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Electrophysiological recordings showing allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains with specific sybodies
<p>Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat (LRR) domains. Despite their known molecular architecture, the mechanism of activation and the role of the LRR domains in this process has remained elusive. Here we have addressed this question by generating synthetic nanobodies, termed sybodies, which target the LRR domain of the obligatory subunit LRRC8A.We used these binders to investigate their interaction with homomeric LRRC8A channels by cryo-electron microscopy and the consequent effect on channel activation by electrophysiology. The five identified sybodies either inhibit or enhance activity by binding to distinct epitopes of the LRR domain, thereby altering channel conformations. In combination, our work provides a set of specific modulators of LRRC8 proteins and reveals the role of their cytoplasmic domains as regulators of channel activity by allosteric mechanisms.</p>
Comparison to results reported in prior work [14] which solves PVC for specific k
<p>Comparison to results reported in prior work [14] which solves PVC for specific k</p>
External RNA-seq dataset for manuscript entitled "Downregulated dual-specificity protein phosphatase 1 in ovarian carcinoma: a comprehensive study with multiple methods"
<p>RNA-seq dataset of ovarian cancer from TCGA and normal ovary from GTEx database</p>
External microarray datasets for manuscript entitled "Downregulated dual-specificity protein phosphatase 1 in ovarian carcinoma: a comprehensive study with multiple methods"
<p>Microarrays related to ovarian carcinoma from GEO database</p>
Data from: Inter-specific variation in the potential for upland rush management advocated by agri-environment schemes to increase breeding wader densities
<p>Encroachment of rush Juncus spp. in the United Kingdom uplands poses a threat to declining wader populations due to taller, denser swards that can limit foraging and breeding habitat quality for some species. Rush management via cutting, implemented through agri-environment schemes (AESs), could thus increase wader abundance, but there is insufficient assessment and understanding of how rush management influences upland waders. Across two upland regions of England [South West Peak (SWP) and Geltsdale nature reserve, Cumbria], we surveyed waders over four visits in fields where rush was managed according to AES prescriptions (treatment; n = 21) and fields without rush management that were otherwise ecologically similar (control; n = 22) to assess how the densities of breeding wader pairs respond to rush management in the short-term. We find evidence for regional variation in the response of waders to rush management, with densities of Common Snipe Gallinago gallinago significantly higher in treatment than control fields in the SWP, but not Geltsdale. There were no statistically significant responses to treatment on densities of Eurasian Curlew Numenius arquata or Northern Lapwing Vanellus vanellus. The 95% confidence intervals for the treatment parameter estimates suggest that this may be due to limited statistical power in the case of Lapwing. For Curlew, however, any potential increases in densities are negligible. There was no evidence that variation in rush cover, which ranged from 10 to 70%, influenced densities of any of our three focal species. Our results suggest that rush management through AES prescriptions delivered in isolation of other interventions may not lead to general increases in breeding wader densities in the short-term, but benefits may arise in some situations due to regional and inter-specific variation in effectiveness. Rush management supported with interventions that improve soil conditions and thus food availability, or reduce predation pressure, may enable AES rush management to generate benefits. Additional research is required to maximise the potential benefits of rush management for each species through the development of prescriptions that tailor to individual species' optimum sward structure.</p>
Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation
<p><i>Pogona vitticeps</i> has female heterogamety (ZZ/ZW) but the master sex determining gene is unknown, as is the case for all reptiles. We show that <i>nr5a1</i>, a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-<i>nr5a1</i> and W-<i>nr5a1</i>), which are both expressed and can recombine. Three transcript isoforms of Z-<i>nr5a1</i> were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced sixteen isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-<i>nr5a1</i>) is likely to produce truncated polypeptides that could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosomes affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the GSD system of <i>P. vitticeps</i> is a W-borne dominant female-determiner that may be controlled epigenetically.</p>
Raw data of body-specific attention to the hands and feet in healthy adults
<p>To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective. The study included two groups of 27 right-handed and right-footed healthy adults, respectively. Visual detection tasks were used to measure body-specific attention. We measured reaction times to visual stimuli on or off the self-body and calculated the index of body-specific attention score to subtract the reaction time on self-body from that off one. Participants were classified into low and high attention groups based on each left and right body-specific attention index. For motor functions, Experiment 1 comprised handgrip strength and ball-rotation tasks for the hands, and Experiment 2 comprised toe grip strength involved in postural control for the feet. For sensory functions, the tactile thresholds of the hands and feet were measured. The results showed that, in both hands, the reaction time to visual stimuli on the hand was significantly lesser than that offhand. In the foot, this facilitation effect was observed in the right foot but not the left, which showed the correlation between body-specific attention and the normalized toe gripping force, suggesting that body-specific attention affected postural control. In the hand, the number of rotations of the ball was higher in the high than in the low attention group, regardless of the elaboration exercise difficulty or the left or right hand. However, this relation was not observed in the handgripping task. Thus, body-specific attention to the hand is an important component of elaborate movements. The tactile threshold was higher in the high than in the low attention group, regardless of the side in hand and foot. The results suggested that more body-specific attention is directed to the limbs with lower tactile abilities, supporting the sensory information reaching the brain. Therefore, we suggested that body-specific attention regulates the sensory information to help motor control.</p>
Predicting atrial fibrillation recurrence by combining population data and virtual cohorts of patient-specific left atrial models
<p><strong>Abstract</strong></p> <p><strong>Background: </strong>Current ablation therapy for atrial fibrillation is sub-optimal and long-term response is challenging to predict. Clinical trials identify bedside properties that provide only modest prediction of long-term response in populations, while patient-specific models in small cohorts primarily explain acute response to ablation. We aimed to predict long-term atrial fibrillation recurrence after ablation in large cohorts, by using machine learning to complement biophysical simulations by encoding more inter-individual variability.</p> <p><strong>Methods: </strong>Patient-specific models were constructed for 100 atrial fibrillation patients (43 paroxysmal, 41 persistent, 16 long-standing persistent), undergoing first ablation. Patients were followed for 1-year using ambulatory ECG monitoring. Each patient-specific biophysical model combined differing fibrosis patterns, fibre orientation maps, electrical properties and ablation patterns to capture uncertainty in atrial properties and to test the ability of the tissue to sustain fibrillation. These simulation stress tests of different model variants were post-processed to calculate atrial fibrillation simulation metrics. Machine learning classifiers were trained to predict atrial fibrillation recurrence using features from the patient history, imaging and atrial fibrillation simulation metrics.</p> <p><strong>Results: </strong>We performed 1100 atrial fibrillation ablation simulations across 100 patient-specific models. Models based on simulation stress tests alone showed a maximum accuracy of 0.63 for predicting long-term fibrillation recurrence. Classifiers trained to history, imaging and simulation stress tests (average ten-fold cross-validation area under the curve 0.85 ± 0.09, recall 0.80 ± 0.13, precision 0.74 ± 0.13) outperformed those trained to history and imaging (area under the curve 0.66 ± 0.17), or history alone (area under the curve 0.61 ± 0.14). </p> <p><strong>Conclusion: </strong>A novel computational pipeline accurately predicted long-term atrial fibrillation recurrence in individual patients by combining outcome data with patient-specific acute simulation response. This technique could help to personalise selection for atrial fibrillation ablation.</p> <p><strong>Dataset Description: </strong>We include surface meshes in vtk format, consisting of the nodes, triangular elements, the atrial coordinate fields defined on the nodes, and the endocardial and epicardial fibre fields defined on the elements. </p> <p>We also include universal atrial coordinate fields alpha and beta, which are a lateral-septal coordinate and posterior-anterior coordinate for the LA. More details on the coordinate construction are given in our manuscript and <a href="https://www.ncbi.nlm.nih.gov/pubmed/31026761">https://www.ncbi.nlm.nih.gov/pubmed/31026761</a>. These coordinates can be used for registering datasets. </p> <p><strong>Publication</strong>: https://pubmed.ncbi.nlm.nih.gov/35089057/</p>
Epitope-specific anti-C1Q autoantibodies in systemic Lupus Erythematosus
<p><strong>Objective</strong></p> <p>In patients with <span>systemic lupus erythematosus</span> (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.</p> <p><strong>Methods</strong></p> <p class="MsoNoSpacing">First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.</p> <p><strong>Results</strong></p> <p>The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.</p> <p><strong>Conclusion</strong></p> <p>In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.</p>
The contribution of extra-pair paternity to the variation in lifetime and age-specific male reproductive success in a socially monogamous species
<p>In socially monogamous species, extra-pair paternity (EPP) is predicted to increase variance in male reproductive success beyond that resulting from genetic monogamy, thus increasing the 'opportunity for selection' (maximum strength of selection that can act on a trait). This prediction is challenging to investigate in wild populations because lifetime reproduction data are often incomplete. Moreover, age-specific variances in reproductive success have been rarely quantified. We analysed 21 years of near-complete social and genetic reproduction data from an insular population of Seychelles warblers (<em>Acrocephalus sechellensis</em>). We quantified the contribution of EPP to lifetime and age-specific opportunities for selection in males. We also compared the variance in male genetic reproductive success (RS) vs. social ('apparent') reproductive success (RSap) to assess if EPP increased the opportunity for selection over that resulting from genetic monogamy. EPP contributed substantially to the variance in lifetime RS, despite not causing a statistically significant excess of this over the variance in lifetime RSap. Partitioning the opportunity for selection into age-specific (co)variance components, showed that EPP provided a substantial contribution at most ages, varying with age. Therefore, in Seychelles warblers EPP likely provides an age-dependent contribution to the opportunity for selection, which can influence evolutionary processes in age-structured populations.</p>
Specific mutations in the cholesterol-binding site of APP alter its processing and favor the production of shorter, less toxic Aβ peptides.
<p>Mass Spectrometry data of Abeta secreted peptides from HEK293 stable clones expressing APP or APPK28A treated or not with methylbetacyclodextrin-cholesterol.</p>
Data for Olive et al., Removal of waterborne viruses by Tetrahymena pyriformis is virus-specific and coincides with changes in protist swimming speed, Environmental Science and Technology, 2022 (https://doi.org/10.1021/acs.est.1c05518)
<p>This entry contains the data shown in: Olive et al., <em>Removal of waterborne viruses by Tetrahymena pyriformis is virus-specific and coincides with changes in protist swimming speed,</em> Environmental Science and Technology, 2022 (https://doi.org/10.1021/acs.est.1c05518)</p> <p>Net removal values (log10 C/C0 or log10 N/N0) shown in Figures 1 and 4</p> <p>Raw data used to calculate net removal values in Figure 1</p> <p>Raw removal values shown in Figure 2</p> <p>Raw data for protist movement analysis shown in Figure 3</p> <p>R code used for protist movement analysis (as text file)</p> <p>Raw data for all Supporting Figures (S1-S6)</p>
Data related to the manuscript "Sequence-specific aggregation of magnetic nanoparticles and single-stranded DNA amplification products for detection of antibiotic resistance gene sul1."
<p>Absorbance and AC susceptometry raw and processed excel files used.</p>
Age-specific habitat preference, carrying capacity, and landscape structure determine the response of population spatial variability to fishing-driven age truncation
<p>1. Understanding the mechanisms underlying spatial variability of exploited fish is critical for the sustainable management of fish stocks. Empirical studies suggest that size-selective fishing can elevate fish population spatial variability (i.e., more heterogeneous distribution) through age truncation, making the population less resilient to changing environment. However, species differ in how their spatial variability respond to age truncation and the underlying mechanisms remain unclear.</p> <p>2. We hypothesize that age-specific habitat preference, together with environmental carrying capacity and landscape structure, determines the response of population spatial variability to fishing-induced age truncation. To test these hypotheses, we design an individual-based model of an age-structured fish population on a two-dimensional landscape under size-selective fishing. Individual fish reproduces and survives, and moves between habitats according to age-specific habitat preference and density-dependent habitat selection.</p> <p>3. Population spatial variability elevates with increasing age truncation and the response is stronger for populations with stronger age-specific habitat preference. On a gradient landscape, reducing carrying capacity elevates the relative importance of density-dependence in habitat selection, which weakens the response of spatial variability to age truncation for populations with strong age-specific habitat preference. On a fragmented landscape, both populations with strong and weak age-specific habitat preferences are restricted at local optimal habitats, and reducing carrying capacity weakens the responses of spatial variability to age truncation for both populations.</p> <p>4. Synthesis and applications. We demonstrate that to track and predict the changes in population spatial variability under exploitation, it is essential to consider the interactive effects of age-specific habitat preference, carrying capacity, and landscape structure. To improve spatial management in fisheries, it is crucial to enhance empirical and theoretical developments in the methodology to quantify age-specific habitat preference of marine fish, and to understand how climatic change influences carrying capacity and landscape continuity.</p>
Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT
<p>Underlying data of the<em> in silico</em> work performed in this study. </p> <p>1. i-Tasser predictions for HTTExon1Q<sub>48 </sub></p> <p>2. HDOCK results of DNAJB1-HTTExon1Q<sub>48 </sub>docking</p> <p>3. TIGER2h structures and trajectories. The original data and filtered trajectories for the individual clusters</p> <p>4. MD Simulation structures and trajectories for DNAJB1 protein variants alone and as complexes with HTTExon1Q<sub>48.</sub></p>
Fig. 1 in Patterns of tooth crown wear in Dryomys nitedula (Mammalia, Rodentia): age-related variation in the light of annual cycle specifics based on museum collections
Fig. 1. Geographic details of the studied sample: record localities and the southern boundary of the forest dormouse's distribution.
Fig. 1 in The Role Of Different Mollusk Species In Maintaining The Transmission Of Polyhostal Trematode Species In Ukrainian Polissya Waters: The Specificity Of Trematode Parthenogenetic Generations To Mollusk Hosts
Fig. 1. The distribution of polyxenic trematode species in the parthenitae host species of mollusks: A — O. ranae; B — P. elegans.
Strong migratory connectivity indicates Willets need subspecies-specific conservation strategies
<p>By combining all available banding and tracking data, we found that Willets (<em>Tringa semipalmata</em>) have strong migratory connectivity between breeding and nonbreeding locations at the range-wide and subspecies levels, exposing the two subspecies to varying threats such as hunting for the eastern subspecies (<em>T. s. semipalmata</em>) and climatically-altered coastal habitats for both subspecies. We found that Western Willets (<em>T. s. inornata</em>) primarily used nonbreeding habitats along the Pacific Coast of the United States, although their reported nonbreeding range extends to the U.S. Atlantic and Gulf Coasts and the Pacific Coast of Central and South America. Eastern Willets wintered in Central and South America, which covers much of the subspecies' known nonbreeding range. By quantifying migratory connectivity within and between two subspecies, we could suggest subspecies-specific threats and potential limiting factors in the breeding and nonbreeding periods of the annual cycle of a declining migratory shorebird. Effective management of the species will likely require a range of conservation strategies across the diverse nonbreeding regions the two subspecies occupy within the United States, Central America, and South America. However, more data are needed from Willets breeding in mid-continent North America to understand the complete extent of overlap of the two subspecies throughout the annual cycle. The strong migratory connectivity documented here highlights the need to manage Willets by subspecies and protect a diversity of breeding and nonbreeding habitats, which will benefit the conservation of other shorebird species that overlap with Willets throughout the annual cycle.</p>
Genome size drives morphological evolution in organ-specific ways
<p class="MsoNormal">Morphogenesis is an emergent property of biochemical and cellular interactions during development. Genome size and the correlated trait of cell size can influence these interactions through effects on developmental rate and tissue geometry, ultimately driving the evolution of morphology. We tested whether variation in genome and body size is related to morphological variation in the heart and liver using nine species of the salamander genus <em>Plethodon</em> (genome sizes 29–67 gigabases). Our results show that overall organ size is a function of body size, whereas tissue structure changes dramatically with evolutionary increases in genome size. In the heart, increased genome size is correlated with a reduction of myocardia in the ventricle, yielding proportionally less force–producing mass and greater intertrabecular space. In the liver, increased genome size is correlated with fewer and larger vascular structures, positioning hepatocytes farther from the circulatory vessels that transport key metabolites. Although these structural changes should have obvious impacts on organ function, their effects on organismal performance and fitness may be negligible because low metabolic rates in salamanders relax selective pressure on function of key metabolic organs. Overall, this study suggests large genome and cell size influence the developmental systems involved in heart and liver morphogenesis.</p>
Coronin1C is a GDP-specific Rab44 effector that controls oste-oclast formation by regulating cell motility in macrophages
<p>This is a video file.</p>
ScienceDex guides
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.