bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary exosomal miR-1307-5p predicts disease aggressiveness and poor prognosis in oral squamous cell carcinoma patients
Authors: Patel Aditi , Patel Shanaya , Patel Parina , Mandlik Dushyant , Patel Kaustubh , Tanavde Vivek
Published: July 2022

Background

Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach.

Method

Small RNA and transcriptome sequencing profiles of tumour tissues and salivary exosomes from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using the Cancer Genome Atlas database and performing Real-time PCR on a larger patient cohort. Potential target genes, miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools.

Results

Salivary exosomes (size: 30-50nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance in these patients. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4, and RNF114.

Conclusion

Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.
Hi-TrAC reveals fractal nesting of super-enhancers
Authors: Cao Yaqiang , Liu Shuai , Cui Kairong , Tang Qingsong , Zhao Keji
Published: July 2022

Eukaryotic genome spatial folding plays a key role in genome function. Decoding the principles and dynamics of 3D genome organization depends on improving technologies to achieve higher resolution. Chromatin domains have been suggested as regulatory micro-environments, whose identification is crucial to understand the genome architecture. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among genomic accessible regulatory regions, allows us to examine active domains with limited sequencing depths at a high resolution. Hi-TrAC can detect active sub-TADs with a median size of 100kb, most of which harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These active sub-TADs are characterized by highly enriched signals of histone mark H3K4me1 and chromatin-binding proteins, including Cohesin complex. We show that knocking down core subunit of the Cohesin complex using shRNAs in human cells or decreasing the H3K4me1 modification by deleting the H3K4 methyltransferase Mll4 gene in mouse Th17 cells disrupted the sub-TADs structure. In summary, Hi-TrAC serves as a compatible and highly responsive approach to studying dynamic changes of active sub-TADs, allowing us more explicit insights into delicate genome structures and functions.

Highlights

-

Hi-TrAC detects active sub-TADs with a median size of 100 kb.

-

Hi-TrAC reveals a block-to-block interaction pattern between super-enhancers, and fractal structures within super-enhancers.

-

Active sub-TADs are disrupted by the knockdown of RAD21.

-

Active sub-TADs interaction densities are decreased by the knockout of Mll4.
A stable, distributed code for cue value in mouse cortex during reward learning
Authors: Ottenheimer David J. , Hjort Madelyn M. , Bowen Anna J. , Steinmetz Nicholas A. , Stuber Garret D.
Published: July 2022

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of pre-frontal cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.
Warmer temperatures favor slower-growing bacteria in natural marine communities
Authors: Abreu Clare I. , Dal Bello Martina , Bunse Carina , Pinhassi Jarone , Gore Jeff
Published: July 2022

Earth’s life-sustaining oceans harbor diverse bacterial communities that display varying composition across time and space. While particular patterns of variation have been linked to a range of factors, unifying rules are lacking, preventing the prediction of future changes. Here, analyzing the distribution of fast- and slow-growing bacteria in ocean datasets spanning seasons, latitude, and depth, we show that higher seawater temperatures universally favor slower-growing taxa, in agreement with theoretical predictions. Our results explain why slow growers dominate at the ocean surface, during summer, and near the tropics, and provide a framework to understand how bacterial communities will change in a warmer world.
Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis
Authors: Zyla-Jackson Katarzyna , Walton Dorothy A. , Plafker Kendra S. , Kovats Susan , Georgescu Constantin , Brush Richard S. , Tytanic Madison , Agbaga Martin-Paul , Plafker Scott M.
Published: July 2022

Five to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the central nervous system, these treatments can be limiting for subsets of patients due to adverse effects and expense. To circumvent these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by people with multiple sclerosis (MS). Here, we report that limiting dietary carbohydrates by feeding mice a ketogenic diet (KD) enriched in medium chain triglycerides, α-linolenic acid, and fiber is effective at mitigating EAE-induced optic neuritis and motor deficits. The KD was efficacious when fed as a preventive regimen prior to EAE immunization as well as when initiated as an interventional regimen following the onset of EAE symptoms. The KD minimally impacted body weight during the experimental time course, increased circulating ketones, prevented motor and ocular deficits, preserved myelination of the optic nerve, and reduced infiltration of immune cells to optic nerves. The KD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with EAE-mediated pathological inflammation. In light of ongoing clinical trials using dietary strategies to treat people with MS, these findings support that a KD promotes a systemic anti-inflammatory milieu and ameliorates autoimmune-induced demyelinating visual and motor deficits.
The breast cancer pro-metastatic phenotype requires concomitant hyper-activation of ECM remodeling and dsRNA-IFN1 signaling in rare clone cells
Authors: Roda Niccoló , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe
Published: July 2022

The molecular determinants of breast cancer (BC) pro-metastatic phenotype are largely unknown. Here, we leveraged lentiviral barcoding coupled to single-cell RNA sequencing to trace clonal and transcriptional evolution during BC metastatization. We showed that metastases derive from rare pro-metastatic clones that are under-represented in primary tumors. Both low clonal-fitness and high metastatic-potential are independent of clonal origin. Differential expression and classification analyses revealed that the pro-metastatic phenotype is acquired in rare cells by concomitant hyper-activation of extracellular-matrix remodeling, dsRNA-interferon signaling, and stress-response pathways. Notably, genetic silencing of single pro-metastatic genes from different pathways significantly impairs migration in vitro and metastatization in vivo, with negligible effects on cell proliferation and tumor growth. In addition, gene-expression signatures from identified pro-metastatic genes predicts metastatic progression in BC patients, independently of known prognostic factors. This study elucidates previously unknown mechanisms of BC metastatization, and provides novel prognosis predictors and therapeutic targets for metastasis prevention.
Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter
Authors: Mumford Thomas R. , Rae Diarmid , Brackhahn Emily , Idris Abbas , Gonzalez-Martinez David , Pal Ayush Aditya , Chung Michael C. , Guan Juan , Rhoades Elizabeth , Bugaj Lukasz J.
Published: July 2022

Protein clustering plays numerous roles in cell physiology and disease. However, protein oligomers can be difficult to detect because they are often too small to appear as puncta in conventional fluorescence microscopy. Here we describe a fluorescent reporter strategy that detects protein clusters with high sensitivity, called CluMPS (ClustersMagnified byPhaseSeparation). A CluMPS reporter detects and visually amplifies even small clusters of a binding partner, generating large, quantifiable fluorescence condensates. We use computational modeling and optogenetic clustering to demonstrate that CluMPS can detect small oligomers and behaves rationally according to key system parameters. CluMPS detected small aggregates of pathological proteins where the corresponding GFP fusions appeared diffuse. CluMPS also detected and tracked clusters of unmodified and tagged endogenous proteins, and orthogonal CluMPS probes could be multiplexed in cells. CluMPS provides a powerful yet straightforward approach to observe higher-order protein assembly in its native cellular context.
Deep-Learning for Automated Markerless Tracking of Infants General Movements
Authors: Abbasi H. , Mollet S.R , Williams S.A. , Lim L. , Battin M.R. , Besier T.F. , McMorland A.J.C.
Published: July 2022

The presence of abnormal infant General Movements (GMs) is a strong predictor of progressive neurodevelopmental disorders, including cerebral palsy (CP). Automation of the assessment will overcome scalability barriers that limit its delivery to at-risk individuals.

Here, we report a robust markerless pose-estimation scheme, based on advanced deep-learning technology, to track infant movements in consumer mobile device video recordings. Two deep neural network models, namely Efficientnet-b6 and resnet152, were trained on manually annotated data across twelve anatomical locations (3 per limb) in 12 videos from 6 full-term infants (mean age = 17.33 (SD 2.9) wks, 4 male, 2 female), using the DeepLabCut™framework.K-fold cross-validation indicates the generalization capability of the deep-nets for GM tracking on out-of-domain data with an overall performance of 95.52% (SD 2.43) from the best performing model (Efficientnet-b6) across all infants (performance range: 84.32– 99.24% across all anatomical locations). The paper further introduces an automatic, unsupervised strategy for performance evaluation on extensive out-of-domain recordings through a fusion of likelihoods from a Kalman filter and the deep-net.

Findings indicate the possibility of establishing an automated GM tracking platform, as a suitable alternative to, or support for, the current observational protocols for early diagnosis of neurodevelopmental disorders in early infancy.
BREAKING THE TIGHT GENETIC LINKAGE BETWEEN THEa1ANDsh2GENES LED TO THE DEVELOPMENT OF ANTHOCYANIN-RICH PURPLE-PERICARP SUPER-SWEETCORN
Authors: Anirban Apurba , Hayward Alice , Hong Hung T , Masouleh Ardashir Kharabian , Henry Robert J , O’Hare Tim J
Published: July 2022

The existence of purple-pericarp super-sweetcorn based on the most common supersweet mutation,shrunken2(sh2), has not been previously reported, partly due to its extremely tight genetic linkage to a non-functional anthocyanin biosynthesis gene,anthocyaninless1(a1). Generally, both aleurone- and pericarp-pigmented purple corn is starchy, the latter of which contains significantly higher anthocyanin compared to the former. The development of purple-pericarp super-sweetcorn is dependent on breaking thea1-sh2tight genetic linkage, which occurs at a very low frequency of <1 in 1000 meiotic crossovers. Here, to develop purple-pericarp super-sweetcorn, an initial cross between a male purple-pericarp maize (purple-round seed), ‘Costa Rica’ (A1Sh2.A1Sh2) and a female whiteshrunken2super-sweetcorn (white-shrunken seed), ‘Tims-white’ (a1sh2.a1sh2), was conducted. Subsequent self-pollination based on purple-pericarp-shrunken kernels identified a small frequency (0.08%) of initial heterozygous F3 segregants (A1a1.sh2sh2) producing a fullysh2cob with a purple-pericarp phenotype, enabled by breaking the close genetic linkage between thea1andsh2genes. Resulting rounds of self-pollination generated a F6 homozygous purple-pericarp super-sweetcorn (A1A1.sh2sh2) line, ‘Tim1’. Genome sequencing revealed a recombination break between thea1andyz1genes of thea1-yz1-x1-sh2multigenic interval, with the sequence pattern of ‘Tim1’ similar to the ‘Costa Rica’ parent, and after the linkage break, similar to the ‘Tims-white’ parent. The novel purple-pericarp super-sweetcorn produced a similar concentration of anthocyanin and sugar as in its purple-pericarp maize and white super-sweetcorn parents, respectively, potentially adding a broader range of health benefits than currently exists with standard yellow/white sweetcorn.
Robust, single-shot, optical autofocus system utilizing cylindrical lenses to provide high precision and long range of operation
Authors: Lightley J. , Kumar S. , Garcia E. , Alexandrov Y. , Dunsby C. , Neil M.A.A. , French P.M.W.
Published: July 2022

We present a robust, “real-time” optical autofocus system for microscopy that provides high accuracy (<230 nm) and long range (∼130 µm) with a 1.4 numerical aperture oil immersion objective lens. This autofocus can operate in a closed loop, single-shot functionality over a range of ±37.5 µm and can also operate as a 2-step process up to ±68 µm. A real-time autofocus capability is useful for experiments with long image data acquisition times, including single molecule localization microscopy, that may be impacted by defocusing resulting from drift of components, e.g., due to changes in temperature or mechanical drift. It is also vital for automated slide scanning or multiwell plate imaging where the sample may not be in the same horizontal plane for every field of view during the image data acquisition. To realise high precision and long range, we implement orthogonal optical readouts using cylindrical lenses. We demonstrate the performance of this new optical autofocus system with automated multiwell plate imaging and single molecule localisation microscopy and illustrate the benefit of using a superluminescent diode as the autofocus light source.
Multi-chamber cardioids unravel human heart development and cardiac defects
Authors: Schmidt Clara , Deyett Alison , Ilmer Tobias , Caballero Aranxa Torres , Haendeler Simon , Pimpale Lokesh , Netzer Michael A. , Ginistrelli Lavinia Ceci , Cirigliano Martina , Mancheno Estela Juncosa , Reumann Daniel , Tavernini Katherina , Hering Steffen , Hofbauer Pablo , Mendjan Sasha
Published: July 2022

The number one cause of human fetal death are defects in heart development. Because the human embryonic heart is inaccessible, and the impacts of mutations, drugs, and environmental factors on the specialized functions of different heart compartments are not captured by in vitro models, determining the underlying causes is difficult. Here, we established a human cardioid platform that recapitulates the development of all major embryonic heart compartments, including right and left ventricles, atria, outflow tract, and atrioventricular canal. By leveraging both 2D and 3D differentiation, we efficiently generated progenitor subsets with distinct first, anterior, and posterior second heart field identities. This advance enabled the reproducible generation of cardioids with compartment-specific in vivo-like gene expression profiles, morphologies, and functions. We used this platform to unravel the ontogeny of signal and contraction propagation between interacting heart chambers and dissect how genetic and environmental factors cause region-specific defects in the developing human heart.
Transcriptomic and proteomic profiling of NaV1.8-expressing mouse nociceptors
Authors: Schmidt Manuela , Sondermann Julia Regina , Gomez-Varela David , Millet Queensta , Wood John N , Zhao Jing
Published: July 2022

Nociceptors play an essential role in both acute pain and chronic pain conditions. and have recently been classified into distinct subsets using single-cell transcriptional profiling. In this study, we examined protein levels in dorsal root ganglia using DIA Mass-spectrometry technologies with NaV1.8Cre+/-; ROSA26-flox-stop-flox-DTA (Diphtheria toxin fragment A) mutant mice (NaV1.8Cre-DTA), in which NaV1.8-expressing neurons (mainly nociceptors) in dorsal root ganglia (DRG) were ablated. The results show that 353 transcripts and 78 proteins, including nociceptor-specific sodium channels NaV1.8 (Scn10a) and NaV1.9 (Scn11a), were specifically expressed in nociceptors of DRG. A comparative analysis revealed that about 40% of nociceptor-specific proteins are shared within the nociceptor-specific transcript dataset. Scatter plots show that the proteome and transcriptome datasets in nociceptors have a moderate correlation (r = 0.4825), indicating the existence of post-transcriptional and post-translational gene regulation in nociceptors. This combined profiling study provides a unique resource for sensory studies, especially for pain research.
FrangiPANe, a tool for creating a panreference using left behind reads
Authors: Christine Tranchant-Dubreuil , Clothilde Chenal , Mathieu Blaison , Laurence Albar , Valentin Klein , Cédric Mariac , Wing Rod A. , Yves Vigouroux , Francois Sabot
Published: July 2022

We present here FrangiPANe, a pipeline developed to build panreference using short reads through a map-then-assemble strategy. Applying it to 248 African rice genomes using an improved CG14 reference genome, we identified an average of 8 Mb of new sequences and 5,290 new contigs per individual. In total, 1.4 G of new sequences, consisting of 1,306,676 contigs, were assembled. We validated 97.7% of the contigs of the TOG5681 cultivar individual assembly from short reads on a newly long reads genome assembly of the same TOG5681 cultivar.

FrangiPANe also allowed the anchoring of 31.5% of the new contigs within the CG14 reference genome, with a 92.5% accuracy at 2kb span. We annotated in addition 3,252 new genes absent from the reference.

FrangiPANe was developed as a modular and interactive application to simplify the construction of a panreference using the map-then-assemble approach. It is available as a Docker image containing (i) a Jupyter notebook centralizing codes, documentation and interactive visualization of results, (ii) python scripts and (iii) all the software and libraries requested for each step of the analysis.

We foreseen our approach will help leverage large-scale illumina dataset for pangenome studies in GWAS or detection of selection.
POLLINATOR GROOMING BEHAVIOR ALTERS POLLEN LANDSCAPES ON BEES’ BODIES AND INCREASES POLLEN CARRYOVER TO OTHER FLOWERS
Authors: Marcelo Vanessa Gonzaga , Darcie Marquitti Flávia Maria , Vallejo-Marín Mario , Brito Vinícius Lourenço Garcia de
Published: July 2022

Pollen participates both as the carrier of male gametes in the reproduction of flowering plants and as a key resource exploited by floral visitors, especially bees. Pollinator behavior significantly alters the patterns of pollen removal and deposition, often called pollen fates. To date, few theoretical investigations have attempted to jointly model patterns of pollen transfer and pollinator behavior, and empirical studies are restricted to species to which pollen movement can be tracked. Here we use a spatially explicit agent-based modeling approach, to determine how bee grooming behavior may alter pollen fates and affect plant reproduction. Specifically, we asked whether pollen mixing and removal during pollen grooming may change the “pollen landscape” on a bee’s body consequently affecting both pollen export by the anthers and deposition onto stigmas. Our model shows that both mixing and removal behaviors restructure the “pollen landscape” on the bee’s body, increasing pollen carryover (deposition in consecutive visits), and increasing pollen diversity (number of pollen donors) onto stigmas in sequential flower visits. Our results counterintuitively show that pollen grooming may have a positive effect on both male and female finesses during plant reproduction.
Conditional degradation of UNC-31/CAPS enables spatiotemporal analysis of neuropeptide function
Authors: Cornell Rebecca , Cao Wei , Liu Jie , Pocock Roger
Published: July 2022

Neuropeptide release from dense-core vesicles in Caenorhabditis elegans is promoted by UNC-31, ortholog of the calcium-dependent activator protein for secretion (CAPS). Loss of UNC-31 causes multiple phenotypes in C. elegans including reduced motility, retention of late-stage eggs and reduction in evoked synaptic release. However, the ability to analyze UNC-31 function over discrete timescales and in specific neurons is lacking. Here, we generated and validated a tool to enable UNC-31 expression and spatiotemporal functional analysis. We show that endogenously tagged UNC-31 is expressed in major ganglia and nerve cords from late-embryonic stages through to adult. Using the auxin-inducible degradation system, we depleted UNC-31 post-embryonically from the nervous system and revealed defects in egg-laying, locomotion and vesicle release that were comparable to unc-31 null mutant animals. In addition, we found that depleting UNC-31 specifically from the BAG sensory neurons causes increased intestinal fat storage, highlighting the spatial sensitivity of this system. Together, this protein degradation tool may be used to facilitate studies of neuropeptide function at precise cellular and temporal scales.

Significance statement

Animal behavior and physiology is controlled by neuropeptides that are released from specific neuronal sources. The ability to dissect discrete neuropeptide functions requires precise manipulation of neuropeptide release. We have developed and validated a tool that enables precise spatiotemporal regulation of neuropeptide release that will enable researchers to examine neuropeptide function at exceptional resolution.
Adrenal sympathetic nerve mediated the anti-inflammatory effect of electroacupuncture at ST25 acupoint on a rat model of sepsis
Authors: Zhang Ziyi , Cui Xiang , Liu Kun , Gao Xinyan , Zhou QingChen , Xi Hanqing , Zhao Yingkun , Zhang Dingdan , Zhu Bing
Published: July 2022

Acupuncture plays a vital anti-inflammatory action on sepsis through activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating sympathoadrenal medullary pathway and evaluate EA’s anti-inflammatory effect on sepsis. To explore the optimum parameter of EA at homosegmental acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley (SD) rats were evaluated byin vivoelectrophysiological recording, and the levels of norepinephrine (NE) and its metabolites were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rat was given intraperitoneal injection lipopolysaccharide to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1β, and IL-10 were evaluated after EA application. We observed that 3 mA is the optimal intensity on activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3 mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1β and upregulated anti-inflammatory cytokine IL-10 compared to the Lipopolysaccharide (LPS)-treated group. Overall, these data suggest that 3 mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect on sepsis.

Highlights

3 mA single shock ES at ST25 drove adrenal sympathetic nerve reflexs.

3 mA EA at ST25 upregulated NE concentration in peripheral blood.

EA at ST25 improved the survival rate in a rat of LPS-induced sepsis model.

EA at the ST25 upregulated anti-inflammatory IL10 and downregulated pro-inflammatory IL1β and IL-6 in LPS-treated rats.
Identification and current palaeobiological understanding of “Keratosa”-type non-spicular demosponge fossils in carbonates: with a new example from the lowermost Triassic, Armenia
Authors: Luo Cui , Pei Yu , Richoz Sylvain , Li Qijian , Reitner Joachim
Published: July 2022

Fossilised fibrous skeletons of non-spicular demosponges have been reported in carbonates throughout the Phanerozoic and recently from rocks dated back to 890 Ma ago. These records expanded our understanding of metazoans in multiple aspects, including their early evolution, the cryptic ecology in fossil reefs, and recovery after mass extinction events. However, debates and confusion persist on the differentiation of these fossils from other biogenic or abiotic structures. Here we propose six identification criteria based on established taphonomical models and biological characteristics of these sponges (“Keratosa”sensuMinchin, 1900). Besides, sponge fossils of this kind from the lowermost Triassic of Chanakhchi (Armenia) are described with a 3-D reconstruction to exemplify the application of these criteria in the recognition of such organisms. Subsequently, the state-of-the-art understanding of the taxonomy and evolution of these fossil sponges, a previously poorly addressed topic, is summarized. The morphology of the Triassic Chanakhchi fossils indicates an affinity with Verongimorphs, a group that may have evolved by the Cambrian Age 3. Other than that, more efforts are still required to explore the taxonomic diversity and evolutionary details in the accumulating data of these fossil non-spicular demosponges.
Bird assemblages in a peri-urban landscape in eastern India
Authors: Karjee Ratnesh , Palei Himanshu Shekhar , Konwar Abhijit , Gogoi Anshuman , Mishra Rabindra Kumar
Published: July 2022

Across the tropics, human settlements and agricultural lands have rapidly replaced the natural habitat; however, our understanding of the biodiversity value in such human-dominated landscapes is limited. To study the effects of heterogeneous habitats on bird diversity in the peri-urban landscape, we surveyed four different habitat types (residential areas, cropland and wasteland, water bodies, and sal forest) from February 2018 to January 2019. During the survey, 117 bird species were recorded belonging to 48 families and 98 genera in the study area. We observed that cropland and wasteland harboured rich avian diversity, among other sites. Both the Non-parametric Multidimensional Scale (NMDS) and one-way ANOVA Significant Test showed significant variations in bird species composition among habitats. Our study could be helpful in future conservation and management of the birds’ diversity to make peri-urban habitats more favorable.
Discovering functionally important sites in proteins
Authors: Cagiada Matteo , Bottaro Sandro , Lindemose Søren , Schenstrøm Signe M. , Stein Amelie , Hartmann-Petersen Rasmus , Lindorff-Larsen Kresten
Published: July 2022

Proteins play important roles in biology, biotechnology and pharmacology, and missense variants are a common cause of disease. Discovering functionally important sites in proteins is a central but difficult problem because of the lack of large, systematic data sets. Sequence conservation can highlight residues that are functionally important but is often convoluted with a signal for preserving structural stability. We here present a machine learning method to predict functional sites by combining statistical models for protein sequences with biophysical models of stability. We train the model using multiplexed experimental data on variant effects and validate it broadly. We show how the model can be used to discover active sites, as well as regulatory and binding sites. We illustrate the utility of the model by prospective prediction and subsequent experimental validation on the functional consequences of missense variants inHPRT1which may cause Lesch-Nyhan syndrome, and pinpoint the molecular mechanisms by which they cause disease.
Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport
Authors: Bojarskaite Laura , Bjørnstad Daniel M. , Vallet Alexandra , Binder Kristin M. Gullestad , Cunen Céline , Heuser Kjell , Kuchta Miroslav , Mardal Kent-Andre , Enger Rune
Published: July 2022

Perivascular spaces (PVS) are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. Using two-photon imaging of naturally sleeping mice we demonstrate sleep cycle-dependent PVS dynamics – slow, large-amplitude oscillations in NREM, a reduction in REM and an enlargement upon awakening at the end of a sleep cycle. By biomechanical modeling we demonstrate that these sleep cycle-dependent PVS dynamics drive fluid flow and solute transport.
EEG frequency tagging evidence of intact social interaction recognition in adults with autism
Authors: Oomen Danna , Cracco Emiel , Brass Marcel , Wiersema Jan R.
Published: July 2022

To explain the social difficulties in autism, a large amount of research has been conducted on the neural correlates of social perception. However, this research has mostly used basic social stimuli (e.g. eyes, faces, hands, single agent), not resembling the complexity of what we encounter in our daily social lives, and as such, the situations people with autism experience difficulties in. A more complex stimulus that we do come across often and is also highly relevant for social functioning is that of third-party social interactions. Here, we investigated if individuals with and without autism process third-party social interactions differently. More specifically, we measured neural responses to social scenes depicting either social interaction or not with an electroencephalogram (EEG) frequency tagging task and compared these responses between adults with and without autism (N = 61). The results revealed an enhanced response to social scenes with interaction, replicating previous findings in a neurotypical sample (Oomen et al., 2022). Crucially, this effect was found in both groups with no difference between them. This suggest that social interaction recognition is not anomalous in adults with autism and cannot explain the social difficulties adults with autism experience.

Lay abstract

People with autism have social difficulties and are thought to experience the world differently. To better understand these differences, research has studied how the brain of people with and without autism processes social stimuli. However, this research has mostly used basic social stimuli (e.g. eyes, faces, hands, and single agents). Such stimuli do not resemble the complexity of daily life, where we typically do not come across isolated body parts, but instead have to make sense of complex social scenes with multiple people. To do so, it is imperative that we are able to recognize social interaction. Hence, if social interaction processing is anomalous, this could have pervasive consequences for social functioning more generally. Here, we used brain imaging to test if adults with autism process social interaction scenes differently than adults without autism. In line with previous findings from a neurotypical sample (Oomen et al. (2022), we found that social scenes depicting interaction elicited stronger brain responses than social scenes not depicting interaction. Crucially, this effect was found in both groups with no difference between them. These findings suggest that the fundamental process of social interaction recognition is not anomalous in adults with autism.
The functional form of value normalization in human reinforcement learning
Authors: Bavard Sophie , Palminteri Stefano
Published: July 2022

Reinforcement learning research in humans and other species indicates that rewards are represented in a context-dependent manner. More specifically, reward representations seem to be normalized as a function of the value of the alternative options. The dominant view postulates that value context-dependence is achieved via a divisive normalization rule, inspired by perceptual decision-making research. However, behavioral and neural evidence points to another plausible mechanism: range normalization. Critically, previous experimental designs were ill-suited to disentangle the divisive and the range normalization accounts, which generate similar behavioral predictions in many circumstances. To address this question, we designed a new learning task where we manipulated, across learning contexts, the number of options and the value ranges. Behavioral and computational analyses falsify the divisive normalization account and rather provide support for the range normalization rule. Together, these results shed new light on the computational mechanisms underlying context-dependence in learning and decision-making.
Emphasis on peripheral vision is accompanied by pupil dilation
Authors: Vilotijević Ana , Mathôt Sebastiaan
Published: July 2022

People are best able to detect stimuli in peripheral vision when their pupils are large, and best able to discriminate stimuli in central vision when their pupils are small. However, it is unclear whether our visual system makes use of this by dilating the pupils when attention is directed towards peripheral vision. Therefore, we tested whether pupil size adapts to the ‘breadth’ of attention. We found that pupils dilate with increasing attentional breadth, both when attention is diffusely spread and when attention is directed at specific locations in peripheral vision. We further found a correlation with performance, suggesting a functional benefit of this effect. Based on our results and others, we propose that cognitively driven pupil dilation is not an epiphenomenal marker of Locus Coeruleus activity, as is often assumed, but rather is an adaptive response that reflects an emphasis on peripheral vision.
The Phylotranscriptomic Hourglass Pattern in Fungi: An Updated Model
Authors: Xie Yichun , Kwan Hoi Shan , Chan Po Lam , Wu Wen Jie , Chiou Jiachi , Chang Jinhui
Published: July 2022

The “developmental hourglass” describes the morphological convergence to a conserved form at mid-stages of animal embryogenesis. The molecular hourglass pattern during embryogenesis was also identified across kingdoms. Previously, we reported young fruiting body as the conserved “waist” in mushroom-forming “developmental hourglass”. However, its robustness is doubted because of the fungal diversity. Additionally, fungi lack embryogenesis, and develop directly from spore to hyphae with morphological similarities during the transition. Here, we updated the “developmental hourglass” model in the life cycle of fungi, namely, spore germination, vegetative growth, and sexual reproduction. Germinating spores, both sexual and asexual, showed the strongest transcriptomic conservation signals across the phyla Mucoromycota, Ascomycota and Basidiomycota. Cross kingdom comparisons revealed high expression levels of “information storage and processing” genes at the waist stages of embryonic and non-embryonic developments in animals, plants, and fungi. The “developmental hourglass” might reflect the mutual transcriptome switches on developmental transitions in eukaryotes that are additional to embryonic organogenesis.

Highlights

Updated fungal molecular “developmental hourglass” model in the life cycle of fungi

Germinating spores are the evolutionarily conserved “waist” across fungal phyla

High expression levels of “information storage and processing” genes at the waist stages in the embryonic and non-embryonic hourglasses across kingdoms

“Developmental hourglass” may reflect the mutual transcriptome switches on developmental transitions in eukaryotes
Individual-level Functional Connectivity Predicts Cognitive Control Efficiency
Authors: Deck Benjamin L. , Kelkar Apoorva , Erickson Brian , Erani Fareshte , McConathey Eric , Sacchetti Daniela , Faseyitan Olu , Hamilton Roy , Medaglia John D.
Published: July 2022

Cognitive control (CC) is a vital component of cognition associated with problem-solving in everyday life. Many neurological and neuropsychiatric conditions have deficits associated with CC. CC is composed of multiple behaviors including switching, inhibiting, and updating. The fronto-parietal control network B (FPCN-B), the dorsal attention network (DAN), the cingulo-opercular network (CON) and the dorsal default-mode network (dorsal-DMN) have been associated with switching and inhibiting behaviors. However, our understanding of how these brain regions interact to bring about CC behaviors is still unclear. In the current study, participants performed two in-scanner tasks that required switching and inhibiting. We then used a series of support vector regression (SVR) models containing individually-estimated functional connectivity between the networks of interest derived during tasks and at rest to predict inhibition and switching behaviors in individual subjects. We observed that the combination of between-network connectivity from these individually estimated functional networks predicted accurate and timely inhibition and switching behaviors in individuals. We also observed that the relationships between canonical task-positive and task-negative networks predicted inhibiting and switching behaviors. Finally, we observed a functional dissociation between the FPCN-A and FPCNB during rest, and task performance predicted inhibiting and switching behaviors. These results suggest that individually estimated networks can predict individual CC behaviors, that between-network functional connectivity estimated within individuals is vital to understanding how CC arises, and that the fractionation of the FPCN and the DMN may be associated with different behaviors than their canonically accepted behaviors.
leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts
Authors: Shin Kwangdeok , Begeman Ian J. , Cao Jingli , Kang Junsu
Published: July 2022

Zebrafish possess a remarkable regenerative capacity, which is mediated by the induction of various genes upon injury. Injury-dependent transcription is governed by the tissue regeneration enhancer elements (TREEs). Here, we utilized leptin b (lepb), an injury-specific factor, and its TREE to dissect heterogeneity of non-cardiomyocytes (CMs) in regenerating zebrafish hearts. Our single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the endothelium/endocardium(EC) is activated to induce distinct subpopulations upon cardiac injury. We demonstrated that lepb can be utilized as a regeneration-specific marker to subset injury-activated ECs. lepb+ ECs robustly induce pro-regenerative factors, implicating lepb+ ECs as a signaling center to interact with other cardiac cells. Our scRNA-seq analysis identified that lepb is also produced by specific subpopulation of epicardium (Epi) and epicardium-derived cells (EPDCs). To determine lepb labels injury-emerging non-CM cells, we tested the activity of lepb-linked regeneration enhancer (LEN) with chromatin accessibility profiles and transgenic lines. While non-detectable in uninjured hearts, LEN directs EC and Epi/EPDC expression upon injury. The endogenous LEN activity was assessed using LEN deletion lines, demonstrating that LEN deletion abolished injury-dependent expression of lepb, but not other nearby genes. Our integrative analyses identify regeneration-emerging cell types and factors, leading to the discovery of regenerative features of hearts.
Improving deep learning-based segmentation of diatoms in gigapixel-sized virtual slides by object-based tile positioning and object integrity constraint
Authors: Kloster Michael , Burfeid-Castellanos Andrea M. , Langenkämper Daniel , Nattkemper Tim W. , Beszteri Bánk
Published: July 2022

Diatoms represent one of the morphologically and taxonomically most diverse groups of microscopic eukaryotes. Light microscopy-based taxonomic identification and enumeration of frustules, the silica shells of these microalgae, is broadly used in aquatic ecology and biomonitoring. One key step in emerging digital variants of such investigations is segmentation, a task that has been addressed before, but usually in manually captured megapixel-sized images of individual diatom cells with a mostly clean background. In this paper, we applied deep learning-based segmentation methods to gigapixel-sized, high-resolution scans of diatom slides with a realistically cluttered background. This setup requires large slide scans to be subdivided into small images (tiles) to apply a segmentation model to them. This subdivision (tiling), when done using a sliding window approach, often leads to cropping relevant objects at the boundaries of individual tiles. We hypothesized that in the case of diatom analysis, reducing the amount of such cropped objects in the training data can improve segmentation performance by allowing for a better discrimination of relevant, intact frustules or valves from small diatom fragments, which are considered irrelevant when counting diatoms. We tested this hypothesis by comparing a standard sliding window / fixed-stride tiling approach with two new approaches we term object-based tile positioning with and without object integrity constraint. With all three tiling approaches, we trained Mask-R-CNN and U-Net models with different amounts of training data and compared their performance. Object-based tiling with object integrity constraint led to an improvement in pixel-based precision by 12–17 percentage points without substantially impairing recall when compared with standard sliding window tiling. We thus propose that training segmentation models with object-based tiling schemes can improve diatom segmentation from large gigapixel-sized images but could potentially also be relevant for other image domains.
Organization and Dynamics of Crosslinked Actin Filaments in Confined Environments
Authors: Akenuwa Oghosa H. , Abel Steven M.
Published: July 2022

The organization of the actin cytoskeleton is impacted by the interplay between physical confinement, features of crosslinking proteins, and deformations of semiflexible actin filaments. Some crosslinking proteins preferentially bind filaments in parallel, while others bind more indiscriminately. However, a quantitative understanding of how the mode of binding influences the assembly of actin networks in confined environments is lacking. Here we employ coarse-grained computer simulations to study the dynamics and organization of semiflexible actin filaments in confined regions upon the addition of crosslinkers. We characterize how the emergent behavior is influenced by the system shape, the number and type of crosslinking proteins, and the length of filaments. Structures include isolated clusters of filaments, highly connected filament bundles, and networks of interconnected bundles and loops. Elongation of one dimension of the system promotes the formation of long bundles that align with the elongated axis. Dynamics are governed by rapid crosslinking into aggregates, followed by a slower change in their shape and connectivity. Crosslinking decreases the average bending energy of short or sparsely connected filaments by suppressing shape fluctuations. However, it increases the average bending energy in highly connected networks because filament bundles become deformed and small numbers of filaments exhibit long-lived, highly unfavorable configurations. Indiscriminate crosslinking promotes the formation of high-energy configurations due to the increased likelihood of unfavorable, difficult-to-relax configurations at early times. Taken together, this work demonstrates physical mechanisms by which crosslinker binding and physical confinement impact the emergent behavior of actin networks, which is relevant both in cells and in synthetic environments.

SIGNIFICANCE

The actin cytoskeleton is vital for intracellular transport, yet it remains challenging to understand how its organization is impacted by the interplay between physical confinement and the crosslinking of semiflexible actin filaments. In this study, we explore how the mode of crosslinker binding and the shape of the confining region impact the assembly and organization of actin filaments. The dynamics are governed by rapid crosslinking of spatially proximal filaments into aggregates, followed by slower relaxation of their shape and connectivity. Indiscriminate crosslinking promotes more highly connected networks, greater curvature of long filament bundles, and a subset of filaments in highly unfavorable configurations. The results provide insight into mechanisms influencing the cytoskeleton in cells and in reconstituted systems.
Changes in adenosine and neurotrophic signaling in the SOD1G93A mouse model of amyotrophic lateral sclerosis: modulation by chronic caffeine intake
Authors: Rei Nádia , Valente Cláudia A. , Vaz Sandra H. , Farinha-Ferreira Miguel , Ribeiro Joaquim A. , Sebastião Ana M.
Published: July 2022

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of corticospinal tract motor neurons. Previous studies showed that adenosine-mediated neuromodulation is disturbed in ALS and that vascular endothelial growth factor (VEGF) has a neuroprotective function in ALS mouse models. We evaluated how adenosine (A1R and A2AR) and VEGF (VEGFA, VEGFB, VEGFR-1 and VEGFR-2) system markers are altered in the cortex and spinal cord of pre-symptomatic and symptomatic SOD1G93A mice. We then assessed if/how chronic treatment of SOD1G93A mice with a widely consumed adenosine receptor antagonist, caffeine, modulates VEGF system and/or the levels of Brain-derived Neurotrophic Factor (BDNF), known to be under control of A2AR. We found out decreases in A1R and increases in A2AR levels even before disease onset. Concerning the VEGF system, we detected increases of VEGFB and VEGFR-2 levels in the spinal cord at pre-symptomatic stage, which reverses at the symptomatic stage, and decreases of VEGFA levels in the cortex, in very late disease states. Chronic treatment with caffeine rescued cortical A1R levels in SOD1G93A mice, bringing them to control levels, while rendering VEGF signaling nearly unaffected. In contrast, BDNF levels were significantly affected in SOD1G93A mice treated with caffeine, being decreased in the cortex and increased in spinal the cord. Altogether, these findings suggest an early dysfunction of the adenosinergic system in ALS and highlights the possibility that the negative influence of caffeine previously reported in ALS animal models results from interference with BDNF rather than with the VEGF signaling molecules.