bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrothermal physiology and climate vulnerability in amphibians
Authors: Greenberg Dan A. , Palen Wendy J.
Published: February 2021

Concerns over the consequences of global climate change for biodiversity have spurred a renewed interest in organismal thermal physiology. However, temperature is only one of many environmental axes poised to change in the future. In particular, hydrologic regimes are also expected to shift concurrently with temperature in many regions, yet our understanding of how thermal and hydration physiology jointly affect performance and fitness is still limited for most taxonomic groups. Here, we investigated the relationship between functional performance, hydration state and temperature in three ecologically distinct amphibians, and compare how temperature and water loss can concurrently limit activity under current climate conditions. We found that performance was maintained across a broad range of hydration states in all three species, but then declines abruptly after a threshold of 20–30% mass loss. This rapid performance decline was accelerated when individuals were exposed to warmer temperatures. Combining our empirical hydrothermal performance curves with species-specific biophysical models, we estimated that dehydration can increase restrictions on species' activity by up to 60% compared to restriction by temperature alone. These results illustrate the importance of integrating species' hydration physiology into forecasts of climate vulnerability, as omitting this axis may significantly underestimate the effects of future climate change on Earth's biological diversity.
Flightlessness in insects enhances diversification and determines assemblage structure across whole communities
Authors: Salces-Castellano Antonia , Andújar Carmelo , López Heriberto , Pérez-Delgado Antonio J. , Arribas Paula , Emerson Brent C.
Published: February 2021

Dispersal limitation has been recurrently suggested to shape both macroecological patterns and microevolutionary processes within invertebrates. However, because of potential interactions among biological, environmental, temporal, and spatial variables, causal links among flight-related traits, diversification and spatial patterns of community assembly remain elusive. Integrating genetic variation within species across whole insect assemblages, within a simplified spatial and environmental framework, can be used to reduce the impact of these potentially confounding variables. Here, we used standardized sampling and mitochondrial DNA sequencing for a whole-community characterization of the beetle fauna inhabiting a singular forested habitat (laurel forest) within an oceanic archipelago setting (Canary Islands). The spatial structure of species assemblages together with species-level genetic diversity was compared at the archipelago and island scales for 104 winged and 110 wingless beetle lineages. We found that wingless beetle lineages have: (i) smaller range sizes at the archipelago scale, (ii) lower representation in younger island communities, (iii) stronger population genetic structure, and (iv) greater spatial structuring of species assemblages between and within islands. Our results reveal that dispersal limitation is a fundamental trait driving diversity patterns at multiple hierarchical levels by promoting spatial diversification and affecting the spatial configuration of entire assemblages at both island and archipelago scales.
Complete genome characterization of human noroviruses allows comparison of minor alleles during acute and chronic infections
Authors: Kelly Daniel , Jere Khuzwayo C. , Darby Alistair C. , Allen David J. , Iturriza-Gómara Miren
Published: February 2021

Human noroviruses (HuNoVs) circulate globally, affect all age groups and place a substantial burden upon health services. High genetic diversity leading to antigenic variation plays a significant role in HuNoV epidemiology, driving periodic global emergence of epidemic variants. Studies have suggested that immunocompromised individuals may be a reservoir for such epidemic variants, but studies investigating the diversity and emergence of HuNoV variants in immunocompetent individuals are underrepresented. To address this, we sequenced the genomes of HuNoVs present in samples collected longitudinally from one immunocompetent (acute infection) and one immunocompromised (chronic infection) patient. A broadly reactive HuNoV capture-based method was used to concentrate the virus present in these specimens prior to massively parallel sequencing to recover near complete viral genomes. Using a novel bioinformatics pipeline, we demonstrated that persistent minor alleles were present in both acute and chronic infections, and that minor allele frequencies represented a larger proportion of the population during chronic infection. In acute infection, minor alleles were more evenly spread across the genome, although present at much lower frequencies, and therefore difficult to discern from error. By contrast, in the chronic infection, more minor alleles were present in the minor structural protein. No non-synonymous minor alleles were detected in the major structural protein over the short sampling period of the HuNoV chronic infection, suggesting where immune pressure is variable or non-existent, epidemic variants could emerge over longer periods of infection by random chance.
Description of Paenibacillus dokdonensis sp. nov., a new bacterium isolated from soil
Authors: Paek Jayoung , Bai Lu , Shin Yeseul , Kim Hongik , Kook Joong-Ki , Chang Young-Hyo
Published: February 2021

Two strains isolated from soil samples were designated as YH-JAE5T and YH-JAE2. The isolates were facultative anaerobic, Gram-stain-variable, motile, rod-shaped bacteria. Phylogenetic analysis indicated that the isolates belonged to the genus

Paenibacillus

, but the 16S rRNA gene sequence similarities were <98 % when compared with other species within the genus. Analysis of rpoB gene revealed the isolates formed a sub-cluster with

P. chibensis

. The only menaquinone identified was MK-7. The two isolates contained meso-diaminopimelic acid within their cell wall peptidoglycan. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phospholipid, aminophospholipids, and lipids. The major fatty acids were C15 : 0 anteiso and C15 : 0 iso. The average nucleotide identity, average amino acid identity, and digital DNA–DNA hybridization values between isolate YH-JAE5T and the most closely related reference strain (

Paenibacillus chibensis

KCTC 3758T) were 81.7, 84.8 and 23.4 %, respectively. The G+C content of the genomic DNA was 47.4 mol%. Thus, the polyphasic data revealed that YH-JAE2 (=KCTC 43239=JCM 34435) and YH-JAE5T (=KCTC 43059=JCM 33533) represent a new species. The name Paenibacillus dokdonensis sp. nov. is proposed.
Overall burden and characteristics of COVID-19 in the United States during 2020
Authors: Pei Sen , Yamana Teresa K. , Kandula Sasikiran , Galanti Marta , Shaman Jeffrey
Published: February 2021

The COVID-19 pandemic disrupted health systems and economies throughout the world during 2020 and was particularly devastating for the United States. Many of epidemiological features that produced observed rates of morbidity and mortality have not been thoroughly assessed. Here we use a data-driven model-inference approach to simulate the pandemic at county-scale in the United States during 2020 and estimate critical, time-varying epidemiological properties underpinning the dynamics of the virus. The pandemic in the US during 2020 was characterized by an overall ascertainment rate of 21.6% (95% credible interval (CI):18.9 – 25.5%). Population susceptibility at year’s end was 68.8% (63.4 – 75.3%), indicating roughly one third of the US population had been infected. Community infectious rates, the percentage of people harboring a contagious infection, rose above 0.8% (0.6 – 1.0%) before the end of the year, and were as high as 2.4% in some major metropolitan areas. In contrast, the infection fatality rate fell to 0.3% by year’s end; however, community control of transmission, estimated from trends of the time-varying reproduction number, Rt, slackened during successive pandemic waves. In the coming months, as vaccines are distributed and administered and new more transmissible virus variants emerge and spread, greater use of non-pharmaceutical interventions will be needed.
COVID-19 European regional tracker
Authors: Naqvi Asjad
Published: February 2021

This Tracker presents data on daily COVID-19 cases at the sub-national level for 26 European countries from January 2020 till present. Country-level data sources are identified and processed to form a homogenized panel at the NUTS 3 or NUTS 2 level, the two lowest standardized administrative units of Europe. The strengths and weaknesses of each country dataset are discussed in detail. The raw data, spatial layers, the code, and the final homogenized files are provided in an online repository for replication. The data highlights the spatial distribution of cases both within and across countries that can be utilized for a disaggregated analysis on the impacts of the pandemic. The Tracker is updated monthly to expand its coverage.
Versatile live attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity
Authors: Yoshida Akiho , Okamura Shinya , Torii Shiho , Komatsu Sayuri , Miyazato Paola , Ueno Shiori , Suzuki Hidehiko , Kamitani Wataru , Ono Chikako , Matsuura Yoshiharu , Takekawa Shiro , Yamanishi Koichi , Ebina Hirotaka
Published: February 2021

Live attenuated vaccines are generally highly effective. Here, we aimed to develop one against SARS-CoV-2, based on the identification of three types of temperature-sensitive (TS) strains with mutations in nonstructural proteins (nsp), impaired proliferation at 37-39°C, and the capacity to induce protective immunity in Syrian hamsters. To develop a live-attenuated vaccine, we generated a virus that combined all these TS-associated mutations (rTS-all), which showed a robust TS phenotype in vitro and high attenuation in vivo. The vaccine induced an effective cross-reactive immune response and protected hamsters against homologous or heterologous viral challenges. Importantly, rTS-all rarely reverted to the wild-type phenotype. By combining these mutations with an Omicron spike protein to construct a recombinant virus, protection against the Omicron strain was obtained. We show that immediate and effective live-attenuated vaccine candidates against SARS-CoV-2 variants may be developed using rTS-all as a backbone to incorporate the spike protein of the variants.
Role of the ubiquitin ligase ITCH in clathrin-mediated endocytosis of the epidermal growth factor receptor
Authors: Ayoubi Riham , McPherson Peter S. , Angers Annie
Published: February 2021

Once activated by ligand, epidermal growth factor receptor (EGFR) is endocytosed in clathrin-coated pits. ITCH is an E3 ubiquitin ligase that interacts with and ubiquitinates several proteins involved in clathrin-mediated endocytosis (CME) including endophilin. To further investigate the function of ITCH in EGFR endocytosis, the internalization of fluorescent EGF was measured in ITCH-/-HeLa cells. In the absence of ITCH, there was a significant decrease in the CME of EGF. Rescue experiments using wild-type ITCH confirmed the importance of the protein for normal EGF uptake. ITCH point mutations that disrupt the interaction of ITCH with endophilin failed to rescue the defects in EGFR uptake, as did a non-catalytic form of ITCH. ITCH-/-cells also displayed a delay in the rate of phospho-EGFR degradation as well as prolonged ERK1/2 signaling. Our study uncovers a pathway regulating EGFR trafficking and reveals for the first time that the protein ITCH is required for CME of EGFR.
Laminar compartmentalization of attention modulation in area V4 aligns with the demands of visual processing hierarchy in the cortex
Authors: Wang Xiang , Nandy Anirvan S. , Jadi Monika P.
Published: February 2021

Contrast is a key feature of the visual scene that aids object recognition. Attention has been shown to selectively enhance the responses to low contrast stimuli in visual area V4, a critical hub that sends projections both up and down the visual hierarchy. Veridical encoding of contrast information is a key computation in early visual areas, while later stages encode higher level features that benefit from improved sensitivity to low contrast. How area V4 meets these distinct information processing demands in the attentive state is not known. We found that attentional modulation of contrast responses in area V4 is cortical layer and cell-class specific. Putative excitatory neurons in the superficial output layers that project to higher areas show enhanced boosting of low contrast information. On the other hand, putative excitatory neurons of deep output layers that project to early visual areas exhibit contrast-independent scaling. Computational modeling revealed that such layer-wise differences may result from variations in spatial integration extent of inhibitory neurons. These findings reveal that the nature of interactions between attention and contrast in V4 is highly compartmentalized, in alignment with the demands of the visual processing hierarchy.
Diversity of excitatory release sites
Authors: Karlocai Maria Rita , Heredi Judit , Benedek Tünde , Holderith Noemi , Lorincz Andrea , Nusser Zoltan
Published: February 2021

The molecular mechanisms underlying the diversity of cortical glutamatergic synapses is still only partially understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High resolution molecular analysis of functionally characterized synapses reveals highly variable Munc13-1 content of AZs that possess the sameN. Replica immunolabeling also shows a 3-fold variability in the Munc13-1 content of AZs of identical size. Munc13-1 is clustered within the AZs; cluster size and density are also variable. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.
Neurovascular unit alterations in the growth restricted newborn are improved following ibuprofen treatment
Authors: Chand Kirat K. , Miller Stephanie M. , Cowin Gary J. , Mohanty Lipsa , Pienaar Jany , Colditz Paul B. , Bjorkman Stella Tracey , Wixey Julie A.
Published: February 2021

Fetal brain development is particularly vulnerable to the effects of fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant. Adverse outcomes range from behavioural and learning disorders through to cerebral palsy. Unfortunately, no treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, a non-steroidal anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. We used a preclinical piglet model of growth restriction in which FGR occurs spontaneously. Newborn FGR (birthweight <10thcentile) and normally grown piglets were collected on day of birth and oral ibuprofen was administered daily for 3 days (20mg/kg/day, day 1 and 10mg/kg/day days 2 and 3). FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident in the microvasculature where leakage was present, suggestive of structural deficits to the NVU. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen treatment also attenuated albumin and IgG leakage. There were no alterations to angiogenesis, or blood vessel proliferation in treated-FGR piglets. These findings suggest postnatal administration of ibuprofen on day of birth modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.
Change of information by positive frequency-dependent selection in two very different models (laser-like and chirality of shell-coiling in the snailPartula suturalis)
Authors: Tiefenbrunner W. A.
Published: February 2021

Although according to the second law of thermodynamics the world tends toward maximum disorder, over millions of years evolution has given rise to an enormous variety of complex organisms. To explain this, one must assume that natural selection is a process of information acquisition. Since some years an information theory of selection exists that can quantify this change and thus helps to understand the apparent contradiction between the existence of biological complexity and the tendency toward disorder that generally prevails in nature. Here I apply this theory to examples of frequency-dependent selection (this means: in which phenotype frequency determines its fitness).

The snailPartula suturalisgave an evolutionary and ecologically unique and hence very valuable example of this type of selection before it became extinct about thirty years ago on its native island. Spatially separated populations with left- and right-coiled shells occurred on Moorea, but also hybridization zones. Since both types of shells were the same except for chirality, the question is whether selection happened at all. The inheritance of this character is monogenic and in this respect simple, but is complicated by the fact that it is the maternal genotype, not the own, that determines the phenotype. This causes that for the calculation of the information change by selection not the genotype or phenotype frequencies are sufficient, but one must consider their combination. The simulation shows that frequency-dependent selection inP. suturalisindeed increased information.

It has already been shown that selection can also be important outside animate nature, for example in the generation of laser light, which has extraordinary properties: it is monochromatic, monoaxial and monophasic. Phase selection is frequency(=density)-dependent and therefore of interest here. In selection theory the mean fitness ω is of special significance. In a laser-like model, in modeling phase selection, we find that ω=1+A2, where A2is the the light intensity or the square of the amplitude, respectively. During selection, ω increases and, in parallel, since selection is a process of information acquisition, so does the information. Because of the connection between ω and A2this also means for the laser-like model that – assuming a constant number of photons – a larger amplitude always means more information (less entropy).
Seasonal Dynamics in the Number and Composition of Coliform Bacteria in Drinking Water Reservoirs
Authors: Reitter Carolin , Petzoldt Heike , Korth Andreas , Schwab Felix , Stange Claudia , Hambsch Beate , Tiehm Andreas , Lagkouvardos Ilias , Gescher Johannes , Hügler Michael
Published: February 2021

Worldwide, surface waters like lakes and reservoirs are one of the major sources for drinking water production, especially in regions with water scarcity. In the last decades, they have undergone significant changes due to climate change. This includes not only an increase of the water temperature but also microbiological changes. In recent years, increased numbers of coliform bacteria have been observed in these surface waters. In our monitoring study we analyzed two drinking water reservoirs (Klingenberg and Kleine Kinzig Reservoir) over a two-year period in 2018 and 2019. We detected high numbers of coliform bacteria up to 2.4 x 104bacteria per 100 ml during summer months, representing an increase of four orders of magnitude compared to winter. Diversity decreased to one or two species that dominated the entire water body, namelyEnterobacter asburiaeandLelliottiaspp., depending on the reservoir. Interestingly, the same, very closely related strains have been found in several reservoirs from different regions. Fecal indicator bacteriaEscherichia coliand enterococci could only be detected in low concentrations. Furthermore, fecal marker genes were not detected in the reservoir, indicating that high concentrations of coliform bacteria were not due to fecal contamination. Microbial community revealedFrankialesandBurkholderialesas dominant orders.Enterobacterales,however, only had a frequency of 0.04% within the microbial community, which is not significantly affected by the extreme change in coliform bacteria number. Redundancy analysis revealed water temperature, oxygen as well as nutrients and metals (phosphate, manganese) as factors affecting the dominant species. We conclude that this sudden increase of coliform bacteria is an autochthonic process that can be considered as a mass proliferation or “coliform bloom” within the reservoir. It is correlated to higher water temperatures in summer and is therefore expected to occur more frequently in the near future, challenging drinking water production.

Highlights

Coliform bacteria proliferate in drinking water reservoirsto values above104per 100 ml

The generaLelliottiaandEnterobacter can form these “coliform blooms”

Mass proliferation is an autochthonic process, not related to fecal contaminations

It is related to water temperature and appears mainly in summer

It is expected to occur more often in future due to climate change

Graphical abstract
A chicken IgY can efficiently inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2 binding domain in vitro
Authors: Wei Jingchen , Lu Yunfei , Rui Ying , Zhu Xuanyu , He Songqing , Wu Shuwen , Xu Qing
Published: February 2021

COVID-19 pneumonia has now spread widely in the world. Currently, no specific antiviral drugs are available. The vaccine is the most effective way to control the epidemic. Passive immune antibodies are also an effective method to prevent and cure COVID-19 pneumonia. We used the SARS-CoV-2 S receptor-binding domain (RBD) as an antigen to immunize layers in order to extract, separate, and purify SARS-CoV-2-IgY from egg yolk. SARS-CoV-2-IgY (S-IgY)can block the entry of SARS-CoV-2 into the Cells and reduce the viral load in cells. The Half effective concentration (EC50) of W3-IgY (S-IgY in the third week after immunization) is 1.35 ± 0.15nM. The EC50of W9-IgY (S-IgY in the ninth week after immunization) is 2.76 ± 1.54 nM. When the dose of S-IgY is 55 nM, the fluorescence representing intracellular viral protein is obviously weakened in Immunofluorescence microscopy.

Results of Sars-CoV-2 /Vero E6 cell experiment confirmed that S-IgY has a strong antiviral effect on SARS-CoV-2, and its (EC50) is 27.78 ±1.54 nMvs3,259 ± 159.62 nM of Redesivir (differ > 106 timesP<0.001).

S-IgY can inhibit the entry and replication of SARS-CoV-2, which is related to its targeting the ACE2 binding domain.

S-IgY is safe, efficient, stable, and easy to obtain. This antibody can be an effective tool for preventing and treating COVID-19 pneumonia.

Abstract Figure

Fig. 1.

Graphical Abstract

The figure briefly illustrates that the preparation and extraction of S-IgY and its anti-S-CoV-2 mechanism is to inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2.
scGAE: topology-preserving dimensionality reduction for single-cell RNA-seq data using graph autoencoder
Authors: Luo Zixiang , Xu Chenyu , Zhang Zhen , Jin Wenfei
Published: February 2021

Dimensionality reduction is crucial for the visualization and interpretation of the high-dimensional single-cell RNA sequencing (scRNA-seq) data. However, preserving topological structure among cells to low dimensional space remains a challenge. Here, we present the single-cell graph autoencoder (scGAE), a dimensionality reduction method that preserves topological structure in scRNA-seq data. scGAE builds a cell graph and uses a multitask-oriented graph autoencoder to preserve topological structure information and feature information in scRNA-seq data simultaneously. We further extended scGAE for scRNA-seq data visualization, clustering, and trajectory inference. Analyses of simulated data showed that scGAE accurately reconstructs developmental trajectory and separates discrete cell clusters under different scenarios, outperforming recently developed deep learning methods. Furthermore, implementation of scGAE on empirical data showed scGAE provided novel insights into cell developmental lineages and preserved inter-cluster distances.
Simulating homeostatic, allostatic and goal-directed forms of interoceptive control using Active Inference
Authors: Tschantz Alexander , Barca Laura , Maisto Domenico , Buckley Christopher L. , Seth Anil K. , Pezzulo Giovanni
Published: February 2021

The adaptive regulation of bodily and interoceptive parameters, such as body temperature, thirst and hunger is a central problem for any biological organism. Here, we present a series of simulations using the framework of Active Inference to formally characterize interoceptive control and some of its dysfunctions. We start from the premise that the goal of interoceptive control is to minimize a discrepancy between expected and actual interoceptive sensations (i.e., a prediction error or free energy). Importantly, living organisms can achieve this goal by using various forms of interoceptive control: homeostatic, allostatic and goal-directed. We provide a computationally-guided analysis of these different forms of interoceptive control, by showing that they correspond to distinct generative models within Active Inference. Furthermore, we illustrate how these generative models may support empirical research, by predicting physiological and brain signals that may accompany both adaptive and maladaptive interoceptive control.

Highlights

We use Active Inference to provide formal models of interoceptive control

We model homeostatic, allostatic and goal-directed forms of interoceptive control

Our simulations illustrate both adaptive interoceptive control and its dysfunctions

We discuss how the models can aid empirical research on interoception
Decoupling alignment strategy from feature quantification using a standard alignment incidence data structure
Authors: Choi Kwangbom , Vincent Matthew J. , Churchill Gary A.
Published: February 2021

The abundance of genomic feature such as gene expression is often estimated from observed total number of alignment incidences in the targeted genome regions. We introduce a generic data structure and associated file format for alignment incidence data so that method developers can create novel pipelines comprising models, each optimal for read alignment, post-alignment QC, and quantification across multiple sequencing modalities.

Availability and Implementation

alntoolssoftware is freely available athttps://github.com/churchill-lab/alntoolsunder MIT license.

Contact

kb.choi@jax.orgorgary.churchill@jax.org
Positive selection in multiple salivary gland proteins of Anophelinae reveals potential targets for vector control
Authors: Freitas Lucas , Nery Mariana F.
Published: February 2021

Anophelesis a genus belonging to the Culicidae family, which has great medical importance due to its role as a vector ofPlasmodium, the parasite responsible for malaria. FromAnopheles’functional genomics, great focus has been given to the salivary gland proteins (SGPs) group. This class of proteins is essential to blood-feeding behavior as they have attributes such as vasodilators and anti-clotting properties. Recently, a comprehensive review onAnophelesSGPs was performed, however the authors did not deeply explore the adaptive molecular evolution of these genes. In this context, this work aimed to perform a more detailed analysis of the adaptive molecular evolution of SGPs inAnopheles, carrying out positive selection and gene families evolution analysis on 824 SGPs. Our results show that most SGPs have positively selected sites that can be used as targets in the development of new strategies for vector control. Notably, we were not able to find any evidence of an accelerated shift in the copy-number variation of SGPs compared with other proteins, as suggested in previous works.

Significance Statement

Salivary gland proteins (SGPs) are essential to blood-feeding behavior inAnophelesand they are the most studied class of proteins in blood-feeding insects. However a proper molecular evolution analysis on SGPs inAnophelesis missing. In our analyses we observed that most SGPs have positively selected sites and we were not able to find any evidence of an accelerated shift in the copy-number of SGPs compared with other proteins, as stated in the literature. Our results can open new venues in the development of new strategies for vector control.
Higher-order visual areas broaden stimulus responsiveness in mouse primary visual cortex
Authors: oude Lohuis Matthijs N. , Cantón Alexis Cerván , Pennartz Cyriel M. A. , Olcese Umberto
Published: February 2021

Over the past few years, the various areas that surround the primary visual cortex in the mouse have been associated with many functions, ranging from higher-order visual processing to decision making. Recently, some studies have shown that higher-order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here we studied howin vivooptogenetic inactivation of two higher-order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher-order visual areas similarly modulate early visual processing. In particular, these areas broaden stimulus responsiveness in the primary visual cortex, by amplifying sensory-evoked responses for stimuli not moving along the orientation preferred by individual neurons. Thus, feedback from higher-order visual areas amplifies V1 responses to non-preferred stimuli, which may aid their detection.
Corticotropin-releasing factor distribution in the brain of the brown anole lizard
Authors: Kabelik David
Published: February 2021

Corticotropin-releasing factor (CRF) is best known for its involvement in peripheral glucocorticoid release across vertebrate species. However, CRF is also produced and released throughout various brain regions to regulate central aspects of the stress response. While these various CRF populations have been described extensively in mammals, less is known about their distributions in other amniotes, and only a handful of studies have ever examined CRF distributions in reptiles. Out study is the first to map CRF cell and fiber distributions in the brain of a lizard, the brown anole (Anolis sagrei). Our results indicate that brown anole CRF distributions are highly similar to those in snakes and turtles. However, unlike in these other reptile species, we find immunofluorescent CRF neurons in a few additional brown anole locations, most notably the supraoptic nucleus. The CRF distribution in the present study is also similar to published CRF descriptions in mammals and birds, although our findings, as well as the other published reports in reptiles, collectively suggest that reptiles possess a slightly more restricted distribution of CRF cell populations than do mammals and birds.
Supervised Semantic Similarity
Authors: Sousa Rita T. , Silva Sara , Pesquita Catia
Published: February 2021

Background

Semantic similarity between concepts in knowledge graphs is essential for several bioinformatics applications, including the prediction of protein-protein interactions and the discovery of associations between diseases and genes. Although knowledge graphs describe entities in terms of several perspectives (or semantic aspects), state-of-the-art semantic similarity measures are general-purpose. This can represent a challenge since different use cases for the application of semantic similarity may need different similarity perspectives and ultimately depend on expert knowledge for manual fine-tuning.

Results

We present a new approach that uses supervised machine learning to tailor aspect-oriented semantic similarity measures to fit a particular view on biological similarity or relatedness. We implement and evaluate it using different combinations of representative semantic similarity measures and machine learning methods with four biological similarity views: protein-protein interaction, protein function similarity, protein sequence similarity and phenotype-based gene similarity.

Conclusions

The results demonstrate that our approach outperforms non-supervised methods, producing semantic similarity models that fit different biological perspectives significantly better than the commonly used manual combinations of semantic aspects.
From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits
Authors: Sun Quan , Crowley Cheynna A. , Huang Le , Wen Jia , Chen Jiawen , Bao Erik L. , Auer Paul L. , Lettre Guillaume , Reiner Alexander P. , Sankaran Vijay G. , Raffield Laura M. , Li Yun
Published: February 2021

Genome-wide association studies (GWAS) have identified hundreds of thousands of genetic variants associated with complex diseases and traits. However, most variants are noncoding and not clearly linked to genes, making it challenging to interpret these GWAS signals. We present a systematic variant-to-function study, prioritizing the most likely functional elements of the genome for experimental follow-up, for >148,000 variants identified for hematological traits. Specifically, we developed VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny (http://shiny.bios.unc.edu/vampire/). This tool efficiently integrates and displays information from multiple complementary sources, including epigenomic signatures from blood cell relevant tissues or cells, functional and conservation summary scores, variant impact on protein and gene expression, chromatin conformation information, as well as publicly available GWAS and phenome-wide association study (PheWAS) results. Leveraging data generated from independently performed functional validation experiments, we demonstrate that our prioritized variants, genes, or variant-gene links are significantly more likely to be experimentally validated. This study not only has important implications for systematic and efficient revelation of functional mechanisms underlying GWAS variants for hematological traits, but also provides a prototype that can be adapted to many other complex traits, paving the path for efficient variant to function (V2F) analyses.
Development of chemosynthetic microbial communities in organic falls deployed in the deep Southwest Atlantic Ocean
Authors: Amendola Augusto M. , Peres Francielli V. , Moreira Julio C. F. , Sumida Paulo Y. G. , Paula Fabiana S. , Pellizari Vivian H.
Published: February 2021

The assembly and successional processes of microbial communities inhabiting deep-sea whale and wood falls are highly complex and vastly unknown, as a myriad of factors may affect the development of a chemosynthetic-based ecosystem on these organic islands. The chemoautotrophy supported by organic substrates is the basis of long-lasting ecosystems, considered biodiversity hotspots in the oligotrophic deep sea. Understanding how these microbial communities develop and the factors affecting them could shed light on processes related to the maintenance of biodiversity in this environment. We performed a whale- and wood-fall experiment in the southwest Atlantic on the Brazilian continental margin and investigated biofilm-forming bacterial and archaeal communities colonising these substrates, deployed at 1500 and 3300 m depth. The composition of the prokaryotic communities shared some similarities with previously reported organic falls in the north Pacific and the Mediterranean Sea, mainly regarding sulphur oxidising chemolithotrophic taxa from the phyla Campylobacterota and Proteobacteria. Communities were found to be highly different between the organic substrates, as whale fall associated biofilms presented a higher dominance of sulphur oxidising chemolithotrophs. We also observed a significant difference between the two sites, with the whale associated communities at the 1500 isobath presenting a faster establishment of the chemosynthetic taxa.
Nanoscale resolution of microbial fiber degradation in action
Authors: Tatlı Meltem , Moraïs Sarah , Tovar-Herrera Omar E. , Bomble Yannick , Bayer Edward A. , Medalia Ohad , Mizrahi Itzhak
Published: February 2021

Deconstruction of plant cell walls is imperative to global carbon cycling and sustainability efforts. Selected microbes degrade plant fibers using extremely efficient multi-enzymatic cellulosomes assemblies. Organization of cellulosomes on the bacterial cell surface and their ecological regulation remain elusive. By combining structural methodologies with molecular and biochemical approaches on the canonicalClostridium thermocellumsystem, we provide an unprecedented view into the in-situ structure and distribution of cellulosomal enzymes while interacting with their cellulosic substrate during fiber degradation. Structural exploration of growing cultures revealed isogenic phenotypic heterogeneity of cellulosome organization on single cells across the bacterial population, suggesting a division-of labor strategy driven by product-dependent dynamics. This study demonstrates how structural biology under near-physiological conditions can be employed to develop ecological hypotheses to understand microbial plant-fiber degradation at the single-cell nanoscale level.

One Sentence Summary

This study contributes critical insights into thein-situorganization of cellulosomes and their cellulosic substrates and provides evidence for phenotypic heterogeneity, with dynamic, growth phase-dependent organization of the fiber-degrading machinery.
Parallel processing of working memory and temporal information by distinct types of cortical projection neurons
Authors: Bae Jung Won , Jeong Huijeong , Bae Chanmee , Lee Hyeonsu , Paik Se-Bum , Jung Min Whan
Published: February 2021

It is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the medial prefrontal cortex of mice performing a delayed response task. We found that IT neurons, but not PT neurons, convey significant working memory-related signals. We also found that the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons convey far more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.
Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells
Authors: Vasseur Maxence Le , Friedman Jonathan R. , Jost Marco , Xu Jiawei , Yamada Justin , Kampmann Martin , Horlbeck Max A. , Salemi Michelle R. , Phinney Brett S. , Weissman Jonathan S. , Nunnari Jodi
Published: February 2021

Dysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified OCIA domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. We find that OCIAD1 is an inner mitochondrial membrane protein that forms a complex with supramolecular prohibitin assemblies. Our data indicate that OCIAD1 is required for maintenance of normal steady state levels of Complex III and the proteolytic processing of the catalytic subunit cytochromec1(CYC1). In OCIAD1 depleted mitochondria, unprocessed CYC1 is hemylated and incorporated into Complex III. We propose that OCIAD1 acts as an adaptor within prohibitin assemblies to stabilize and/or chaperone CYC1 and to facilitate its proteolytic processing by the IMMP2L protease.
IRONMAN Tunes Responses to Iron Deficiency in Concert with Environmental pH
Authors: Gautam Chandan Kumar , Tsai Huei-Hsuan , Schmidt Wolfgang
Published: February 2021

Iron (Fe) is an essential mineral element which governs the composition of natural plant communities and limits crop yield in agricultural ecosystems due to its extremely low availability in most soils, particularly at alkaline pH. To extract sufficient Fe from the soil under such conditions, some plants includingArabidopsis thalianasecrete Fe-mobilizing phenylpropanoids, which mobilize sparingly soluble Fe hydroxides by reduction and chelation. We show here that ectopic expression of theIRONMANpeptidesIMA1andIMA2improves growth on calcareous soil by inducing the biosynthesis and secretion of the catecholic coumarin fraxetin (7,8-dihydroxy-6-methoxycoumarin) through increased expression ofMYB72andSCOPOLETIN 8-HYDROXYLASE(S8H), a response which is strictly dependent on elevated environmental pH (pHe). By contrast, transcription of the cytochrome P450 family proteinCYP82C4,catalyzing the subsequent hydroxylation of fraxetin to sideretin, which forms less stable complexes with iron, was strongly repressed under such conditions. Luciferase reporter assays in transiently transformed protoplasts showed that IMA1/IMA2 peptides are translated and modulate the expression ofCYP82C4andMYB72by acting as transcriptional coactivators. It is concluded that IMA peptides regulate processes supporting Fe uptake at both acidic and elevated pH by controlling gene expression upstream of or in concert with a putative pHesignal to adapt the plant to the prevailing edaphic conditions. This regulatory pattern confers tolerance to calcareous soils by extending the pH range in which Fe can be efficiently absorbed from the soil. Altering the expression of IMA peptides provides a novel route for generating plants adapted to calcareous soils.

One sentence summary

Ectopic expression of IRONMAN peptides improves growth under iron-limiting conditions by inducing responses to limited iron availability in accordance with the environmental pH.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Wolfgang Schmidt (wosh@gate.sinica.edu.tw).
The neural G protein Gαotagged with GFP at an internal loop is functional inC. elegans
Authors: Kumar Santosh , Olson Andrew C. , Koelle Michael R.
Published: February 2021

Gαois the alpha subunit of the major heterotrimeric G protein in neurons and mediates signaling by every known neurotransmitter, yet the signaling mechanisms activated by Gαoremain to be fully elucidated. Genetic analysis inCaenorhabditis eleganshas shown that Gαosignaling inhibits neuronal activity and neurotransmitter release, but studies of the molecular mechanisms underlying these effects have been limited by lack of tools to complement genetic studies with other experimental approaches. Here we demonstrate that inserting the green fluorescent protein (GFP) into an internal loop of the Gαoprotein results in a tagged protein that is functionalin vivoand that facilitates cell biological and biochemical studies of Gαo. Transgenic expression of Gαo-GFP rescues the defects caused by loss of endogenous Gαoin assays of egg laying and locomotion behaviors. Defects in body morphology caused by loss of Gαoare also rescued by Gαo-GFP. The Gαo-GFP protein is localized to the plasma membrane of neurons, mimicking localization of endogenous Gαo. Using GFP as an epitope tag, Gαo-GFP can be immunoprecipitated fromC. eleganslysates to purify Gαoprotein complexes. The Gαo-GFP transgene reported in this study enables studies involvingin vivolocalization and biochemical purification of Gαoto complement the already well-developed genetic analysis of Gαosignaling.
Deep Behavioral Phenotyping of Mouse Autism Models using Open-Field Behavior
Authors: Klibaite Ugne , Kislin Mikhail , Verpeut Jessica L. , Sun Xiaoting , Shaevitz Joshua W. , Wang Samuel S.-H.
Published: February 2021

Abstract

Autism is noted for both its genotypic and phenotypic diversity. Repetitive action, resistance to environmental change, and motor disruptions vary from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we use advances in computer vision and deep learning to develop a framework for characterizing mouse behavior on multiple time scales using a single popular behavioral assay, the open field test. We observed male and female C57BL/6J mice to develop a dynamic baseline of adaptive behavior over multiple days. We then examined two rodent models of autism, a cerebellum-specific model, L7-Tsc1, and a whole-brain knockout model, Cntnap2. Both Cntnap2 knockout and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure-to-adapt took the form of maintained ambling, turning, and locomotion, and an overall decrease in grooming. Adaptation in Cntnap2 knockout mice more broadly resembled that of wild-type. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics.
Molecular origin of somatostatin-positive neuron vulnerability
Authors: Tomoda Toshifumi , Sumitomo Akiko , Newton Dwight , Sibille Etienne
Published: February 2021

Reduced somatostatin (SST) and SST-positive (SST+) neurons are hallmarks of neurological disorders and associated with mood disturbances, but their origin are unknown. Chronic psychosocial stress induces behavioral emotionality deficits and deregulates unfolded protein response (UPR) of the endoplasmic reticulum (ER) preferentially in SST+neurons. Here we confirm that chronic stress increases ER stress levels in SST+neurons of mouse prefrontal cortex, and show that genetically suppressing ER stress in SST+neurons, but not in pyramidal neurons, normalized psychosocial stress-induced behavioral emotionality. Forced expression of SST precursor protein (preproSST), mimicking psychosocial stress-induced early proteomic changes, induces ER stress, whereas mature SST or processing-incompetent preproSST does not. Biochemical analyses further show that psychosocial stress induces SST protein aggregation under elevated ER stress conditions. These results demonstrate that SST processing is a SST+neuron-intrinsic vulnerability factor under conditions of sustained or over-activated UPR in the ER, hence negatively impacting SST+neuron functions.