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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 217 records · Page 12Linked to original sources
bioRxiv2024

Why models underestimate tropical forest productivity: a case study in West Africa

Tropical forests dominate terrestrial photosynthesis, yet there are major contradictions in our understanding due to a lack of field studies, especially outside the tropical Americas. A recent field study indicated that West African forests have among the highest forests gross primary productivity (GPP) yet observed, contradicting models that rank them lower than Amazonian forests. Here, we explore possible reasons for this data-model mismatch. We found the in situ GPP measurements higher than multiple global GPP products at the studied sites in Ghana. The underestimation of GPP by models largely disappears when a standard photosynthesis model is informed by local field-measured values of (a) fractional absorbed photosynthetic radiation (fAPAR), and (b) photosynthetic traits. Satellites systematically underestimate fAPAR in the tropics due to cloud contamination issues. The study highlights the potential widespread underestimation of tropical forests GPP and carbon cycling and hints at the ways forward for model and input data improvement. Related manuscriptThe recent field study mentioned above is a manuscript currently accepted by Nature Communications (manuscript id NCOMMS-23-37419), which is available as a preprint https://www.researchsquare.com/article/rs-3136892/v1 Codes and data availabilityAll data and codes underlying the study are currently shared via Github (link here) which will be made available through Zenodo upon acceptance.

ecology↗
bioRxiv2024

BZR1 promotes pluripotency acquisition and callus development through direct regulation of ARF7 and ARF19

Plants have the remarkable ability to regenerate whole organisms through formation of pluripotent cell masses from somatic cells. Cellular programs leading to fate change of somatic to pluripotent cells resembles lateral root (LR) formation and both are chiefly regulated by auxin. Brassinosteroid signalling also plays an important role during LR formation but little is known about the direct link between auxin and brassinosteroid components, such as BZR1 and BES1, in relation to pluripotency acquisition. Here we show that gain-of-function mutants bzr1-D and bes1-D exhibit altered callus formation, yet disruption of these transcription factors does not produce major changes to callus formation or de novo organogenesis. Moreover, our data reveals that BZR1 displays enhanced expression in callus tissue and directly binds to the promoters of ARF7 and ARF19, two master pluripotency regulators, leading to their enhanced transcription. Remarkably, we see abrogation of callus formation in bzr1-D upon disruption of ARF7 and ARF19, emphasizing that BZR1 callus phenotype is dependent on these two auxin signalling components. In conclusion, we depict a link between ARF7, ARF19 and BZR1 in the promotion of pluripotency acquisition, portraying BZR1 as a major supporting factor in callus formation. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

plant biology↗
bioRxiv2024

Shewanella is a putative producer of polyunsaturated fatty acids in the gut soil of the composting earthworm Eisenia fetida

Withdrawal StatementThe authors have withdrawn this manuscript owing to a duplicate posting of manuscript number BIORXIV/2024/587473. 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. The correct preprint can be found at doi.org/10.1101/2024.03.31.587473.

microbiology↗
bioRxiv2024

Immune regulators EDS1 and PAD4 constrain ADR1-dependent disease resistance in rice

Withdrawal StatementThe authors have withdrawn this manuscript owing to finding inconsistencies in genotyping of kitaake rice eds1 pad4 double mutant lines and to establishing that combined loss of EDS1 and PAD4 does not underlie the stunted autoimmune-like phenotype reported in this 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 authors: Jane Parker, Thomas Kroj and Haitao Cui (co-corresponding)

plant biology↗
bioRxiv2024

Roles of the 5-HT1A receptor in zebrafish responses to potential threat and in sociality

Anxiety is a normal emotion representing a reaction to potential danger, whereas fear can be defined as a reaction to real, explicit danger. Anxiety-like behavior in animal models has been associated with differences in the serotonergic system. Treatment of zebrafish cohorts with 8-OH-DPAT, a full agonist at the 5-HT1A receptor, decreased anxiety-like behavior in the novel tank test, but increased it in the phototaxis (light-dark preference) assay, both considered assays for anxiety-like behavior for this species. The same treatment decreased social approach in both the social investigation and social novelty phases of the social preference test. Blocking the 5-HT1A receptor with WAY 100,635 shifted the dose-response curve for the novel tank test rightward. These effects suggest a participation of the 5-HT 1A heteroreceptors in zebrafish anxiety and social preference, increasing anxiety and decreasing sociality. Thus, the study of this receptor is important for a better understanding of anxiety-like behavior in zebrafish and its relationship with similar phenomena in vertebrates. Preprint: https://www.biorxiv.org/content/10.1101/2024.04.17.588464v1 Data: https://github.com/lanec-unifesspa/5HT/tree/main/5HT1A Lay summaryThis study looked at how a certain type of protein, the 5-HT1A receptor, affected anxiety in zebrafish. Its important to understand that anxiety is a normal feeling we all get when were worried or scared about something, while fear is a reaction to an immediate danger. The researchers wanted to see how a specific drug that activates the 5-HT1A receptor, 8-OH-DPAT, affected the behavior of the fish. They used different tests to see how the fish reacted in different situations. When the fish were given the drug, their anxiety-like behavior decreased in one test where they were put in a new tank. But in another test where they had to choose between light and dark areas, their anxiety-like behavior actually increased. It also made the fish less interested in being social with other fish. When a drug that blocks the 5-HT1A receptor, WAY 100,635, was give together with 8-OH-DPAT, evidence was found for a receptor reserve. The researchers found that this drug affected the way the fish behaved in these situations. It seemed to make them more anxious in some cases and less interested in being social. This tells us that the receptor has an impact on how the fish are feeling, which can help us learn more about anxiety in zebrafish and, potentially, in other animals too, including humans. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/588464v3_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@14b3f13org.highwire.dtl.DTLVardef@11a2217org.highwire.dtl.DTLVardef@b42602org.highwire.dtl.DTLVardef@12b51c4_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance statementThis research indicates that 5-HT1A heteroreceptors play a key role in increasing anxiety and decreasing sociality across vertebrates, shedding light on neural mechanisms that could inform treatments for anxiety-related disorders.

neuroscience↗
bioRxiv2024

The Unexpected Membrane Targeting of Marchantia Short PIN Auxin Exporters Illuminates Sequence Determinants and Evolutionary Significance

The plant hormone auxin and its directional transport are crucial for growth and development. PIN auxin transporters, on account of their polarized distribution, are instrumental in guiding auxin flow across tissues. Based on protein length and subcellular localization, the PIN family is classified into two groups: plasma membrane (PM)-localized long PINs and endoplasmic reticulum (ER)-localized short PINs. The origin of PINs was traced to the alga Klebsormidium, with a single PM-localized long KfPIN. Bryophytes, the earliest land plant clade, represent the initial clade harboring the short PINs. We tracked the evolutionary trajectory of the short PINs and explored their function and localization in the model bryophyte Marchantia polymorpha, which carries four short and one long PIN. Our findings reveal that all short MpPINs can export auxin, and they are all PM-localized with MpPINX and MpPINW exhibiting asymmetric distribution. We identified a unique miniW domain within the MpPINW hydrophilic loop region, which is sufficient for its PM localization. Phosphorylation site mutations within the miniW domain abolish the PM localization. These findings not only identify the essential sequence determinant of PINs PM localization but also provide a unique insight into the evolution of ER-localized PINs. Short MpPINW, which is evolutionarily positioned between the ancestral long PINs and contemporary short PINs, still preserves the critical region essential for its PM localization. We propose that throughout land plant evolution, the unique miniW domain has been gradually lost thus converting the PM-localized short PINs in bryophytes to ER-localized short PINs in angiosperms. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

plant biology↗
bioRxiv2024

Reversible host cell surface remodelling limits immune recognition and maximizes transmission of Plasmodium falciparum gametocytes

Reducing malaria transmission has been a major pillar of control programmes and is considered crucial for achieving malaria elimination. Gametocytes, the transmissible forms of the P. falciparum parasite, arise during the blood stage of the parasite and develop through 5 morphologically distinct stages. Immature gametocytes (stage I-IV) sequester and develop in the extravascular niche of the bone marrow and possibly spleen. Only mature stage V gametocytes re-enter peripheral circulation to be taken up by mosquitoes for successful onward transmission. We have recently shown that immature, but not mature gametocytes are targets of host immune responses and identified putative target surface antigens. We hypothesize that these antigens play a role in gametocyte sequestration and contribute to acquired transmission-reducing immunity. Here we demonstrate that surface antigen expression, serum reactivity by human IgG, and opsonic phagocytosis by macrophages all show similar dynamics during gametocyte maturation, i.e., on in immature and off in mature gametocytes. Moreover, the switch in surface reactivity coincides with reversal in phosphatidylserine (PS) surface exposure, a marker for red blood cell age and clearance. PS is exposed on the surface of immature gametocytes (as well as in late asexual stages) but is removed from the surface in later gametocyte stages (IV-V). Using parasite reverse genetics and drug perturbations, we confirm that parasite protein export into the host cell and phospholipid scramblase activity are required for the observed surface modifications in asexual and sexual P. falciparum stages. These findings suggest that the dynamic surface remodelling allows (i) immature gametocyte sequestration in bone marrow and (ii) mature gametocyte release into peripheral circulation and immune evasion, therefore contributing to mature gametocyte survival in vivo and onward transmission to mosquitoes. Importantly, blocking scramblase activity during gametocyte maturation results in efficient clearance of mature gametocytes, revealing a potential path for transmission blocking interventions. Our studies have important implications for our understanding of parasite biology and form a starting point for novel intervention strategies to simultaneously reduce parasite burden and transmission. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

microbiology↗
bioRxiv2024

Ovarian Autotransplantation and experimental life span improvement

Withdrawal StatementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2024/592661 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. The correct preprint can be found at doi: 10.1101/2024.05.06.592661

physiology↗
bioRxiv2024

Mechanisms of axoneme and centriole elimination in Naegleria gruberi

The excavate Naegleria gruberi, a basal eukaryote related to the "brain eating" Naegleria fowleri, can transform transiently from an amoeboid life form lacking flagella and centrioles to a flagellate life form where these elements are present, followed by reversion to an amoeboid state. The mechanisms imparting elimination of axonemes and centrioles during this reversion process are not known. Here, we uncover that flagella primarily fold onto the cell surface and fuse within milliseconds with the plasma membrane. Once internalized, axonemes are severed by Spastin into equally-sized fragments, which are then enclosed by membranes, after which their contents are eliminated through the lysosomal pathway. Moreover, we discovered that centrioles undergo progressive K63 autophagy-linked poly-ubiquitination and K48 proteasome-promoting poly-ubiquitination, and that ubiquitination occurs next to centriolar microtubules. Most centrioles are eliminated in lysosomes or the cytoplasm in a lysosomal- and proteasome-dependent manner. Strikingly, we uncover in addition that centrioles can be shed in the extracellular milieu and taken up by other cells. Collectively, these findings reveal fundamental mechanisms governing the elimination of essential cellular constituents in Naegleria that may operate broadly in eukaryotic systems. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

cell biology↗
bioRxiv2024

Gap-App: A sex-distinct AI-based predictor for pancreatic ductal adenocarcinoma survival as a web application open to patients and physicians

Withdrawal StatementThe authors have withdrawn this manuscript because the final version, now accepted by Cancer Letters, underwent substantial revisions during peer review that significantly changed the conclusions of the study. The AI models deployed are entirely different from those in the preprint, and the performance metrics originally reported (e.g., accuracy, precision) are no longer valid. 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.

bioinformatics↗
bioRxiv2024

Transient Naive Treatment (TNT) iPS cells do not feature Sendai virus expression: Response to Sendai virus persistence questions the transient naive reprogramming method for iPSC generation

SummaryThe Transient Naive Treatment (TNT) reprogramming method involves a brief period of culturing in naive media early in the reprogramming process. Through conducting extensive molecular, epigenetic, and functional analyses on numerous induced pluripotent stem cell lines, we have demonstrated that TNT reprogramming facilitates epigenetic memory erasure and produces induced pluripotent stem (iPS) cells more similar to embryonic stem (ES) cells than conventional reprogramming methods1. In 2024, De Los Angeles et al. posted a contradictory results preprint on bioRxiv titled Sendai virus persistence questions the transient naive reprogramming method for iPSC generation2. Their claims include: 1) that Sendai virus expression in naive cultured cells questions the TNT reprogramming method, 2) the possible selection of cells (clonal expansion) with Sendai virus expression during TNT reprogramming, 3) Sendai virus genes being expressed in control samples implying a potential sample mix-up. Here, we demonstrate these claims are not directly supported by the data, and emphasize that we assessed the possibility of cell sub-population selection experimentally in Buckberry et al. (2023). Moreover, our re-analyses of the data in the context of Sendai virus expression during reprogramming actually highlight the advantages of TNT reprogramming concerning the timing of the naive media treatment and the absence of detectable Sendai virus gene expression.

developmental biology↗
bioRxiv2024

The Neural efficiency score: Validation and application

Withdrawal statementThe authors have withdrawn this manuscript because it has been substantially revised, expanded, and re-titled. The updated, revised, expanded and retitled version will be submitted as a new 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↗
bioRxiv2024

Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants

Withdrawal StatementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2023/532793. 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. The correct preprint can be found at doi: 10.1101/2023.03.15.532793

biophysics↗
bioRxiv2024

Looking for unique signals of human expansion from Africa: Beyond diversity

There are known to be different views on which portion of Africa modern humans globally spread from. Biological diversities have been employed to estimate the origin of our global expansion. These diversities vary with geographical distance from Africa, thereby expressing the signal of the expansion. In preprints, the signal supposedly appeared beyond diversity - in cranial sexual size dimorphism and a cranial shape distance-based measure. Compared to when diversity is used alone, the addition to analysis of variables which are beyond diversity could improve recovery of the signal, therefore improving origin identification. I explored this through cranial and genetic measures which had been calculated in prior studies. Various analyses were used, e.g., ridge regression and Mantel tests. Amongst cranial variables (shape diversity, sexual size dimorphism, and a shape distance-based measure), only dimorphism had a unique portion of the expansion signal. In comparison to when diversity was utilised alone, the additional use of dimorphism and the distance-based measure did not substantially impact signal recovery. However, their addition possibly improved origin identification, reducing by 46% the size of the geographical area which may have the origin. This smaller area approximately matched southern Africa, however, it was not only in the south. It was questionable if the signal was present in a genetic distance-based measure, which called into question whether the expansion signal is truly present in the cranial shape distance-based measure. Analysis suggested that the apparent presence of the signal in distance-based measures is affected by the representation of Oceanian populations. This study supports cranial sexual size dimorphism being a helpful indicator of the expansion whilst calling into question whether biological distance-based measures are indicators. Clarity remains missing on which African region was the origin.

evolutionary biology↗
bioRxiv2024

Patient-derived colon epithelial organoids reveal lipid-related metabolic dysfunction in pediatric ulcerative colitis

Background & AimsUlcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Patient-derived organoids recapitulate complexities of the parent tissue in health and disease; however, whether colon organoids (colonoids) model metabolic impairments in the pediatric UC epithelium is unclear. This study determined the functional metabolic differences in the colon epithelia using epithelial colonoids from pediatric patients. MethodsWe developed biopsy-derived colonoids from pediatric patients with endoscopically active UC, inactive UC, and those without endoscopic or histologic evidence of colon inflammation (non-IBD controls). We extensively interrogated metabolic dysregulation through extracellular flux analyses and tested potential therapies that recapitulate or ameliorate such metabolic dysfunction. ResultsEpithelial colonoids from active UC patients exhibit elevated oxygen consumption and proton leak supported by enhanced glycolytic capacity and dysregulated lipid metabolism. The hypermetabolic features in active UC colonoids were associated with increased cellular stress and chemokine secretion, specifically during differentiation. Transcriptomic and pathway analyses indicated a role for PPAR- in lipid-induced hypermetabolism in active UC colonoids, which was validated by PPAR- activation in non-IBD colonoids. Accordingly, limiting neutral lipid accumulation in active UC colonoids through pharmacological inhibition of PPAR- induced a metabolic shift towards glucose consumption, suppressed hypermetabolism and chemokine secretion, and improved cellular stress markers. Control and inactive UC colonoids had similar metabolic and transcriptomic profiles. ConclusionsOur pediatric colonoids revealed significant lipid-related metabolic dysregulation in the pediatric UC epithelium that may be alleviated by PPAR- inhibition. This study supports the advancement of colonoids as a preclinical human model for testing epithelial-directed therapies against such metabolic dysfunction. What You Need to KnowO_ST_ABSBackground and ContextC_ST_ABSColon mucosa healing in pediatric UC requires reinstating normal epithelial function but a lack of human preclinical models of the diseased epithelium hinders the development of epithelial-directed interventions. New FindingsUsing colon biopsy-derived epithelial organoids, samples from pediatric patients with active UC show hyperactive metabolic function largely driven by enhanced lipid metabolism. Pharmacologic inhibition of lipid metabolism alleviates metabolic dysfunction, cellular stress, and chemokine production. LimitationsThough our epithelial colon organoids from active UC patients show targetable metabolic and molecular features from non-IBD controls, they were cultured under sterile conditions, which may not fully capture any potential real-time contributions of the complex inflammatory milieu typically present in the disease. Clinical Research RelevanceCurrent therapies for pediatric UC mainly target the immune system despite the need for epithelial healing to sustain remission. We identified a pharmacologic target that regulates epithelial metabolism and can be developed for epithelial-directed therapy in UC. Basic Research RelevancePediatric UC patient tissue adult stem cell-derived colon epithelial organoids retain disease-associated metabolic pathology and can serve as preclinical human models of disease. Excess reliance on lipids as an energy source leads to oxidative and inflammatory dysfunction in pediatric UC colon organoids. Preprint: This manuscript is currently on bioRxiv. doi: https://doi.org/10.1101/2024.08.22.609271 Lay Summary: Using patient tissue-derived colon epithelial organoids, the investigators identified epithelial metabolic dysfunction and inflammation in pediatric ulcerative colitis that can be alleviated by PPAR-a inhibition.

physiology↗
bioRxiv2024

Bovine dendritic-cell subsets in lymphoid and non-lymphoid tissues: work in progress

Bovine dendritic-cell subsets can be readily identified in flow cytometry by staining for Flt3, CD4 and CD13. While this gating strategy could be confirmed by bulk RNA-seq of subsets sorted from peripheral blood mononuclear cells, it remains to be determined if the same gating strategy can be applied to gate on cDC1, cDC2 and pDC within lymphoid and non-lymphoid tissues. With this preprint we aim to inform on the current status of phenotyping experiments performed on Flt3+ cells in mesenteric lymph nodes, spleen and lung of cattle. Distinct DC subsets can be gated in all tissues based on CD4 and CD13, with high frequencies of Flt3+CD13+ cells (putative cDC1) detected in the lung. Further phenotyping performed on lymph node cells (in particular CADM1, CD26 and CD123) support the subset classification analogous to blood, with pDC being Flt3+CD4+CD13- and cDC1 being Flt3+CD4-CD13+. Heterogeneous expression of CADM1 and CD26 on Flt3+CD4-CD13- putative cDC2 warrants further investigations.

immunology↗