive disorders. Here we test the hypothesis that STEP may contribute to some of the aberrant behaviors present in the VPA-induced mouse model of ASD.In uteroVPA exposure of pregnant dams results in autistic-like behavior in the pups, which is associated with a significant increase in the STEP expression in the prefrontal cortex. The elevated STEP protein levels are correlated with increased dephosphorylation of STEP substrates GluN2B, Pyk2 and ERK, suggesting upregulated STEP activity. Moreover, pharmacological inhibition of STEP rescues the sociability, repetitive and abnormal anxiety phenotypes commonly associated with ASD. These data suggest that STEP may play a role in the VPA model of ASD and STEP inhibition may have a potential therapeutic benefit in this model.
Image-based elastography of heterochromatin and euchromatin domains in the deforming cell nucleus
Authors: Ghosh Soham , Cuevas Victor Crespo , Seelbinder Benjamin , Neu Corey P.
Published: April 2020

Chromatin of the eukaryotic cell nucleus comprises of microscopically dense heterochromatin and loosely packed euchromatin domains, each with distinct transcriptional ability and roles in cellular mechanotransduction. While recent methods have been developed to characterize the nucleus, measurement of intranuclear mechanics remains largely unknown. Here, we describe the development ofnuclear elastography, which combines microscopic imaging and computational modeling to quantify the relative elasticity of the heterochromatin and euchromatin domains. Using contracting murine embryonic cardiomyocytes, nuclear elastography reveals that the heterochromatin is almost four times stiffer than the euchromatin at peak deformation. The relative elasticity between the two domains changes rapidly during the active deformation of the cardiomyocyte in the normal physiological condition but progresses more slowly in cells cultured in a mechanically stiff environment, although the relative stiffness at peak deformation does not change. Further, we found that the disruption of the LINC complex in cardiomyocytes compromises the intranuclear elasticity distribution resulting in elastically similar heterochromatin and euchromatin. These results provide insight into the elastography dynamics of heterochromatin and euchromatin domains, and provide a non-invasive framework to further investigate the mechanobiological function of subcellular and subnuclear domains limited only by the spatiotemporal resolution of the image acquisition method.
Disrupted copper availability in sporadic ALS: Implications for CuII(atsm) as a treatment option
Authors: Hilton James BW , Kysenius Kai , Liddell Jeffrey R , Rautengarten Carsten , Mercer Stephen W. , Paul Bence , Beckman Joseph S , McLean Catriona A. , White Anthony R , Donnelly Paul S , Bush Ashley I , Hare Dominic J , Roberts Blaine R , Crouch Peter J
Published: April 2020

Objective

The copper compound CuII(atsm) is in phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) consistently and reproducibly ameliorates neurodegeneration in mutant SOD1 mouse models of ALS where its neuroprotective activity has been ascribed in part to improving availability of copper to essential cuproenzymes. However, SOD1 mutations cause only ~2% of ALS cases with most cases being of unknown aetiology. Therapeutic pertinence of CuII(atsm) to sporadic ALS is therefore unclear.

Methods

We assayed post-mortem spinal cord tissue from sporadic cases of ALS for the anatomical and biochemical distribution of copper, the expression of genes involved in copper handling, and the activities of cuproenzymes.

Results

The natural distribution of copper is disrupted in sporadic ALS. The ALS-affected tissue has a molecular signature consistent with an unsatiated requirement for copper and cuproenzyme activity is affected. Copper levels are decreased in the ventral grey matter, the primary anatomical site of neuronal loss in ALS.

Interpretation

Mice expressing mutant SOD1 recapitulate salient features of ALS. The unsatiated requirement for copper that is evident in these mice is a biochemical target for CuII(atsm). Evidences provided here for disrupted copper bioavailability in human cases of sporadic ALS indicate that a therapeutic mechanism for CuII(atsm) involving copper bioavailability is pertinent to sporadic cases of ALS, and not just those involving mutant SOD1.
Identifying contextually relevant improvement measures, illustrated by a case of executive walkrounds
Authors: Reed Nick J. , Wilson Natalie , Hayes Kathryn J.
Published: April 2020

Purpose

A method to engage salient organisational stakeholders in identifying and ranking measures of healthcare improvement programs is described. The method is illustrated using Executive WalkRounds (EWRs) in a multi-site Australian Health District.

Design/methodology/approach

Subject matter experts (SMEs) conducted document analysis, identified potential EWRs measures, created driver diagrams and then eliminated weak measures. Next, a panel of executives skilled in EWRs ranked and ratified the potential measures using a modified Delphi technique.

Findings

EWRs measurement selection demonstrated the feasibility of the method. Of the total time to complete the method 79% was contributed by SMEs, 14% by administration personnel and 7% by executives. Document analysis revealed three main EWRs aims. Ten of 28 potential measures were eliminated by the SME review. After repeated Delphi rounds the executive panel achieved consensus (75% cut-off) on seven measures. One outcome, one process and one implementation fidelity metric were selected to measure and monitor the impact of EWRs in the health district.

Practical implications

Perceptions of weak relationships between measures and intended improvements can lead to practitioner scepticism. This work offers a structured method to combine the technical expertise of SMEs with the practical knowledge of healthcare staff in selecting improvement measures.

Originality/value

This research describes and demonstrates a novel method to systematically leverage formal and practical types of expertise to select measures that are strongly linked to local quality improvement goals. The method can be applied in diverse healthcare settings.
Evidence for altered insulin signalling in the brains of genetic absence epilepsy rats from Strasbourg
Authors: Sekar Sathiya , Marks Wendie N. , Gopalakrishnan Venkat , Greba Quentin , Snutch Terrance P. , Howland John G. , Taghibiglou Changiz
Published: April 2020

Insulin‐mediated signalling in the brain is critical for neuronal functioning. Insulin resistance is implicated in the development of some neurological diseases, although changes associated with absence epilepsy have not been established yet. Therefore, we examined the major components of PI3K/Akt‐mediated insulin signalling in cortical, thalamic, and hippocampal tissues collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non‐Epileptic Control (NEC) rats. Insulin levels were also measured in plasma and cerebrospinal fluid (CSF). For the brain samples, the nuclear fraction (NF) and total homogenate (TH) were isolated and investigated for insulin signalling markers including insulin receptor beta (IRβ), IR substrate‐1 and 2 (IRS1 & 2), phosphatase and tensin homologue (PTEN), phosphoinositide 3‐kinase phospho‐85 alpha (PI3K p85α), phosphatidylinositol 4,5‐bisphosphate, phosphatidylinositol (3,4,5)‐trisphosphate, protein kinase B (PKB/Akt1/2/3), glucose transporter‐1 and 4 (GLUT1 & 4) and glycogen synthase kinase‐3β (GSK3β) using western blotting. A significant increase in PTEN and GSK3β levels and decreased PI3K p85α and pAkt1/2/3 levels were observed in NF of GAERS cortical and hippocampal tissues. IRβ, IRS1, GLUT1, and GLUT4 levels were significantly decreased in hippocampal TH of GAERS compared to NEC. A non‐significant increase in insulin levels was observed in plasma and CSF of GAERS rats. An insulin sensitivity assay showed decreased p‐Akt level in cortical and hippocampal tissues. Together, altered hippocampal insulin signalling was more prominent in NF and TH compared to cortical and thalamic regions in GAERS. Restoring insulin signalling may improve the pathophysiology displayed by GAERS, including the spike‐and‐wave discharges that relate to absence seizures in patients.
Home range variability, spatial aggregation, and excursions of Akodon azarae and Oligoryzomys flavescens in Pampean agroecosystems
Authors: GOROSITO Irene , BENÍTEZ Ailén , BUSCH Maria
Published: April 2020

Rodents are reservoirs of various types of hantavirus, some of which are agents of hantavirus pulmonary syndrome in humans. Each hantavirus is associated with a single rodent host species but successive spill‐over events may eventually lead to host‐switching and new species’ becoming host of a given pathogen. This study aims to gain an understanding of the spatial ecology of two hantavirus‐host species, Akodon azarae, and Oligoryzomys flavescens, by identifying factors modulating their home range sizes and stability, and by evaluating intra‐ and interspecific spatial aggregation for these species and a third one—Oxymycterus rufus—living in sympatry. For this, eleven capture‐mark‐recapture surveys were carried out, spanning 22 months.

We found that A. azarae males have larger and more mobile home ranges than females, independently of the season. Consequently, males could likely have a more relevant role in the transmission of hantavirus because of their greater exposure both to a higher number of contacts between individuals and viral contamination of the environment. Contrasting, O. flavescens individuals showed negligible displacements of their home range through time, which could limit the range of hantavirus spread in host populations. Since O. flavescens is host to Lechiguanas hantavirus (pathogenic to humans) this result encompasses epidemiological relevance, for it may imply the existence of local foci of infection. Additionally, individuals of both species performed excursions outside their home ranges. These events could enable hantavirus spread over distances beyond the normal range of movements and lead to new hantavirus outbreaks in formerly non‐infected rodent populations, favoring the persistence of the virus in nature.
Teaching Hispanic Restaurant Workers: Translanguaging as Culturally Sustaining Pedagogy
Authors: Emerick Mark R. , Hoffman Brooke Y. , Kanno Yasuko
Published: April 2020

In this article, we make a case for incorporating translanguaging pedagogy into the framework of Culturally Sustaining Pedagogy (CSP). Drawing on data from a one‐year ethnographic study of an adult ESL program, we show how teachers believed in and attempted to create spaces for translanguaging and CSP but in practice fell short. We conclude that translanguaging is most powerful when understood as a component of CSP but call for more research in this area.
Amoxicillin‐induced gut dysbiosis influences estrous cycle in mice and cytokine expression in the ovary and the caecum
Authors: Silva Evandro Neves , Martins Thaís Viana Fialho , Miyauchi‐Tavares Tatimara Maria , Miranda Bianca Aparecida Expedito , dos Santos Gabriela de Assis , Rosa Caio Pupin , Santos Jeferson Antônio , Novaes Rômulo Dias , de Almeida Leonardo Augusto , Corsetti Patrícia Paiva
Published: April 2020

Problem

Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin‐induced gut dysbiosis and its influence on the oestrous cycle in mice.

Method of study

Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL‐1β and IL‐10 genes and histological analysis.

Results

Amoxicillin‐treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS‐treated group indicating that amoxicillin treatment‐induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin‐induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL‐1β was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL‐10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non‐dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non‐dysbiotic mice.

Conclusion

The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.
Sex of the first‐born and obstetric complications in the subsequent birth. A study of 2.3 million second births from Denmark, Finland, Norway, and Sweden
Authors: Mortensen Laust H. , Cnattingius Sven , Gissler Mika , Klungsøyr Kari , Skjærven Rolv , Nybo Andersen Anne‐Marie , Nielsen Henriette S.
Published: April 2020

Introduction

Studies have shown associations between a first‐born boy and increased risks of pregnancy loss, stillbirth, decreased birthweight, and preterm birth in subsequent pregnancies, but with limited precision.

Material and Methods

We examined associations between sex of the first‐born and obstetric complications in second births. We calculated the relative risks (RR)s of preeclampsia/eclampsia, placental abruption, stillbirth, and preterm birth in approximately 2.3 million second births comparing women with a preceding first‐born boy to those with a first‐born girl using the Medical Birth Registries of Denmark, Finland, Norway, and Sweden 1980‐2008.

Results

In second births following a first‐born boy rather than a girl, the RR was 4% higher for preeclampsia/eclampsia (RR = 1.04, 95% CI 1.02‐1.06), 9% higher for placental abruption (RR = 1.09, 95% CI 1.05‐1.13), 9% higher for stillbirth (RR = 1.09, 95% CI 1.04‐1.14), and 8% higher for preterm birth (RR = 1.08, 95% CI 1.07‐1.09). The population attributable risks ranged from 2% to 4.5%.

Conclusions

Male sex of the first‐born is associated with small increases in risks of obstetric complications in the second birth. Exploration of the underlying mechanisms is needed to increase our knowledge and treatment options for these serious obstetric complications.
Identity Continuity Protects Academic Performance, Retention, and Life Satisfaction among International Students
Authors: Cruwys Tegan , Ng Nikole W.K. , Haslam S. Alexander , Haslam Catherine
Published: April 2020

International students transitioning to university undergo dramatic changes in social identity, with a need to adapt to a new culture, language, environment, and way of living. This paper explores the impact of this social identity change on academic performance, academic retention, mental health, and life satisfaction. The Social Identity Model of Identity Change (SIMIC) predicts that during life transitions of this form, an individual’s group memberships and associated social identities can protect them from the negative effects of life change. This longitudinal study tested SIMIC among international students (N = 210) transitioning to study overseas, with data collected at three time points across a Foundation Year programme in a large Australian university. Consistent with SIMIC, continuity of social identities predicted higher academic performance and better life satisfaction, and indirectly predicted student retention over time.
Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions
Authors: Rizaner Nahit , Uzun Sercan , Fraser Scott P. , Djamgoz Mustafa B. A. , Altun Seyhan
Published: April 2020

Anti‐invasive effects of riluzole and ranolazine, a neuro‐protectant and an anti‐anginal drug, respectively, on Mat‐LyLu rat prostate cancer (PCa) cells were tested in vitro (a) at non‐toxic doses and (b) under both normoxic and hypoxic conditions, the latter common to growing tumours. Tetrodotoxin (TTX) was used as a positive control. Hypoxia had no effect on cell viability but reduced growth at 48 hours. Riluzole (5 μmol/L) or ranolazine (20 μmol/L) had no effect on cell viability or growth under normoxia or hypoxia over 24 hours. Matrigel invasion was not affected by hypoxia but inhibited by TTX, ranolazine and riluzole under a range of conditions. The expression of Nav1.7 mRNA, the prevailing, pro‐invasive voltage‐gated sodium channel α‐subunit (VGSCα), was up‐regulated by hypoxia. Riluzole had no effect on Nav1.7 mRNA expression in normoxia but significantly reduced it in hypoxia. VGSCα protein expression in plasma membrane was reduced in hypoxia; riluzole increased it but only under hypoxia. It was concluded (a) that riluzole and ranolazine have anti‐invasive effects on rat PCa cells and (b) that Nav1.7 mRNA and protein expression can be modulated by riluzole under hypoxia. Overall, therefore, riluzole and ranolazine may ultimately be “repurposed” as anti‐metastatic drugs against PCa.
Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes
Authors: Hino Hirotsugu , Iriyama Noriyoshi , Kokuba Hiroko , Kazama Hiromi , Moriya Shota , Takano Naoharu , Hiramoto Masaki , Aizawa Shin , Miyazawa Keisuke
Published: April 2020

In the cell cycle, the G1/S transition is controlled by the cyclin‐dependent kinase (CDK) 4/6‐cyclin D complex. Constitutive activation of CDK4/6 dysregulates G1/S transition, leading to oncogenic transformation. We found that 3 CDK4/6 inhibitors, abemaciclib, ribociclib, and palbociclib, exerted a cytocidal effect as well as a cytostatic effect at the G1 phase in cancer cell lines, including A549 human non–small cell lung cancer cells. Among these inhibitors, abemaciclib exhibited the most potent cytotoxic effect. The cell‐death phenotype induced by abemaciclib, which entailed formation of multiple cytoplasmic vacuoles, was not consistent with apoptosis or necroptosis. Abemaciclib blocked autophagic flux, resulting in accumulation of autophagosomes, however vacuole formation and cell death induced by abemaciclib were independent of autophagy. In addition, methuosis, a cell‐death phenotype characterized by vacuole formation induced by excessive macropinocytosis, was excluded because the vacuoles did not incorporate fluorescent dextran. Of note, both formation of vacuoles and induction of cell death in response to abemaciclib were inhibited by vacuolar‐type ATPase (V‐ATPase) inhibitors such as bafilomycin A1 and concanamycin A. Live‐cell imaging revealed that the abemaciclib‐induced vacuoles were derived from lysosomes that expanded following acidification. Transmission electron microscopy revealed that these vacuoles contained undigested debris and remnants of organelles. Cycloheximide chase assay revealed that lysosomal turnover was blocked by abemaciclib. Furthermore, mTORC1 inhibition along with partial lysosomal membrane permeabilization occurred after abemaciclib treatment. Together, these results indicate that, in cancer cells, abemaciclib induces a unique form of cell death accompanied by swollen and dysfunctional lysosomes.
COVID‐19 impact on fruit and vegetable markets
Authors: Richards Timothy J. , Rickard Bradley
Published: April 2020

Canadian fruit and vegetable markets were significantly impacted by the spread of the novel coronavirus SARS‐CoV‐2 (and COVID‐19 disease), beginning in March 2020. Due to the closure of restaurants, bars, and schools, produce growers and distributors were forced to shift supplies almost entirely from the foodservice to the retail channel. Shippers reported labor and logistical constraints in making the change, but the fresh produce supply chain remained robust. In the long term, we expect lasting changes in consumers’ online food‐purchasing habits, heightened constraints on immigrant labor markets, and tighter concentration in fresh produce distribution and perhaps retailing.
The teleological stance: Past, present, and future
Authors: Juvrud Joshua , Gredebäck Gustaf
Published: April 2020

We review the support for, and criticisms of, the teleological stance theory, often described as a foundation for goal‐directed action understanding early in life. A major point of contention in the literature has been how teleological processes and assumptions of rationality are represented and understood in infancy, and this debate has been largely centered on three paradigms. Visual habituation studies assess infant's abilities to retrospectively assess teleological processes; the presence of such processes is supported by the literature. Rational imitation is a phenomenon that has been questioned both theoretically and empirically, and there is currently little support for this concept in the literature. The involvement of teleological processes in action prediction is unclear. To date, the ontology of teleological processes remains unspecified. To remedy this, we present a new action‐based theory of teleological processes (here referred to as the embodied account of teleological processes), based on the development of goal‐directed reaching with its origin during the fetal period and continuous development over the first few months of life.
Multicenter evaluation of analytical performances of platelet counts and platelet parameters: Carryover, precision, and stability
Authors: Gioia Maria , Da Rin Giorgio , Manenti Barbara , Birindelli Sarah , Ciardelli Maria Laura , Gentile Roberto , Beretta Gianluca , Lorusso Giuseppe , Avino Daniela , Di Fabio Anna Maria , Dima Francesco , Fanelli Alessandra , Lorubbio Maria , Francione Sara , Marincheva Galina , Marini Alessandra , Papa Angela , Giannelli Elena , Pajola Rachele , Panzeri Andrea , Pipitone Silvia , Benegiamo Anna , Rolla Roberta , Vidali Matteo , Buoro Sabrina
Published: April 2020

Introduction

The correctness of the results of automated platelet analysis is still highly debated. The aim of this multicenter study, conducted according to international guidelines, was to verify the analytical performance of nine different types of hematology analyzers (HAs) in the automated platelet analysis.

Methods

Four hundred eighty‐six peripheral blood samples (PB), collected in K3EDTA tubes, were analyzed by ABX Pentra, ADVIA2120i, BC‐6800, BC‐6800 Plus, Cell‐DYN Sapphire, DxH800, XE‐2100, XE‐5000, XN‐20 with PLT‐F App. Within‐run imprecision and between‐run imprecision were carried out using PB and material control, respectively. The carryover, low limit of quantification (LoQ), and the PB stability were evaluated.

Results

The carryover was absent for all HAs. The LoQ of PLT ranged between 2.0 (Cell‐Dyn Sapphire) and 25.0 × 109/L (ADVIA 2120i), while immature platelet fraction (IPF) ranged between 1.0 (XN‐20) and 12.0 × 109/L (XE‐5000). The imprecision (%CV) increases as the platelet count decreases. No HAs showed desirable CVAPS for PLT counts less than 50.0 × 109/L, with the exception of Cell‐DYN Sapphire (CV 3.0% with PLT‐O mean value of 26.7 × 109/L), XN‐20 (CV 2.4% with PLT‐F mean value of 21.5 × 109/L), and BC‐6800 Plus (CV 1.9% with PLT‐O mean value of 26.5 × 109/L). The sample stability ranged between under two hours for MPV by ADVIA2120i and 8 hours for other PLT parameters and HAs.

Conclusion

The findings of this study may provide useful information regarding carryover, precision, and stability of platelet counts and parameters, especially in thrombocytopenic samples. Moreover, the stability of sample for platelet analysis is conditioned by the HA and by temperature and storage time.
Positioning immobile critically ill patients who are at risk of pressure injuries using a purpose‐designed positioning device and usual care equipment: An observational feasibility study
Authors: Sousa Ines , Kapp Suzanne , Santamaria Nick
Published: April 2020

The prevalence of pressure injuries in the intensive care unit (ICU) setting is high with rates ranging from 13.1% to 45.5%. Evaluation of interventions to prevent pressure injuries should be informed by preliminary research to identify factors that should be considered during the design of future trials. The study objectives were to evaluate the process of participant recruitment and monitoring in the ICU; measure the maintenance of body angle (in the side‐lying lateral tilt position) and head and neck alignment angle (in the supine position) among immobile critically ill patients when using a purpose‐designed positioning device and usual care equipment, and; ascertain the time required to position patients with the purpose‐designed positioning device and the usual care equipment. A prospective, observational, feasibility study was conducted in an ICU in Victoria, Australia. The sample was immobile critically ill adults at high‐risk of developing pressure injuries. The usual care interventions were pillows, foam wedges, and rolled towels, and the intervention device was the Z‐Flo Fluidized Positioner. The body angle and head and neck alignment were measured on six occasions (at baseline, 1 hour, and 2 hours). The time required for positioning was also measured. The sample was predominately male (n = 5, 62%) with a mean age of 59 years. The majority of patients (n = 106, 92.2%) were not immobile and therefore were ineligible to participate. A total of 48 turning and positioning interventions were observed. For the side‐lying lateral tilt position, the degree of difference from baseline to 2 hours was no more than three degrees for all the devices (the Fluidized Positioner 25°‐26°, the foam wedge 29°‐27°, and the pillow 23°‐21°). For the head and neck position, the degree of difference from baseline to 2 hours was the greatest for the pillow and rolled towel (78°‐71°, a difference of 7°) and the pillow alone (79°‐74°, a difference of 5°). The degree of difference was the lowest for the Fluidized Positioner (84°‐86°, a difference of 2°). Future research to evaluate positioning equipment in the ICU should consider patient eligibility characteristics, particularly immobility. The conduct of preliminary studies to inform the design of larger pressure injury prevention trials is recommended.
High‐pressure structural investigation on lead‐free piezoelectric 0.5Ba(Ti0.8Zr0.2)O3 ‐ 0.5(Ba0.7Ca0.3)TiO3
Authors: Mondal Anshuman , Saha Pinku , Ghosh Bishnupada , Sahu Mrinmay , Mukherjee Goutam Dev , Ranjan Rajeev , Brajesh Kumar
Published: April 2020

The solid solution 0.5Ba(Ti0.8Zr0.2)O3 − 0.5(Ba0.7Ca0.3)T iO3 (BCZT) has become a promising member of the lead‐free piezoelectric materials because of its exceptionally high piezoelectric properties. In this study, we focus on studying pressure‐dependent Raman spectroscopy, powder x‐ray diffraction, and dielectric constant measurements on BCZT. The data show several structural transitions are present, where the system from ambient mixed phase (tetragonal P4mm + orthorhombic Amm2) transforms into single phase (P4mm) at 0.3 GPa, then converts into cubic phase (Pm3m) at 4.8 GPa followed by another possible structural re‐ordering around 10 GPa. Although there have been a lot of unanimity with the ambient crystallographic state of BCZT, our analysis justifies the presence of an intermediate orthorhombic phase in the Morphological Phase Boundary (MPB) of BCZT phase diagram. The transformation tetragonal to cubic is indicated by the Raman mode softening, unit cell volume change, and the (Ti/Zr)O6 octahedra distortion, which coincides with the well‐known ferroelectric‐paraelectric transition of the system. The sudden drop in the dielectric constant value at 4.7 GPa also confirms the loss of ferroelectric nature of the BCZT ceramic.