bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contact Stiffness Provides a Unified Frame of Reference for Understanding the Effects of Extracellular Matrix Mechanics on Cell Behaviors
Authors: Zhao Peng , Zhang Zhaoyi , Zheng Yang , Gao Yina , Cao Jialing , Jiang Mingwei , Jiang Yuxuan , Gao Li , Du Jing , Cao Yanping 
Published: September 2022

SUMMARYIn interactions between cells and extracellular matrices (ECMs), contact mechanics theory indicates that local ECM deformation depends on both local and non-local forces imposed by cells. In the present study, we investigated the use of a comprehensive variable, contact stiffness (CS), to interpret cell-ECM interactions. CS defines the relationship between the local ECM deformation and the total force from a cell, integrating the effects of individual variables including ECM stiffness, ECM thickness, and cell adhesion area. Through assessments of ECM mechanosensing by human mesenchymal stem cells (hMSCs) under varied CS conditions, we showed that CS scaled well with both yes-associated protein (YAP) activity and the extent of stem cell differentiation. To reveal the cross-scale mechanism underlying mechanosensing, we propose a CS-based motor clutch model, which suggests that various mechanical stimuli affect cells by altering the CS, thus altering the reaction force from the ECM. Using the proposed model, we revealed the contributions of cell architecture evolution to stem cell differentiation and predicted the influence of a non-adjacent ECM layer on cellular mechanosensing. These results demonstrate that the use of CS provides a quantitative predictive framework that allows researchers to address longstanding questions about the effects of ECM mechanics on cell behaviors.
CIDP: A multi-functional platform for designing CRISPR sgRNAs
Authors: Xu Dong , Zhang Jin , Zhao Xianjia , Jiang Heling , Ma Xiongfeng , Pan Weihua 
Published: September 2022

AbstractMost of sgRNA-design tools can be run under the precondition of the choice of closely-related species. However, it is hard to select an ideal closely-related species, as more and more different species were studied, and this situation was particular seriously in plant studies. Here, we introduced a new software, CRISPR Integrated Design Platform (CIDP), to solve the problem by allowing users to input genomic sequences for designing sgRNAs. The main function of CIDP was to design sgRNAs after building the sgRNA database using the input genomic sequences. Furthermore, in order to minimize the off-target effects, CIDP will search sgRNAs that appear only once across the whole genome on the target sequences. Meanwhile, CIDP set relevant functions to identify shared sgRNAs of a group of genes. Moreover, we also set primer design and sequence extraction functions in CIDP to help users design sgRNAs efficiently.
A time and single-cell resolved model of hematopoiesis
Authors: Kucinski Iwo , Campos Joana , Barile Melania , Severi Francesco , Bohin Natacha , Moreira Pedro N , Allen Lewis , Lawson Hannah , Haltalli Myriam L R , Kinston Sarah J , O’Carroll Dónal , Kranc Kamil R , Göttgens Berthold 
Published: September 2022

AbstractThe paradigmatic tree model of hematopoiesis is increasingly recognized to be limited as it is based on heterogeneous populations and largely inferred from non-homeostatic cell fate assays. Here, we combine persistent labeling with time-series single-cell RNA-Seq to build the first real- time, quantitative model of in vivo tissue dynamics for any mammalian organ. We couple cascading single-cell expression patterns with dynamic changes in differentiation and growth speeds. The resulting explicit linkage between single cell molecular states and cellular behavior reveals widely varying self-renewal and differentiation properties across distinct lineages. Transplanted stem cells show strong acceleration of neutrophil differentiation, illustrating how the new model can quantify the impact of perturbations. Our reconstruction of dynamic behavior from snapshot measurements is akin to how a Kinetoscope allows sequential images to merge into a movie. We posit that this approach is broadly applicable to empower single cell genomics to reveal important tissue scale dynamics information.HighlightsCell flux analysis reveals high-resolution kinetics of native bone marrow hematopoiesisQuantitative model simulates cell behavior in real-time and connects it with gene expression patternsDistinct lineage-affiliated progenitors have unique self-renewal and differentiation propertiesTransplanted HSCs display accelerated stage- and lineage-specific differentiation
AYUKA: A toolkit for fast viral genotyping using whole genome sequencing
Authors: Guerra-Assunção José Afonso , Goldstein Richard , Breuer Judith 
Published: September 2022

AbstractTechnological advances enabled the frequent use of whole genome sequencing in the clinical microbiology laboratory. While generating data is now easier than ever, the computational resources and expertise required for analysis are still a challenge for clinical applications. Since it is not always possible to collect clinical specimens at the peak viral load, sequencing results are also not always amenable for analysis with bioinformatics pipelines that always require high quality data.Here we present a fast and reliable method, we named AYUKA, for analysis of viral sequencing data that does not require data pre-processing and provides quality control metrics including estimates for sequencing depth and genome coverage, as well as identifying the viral genotypes in a sample and distinguishing mixed infection from recombinants.This method can be applied to any virus where a classification by genotype is employed and determining it is relevant. We generated a validation dataset composed of cultured and sequenced reference adenoviruses from distinct species, that we compared with the gold standard clinical processing pipeline currently implemented to demonstrate reliability. The validation shows better sensitivity than mapping and perfect specificity in detecting the correct genotypes and in a wide range of adenovirus species. Run time was consistently under one minute per sample on a standard laptop, allowing the analysis of more than 100 samples per hour.This open-source method is available at https://github.com/afonsoguerra/AYUKA and precomputed databases are available at https://zenodo.org/record/6521576 allowing analysis of raw data straight from the sequencer within minutes on a standard computer, with minimum setup or expertise required to perform the analysis.The information contained within the AYUKA report can be of use for both the clinical team that collected the sample, but also for guiding the bioinformatics analysis team in the in-depth downstream analyses and genetic epidemiology investigations.
Red light-emitting short Mango-based system enables tracking a mycobacterial small noncoding RNA in infected macrophages
Authors: Bychenko Oksana S. , Khrulev Alexei A. , Svetlova Julia I. , Tsvetkov Vladimir B. , Kamzeeva Polina N. , Skvortsova Yulia V. , Tupertsev Boris S. , Ivanov Igor A. , Aseev Leonid V. , Khodarovich Yuriy M. , Belyaev Evgeny S. , Kozlovskaya Liubov I. , Zatsepin Timofei S. , Azhikina Tatyana L. , Varizhuk Anna M. , Aralov Andrey V. 
Published: September 2022

AbstractProgress in the studies of RNA metabolism and function relies largely on molecular imaging systems, including those comprising a fluorogenic dye and an aptamer-based fluorescence-activating tag. G4 aptamers of Mango family, typically combined with a duplex/hairpin scaffold, activate fluorescence of a green-emitting dye TO1-biotin and hold great promise for intracellular RNA tracking. Here, we report a new Mango-based imaging platform. Its key advantages are tunability of spectral properties and applicability for visualization of small RNA molecules that require minimal tag size. The former advantage is due to an expanded (green-to-red-emitting) palette of TO1-inspired fluorogenic dyes, and the latter is ensured by the truncated duplex scaffold. To illustrate applicability of the improved platform, we tagged Mycobacterium tuberculosis sncRNA with the shortened aptamer-scaffold tag and visualized it in bacteria and bacteria-infected macrophages using the new red light-emitting Mango-activated dye.
Topical GZ21T inhibits the growth of actinic keratoses in a UVB induced model of skin carcinogenesis
Authors: Bordeaux Zachary A. , Choi Justin , Braun Gabriella , Davis Cole , Marani Melika , Lee Kevin , Samuel Christeen , Adams Jackson , Windom Reed , Pollizzi Anthony , Kambala Anusha , Cornman Hannah , Reddy Sriya V. , Lu Weiying , Oladipo Olusola O. , Alphonse Martin P. , West Cameron E. , Kwatra Shawn G. , Kwatra Madan M. 
Published: September 2022

ABSTRACTActinic keratoses (AKs) are premalignant intraepidermal neoplasms that occur as a result of cumulative sun damage. AKs commonly relapse, and up to 16% undergo malignant transformation into cutaneous squamous cell carcinoma (cSCC). There is a need for novel therapies that reduce the quantity and surface area of AKs as well as prevent malignant transformation to cSCCs. We recently showed that GZ17-6.02, an anti-cancer agent composed of curcumin, haramine, and isovanillin, inhibited the growth of H297.T cells. The present study evaluated the efficacy of a novel topical formulation of GZ17-6.02, known as GZ21T, in a murine model of AK generated by exposing SKH1 mice to ultraviolet irradiation. Treatment of mice with topical GZ21T inhibited the growth of AKs by decreasing both lesion count (p=.028) and surface area occupied by tumor (p=.026). GZ21T also suppressed the progression of AKs to cSCC by decreasing the count (p=.047) and surface area (p=.049) of lesions more likely to represent cSCC. RNA sequencing and proteomic analyses revealed that GZ21T suppressed several pathways, including MAPK (p=.026), Pi3K-Akt (p=.028), HIF-1α (p=.030), Wnt (p=.031), insulin (p=.011), and ErbB (p=.006) signaling. GZ21T also upregulated the autophagy-promoting protein AMPK, while suppressing proteins such as PD-L1, glutaminase, pAkt1 S473, and eEF2K.GRAPHICAL ABSTRACT
Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice
Authors: Prompetchara Eakachai , Ketloy Chutitorn , Alameh Mohamad-Gabriel , Tarakhet Kittipan , Kaewpang Papatsara , Yostrerat Nongnaphat , Pitakpolrat Patrawadee , Buranapraditkun Supranee , Manopwisedcharoen Suwimon , Thitithanyanont Arunee , Jongkaewwattana Anan , Hunsawong Taweewan , Im-Erbsin Rawiwan , Reed Matthew , Wijagkanalan Wassana , Patarakul Kanitha , Palaga Tanapat , Lam Kieu , Heyes James , Weissman Drew , Ruxrungtham Kiat 
Published: September 2022

AbstractEstablishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP) “ChulaCov19”. In BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 μg given 2 doses, 21 days apart, elicited robust neutralizing antibody (NAb) and T cells responses in a dose-dependent relationship. The geometric mean titer (GMT) of micro-virus neutralizing (micro-VNT) antibody against wild-type virus was 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induced better cross-neutralizing antibody against Delta and Omicron variants. This elicited specific immunogenicity was significantly higher than those induced by homologous prime-boost with inactivated (CoronaVac) or viral vector (AZD1222) vaccine. In heterologous prime-boost study, mice primed with either CoronaVac or AZD1222 vaccine and boosted with 5 μg ChulaCov19 generated NAb 7-fold higher against wild-type virus (WT) and was also significantly higher against Omicron (BA.1 and BA.4/5) than homologous CoronaVac or AZD1222 vaccination. AZD1222-prime/mRNA-boost had mean spike-specific IFNγ positive T cells of 3,725 SFC/106 splenocytes, which was significantly higher than all groups except homologous ChulaCov19. Challenge study in human-ACE-2-expressing transgenic mice showed that ChulaCov19 at 1 μg or 10 μg protected mice from COVID-19 symptoms, prevented SARS-CoV-2 viremia, significantly reduced tissue viral load in nasal turbinate, brain, and lung tissues 99.9-100%, and without anamnestic of Ab response which indicated its protective efficacy. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or a boost vaccination and has entered clinical development.
Phosphoproteomics data-driven signalling network inference: does it work?
Authors: Sriraja Lourdes O. , Werhli Adriano , Petsalaki Evangelia 
Published: September 2022

AbstractThe advent in high throughput global phosphoproteome profiling has led to wide phosphosite coverage and therefore the need to predict kinase substrate associations from these datasets. However, for multiple substrates, the regulatory kinase is unknown due to biased and incomplete interactome databases. In this study we compare the performance of six pairwise measures to predict kinase substrate associations using a purely data driven approach on publicly available dynamic time resolved and perturbation phosphoproteome data using mass spectrometry profiling. First, we validated the performance of these measures using as a reference both a literature-based phosphosite-specific protein interaction network and a predicted kinase substrate (KS) interactions set. The overall performance in predicting kinase-substrate associations using pairwise measures across both database-derived and predicted interactomes was poor. To expand into the wider interactome space, the performance of these measures was evaluated against a network compiled from pairs of substrates regulated by the same kinase (substrate-substrate associations). Similar to the kinase substrate predictions, a purely statistical approach to predict substrate-substrate associations was also poor. However, the addition of a sequence similarity filter for substrate-substrate associations led to a boost in performance and to the inference of statistically significant substrate-substrate associations. Our findings imply that the use of a filter to reduce the search space, such as a sequence similarity filter, can be used prior to the application of network inference methods to reduce noise and boost the signal. We also find that the current gold standard for reference sets is not adequate for evaluation as it is limited and context-agnostic. Therefore, there is a need for additional evaluation methods that have increased coverage and take into consideration the context-specific nature of kinase substrate associations.
The Intestinal Microbiome, Dietary Habits, and Physical and Psychological Resilience in Postpartum Women
Authors: Matsunaga Michiko , Takeuchi Mariko , Watanabe Satoshi , Takeda Aya K. , Kikusui Takefumi , Mogi Kazutaka , Nagasawa Miho , Hagihara Keisuke , Myowa Masako 
Published: September 2022

AbstractThe population of postpartum women suffering from mental illness is increasing steadily, particularly under conditions of the COVID-19 pandemic. Identifying factors that contribute to resilience in postpartum women is urgently needed to decrease risks of poor physical and psychological functioning. Studies have linked variations in the intestinal microbiota to depression in clinical samples, but the impacts in postpartum women in a Japanese population are unknown. We conducted two studies to examine the links between intestinal microbiota, physical condition, and psychological state in nonclinical, postpartum Japanese women. Our results show that decreasing Lachnospira and alpha diversity of microbiome is related to high mental health risk (i.e., parenting stress and/or depression). Psychological resilience and physical conditions were associated with relative abundances of genera Blautia, Clostridium, Eggerthella. This study contributes to further understanding of the gut-brain axis mechanisms and supports proposals for interventions to enhance resilience in postpartum women.
DESIGNING OF CUSTOM BARCODES FOR SEQUENCING ON THE MGI PLATFORM
Authors: Bulusheva Irina , Shmitko Anna , Vasiliadis Julia , Suchalko Oleg , Syrko Denis , Belova Vera , Korostin Dmitriy 
Published: September 2022

AbstractThe recently launched MGI platform (DNBSEQ-G50, -G400 and -T7 sequencers) has been gaining popularity for next-generation sequencing. However, the barcode set for library preparation provided by the manufacturer has certain limitations on the number of samples that can be sequenced at a time and the compatibility of barcodes from different or incomplete sets as well as a ratio between the samples.In this paper, we present a protocol for designing custom barcodes expanding the pre-existing barcode set and demonstrate its performance on the MGI Tech Co. Ltd. (China) machines. We developed a universal “quad method” which allows for simultaneous sequencing of any number of samples up to 252 per lane which is multiple of 4 or 4n+2. Here, we describe this method, its analysis, verification, and integration into the sequencing as well as its validation for sequencing using the DNBSEQ G-400 machine.
Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors
Authors: Bhin Jinhyuk , Dias Mariana Paes , Gogola Ewa , Rolfs Frank , Piersma Sander R. , de Bruijn Roebi , de Ruiter Julian R. , van den Broek Bram , Duarte Alexandra A. , Sol Wendy , van der Heijden Ingrid , Bakker Lara , Kaiponen Taina S. , Lieftink Cor , Morris Ben , Beijersbergen Roderick L. , van de Ven Marieke , Jimenez Connie R. , Wessels Lodewyk F. A. , Rottenberg Sven , Jonkers Jos 
Published: September 2022

SUMMARYBRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR-defect, BRCA1/2-deficient cancers are sensitive to poly(ADP-ribose) polymerase inhibitors (PARPi) but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, but their relevance in the clinic remains elusive. To investigate which BRCA1/2-independent mechanisms drive spontaneous resistance in vivo, we combined molecular profiling with functional analysis of the HR status of matched PARPi-naïve and PARPi-resistant mouse mammary tumors harboring large intragenic deletions that prevent functional restoration of BRCA1/2. We observed restoration of HR in 64% of PARPi-resistant BRCA1-deficient tumors but none in the PARPi-resistant BRCA2-deficient tumors. Moreover, we found that 53BP1 loss is the prevalent resistance mechanism in HR-proficient BRCA1-deficient tumors, whereas resistance in BRCA2-deficient tumors is mainly induced by the loss of PARG. Our combined multi-omics analysis catalogued additional genes and pathways potentially involved in modulating PARPi response.
Genome-wide metabolite quantitative trait loci analysis (mQTL) in red blood cells from volunteer blood donors
Authors: Moore Amy , Busch Michael P , Dziewulska Karolina , Francis Richard O. , Hod Eldad A. , Zimring James C , D’Alessandro Angelo , Page Grier P 
Published: September 2022

AbstractThe Red Blood Cell (RBC)-Omics study, part of the larger NHLBI-funded Recipient Epidemiology and Donor Evaluation Study (REDS-III), aims to understand the genetic contribution to blood donor RBC characteristics. Previous work identified donor demographic, behavioral, genetic and metabolic underpinnings to blood donation, storage, and - to a lesser extent - transfusion outcomes, but none have yet linked the genetic and metabolic bodies of work. We performed a Genome-Wide Association (GWA) analysis using RBC-Omics study participants with generated untargeted metabolomics data to identify metabolite quantitative trait loci (mQTL) in RBCs. We performed GWA analyses of 382 metabolites in 243 individuals imputed using the 1000 Genomes Project phase 3 all-ancestry reference panel. Analyses were conducted using ProbABEL and adjusted for sex, age, donation center, number of whole blood donations in the past two years, and first ten principal components of ancestry. Our results identified 423 independent genetic loci associated with 132 metabolites (p < 5×10−8). Potentially novel locus-metabolite associations were identified for FLVCR1 and choline, and for LPCAT3 and the lysophosphatidylserine 16.0, 18.0, 18.1, and 18.2; these associations are supported by published rare disease and mouse studies. We also confirmed previous metabolite GWA results for associations including N(6)-Methyl-L-lysine and PYROXD2, and various carnitines and SLC22A16. Association between pyruvate levels and G6PD polymorphisms was validated in an independent cohort and novel murine models of G6PD deficiency (African and Mediterranean variants). We demonstrate that it is possible to perform metabolomics-scale GWA analyses with a modest, trans-ancestry sample size.Key pointsMetabolite heterogeneity in fresh (<14 day old) RBCs donated by volunteer donors is linked to genetic polymorphisms;We report 2,831 high-confidence SNP-metabolite linkages (p < 5.0 × 10−8). Pyruvate levels in fresh RBCs are associated with glucose-6-phosphate dehydrogenase (G6PD) status
MOAHIT: a web tool for visualizing tumor multi-omics data with human anatomy heatmaps
Authors: Zhou Chaozheng , Lin Anqi , Li Mengyao , Qi Chang , Zhang Jian , Luo Peng 
Published: September 2022

AbstractMulti-omics data plays an important role in cancer research, helping clinicians to better explore drug targets and biomarkers. At present, there exist several databases including TCGA (the Cancer Genome Atlas) and GDSC (Genomics of Drug Sensitivity in Cancer), which contain multi omics data on multiple cancer species, as well as various web tools for analyzing the multi-omics data, which are widely used in oncology research. Tumor heterogeneity is a widespread phenomenon, reflected by differences in multi-omics data of cancers originating from different tissues and organs. However, there is a lack of convenient analysis and visualization tools to explore tumor heterogeneity. As a result, we developed a web tool called Multi-Omics Anatomy Heatmap in Tumors (MOAHIT) based on shiny programming. This tool enables users to analyze and visualize the heterogeneity of human tissues. In addition, MOAHIT enables users to produce a beautiful human anatomy heatmap to visualize the heterogeneity between distinct cancers in the multi-omics data.
Antibiotics that affect translation can antagonize phage infectivity by interfering with the deployment of counter-defences
Authors: Pons Benoit J. , Dimitriu Tatiana , Westra Edze R. , van Houte Stineke 
Published: September 2022

AbstractIt is becoming increasingly clear that antibiotics can both positively and negatively impact the infectivity of bacteriophages (phage), but the underlying mechanisms often remain unclear. Here we demonstrate that antibiotics that target the protein translation machinery can fundamentally alter the outcome of bacteria-phage interactions by interfering with the production of phage-encoded counter-defence proteins. Specifically, using Pseudomonas aeruginosa PA14 and phage DMS3vir as a model, we show that bacteria with CRISPR-Cas immune systems have elevated levels of immunity against phage that encode anti-CRISPR (acr) genes when translation inhibitors are present in the environment. CRISPR-Cas are highly prevalent defence systems that enable bacteria to detect and destroy phage genomes in a sequence-specific manner. In response, many phages encode acr genes that are expressed immediately following infection to inhibit key steps of the CRISPR-Cas immune response. Our data show that while phage carrying acr genes can amplify efficiently on bacteria with CRISPR-Cas immune systems in the absence of antibiotics, the presence of antibiotics that act on protein translation prevents phage amplification, while protecting bacteria from lysis. These results help to understand how antibiotics-phage synergy and antagonism depend on the molecular interactions that define phage infectivity and host immunity.