bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shifts and rebound in microbial community function following repeated introduction of a novel species
Authors: Leale Alanna M. , Marquez Francisca Reyes , Zwaan Bas , Smid Eddy J. , Schoustra Sijmen 
Published: April 2024

ABSTRACTNatural microbial communities continually encounter novel species that may successfully establish or simply be transient, yet both outcomes can alter the resident community composition and function. Preserving natural microbial communities and innovating synthetic ones requires insight on the immediate and long-term impact of species introductions on both composition and function. For instance, it remains unclear whether there are gradual and long-term impacts from repeated invasions where the introduced species fails to establish – so-called failed invaders. To investigate the persistent impacts by failed invaders, we present an experimental test of community stability over multiple generations against repeated novel species introduction. We propagated a natural microbial community from a traditional fermented milk beverage for approximately 100 generations, with or without, repeated introduction ofEscherichia coliat each transfer. Community function was determined by metabolic profiling, and we observed alterations therein immediately afterE. coliintroduction, followed by recovery, or rebound once ceased. In contrast to this proxy of community function, changes in the bacterial community composition were never detected. Our results evidence that community composition and function do not necessarily respond in parallel to an introduced species, potentially due to genotypic changes below species level detection or metabolic plasticity. Our work shows an ability for functional recovery in microbial communities and contributes insight on long-term community stability to sustained disturbances.
Profiling the organ membrane proteome dysregulation in the context of liver disease
Authors: Antony Frank , Brough Zora , Orangi Mona , Aoki Hiroyuki , Babu Mohan , van Hoa Franck Duong 
Published: April 2024

AbstractAlcohol consumption and high-fat diets often coincide in Western society, exerting negative synergistic effects on the liver. While many studies have demonstrated the impact of ALD and NAFLD on organ protein expression, none have offered a comprehensive view of the dysregulation at the level of the membrane proteome. In this study, we utilize peptidisc and solvent precipitation (SP4) methods to isolate and compare the membrane protein content of the liver with its unique biological functions. Using mice treated with a high-fat diet and ethanol in drinking water, we identified 1,563 liver proteins, with 46% predicted to have a transmembrane segment. Among these, 106 integral membrane proteins are dysregulated compared to the untreated sample. Gene ontology analysis reveals several dysregulated membrane processes associated with lipid metabolism, cell adhesion, xenobiotic processing, and mitochondrial membrane formation. Pathways related to cholesterol and bile acid transport are also mutually affected, suggesting an adaptive mechanism to counter the steatosis of the liver model. Our peptidisc-based membrane proteome profiling thus emerges as an effective way to gain insights into the role of the transmembrane proteome in disease development, warranting further in-depth analysis of the individual effect of the identified dysregulated membrane proteins.
Individual contralesional recruitment in the context of structural reserve in early motor reorganization after stroke
Authors: Mustin Maike , Hensel Lukas , Fink Gereon R. , Grefkes Christian , Tscherpel Caroline 
Published: April 2024

ABSTRACTThe concept of structural reserve in stroke reorganization assumes that the relevance of the contralesional hemisphere strongly depends on the brain tissue spared by the lesion in the affected hemisphere. Recent studies, however, have indicated that the contralesional hemisphere’s impact exhibits region-specific variability with concurrently existing maladaptive and supportive influences. This challenges traditional views, necessitating a nuanced investigation of contralesional motor areas and their interaction with ipsilesional networks.Our study focused on the functional role of contralesional key motor areas and lesion-induced connectome disruption early after stroke.Online TMS data of twenty-five stroke patients was analyzed to disentangle interindividual differences in the functional roles of contralesional primary motor cortex (M1), dorsal premotor cortex (dPMC), and anterior interparietal sulcus (aIPS) for motor function. Connectome-based lesion symptom mapping and corticospinal tract lesion quantification were used to investigate how TMS effects depend on ipsilesional structural network properties.At group and individual levels, TMS interference with contralesional M1 and aIPS but not dPMC led to improved performance early after stroke. At the connectome level, a more disturbing role of contralesional M1 was related to a more severe disruption of the structural integrity of ipsilesional M1 in the affected motor network. In contrast, a detrimental influence of contralesional aIPS was linked to less disruption of the ipsilesional M1 connectivity.Our findings indicate that contralesional areas distinctively interfere with motor performance early after stroke depending on ipsilesional structural integrity, extending the concept of structural reserve to regional specificity in recovery of function.
Seasonal Variations and the Associated Factors of Acute Appendicitis at a Tertiary Hospital: A Case of SPHMMC, Addis Ababa, Ethiopia
Authors: Daniel Lohide , Negash Fekadu 
Published: April 2024

AbstractBackgroundAcute appendicitis, a surgical emergency, is a prevalent pathology with uncertain etiology, influenced by various factors and seasonal variations.ObjectiveTo determine the seasonal variations and the associated factors of Acute Appendicitis.MethodsThe study analyzed demographic features, seasonal variation, length of hospital stay, and surgical treatment outcomes in 384 patients treated from 01/01/2022 to 31/12/ 2022 G.C. The patients were presented in four different seasons; December-February as winter, March-May as autumn, June-August as summer, and September-Nov as spring, which were assessed to describe seasonal variation and compare to what are observed in other countries. SPSS version 26 was used for all the statistical assessments and analyses.ResultsOut of all 384 patients, 64.3% were males and 35.7% were females. The mean age was 20.8, male: female, 1.8:1. The majority of patients were in their 2nd and 3rd decades of life, and more common in the male 10–19 age group (22.1%). 23.9% of cases were observed in autumn, 22.7% in winter, 20.6% in spring, and 32.8% in summer. 10.1% increase in summer as compared to winter, 8.9% increase as compared to autumn, and 12.2% increase as compared to spring. The highest admissions were in the summer (32.8%). July had the highest number of cases (12.5%), which coincided with heavy rainy months, the rainiest days, and the lowest sunlight hours. The highest rainfall was observed in July (386mm) and August (491 mm), and the lowest sunlight hours were observed in July (6.1 hours) and August (5.9 hours), respectively. Monthly cases correlated positively with rainfall (Pearson’s R =.637, p<.05) and negatively with sunlight hours (Pearson’s R = -.618, p<.05). Complicated cases were slightly more common (50.9%), more in the 10–19 age group. Males had more complicated cases (38.3%) than females (20.8%). Complicated cases tend to present after 48 hours. The commonest postoperative complication was wound infection (5.5%). The mean length of hospital stay was 2.47 days, with no death was reported in the study period.ConclusionPeak appendicitis in summer is linked to rainfall and sunlight hours, affecting the 11-20 age groups.
Unravelling biomolecular and community grammars of RNA granules via machine learning
Authors: Ban Zhan , Yan Yan , Dawson Kenneth A. 
Published: April 2024

AbstractRNA granules are dynamic compartments within cells that play a crucial role in posttranscriptional regulation of gene expression. They are associated with a variety of human neurodegenerative diseases. While RNA granules play vital roles in cellular functions, the comprehension of their assembly has remained elusive.In this study, we employed robust machine learning models combining residue content and physicochemical features to accurately identify potential RNA granule (i.e.,stress granule and P-body) proteome within the human proteome. Our models achieved good performance with high areas under the receiver operating characteristic curve of up to 0.88, outperforming previous liquid-liquid phase separation models. Intriguingly, the predicted RNA granule proteome reveals a significant enrichment in biological functions and domains associated with RNA granule-related processes, mirroring findings from observed high-confidence RNA granule protein datasets. Furthermore, our analysis unveils critical physicochemical attributes, notably hydrophobicity, influencing the formation of RNA granules.Using the constructed model, we uncovered the central roles of RNA granule proteins with high propensities within the comprehensive RNA granule protein-protein interaction (PPI) network and their commonality in diverse RNA granules. Furthermore, we identified prominent clusters with dense PPIs, significantly contributing to critical biological processes within diverse RNA granules, including translation, mRNA decay, rRNA processing, and mRNA splicing. This analysis proposes a hypothesis: dense PPI clusters are integral functional subunits, constituting relatively stable ‘cores’ within diverse RNA granules.In conclusion, this study provides a comprehensive molecular and community-based foundation for understanding the importance of PPIs in the stability of RNA granule formation and functionality. This analysis contributes to a deeper and more comprehensive understanding of the intricate nature of RNA granules and opens avenues for future research and therapeutic interventions targeting RNA granule- related diseases.
Consensus Guidelines for the Management of Peritoneal Surface Malignancies: Introduction and Methodology
Authors:   PSM Writing Group,   PSM Consortium Group, Turaga Kiran K. 
Published: April 2024

ABSTRACTIntroductionThe management of peritoneal surface malignancies (PSM) remains a challenge, characterized by limited high-level evidence and reliance on expert opinions. This paper outlines the methodology used in the development of clinical management pathways for PSM.MethodsBuilding upon the Chicago Consensus Guidelines, a multidisciplinary North American panel was surveyed using a Modified Delphi technique to gauge the levels of agreement with clinical management pathways. Rapid systematic reviews were undertaken to address contentious questions specific to disease sites, which were structured using the Population, Intervention, Comparator, Outcome framework.ResultsTwo consecutive rounds of voting were conducted between June 2023 and February 2024, addressing nine pathways spanning various conditions associated with PSM (colorectal, appendiceal, gastric, and neuroendocrine neoplasms, peritoneal mesothelioma, and gastrointestinal obstruction). The first Delphi consensus round involved 228 participants, of which 198 (87%) responded in the second round. Over 90% consensus was achieved in most blocks across all pathways. Eleven rapid systematic reviews were conducted, including 183 studies cumulatively out of 13,595 abstracts screened through PubMed. Perspectives from patient advocates and international experts were incorporated into these guidelines. The consortium’s multilevel approach also involved the creation of a peritoneal oncology curriculum, recommendations for billing and coding, and shared resources for perioperative care and patient information.ConclusionExperts indicated high levels of agreement with most pathway blocks across disease sites. These guidelines do not replace the need for high-level evidence but serve as guiding principles for critical decisions within the current landscape of PSM care.
Assessment of chemical methods in the removal of the spore coat and exosporium layers ofClostridioides difficileSpores
Authors: Sanchez Javier , Romero-Rodriguez Alba , Troncoso-Cotal Scarlett , Paredes-Sabja Daniel 
Published: April 2024

AbstractClostridioides difficilespores are essential for initiation, recurrence and transmission of the disease. The spore surface layers are composed of an outermost exosporium layer that surrounds another proteinaceous layer, the spore coat. These spore surfaces layers are responsible for initial interactions with the host and spore resistance properties contributing to transmission and recurrence of CDI. During spore-development, assembly of both layers is tightly interconnected thus studying the surface is essential for understanding the assembly of these layers and identification of potential targets for therapeutics. Several spore coat /exosporium extraction methods have utilized different extraction procedures making comparison across studies difficult and their impact on spore surface layer properties remains unclear. Here, we tested how commonly used chemical methods remove the spore coat /exosporium layers, analyzing treated-spores by phase contrast microscopy, transmission electron microscopy, western blotting, and lysozyme-triggered germination to functionally characterize the extraction efficiency of these treatment on these layers. Our results provide a systematic analysis and offer a platform for future spore coat and exosporium-related studies.
Anchor-Enhanced Bead Design for Reduced Oligonucleotide Synthesis Errors in Single-cell sequencing
Authors: Sun Jianfeng , Philpott Martin , Loi Danson , Hoffman Gabriela , Robson Jonathan , Mehta Neelam , Calcutt Eleanor , Gamble Vicki , Brown Tom , Brown Tom , Oppermann Udo , Cribbs Adam P 
Published: April 2024

AbstractSingle-cell transcriptomics, reliant on the incorporation of barcodes and unique molecular identifiers (UMIs) into captured polyA+ mRNA, faces a significant challenge due to synthesis errors in oligonucleotide capture sequences. These inaccuracies, which are especially problematic in long-read sequencing, impair the precise identification of sequences and result in inaccuracies in UMI deduplication. To mitigate this issue, we have modified the oligonucleotide capture design, which integrates an interposed anchor between the barcode and UMI, and a ‘V’ base anchor adjacent to the polyA capture region. This configuration is devised to ensure compatibility with both short and long-read sequencing technologies, facilitating improved UMI recovery and enhanced feature detection, thereby improving the efficacy of droplet-based sequencing methods.
Robust single nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity
Authors: So Jisun , Strobel Olivia , Wann Jamie , Kim Kyungchan , Paul Avishek , Acri Dominic J. , Dabin Luke C. , Peng Gang , Kim Jungsu , Roh Hyun Cheol 
Published: April 2024

ABSTRACTSingle nucleus RNA sequencing (snRNA-seq), an alternative to single cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.
DNA targeting by compact Cas9d and its resurrected ancestor
Authors: Ocampo Rodrigo Fregoso , Bravo Jack P. K. , Dangerfield Tyler , Nocedal Isabel , Jirde Samatar , Alexander Lisa M. , Das Anjali , Nielsen Sarah , Johnson Kenneth A. , Brown Christopher T. , Butterfield Cristina N. , Goltsman Daniela S. A. , Taylor David W. 
Published: April 2024

AbstractThe type II-A CRISPR effector SpCas9 has gained widespread popularity as an efficient and programmable genome editing tool. However, much remains to be known about novel compact variants that may overcome some limitations of current systems1,2. Recently, alternative CRISPR-Cas systems with highly compact nucleases capable of genome editing in mammalian cells have been discovered through metagenomic analysis of uncultivated microbes, including Cas9d (a type II-D CRISPR-Cas effector)3. Here, we report the cryo-EM structures of a Cas9d nuclease (747 amino acids in length) in multiple functional states, revealing a stepwise process of DNA targeting involving a conformational switch in a REC2 domain insertion. Our structures provide insights into the intricately folded guide RNA which acts as a structural scaffold to anchor small, flexible protein domains and facilitate DNA target recognition. We find that the sgRNA can be truncated by up to ∼25% yet still retain activityin vivo. We also show that despite preferentially targeting an NGG PAM, Cas9d exhibits a unique mechanism for PAM recognition. Finally, we identify the first Cas9d smaller than 800 amino acids exhibiting robust nuclease activity in mammalian cells. Using ancestral sequence reconstruction, we demonstrate that it is possible to generate compact nucleases capable of efficient genome editing by expanding the diversity of Cas9d families. Collectively, our results provide mechanistic insights into the evolution and DNA targeting of diverse type II CRISPR-Cas systems, providing a molecular blueprint for future rational re-engineering of minimal RNA-guided DNA nucleases.
Use of steric blocking antisense oligonucleotides for the targeted inhibition of junction containing precursor microRNAs
Authors: Ma Sicong , Howden Samantha A. , Keane Sarah C. 
Published: April 2024

ABSTRACTAntisense oligonucleotides (ASOs) are widely used as therapeutics for neurodegenerative diseases, cancers, and virus infections. One class of ASOs functions to enhance protein expression by sequestering the mature microRNA (miRNA) in a double-stranded structure within the RNA-induced silencing complex (RISC). An alternative approach for the targeted control of gene expression is to use ASOs that bind to the pre-elements of miRNAs (pre-miRNAs) and modulate their enzymatic processing. Here, we demonstrate that ASOs can be used to disrupt a specific structural feature, “junction,” within pre-miR-31 that is important in directing efficient processing by the Dicer/TRBP complex. Furthermore, we extend and validate this strategy to pre-miR-144, which has a similar junction-dependent structure-function relationship. We found that a significant number of human pre-miRNAs are predicted to contain junctions, and validated our ASO approach on several members of this group. Importantly, we also verified the application of junction-targeting ASOs for the specific inhibition of pre-miRNA processingin cell. Our study reemphasizes the important roles of RNA structure in regulating Dicer/TRBP processing of pre-miRNAs and provides the framework to develop structure-informed ASOs that serve to inhibit miRNA production.
Identification and characterization of a synaptic active zone assembly protein
Authors: Lützkendorf J. , Matkovic-Rachid T. , Götz T. , Liu S. , Ghelani T. , Maglione M. , Grieger M. , Putignano S. , Gao L. , Gimber N. , Schmoranzer J. , Stawrakakis A. , Walter A.M. , Heine M. , Wahl M.C. , Mielke T. , Liu F. , Sigrist S.J. 
Published: April 2024

AbstractAt presynaptic active zones (AZs), scaffold proteins play a crucial role in coordinating synaptic vesicle (SV) release and forming intricate nanoarchitectures essential for synaptic function. Despite their suspected importance, factors governing the assembly of nanoscale AZ scaffolds have remained elusive. Here, we identify “Blobby” as a novel regulator of AZ nanopatterning, localized within the AZ scaffold. Genetic loss of the extended Blobby protein led to aberrant accumulation of AZ scaffold proteins (“blobs”) and disrupted the nanoscale architecture of the AZ scaffold, resulting in a significant reduction in the packing density of voltage-gated Ca2+channels at AZs, as observed through intravital single-molecule imaging. This disruption correlated with decreased evoked synaptic currents and SV release probability. Our findings suggest that Blobby plays a crucial role in switching the AZ scaffold into a state which allows to fine-tune the dynamic nanopatterning of Ca2+channels to maintain proper release.
A functional screen uncovers circular RNAs regulating excitatory synaptogenesis in hippocampal neurons
Authors: Kelly Darren , Bicker Silvia , Winterer Jochen , Nanda Prakruti , Germain Pierre-Luc , Dieterich Christoph , Schratt Gerhard 
Published: April 2024

AbstractCircular RNAs (circRNAs) are an expanding class of largely unexplored RNAs which are prominently enriched in the mammalian brain. Here, we systematically interrogated their role in excitatory synaptogenesis of rat hippocampal neurons using RNA interference. Thereby, we identified seven circRNAs as negative regulators of excitatory synapse formation, many of which contain high-affinity microRNA binding sites. Knockdown of one of these candidates, circRERE, surprisingly promoted the formation of electrophysiologically silent synapses. Mechanistically, circRERE knockdown resulted in a preferential upregulation of synaptic mRNAs containing binding sites for miR-128-3p because of a reduced protective interaction between miR-128-3p and circRERE. Accordingly, overexpression of circRERE rescued exaggerated synapse formation upon circRERE knockdown in a miR-128-3p binding site-specific manner. Overall, our results uncover circRERE-mediated stabilization of miR-128-3p as a novel mechanism to restrict the formation of silent excitatory synaptic co-clusters and more generally implicate circRNA-dependent microRNA regulation in the control of synapse development and function.
Empirical evidence for the validity of the job crafting scale (JCS) in a Portuguese setting
Authors: Viseu João , Santos Joana , Semedo Carla Santarém , Bakker Arnold B. , Tims Maria , Agrela Sara , Lagareiro Beatriz 
Published: April 2024

Purpose
This study aims to adapt and validate the Job Crafting Scale (JCS), a measure based on the conceptualization of job crafting of the job demands–resources theory, for a sample of Portuguese workers and to test its psychometric properties regarding validity (factor, convergent, discriminant, and criterion) and reliability.

Design/methodology/approach
Two subsamples (n1 = 315 and n2 = 329) of Portuguese workers aged 18 years old and over participated in this research. Exploratory factor analysis and confirmatory factor analysis were used to assess the factor structure.

Findings
The results indicated that the Portuguese version of the JCS, with 18 items, has a factor structure composed of four-correlated factors. Furthermore, the results demonstrated the existence of factor, discriminant, and criterion validity, as well as reliability.

Originality/value
This study provides a job crafting measure adapted to the Portuguese language that can serve as a diagnostic tool for workers and organizations.