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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 181 records · Page 10Linked to original sources
bioRxiv2022

Mitochondrial perturbations enhance cell-mediated innate immunity in Drosophila

Withdrawal StatementThe authors have withdrawn version 2 of this manuscript due to the erroneous revision with a related but different manuscript, which can now be found under doi: 10.1101/2024.03.28.587162. Note that version 1 of this preprint is correct and has now been published as doi: 10.1186/s12915-024-01858-5, which should be used for citation purposes. If you have any questions, please contact the corresponding author (Tiina S. Salminen, tiina.s.salminen@tuni.fi).

immunology↗
bioRxiv2022

Depletion of Plasma Membrane PI4P by ORP5 Requires Hydrolysis by SAC1 in Acceptor Membranes

The authors have withdrawn their manuscript because the central conclusion is incorrect. We discovered this while revising the paper after peer review. In the original submission, we described ectopic targeting of the PI4P transfer protein, ORP5. We reported that when combined with orthogonal targeting of SAC1 to the mitochondrial outer membrane, ORP5 facilitates depletion of PM PI4P when targeted to PM-mitochondria contact sites. New experiments revealed that orthogonal targeting of SAC1 to the mitochondria alone is sufficient to deplete PM PI4P; ORP5 is not required. Thus, although the data reported in the manuscript are valid and reproducible, the conclusion was incorrect. We are currently performing additional experiments to better characterize and understand the effects of mitochondrially-targeted SAC1 on PM pools of PI4P. We will post a new manuscript detailing these findings on bioRXiv, which will be submitted for peer review at the original journal as a revision. In the meantime, we are withdrawing the preprint so as not to mislead the field with the erroneous conclusion. We sincerely apologize to anyone whose work was misdirected by our honest mistake. Therefore, the authors do not wish this work to be cited as reference for the project in its present form. If you have any questions, please contact the corresponding author.

cell biology↗
bioRxiv2022

RefDeduR: A text-normalization and decision-tree aided R package enabling accurate and high-throughput reference deduplication for large datasets

As the scientific literature grows exponentially and research becomes increasingly interdisciplinary, accurate and high-throughput reference deduplication is vital in evidence synthesis studies (e.g., systematic reviews, meta-analyses) to ensure the completeness of datasets while reducing the manual screening burden. Existing tools fail to fulfill these emerging needs, as they are often labor-intensive, insufficient in accuracy, and limited to clinical fields. Here, we present RefDeduR, a text-normalization and decision-tree aided R package that enables accurate and high-throughput reference deduplication. We modularize the pipeline into text normalization, three-step exact matching, and two-step fuzzy matching processes. We also introduce a decision-tree algorithm, consider preprints when they co-exist with a peer-reviewed version, and provide actionable recommendations. Therefore, the tool is customizable, accurate, high-throughput, and practical. RefDeduR provides an effective solution to perform reference deduplication and represents a valuable advance in expanding the open-source toolkit to support evidence synthesis research.

scientific communication and education↗
bioRxiv2022

Radical pair based magnetic field effects in cells: the importance of photoexcitation conditions and single cell measurements

A recent publication1 on the bioRxiv preprint server aims to replicate our observation of magnetic field effects on the autofluorescence of HeLa cells2, but is unable to reproduce the effects described in our original work. Here we examine this new study and demonstrate, based on a model of the reaction photocycle, why the differences in the measurement conditions used render the experiment unlikely to be able to observe the originally reported effect. In addition, we highlight substantial problems in the quality of the data in the replicate study and reiterate the advantages of the direct modulation, single cell measurement approach presented in the original work over a more standard statistical approach.

cell biology↗
bioRxiv2022

Ultrastructural characterization of a viral RNA and G-protein containing, membranous organelle formed in respiratory syncytial virus infected cells

Withdrawal statementThe authors have withdrawn their manuscript because since deposition of this preprint, they have become aware of the possibility that the findings reported may be an artefact. Carter et al. (J Struct Biol 2018 Jan;201(1):15-25. doi: 10.1016/j.jsb.2017.10.009) have reported that multilamellar bodies exhibit autofluorescence under cryogenic conditions. Thus, there is a possibility that stress induced by virus infection may stimulate formation of the features reported in this article, and autofluorescence, rather than specific labelling led them to identify the puncta as compartments containing RSV proteins or genomes. They are working to address these issues. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

microbiology↗
bioRxiv2022

Gene complementation analysis suggests that dodder plants (Cuscuta spp.) do not depend on the host FT protein for flowering

Dodder (Cuscuta spp.) is a genus of parasitic plants that form physiological bridges (haustoria) with their hosts to facilitate the transfer of water and nutrients. The parasites also repurpose nucleic acids and proteins translocating through the haustoria, potentially including the host florigen protein (FT), which is postulated to trigger floral transition in the parasite. Here, we identified the endogenous FT-FD flowering module in Cuscuta campestris. We detected the expression of two parasite-encoded C. campestris (Cc)FT genes in haustoria, whereas a newly found CcFD-like gene was expressed ubiquitously. C. campestris flowered while growing on mutant tobacco plants lacking the floral activators NtFT4 and NtFT5, indicating that host FT proteins are not required to initiate the parasites floral transition. We also showed that CcFT1 (identical to CaFT from Cuscuta australis) and CcFT2 can rescue a non-flowering Ntft4-Ntft5- double knockout tobacco phenotype. Together, our results show that Cuscuta spp. produce a potent endogenous florigen as well as other proteins likely to be involved in floral transition. FT gene expression profiles in the haustoria suggest that Cuscuta spp. transition to flowering at least partly in response to host signals (e.g., sugars) that can activate the parasites FT-FD module. Although C. campestris and C. australis appear not to depend on the host FT protein for floral transition, the nature of the mobile host signals that influence floral development in these parasites remain unclear. Significance StatementParasitic higher plants are known for their sophisticated adaptations that facilitate the transfer of water and nutrients from their hosts. They can also synchronize their transition from vegetative to reproductive development to match the host plant. Despite this high degree of synchronization, dodder plants maintain a potent endogenous floral activator module, which enables the parasite to switch to reproductive development autonomously. Synchronization must therefore involve other stimuli from the host plant, which are currently unknown. Understanding the environmental cues that trigger flowering, and the corresponding network of genetic and physiological regulators and integrators, may lead to new strategies that reduce the reproductive fitness of parasitic plants to protect crops and ensure food security. Data ServersThis article is available as preprint (ID: BIORXIV/2022/520981) at https://www.biorxiv.org under the CC BY-NC 4.0 license. Reusable data files have been deposited at https://datadryad.org, accessible during peer-review under: https://datadryad.org/stash/share/DK8Olh2VqFwbGNL0GtkGt24dD0GhWhJn82oLBC1XK70

plant biology↗
bioRxiv2023

Refined novel techniques for long term cryo-storage using vitrification and laser warming

Vitrification and ultra-rapid laser warming technique is an important approach for cryopreservation of animal embryos and oocytes, as well as other cells with medicinal, genetic, and agricultural value. We believe that the long term cryo-storage after vitrification and for the following laser warming has only been achieved to date using our customized device which was first attempted to be developed in our study. In the present study, we focused on developing alignment and bonding techniques for special cryo-jig which were assembling jig tool and jig holder in one piece. This newly produced customized cryo-jig was demonstrated to have significantly high laser striking accuracy of 95% and a successful rewarming rate of 62%. This study was experimentally demonstrate an refined novel device for improvement of laser striking accuracy after long term cryo-storage using vitrification and laser warming technique. In addition, the customized device described herein was successfully applied to a biological sample with over a thousand coral larvae in long term cryo-storage (The first cryo-repository for coral larvae; the results related to coral cryobanking and repositry described in this preprint will be published separately in details). We anticipate that our core findings will provide further examples of cryobanking applications that use vitrification and nano-laser warming to help a wide range of cells and tissues from diverse species.

bioengineering↗
bioRxiv2023

Specificity Guides Interpretation: On H3K4 Methylation at Enhancers and Broad Promoters

In 2018, we used internally calibrated chromatin immunoprecipitation (ICeChIP) to find that many of the most commonly used antibodies against H3K4 methylforms had significant off-target binding, which compromised the findings of at least eight literature paradigms that used these antibodies for ChIP-seq (Shah et al., 2018). In many cases, we were able to recapitulate the prior findings in K562 cells with the original, low-quality antibody, only to find that the models did not hold up to scrutiny with highly specific reagents and quantitative calibration. In a recent preprint originally prepared as a Letter to the Editor of Molecular Cell, though they agree with our overarching conclusions, Pekowska and colleagues take issue with analyses presented for two relatively minor points of the paper (Pekowska et al., 2023). We are puzzled by the assertion that these two points constitute the "bulk" of our findings, nor is it clear which components of our "analytical design" they find problematic. We feel their critique, however mild, is misguided.

molecular biology↗
bioRxiv2023

Enhanced transmissibility, infectivity and immune resistance of the SARS-CoV-2 Omicron XBB.1.5 variant

In 2022, we have elucidated the characteristics of a variety of newly emerging SARS-CoV-2 Omicron subvariants. At the end of 2022, the XBB.1.5 variant, an descendant of XBB.1 that acquired the S:F486P substitution, emerged and is rapidly spreading in the USA and is the latest variant of concern. Although the features of XBB.1.5 was already reported by another group as a preprint, we think multiple and independent evaluations important, and these reports are crucial for sustained global health. In this study, our epidemic dynamics analysis revealed that the relative effective reproduction number (Re) of XBB.1.5 is more than 1.2-fold greater than that of the parental XBB.1, and XBB.1.5 is outcompeting BQ.1.1, the predominant lineage in the USA as of December 2022. Our data suggest that XBB.1.5 will rapidly spread worldwide in the near future. Yeast surface display assay and pseudovirus assay respectively showed that the ACE2 binding affinity and infectivity of XBB.1.5 is 4.3-fold and 3.3-fold higher than those of XBB.1, respectively. Moreover, neutralization assay revealed that XBB.1.5 is robustly resistant to BA.2 breakthrough infection sera (41-fold versus B.1.1, 20-fold versus BA.2) and BA.5 breakthrough infection sera (32-fold versus B.1.1, 9.5-fold versus BA.5), respectively. Because the immune resistance of XBB.1.5 is comparable to that of XBB.1, our results suggest that XBB.1.5 is the most successful XBB lineage as of January 2023 by acquiring the S:F486P substitution to augment ACE2 binding affinity without losing remarkable immune resistance, which leads to greater transmissibility.

microbiology↗
bioRxiv2023

Genetics of continuous colour variation in a pair of sympatric sulphur butterflies

Continuous colour polymorphisms can serve as a tractable model for the genetic and developmental architecture of traits, but identification of the causative genetic loci is complex due to the number of individuals needed, and the challenges of scoring continuously varying traits. Here we investigated continuous colour variation in Colias eurytheme and C. philodice, two sister species of sulphur butterflies that hybridise in sympatry. Using Quantitative Trait Locus (QTL) analysis of 483 individuals from interspecific crosses and an high-throughput method of colour quantification, we found that two interacting large effect loci explain around 70% of the heritable variation in orange-to-yellow chromaticity. Knockouts of red Malphighian tubules (red), a candidate gene at the primary QTL likely involved in endosomal maturation, resulted in depigmented wing scales showing disorganised pterin granules. The Z sex chromosome contains a large secondary colour QTL that includes the transcription factor bric-a-brac (bab), which we show can act as a modulator of orange pigmentation in addition to its previously-described role in specifying UV-iridescence. We also describe the QTL architecture of other continuously varying traits, and that wing size maps to the Z chromosome, supporting a Large-X effect model where the genetic control of species-defining traits is enriched on sex chromosomes. This study sheds light on the genetic architecture of a continuously varying trait, and illustrates the power of using automated measurement to score phenotypes that are not always conspicuous to the human eye. ForewordThe colour phenotypes in this article involve nuanced gradations of yellow and orange that may be difficult to perceive for people who are colour vision deficient. Hue-shifted versions of all main figures are accessible online for dichromat readers (BioRxiv preprint: Supplementary Material).

genetics↗
bioRxiv2023

The influence of the bullseye versus standard fixation cross on eye movements and classifying natural images from EEG

Withdrawn StatementThe authors have withdrawn this manuscript because we detected fundamental errors in the formula we used to convert eye tracking data (x and y coordinates) from pixels to degrees. After addressing these errors, the results changed considerably. On the one hand, the behavioral results point towards differences for the bullseye versus the standard fixation cross different and larger than originally reported. However, the eyetracking decoding difference between standard and bullseye fixation cross is no longer significant. Therefore, the main claim of the paper - that bullseye fixation cross leads to lower eye movements compared to standard fixation cross, in turn resulting in lower decoding performance of object identity for eyetracking and EEG data - no longer stands. Given this change in the main results, we therefore withdraw the preprint.. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗
bioRxiv2023

A reproducible benchmark of resting-state fMRI denoising strategies using fMRIPrep and Nilearn

Reducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or implementations change. In this work, we present a denoising benchmark featuring a range of denoising strategies, datasets and evaluation metrics for connectivity analyses, based on the popular fMRIprep software. The benchmark is implemented in a fully reproducible framework, where the provided research objects enable readers to reproduce or modify core computations, as well as the figures of the article using the Jupyter Book project and the Neurolibre reproducible preprint server (https://neurolibre.org/). We demonstrate how such a reproducible benchmark can be used for continuous evaluation of research software, by comparing two versions of the fMRIprep software package. The majority of benchmark results were consistent with prior literature. Scrubbing, a technique which excludes time points with excessive motion, combined with global signal regression, is generally effective at noise removal. Scrubbing however disrupts the continuous sampling of brain images and is incompatible with some statistical analyses, e.g. auto-regressive modeling. In this case, a simple strategy using motion parameters, average activity in select brain compartments, and global signal regression should be preferred. Importantly, we found that certain denoising strategies behave inconsistently across datasets and/or versions of fMRIPrep, or had a different behavior than in previously published benchmarks. This work will hopefully provide useful guidelines for the fMRIprep users community, and highlight the importance of continuous evaluation of research methods. Our reproducible benchmark infrastructure will facilitate such continuous evaluation in the future, and may also be applied broadly to different tools or even research fields.

neuroscience↗
bioRxiv2023

Social aging trajectories are sex-specific, sensitive to adolescent stress, and most robustly revealed during social tests with familiar stimuli

Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important during aging. However, social behavior and social cognition decline naturally during aging across species. Social behaviors are in part supported by the reward circuitry, a network of brain regions that develops during adolescence. We published that male and female rats undergo adolescent social development during sex-specific periods, pre-early adolescence in females and early-mid adolescence males. Although males and females have highly dimorphic development, expression, and valuation of social behaviors, there is relatively little data indicating whether social aging is the same or different between the sexes. Thus, we sought to test two hypotheses: (1) natural social aging will be sex-speciifc, and (2) social isolation stress restricted to sex-specific adolescent critical periods for social development would impact social aging in sex-specific ways. To do this, we bred male and female rats in-house, and divided them randomly to receive either social isolation for one week during each sexs respective critical period, or no manipulation. We followed their social aging trajectory with a battery of five tests at 3, 7, and 11 months of age. We observed clear social aging signatures in all tests administered, but sex differences in natural social aging were most robustly observed when a familiar social stimulus was included in the test. We also observed that adolescent isolation did impact social behavior, in both age-independent and age-dependent ways, that were entirely sex-specific. Please note, this preprint will not be pushed further to publication (by me, AMK), as I am leaving academia. So, its going to be written more conversationally.

neuroscience↗
bioRxiv2023

Microglia-mediated synaptic pruning in the nucleus accumbens during adolescence: A preliminary study of the proteomic consequences and putative female-specific pruning target

Adolescence is a period of copious neural development, particularly in the reward circuitry of the brain, and reward-related behavioral development, including social development. One neurodevelopmental mechanism that appears to be common across brain regions and developmental periods is the requirement for synaptic pruning to produce mature neural communication and circuits. We published that microglia-C3-mediated synaptic pruning also occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. However, both the adolescent stage in which microglial pruning occurred, and the synaptic pruning target, were sex specific. NAc pruning occurred between early and mid-adolescence in male rats to eliminate dopamine D1 receptors (D1rs), and between pre- and early adolescence in female rats (P20-30) to eliminate an unknown, non-D1r target. In this report, we sought to better understand the proteomic consequences of microglial pruning in the NAc, and what the female pruning target might be. To do this, we inhibited microglial pruning in the NAc during each sexs pruning period and collected tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the proteomic consequences of inhibiting microglial pruning in the NAc were inversely proportional between the sexes, and a novel, female-specific pruning target may be Lynx1. Please note, if this preprint will be pushed further to publication it will not be by me (AMK), as I am leaving academia. So, Im going to write more conversationally.

neuroscience↗
bioRxiv2023

Microglial synaptic pruning in the nucleus accumbens during adolescence sex-specifically influences splenic immune outcomes

Strong social support promotes a variety of positive health outcomes in humans and rodent models, while social isolation in rodents shortens lifespan, perceived social isolation (i.e. loneliness) can increase mortality by up to 50% in humans. How social relationships lead to these drastic health effects is unclear, but may involve modulation of the peripheral immune system. The reward circuitry of the brain and social behaviors undergo a critical period of development during adolescence. We published that microglia-mediated synaptic pruning occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. We hypothesized that if reward circuitry activity and social relationships directly impact the peripheral immune system, then natural developmental changes in the reward circuitry and social behaviors during adolescence should also directly impact the peripheral immune system. To test this, we inhibited microglial pruning in the NAc during adolescence, and then collected spleen tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the global proteomic consequences of inhibiting microglial pruning in the NAc were similar between the sexes, but target-specific examination suggests that NAc pruning impacts Th1 cell-related immune markers in the spleen in males, but not females, and broad neurochemical systems in the spleen in females, but not males. Please note, if this preprint will be pushed further to publication it will not be by me (AMK), as I am leaving academia. So, Im going to write more conversationally.

neuroscience↗
bioRxiv2023

Direct prediction of intrinsically disordered protein conformational properties from sequence

Intrinsically disordered regions (IDRs) are ubiquitous across all domains of life and play a range of functional roles. While folded domains are generally well-described by a single 3D structure, IDRs exist in a collection of interconverting states known as an ensemble. This structural heterogeneity means IDRs are largely absent from the PDB, contributing to a lack of computational approaches to predict ensemble conformational properties from sequence. Here we combine rational sequence design, large-scale molecular simulations, and deep learning to develop ALBATROSS, a deep learning model for predicting IDR ensemble dimensions from sequence. ALBATROSS enables the instantaneous prediction of ensemble average properties at proteome-wide scale. ALBATROSS is lightweight, easy-to-use, and accessible as both a locally installable software package and a point-and-click style interface in the cloud. We first demonstrate the applicability of our predictors by examining the generalizability of sequence-ensemble relationships in IDRs. Then, we leverage the high-throughput nature of ALBATROSS to characterize emergent biophysical behavior of IDRs within and between proteomes. Update from previous versionO_LIThis preprint reports an updated version of the ALBATROSS network weights trained on simulations of over 42,000 sequences. C_LIO_LIIn addition, we provide new colab notebooks that enable proteome-wide IDR prediction and annotation in minutes. C_LIO_LIAll conclusions and observations made in versions 1 and 2 of this manuscript remain true and robust. C_LI

biophysics↗