bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years
Authors: Marfil-Garza Braulio A. , Hefler Joshua , Verhoeff Kevin , Lam Anna , Dajani Khaled , Anderson Blaire , O’Gorman Doug , Kin Tatsuya , Bello-Chavolla Omar Yaxmehen , Grynoch Donald , Halpin Anne , Campbell Patricia M. , Senior Peter A. , Bigam David , Shapiro A.M. James 
Published: December 2022

Objective:
To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation.

Summary Background Data:
Studies describing long-term outcomes with ITx and PTx are scarce.

Methods:
We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ
2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented.

Results:
Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively (P=0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04–4.17, P=0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively (P=0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8–4.6) and 6.7 (IQR 2.9–12.4) year for ITx and PTx, respectively (P=2.2×10-22). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively (P=0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P=7.4×10-7, time, P=4.8×10-6, group*time, P=1.2×10-7). Procedure-related complications and hospital readmissions were higher after PTx (P=2.5×10-32 and P=6.4×10-112, respectively).

Conclusions:
PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.
Loss of species richness with land use intensity is explained by a reduction in niche differences
Authors: Godoy Oscar , Granjel Rodrigo R. , van der Plas Fons , Soliveres Santiago , Penone Caterina , Saiz Hugo , Hölzel Norbet , Prati Daniel , Fischer Markus , Allan Eric 
Published: December 2022

AbstractIncreases in land use intensity (LUI) reduce species richness. However, we have a poor understanding of how underlying coexistence mechanisms are altered by land use and whether diversity loss occurs due to changes in plant-plant interactions (competition and facilitation) or in species intrinsic growth rates. We expect that LUI could reduce stabilizing niche differences and the indirect interactions that promote coexistence (e.g., intransitivity), while increasing competitive inequalities between species. To test the importance of these different processes, we use 8-yr time series from 150 grasslands differing in LUI to evaluate the role of direct and indirect interactions in promoting coexistence between 50 plant species. We show that LUI reduces the number of coexisting species mostly by causing a non-linear reduction in niche differences, rather than by enhancing competitive inequalities. However, surprisingly, niche differences remained important in stabilizing coexistence between those species remaining at high LUI. Indirect interactions were generally less important than direct ones, and played a moderate role in promoting coexistence in smaller assemblages of species at intermediate LUI. Our models could accurately reproduce the decline in diversity seen with LUI, indicating that our time series approach captures the important interactions between species. By analyzing land use effects through recent advances in structural stability applied to community ecology we provide a more mechanistic understanding of its effects. Our results highlight the importance of identifying the niche differences that are lost with increasing LUI, to better predict and manage effects of land use on biodiversity.Significant statementHuman land use is a major threat to grassland biodiversity. Grasslands with high rates of fertilization, grazing and mowing, contain many fewer plant species. Knowing the underlying causes is necessary for a better management of biodiversity. Here we apply ecological theory to spatiotemporal data on changes in plant abundance in managed grasslands in central Europe. We show that the observed decline in diversity can be explained by how interactions among plant species change with increases in land use intensity. In particular, intensive land use removes the stabilizing effect of self-limiting processes that buffer species against extinction as well as limit competitive dominance. Therefore, actions to promote these stabilizing dynamics among interacting species seem key to restore plant diversity.
Detecting remote homolog using structure alignment algorithms and machine learning
Authors: de Sousa Costa Priscila Caroline , Sakamoto Tetsu 
Published: December 2022

AbstractRemote homolog detection is a classic problem in Bioinformatics. It attempts to identify distantly related proteins sharing a similar structure. Methods that can accurately detect remote homologs benefit protein functional annotation. Recent computational advances in methods predicting the three-dimensional structure of a protein from amino acid sequences allow the massive use of structural data to develop new tools for identifying remote homologs. In this work, we created a discriminative SVM-based method based on structural alignment algorithms (FATCAT, TM-Align, and LovoAlign) to detect whether a protein is a remote homolog with any proteins in the SCOPe database. The final model showed a ROC AUC of 0.9191.
The use of a graph database is a complementary approach to a classical similarity search for identifying commercially available fragment merges
Authors: Wills Stephanie , Sanchez-Garcia Ruben , Roughley Stephen D. , Merritt Andy , Hubbard Roderick E. , Dudgeon Tim , Davidson James , von Delft Frank , Deane Charlotte M. 
Published: December 2022

AbstractFragment screening using X-ray crystallography can yield rich structural data to help guide the optimization of low-molecular-weight compounds into more potent binders. Fragment merging, whereby substructural motifs from partially overlapping fragments are incorporated into a single larger compound, represents a potentially powerful and efficient approach for increasing potency. Searching commercial catalogues provides one useful way to quickly and cheaply identify follow-up compounds for purchase and further screening, and circumvents the challenge of synthetic accessibility. The Fragment Network is a graph database that provides a novel way to explore the chemical space surrounding fragment hits. We use an iteration of the database containing >120 million catalogue compounds to find fragment merges for four XChem fragment screening campaigns. Retrieved molecules were filtered using a pipeline of 2D and 3D filters and contrasted against a traditional fingerprint-based similarity search. The two search techniques were found to have complementary results, identifying merges in different regions of chemical space. Both techniques were able to identify merges that are predicted to replicate the interactions made by the parent fragments. This work demonstrates the use of the Fragment Network to increase the yield of fragment merges beyond that of a classical catalogue search, thus increasing the likelihood of finding promising follow-up compounds. We present a pipeline that is able to systematically exploit all known fragment hits by performing large-scale enumeration of all possible fragment pairs for merging.
Structure modeling and specificity of peptide-MHC class I interactions using geometric deep learning
Authors: Aronson Alon , Hochner Tanya , Cohen Tomer , Schneidman-Duhovny Dina 
Published: December 2022

AbstractMajor Histocompatibility Complex (MHC) plays a major role in the adaptive immune response by recognizing foreign proteins through binding to their peptides. In humans alone there are several hundred different MHC alleles, where each allele binds a specific subset of peptides. The peptide-MHC complex on a cell surface is identified by a T-cell receptor (TCR) and this binding invokes an immune response. Therefore, predicting the binding specificity of peptide-MHC pairs is necessary for understanding the immune recognition mechanism. Here, we develop an end-to-end novel deep learning model, MHCfold, that consists of structure and specificity prediction modules for simultaneous modeling of peptide-MHC class I (pMHCI) complexes and prediction of their specificity based on their modeled structure. MHCfold produces highly accurate structures of pMHCI complexes with mean Cα RMSD of 0.98Å and 1.50Å for the MHC α chain and the peptide, respectively. The binding specificity is also predicted with high accuracy (mean AUC of 0.94). Furthermore, the structure modeling component is orders of magnitudes faster than state-of-the-art methods (modeling of 100,000 pMHCI pairs in four hours on a standard computer), enabling high-throughput applications for large immunopeptidomics datasets. While peptide-MHC specificity can be accurately predicted from the sequence alone, TCR specificity prediction likely requires modeling of the 3D structures. We anticipate our model can be further used in structure-based prediction of TCR specificity.MHCfold is available @https://github.com/dina-lab3D/MHCfold
Estimating admixture pedigrees of recent hybrids without a contiguous reference genome
Authors: Garcia-Erill Genís , Hanghøj Kristian , Heller Rasmus , Wiuf Carsten , Albrechtsen Anders 
Published: December 2022

AbstractThe genome of recently admixed individuals or hybrids have characteristic genetic patterns that can be used to learn about their recent admixture history. One of these are patterns of interancestry heterozygosity, which can be inferred from SNP data from either called genotypes or genotype likelihoods, without the need for information on genomic location. This makes them applicable to a wide range of data that are often used in evolutionary and conservation genomic studies, such as low-depth sequencing mapped to scaffolds and reduced representation sequencing. Here we implement maximum likelihood estimation of interancestry heterozygosity patterns using two complementary models. We furthermore developapoh(Admixture Pedigrees Of Hybrids), a software that uses estimates of paired ancestry proportions to detect recently admixed individuals or hybrids, and to find the most compatible recent admixture pedigree. It furthermore calculates several hybrid indices that make it easier to identify and rank possible admixture pedigrees that could give rise to the estimated patterns. We implementedapohboth as a command line tool and as a Graphical User Interface that allows the user to automatically and interactively explore, rank and visualize compatible recent admixture pedigrees, and calculate the different summary indices. We validate the performance of the method using admixed family trios from the 1000 Genomes Project. In addition, we show its applicability on identifying recent hybrids from RAD-seq data of Grant’s gazelle (Nanger grantiandNanger petersii) and whole genome low depth data of waterbuck (Kobus ellipsiprymnus) which shows complex admixture of up to four populations.
Genomic description of critical upstream cannabinoid biosynthesis genes
Authors: Innes Peter A. , Vergara Daniela 
Published: December 2022

AbstractCannabinoid production is one of the key attributes of the plantCannabis sativaand the characterization of the genes involved is an essential first step to develop tools for their optimization. We used bioinformatic approaches to annotate and explore variation in the coding genes for critical enzymes comprising the cannabinoid pathway: Olivetol Synthase (OLS), Olivetolic Acid Cyclase (OAC), and Cannabigerolic Acid Synthase (CBGAS), in multipleC. sativagenomes. These upstream genes of the Cannabinoid Oxidocyclase Genes THCAS, CBDAS, and CBCAS generate the necessary precursor molecules to produce the cannabinoids THC and CBD. We found that these genes vary in copy number and confirm that OLS, OAC, CBGAS, and the Cannabinoid Oxidocyclases are on separate chromosomes, while homologs are found in proximity. CBGAS, located on Chromosome X, suggests potential dosage effects in female plants. Except for the Cannabinoid Oxidocyclase genes, the other genes have multiple exons, up to 10 in CBGAS. Through differential exon usage explorations in CBGAS we found evidence for potential regulatory differences. This study provides valuable insight on the genomic identity and variation of cannabinoid biosynthesis genes that will benefit future research on the origin and evolution of this pathway, driver of economic, social, and medicinal value.
Characterization of sperm motility signaling pathway in a gonochoric coral suggests conservation across sexual systems
Authors: Glass Benjamin H. , Ashey Jill , Okongwu Amarachukwu R. , Putnam Hollie M. , Barott Katie L. 
Published: December 2022

AbstractMany marine invertebrates liberate their gametes into the water column broadcast spawning, where fertilization hinges upon the successful activation of sperm motility. Here, we investigated the molecular mechanisms underpinning sperm motility in the broadcast spawning coralAstrangia poculata. We found that cytosolic alkalinization activates the pH-sensing enzyme soluble adenylyl cyclase (sAC), followed by motility, inA. poculatasperm. In addition, we show for the first time in any cnidarian that sAC activity is required to activate protein kinase A (PKA) in sperm, and that PKA activity is required for the initiation of sperm motility. Ultrastructures ofA. poculatasperm displayed morphological homology to other gonochoric cnidarians, and investigation of cnidarian proteomes revealed that sAC, the central signaling node in the sperm motility pathway, demonstrates broad structural and functional conservation across a diversity of cnidarian species. Ultimately, these results suggest that the role of sAC signaling in sperm motility is conserved between sperm from gonochoric and hermaphroditic corals, which is surprising given their morphological dissimilarities. This study also offers insight into the evolution of the mechanisms controlling metazoan sperm motility.Summary statementFor broadcast spawning marine invertebrates, the initiation of sperm motility is essential for fertilization. Here, we provide evidence for conservation of a sperm motility pathway across sexual systems in corals.
Not quite lost in translation: Mistranslation alters adaptive landscape topography and the dynamics of evolution
Authors: Schmutzer Michael , Wagner Andreas 
Published: December 2022

AbstractMistranslation – the erroneous incorporation of amino acids into nascent proteins – is a source of protein variation that is orders of magnitude more frequent than DNA mutation. Like other sources of nongenetic variation, it can affect adaptive evolution. We study the evolutionary consequences of mistranslation with experimental data on mistranslation rates applied to three empirical adaptive landscapes. We find that mistranslation generally flattens adaptive landscapes by reducing the fitness of high fitness genotypes and increasing that of low fitness genotypes, but it does not affect all genotypes equally. Most importantly, it increases genetic variation available to selection by rendering many neutral DNA mutations non-neutral. Mistranslation also renders some beneficial mutations deleterious and vice versa. It increases the probability of fixation of 3 to 8 percent of beneficial mutations. Even though mistranslation increases the incidence of epistasis, it also allows populations evolving on a rugged landscape to evolve modestly higher fitness. Our observations show that mistranslation is an important source of non-genetic variation that can affect adaptive evolution on fitness landscapes in multiple ways.
A pan-cnidarian microRNA is an ancient biogenesis regulator of stinging cells
Authors: Fridrich Arie , Salinas-Saaverda Miguel , Kozlolvski Itamar , Surm Joachim M , Chrysostomou Eleni , Tripathi Abhinandan M , Frank Uri , Moran Yehu 
Published: December 2022

AbstractAn ancient evolutionary innovation of a novel cell-type, the stinging cell (cnidocyte), appeared >600 million years ago in the phylum Cnidaria (sea anemones, corals, hydroids, and jellyfish). A complex bursting nano-injector of venom, the cnidocyst, is embedded in cnidocytes and enables cnidarians paralyzing prey and predators, contributing to this phylum’s evolutionary success. In this work, we show that post-transcriptional regulation by a pan-cnidarian microRNA, miR-2022, is essential for biogenesis of these cells. By manipulation of miR-2022 levels in a transgenic reporter line of cnidocytes in the sea anemoneNematostella vectensis, followed by transcriptomics, single-cell data analysis, prey paralysis assays, and cell sorting of transgenic cnidocytes, we reveal that miR-2022 enables cnidocyte biogenesis, while exhibiting a conserved expression domain with its targets in cnidocytes of other cnidarian species. Thus, here we reveal one of nature’s most ancient microRNA-regulated processes by studying the functional basis for its conservation.
DNA-protein quasi-mapping for rapid differential gene expression analysis in non-model organisms
Authors: Santiago Kyle Christian L. , Shrestha Anish M.S. 
Published: December 2022

AbstractBackgroundConventional differential gene expression analysis pipelines for non-model organisms require computationally expensive transcriptome assembly. We recently proposed an alternative strategy of directly aligning RNA-seq reads to a protein database, and demonstrated drastic improvements in speed, memory usage, and accuracy in identifying differentially expressed genes.ResultHere we report a further speed-up by replacing DNA-protein alignment by quasi-mapping, making our pipeline>1000 × faster than assembly-based approach, and still more accurate. We also compare quasi-mapping to other mapping techniques, and show that it is faster but at the cost of sensitivity.ConclusionWe provide a quick-and-dirty differential gene expression analysis pipeline for non-model organisms without a reference transcriptome, which directly quasi-maps RNA-seq reads to a reference protein database, avoiding computationally expensive transcriptome assembly.
Polo-like kinase 4 (Plk4) potentiatesanoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype
Authors: Fonseca Irina , Horta Cíntia , Ribeiro Ana Sofia , Sousa Barbara , Marteil Gaëlle , Bettencourt-Dias Mónica , Paredes Joana 
Published: December 2022

AbstractPolo-like kinase 4 (Plk4), the major regulator of centriole biogenesis, has emerged as a putative therapeutic target in cancer due to its abnormal expression in human carcinomas, leading to centrosome number deregulation, mitotic defects and chromosomal instability. Moreover, Plk4 deregulation promotes tumor growth and metastasis in mouse models and is significantly associated with poor patient prognosis.Here, we further investigate the role of Plk4 in carcinogenesis and show that its overexpression significantly potentiates resistance to cell death byanoikisof non-tumorigenic p53 knock-out (p53KO) mammary epithelial cells. Importantly, this effect is independent of Plk4’s role in centrosome biogenesis, suggesting that this kinase has additional cellular functions. Interestingly, the Plk4-inducedanoikisresistance is associated with the induction of a stable hybrid epithelial-mesenchymal phenotype and is partially dependent on P-cadherin upregulation. Furthermore, we found that the conditioned media of Plk4-induced p53KO mammary epithelial cells also inducesanoikisresistance of breast cancer cells in a paracrine way, being also partially dependent on soluble P-cadherin secretion.Our work shows, for the first time, that high expression levels of Plk4 induceanoikisresistance of both mammary epithelial cells with p53KO background, as well as of breast cancer cells exposed to their secretome, which is partially mediated through P-cadherin upregulation. These results reinforce the idea that Plk4, independently of its role in centrosome biogenesis, functions as an oncogene, by impacting the tumor microenvironment to promote malignancy.
Label-free and high-throughput removal of residual undifferentiated cells from iPSC-derived spinal-cord progenitor cells
Authors: Nguyen Tan Dai , Chooi Wai Hon , Jeon Hyungkook , Chen Jiahui , Roxby Daniel Ninio , Zu Yao Jerome Tan , Yi-Pin Lee Cheryl , Ng Shi-Yan , Chew Sing Yian , Han Jongyoon 
Published: December 2022

SummaryThe transplantation of spinal cord progenitor cells (SCPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on treating spinal cord injury (SCI). However, the presence of residual undifferentiated iPSCs amongst their differentiated progeny poses a high risk as it can develop teratomas or other types of tumors post-transplantation. Despite the need to remove these residual undifferentiated iPSCs, no specific surface markers can identify them for subsequent removal. By profiling the size of SCPCs after a 10-day differentiation process, we found that the large-sized group contains significantly more cells expressing pluripotent markers. In this study, we employed a sized-based, label-free separation using an inertial microfluidic-based device to remove tumor-risk cells. The device can reduce the number of undifferentiated cells from an SCPC population with high throughput (i.e., > 3 million cells per minute) without affecting cell viability and functions. The sorted cells were verified with immunofluorescence staining, flow cytometry analysis, and colony culture assay. We demonstrated the capabilities of our technology to reduce the percentage of OCT4-positive cells. Our technology has great potential for the ‘downstream processing’ of cell manufacturing workflow, ensuring better quality and safety of transplanted cells.
Dashing Growth Curves – a web application for rapid and interactive analysis of microbial growth curves
Authors: Reiter Michael A. , Vorholt Julia A. 
Published: December 2022

AbstractBackgroundRecording and analyzing microbial growth is a routine task in the life sciences. Microplate readers that record dozens to hundreds of growth curves simultaneously are increasingly used for this task, raising the demand for their rapid and reliable analysis.ResultsHere, we present Dashing Growth Curves, an interactive web application (http://dashing-growth-curves.ethz.ch/) that enables researchers to quickly visualize and analyze growth curves without coding knowledge and independent of operating system. Growth curves can be fitted with Logistic or Gompertz growth models, or manually by selecting the linear growth phase in a logarithmic plot. Furthermore, Dashing Growth Curves automatically groups replicate samples and generates downloadable plots for extracted growth parameters such as growth rate or lag time.ConclusionsDashing Growth Curves is an open-source web application that reduces the time required to analyze microbial growth curves from hours to minutes.