bluuebunny/crossref_metadata_2025 huggingface dataset:
Clavicle Fractures
Authors: Ramponi Denise R. , Jo Cerepani Mary
Published: April 2021

Clavicle fractures are commonly seen in children and young adults. A case of a 30-year-old woman sustaining a clavicle fracture while riding a bike is highlighted. The most common cause is strong fall with the injured arm at one's side, often in contact sports injuries. The clavicle is divided into thirds: medial (proximal), middle (midshaft), and lateral (distal) thirds. Eighty percent of clavicle fractures occur in the middle third of the clavicle, and nearly half of those midshaft fractures are displaced. Goals of initial treatment are to reduce pain and limit motion of the fracture fragments until bone union with either sling or figure-of-eight dressing. Surgical treatment has recently shown reduction of the nonunion rate and decreases the time for fracture union compared with nonsurgical treatment.
Variation in Participation in Nurse-Driven Emergency Department Hepatitis C Screening
Authors: Lane Bennett H. , Ancona Rachel M. , Lyons Michael S. , Punches Brittany E.
Published: April 2021

Emergency departments (EDs) are an important potential site for public health screening programs, although implementation of such programs can be challenging. Potential barriers include system-level issues (e.g., funding and time pressures) and individual provider-level issues (e.g., awareness and acceptance). This cross-sectional evaluation of a nurse-driven, triage-based hepatitis C virus (HCV) screening program in an urban, academic ED assessed variation in nurse participation from April to November 2017. For this program, electronic health record (EHR) prompts for HCV screening were integrated into nurses' triage workflow. Process measures evaluating HCV screening participation were abstracted from the EHR for all ED encounters with patient year of birth between 1945 and 1965. Registered nurses who routinely worked in triage and were full-time employees throughout the study period were included for analysis. The primary outcome was the proportion of eligible ED encounters with completed HCV screening, by nurse. Of 14,375 ED encounters, 3,375 (23.5%, 95% confidence interval [CI]: 22.8, 24.2) had completed HCV screening and 1,408 (9.8%, 95% CI: 3.9, 10.3) had HCV screening EHR sections opened by the triage nurse but closed without action; the remainder of encounters had no activity in HCV screening EHR sections. Among the 93 eligible nurses, 22 nurses (24%, 95% CI: 16, 34) completed HCV screening for more than 70% of encounters, whereas 10 nurses (11%, 95% CI: 6, 19) never completed HCV screening. The proportion of eligible encounters with completed HCV screening was 11.0% higher (95% CI: 9.8, 12.6) for encounters seen between 7 a.m. and 7 p.m. than between 7 p.m. and 7 a.m. (27.5% and 16.3%, respectively). In conclusion, wide variation in individual nurse participation in HCV screening suggests individual-level barriers are a more significant barrier to ED screening than previously recognized. Implementation research should expand beyond questions of resource availability and procedural streamlining to evaluate and address staff knowledge, beliefs, attitudes, and motivation.
Xanthohumol protect cognitive performance in diabetic model rats by inhibiting protein kinase B/nuclear factor kappa-B pathway
Authors: Ma Shanbo , Zhang Rui , Li Long , Qu Hui , Wang Jin , Yang Qian , Guo Chao , Miao Shan , Shi Xiaopeng
Published: April 2021

Xanthohumol (XN, 2′, 4′, 4-trihydroxy-6′-methoxy-3′-prenylchalcone), a polyphenol chalcone from hops (Humulus lupulus), has received increasing attention due to its multiple pharmacologic activities. As an active component in beers, its presence has been suggested to be linked to the epidemiologic observation of the beneficial effect of regular beer drinking. But regarding cardiovascular and immunologic effects of polyphenols and ethanol, benefits of beer drinking in patients with diabetes were still in doubt. Diabetes was induced in male Sprague–Dawley rats by administering a high-fat diet and an intraperitoneal 30 mg/kg streptozotocin injection. The animals were treated orally with saline or XN at 50 mg/kg/d for 4 weeks. At the end of the treatment, hippocampus from different groups were collected for biochemical examination. In this study, we found XN inhibit phosphorylation of protein kinase B and nuclear factor kappa-B which was overactivated in diabetic rats, followed by decreased blood glucose and increased body weight. Additionally, XN treatment significantly increased freezing time in a fear memory test. In further research, we found XN increased synaptic plasticity and dendritic spine density, while decreased reactive oxygen species in hippocampus slices from diabetic rats. All these results indicate that XN might be a promising drug to treat diabetic encephalopathy.
Expression of ghrelin or growth hormone secretagogue receptor in the brain of postpartum stress mice
Authors: Xing Jing-Wei , Tian Xin-Yun , Chen Man-Man , Peng Xiu-Hua , Gao Pengfei
Published: April 2021

Postpartum depression is one of the most common mental diseases that occur in women after childbirth; this disorder is extremely painful for women and represents a major burden on the society. Therefore, we designed this study to explore the possible material basis of the disease, and provide potential novel antidepressants therapy using a mouse model. We established a postpartum immobilization stress model. Maternal body weight changes and food intake were recorded for half a month after delivery, and levels of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR) were measured. The mice in the immobilization stress group showed stress activity as well as low body weight and low feeding status. Ghrelin expression was elevated in blood whereas ghrelin or GHSR expression decreased in the hippocampus and prefrontal cortex of the immobilization stress mice, and the number of ghrelin-active and GHSR cells reduced.
Protective effect of metformin against ovariectomy induced depressive- and anxiety-like behaviours in rats: role of oxidative stress
Authors: Turan Inci , Sayan Özaçmak Hale , Erdem Salih , Ergenc Meryem , Ozacmak Veysel Haktan
Published: April 2021

Several studies have shown that low estrogen levels can lead to an increase in the incidence of depression and anxiety during menopause. The hippocampus and prefrontal cortex are parts of the brain involved in depressive- and anxiety-like behaviors. Recent studies have revealed that metformin has neuroprotective effects mainly due to its antioxidant properties. The aim of the present study was to examine the therapeutic potential of metformin in depressive- and anxiety-like behavior as well as oxidative stress in the prefrontal cortex and hippocampus of ovariectomized rats. Young female Wistar Albino rats were distributed into four groups (n:8): control, metformin-administered control, ovariectomized and metformin administered ovariectomized groups. Metformin (25 mg/kg) was administered daily by oral gavage for 2 weeks. Forced swimming test and open field test were performed to evaluate depression- and anxiety-like behaviors, respectively. Following the treatment with metformin, the tissues of the hippocampus and prefrontal cortex were isolated for the measurement of malondialdehyde, reduced glutathione and ascorbic acid contents. Ovariectomy resulted in depressive- and anxiety-like behaviors, and besides, increased content of malondialdehyde in both prefrontal cortex and hippocampus. The levels of ascorbic acid and glutathione were found to be reduced in ovariectomized rats. Metformin treatment significantly decreased depressive behaviour and malondialdehyde content in the prefrontal cortex. Reducing oxidative stress of the prefrontal cortex was suggested as a possible mechanism implicated in the beneficial effects of metformin on ovariectomy-induced depressive-like behaviour. We believe that the therapeutic efficiency of metformin needs to be tested for potential clinical use in surgical menopause or gonadal hormone deficiency women with depression.
Event-related potentials reveal that bilinguals are more efficient in resolving conflict than monolinguals
Authors: Botezatu Mona Roxana , Miller Carol A. , Johnson Jaclyn , Misra Maya
Published: April 2021

In the current study, we evaluated behavioral and electrophysiological evidence to determine whether bilinguals differ from monolinguals in the efficiency of response inhibition. Bilinguals and matched monolingual controls performed the flanker task while behavioral and electrophysiological measures were collected. Participants were slower and less accurate in responding to incongruent trials, but the magnitude of the behavioral effect of congruence was not modulated by participant group. The electrophysiological data revealed a biphasic N200/P300 signature. Incongruent trials elicited a larger N200 response, followed by a larger P300 response than congruent trials. The mean amplitude of the N200 component, a marker of conflict detection, was not modulated by group, suggesting that monolinguals and bilinguals did not differ on the ability to detect conflict. However, the mean amplitude of the P300 component, an index of response inhibition, was smaller in bilinguals than monolinguals. This indicates that bilinguals may be more efficient in resolving response conflict relative to monolinguals. Even though the two groups do not differ in behavioral task performance, the event-related potential (ERP) data suggest that monolinguals may be working harder to reach similar patterns of performance as bilinguals. The P300 magnitude correlated positively with picture naming latencies and negatively with Operation Span scores, suggesting that the ERP response to nonlinguistic conflict resolution may capture individual differences in language proficiency and cognitive resources.
Poria cocos polysaccharide attenuates damage of nervus in Alzheimer’s disease rat model induced by D-galactose and aluminum trichloride
Authors: Zhou Xibin , Zhang Yuxing , Jiang Yiqian , Zhou Chunxiang , Ling Yun
Published: April 2021

Poria cocos polysaccharide (PCP) is a compound from Poria cocos, and which is used as a classical tonic agent. This article aims to investigate the effects of PCP on neuronal damage of hippocampus and cognitive function in a rat model of Alzheimer’s disease induced by D-galactose and aluminum trichloride. Oxiracetam (ORC) was used as a positive drug in this experiment. The rats were treated with PCP at doses of 100, 200 and 300 mg/kg/day for 30 days and ORC at dose of 346 mg/kg/day after modeling. The results of behavioral test showed that PCP could prevent cognitive decline in Alzheimer’s disease rats as assessed by Y-maze test and Morris water maze test. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with PCP. Moreover, PCP could reduce neuronal apoptosis in hippocampus of Alzheimer’s disease rats. Furthermore, the activities of superoxide dismutase in the hippocampus were elevated by PCP administration, while acetyl cholinesterase, reactive oxygen, malondialdehyde and inflammatory factors levels were reduced. In addition, we found PCP could attenuate MAPK/NF-κB signal pathway in the hippocampus. All results illustrated that PCP could exert neuroprotective effects at least partly through alleviating oxidative stress, apoptosis, inflammation and inhibiting the MAPK/NF-κB pathway in Alzheimer’s disease rats induced by D-galactose and aluminum trichloride.
PATTERNS OF OCCUPATIONAL MORBIDITY IN ZAMBIA, 2008-2018: A DESCRIPTIVE DATABASE STUDY
Authors: Zambwe M. , Bwembya P.C. , Mutemwa R. , Gasana J.
Published: April 2021

OBJECTIVE

This study aimed to describe characteristics of occupational morbidity in Zambia over an eleven year period: 2008-2018.

METHODS

A descriptive retrospective observational study based on compensation claims database from the Workers Compensation Fund Control Board (WCFCB) in Zambia over the period 2008 to 2018 was conducted. All the accepted compensation claims at WCFCB during the period 2008 to 2018 were reviewed. The reference population of the study was all workers in Zambia covered by WCFCB at the time. All the accepted compensation claims during the period were taken up into the study. Stata version 14 was used to analyze the data, and make descriptive tables and graphs.

RESULTS

The total number of reviewed and analyzed cases was 8,009. The gender most affected by occupational morbidity was males (94%). Married males were more affected (72%) compared to single males. However, single females were more affected than the married females at 4% and 2%, respectively. The major morbidity types were wounds (30%), fractures (29%), and amputations (17%). The biggest contributing industries to the cause of occupational morbidity were manufacturing (27%), and mining (19%). Lusaka and Copperbelt regions were the main epicenters at 49% and 34% respectively.

CONCLUSION

Wounds, fractures and amputations were the most prominent types of occupational morbidity. Traditional gender-based practices of married males seem to underlie their over-exposure to occupational hazards. Manufacturing sector which is poorly regulated compared to the mining sector, was the highest contributor to the occupational morbidity. The manufacturing sector should be subjected to stronger government regulation and inspectorate, with emphasis on compliance to relevant international occupational health and safety protocols.

ARTICLE SUMMARY

Strengths and limitations of the study

The study utilized the WCFCB injury and disease compensation claims data as a proxy to establish the national burden of occupational morbidity in Zambia during the study period, hence contributing to the body of knowledge.

WCFCB does not cover government ministries and the informal sector in the country which accounts for about 89.3% of the total labour force, the injuries and diseases being contracted in the foretasted sectors were never reported to the institution; and hence making findings of our study an understatement of the actual national burden.

Since submission of compensation claims is generally motivated by receiving monetary benefits for an injury or disease contracted, cases of less magnitude are not reported to WCFCB, hence could not be captured in the study.

Out of many diseases WCFCB only recognize pneumoconiosis and pulmonary tuberculosis as occupational diseases, hence our study could only assess those two making the study an understatement of the actual occupational disease burden.
Prediction of RNA-protein interactions using a nucleotide language model
Authors: Yamada Keisuke , Hamada Michiaki
Published: April 2021

Motivation

The accumulation of sequencing data has enabled researchers to predict the interactions between RNA sequences and RNA-binding proteins (RBPs) using novel machine learning techniques. However, existing models are often difficult to interpret and require additional information to sequences. Bidirectional encoder representations from Transformer (BERT) is a language-based deep learning model that is highly interpretable. Therefore, a model based on BERT architecture can potentially overcome such limitations.

Results

Here, we propose BERT-RBP as a model to predict RNA-RBP interactions by adapting the BERT architecture pre-trained on a human reference genome. Our model outperformed state-of-the-art prediction models using the eCLIP-seq data of 154 RBPs. The detailed analysis further revealed that BERT-RBP could recognize both the transcript region type and RNA secondary structure only from sequence information. Overall, the results provide insights into the fine-tuning mechanism of BERT in biological contexts and provide evidence of the applicability of the model to other RNA-related problems.

Availability

Python source codes are freely available athttps://github.com/kkyamada/bert-rbp.

Contact

mhamada@waseda.jp
DeepRegFinder: Deep Learning-Based Regulatory Elements Finder
Authors: Ramakrishnan Aarthi , Wangensteen George , Kim Sarah , Nestler Eric J. , Shen Li
Published: April 2021

Motivation

Enhancers and promoters are important classes of DNA regulatory elements that control gene expression. Identifying them at the genomic scale is a critical and challenging task in bioinformatics. The most successful method so far is to train machine learning models on known enhancer and promoter sites and predict them at other genomic regions using ChIP-seq and related data.

Results

We have developed a highly customizable program called DeepRegFinder which automates data processing, model training and genome-wide prediction of enhancers and promoters using convolutional and recurrent neural networks. Our program further classifies the enhancers and promoters into active and poised states to facilitate downstream analysis. Based on mean average precision scores of different classes across multiple cell types, our method significantly outperforms the existing algorithms.

Availability

https://github.com/shenlab-sinai/DeepRegFinder
Helios is a marker, not a driver, of human Treg stability
Authors: Lam Avery J. , Uday Prakruti , Gillies Jana K. , Levings Megan K.
Published: April 2021

Regulatory T cell (Treg) therapy holds promise as a potentially curative approach to establish immune tolerance in transplantation and autoimmune disease. An outstanding question is whether therapeutic Tregs have the potential to transdifferentiate into effector T cells and thus exacerbate rather than suppress immune responses. In mice, the transcription factor Helios is thought to promote Tregs lineage stability in a range of inflammatory contexts. In humans, the role of Helios in Tregs is less clear, in part due to the inability to enrich and study subsets of Helios-positive versus Helios-negative Tregs. Using an in vitro expansion system, we found that loss of high Helios expression and emergence of an intermediate Helios (Heliosmid)-expressing population correlated with Treg destabilization. We then used CRISPR/Cas9 to genetically ablate Helios expression in human naive or memory Tregs and found that Helios-knockout and unedited Tregs were equivalent in their suppressive function and stability in inflammation. Thus, high Helios expression is a marker, but not a driver, of human Treg stability in vitro. These data highlight the importance of monitoring Helios expression in therapeutic Treg manufacturing and provide new insight into the biological function of this transcription factor in human T cells.
Transcriptome diversity is a systematic source of bias in RNA-sequencing data
Authors: García-Nieto Pablo E. , Wang Ban , Fraser Hunter B.
Published: April 2021

Background

RNA sequencing has been widely used as an essential tool to probe gene expression. While standard practices have been established to analyze RNA-seq data, it is still challenging to detect and remove artifactual signals. Several factors such as sex, age, and sequencing technology have been found to bias these estimates. Probabilistic estimation of expression residuals (PEER) has been used to account for some systematic effects, but it has remained challenging to interpret these PEER factors.

Results

Here we show that transcriptome diversity – a simple metric based on Shannon entropy – explains a large portion of variability in gene expression, and is a major factor detected by PEER. We then show that transcriptome diversity has significant associations with multiple technical and biological variables across diverse organisms and datasets. This prevalent confounding factor provides a simple explanation for a major source of systematic biases in gene expression estimates.

Conclusions

Our results show that transcriptome diversity is a metric that captures a systematic bias in RNA-seq and is the strongest known factor encoded in PEER covariates.
Visual temporal integration by multi-level regularities fosters the emergence of dynamic conscious experience
Authors: Hu Ruichen , Yuan Peijun , Wang Ying , Jiang Yi
Published: April 2021

The relationship between information integration and visual awareness is central to contemporary theories and research on human consciousness. While there is evidence that humans are adept at integrating spatially structured information to form a coherent conscious percept, to date, little is known about how we integrate visual information over time based on its temporal structure and whether such temporal integration process contributes to our awareness of the dynamic world. Using binocular rivalry, we demonstrated that a diverse set of structured visual streams, constituted either by idiom, shape, or motion stimuli, predominated over their non-structured but otherwise matched counterparts in the competition for conscious access. Despite the apparent resemblance, there was a substantial dissociation of these observed privileges between the semantic- and perceptual-level structures, specifically regarding their resistance to spatiotemporal perturbations and demands for conscious processing over the visual integration process. These findings corroborate the essential role of structure-guided information integration in the generation of conscious content and highlight temporal integration by multi-level regularities as a fundamental mechanism to foster the emergence of continuous conscious experience.
Floral scents of a deceptive plant are hyperdiverse and under population-specific phenotypic selection
Authors: Eva Gfrerer , Danae Laina , Marc Gibernau , Roman Fuchs , Martin Happ , Till Tolasch , Wolfgang Trutschnig , Hörger Anja C. , Peter Comes Hans , Stefan Dötterl
Published: April 2021

Floral scent is a key mediator in plant-pollinator interactions; however, little is known to what extent intraspecific scent variation is shaped by phenotypic selection, with no information yet in deceptive plants. We recorded 291 scent compounds in deceptive moth fly-pollinated Arum maculatumfrom various populations north vs. south of the Alps, the highest number so far reported in a single plant species. Scent and fruit set differed between regions, and some, but not all differences in scent could be explained by differential phenotypic selection in northern vs. southern populations. Our study is the first to provide evidence that phenotypic selection is involved in shaping geographic patterns of floral scent in deceptive plants. The hyperdiverse scent ofA. maculatummight result from the plant’s imitation of various brood substrates of its pollinators.
Towards comprehensive plasma proteomics by orthogonal protease digestion
Authors: Fossati Andrea , Richards Alicia L. , Chen Kuei-Ho , Jaganath Devan , Cattamanchi Adithya , Ernst Joel D. , Swaney Danielle L.
Published: April 2021

Rapid and consistent protein identification across large clinical cohorts is an important goal for clinical proteomics. With the development of data-independent technologies (DIA/SWATH-MS), it is now possible to analyze hundreds of samples with great reproducibility and quantitative accuracy. However, this technology benefits from empirically derived spectral libraries that define the detectable set of peptides and proteins. Here we apply a simple and accessible tip-based workflow for the generation of spectral libraries to provide a comprehensive overview on the plasma proteome in individuals with and without active tuberculosis (TB). To boost protein coverage, we utilized non-conventional proteases such as GluC and AspN together with the gold standard trypsin, identifying more than 30,000 peptides mapping to 3,309 proteins. Application of this library to quantify plasma proteome differences in TB infection recovered more than 400 proteins in 50 minutes of MS-acquisition, including diagnosticMycobacterium tuberculosis(Mtb) proteins that have previously been detectable primarily by antibody-based assays and intracellular proteins not previously described to be in plasma.
Distinct gene expression dynamics in germ line and somatic tissue during ovariole morphogenesis inDrosophila melanogaster
Authors: Tarikere Shreeharsha , Ylla Guillem , Extavour Cassandra G.
Published: April 2021

The survival and evolution of a species is a function of the number of offspring it can produce. In insects the number of eggs that an ovary can produce is a major determinant of reproductive capacity. Insect ovaries are made up of tubular egg-producing subunits called ovarioles, whose number largely determines the number of eggs that can be potentially laid. Ovariole number is directly determined by the number of cellular structures called terminal filaments, which are stacks of cells that assemble in the larval ovary. Elucidating the developmental and regulatory mechanisms of terminal filament formation is thus key to understanding the regulation of insect reproduction through ovariole number regulation. We systematically measured mRNA expression of all cells in the larval ovary at the beginning, middle and end of terminal filament formation. We also separated somatic and germ line cells during these stages and assessed their tissue-specific gene expression during larval ovary development. We found that the number of differentially expressed somatic genes is highest during late stages of terminal filament formation and includes many signaling pathways that govern ovary development. We also show that germ line tissue, in contrast, shows greater differential expression during early stages of terminal filament formation, and highly expressed germ line genes at these stages largely control cell division and DNA repair. We provide a tissue-specific and temporal transcriptomic dataset of gene expression in the developing larval ovary as a resource to study insect reproduction.
OTX2 homeoprotein functions in adult choroid plexus
Authors: Planques Anabelle , Moreira Vanessa Oliveira , Benacom David , Bernard Clémence , Jourdren Laurent , Blugeon Corinne , Dingli Florent , Masson Vanessa , Loew Damarys , Prochiantz Alain , Di Nardo Ariel A.
Published: April 2021

Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We show thatOtx2expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and ventricular-subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.
Genetic determinants of endophytism in the Arabidopsis root mycobiome
Authors: Mesny Fantin , Miyauchi Shingo , Thiergart Thorsten , Pickel Brigitte , Atanasova Lea , Karlsson Magnus , Hüttel Bruno , Barry Kerrie W. , Haridas Sajeet , Chen Cindy , Bauer Diane , Andreopoulos William , Pangilinan Jasmyn , LaButti Kurt , Riley Robert , Lipzen Anna , Clum Alicia , Drula Elodie , Henrissat Bernard , Kohler Annegret , Grigoriev Igor V. , Martin Francis M. , Hacquard Stéphane
Published: April 2021

Roots of Arabidopsis thaliana do not engage in symbiotic associations with mycorrhizal fungi but host taxonomically diverse fungal communities that influence health and disease states. We sequenced the genomes of 41 fungal isolates representative of the A. thaliana root mycobiota for comparative analysis with 79 other plant-associated fungi. We report that root mycobiota members evolved from ancestors with diverse lifestyles and retained large repertoires of plant cell wall-degrading enzymes (PCWDEs) and effector-like small secreted proteins. We identified a set of 84 gene families predicting best endophytism, including families encoding PCWDEs acting on xylan (GH10) and cellulose (AA9). These genes also belong to a core transcriptional response induced by phylogenetically-distant mycobiota members in A. thaliana roots. Recolonization experiments with individual fungi indicated that strains with detrimental effects in mono-association with the host not only colonize roots more aggressively than those with beneficial activities but also dominate in natural root samples. We identified and validated the pectin degrading enzyme family PL1_7 as a key component linking aggressiveness of endophytic colonization to plant health.
A strategy for mapping biophysical to abstract neuronal network models applied to primary visual cortex
Authors: Chizhov Anton V. , Graham Lyle J.
Published: April 2021

A fundamental challenge for the theoretical study of neuronal networks is to make the link between complex biophysical models based directly on experimental data, to progressively simpler mathematical models that allow the derivation of general operating principles. We present a strategy that successively maps a relatively detailed biophysical population model, comprising conductance-based Hodgkin-Huxley type neuron models with connectivity rules derived from anatomical data, to various representations with fewer parameters, finishing with a firing rate network model that permits analysis. We apply this methodology to primary visual cortex of higher mammals, focusing on the functional property of stimulus orientation selectivity of receptive fields of individual neurons. The mapping produces compact expressions for the parameters of the abstract model that clearly identify the impact of specific electrophysiological and anatomical parameters on the analytical results, in particular as manifested by specific functional signatures of visual cortex, including input-output sharpening, conductance invariance, virtual rotation and the tilt after effect. Importantly, qualitative differences between model behaviours point out consequences of various simplifications. The strategy may be applied to other neuronal systems with appropriate modifications.

Author summary

A hierarchy of theoretical approaches to study a neuronal network depends on a tradeoff between biological fidelity and mathematical tractibility. Biophysically-detailed models consider cellular mechanisms and anatomically defined synaptic circuits, but are often too complex to reveal insights into fundamental principles. In contrast, increasingly abstract reduced models facilitate analytical insights. To better ground the latter to the underlying biology, we describe a systematic procedure to move across the model hierarchy that allows understanding how changes in biological parameters - physiological, pathophysiological, or because of new data - impact the behaviour of the network. We apply this approach to mammalian primary visual cortex, and examine how the different models in the hierarchy reproduce functional signatures of this area, in particular the tuning of neurons to the orientation of a visual stimulus. Our work provides a navigation of the complex parameter space of neural network models faithful to biology, as well as highlighting how simplifications made for mathematical convenience can fundamentally change their behaviour.
Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
Authors: Schmitz Judith , Zheng Mo , Lui Kelvin F. H. , McBride Catherine , Ho Connie S.-H. , Paracchini Silvia
Published: April 2021

Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n≤ 5 028 family trios) and SNP-based heritability (SNP-h2,n≤ 5 931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n= 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2for quantitative handedness and footedness was .21 and .23, respectively, which is higher than the SNP-h2reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (.45) compared to a binary measure for writing hand (.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.
Formic acid modulates latency and accuracy of nestmate recognition in carpenter ants
Authors: Baracchi David , Giurfa Martin , d’Ettorre Patrizia
Published: April 2021

Decision-making processes face the dilemma of being accurate or faster, a phenomenon that has been described as speed-accuracy trade-off (SAT) in numerous studies on animal behaviour. In social insects, discriminating between colony members and aliens is subjected to this trade-off as rapid and accurate rejection of enemies is of primary importance for the maintenance and ecological success of insect societies. Recognition cues distinguishing aliens from nestmates are embedded in the cuticular hydrocarbon (CHC) layer and vary among colonies. In walking carpenter ants, exposure to formic acid (FA), an alarm pheromone, improves accuracy of nestmate recognition by decreasing both alien acceptance and nestmate rejection. Here we studied the effect of FA exposure on the spontaneous aggressive mandible opening response of harnessedCamponotus aethiopsants presented with either nestmate or alien CHCs. FA modulated both MOR accuracy and the latency to respond to odours of conspecifics. In particular, FA decreased MOR towards nestmates but increased it towards aliens. Furthermore, FA decreased MOR latency towards aliens but not towards nestmates. As response latency can be used as a proxy of response speed, we conclude that contrary to the prediction of the SAT theory, ants did not trade off speed against accuracy in the process of nestmate recognition.

Summary statement

Exposure to an alarm pheromone increases both latency and accuracy of the response to recognition cues in ants
Suboptimal proteome allocation during changing environments constrains bacterial response and growth recovery
Authors: Balakrishnan Rohan , Hwa Terence , Cremer Jonas
Published: April 2021

To sustain growth in fluctuating environments microbial organisms must respond appropriately. The response generally requires the synthesis of novel proteins, but this synthesis can be impeded due to the depletion of biosynthetic precursors when growth conditions vary. Microbes must thus devise effective response strategies to manage depleting precursors. To better understand these strategies, we here investigate the active response ofEscherichia colito changes in nutrient conditions, connecting transient gene-expression behavior to growth phenotypes. By synthetically modifying the gene expression during changing growth conditions, we show how the competition by genes for the limited protein synthesis capacity constrains the cellular response. Despite this constraint, cells substantially express genes that are not required, severely slowing down the response. These findings highlight that cells do not optimize growth and recovery in every encountered environment but rather exhibit hardwired response strategies that may have evolved to promote growth and fitness in their native environment and include the regulation of multiple genes. The constraint and the suboptimality of the cellular response uncovered in this study provides a conceptual framework relevant for many research applications, from the prediction of evolution and adaptation to the improvement of gene circuits in biotechnology.
Illuminati, a novel form of gene expression plasticity inDrosophilaneural stem cells
Authors: Goupil Alix , Heinen Jan Peter , Rossi Fabrizio , Salame Riham , Pennetier Carole , Simon Anthony , Skorski Patricia , Lauzao Anxela , Bardin Allison , Basto Renata , Gonzalez Cayetano
Published: April 2021

With the aim of developing a genetic instability (GI) sensor invivowe used the well-established Gal80/Gal4-UAS system combined with a visual GFP marker inDrosophila. We generated a collection of 25Drosophilalines carrying GAL80 transgenes in different locations in all major chromosomes (X, Y, II, and III). We found low rates of GFP cells in epithelial tissues such as wing discs. In contrast, in larval brains, GFP positive clusters containing neural stem cells- also called neuroblasts (NBs)- and their offspring, were highly frequent. Using genetic and imaging-based approaches, we show that GFP NBs do not result from aneuploidy or mutations in theGAL80gene, but rather by stochastic repression ofGAL80expression. We named this novel type of gene expression instability Illuminati. Importantly, Illuminati frequency is influenced by environmental and stress conditions. Further, we found that once established, Illuminati can be propagated over many cell cycles.
DE-STRESS: A user-friendly web application for the evaluation of protein designs
Authors: Stam Michael J. , Wood Christopher W.
Published: April 2021

De novo protein design is a rapidly growing field and there are now many interesting and useful examples of designed proteins in the literature. However, most designs could be classed as failures when characterised in the lab, usually as a result of low expression, misfolding, aggregation or lack of function. This high attrition rate makes protein design unreliable and costly. It is possible that some of these failures could be caught earlier in the design process if it were quick and easy to generate information and a set of high-quality metrics regarding designs, which could be used to make reproducible and data-driven decisions about which designs to characterise experimentally.

We present DE-STRESS (DEsigned STRucture Evaluation ServiceS), a web application for evaluating structural models of designed and engineered proteins. DE-STRESS has been designed to be simple, intuitive to use and responsive. It provides a wealth of information regarding designs, as well as tools to help contextualise the results and formally describe the properties that a design requires to be fit for purpose.

Availability

DE-STRESS is available for non-commercial use, without registration, through the following website: https://pragmaticproteindesign.bio.ed.ac.uk/de-stress/. Source code for the application is available on GitHub: https://github.com/wells-wood-research/de-stress. The data used to generate reference sets is available through a GraphQL API, with the following URL: https://pragmaticproteindesign.bio.ed.ac.uk/big-structure/graphql.
An organelle inheritance pathway during polarized cell growth
Authors: Li Kathryn W , Pedersen Ross TA , Lu Michelle S , Drubin David G
Published: April 2021

Some organelles cannot be synthesized anew, so they are segregated into daughter cells during cell division. InSaccharomyces cerevisiae, daughter cells bud from mother cells and are populated by organelles inherited from the mothers. To determine whether this organelle inheritance occurs in a stereotyped manner, we tracked organelles using fluorescence microscopy. We describe a program for organelle inheritance in budding yeast. The cortical endoplasmic reticulum (ER) and peroxisomes are inherited concomitant with bud emergence. Next, vacuoles are inherited in small buds, followed closely by mitochondria. Finally, the nucleus and perinuclear ER are inherited when buds have nearly reached their maximal size. Because organelle inheritance timing correlates with bud morphology, which is coupled to the cell cycle, we tested whether organelle inheritance order is controlled by the cell cycle. By arresting cell cycle progression but allowing continued bud growth, we determined that organelle inheritance still occurs without cell cycle progression past S-phase, and that the general inheritance order is maintained. Thus, organelle inheritance follows a preferred order during polarized cell division, but it is not controlled exclusively by cell cycle signaling.

Summary statement

Organelles are interconnected by contact sites, but they must be inherited from mother cells into buds during budding yeast mitosis. We report that this process occurs in a preferred sequence.
Cannabis Vapour Exposure Alters Neural Circuit Oscillatory Activity In A Neurodevelopmental Model Of Schizophrenia: Exploring The Differential Impact Of Cannabis Constituents
Authors: Jenkins Bryan W. , Buckhalter Shoshana , Perreault Melissa L. , Khokhar Jibran Y.
Published: April 2021

Cannabis use is highly prevalent in patients with schizophrenia and worsens the course of the disorder. To understand the causal impacts of cannabis on schizophrenia-related oscillatory disruptions, we herein investigated the impact of exposure to cannabis vapour (containing delta-9-tetrahydrocannabinol [THC] or balanced THC and cannabidiol [CBD]) on oscillatory activity in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia. Male Sprague Dawley rats underwent NVHL or sham surgeries on postnatal day 7. In adulthood, electrodes were implanted targeting the cingulate cortex (Cg), the prefrontal cortex (PFC), the dorsal hippocampus (HIP), and the nucleus accumbens (NAc). Local field potential recordings were obtained following exposure to two strains of vapourized cannabis flower (with ~10% THC or ~10% balanced THC:CBD) in a cross-over design with a two-week wash-out period between exposures. Compared to controls, NVHL rats had reduced baseline gamma power in the Cg, dHIP, and NAc, and reduced high-gamma coherence between the dHIP-Cg. THC-only vapour broadly suppressed oscillatory power and coherence, even beyond the baseline suppressions observed in NHVL rats. Balanced THC:CBD vapour appeared to ameliorate the THC-induced impacts on power and coherence in both sham and NVHL rats. For NVHL rats, THC-only vapour also normalized the baseline dHIP-Cg high-gamma coherence deficits. NHVL rats also demonstrated a 20ms delay in dHIP theta to high-gamma phase coupling, which was ameliorated by both exposures in the PFC and NAc. In conclusion, THC-only cannabis vapour suppressed oscillatory activity in NVHL and sham rats, while balanced THC:CBD vapour may ameliorate some of these effects.
Recombination patterns in coronaviruses
Authors: Müller Nicola F. , Kistler Kathryn E. , Bedford Trevor
Published: April 2021

As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.
Quantifying the potential for red blood cell β-adrenergic sodium-proton exchangers to protect oxygen transport in hypoxic and hypercapnic white seabass
Authors: Harter Till S. , Clifford Alexander M. , Tresguerres Martin
Published: April 2021

White seabass (Atractoscion nobilis) are increasingly experiencing periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O2carrier in the blood and in many teleost fishes Hb-O2binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically-stimulated sodium-proton-exchangers (β-NHE). We hypothesized that RBC β-NHEs in white seabass are an important mechanism that can protect the blood O2-carrying capacity during hypoxia and hypercapnia. We determined the O2-binding characteristics of white seabass blood, the response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O2saturation. White seabass had typical teleost Hb characteristics, with a moderate O2affinity (PO2at half-saturation; P502.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). The presence of RBC β-NHEs was confirmed by functional, molecular and bioinformatic data and super-resolution imaging revealed, for the first time, the subcellular location of β-NHE protein in vesicle-like structures and on the RBC membrane, and its translocation after adrenergic stimulation. The activation of RBC β-NHEs increased Hb-O2saturation by ∼8% in normoxia at 1 kPa PCO2, and by up to 20% in hypoxia. Our results confirm that RBC β-NHE activity in white seabass has great potential to protect arterial O2transport in environmentally relevant conditions of hypoxia and hypercapnia, but also reveal a potential vulnerability of fish to combinations of these stressors.
Systematic morphological and morphometric analysis of identified olfactory receptor neurons inDrosophila melanogaster
Authors: Gonzales Cesar Nava , McKaughan Quintyn , Bushong Eric A , Cauwenberghs Kalyani , Ng Renny , Madany Matthew , Ellisman Mark H , Su Chih-Ying
Published: April 2021

The biophysical properties of sensory neurons are influenced by their morphometric and morphological features, whose precise measurements require high-quality volume electron microscopy (EM). However, systematic surveys of these nanoscale characteristics for identified neurons are scarce. Here, we characterize the morphology ofDrosophilaolfactory receptor neurons (ORNs) across the majority of genetically identified sensory hairs. By analyzing serial block-face electron microscopy (SBEM) images of cryofixed antennal tissues, we compile an extensive morphometric dataset based on 122 reconstructed 3D models of 33 identified ORN types. In addition, we observe multiple novel features—including extracellular vacuoles within sensillum lumen, intricate dendritic branching, mitochondria enrichment in select ORNs, novel sensillum types, and empty sensilla containing no neurons—which raise new questions pertinent to cell biology and sensory neurobiology. Our systematic survey is critical for future investigations into how the size and shape of sensory neurons influence their responses, sensitivity and circuit function.