bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of cruciate ligament surgery in Japan: A retrospective cohort study from 2014 to 2019
Authors: Uchino Shota , Taguri Masataka 
Published: July 2023

AbstractUnderstanding the incidence and trends of cruciate ligament (CL) surgeries in Japan is crucial for providing effective healthcare services. This study aimed to use open data available from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) to determine the changes over time in CL surgeries and to analyze the characteristics of the Japanese population in terms of sex and age. We retrospectively identified CL surgeries of the knee joint registered from April 2014 to March 2020 using the NDB open data. Data on sex, age, and practice were extracted to determine the number of cases per 100,000 population. Trends in the annual incidence of CL surgeries were evaluated using Poisson regression analysis. In total, 112,686 CL surgeries were performed from 2014 to 2019. Arthroscopic ligament reconstruction accounted for 98% of all the cases. The number of surgeries performed had increased significantly from 16,975 in 2014 to 19,735 in 2019 (P<0.001). Overall, CL surgeries were most common in the 15–19 years age group, followed by the 20–29 years age group. However, these trends differed between males and females. The incidence of CL surgery in Japan has increased, and its characteristics vary by gender and age. These characteristics have been identified not only in younger patients but also in middle-aged and older patients. It would be valuable to further investigate the general patterns of CL surgery in Japan.
Influence of Geographical Aspect and Topography on Canopy Openness in Tropical Rainforests of Sri Lanka along an Altitudinal Gradient
Authors: Madhumali R.M.C. , Wahala W.M.P.S.B. , Sanjeewani H.K.N. , Samarasinghe D.P. , De Costa W.A.J.M. 
Published: July 2023

ABSTRACTSolar radiation energy is a limiting factor for forest growth in humid tropical environments. Radiation incident on a forest canopy varies with azimuth angle of incident radiation and aspect of the forest terrain. The objective of this work was to determine the influence of the geographical aspect and azimuth of incident radiation on the canopy structure of tropical rainforests of Sri Lanka (TRFSL). Hemispherical photography was used to capture canopy images of TRFSLs in ten permanent sampling plots across an altitudinal range from 117 m to 2132 m above mean sea level. Fraction of visible sky (Vsky) in 144 sectors of the canopy hemisphere, defined by 18 zenith angle (ZnA) × 8 azimuth angle (AzA) segments, was determined using image analysis. Canopy openness, quantified as Vskyof the overall hemisphere, increased with increasing altitude. Canopy leaf area index, decreased linearly with altitude and had a negative relationship with Vsky. Canopy openness of the top one-third (ZnA=0°–30°) of the hemisphere (Vsky(0-30)) was significantly (p<0.05) lower on the east (AzA=90°) than on the west (AzA=270°) in a majority of plots. Similarly, Vsky(0-30)was lower on the northern (AzA=0°) than the southern (AzA =180°) canopy segment. These patterns were altered in plots where nearby mountains and slope aspect of the plot influenced incident radiation. These observations suggest a hypothesis that canopies of TRFSL are structured to maximize radiation capture by allocating more leaf area, and therefore having lower canopy openness, on sides of the canopy which face directions of greater radiation receipt.
Structure and Biosynthesis of Hectoramide B, a Linear Depsipeptide from the Marine CyanobacteriumMoorena producensJHB Discovered via Co-culture withCandida albicans
Authors: Ngo Thuan-Ethan , Ecker Andrew , Guild Aurora , Remmel Ariana , Boudreau Paul D. , Alexander Kelsey L. , Naman C. Benjamin , Glukhov Evgenia , Avalon Nicole E. , Shende Vikram V. , Gerwick Lena , Gerwick William H. 
Published: July 2023

ABSTRACTThe tropical marine cyanobacteriumMoorena producensJHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies of this strain led to the discovery of several novel compounds such as the hectochlorins and jamaicamides; however, bioinformatic analyses of its genome suggested that there were many more cryptic biosynthetic gene clusters yet to be characterized. To potentially stimulate the production of novel compounds from this strain, it was co-cultured withCandida albicans. From this experiment, we observed the increased production of a new compound that we characterize here as hectoramide B. Bioinformatic analysis of theM. producensJHB genome enabled the identification of a putative biosynthetic gene cluster responsible for hectoramide B biosynthesis. This work demonstrates that co-culture competition experiments can be a valuable method to facilitate the discovery of novel natural products from cyanobacteria.Abstract Figure
Inference of host-pathogen interaction matrices from genome-wide polymorphism data
Authors: Märkle Hanna , John Sona , Metzger Lukas , Consortium STOP-HCV , Azim Ansari M , Pedergnana Vincent , Tellier Aurélien 
Published: July 2023

AbstractCoevolution is defined as the evolutionary change in one antagonist (host) in response to changes in the other antagonist (pathogen). At the genetic level, these changes are determined by genotype x genotype (GxG) interactions. We build on a general theoretical model of a host-pathogen interaction to derive four indices to retrieve key features of GxG interactions. The four developed indices extract relevant information from polymorphism data of randomly sampled uninfected hosts as well as infected hosts and their respective pathogen strains. Using these indices as summary statistics in an Approximate Bayesian Computation method, we can show their power to discriminate between GxG interaction matrices. Second, we apply our ABC method to a SNP data set of 451 European humans and their infecting Hepatitis C Virus (HCV) strains supplemented by polymorphism data of 503 individuals from the 1,000 genomes project. As our indices encompass and extend previous natural co-GWAs we recover many of the associations previously reported for this dataset and infer their underlying interaction matrix. We reveal a new candidate gene for resistance to HCV in the human genome, and two groups of significant GxG associations exhibiting gene-for-gene interactions. We suggest that the inferred types of GxG interactions result from the recent expansion, adaptation and low prevalence of the HCV virus population in Europe.Significance statementWhy are some host individuals susceptible/resistant to infection by certain pathogen genotypes and others not? Understanding the genetic characteristics of genes driving host-pathogen interactions is crucial to predict epidemics. We develop four indices based on a mathematical model and build a Bayesian statistical method computing these indices on full genome data of infected hosts and their infecting pathogen strains and data of non-infected hosts. We can pinpoint the genes underlying host-pathogen interactions and infer their characteristics. Applying our framework to data from European humans and the Hepatitis C virus, we discover a new potential resistance gene in humans and reveal how the virus has adapted in the last 150 years to match the genetic diversity of the European human population.
Directional Sensitivity of Cortical Neurons Towards TMS Induced Electric Fields
Authors: Weise Konstantin , Worbs Torge , Kalloch Benjamin , Souza Victor H. , Jaquier Aurélien Tristan , Geit Werner Van , Thielscher Axel , Knösche Thomas R. 
Published: July 2023

AbstractWe derived computationally efficient average response models of different types of cortical neurons, which are subject to external electric fields from Transcranial Magnetic Stimulation. We used 24 reconstructions of pyramidal cells (PC) from layer 2/3, 245 small, nested, and large basket cells from layer 4, and 30 PC from layer 5 with different morphologies for deriving average models. With these models, it is possible to efficiently estimate the stimulation thresholds depending on the underlying electric field distribution in the brain, without having to implement and compute complex neuron compartment models. The stimulation thresholds were determined by exposing the neurons to TMS-induced electric fields with different angles, intensities, pulse waveforms, and field decays along the somato-dendritic axis. The derived average response models were verified by reference simulations using a high-resolution realistic head model containing several million neurons. Differences of only 1-2% between the average model and the average response of the reference cells were observed, while the computation time was only a fraction of a second compared to several weeks using the cells. Finally, we compared the model behavior to TMS experiments and observed high correspondence to the orientation sensitivity of motor evoked potentials. The derived models were compared to the classical cortical column cosine model and to simplified ball-and-stick neurons. It was shown that both models oversimplify the complex interplay between the electric field and the neurons and do not adequately represent the directional sensitivity of the different cell types.The derived models are simple to apply and only require the TMS induced electric field in the brain as input variable. The models and code are available to the general public in open-source repositories for integration into TMS studies to estimate the expected stimulation thresholds for an improved dosing and treatment planning in the future.
Cross-regulation between proteome reallocation and metabolic flux redistribution governs bacterial growth transition kinetics
Authors: Yuan Huili , Bai Yang , Li Xuefei , Fu Xiongfei 
Published: July 2023

AbstractBacteria need to adjust their metabolism and protein synthesis simultaneously to adapt to changing nutrient conditions. It’s still a grand challenge to predict how cells coordinate such adaptation due to the cross-regulation between the metabolic fluxes and the protein synthesis. Here we developed a dynamic Constrained Allocation Flux Balance Analysis method (dCAFBA), which integrates flux-controlled proteome allocation and protein limited flux balance analysis. This framework can predict the redistribution dynamics of metabolic fluxes without requiring detailed enzyme parameters. We reveal that during nutrient up-shifts, the calculated metabolic fluxes change in agreement with experimental measurements of enzyme protein dynamics. During nutrient down-shifts, we uncover a switch of metabolic bottleneck from carbon uptake proteins to metabolic enzymes, which disrupts the coordination between metabolic flux and their enzyme abundance. Our method provides a quantitative framework to investigate cellular metabolism under varying environments and reveals insights into bacterial adaptation strategies.
Filter-aided extracellular vesicle enrichment (FAEVEr) for proteomics
Authors: Pauwels Jarne , Van de Steene Tessa , Van de Velde Jana , Muyer Freya De , Pauw Danaë De , Baeke Femke , Eyckerman Sven , Gevaert Kris 
Published: July 2023

AbstractExtracellular vesicles (EVs), membrane-delimited nanovesicles that are secreted by cells into the extracellular environment, are gaining substantial interest due to their involvement in cellular homeostasis and their contribution to disease pathology. The latter in particular has led to an exponential increase in interest in EVs as they are considered to be circulating packages containing potential biomarkers and are also a possible biological means to deliver drugs in a cell-specific manner. However, several challenges hamper straightforward proteome analysis of EVs as they are generally low abundant and reside in complex biological matrices. These matrices typically contain abundant protein concentrations that vastly exceed those of the EV proteome. Therefore, extensive EV isolation and purification protocols are imperative and many have been developed, including (density) ultracentrifugation, size-exclusion and precipitation methods. Here, we describe filter-aided extracellular vesicle enrichment (FAEVEr) as an approach based on 300 kDa MWCO filtration that allows the processing of multiple samples in parallel within a reasonable timeframe and at moderate cost. We demonstrate that FAEVEr is capable of quantitatively retaining EV particles on filters, whilst allowing extensive washing with the mild detergent TWEEN-20 to remove interfering non-EV proteins. The retained particles are directly lysed on the filter for a complete recovery of the EV protein cargo towards proteome analysis. Here, we validate and optimize FAEVEr on recombinant EV material and apply it on conditioned medium as well as on complex serum. Our results indicate that EVs isolated from MCF7 cells cultured with or without serum have a drastic different proteome because of nutrient deprivation.
TRIB1 modulates transcriptional programming in breast cancer cells to regulate cell proliferation
Authors: McMillan Hamish D. , Papachristou Evangelia K. , Hazlett Jody , Omarjee Soleilmane , Carroll Jason S. , Black Michael A. , Mace Peter D. , Dunbier Anita K. 
Published: July 2023

AbstractThe pseudokinase Tribbles Homolog 1 (TRIB1) is a known driver of tumorigenesis in acute myeloid leukemia and is encoded upstream of the oncogeneMYCat the 8q24 locus. We observed thatTRIB1/MYCco-amplification is associated with decreased relapse-free and overall survival in breast cancer patients, but the role ofTRIB1in this disease has not been well characterized.TRIB1knockdown in multiple breast cancer cell lines inhibited cell proliferation and suppressedMYCexpression, implicatingTRIB1in breast cancer cell proliferation. Transcriptomic and cell cycle analysis revealed cell cycle regulation as the likely mechanism through whichTRIB1influences breast cancer cell proliferation.TRIB1knockdown also resulted in significant changes in both estrogen receptor (ER) and β-catenin associated transcription. Interrogating the TRIB1 interactome in breast cancer cells by qPLEX-RIME reinforced the known association between TRIB1 and ubiquitination, while revealing a range of previously undescribed TRIB1 associated factors. Further analysis of the association between TRIB1, β-catenin and FERMT2 suggests TRIB1 may regulate β-catenin activity by controlling the levels of both β-catenin, and its co-factor FERMT2. Together, these results suggest that coregulation of β-catenin and ER-driven transcription by TRIB1, facilitates regulation ofMYCexpression and breast cancer cell proliferation.SignificanceThe pseudokinaseTRIB1is frequently co-amplified in breast cancers with the potent oncogeneMYC, although the functional consequences of this event are not well understood. This study demonstratesTRIB1is a regulator of cell cycle progression andMYCexpression in breast cancer cells. It also profilesTRIB1-associated proteins in breast cancer cells, demonstrating conservation of TRIB1’s canonical interaction with COP1 and reveals associations with members of the wider ubiquitination machinery, a range of transcriptional regulators and chromatin remodelers. The data presented provide insight into the function of TRIB1 in breast cancer and the role of TRIB1 in transcriptional regulation.
SoMAS: Finding somatic mutations associated with alternative splicing in human cancers
Authors: Tan Hua , Gotea Valer , Seidel Nancy E. , Holland David O. , Fedkenheuer Kevin , Jaiswal Sushil K. , Bang-Christensen Sara , Elnitski Laura 
Published: July 2023

AbstractAberrant alternative splicing is prevalent in cancer and affects most cancer hallmarks involving proliferation, angiogenesis, and invasion. Somatic point mutations can exert their cancer-driving functions via splicing disruption. We propose “SoMAS” (SomaticMutation associated withAlternativeSplicing), an efficient computational pipeline based on principal component analysis techniques, to explore the role of somatic mutations in shaping the landscape of alternative splicing via bothcis- andtrans-acting mechanisms. Applying SoMAS to 33 cancer types consisting of 9,738 tumor samples in The Cancer Genome Atlas, we identified 908 somatically mutated genes significantly associated with altered isoform expression in three or more cancer types. These genes include many well-known oncogenes/suppressor genes, RNA binding protein and splicing factor genes with both biological and clinical significance. Many of our identified SoMAS genes were corroborated to affect gene splicing by independent cohorts and/or methodologies. With SoMAS, we for the first time demonstrate the potential network of somatic mutations associated with the overall splicing profiles of cancer transcriptomes, bridging the genetic and epigenetic regulation of human tumorigenesis in an innovative way.
Exploring G-quadruplex structure inPRCC-TFE3fusion Oncogene: Plausible use as anti cancer therapy for translocation Renal cell carcinoma (tRCC)
Authors: Neha  , Das Parimal 
Published: July 2023

AbstractTheTFE3fusion gene, byproduct of Xp11.2 translocation, is the diagnostic marker for translocation renal cell carcinoma (tRCC). Absence of any clinically recognized therapy for tRCC, pressing a need to create novel and efficient therapeutic approaches. Previous studies shown that stabilization of the G-quadruplex structure in oncogenes suppresses their expression machinery. To combat the oncogenesis caused by fusion genes, our objective is to locate and stabilize the G-quadruplex structure within thePRCC-TFE3fusion gene. Using the Quadruplex- forming G Rich Sequences (QGRS) mapper and the Non-B DNA motif search tool (nBMST) online server, we found putative G-quadruplex forming sequences (PQS) in thePRCC-TFE3fusion gene. Circular dichroism demonstrating a parallel G-quadruplex in the targeted sequence. Fluorescence and UV-vis spectroscopy results suggest that pyridostatin binds to this newly discovered G-quadruplex. The PCR stop assay, as well as transcriptional or translational inhibition by PQS, revealed that stable G-quadruplex formation affects biological processes. Confocal microscopy of HEK293T cells transfected with the fusion transcript confirmed G- quadruplexes formation in cell. This investigation may shed light on G-quadruplex’s functions in fusion genes and may help in the development of therapies specifically targeted against fusion oncogenes, which would enhance the capability of current tRCC therapy approach.
Activation of goblet cell stress sensor IRE1β is controlled by the mucin chaperone AGR2
Authors: Cloots Eva , Guilbert Phaedra , Provost Mathias , Neidhardt Lisa , Van de Velde Evelien , Fayazpour Farzaneh , Sutter Delphine De , Savvides Savvas N. , Eyckerman Sven , Janssens Sophie 
Published: July 2023

AbstractAs secretory cells specialized in the production of mucins, intestinal goblet cells are challenged by the need for efficient protein folding. Goblet cells express Inositol-Requiring Enzyme 1β (IRE1β), a unique unfolded protein response (UPR) sensor that is part of an adaptive mechanism that regulates the demands of mucin production and secretion. However, how IRE1β activity is tuned to mucus folding load remains unknown. We identified the disulfide isomerase and mucin chaperone AGR2 as a goblet cell specific protein that crucially regulates IRE1β-, but not IRE1α-mediated signaling. AGR2 binding to IRE1β disrupts IRE1β dimerization, thereby blocking its downstream endonuclease activity. Depletion of endogenous AGR2 from goblet cells induces spontaneous IRE1β activation, suggesting that alterations in AGR2 availability in the endoplasmic reticulum sets the threshold for IRE1β activation. We found that AGR2 mutants lacking their catalytic cysteine or displaying the disease-associated mutation H117Y were no longer able to dampen IRE1β activity. Collectively, these results demonstrate that AGR2 is a central chaperone regulating the goblet cell UPR by acting as a rheostat of IRE1β endonuclease activity.
Bioinformatic correction of bacterial morphology-based extraction bias and chimeras in microbiome sequencing data
Authors: Rauer Luise , De Tomassi Amedeo , Müller Christian L. , Hülpüsch Claudia , Traidl-Hoffmann Claudia , Reiger Matthias , Neumann Avidan U. 
Published: July 2023

IntroductionMicrobiome amplicon sequencing data are distorted by multiple protocol-dependent biases, originating from bacterial DNA extraction, contamination, sequence errors, and chimeras. In particular, extraction bias is a major confounder in sequencing-based microbiome analyses, with no correction method available to date. Here, we suggest using mock community controls to bioinformatically correct extraction bias based on morphological properties.MethodsWe compared dilution series of 3 mock communities with an even or staggered composition. DNA was extracted with 8 different extraction protocols (2 buffers, 2 extraction kits, 2 lysis conditions). Extracted DNA was sequenced (V1-V3 16S rRNA gene) together with corresponding DNA mocks. Sequences were denoised using DADA2, and annotated by matching against mock reference genomes.ResultsMicrobiome composition was significantly different between extraction kits and lysis conditions, but not between buffers. Independent of the extraction protocol, chimera formation increased with high input cell number. Contaminants originated mostly from buffers, and considerable cross-contamination was observed in low-input samples. Comparison of microbiome composition of the cell mocks to corresponding DNA mocks revealed taxon-specific protocol-dependent extraction bias. Strikingly, this extraction bias per species was predictable by bacterial cell morphology. Morphology-based bioinformatic correction of extraction bias significantly improved sample compositions when applied to different samples, even with different taxa.ConclusionsOur results indicate that higher DNA density increases chimera formation during PCR amplification. Furthermore, we show that bioinformatic correction of extraction bias is feasible based on bacterial cell morphology.
A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
Authors: Suzuki Sho W. , West Matthew , Zhang Yichen , Fan Jenny S. , Roberts Rachel T. , Odorizzi Greg , Emr Scott D. 
Published: July 2023

ABSTRACTEndosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intralumenal vesicles (ILVs) at endosomes byEndosomalSortingComplexRequired forTransport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB formation.