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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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Preprints vs. Journal Articles: Citation Impact in COVID-19 Research

Focusing on article and citation count, this study examined 110 academic journals whose papers on COVID-19 were indexed in PubMed from 2020 to 2023. To analyze these journals characteristics, this study introduced the concepts of paper ratio, citation ratio, and citation impact. Journals with similar trends in paper and citation count were positioned near the diagonal on a two-dimensional graph (y=x) with paper ratio on the x-axis and citation ratio on the y-axis, indicating a slope close to 1. Conversely, the greater the disparity between paper ratio and citation ratio, the wider the angle between the journals position and the diagonal. Of the 110 journals in 2020, 83 were above the diagonal with a citation impact greater than 1, while 27 were below the diagonal with a citation impact of 1 or lower. Notably, nine journals--BMC Health Services Research, Genome Medicine, Nature, Annals of Epidemiology, BMC Bioinformatics, Nature Microbiology, PLoS Computational Biology, Medicine (Baltimore), and Journal of Clinical Investigation--showed high citation impact, with preprint-distributed papers being cited nearly five times more than directly submitted papers. This study demonstrates that articles initially distributed as preprints in these journals tend to receive substantially more citations than directly submitted ones.

scientific communication and education↗

Have AI-Generated Texts from LLM Infiltrated the Realm of Scientific Writing? A Large-Scale Analysis of Preprint Platforms

Since the release of ChatGPT in 2022, AI-generated texts have inevitably permeated various types of writing, sparking debates about the quality and quantity of content produced by such large language models (LLM). This study investigates a critical question: Have AI-generated texts from LLM infiltrated the realm of scientific writing, and if so, to what extent and in what setting? By analyzing a dataset comprised of preprint manuscripts uploaded to arXiv, bioRxiv, and medRxiv over the past two years, we confirmed and quantified the widespread influence of AI-generated texts in scientific publications using the latest LLM-text detection technique, the Binoculars LLM-detector. Further analyses with this tool reveal that: (1) the AI influence correlates with the trend of ChatGPT web searches; (2) it is widespread across many scientific domains but exhibits distinct impacts within them (highest: computer science, engineering sciences); (3) the influence varies with authors who have different language speaking backgrounds and geographic regions according to the location of their affiliations (Italy, China, etc.); (4) AI-generated texts are used in various content types in manuscripts (most significant: hypothesis formulation, conclusion summarization); (5) AI usage has a positive influence on papers impact, measured by its citation numbers. Based on these findings, suggestions about the advantages and regulation of AI-augmented scientific writing are discussed.

scientific communication and education↗

The Effectiveness of China’s National Forest Protection Program and National-level Nature Reserves, 2000 to 2010: PREPRINT

There is profound interest in knowing the degree to which Chinas institutions are capable of protecting its natural forests and biodiversity in the face of economic and political change. Chinas two most important forest protection policies are its National Forest Protection Program (NFPP) and its National-level Nature Reserves (NNRs). The NFPP was implemented in 17 provinces starting in the year 2000 in response to deforestation-caused flooding. We used MODIS data (MOD13Q1) to estimate forest cover and forest loss across mainland China, and we report that 1.765 million km2 or 18.7% of mainland China was covered in forest (12.3%, canopy cover > 70%) and woodland (6.4%, 40% [&le;] canopy cover < 70%) in 2000. By 2010, a total of 480,203 km2 of forest + woodland was lost, amounting to an annual deforestation rate of 2.7%. The forest-only loss was 127,473 km2, or 1.05% annually. The three most rapidly deforested provinces were outside NFPP jurisdiction, in the southeast. Within the NFPP provinces, the annual forest + woodland loss rate was 2.26%, and the forest-only rate was 0.62%. Because these loss rates are likely overestimates, China appears to have achieved, and even exceeded, its NFPP target of reducing deforestation to 1.1% annually in the target provinces. We also assemble the first-ever polygon dataset for Chinas forested NNRs (n = 237), which covered 74,030 km2 in 2000. Conventional unmatched and covariate-matching analyses both find that about two-thirds of Chinas NNRs exhibit effectiveness in protecting forest cover and that within-NNR deforestation rates are higher in provinces that have higher overall deforestation.

Ecology↗

Preprint: A robust peptidomics mass spectrometry platform for measuring oxytocin in plasma and serum

Current approaches to measuring the cyclic peptide oxytocin in plasma/serum are associated with poor selectivity and/or inadequate sensitivity. We here describe a high performance nano liquid chromatography-mass spectrometry platform for measuring OT in human plasma/serum. The platform is extremely robust, allowing laborious sample clean-up steps to be omitted. OT binds strongly to plasma proteins, but a reduction/alkylation procedure breaks this bond, allowing ample detection of total OT. The method showed excellent quantitation properties, and was used to determine total OT levels to 0.5-1.2 ng/mL (evaluated with human plasma and cord serum). The method is compatible with accessible mass spectrometry instrumentation, finally allowing selective and easily comparable oxytocin measurements.

Neuroscience↗

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. BioRXiv preprint.

The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly -helical fibrinogen to fibrin, with a binding mechanism involving knobs and holes but with otherwise littl change in protein secondary structure. We recognise, however, that extremely unusual mutations, or mechanical stressing, can cause fibrinogen to adopt a conformation containing extensive {beta}-sheets. Similarly, prions can change morphology from a largely alpha-helical to a largely {beta}-sheet conformation, and the latter catalyses both the transition and the self-organising polymerisation of the {beta}-sheet structures. Many other proteins can do this, where it is known as amyloidogenesis. When fibrin is formed in samples from patients harbouring different diseases it can have widely varying diameters and morphologies. We here develop the idea, and summarise the evidence, that in many cases the anomalous fibrin fibre formation seen in such diseases actually amounts to amyloidogenesis. In particular, fibrin can interact withthe amyloid-{beta} (A{beta}) protein that is misfolded in Alzheimer's disease. Seeing these unusual fibrin morphologies as true amyloids explains a great deal about fibrin(ogen) biology that was previously opaque, and provides novel strategies for treating such coagulopathies. The literature on blood clotting can usefully both inform and be informed by that on prions and on the many other widely recognised ({beta})-amyloid proteins.\n\n\"Novel but physiologically important factors that affect fibrinolysis have seldom been discovered and characterized in recent years\" [1]

Pathology↗

To what extent are the terminal stages of sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome actually driven by a prion/amyloid form of fibrin? bioRxiv preprint.

A well-established development of increasing disease severity leads from sepsis through septic shock, SIRS, multiple organ dysfunction syndrome and cellular and organismal death. We argue that a chief culprit is the LPS-induced anomalous coagulation of fibrinogen to produce a form of fibrin that is at once inflammatory, resistant to fibrinolysis, and underpins the disseminated intravascular coagulation commonly observed in sepsis. In particular, we argue that the form of fibrin produced is anomalous because much of its normal -helical content is transformed to {beta}-sheets, as occurs in established amyloidogenic and prion diseases. We hypothesise that these processes play a major role in the passage along the above pathways to organismal death, and that inhibiting them would be of great therapeutic value, a claim for which there is emerging evidence.

Immunology↗

Assessing data quality in citizen science - preprint

Ecological and environmental citizen science projects have enormous potential to advance science, influence policy, and guide resource management by producing datasets that are otherwise infeasible to generate. This potential can only be realized, though, if the datasets are of high quality. While scientists are often skeptical of the ability of unpaid volunteers to produce accurate datasets, a growing body of publications clearly shows that diverse types of citizen science projects can produce data with accuracy equal to or surpassing that of professionals. Successful projects rely on a suite of methods to boost data accuracy and account for bias, including iterative project development, volunteer training and testing, expert validation, replication across volunteers, and statistical modeling of systematic error. Each citizen science dataset should therefore be judged individually, according to project design and application, rather than assumed to be substandard simply because volunteers generated it.

Preprint↗

Preprint: Environmentally-Friendly Workflow Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking For the Discovery of Potent Anti-Viral Leads From Plants

A supercritical fluid chromatography-based targeted purification workflow using tandem mass spectrometry and molecular networking was developed to analyze, annotate and isolate secondary metabolites from complex mixture. This approach was applied for targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorboids esters, were present in the samples. The purification procedure using semi-preparative-supercritical fluid chromatography led to the isolation and identification of two jatrophane esters (13 and 14) and four 4-deoxyphorbol esters (15-18). Compound 16 was found to display antiviral activity against chikungunya virus (EC50 = 0.45 {micro}M), while compound 15 was found to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC50 = 13 nM). This study showed that supercritical fluid chromatography-based workflow and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeted molecules of interest, while minimizing the use of toxic solvents.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC=\"FIGDIR/small/106153_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@191802aorg.highwire.dtl.DTLVardef@1755ab8org.highwire.dtl.DTLVardef@196edf5org.highwire.dtl.DTLVardef@1e0a1e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

Preprint peer review enhances undergraduate biology students' disciplinary literacy and sense of belonging in STEM

Undergraduate education on science publishing and peer review is limited compared to the focus on experimental research. Since peer review is integral to the scientific process and central to the identity of a scientist, we envision a paradigm shift that makes teaching peer review integral to undergraduate science education, and hypothesize that this may facilitate the development of students scientific literacy and identity formation. To this end, we developed a curriculum for biology undergraduates to learn about the mechanisms of peer review, then write and publish their own peer reviews as a way to authentically join the scientific community of practice. The curriculum was implemented as a semester-long intervention in one class and as a module intervention embedded into a discipline-based class on vaccines. Before and after both interventions, we measured students scientific literacy, including peer review ability, using quantitative methods. We also carried out a longitudinal qualitative assessment of students perceptions of their scientific literacy and identity using thematic analysis of students writing. Here, we present data on the improvement in peer review ability of undergraduates in both classes, and data on the curriculums interrelated impact on students development of scientific literacy, identity, and belonging in academic and professional spaces. These data suggest that undergraduates can and should be trained in peer review to foster the interrelated development of their scientific literacy, scientific identity, and sense of belonging in science.

scientific communication and education↗

Preprint: Triggered sequential viral-transduction from collagen-based scaffolds for tissue regeneration

Chronic wounds are a major healthcare issue that are recalcitrant to many traditional treatments. Increasingly, tissue engineering scaffolds are being developed and translated to promote their healing. To control signaling in the wound environment, gene therapy approaches are being explored, with adeno-associated virus (AAV) becoming increasingly popular. One critical challenge in chronic wound healing is that the wounds do not progress through the typical wound healing cascade, with signaling getting stuck in the inflammatory/immature tissue formation phase. This motivated us to develop a system capable of triggered sequential release of viral vectors to drive coordinated signaling. By housing this system within a collagen-glycosaminoglycan (GAG) scaffold, we aim to provide a proven extracellular matrix template as well as the correct signaling profile for closure of chronic wounds. Our system consists of two alginate pockets within the collagen-GAG scaffold, which we use to control the release of AAV. The first pocket allows diffusion of one AAV therapeutic and the second pocket can be ultrasound-triggered using low-frequency stimulation to release the second therapeutic. Initially, we developed and characterized the system using a reporter AAV. At our high AAV loading, we got sustained release and GFP expression in HEK293T cells over 9 days from our system in vitro, but lower loading had minimal transduction. When this lower group was triggered with ultrasound, cells were successfully transduced. Finally, we demonstrated sequential release of AAV encoding clinically-relevant genes for angiogenesis. This system has the potential for broad applicability as it can be readily adapted to mimic a range of biological pathways.

bioengineering↗

A decade after being listed as Endangered: Japanese eel stock inferred from fishery-dependent and independent monitoring records (Preprint)

This study assesses recent trends in the abundance of Japanese eels (Anguilla japonica), which have been listed as Endangered on the IUCN Red List of Threatened Species since 2014, by updating previously reported coastal fisheries datasets and incorporating new freshwater data and scientific monitoring records for glass eels in Japan and Taiwan. Catch-per-unit-effort (CPUE) data for yellow and silver eels revealed statistically significant declines in seven of eight datasets, with projected reductions over three generations (24 years) ranging from 79.2% to 99.9%. In contrast, no significant temporal trends were detected in the CPUE of glass eels, likely due to high interannual variability driven by oceanic conditions. The integration of freshwater and coastal data, along with fishery-independent monitoring, enhances the reliability of these indicators. The results provided in this study represent the best currently available indicators of Japanese eel population dynamics.

ecology↗

Target-enriched sequencing enables genomic characterization within diverse microbial populations - a preprint

Characterizing microbial genetic sequences and key variants is critical for understanding pathogen ecology, transmission, and clinical impact. Yet, conventional metagenomic sequencing often yields too few on-target reads to move beyond species-level identification. We developed a target-enriched (TE) metagenomic workflow, including bait design, an optimized TE shotgun protocol, and the VARIANT++ pipeline, to recover and classify reads at a clustered genomic sequence-variant (GSV) level (see Graphical abstract). The computational component clusters reference genomes by average nucleotide identity, builds a GSV database, and integrates Kraken2, Themisto, and mSWEEP to increase call confidence while reducing false positives. Using Mannheimia haemolytica (Mh), the primary cause of bovine respiratory disease, we designed 114,375 DNA baits targeting sequences across 70 reference genomes. TE libraries from nasopharyngeal swabs of feedlot cattle achieved >250-fold increases in on-target Mh reads ([~]2.5% of non-host reads on average) compared with conventional shotgun sequencing, despite using one-quarter the sequencing depth. This variant-level resolution revealed six GSVs; most samples contained at least two, indicating variant mixtures difficult to detect with culture- or shotgun-based surveys. Because the approach leverages available reference sequences, it can be reconfigured for other microbial targets. TE metagenomics paired with genome-similarity clustering provides a scalable approach to variant-level characterization from complex microbial populations. O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/684174v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@5a7247org.highwire.dtl.DTLVardef@4ccf1org.highwire.dtl.DTLVardef@12b0413org.highwire.dtl.DTLVardef@118a0ec_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Overview of the components in our three-part workflow. C_FIG

genomics↗

Enhancer prediction in the human genome by probabilistic modeling of the chromatin feature patterns

BackgroundThe binding sites of transcription factors (TFs) and the localisation of histone modifications in the human genome can be quantified by the chromatin immunoprecipitation assay coupled with next-generation sequencing (ChIP-seq). The resulting chromatin feature data has been successfully adopted for genome-wide enhancer identification by several unsupervised and supervised machine learning methods. However, the current methods predict different numbers and different sets of enhancers for the same cell type and do not utilise the pattern of the ChIP-seq coverage profiles efficiently. ResultsIn this work, we propose a PRobabilistic Enhancer PRedictIoN Tool (PREPRINT) that assumes characteristic coverage patterns of chromatin features at enhancers and employs a statistical model to account for their variability. PREPRINT defines probabilistic distance measures to quantify the similarity of the genomic query regions and the characteristic coverage patterns. The probabilistic scores of the enhancer and non-enhancer samples are utilised to train a kernel-based classifier. The performance of the method is demonstrated on ENCODE data for two cell lines. The predicted enhancers are computationally validated based on the transcriptional regulatory protein binding sites and compared to the predictions obtained by state-of-the-art methods. ConclusionPREPRINT performs favorably to the state-of-the-art methods, especially when requiring the methods to predict a larger set of enhancers. PREPRINT generalises successfully to data from cell type not utilised for training, and often the PREPRINT performs better than the previous methods. The PREPRINT enhancers are less sensitive to the choice of prediction threshold. PREPRINT identifies biologically validated enhancers not predicted by the competing methods. The enhancers predicted by PREPRINT can aid the genome interpretation in functional genomics and clinical studies. Availabilityhttps://github.com/MariaOsmala/preprint Contactmaria.osmala@aalto.fi

bioinformatics↗

A high throughput CRISPR perturbation screen identifies epigenetic regulators impacting primordial germ cell development

Withdrawal StatementThe authors have withdrawn this manuscript due this manuscript merging with another preprint (BIORXIV/2024/580543). 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 merged preprint can be found at doi: 10.1101/2024.02.15.580543" The original version of 580543 described the development and characterization of the engineered mouse embryonic stem cells (ESCs) that could be differentiated into primordial germ cell-like cells (PGCLCs) in a scalable and efficient manner. Those cells were used to conduct the large screen (and other experiments) described in this withdrawn preprint. We merged the two manuscripts at the recommendation of a journal editor to which we sent the two papers for concurrent consideration. There are no substantive differences in the content merged preprint vs. this withdrawn preprint or the original version of 580543.

developmental biology↗

Behavioral activity increases neuronal activity in the circadian clock of diurnal Arvicanthis ansorgei

2.The central circadian clock, located in the suprachiasmatic nucleus (SCN) within the brain, regulates daily patterns of activity and physiology. Many studies indicate that exercise at specific times throughout the day can help maintain proper circadian rhythms. In nocturnal animals, even moderate levels of physical activity suppress the neuronal discharge rate of the SCN. Given that such a mechanism would likely be counter-effective in diurnal animals, we measured the firing rate of SCN neurons in freely moving diurnal Arvicanthis ansorgei using implanted microelectrodes. We found that SCN firing was acutely increased rather than decreased both during brief (seconds) and long (hours) bouts of activity, and returned to baseline levels after behavioral activity ceased. We also found that daytime activity increases the strength of the SCN rhythm, as expected for day-active animals. To determine whether the acute increases in firing are produced within the SCN or in response to input from outside the SCN, we performed ex vivo recordings in which afferent inputs are severed. We found no intrinsic increment occurring in the isolated SCN. These findings suggest that the excitatory effect on the SCNs neuronal firing rate comes from areas that lie outside the SCN, presumably those that are affected by the animals activity. We conclude that exercise has opposite effects on the clock between nocturnal and diurnal rodents, and identified how exercise strengthens the neuronal discharge rhythm in the clock of a diurnal animal. 3. Significance statementOur biological clock controls behavioral activity rhythms by generating a 24-pattern of electrical activity. The electrical activity serves as output of the clock and is high during the day and low during the night. Physical activity, being under strong control of the clock, acts vice versa, and affects the electrical activity of the clock. In nocturnal animals, behavioral activity inhibits the clocks firing rate. Here, we examined the effect of behavioral activity on the brains clock in the diurnal rodent, Arvicanthis. When the animal is active, the clocks electrical activity is enhanced, rather than decreased. Thus, a diurnal animal can increase the strength of its own clock, by being active during the day. Preprint ServersThe manuscript was deposited as a preprint in bioRxiv preprint doi: https://doi.org/10.1101/2022.05.31.493966; this version posted June 1, 2022. The copyright holder for this preprintin bioRxiv, made available under aCC-BY-NC-ND 4.0 International license (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ClassificationBiological Sciences, Physiology

neuroscience↗

SAUNA - Simulated Annealing for Unique Nucleosome Arrangements from Cell-Free DNA-Sequencing Data

WithdrawalThis preprint has been withdrawn by the authors. While the preprint cites the work by Schoepflin et al. (2013) (reference [20] in the preprint), it has been brought to the authors attention that the preprint may not appropriately acknowledge the extent to which their work depends on the work by Schoepflin et al. (2013). The authors apologize for this oversight and want to emphasize that they did not intend to misattribute the work of Schoepflin et al. (2013) and want to thank them for the code of NucPosSimulator which is a core component of SAUNAs algorithm. Therefore, the authors do not wish this work to be cited as reference for the project. For any questions, please contact the corresponding author.

bioinformatics↗

Rigorous equations for isothermal titration calorimetry: theoretical and practical consequences

The author has withdrawn his manuscript because: The withdrawn preprint was about methodological aspects in Isothermal Titration Calorimetry (ITC) used to obtain thermodynamic information about reactions like A + B {rightleftarrows} C where A is initially in the cell and B injected from a syringe. The preprint considered the two possible methods in ITC: 1/ the Multiple Injection Method (MIM) making use of short-time injections separated by sufficient time to allow the reaction to reach equilibrium before a new injection. 2/ the Single Injection Method (SIM) making use of a slow continuous injection. The first result mentioned is about a new equation linking the rate of heat evolution with the injected volume (equations 9 and 10). With this equation and with the hypothesis that there is always perfect mixing of the cell content it was concluded that an ideal titration curve (i.e. not affected by any external influence) for a simple reaction like A + B {rightleftarrows} C cannot change sign (section 3.2). This conclusion turns out to be incorrect when taking in consideration real conditions with imperfect mixing, particularly with MIM using injections often of very short duration, which prevents from reaching perfect mixing. The major problem is that this erroneous conclusion was accompanied with comparisons of the results from well-established programs, which led to the conclusion that these were in error on this point (section 3.6). I therefore felt necessary to withdraw this preprint to avoid casting doubts unduly on these programs used extensively. Note that many other aspects in this preprint remain correct (section 3.8). A new version of this work, limited to SIM and considering imperfect mixing, will be submitted for publication under the title: "Isothermal titration calorimetry in the single-injection mode with imperfect mixing". If you have any questions, please contact me at dumasp@igbmc.fr or at p.dumas@unistra.fr Sorry for the inconvenience. Philippe Dumas November 6, 2021

biophysics↗

Funding deadlines act as a zeitgeber for science

Funders decide which science is paid for. Whether they also shape when it becomes public has been hard to test. Across 376,542 preprints on bioRxiv and medRxiv, the US share rose by 2.3 to 2.7 percentage points in the four weeks before due dates for the main research grant of the National Institutes of Health (NIH) and dropped on the date. About one in eleven US preprints in those weeks was attributable to the deadline, and fields that depend least on NIH rose least. Among 15,906 funded investigators, the share of preprints posted in the four weeks before their own deadline was 9% higher than in other four-month cycles, and these preprints resembled the later grant without being more highly cited. Repeated before every due date, this individual surge matches the national peak's timing within a week. NIH's application calendar, like its funding, shapes when US biomedical science becomes public.

scientific communication and education↗