bluuebunny/crossref_metadata_2025 huggingface dataset:
Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway
Authors: Wu Qin , Dong Jiajun , Cheng Yahong , Jiang Gaofeng
Published: October 2021

A large body of research has established diabetes-related cognitive deterioration, sometimes known as “diabetic encephalopathy.” Current evidence supports that oxidative stress, neuronal apoptosis, and cerebral microcirculation weakness are associated with cognition deficits induced by diabetes. The present study explores the effect of propionate on neurological deficits, cerebral blood flow, and oxidative stress in diabetic mice. Propionate can markedly improve neurological function, which is correlated with its capabilities of stimulating nitric oxide (NO) production, increasing cerebral microcirculation, suppressing oxidative stress and reducing neuron loss in the hippocampus. In addition, the results of Western Blotting indicated that the brain-protective function of propionate in streptozocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) mice is related to phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt)/endothelial nitric oxide synthase(eNOS) signaling pathway. In a diabetic mouse model, propionate reduces cerebral microcirculation, hippocampus apoptosis, and neurological impairment. Thus, propionate, now employed as a food preservative, may also help slow diabetes-induced cognitive loss.

Graphical Abstract

Highlights

Propionate ameliorates diabetic-induced depression-like behavior, spatial learning and memory deficits.

Propionate increases cerebral microcirculation by enhancing NO production in diabetic mice.

Propionate suppresses oxidative stress and reduces neuron loss in the hippocampus.

The brain-protective function of propionate is related to PI3K/Akt/eNOS signaling pathway.
City climate and landscape structure shape pollinators, nectar and transported pollen along a gradient of urbanization
Authors: Biella Paolo , Tommasi Nicola , Guzzetti Lorenzo , Pioltelli Emiliano , Labra Massimo , Galimberti Andrea
Published: October 2021

Urbanization gradients influence both landscape and climate and provide opportunity for understanding how species, especially plants and pollinators, respond to artificially driven environmental transitions.

Here, we investigated several aspects of pollination along an urbanization gradient in landscape and climate. We quantified wild hoverfly and bee abundances with trapping, standing crop of nectar with spectrophotometer, and the pollen transported by flower-visitors with DNA-metabarcoding, in 40 independent sites from seminatural to built-up areas in Northern Italy.

Linear and nonlinear relationships were detected along the urbanization gradient. Pollinator abundances increased until 22% of impervious surface, dropping by 34% after that, and it also decreased with green patch distance and urban park size. Thus, suburban landscapes host more pollinators than highly cemented or seminatural areas. Moreover, pollinators diminished by up to 45% in areas with low temperature seasonality: urbanized areas likely posing thermic stress. Furthermore, the sugar mass available in nectar increased by 91% with impervious cover, indicating that city nectars were less consumed or flowers more productive. Furthermore, the species richness of pollen decreased by 32% in highly urbanized areas, and with a high incidence of exotic plants, hinting for anthropized plant communities.

Synthesis and applications. Urbanization influences pollinator abundances, nectar resources and transported pollen. Pollinators are negatively affected by a thermally harsh climate in highly urbanized areas with isolated green areas and large parks. Suburban landscapes demonstrated the highest pollinator presence. In the city core, flowers contained more nectary sugar, while pollinators collected pollen from a small number of plants, mainly exotic. These findings highlight the influence of urban landscape structure and climate on pollinators and plants, showing that cities are heterogenous realities. Patterns from this study will serve as basis for pollinator-friendly planning and management of urban landscapes.
Cofilin regulates actin network homeostasis and microvilli length in mouse oocytes
Authors: Bourdais Anne , Dehapiot Benoit , Halet Guillaume
Published: October 2021

How multiple actin networks coexist in a common cytoplasm, while competing for a shared pool of monomers, is still an ongoing question. This is exemplified by meiotic maturation in the mouse oocyte, which relies on the dynamic remodeling of distinct cortical and cytoplasmic F-actin networks. Here we show that the conserved actin-depolymerizing factor cofilin is activated in a switch-like manner at meiosis resumption from prophase arrest. Interfering with cofilin activation during maturation resulted in widespread microvilli elongation, while cytoplasmic F-actin was depleted, leading to defects in spindle migration and polar body extrusion. In contrast, cofilin inactivation in metaphase II-arrested oocytes resulted in a shutdown of F-actin dynamics, along with a dramatic overgrowth of the polarized actin cap. However, inhibition of the Arp2/3 complex to promote actin cap disassembly elicited ectopic microvilli outgrowth in the polarized cortex. These data establish cofilin as a key player in actin network homeostasis in oocytes, and reveal that microvilli can act as a sink for monomers upon disassembly of a competing network.
Remarkable Adsorption Performance of Rutile TiO2 (110) Nanosheet for DNA Nucleobases: A First-Principles Study
Authors: Yang Jin , Liu Wen , Hu Qiang , Hu Shuhuan , Chi Zonglin , Han Yizhang , Meng Fanchao
Published: October 2021

The remarkable biocompatibility and supreme physical properties of nanostructured TiO2 have promised itself a strong future for biomedical applications. The present study reported a theoretical study on the adsorption of rutile TiO2 (110) nanosheet for DNA nucleobases using first-principles calculations. The calculations of the binding energy and work function demonstrate that the TiO2 nanosheet has remarkable adsorption strength to the DNA nucleobases, being more than 20 times larger than that of graphene and its derivatives. Further electronic band structure and density of state calculations elucidate the interaction mechanisms, which originate from dramatically reduced energy levels and strong hybridization of the 2p orbital of C, N and/or O with 3d orbital of Ti atoms near the Fermi level. The study directs a promising material at applications in DNA sensors and sequencers.
Microtubule disassembly by caspases is the rate-limiting step of cell extrusion
Authors: Villars Alexis , Matamoro-Vidal Alexis , Levillayer Florence , Levayer Romain
Published: October 2021

Epithelial cell death is essential for tissue homeostasis, robustness and morphogenesis. The expulsion of epithelial cells following caspase activation requires well-orchestrated remodeling steps leading to cell elimination without impairing tissue sealing. While numerous studies have provided insight about the process of cell extrusion, we still know very little about the relationship between caspase activation and the remodeling steps of cell extrusion. Moreover, most studies of cell extrusion focused on the regulation of actomyosin and steps leading to the formation of a supracellular contractile ring. However, the contribution of other cellular factors to cell extrusion has been poorly explored. Using the Drosophila pupal notum, a single layer epithelium where most extrusion events are caspase-dependent, we first showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration/dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. We confirmed that local and rapid increase/decrease of microtubules is sufficient to respectively expand/constrict cell apical area. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting steps of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.
DAF-2/insulin IGF-1 receptor regulates motility during ageing by integrating opposite signaling from muscle and neuronal tissues
Authors: Roy Charline , Molin Laurent , Alcolei Allan , Solyga Mathilde , Bonneau Benjamin , Vachon Camille , Bessereau Jean-Louis , Solari Florence
Published: October 2021

During ageing, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In C. elegans, mutants of the insulin-IGF-1 receptor DAF-2/IIRc represent a paradigm of healthy ageing, as their increased lifespan is accompanied by a delay in age-related loss of motility. However, these animals are less mobile than wild-type animals in early adulthood. Here we investigated the DAF-2/IIRc- dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc. As previously reported, inactivation of DAF-2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2/IIRc prevented the age-related loss of motility. In 1-day-old adults, DAF-2/IIRc depletion in neurons reduced motility in a DAF-16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middleage animals improved their motility independently of DAF-16/FOXO but required UNC-120/SRF.

Yet, neuronal or muscle DAF-2/IIRc depletion both preserved the mitochondria network in ageing muscle. Overall, these results show that the motility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.
Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents
Authors: Sirmpilatze Nikoloz , Mylius Judith , Ortiz-Rios Michael , Baudewig Jürgen , Paasonen Jaakko , Golkowski Daniel , Ranft Andreas , Ilg Rüdiger , Gröhn Olli , Boretius Susann
Published: October 2021

During deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats. At first, we determined the fMRI signatures of burst-suppression in human EEG-fMRI data. Applying this method to animal fMRI datasets, we found distinct burst-suppression signatures in all species. The burst-suppression maps revealed a marked inter-species difference: in rats the entire neocortex engaged in burst-suppression, while in primates most sensory areas were excluded—predominantly the primary visual cortex. We anticipate that the identified species-specific fMRI signatures and whole-brain maps will guide future targeted studies investigating the cellular and molecular mechanisms of burst-suppression in unconscious states.
Astrocytic urea cycle detoxifies Aβ-derived ammonia while impairing memory in Alzheimer’s disease
Authors: Ju Yeon Ha , Bhalla Mridula , Hyeon Seung Jae , Oh Ju Eun , Yoo Seonguk , Chae Uikyu , Kwon Jae , Koh Wuhyun , Lim Jiwoon , Park Yongmin Mason , Lee Junghee , Cho Il-Joo , Lee Hyunbeom , Ryu Hoon , Lee C. Justin
Published: October 2021

Alzheimer’s disease (AD) is one of the foremost neurodegenerative diseases, characterized by beta-amyloid (Aβ) plaques and significant progressive memory loss. In AD, astrocytes are known to take up and clear Aβ plaques. However, how Aβ induces pathogenesis and memory impairment in AD remains elusive. We report that normal astrocytes show non-cyclic urea metabolism, whereas Aβ-treated astrocytes show switched-on urea cycle with upregulated enzymes and accumulated entering-metabolite aspartate, starting-substrate ammonia, end-product urea, and side-product putrescine. Gene-silencing of astrocytic ornithine decarboxylase-1 (ODC1), facilitating ornithine-to-putrescine conversion, boosts urea cycle and eliminates aberrant putrescine and its toxic by-products ammonia, H2O2, and GABA to recover from reactive astrogliosis and memory impairment in AD model. Our findings implicate that astrocytic urea cycle exerts opposing roles of beneficial Aβ detoxification and detrimental memory impairment in AD. We propose ODC1-inhibition as a promising therapeutic strategy for AD to facilitate removal of toxic molecules and prevent memory loss.
Eyeblink conditioning performance and brain-wide C-fos expression in male and female mice
Authors: Oyaga Maria Roa , Serra Ines , Kurup Devika , Koekkoek Sebastiaan K.E. , Badura Aleksandra
Published: October 2021

The functional and molecular sources of behavioral variability in mice are not fully understood. As a consequence, the predominant use of male mice has become a standard in animal research, under the assumption that males are less variable than females. Similarly, to homogenize genetic background, neuroscience studies have almost exclusively used the C57BL/6 (B6) strain. Here, we examined individual differences in performance in the context of associative learning. We performed delayed eyeblink conditioning while recording locomotor activity in mice from both sexes in two strains (B6 and B6CBAF1). Further, we used a C-FOS immunostaining approach to explore brain areas involved in eyeblink conditioning across subjects and correlate them with behavioral performance. We found that B6 male and female mice show comparable variability in this task and that females reach higher learning scores. We found a strong positive correlation across sexes between learning scores and voluntary locomotion. C-FOS immunostainings revealed positive correlations between C-FOS positive cell density and learning in the cerebellar cortex, as well as multiple previously unreported extra-cerebellar areas. We found consistent and comparable correlations in eyeblink performance and C-fos expression in B6 and B6CBAF1 females and males. Taken together, we show that differences in motor behavior and activity across brain areas correlate with learning scores during eyeblink conditioning across strains and sexes.
Attention please: modeling global and local context in glycan structure-function relationships
Authors: Dai Bowen , Mattox Daniel E , Bailey-Kellogg Chris
Published: October 2021

Glycans are found across the tree of life with remarkable structural diversity enabling critical contributions to diverse biological processes, ranging from facilitating host-pathogen interactions to regulating mitosis & DNA damage repair. While functional motifs within glycan structures are largely responsible for mediating interactions, thecontextsin which the motifs are presented can drastically impact these interactions and their downstream effects. Here, we demonstrate the first deep learning method to represent both local and global context in the study of glycan structure-function relationships. Our method, glyBERT, encodes glycans with a branched biochemical language and employs an attention-based deep language model to learn biologically relevant glycan representations focused on the most important components within their global structures. Applying glyBERT to a variety of prediction tasks confirms the value of capturing rich context-dependent patterns in this attention-based model: the same monosaccharides and glycan motifs are represented differently in different contexts and thereby enable improved predictive performance relative to the previous state-of-the-art approaches. Furthermore, glyBERT supports generative exploration of context-dependent glycan structure-function space, moving from one glycan to “nearby” glycans so as to maintain or alter predicted functional properties. In a case study application to altering glycan immunogenicity, this generative process reveals the learned contextual determinants of immunogenicity while yielding both known and novel, realistic glycan structures with altered predicted immunogenicity. In summary, modeling the context dependence of glycan motifs is critical for investigating overall glycan functionality and can enable further exploration of glycan structure-function space to inform new hypotheses and synthetic efforts.
A Golden Gate-based Plasmid Library for the Rapid Assembly of Biotin Ligase Constructs for Proximity Labelling
Authors: Goslin Kevin , Finocchio Andrea , Wellmer Frank
Published: October 2021

Proximity-labelling has emerged as a powerful tool for the detection of weak and transient interactions between proteins as well as the characterization of subcellular proteomes. One proximity labelling approach makes use of a promiscuous bacterial biotin ligase, termed BioID. Expression of BioID (or of its derivates TurboID and MiniTurbo) fused to a bait protein results in the biotinylation of proximal proteins. These biotinylated proteins can then be isolated by affinity purification using streptavidin-coated beads and identified by mass spectrometry. To facilitate the use of proximity-labelling in plants, we have generated a collection of constructs that can be used for the rapid cloning of TurboID and MiniTurbo fusion proteins using the Golden Gate cloning method. To allow for the use of the constructs in a range of experiments we have designed assembly modules that encode the biotin ligases fused to different linkers as well as different commonly used subcellular localization sequences. We demonstrate the functionality of these vectors through biotinylation assays in tobacco (Nicotiana benthamiana) plants.
Open-source low-cost cardiac optical mapping system
Authors: Rybashlykov D. , Brennan J. , Lin Z. , Efimov I.R. , Syunyaev R.
Published: October 2021

Fluorescent imaging with voltage- or calcium-sensitive dyes, i.e. optical mapping, is one of the indispensable modern techniques to study cardiac electrophysiology, unsurpassed by temporal and spatial resolution. High-speed CMOS cameras capable of optical registration of action potential propagation are in general very costly. We present a complete solution priced below US$ 1,000 (including camera and lens) at the moment of publication with an open-source image acquisition and processing software. We demonstrate that the iDS UI-3130CP rev.2 camera we used in this study is capable of 200×200 977 frames per second (FPS) action potential recordings from rodent hearts. The signal-to-noise-ratio of a conditioned signal was 16 ± 10 for rodent hearts. A comparison with a specialized MiCAM Ultimate-L camera has shown that signal-to-noise ratio (SNR) is sufficient for accurate measurements of AP waveform, conduction velocity (± 0.04 m/s) and action potential duration (± 7ms) in mouse and rat hearts. We measured the action potential prolongation during 4-aminopyridine administration in mouse heart, showing that proposed system signal quality is adequate for drug studies.
PDXNet Portal: Patient-Derived Xenograft model, data, workflow, and tool discovery
Authors: Koc Soner , Lloyd Michael W. , Grover Jeffrey , Seepo Sara , Subramanian Sai Lakshmi , Ray Manisha , Frech Christian , DiGiovanna John , Webster Phillip , Neuhauser Steven , Srivastava Anuj , Woo Xing Yi , Sanderson Brian J. , White Brian , Lott Paul ,   PDXNet Consortium, Evrard Yvonne A. , Wallace Tiffany A. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Chen Moon S. , Carvajal-Carmona Luis , Welm Alana L. , Welm Bryan E. , Lewis Michael T. , Govindan Ramaswamy , Ding Li , Li Shunquang , Herlyn Meenherd , Davies Mike , Roth Jack , Meric-Bernstam Funda , Robinson Peter N. , Bult Carol J. , Davis-Dusenbery Brandi , Dean Dennis A. , Chuang Jeffrey H. ,   for the PDXNet Consortium Members
Published: October 2021

We created the PDX Network (PDXNet) Portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources (i.e., PDX models, sequencing data, treatment response data, and bioinformatics workflows), to facilitate collaboration among researchers, and to make resources easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols, and training materials for processing PDX data.

The initial portal release highlights PDXNet model and data resources, including 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI’s Patient-Derived Model Repository (PDMR) for public access. These models have 2,822 associated sequencing files from 873 samples across 307 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal also includes results from standardized analysis workflows on PDXNet sequencing files and PDMR data (2,594 samples from 463 patients across 78 disease types). These 15 analysis workflows for whole-exome and RNA-Seq data are freely available, robust, validated, and standardized.

The model and data lists will grow substantially over the next two years and will be continuously updated as new data are available. PDXNet models support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials. The PDXNet portal is a centralized location for these data and resources, which we expect to be of significant utility for the cancer research community.
Alpha cell dysfunction in early type 1 diabetes
Authors: Doliba Nicolai M , Rozo Andrea V , Roman Jeffrey , Qin Wei , Traum Daniel , Gao Long , Liu Jinping , Manduchi Elisabetta , Liu Chengyang , Golson Maria L , Vahedi Golnaz , Naji Ali , Matschinsky Franz M , Atkinson Mark A. , Powers Alvin C , Brissova Marcela , Kaestner Klaus H , Stoffers Doris A ,   for the HPAP Consortium
Published: October 2021

Multiple islet autoantibodies (AAb) predict type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in just ∼15% of single AAb+ (generally against glutamic acid decarboxylase, GADA+) individuals; hence the single GADA+ state may represent an early stage of T1D amenable to interventions. Here, we functionally, histologically, and molecularly phenotype human islets from non-diabetic, GADA+ and T1D donors. Similar to the few remaining beta cells in T1D islets, GADA+ donor islets demonstrated a preserved insulin secretory response. By contrast, alpha cell glucagon secretion was dysregulated in both T1D and GADA+ islets with impaired glucose suppression of glucagon secretion. Single cell RNA sequencing (scRNASeq) of GADA+ alpha cells revealed distinct abnormalities in glycolysis and oxidative phosphorylation pathways and a marked downregulation of PKIB, providing a molecular basis for the loss of glucose suppression and the increased effect of IBMX observed in GADA+ donor islets. The striking observation of a distinct early defect in alpha cell function that precedes beta cell loss in T1D suggests that not only overt disease, but also the progression to T1D itself, is bihormonal in nature.
CellTools algorithm for mapping scRNA-seq query cells to the reference dataset improves the classification of resilient and susceptible retinal ganglion cell types
Authors: Rheaume Bruce A. , Xing Jian , Theune William C. , DeRosa Samantha G. , Trakhtenberg Ephraim F.
Published: October 2021

The clustering of single cell RNA-sequencing (scRNA-seq) data enables the classification of cell types, and the development of integration mapping algorithms has enabled the tracing of altered-from-baseline transcriptomes to their respective cell type origins. Here, we developed an algorithm that removes sources of noise from scRNA-seq reference dataset, and in the next step optimizes weight-assignment to anchors, cumulatively improving the accuracy of query cells mapping to reference dataset. The denoising step of our algorithm also improved the performance of other mapping algorithms. To further demonstrate biological relevance, using our algorithm we determined the type-origin of the 17% of injured retinal ganglion cells (RGCs) that a prior algorithm did not identify. As we found that most of the originally unassigned cells belonged to only some RGC types, a consequent change in the proportions of the surviving types resulted in an amended ranking of resiliency to injury. We also identified new cluster-markers for RGC types, validated two novel markers by immunostaining in retinas, and developed a website for cluster-by-cluster comparison of gene expression between uninjured and injured RGC types. Additional bioinformatic analyses contributed new insights into the global characteristics of RGC types and how axonal injury affects them, showing how dissimilarity between transcriptomes of RGC types increases during maturation and after injury. We further characterized the correspondence between the neonatal and adult RGC types, and showed which cluster markers change expression developmentally or after injury. We also show, for the first time, that global properties of the transcriptome can predict the resilience to injury of at least some cell types. The R-package, CellTools, for the algorithms we developed, will assist scRNA-seq studies across biological fields.
How low can you go? Driving down the DNA input requirements for nanopore sequencing
Authors: Heavens Darren , Chooneea Darren , Giolai Michael , Cuber Piotr , Aanstad Pia , Martin Samuel , Alston Mark , Misra Raju , Clark Matthew D. , Leggett Richard M.
Published: October 2021

The requirement for large amounts of purified DNA limits many sequencing experiments, especially when seeking to avoid pre-amplification or when using third generation technology to sequence molecules directly. We wanted to test the limits of current nanopore sequencing input requirements and devised a set of experiments to evaluate extraction and library preparation approaches for low inputs.

We found an optimised bead beating approach combined with a magnetic bead protocol, rather than traditional spin columns for DNA extraction, improved both molecule length, integrity score and DNA yield. Through reducing the DNA input to as little as 6.25 % of recommended (25 ng versus 400 ng) and reaction volumes in half, library construction can be completed, and sequencing begun within 20 minutes of sample collection.

Applying these approaches, we demonstrated that our pipeline can be used as a cheap and effective method to de novo assemble a genome and identify genes from low quantities and quality of DNA. With our rapid extraction protocol using transportable equipment and low input library construction we were able to generate a de novo assembly from a single insect (Drosophila melanogaster) spanning 125 Mbp / 85 % of the reference genome, over 96.9% complete BUSCO genes, with a contig N50 over 1.2 Mbp, including chromosome arm sized contigs, for a modest consumable cost under £600.
Assessing species coverage and assembly quality of rapidly accumulating sequenced genomes
Authors: Feron Romain , Waterhouse Robert M.
Published: October 2021

Ambitious initiatives to coordinate genome sequencing of Earth’s biodiversity mean that the accumulation of genomic data is growing rapidly. In addition to cataloguing biodiversity, these data provide the basis for understanding biological function and evolution. Accurate and complete genome assemblies offer a comprehensive and reliable foundation upon which to advance our understanding of organismal biology at genetic, species, and ecosystem levels. However, ever-changing sequencing technologies and analysis methods mean that available data are often heterogeneous in quality. In order to guide forthcoming genome generation efforts and promote efficient prioritisation of resources, it is thus essential to define and monitor taxonomic coverage and quality of the data. Here we present an automated analysis workflow that surveys genome assemblies from the United States National Center for Biotechnology Information (NCBI), assesses their completeness using the relevant Benchmarking Universal Single-Copy Orthologue (BUSCO) datasets, and collates the results into an interactively browsable resource. We apply our workflow to produce a community resource of available assemblies from the phylum Arthropoda, the Arthropoda Assembly Assessment Catalogue. Using this resource, we survey current taxonomic coverage and assembly quality at the NCBI, we examine how key assembly metrics relate to gene content completeness, and we compare results from using different BUSCO lineage datasets. These results demonstrate how the workflow can be used to build a community resource that enables large-scale assessments to survey species coverage and data quality of available genome assemblies, and to guide prioritisations for ongoing and future sampling, sequencing, and genome generation initiatives.
Reward timing matters in motor learning
Authors: Vassiliadis Pierre , Lete Aegryan , Duque Julie , Derosiere Gerard
Published: October 2021

Reward can improve motor learning and the consolidation of motor memories. Identifying the features of reward feedback that are critical for motor learning is a necessary step for successful integration into rehabilitation programs. One central feature of reward feedback that may affect motor learning is its timing – that is, the delay after which reward is delivered following movement execution. In fact, research on associative learning has shown that short and long reward delays (e.g., 1 and 6 s following action execution) activate preferentially the striatum and the hippocampus, respectively, which both contribute with varying degrees to motor learning. Given the distinct functional role of these two areas, we hypothesized that reward timing could modulate how people learn and consolidate a new motor skill. In sixty healthy participants, we found that delaying reward delivery by a few seconds influenced motor learning dynamics. Indeed, training with a short reward delay (i.e., 1 s) induced slow, yet continuous gains in performance, while a long reward delay (i.e., 6 s) led to initially high learning rates that were followed by an early plateau in the learning curve and a lower endpoint performance. Moreover, participants who successfully learned the skill with a short reward delay displayed overnight consolidation, while those who trained with a long reward delay exhibited an impairment in the consolidation of the motor memory. Overall, our data show that reward timing affects motor learning, potentially by modulating the engagement of different learning processes, a finding that could be exploited in future rehabilitation programs.
Generative modeling of histology tissue reduces human annotation effort for segmentation model development
Authors: Lutnick Brendon , Sarder Pinaki
Published: October 2021

Segmentation of histology tissue whole side images is an important step for tissue analysis. Given enough annotated training data modern neural networks are capable accurate reproducible segmentation, however, the annotation of training datasets is time consuming. Techniques such as human in the loop annotation attempt to reduce this annotation burden, but still require a large amount of initial annotation. Semi-supervised learning, a technique which leverages both labeled and unlabeled data to learn features has shown promise for easing the burden of annotation. Towards this goal, we employ a recently published semi-supervised method:datasetGANfor the segmentation of glomeruli from renal biopsy images. We compare the performance of models trained usingdatasetGANand traditional annotation and show thatdatasetGANsignificantly reduces the amount of annotation required to develop a highly performing segmentation model. We also explore the usefulness of usingdatasetGANfor transfer learning and find that this greatly enhances the performance when a limited number of whole slide images are used for training.
Stratification in Microbial Communities with Depth and Redox Status in a Eutrophic Lake Across Two Years
Authors: Marick Robert A. , Peterson Benjamin D. , McMahon Katherine D.
Published: October 2021

Bacteria have a profound impact on many key biogeochemical cycles in freshwater lake ecosystems; in turn, the composition of bacteria in the lake is contingent on the chemistry of the water. Many parameters that affect bacterial growth in freshwater ecosystems, such as water temperature, nutrient levels, and redox status, exhibit notable inter-annual differences in addition to seasonal changes. However, little is known about the impact of these inter- and intra-annual differences on the freshwater microbiome, especially in anoxic bottom waters. In this study, we paired biogeochemical field data with 16S rRNA gene amplicon sequencing of depth-discrete samples from a dimictic lake across two open-water seasons to observe variation in the microbiome relative to differences in water chemistry between two years. We found differences in the timing anoxia onset and the redox status in the water column across the two years. Changes in redox status led to major shifts in the microbial community composition. While there was little variation between years in the microbial taxonomic composition at the phyla level, there was substantial interannual variation at more resolved taxonomic levels. Some interannual differences can be explained by links between the predicted metabolic potential of those lineages and the different redox conditions between the two years. These results emphasize the need for repeated monitoring to deduce long-term trends in microbial communities in natural ecosystems and the importance of a comprehensive evaluation of environmental conditions contemporary with any microbiome analysis.

Importance

The results of this study add to the growing body of evidence that microbial communities in natural systems are temporally dynamic on multiple scales, and even more so at highly resolved taxonomic levels. By correlating our analysis of the microbial community with the redox status of the water column we find that many community differences between the years can be in part explained by these parameters. As collecting 16S rRNA data over many years is critical to understanding long term trends in microbial ecology, our study suggests that corresponding water chemistry data could be a powerful tool to help explain microbiome trends.
MspA Porin as a Local Nanopore Probe for Membrane-bound Proteins
Authors: Hoogerheide David P. , Gurnev Philip A. , Gundlach Jens , Laszlo Andrew , Rostovtseva Tatiana K. , Bezrukov Sergey M.
Published: October 2021

Nanopore sensing is based on detection and analysis of nanopore transient conductance changes induced by analyte capture. We have recently shown that α-Synuclein (αSyn), an intrinsically disordered, membrane-active, neuronal protein implicated in Parkinson disease, can be reversibly captured by the VDAC nanopore. The capture process is a highly voltage dependent complexation of the two proteins where transmembrane potential drives the polyanionic C-terminal domain of αSyn into VDAC—exactly the mechanism by which generic nanopore-based interrogation of proteins and polynucleotides proceeds. The complex formation, and the motion of αSyn in the nanopore, thus may be expected to be only indirectly dependent on the pore identity. Here, we confirm this prediction by demonstrating that when VDAC is replaced with a different transmembrane pore, the engineered mycobacterial porin M2MspA, all the qualitative features of the αSyn/nanopore interaction are preserved. The rate of αSyn capture by M2MspA rises exponentially with the applied field, while the residence time displays a crossover behavior, indicating that at voltages >50 mV M2MspA-bound αSyn largely undergoes translocation to the other side of the membrane. The translocation is directly confirmed using the selectivity tag method, in which the polyanionic C-terminal and neutral N-terminal regions of αSyn alter the selectivity of the M2MspA channel differently, allowing direct discrimination of translocation vs retraction for single αSyn molecules. We thus prove that the physical model of the motion of disordered protein chains in the nanopore confinement and the selectivity tag technique are not limited to VDAC but are broadly applicable to nanopore-based protein detection, analysis, and separation technologies.
The functional differences between paralogous regulators define the control of the General Stress Response in Sphingopyxis granuli TFA
Authors: de Dios Rubén , Santero Eduardo , Reyes-Ramírez Francisca
Published: October 2021

Sphingopyxis granuli TFA is a contaminant degrading alphaproteobacterium that responds to adverse conditions by inducing the General Stress Response (GSR), an adaptive response that controls the transcription of a variety of genes to overcome adverse conditions. The GSR triggered by TFA is driven by two extracytoplasmic function σ factors (ECFs), EcfG1 and EcfG2, whose functional differences have been addressed previously, being EcfG2 the main activator. Upstream in this cascade, NepR anti-σ factors directly inhibit EcfG activity under non-stress conditions, whereas PhyR response regulators sequester the NepR elements upon stress sensing to relieve EcfG inhibition. These elements, which are essential mediators of the GSR regulation, are duplicated in TFA, being NepR1 and NepR2, and PhyR1 and PhyR2. Here, based on multiple genetic, phenotypical and biochemical evidences including in vitro transcription assays, we have assigned distinct functional features to each of these paralogs and assessed their contribution to the GSR regulation, dictating its timing and the intensity. We show that different stress signals are differentially integrated into the GSR by PhyR1 and PhyR2, therefore producing different levels of GSR activation. We demonstrate in vitro that both NepR1 and NepR2 bind EcfG1 and EcfG2, although NepR1 produces a more stable interaction than NepR2. Conversely, NepR2 interacts with phosphorylated PhyR1 and PhyR2 more efficiently than NepR1. We propose an integrative model where NepR2 would play a dual negative role: it would directly inhibit the σ factors upon activation of the GSR and it would modulate the GSR activity indirectly by titrating the PhyR regulators.

IMPORTANCE

In Alphaproteobacteria, the General Stress Response (GSR) aims at protecting against a variety of stresses. Needing to integrate different signals, its modulation is capital to produce a proportionate response according to the environmental conditions. Individual alphaproteobacterial species have evolved distinct GSR cascades in which the information flow is usually straightforward to ascertain due to the presence of a single copy of at least one of its main regulators (PhyR, NepR and EcfG), restricting the regulatory possibilities. However, Sphingopyxis granuli TFA encodes two paralogs of each regulator, multiplying the possible regulatory interplays. We demonstrate that functional differences between paralogous GSR regulators allow an intrinsic feedback regulation in this pathway. We provide evidence of a NepR anti-σ factor that exerts a dual negative feedback regulation on the GSR by interacting with the EcfG σ factors and with the PhyR regulators. This would attune its output to the actual needs of the cell.
Hair phenotype diversity across Indriidae lemurs
Authors: Tapanes Elizabeth , Jacobs Rachel L. , Harryman Ian , Louis Edward E. , Irwin Mitchell T. , Kamilar Jason M. , Bradley Brenda J.
Published: October 2021

Objectives

Hair (i.e., pelage/fur) is a salient feature of primate (including human) diversity and evolution— serving functions tied to thermoregulation, protection, camouflage, and signaling—but wild primate pelage evolution remains relatively understudied. Specifically, assessing multiple hypotheses across distinct phylogenetic scales is essential but is rarely conducted. We examine whole body hair color and density variation across Indriidae (Avahi, Indri, Propithecus)—a lineage that, like humans, exhibits vertical posture (i.e., their whole bodies are vertical to the sun).

Materials and Methods

Our analyses consider multiple phylogenetic scales (family-level, genus-level) and hypotheses (e.g., Gloger’s rule, the body cooling hypotheses). We obtain hair color and density from museum and/or wild animals, opsin genotypes from wild animals, and climate data from WorldClim. To analyze our data, we use phylogenetic generalized linear mixed models (PGLMM) using Markov chain Monte Carlo algorithms.

Results

Our results show that across the Indriidae family, darker hair is typical in wetter regions. However, within Propithecus, dark black hair is common in colder forest regions. Results also show pelage redness increases in populations exhibiting enhanced color vision. Lastly, we find follicle density on the crown and limbs increases in dry and open environments.

Discussion

This study highlights how different selective pressures across distinct phylogenetic scales have likely acted on primate hair evolution. Specifically, our data across Propithecus may implicate thermoregulation and is the first empirical evidence of Bogert’s rule in mammals. Our study also provides rare empirical evidence supporting an early hypothesis on hominin hair evolution.
Wild-type Caenorhabditis elegans Isolates Exhibit Distinct Gene Expression Profiles in Response to Microbial Infection
Authors: Lansdon Patrick , Carlson Maci , Ackley Brian D.
Published: October 2021

The soil-dwelling nematode Caenorhabditis elegans serves as a model system to study innate immunity against microbial pathogens. C. elegans have been collected from around the world, where they, presumably, adapted to regional microbial ecologies. Here we use survival assays and RNA- sequencing to better understand how two isolates from disparate climates respond to pathogenic bacteria. We found that, relative to N2 (originally isolated in Bristol, UK), CB4856 (isolated in Hawaii), was more susceptible to the Gram-positive pathogen, Staphylococcus epidermidis, but equally susceptible to Staphylococcus aureus as well as two Gram-negative pathogens, Providencia rettgeri and Pseudomonas aeruginosa. We performed transcriptome analysis of infected worms and found gene- expression profiles were considerably different in an isolate-specific and pathogen-specific manner. We performed GO term analysis to categorize differential gene expression in response to S. epidermidis. In N2, genes that encoded detoxification enzymes and extracellular matrix proteins were significantly enriched, while in CB4856, genes that encoded detoxification enzymes, C-type lectins, and lipid metabolism proteins were enriched, suggesting they have different responses to these bacterial pathogens, despite being the same species. Overall, discerning gene expression signatures in an isolate by pathogen manner can help us to understand the different possibilities for the evolution of immune responses within organisms.
The quantitative contribution of different Photosystem II compartments to non-photochemical quenching in Arabidopsis
Authors: Nicol Lauren , Mascoli Vincenzo , van Amerongen Herbert , Croce Roberta
Published: October 2021

Excess excitation energy in the light-harvesting antenna of Photosystem II (PSII) can cause irreversible damage to the photosynthetic apparatus. In periods of high light intensity, a feedback mechanism known as non-photochemical quenching (NPQ), induces the formation of quenchers which can safely dissipate excess excitation energy as heat. Although quenchers have been identified in more than one compartment of the PSII supercomplex, there is currently no quantitative description of how much NPQ is occurring at each of these locations. Here, we perform time-resolved fluorescence measurements on WT and antenna mutants lacking LHCII (NoL) and all peripheral antenna (Ch1 and Ch1lhcb5). By combining the results with those of steady-state fluorescence experiments we are able to estimate the intrinsic rate of NPQ for each plant and each PSII compartment. It is concluded that 60-70% of quenching occurs in LHCII, 15-20% in the minor antenna and 15-20% in the PSII core.
Insight in the quorum sensing-driven lifestyle of the non-pathogenic Agrobacterium tumefaciens 6N2 and the interactions with the yeast Meyerozyma guilliermondii
Authors: Bertini Elisa Violeta , Torres Mariela Analía , Léger Thibaut , Garcia Camille , Hong Kar-Wai , Chong Teik Min , de Figueroa Lucía I. Castellanos , Chan Kok-Gan , Dessaux Yves , Camadro Jean-Michel , Nieto-Peñalver Carlos Gabriel
Published: October 2021

Agrobacterium tumefaciens is considered a prominent phytopathogen, though most isolates are nonpathogenic. Agrobacteria can inhabit plant tissues interacting with other microorganisms. Yeasts are likewise part of these communities. We analyzed the quorum sensing (QS) systems of A. tumefaciens strain 6N2, and its relevance for the interaction with the yeast Meyerozyma guilliermondii, both sugarcane endophytes. We show that strain 6N2 is nonpathogenic, produces OHC8-HSL, OHC10-HSL, OC12-HSL and OHC12-HSL as QS signals, and possesses a complex QS architecture, with one truncated, two complete systems, and three additional QS-signal receptors. A proteomic approach showed differences in QS-regulated proteins between pure (64 proteins) and dual (33 proteins) cultures. Seven proteins were consistently regulated by quorum sensing in pure and dual cultures. M. guilliermondii proteins influenced by QS activity were also evaluated. Several up- and down- regulated proteins differed depending on the bacterial QS. These results show the importance of the QS regulation in the bacteria-yeast interactions.

Highlights

The avirulent A. tumefaciens 6N2 has two replicons and a complex QS architecture

The profile of QS-regulated proteins is modified in dual cultures with Pa. laurentii

The bacterial QS activity alters the proteome of the yeast Pa. laurentii