bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis
Authors: Li Chao , Li Jiayi , Argall-Knapp Zach , Hendrikse Nathan W. , Farooqui Mehtab A. , Raykowski Bella , King Anna , Nong Serratt 
Published: March 2024

AbstractUsing a combined top-down (i.e., operator-directed) and bottom-up (i.e., cell-directed) strategy, we present an Under-oil Open Microfluidic System (UOMS)-based microtumor model for investigating tumor cell migration and anti-metastasis drug test. Compared to the mainstream closed microfluidics-based microtumor models, the UOMS microtumor model features: i) micrometer-scale lateral resolution of surface patterning with open microfluidic design for flexible spatiotemporal sample manipulation (i.e., top-down); ii) self-organized extracellular matrix (ECM) structures and tumor cell-ECM spontaneous remodeling (i.e., bottom-up); and iii) free physical access to the samples on a device with minimized system disturbance. The UOMS microtumor model is used to test an anti-metastasis drug (incyclinide, aka CMT-3) with a triple negative breast cancer cell line (MDA-MB-231). Thein vitroresults show a suppression of tumor cell migration and ECM remodeling echoing with thein vivomice metastasis results.
Evaluation ofOctopus mayaenzyme activity of the digestive gland and gastric juice
Authors: Pineda-Suazo Daisy , Escobedo-Hinojosa Wendy , Canseco Lenin E. Fabian , Gallardo Pedro , Ojeda Cintia Moguel , Caamal-Monsreal Claudia , Sánchez-Arteaga Ariadna , Rosas Carlos 
Published: March 2024

AbstractBackgroundAs the demand forOctopus mayagrows, sustainable farming practices become essential to prevent overexploitation. Thus, its farming development can be a sustainable alternative to traditional fishing. Understanding the digestive dynamics is essential for devising optimal dietary formulations in aquaculture, particularly the role of enzymes like cathepsins and others. Despite the progress in understanding cephalopod digestion, little is known about the specific functioning of the digestive enzymes responsible for breaking down protein substrates. This knowledge gap underscores the need for further research to ensureO. mayapopulation sustainable management.Methods and ResultsDietary formulations are identified for cephalopods by characterizingO. mayadigestive enzymes present in the digestive gland and gastric juice. The present investigation revealed that acidic proteases showed a peak activity at higher temperatures than alkaline proteases. Inhibitors confirmed the presence of H, L, and D cathepsins. Noteworthy is a lower activation energy of alkaline enzymes compared to acidic, ones highlighting an intriguing aspect ofO. maya’sdigestive physiology.ConclusionOverall, this research provides valuable insights intoO. mayadigestive enzyme functions representing a significant advancement in formulating diets crucial for octopus successful farming that may help to fully understand its physiology.
NEST: Spatially-mapped cell-cell communication patterns using a deep learning-based attention mechanism
Authors: Zohora Fatema Tuz , Flores-Figueroa Eugenia , Li Joshua , Paliwal Deisha , Notta Faiyaz , Schwartz Gregory W. 
Published: March 2024

AbstractDysregulation of communication between cells mediates complex diseases such as cancer and diabetes. However, detecting cell-cell communication (CCC) at scale remains one of the greatest challenges in transcriptomics. While gene expression measured with single-cell RNA sequencing and spatial transcriptomics reinvigorated computational approaches to detecting CCC, most existing methods exhibit high false positive rates, do not integrate spatial proximity of ligand-receptor interactions, and cannot detect CCC between individual cells. We overcome these challenges by presentingNEST (NEural network on Spatial Transcriptomics), which uses a graph attention network paired with an unsupervised contrastive learning approach to decipher patterns of communication while retaining the strength of each signal. We introduce new synthetic benchmarking experiments which demonstrate how NEST outperforms existing tools and detects biologically-relevant CCC along with directionality and confidence across spot- and cell-based technologies measuring several different tissues and diseases. In our applications, NEST identifies T-cell homing signals in human lymph nodes, aggressive cancer CCC in lung adenocarcinoma, and discovers new patterns of communication that act as relay networks in pancreatic cancer. Beyond two-dimensional data, we also highlight NEST’s ability to detect CCC in three-dimensional spatial transcriptomic data.
Plant species richness and the root economics space drive soil fungal communities
Authors: Hennecke Justus , Bassi Leonardo , Albracht Cynthia , Amyntas Angelos , Bergmann Joana , Eisenhauer Nico , Fox Aaron , Heimbold Lea , Heintz-Buschart Anna , Kuyper Thomas W. , Lange Markus , Alves de Souza Yuri Pinheiro , Rai Akanksha , Solbach Marcel Dominik , Mommer Liesje , Weigelt Alexandra 
Published: March 2024

AbstractTrait-based approaches have been increasingly used to relate plants to soil microbial communities. However, the plant organs mediating this plant-microbe interaction – the roots – have been largely overlooked. The recent discovery of the root economics space offers a predictive framework for the structure of soil microbial communities, and specifically soil-borne fungal communities. Applying this novel approach, our study in a grassland plant diversity experiment reveals distinct root trait strategies at the level of the plant community. In addition to significant effects of plant species richness, we show that both axes of the root economics space – the collaboration and conservation gradient – are strong drivers of the composition of the different guilds of soil fungi, including saprotrophic, plant pathogenic, and mycorrhizal fungi. Our results illustrate that the root economics space and plant species richness jointly determine the effects of plants on fungal communities and their potential role in plant health and ecosystem functioning.
Paradigm shift in biomarker translation: a pipeline to generate clinical grade biomarker candidates from DIA-MS discovery
Authors: Fu Qin , Vegesna Manasa , Sundararaman Niveda , Damoc Eugen , Arrey Tabiwang N. , Pashkova Anna , Mengesha Emebet , Debbas Philip , Joung Sandy , Li Dalin , Cheng Susan , Braun Jonathan , McGovern Dermot P.B. , Murray Christopher , Xuan Yue , Eyk Jennifer E. Van 
Published: March 2024

AbstractClinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package. This innovative tool uses the discovery cohort analysis to select precursors, peptides, and proteins that adhere to established targeted assay criteria. TEAQ was applied to Data-Independent Acquisition MS data from plasma samples acquired on an Orbitrap™ Astral™ MS. Identified precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra-protein correlation from 11-point loading curves under three throughputs, to develop a resource for clinical-grade targeted assays. From a clinical cohort of individuals with inflammatory bowel disease (n=492), TEAQ successfully identified 1116 signature peptides for 327 quantifiable proteins from 1180 identified proteins. Embedding stringent selection criteria adaptable to targeted assay development into the analysis of discovery data will streamline the transition to validation and clinical studies.
A humanized knock-inCol6a1mouse recapitulates a deep-intronic splice-activating variant
Authors: Bolduc Véronique , Guirguis Fady , Lubben Berit , Trank Lindsey , Silverstein Sarah , Brull Astrid , Nalls Matthew , Cheng Jun , Garrett Lisa , Bönnemann Carsten G. 
Published: March 2024

AbstractAntisense therapeutics such as splice-modulating antisense oligonucleotides (ASOs) are promising tools to treat diseases caused by splice-altering intronic variants. However, their testing in animal models is hampered by the generally poor sequence conservation of the intervening sequences between human and other species. Here we aimed to model in the mouse a recurrent, deep-intronic, splice-activating,COL6A1variant, associated with a severe form of Collagen VI-related muscular dystrophies (COL6-RDs), for the purpose of testing human-ready antisense therapeuticsin vivo. The variant, c.930+189C>T, creates a donor splice site and inserts a 72-nt-long pseudoexon, which, when translated, acts in a dominant-negative manner, but which can be skipped with ASOs. We created a unique humanized mouse allele (designated as “h”), in which a 1.9 kb of the mouse genomic region encoding the amino-terminus (N-) of the triple helical (TH) domain of collagen α1(VI) was swapped for the human orthologous sequence. In addition, we also created an allele that carries the c.930+189C>T variant on the same humanized knock-in sequence (designated as “h+189T”). We show that in both models, the human exons are spliced seamlessly with the mouse exons to generate a chimeric mouse-human collagen α1(VI) protein. In homozygousCol6a1h+189T/h+189Tmice, the pseudoexon is expressed at levels comparable to those observed in heterozygous patients’ muscle biopsies. WhileCol6a1h/hmice do not show any phenotype compared to wild-type animals,Col6a1h/h+189TandCol6a1h+189T/h+189Tmice have smaller muscle masses and display grip strength deficits detectable as early as 4 weeks of age. The pathogenic h+189T humanized knock-in mouse allele thus recapitulates the pathogenic splicing defects seen in patients’ biopsies and allows testing of human-ready precision antisense therapeutics aimed at skipping the pseudoexon. Given that theCOL6A1N-TH region is a hot-spot for COL6-RD variants, the humanized knock-in mouse model can be utilized as a template to introduce otherCOL6A1pathogenic variants. This unique humanized mouse model thus represents a valuable tool for the development of antisense therapeutics for COL6-RDs.
Reconstructing the dynamics of past coral endosymbiotic algae communities using coral ancient DNA (coraDNA)
Authors: Rey Olivier , Dissard Delphine , Toulza Eve , Guinebert Thomas , Saccas Mathilde , Allienne Jean-François , Butsher John , Zoubir Mourad BenSalah , Iwankow G. , Tougard Christelle , Vidal-Dupiol Jérémie 
Published: March 2024

AbstractMost scleractinian corals are drastically threatened due to global changes but some colonies are intriguingly resistant to heat stress. Coral thermal tolerance partly relies on genomic determinism among the cnidarian compartment but also on the physiology of their associated symbiotic algae (Symbiodiniaceae). In fact, some corals can shift and/or shuffle their associated Symbiodiniaceae communities to temporally cope with heat stress. So far coral adjustments of their endosymbiotic algae were mainly observed at short-term evolutionary time scales and we lack a general vision of coral holobiont evolution at broader timescales. We here combined the use of ancient DNA from a coral core and a metabarcoding approach, to retrace past Symbiodiniaceae communities associated with a living colony ofPorites lobatafrom New Caledonia over the last century. We were able to extract ancient DNA along the coral core at 19 time points dating back to the 1870’s. Overall, we detected 13 OTUs, nine of which were affiliated to the SymbiodiniaceaeCladocopiumclade, one toAzadinium spinosum(Dinophycae); one to the hostP. lobata, the two other OTUs remained unidentified. One OTU was largely predominant and was ubiquitous over all samples. The number of OTUs was marginally correlated to the total number of sequences per sample but not to the age of thecoraDNA sample. We found a generally stable core microbiota associated withP. lobata, although drastic change in community composition was observed in coraDNA samples corresponding to an extreme hot winter temperature event. More generally, this study paves the way for further investigations on the evolutionary dynamics of coral holobionts at the colony level over large temporal scales.
MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats
Authors: Luo Longhua , Wang Zixin , Tong Xuxian , Xiong Tenxian , Chen Minggen , Liu Xiang , Peng Cong , Sun Xiang 
Published: March 2024

AbstractErectile dysfunction (ED) is a male sexual dysfunction with a gradually increasing prevalence, and current treatments are ineffective. This study aims to find a safer and more effective treatment for erectile dysfunction. Bone marrow-derived mesenchymal stem cells (BM-MSCs) treated with VEGFA. The expression of endothelial markers vWF, VE-cadherin and eNOS were determined by overexpressing MALAT1 and CDC42, respectively. The results showed that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs and the expression of endothelial marker-related proteins. Moreover, MALAT1 induced differentiation of BM-MCs to ECs through the CDC42/PAK1/Paxillin pathway was explored by transfecting si-MALAT1 and overexpressing CDC42 as well as PAK1 in the BM-MSCs. Next, miR-206 was overexpressed within BM-MCs to determine CDC42 expression. The binding sites of MALAT1, miR-206 and CDC42 were reported using luciferase. it was found that the MALAT1 competes with CDC42 3’-UTR for binding miR-206, which in turn is involved in differentiating BM-MSCs to ECs. Finally, DMED rat modeling success was demonstrated by APO experiments. MALAT1 overexpression-modified BM-MSCs had significant therapeutic effects in DMED rats.
Delving into human α1,4-galactosyltransferase acceptor specificity: the role of enzyme dimerization
Authors: Mikołajczyk Krzysztof , Wróblewski Karol , Kmiecik Sebastian 
Published: March 2024

AbstractHuman α1,4-galactosyltransferase (A4galt), a Golgi apparatus-resident GT, synthesizes Gb3 glycosphingolipid (GSL) and P1 glycotope on glycoproteins (GPs), which are receptors for Shiga toxin types 1 and 2. Despite the significant role of A4galt in glycosylation processes, the molecular mechanisms underlying its varied acceptor specificities remain poorly understood. Here, we attempted to elucidate A4galt specificity towards GSLs and GPs by exploring its interaction with GTs with various acceptor specificities, GP-specific β1,4-galactosyltransferase 1 (B4galt1) and GSL-specific β1,4-galactosyltransferase isoenzymes 5 and 6 (B4galt5 and B4galt6). Using a novel NanoBiT assay, we found that A4galt can form homodimers and heterodimers with B4galt1 and B4galt5 in two cell lines, human embryonic kidney cells (HEK293) and Chinese hamster ovary cells (CHO-Lec2). We found that A4galt-B4galts heterodimers preferred N-terminally tagged interactions, while in A4galt homodimers, the favored localization of the fused tag depended on the cell line used. Furthermore, by employing AlphaFold for state-of-the-art structural prediction, we analyzed the interactions and structures of these enzyme complexes. Our analysis highlighted that the A4galt-B4galt5 heterodimer exhibited the highest prediction confidence, indicating a significant role of A4galt heterodimerization in determining enzyme specificity toward GSLs and GPs. These findings enhance our knowledge of A4galt acceptor specificity and may contribute to a better comprehension of pathomechanisms of the Shiga toxin-related diseases.
A PTER-dependent pathway of taurine metabolism linked to energy balance
Authors: Wei Wei , Lyu Xuchao , Markhard Andrew L. , Fu Sipei , Mardjuki Rachel E. , Cavanagh Peter E. , Zeng Xianfeng , Rajniak Jakub , Lu Nannan , Xiao Shuke , Zhao Meng , Dolores Moya-Garzon Maria , Truong Steven D. , Chou Jonathan Chiu-Chun , Wat Lianna W. , Chidambaranathan-Reghupaty Saranya , Coassolo Laetitia , Xu Duo , Shen Fangfang , Huang Wentao , Ramirez Cuauhtemoc B. , Jang Cholsoon , Svensson Katrin J. , Fischbach Michael A , Long Jonathan Z. 
Published: March 2024

SummaryTaurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1–3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.
Anatomy of a pest control failure: Introgression of cytochrome P450 337B3 alleles from invasive old-world bollworm into native corn earworm (Lepidoptera: Noctuidae)
Authors: Nufer Marissa I. , Coates Brad S. , Abel Craig A. , O’Neill Patrick , McCracken Morgan , Jain Devendra , Pierce Calvin A. , Glover James , Towles Tyler , Reddy Gadi VP , Perera Omaththage P. 
Published: March 2024

AbstractThe establishment of invasive species populations can threaten the ecological balance in naïve habitats and impact agricultural production practices.Helicoverpa armigera(old-world bollworm, OWBW) andH. zea(corn earworm, CEW) were geographically separated prior to the 2013 report of OWBW invasion into South America. Introgression of OWBW-specific cytochrome P450 337B3 (CYP337B3) gene into CEW was repeatedly detected across South America and the Caribbean. Two hybrids were documented from Texas in 2019. In this study, screening insects collected in Olathe, Colorado, USA, where a failure of pyrethroids to control CEW damage to conventional sweetcorn in 2023 detected 28.6% of insects with the OWBW-specific CYP337B3 marker. Nucleotide sequencing of the CYP337B3 gene identified 73.1 and 26.9% of insects carried CYP337B3v2 and CYP337B3v6 alleles, respectively and 0.15 overall frequency of CYP337B3 alleles. Based on prior data for distinct phylogeographic origins of CYP337B3v2 and v6 alleles, our results indicate Olathe samples were derived from two different introductions; An uncertain source of the v6 allele that was initially reported in West Africa and possibly South American or Caribbean origin of the globally distributed v2 allele. One of the 1618 individuals screened also carried a ribosomal RNA internal transcribed spacer 1 (ITS1) derived from OWBW. Local selection pressures at the Olathe location imposed by repeated pyrethroid exposures are likely attributed to the prevalence of CYP337B3, where control practices hasten the accumulation of phenotypic resistance by adaptive introgression. Pyrethroid and other resistance factors carried by invasive OWBW may continue to impact CEW management tactics across the Americas.
Diversification of an emerging bacterial plant pathogen; insights from the global spread ofXanthomonas euvesicatoriapv.perforans
Authors: Timilsina Sujan , Iruegas-Bocardo Fernanda , Jibrin Mustafa O. , Sharma Anuj , Subedi Aastha , Kaur Amandeep , Minsavage Gerald V. , Huguet-Tapia Jose , Klein-Gordon Jeannie , Adhikari Pragya , Adhikari Tika B. , Cirvilleri Gabriella , de la Barrera Laura Belen Tapia , Bernal Eduardo , Creswell Tom C. , Tien Doan Thi Kieu , Coutinho Teresa A. , Egel Daniel S. , Félix-Gastélum Rubén , Francis David M. , Kebede Misrak , Ivey Melanie Lewis , Louws Frank J. , Luo Laixin , Maynard Elizabeth T. , Miller Sally A. , Thu Nga Nguyen Thi , Osdaghi Ebrahim , Quezado-Duval Alice M. , Roach Rebecca , Rotondo Francesca , Ruhl Gail E. , Shutt Vou M. , Thummabenjapone Petcharat , Trueman Cheryl , Roberts Pamela D. , Jones Jeffrey B. , Vallad Gary E. , Goss Erica M. 
Published: March 2024

AbstractEmerging and re-emerging plant diseases continue to present multifarious threats to global food security. Considerable recent efforts are therefore being channeled towards understanding the nature of pathogen emergence, their spread and evolution.Xanthomonas euvesicatoriapv.perforans (Xep), one of the causal agents of bacterial spot of tomato, rapidly emerged and displaced other bacterial spot xanthomonads in tomato production regions around the world. In less than three decades, it has become a dominant xanthomonad pathogen in tomato production systems across the world and presents a model for understanding diversification of recently emerged bacterial plant pathogens. AlthoughXephas been continuously monitored in Florida since its discovery, the global population structure and evolution at the genome-scale is yet to be fully explored. The objectives of this work were to determine genetic diversity globally to ascertain if different tomato production regions contain genetically distinctXeppopulations, to examine genetic relatedness of strains collected in tomato seed production areas in East Asia and other production regions, and to evaluate variation in type III effectors, which are critical pathogenicity and virulence factors, in relationship to population structure. We used genome data from 270 strains from 13 countries for phylogenetic analysis and characterization ofXopeffector gene diversity among strains. Our results showed notable genetic diversity in the pathogen. We found genetically similar strains in distant tomato production regions, including seed production regions, and diversification over the past 100 years, which is consistent with intercontinental dissemination of the pathogen in hybrid tomato production chains. Evolution of theXeppangenome, including the acquisition and loss of type III secreted effectors, is apparent within and among phylogenetic lineages. The apparent long-distance movement of the pathogen, together with variants that may not yet be widely distributed, poses risks of emergence of new variants in tomato production.