bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring SARS-CoV-2 in sewage: toward sentinels with analytical accuracy
Authors: Calderón-Franco David , Orschler Laura , Lackner Susanne , Agrawal Shelesh , Weissbrodt David G.
Published: July 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemia has been one of the most difficult challenges humankind has recently faced. Wastewater-based epidemiology has emerged as a tool for surveillance and mitigation of potential viral outbreaks, circumventing biases introduced by clinical patient testing. Due to the situation urgency, protocols followed for isolating viral RNA from sewage were not adapted for such sample matrices. In parallel to their implementation for fast collection of data to sustain surveillance and mitigation decisions, molecular protocols need to be harmonized to deliver accurate, reproducible, and comparable analytical outputs. Here we studied analytical variabilities linked to viral RNA isolation methods from sewage. Three different influent wastewater volumes were used to assess the effect of filtered volumes (50, 100 or 500 mL) for capturing viral particles. Three different concentration strategies were tested by electronegative membranes, polyethersulfone membranes, and anion-exchange diethylaminoethyl cellulose columns. To compare the number of viral particles, different RNA isolation methods (column-based vs. magnetic beads) were compared. The effect of extra RNA purification steps and different RT-qPCR strategies (one step vs. two-step) were also evaluated. Results showed that the combination of 500 mL filtration volume through electronegative membranes and without multiple RNA purification steps (using column-based RNA purification) using two-step RT-qPCR avoided false negatives when basal viral load in sewage are present and yielded more consistent results during the surveillance done during the second-wave in Delft (The Hague area, The Netherlands). By paving the way for standardization of methods for the sampling, concentration and molecular detection of SARS-CoV-2 viruses from sewage, these findings can help water and health surveillance authorities to use and trust results coming from wastewater based epidemiology studies in order to anticipate SARS-CoV-2 outbreaks.

Graphical Abstract
Incidence of outbreak-associated COVID-19 cases by industry in Ontario, Canada, April 1, 2020-March 31, 2021
Authors: Buchan Sarah A. , Smith Peter M. , Warren Christine , Murti Michelle , Mustard Cameron , Kim JinHee , Menon Sandya , Brown Kevin A. , van Ingen Trevor , Smith Brendan T.
Published: July 2021

Objectives

The objective of our study was to estimate the rate of workplace outbreak-associated cases of COVID-19 by industry in labour market participants aged 15-69 years who reported working the majority of hours outside the home in Ontario, Canada.

Methods

We conducted a population based cross-sectional study of COVID-19 workplace outbreaks and associated-cases reported in Ontario between April 1, 2020 and March 31, 2021. All outbreaks were manually classified into two digit North American Industry Classification System (NAICS) codes. We obtained denominator data from the Statistics Canada Labour Force Survey in order to estimate the incidence of outbreak-associated cases per 100,000,000 hours amongst individuals who reported the majority of hours were worked outside the home. We performed this analysis across industries and in three distinct time periods.

Results

Overall, 12% of cases were attributed to workplace outbreaks among working age adults across our study period. While incidence varied across the time periods, the five industries with the highest incidence rates across our study period were agriculture; healthcare and social assistance; food manufacturing; educational services; and, transportation and warehousing.

Conclusions

Certain industries have consistently increased incidence of COVID-19 over the course of the pandemic. These results may assist in ongoing efforts to reduce transmission of COVID-19, by prioritizing resources, as well as industry-specific guidance, vaccination, and public health messaging.
Genome-wide contribution of common Short-Tandem Repeats to Parkinson’s Disease genetic risk
Authors: Bustos Bernabe I. , Billingsley Kimberley , Blauwendraat Cornelis , Gibbs J. Raphael , Gan-Or Ziv , Krainc Dimitri , Singleton Andrew B. , Lubbe Steven J. ,   For the International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: July 2021

Parkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component, where most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (Indels). DNA repetitive elements account for >50% of the human genome, however little is known of their contribution to PD etiology. While select short tandem repeats (STRs) within candidate genes have been studied in PD, their genome-wide contribution remains unknown. Here we present the first genome-wide association study (GWAS) of STRs in PD. Through a meta-analysis of 16 imputed GWAS cohorts from the International Parkinson’s Disease Genomic Consortium (IPDGC), totalling 39,087 individuals (16,642 PD cases and 22,445 controls of European ancestry) we identified 34 genome-wide significant STR loci (p < 5.34×10-6), with the strongest signal located inKANSL1(chr17:44205351:[T]11, p=3×10-39, OR=1.31 [CI 95%=1.26-1.36]). Conditional-joint analyses suggested that 4 significant STRs mapping nearbyNDUFAF2, TRIML2, MIRNA-129-1andNCOR1were independent from known PD risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTR) in RNASeq data from 13 brain regions, identified significant associations of STRs influencing the expression of multiple genes, including PD known genes. Further functional annotation of candidate STRs revealed that significant eSTRs withinNUDFAF2andZSWIM7overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here we show that STRs at known and novel candidate PD loci contribute to PD risk, and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting PD risk loci.
Risk factors for SARS-CoV-2 infection and hospitalisation in children and adolescents in Norway: A nationwide population-based study
Authors: Størdal Ketil , Ruiz Paz Lopez-Doriga , Greve-Isdahl Margrethe , Surén Pål , Knudsen Per Kristian , Løvdal Gulseth Hanne , Tapia German
Published: July 2021

Objective

To determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.

Design

Nationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents <18 years of age.

Main outcome measures

Population-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.

Results

Of 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.

Conclusions

Socioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.

What is already known on this topic

Hospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.

Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.

What this study adds

Low family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.

None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.
Survey of SARS-CoV-2 genetic diversity in two major Brazilian cities using a fast and affordable Sanger sequencing strategy
Authors: Dorlass Erick Gustavo , Lourenço Karine Lima , Miserani Magalhães Rubens Daniel , Sato Hugo , Fiorini Alex , Peixoto Renata , Coelho Helena Perez , Telezynski Bruna Larotonda , Scagion Guilherme Pereira , Ometto Tatiana , Thomazelli Luciano Matsumiya , Leal Oliveira Danielle Bruna , Fernandes Ana Paula , Durigon Edison Luiz , Guimarães Fonseca Flavio , Ribeiro Teixeira Santuza Maria
Published: July 2021

Genetic variants of SARS-CoV-2 have been emerging and circulating in many places across the world. Rapid detection of these variants is essential since their dissemination can impact transmission rates, diagnostic procedures, disease severity, response to vaccines or patient management. Sanger sequencing has been used as the preferred approach for variant detection among circulating human immunodeficiency and measles virus genotypes. Using primers to amplify a fragment of the SARS-CoV-2 genome encoding part of the Spike protein, we showed that Sanger sequencing allowed us to rapidly detect the introduction and spread of three distinct SARS-CoV-2 variants in two major Brazilian cities. In both cities, after the predominance of variants closely related to the virus first identified in China, the emergence of the P.2 variant was quickly followed by the identification of the P1 variant, which became dominant in less than one month after it was first detected.
HAPPILEE: The Harvard Automated Processing Pipeline In Low Electrode Electroencephalography, a standardized software for low density EEG and ERP data
Authors: Lopez K.L. , Monachino A.D. , Morales S. , Leach S.C. , Bowers M.E. , Gabard-Durnam L.J.
Published: July 2021

Low-density Electroencephalography (EEG) recordings (e.g. fewer than 32 electrodes) are widely-used in research and clinical practice and enable scalable brain function measurement across a variety of settings and populations. Though a number of automated pipelines have recently been proposed to standardize and optimize EEG preprocessing for high-density systems with state-of-the-art methods, few solutions have emerged that are compatible with low-density systems. However, low-density data often include long recording times and/or large sample sizes that would benefit from similar standardization and automation with contemporary methods. To address this need, we propose the HAPPE In Low Electrode Electroencephalography (HAPPILEE) pipeline as a standardized, automated pipeline optimized for EEG recordings with low density channel layouts of any size. HAPPILEE processes task-free (e.g. resting-state) and task-related EEG, and event-related potential (ERP) data, from raw files through a series of processing steps including filtering, line noise reduction, bad channel detection, artifact rejection from continuous data, segmentation, and bad segment rejection that have all been optimized for low density data. HAPPILEE also includes post-processing reports of data and pipeline quality metrics to facilitate the evaluation and reporting of data quality and processing-related changes to the data in a standardized manner. We describe multiple approaches with both recorded and simulated EEG data to optimize and validate pipeline performance. The HAPPILEE pipeline is freely available as part of HAPPE 2.0 software under the terms of the GNU General Public License at:https://github.com/PINE-Lab/HAPPE.
Atypical development of subcortico-cortical effective connectivity in autism
Authors: Lorenzini Luigi , van Wingen Guido , Cerliani Leonardo
Published: July 2021

Hypersensitivity, stereotyped behaviors and attentional problems in autism spectrum disorder (ASD) are compatible with inefficient filtering of undesired or irrelevant sensory information at early stages of neural processing. This could stem from delays in the neurotypical development of the functional segregation between cortical and subcortical brain processes, as suggested by previous findings of overconnectivity between primary sensory regions and deep brain nuclei in ASD.

To test this hypothesis, we used dynamic causal modelling to quantify the effect of age on the development of (1) cortical functional segregation from subcortical activity and (2) directional influence of subcortical activity on cortical processing in 166 participants with ASD and 193 typically developing controls (TD) from the Autism Brain Imaging Data Exchange (ABIDE).

We found that in TD participants age was significantly associated with increased functional segregation of cortical sensory processing from subcortical activity, paralleled by a decreased influence of subcortical activity on cortical processing. Instead these effects were highly reduced and mostly absent in ASD participants, suggesting a delayed or arrested development of the segregation between subcortical and cortical sensory processing in ASD.

This atypical configuration of subcortico-cortical connectivity in ASD can result in an excessive amount of unprocessed sensory information relayed to the cortex, which is likely to impact cognitive functioning in everyday situations where it is beneficial to limit the influence of basic sensory information on cognitive processing, such as activities requiring focused attention or social interactions.
Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
Authors: Armbruster Moritz , Naskar Saptarnab , Garcia Jacqueline , Sommer Mary , Kim Elliot , Adam Yoav , Haydon Philip G , Boyden Edward S , Cohen Adam E , Dulla Chris G
Published: July 2021

Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+is voltage-dependent, but astrocyte membrane potential (Vm) has been thought to be largely invariant. As a result, these voltage-dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators enabling the measurement of Vmat distal astrocyte processes (DAPs), we report large, rapid, focal, and pathway-specific depolarizations in DAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+efflux and electrogenic glutamate transporters. We find that DAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of sub-cellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.

One Sentence Summary

Genetically encoded voltage imaging of astrocytes shows that presynaptic neuronal activity drives focal astrocyte depolarization, contributing to activity-dependent inhibition of glutamate uptake.
Bark beetles locate fungal symbionts by detecting volatile fungal metabolites of host tree resin monoterpenes
Authors: Kandasamy Dineshkumar , Zaman Rashaduz , Nakamura Yoko , Zhao Tao , Hartmann Henrik , Andersson Martin N , Hammerbacher Almuth , Gershenzon Jonathan
Published: July 2021

Outbreaks of the Eurasian spruce bark beetle (Ips typographus) have decimated millions of hectares of conifer forests in Europe in recent years. The ability of these 3-6 mm long insects to kill mature trees over a short period has been ascribed to two main factors: (1) mass attacks on the host tree to overcome tree defenses and (2) the presence of fungal symbionts that support successful beetle development in the tree. While the role of pheromones in coordinating mass attacks has been well studied, the role of chemical communication in maintaining the fungal symbiosis is poorly understood. We previously demonstrated thatI. typographuscan recognize beneficial fungal symbionts of the generaGrosmannia,EndoconidiophoraandOphiostomaby theirde novosynthesized volatile compounds. Here, we hypothesize that the fungal symbionts of the bark beetles might metabolize spruce resin monoterpenes of the beetle’s host tree, Norway spruce (Picea abies), and that the volatile products could be used as cues by beetles for locating breeding sites with beneficial symbionts. We show thatGrosmannia penicillataand other fungal symbionts altered the profile of spruce bark volatiles by converting the major monoterpenes into an attractive blend of oxygenated derivatives. Bornyl acetate was metabolized to camphor, and α- and β-pinene totrans-4-thujanol and other oxygenated products. Other co-occurring non-beneficial fungi (Trichoderma sp.)also produce oxygenated monoterpenes, but in non-attractive ratios. Extensive electrophysiological measurements showed that the bark beetle possesses dedicated olfactory sensory neurons for oxygenated metabolites. Compounds such as camphor andtrans-4-thujanol attracted beetles at specific doses in olfactory experiments, and the presence of symbiotic fungi enhanced attraction of females to pheromones. Finally, we show that colonization of fungal symbionts on spruce bark diet stimulated beetles to make tunnels into the diet. Collectively, our study suggests that the blends of oxygenated metabolites of conifer monoterpenes produced by fungal symbionts are used by bark beetles as attractive cues to find breeding or feeding sites containing their essential microbial symbionts. The oxygenated metabolites may aid beetles in assessing the presence of the fungus, the defense status of the host tree and the density of conspecifics at potential feeding and breeding sites.
Allotypic variation in antigen processing controls antigenic peptide generation from SARS-CoV-2 S1 Spike Glycoprotein
Authors: Stamatakis George , Samiotaki Martina , Temponeras Ioannis , Panayotou George , Stratikos Efstratios
Published: July 2021

Population genetic variability in immune system genes can often underlie variability in immune responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both SARS-CoV-2 infection severity and long-term immunity, either after recovery or vaccination. A hallmark of COVID-19 is its highly variable severity and breadth of immune responses between individuals. To address the underlying mechanisms behind this phenomenon we analyzed the proteolytic processing of S1 spike glycoprotein precursor antigenic peptides by 10 common allotypes of ER aminopeptidase 1 (ERAP1), a polymorphic intracellular enzyme that can regulate cytotoxic T-lymphocyte responses by generating or destroying antigenic peptides. We utilized a systematic proteomic approach that allows the concurrent analysis of hundreds of trimming reactions in parallel, thus better emulating antigen processing in the cell. While all ERAP1 allotypes were capable of producing optimal ligands for MHC class I molecules, including known SARS-CoV-2 epitopes, they presented significant differences in peptide sequences produced, suggesting allotype-dependent sequence biases. Allotype 10, previously suggested to be enzymatically deficient, was rather found to be functionally distinct from other allotypes. Our findings suggest that common ERAP1 allotypes can be a major source of heterogeneity in antigen processing and through this mechanism contribute to variable immune responses to COVID-19.
Synchronized swarming: Harmonic convergence and acoustic mating dynamics in the malaria mosquito Anopheles gambiae
Authors: Garcia Castillo Stefano S. , Pritts Kevin S. , Krishnan Raksha S. , Harrington Laura C. , League Garrett P.
Published: July 2021

The mosquito Anopheles gambiae is a major African malaria vector, transmitting parasites responsible for significant mortality and disease burden. Malaria declines have stagnated recently due to widespread insecticide resistance among vector populations. Flight acoustics are essential to mosquito mating biology and represent promising alternative targets for mosquito control. However, mosquito swarm acoustics data are limited. Here, for the first time, we present detailed analyses of free-flying male and female An. gambiae flight tones and their harmonization (harmonic convergence) over a complete swarm sequence. Audio analysis of single-sex swarms showed elevated male or female flight tone frequencies and amplitudes during swarming flight with gradual declines to pre-swarm levels over an approximately 35-min period. Analysis of mixed-sex swarms revealed additional increases in flight tone frequencies and amplitudes due to mating activity. Data from mixed-sex swarms suggest harmonic convergence during swarming enhances the efficiency of female detection by synchronizing male and female baseline swarm tones. Further, data from experiments using female swarm tone playbacks to males indicate that harmonic convergence during mating interactions coordinates male scramble competition by acoustically masking mating couple flight tones. These findings advance our knowledge of mosquito swarm acoustics, providing vital information for reproductive control strategies.
Effect of artificial light at night on sleep and metabolism in weaver birds
Authors: Yadav Anupama , Kumar Raj , Tiwari Jyoti , Vaish Vaibhav , Malik Shalie , Rani Sangeeta
Published: July 2021

Artificial light at night is constantly minimizing the span of dark nights’ from the natural light-dark cycle of earth. Over the past century, the ‘lightscape’ of earth has completely changed owing to technological advancements which subsequently changed the lifestyle of human as well as the nearby animal species. This motivated the present study, wherein we investigated the impact of light at night (LAN) on behavior and physiology of a diurnal passerine finch, baya weaver (Ploceus philippinus). A group of bird (N=10) exposed to 12L:12D photoperiod was initially subjected to dark nights (0 lux) for a period of 10 days followed by 5 lux; night light for a span of 4 weeks. First week in LAN served as acute treatment with respect to fourth week (chronic). Acute exposure had more pronounced impact on the behavioral and physiological observations when compared with chronic treatment. The results reveal significant increase in nighttime activity, sleep loss, significant inclusion of drowsiness behavior during the day in response to LAN. Beside these behavioral alterations, changes in physiological parameters such as; reduction in body mass, loss of gradient between pre- and post-prandial blood glucose levels, elevation in plasma corticosterone levels were more prominent during acute exposure of LAN. Plasma metabolites such as triglycerides, total protein, serum glutamic-oxaloacetic transaminase (SGOT) and creatinine concentrations also hiked in response to LAN treatment. Thus, the study broadly enumerates the impact of acute and chronic exposure of LAN on behavior (rest/sleep) and physiology (metabolism) of birds’.
Assessing our capability to predict the presence of respiratory diseases at the age of four using data available at one month of age
Authors: Han Xinyi , Gray Lawrence E. K. , Mahar Robert K. , Carlin John B. , Ranganathan Sarath , Vuillermin Peter J. , Vukcevic Damjan
Published: July 2021

Abstract

Chronic respiratory diseases are often difficult to cure and are likely to originate early in life. Therefore, early identification of such diseases is of interest for early prevention.

We explored the potential to predict these almost from birth; using data at 1 month of age, we attempted to predict disease occurrence 4 years later in life. Our data came from the Barwon Infant Study; after cleaning and processing, we had measurements on 41 variables from 401 participants.

We considered three respiratory diseases: asthma, wheeze and hay fever. As predictors, we used a variety of information that would be available in a clinical setting. Of particular interest to our investigation was whether lung function measurements (newly available at such an early age) would helpfully improve predictive accuracy. We also investigated whether maternal smoking (previously associated with respiratory illnesses) is a helpful predictor.

Our methods included logistic regression as the main model, multiple imputation to deal with missing values, stepwise selection and LASSO to select variables, and cross-validation to assess performance. We measured predictive performance using AUC (area under the receiver operating characteristic curve), sensitivity and specificity.

Broadly, we found that the best models had only modest predictive power for each disease. For example, for asthma we achieved an AUC of 0.67, a sensitivity of 68% and a corresponding specificity of 63%. Performance for the other two diseases was similar.

We also found that our lung function measurements didnotimprove predictive performance; some-what surprisingly, this was also true for maternal smoking. The most useful predictors included, among others, family history of these diseases and variables relating to the size of the infants.

Given the modest performance of these models, our findings suggest that very early prediction of respiratory illnesses is still a challenging task.
Investigation on the current situation of stroke patients in northernern Henan Province of China
Authors: Li Zhenhua , Yang Qingcheng , Zhang Xiangdong , Guo Yanping , Zhang Jiangang , Sun Ke , Yang Junzheng
Published: July 2021

Objectives

To analyze the basic situations and clinical characteristics of stroke patients in our hospital from May 2018 to April 2021, lay a foundation for the prevention and reasonable treatment of stroke patients in northern Henan Province.

Methods

The basic information of 835 stroke patients in our hospital was collected and classified according to age, gender, bad habits, accompanied diseases and drug use before admission to hospital, and severity of the stroke patients were also evaluated according to mRS scoring standard.

Results

A total of 835 stroke patients were collected from May 2018 to April 2021 in our hospital. The age range of stroke patients was 28-95 years old, 96.29% stroke patients was above 40 years old; there were 202 stroke patients with smoking history and 225 stroke patients with drinking history; Among the 835 stroke patients, hypertension, cerebral infarction and diabetes mellitus were the main accompanied diseases. Antihypertensive drugs (506 cases), antiplatelet drugs (208 cases), statins (173 cases) and antidiabetic drugs (143 cases) were the main therapeutic drugs in stroke patients before admission in the northern Henan Province; the results of mRS scoring standard showed that among 835 stroke patients, there were 609 cases with milder symptoms, accounting for 82.84% (there were 330 stroke patients with 1 points, 279 stroke patients with 2 points, and 83 stroke patients with 3 points), and 120 cases with severe symptoms, accounting for 14.37% (55 cases with 4 points, 65 cases with 5 points).

Conclusion

The age of stroke patients in northern Henan Province was mainly over 40 years old, most of stroke patients were in the early stage of stroke; smoking, drinking, hypertension and diabetes mellitus were main risk factors of stroke. And there was a sex difference between male stroke patients and female stroke patients in stroke risk factors smoking and hypertension. those data may help us for active prevention and rational drug use for stroke in clinic.
Single-cell sequencing unravels the cellular diversity that shapes neuro- and gliogenesis in the fast aging killifish (N. furzeri) brain
Authors: Ayana Rajagopal , Zandecki Caroline , Van houcke Jolien , Mariën Valerie , Seuntjens Eve , Arckens Lutgarde
Published: July 2021

The African turquoise killifish combines a short lifespan with spontaneous age-dependent loss of neuroregenerative capacity. The stem cell niches driving neuroregeneration and their molecular signatures remain elusive. To investigate this, we performed scRNA-seq of the adult telencephalon, combined with full-length transcriptomics using ISO-seq. Our results unveil about 25 cell types including neurons and progenitors of glial-and non-glial nature. Subclustering of progenitors identifies four radial glia (RG), and two non-glial progenitor (NGP) cell states. Combining the molecular profiles with spatial mapping of the RG clusters, reveals two spatially divergent astroglia, one ependymal, and one neuroepithelial-like subtype. We propose neuroepithelial-like RG and NGPs to be the start and intercessor populations of both neuro- and gliogenic lineages. Neuronal classification reveals distinct subtypes and lineages corresponding to excitatory and inhibitory neurons. This catalogue of telencephalon cell types is an extensive resource to understand the molecular basis of intrinsic plasticity shaping adult neuro- and gliogenesis.

Highlights

ScRNA-seq and ISO-seq identified a complete cell catalogue of the adult killifish telencephalon

Progenitor diversity revealed the presence of spatially-defined (astro)glial subtypes

A neuroepithelial radial glia population marks the start point of neurogenesis, accompanied by proliferative non-glial progenitors

Immature neurons form transcriptional subgroups that correspond to excitatory and inhibitory mature neuronal cell types

This cellular atlas is a basis for studying neurogenesis and neuro-regeneration upon injury, disease and aging
Single-cell analysis uncovers differential regulation of lung γδ T cell subsets by the co-inhibitory molecules, PD-1 and TIM-3
Authors: Edwards Sarah C. , Hedley Ann , Hoevenaar Wilma H. M. , Glauner Teresa , Wiesheu Robert , Kilbey Anna , Shaw Robin , Boufea Katerina , Batada Nizar , Blyth Karen , Miller Crispin , Kirschner Kristina , Coffelt Seth B.
Published: July 2021

IL-17A-producing γδ T cells within the lung consist of both Vγ6+tissue-resident cells and Vγ4+circulating cells that play important roles in homeostasis, inflammation, infection, tumor progression and metastasis. How these γδ T cell subsets are regulated in the lung environment during homeostasis and cancer remains poorly understood. Using single-cell RNA sequencing and flow cytometry, we show that lung Vγ6+cells express a repertoire of cell surface molecules distinctive from Vγ4+cells, including PD-1 and ICOS. We found that PD-1 functions as a co-inhibitory molecule on Vγ6+cells to reduce IL-17A production, whereas manipulation of ICOS signaling fails to affect IL-17A in Vγ6+cells. In a mammary tumor model, ICOS and PD-1 expression on lung Vγ6+cells remained stable. However, Vγ6+and Vγ4+cells within the lung pre-metastatic niche increased expression of IL-17A, IL-17F, amphiregulin (AREG) and TIM-3 in response to tumor-derived IL-1β and IL-23, where the upregulation of TIM-3 was specific to Vγ4+cells. Inhibition of either PD-1 or TIM-3 in mammary tumor-bearing mice further increased IL-17A by Vγ6+and Vγ4+cells, indicating that both PD-1 and TIM-3 function as negative regulators of IL-17A-producing γδ T cell subsets. Together, these data demonstrate how lung γδ T cell subsets are differentially controlled by co-inhibitory molecules in steady-state and cancer.
Mice and primates use distinct strategies for visual segmentation
Authors: Luongo Francisco J. , Liu Lu , Ho Chun Lum Andy , Hesse Janis K. , Wekselblatt Joseph B. , Lanfranchi Francesco , Huber Daniel , Tsao Doris Y.
Published: July 2021

The rodent visual system has attracted great interest in recent years due to its experimental tractability, but the fundamental mechanisms used by the mouse to represent the visual world remain unclear. In the primate, researchers have argued from both behavioral and neural evidence that a key step in visual representation is “figure-ground segmentation,” the delineation of figures as distinct from backgrounds [1–4]. To determine if mice also show behavioral and neural signatures of figure-ground segmentation, we trained mice on a figure-ground segmentation task where figures were defined by gratings and naturalistic textures moving counterphase to the background. Unlike primates, mice were severely limited in their ability to segment figure from ground using the opponent motion cue, with segmentation behavior strongly dependent on the specific carrier pattern. Remarkably, when mice were forced to localize naturalistic patterns defined by opponent motion, they adopted a strategy of brute force memorization of texture patterns. In contrast, primates, including humans, macaques, and mouse lemurs, could readily segment figures independent of carrier pattern using the opponent motion cue. Consistent with mouse behavior, neural responses to the same stimuli recorded in mouse visual areas V1, RL, and LM also did not support texture-invariant segmentation of figures using opponent motion. Modeling revealed that the texture dependence of both the mouse’s behavior and neural responses could be explained by a feedforward neural network lacking explicit segmentation capabilities. These findings reveal a fundamental limitation in the ability of mice to segment visual objects compared to primates.
Examining the effects of an anti-Salmonella bacteriophage preparation, BAFASAL, on ex vivo human gut microbiome composition and function using a multi-omics approach
Authors: Mayne Janice , Zhang Xu , Butcher James , Walker Krystal , Ning Zhibin , Wójcik Ewelina , Dastych Jarosław , Stintzi Alain , Figeys Daniel
Published: July 2021

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via contamination in our food chain. This foodborne pathogen causes major food losses and human illnesses that result in significant economic impacts. Pathogens such as Salmonella have traditionally been kept at bay through the use of antibiotics, but antibiotic overuse within the food industry has led to the development of numerous multidrug-resistant bacterial strains. Thus, governments are now restricting antibiotic use, forcing the industry to search for alternatives to secure safe food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics as they are natural components of the ecosystem. One example is BAFASEL, a commercial bacteriophage mixture that specifically targets Salmonella and is currently approved for use in poultry farming. However, when specifically used in the industry they can also make their way into humans through our food chain or exposure as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented in animal feeds. To the best of our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in vitro assay called RapidAIM to investigate BAFASAL’s potential impact on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex vivo human gut microbiota composition and function were unaffected by BAFASAL treatment providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

Graphical Abstract
Divergent effects of absolute evidence magnitude on decision accuracy and confidence in perceptual judgements
Authors: Ko Yiu Hong , Feuerriegel Daniel , Turner William , Overhoff Helen , Niessen Eva , Stahl Jutta , Hester Robert , Fink Gereon R. , Weiss Peter H. , Bode Stefan
Published: July 2021

Whether people change their mind after making a perceptual judgement may depend on how confident they are in their decision. Recently, it was shown that, when making perceptual judgements about stimuli containing high levels of ‘absolute evidence’ (i.e., the overall magnitude of sensory evidence across choice options), people make less accurate decisions and are also slower to change their mind and correct their mistakes. Here we report two studies that investigated whether high levels of absolute evidence also lead to increased decision confidence. We used a luminance judgment task in which participants decided which of two dynamic, flickering stimuli was brighter. After making a decision, participants rated their confidence. We manipulated relative evidence (i.e., the mean luminance difference between the two stimuli) and absolute evidence (i.e., the summed luminance of the two stimuli). In the first experiment, we found that higher absolute evidence was associated with decreased decision accuracy but increased decision confidence. In the second experiment, we additionally manipulated the degree of luminance variability to assess whether the observed effects were due to differences in perceived evidence variability. We replicated the results of the first experiment but did not find substantial effects of luminance variability on confidence ratings. Our findings support the view that decisions and confidence judgments are based on partly dissociable sources of information, and suggest that decisions initially made with higher confidence may be more resistant to subsequent changes of mind.
ribofootPrinter: A precision python toolbox for analysis of ribosome profiling data
Authors: Guydosh Nicholas R.
Published: July 2021

Ribosome profiling is a valuable methodology for measuring changes in a cell’s translational program. The approach can report how efficiently mRNA coding sequences are translated and pinpoint positions along mRNAs where ribosomes slow down or arrest. It can also reveal when translation takes place outside coding regions, often with important regulatory consequences. While many useful software tools have emerged to facilitate analysis of these data, packages can become complex and challenging to adapt to specialized needs. In particular, the results of meta analysis of average footprint data around sequence motifs of interest can vary substantially depending on the normalization method that is utilized. We therefore introduce ribofootPrinter, a suite of Python tools designed to offer an accessible and modifiable set of code for analysis of ribosome profiling data. Footprint alignments are made to a simplified transcriptome, keeping the code intuitive, and multiple normalization options help facilitate interpretation of meta analysis, particularly outside coding regions. We believe this tool has promise to carry out sophisticated analysis yet offer simplicity to make it readily understandable and adaptable.
Efficient breeding of industrial brewing yeast strains using CRISPR/Cas9-aided mating-type switching
Authors: Krogerus Kristoffer , Fletcher Eugene , Rettberg Nils , Gibson Brian , Preiss Richard
Published: July 2021

Yeast breeding is a powerful tool for developing and improving brewing yeast in a number of industry-relevant respects. However, breeding of industrial brewing yeast can be challenging, as strains are typically sterile and have large complex genomes. To facilitate breeding, we used the CRISPR/Cas9 system to generate double-stranded breaks in the MAT locus, generating transformants with a single specified mating type. The single mating type remained stable even after loss of the Cas9 plasmid, despite the strains being homothallic, and these strains could be readily mated with other brewing yeast transformants of opposite mating type. As a proof of concept, we applied this technology to generate yeast hybrids with an aim to increase β-lyase activity for fermentation of beer with enhanced hop flavour. First, a genetic and phenotypic pre-screening of 38 strains was carried out in order to identify potential parent strains with high β-lyase activity. Mating-competent transformants of eight parent strains were generated, and these were used to generate over 60 hybrids that were screened for β-lyase activity. Selected phenolic off-flavour positive (POF+) hybrids were further sporulated to generate meiotic segregants with high β-lyase activity, efficient wort fermentation and lack of POF; all traits that are desirable in strains for the fermentation of modern hop-forward beers. Our study demonstrates the power of combining the CRISPR/Cas9 system with classic yeast breeding to facilitate development and diversification of brewing yeast.

Key Points

CRISPR/Cas9-based mating type switching was applied to industrial yeast strains

Transformed strains could be readily mated to form intraspecific hybrids

Hybrids exhibited heterosis for a number of brewing-relevant traits
C-STEM: ENGINEERING NICHE-LIKE MICRO-COMPARTMENTS FOR OPTIMAL AND SCALE-INDEPENDENT EXPANSION OF HUMAN PLURIPOTENT STEM CELLS IN BIOREACTORS
Authors: Cohen Philippe J.R. , Luquet Elisa , Pletenka Justine , Leonard Andrea , Warter Elise , Gurchenkov Basile , Carrere Jessica , Rieu Clement , Hardouin Jerome , Moncaubeig Fabien , Lanero Michael , Quelennec Eddy , Wurtz Helene , Jamet Emilie , Demarco Maelle , banal Celine , Van Liedekerke Paul , Nassoy Pierre , Feyeux Maxime , Lefort Nathalie , Alessandri kevin
Published: July 2021

Human pluripotent stem cells (hPSCs) have emerged as the most promising cellular source for cell therapies. To overcome scale up limitations of classical 2D culture systems, suspension cultures have been developed to meet the need of large-scale culture in regenerative medicine. Despite constant improvements, current protocols relying on the generation of micro-carriers or cell aggregates only achieve moderate amplification performance. Here, guided by reports showing that hPSCs can self-organize in vitro into cysts reminiscent of the epiblast stage in embryo development, we developed a physio-mimetic approach for hPSC culture. We engineered stem cell niche microenvironments inside microfluidics-assisted core-shell microcapsules. We demonstrate that lumenized three-dimensional colonies maximize viability and expansion rates while maintaining pluripotency. By optimizing capsule size and culture conditions, we scale-up this method to industrial scale stirred tank bioreactors and achieve an unprecedented hPSC amplification rate of 282-fold in 6.5 days.
A bacterial derived plant- mimicking cytokinin hormone regulates social behaviour in a rice pathogen
Authors: Deb Sohini , Kumar Chandan , Kumar Rahul , Kaur Amandeep , Ghosh Palash , Jha Gopaljee , Patil Prabhu B. , Chatterjee Subhadeep , Patel Hitendra K. , Sonti Ramesh V.
Published: July 2021

Many plant-associated bacteria produce plant- mimicking hormones which are involved in modulating host physiology. However, their function in modulating bacterial physiology has not been reported. Here we show that the XopQ protein, a type-III effector of the rice pathogen, Xanthomonas oryzae pv. oryzae (Xoo), is involved in cytokinin biosynthesis. Xoo produces and secretes an active form of cytokinin which enables the bacterium to maintain a planktonic lifestyle and promotes virulence. RNA-seq analysis indicates that the cytokinin produced by Xoo is required for the regulation of several genes which are involved in biofilm formation. We have also identified the Xoo isopentenyl transferase gene, which is involved in the cytokinin biosynthesis pathway and is required for maintaining planktonic behaviour and virulence. Furthermore, mutations in the predicted cytokinin receptor kinase (PcrK) and the downstream response regulator (PcrR) of Xoo phenocopy the cytokinin biosynthetic mutants, but are not complemented by supplementation with exogenous cytokinin. Cytokinin biosynthetic functions are encoded in a number of diverse bacterial genomes suggesting that cytokinin may be a widespread signalling molecule in the bacterial kingdom.
Differential diagnosis of autism spectrum disorder, intellectual disability and attention-deficit hyperactivity disorder (ADHD)
Authors: Heyman Michelle , Ledoux Galligan Megan , Salinas Giselle Berenice , Baker Elizabeth , Blacher Jan , Stavropoulos Katherine
Published: July 2021

Purpose

Professionals working with community populations are often presented with complicated cases where it is difficult to determine which diagnosis or diagnoses are appropriate. Differentiating among neurodevelopmental disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder and intellectual disability can be a complex process, especially, as these disorders have some overlapping symptoms and often co-occur in young children. This series of case studies aims to present commonly overlapping symptoms in children who present to clinics with developmental concerns.

Design/methodology/approach

This paper presents three case studies that were completed at a free community ASD screening clinic in Southern California.

Findings

The case studies have common presenting behaviors and symptoms (e.g. social communication difficulties) that often co-occur across diagnoses; explanations for the final diagnoses are given in each case.

Research limitations/implications

Conclusions from these three cases cannot generalize to all children being seen in clinics for neurodevelopmental concerns.

Practical implications

This series of case studies highlights commonly overlapping symptoms in children who present for differential diagnosis with social and/or behavioral concerns. Implications for educational placement and intervention are discussed.

Social implications

These cases highlight the challenges involved in the differential and dual diagnostic process for young children with developmental concerns. Diagnostic considerations can affect later educational placement and opportunities for socialization.

Originality/value

This series of case studies provide practical information for clinicians about how to effectively differentiate between commonly occurring neurodevelopmental disorders, particularly given recent changes to the Diagnostic and Statistical Manual, 5th edition (DSM-5).