bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Analysis of the Cerebrospinal Fluid Proteome Reveals Shared and Unique Differences Between Sporadic and Familial Forms of Amyotrophic Lateral Sclerosis
Authors: Trautwig Adam N. , Fox Edward J. , Dammer Eric B. , Shantaraman Anantharaman , Ping Lingyan , Duong Duc M. , Levey Allan I. , Lah James J. , Fournier Christina N. , McEachin Zachary T. , Glass Jonathan D. , Seyfried Nicholas T. 
Published: March 2024

AbstractBackgroundAmyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10 % of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause of the majority of cases is unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.MethodsWe employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from ALS patients with sporadic disease (n=35), C9orf72 ALS (n=10), and SOD1 ALS (n=6), as well as age-matched healthy controls (n=44) and asymptomatic C9orf72 carriers (n=6). We used differential protein abundance and network analyses to determine how protein profiles vary across disease types in ALS CSF.ResultsIntegrated differential and co-expression network analysis identified proteomic differences between ALS and control, and differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. Groups of proteins also differentiated asymptomatic C9orf72 mutation carriers from those with C9orf72 ALS, marking a pre-symptomatic proteomic signature of C9orf72 ALS. Similarly, additional proteins differentiated asymptomatic from controls. Leveraging additional publicly available ALS and AD proteomic datasets, we validated our ALS CSF network and identified ALS-specific proteins within Module 5 (M5)-Extracellular matrix (e.g., IGF2, RARRES2, LGALS3, GALNT15, and LYZ) and shared biomarkers across neurodegenerative diseases linked to Module 10 (M10)-Ubiquitination/Gluconeogenesis (e.g., NEFL, NEFM, CHIT1, and CHI3L1).ConclusionsThis study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these disease subgroups and points to varying pathogenic pathways that result in disease.
Low intensity repetitive transcranial magnetic stimulation enhances remyelination by newborn and surviving oligodendrocytes in the cuprizone model of toxic demyelination
Authors: Nguyen Phuong Tram , Makowiecki Kalina , Lewis Thomas S , Fortune Alastair , Clutterbuck Mackenzie , Reale Laura , Taylor Bruce V , Rodger Jennifer , Cullen Carlie L , Young Kaylene M 
Published: March 2024

AbstractIn people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs;Pdgfrα-CreERtransgenic mice) or mature OLs (Plp-CreERtransgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Multiple consecutive daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre- existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ∼471µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs and increased the number of surviving OLs that contributed to remyelination in the corpus callosum (CC). As LI-rTMS can non-invasively promote remyelination by modifying the behaviour of new and surviving OLs, it may be suitable as an adjunct intervention to enhance remyelination in people with MS.
ATG6 interacting with NPR1 increasesArabidopsis thalianaresistance toPstDC3000/avrRps4by increasing its nuclear accumulation and stability
Authors: Zhang Baihong , Huang Shuqin , Guo Shuyu , Meng Yixuan , Tian Yuzhen , Zhou Yue , Chen Hang , Li Xue , Zhou Jun , Chen Wenli 
Published: March 2024

AbstractAutophagy-related gene 6 (ATG6) plays a crucial role in plant immunity. Nonexpressor of pathogenesis-related genes1 (NPR1) acts as a signaling hub of plant immunity. However, the relationship between ATG6 and NPR1 is unclear. Here, we find that ATG6 directly interacts with NPR1.ATG6overexpression significantly increased nuclear accumulation of NPR1. Furthermore, we demonstrate thatATG6increases NPR1 protein levels and improves its stability. Interestingly, ATG6 promotes the formation of SINCs (SA-induced NPR1 condensates)-like condensates. Additionally, ATG6 and NPR1 synergistically promote the expression ofpathogenesis-relatedgenes. Further results showed that silencingATG6inNPR1-GFPexacerbatesPstDC3000/avrRps4infection, while double overexpression ofATG6andNPR1synergistically inhibitsPstDC3000/avrRps4infection. In summary, our findings unveil an interplay of NPR1 with ATG6 and elucidate important molecular mechanisms for enhancing plant immunity.HighlightWe unveil a novel relationship in which ATG6 positively regulates NPR1 in plant immunity.
scIDPMs: single-cell RNA-seq imputation using diffusion probabilistic models
Authors: Zhang Zhiqiang , Liu Lin 
Published: March 2024

AbstractSingle-cell RNA sequencing (scRNA-seq) technology is a high-throughput sequencing analysis method that enables the sequencing of mRNA in individual cells, thereby facilitating a more precise understanding of cellular gene expression and metabolic products. This approach reveals cell function and characteristics, making it widely applicable in biological research. However, scRNA-seq data often suffers from false zero values known as dropout events due to limitations in sequencing technology. These dropout events not only mask true gene expression levels but also significantly impact downstream analysis accuracy and reliability. To address this challenge, numerous computational approaches have been proposed for imputing missing gene expression values. Nevertheless, existing imputation methods struggle to fully capture the distribution of dropout values due to the high sparsity of scRNA-seq data and the complexity and randomness associated with gene expression patterns. Recently, probabilistic diffusion models have emerged as deep generative models capable of accurately restoring probability density distributions in domains such as image and audio processing. In this paper, we propose a method called scIDPMs, which utilizes conditional diffusion probabilistic models to impute scRNA-seq data. scIDPMs first identifies dropout sites based on the characteristics of cellular gene expression and then infers the dropout values by conditioning on the available gene expression values, which provide context information for the dropout values. To effectively capture the global features of gene expression profiles, scIDPMs employs a deep neural network with an attention mechanism to optimize the objective function. The performance of scIDPMs was evaluated using both simulated and real scRNA-seq datasets, and compared with eight other imputation methods. The experimental results clearly demonstrated that, in comparison to alternative approaches, scIDPMs exhibited exceptional performance in recovering biologically meaningful gene expression values and enhancing various downstream analyses.
Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features
Authors: Kamarajan Chella , Ardekani Babak A. , Pandey Ashwini K. , Meyers Jacquelyn L. , Chorlian David B. , Kinreich Sivan , Pandey Gayathri , Richard Christian , de Viteri Stacey Saenz , Kuang Weipeng , Porjesz Bernice 
Published: March 2024

AbstractBrain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.
The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development
Authors: Suntharalingham Jenifer P. , del Valle Ignacio , Buonocore Federica , McGlacken-Byrne Sinead M. , Brooks Tony , Ogunbiyi Olumide K. , Liptrot Danielle , Dunton Nathan , Madhan Gaganjit K , Metcalfe Kate , Nel Lydia , Marshall Abigail R. , Ishida Miho , Sebire Neil J. , Moore Gudrun E. , Crespo Berta , Solanky Nita , Conway Gerard S. , Achermann John C. 
Published: March 2024

ABSTRACTMonosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore analyzed the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11-15 weeks post conception (n=78). Although most pseudoautosomal region 1 (PAR1) genes were lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g.,KDM5CandKDM6A), and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast,higherexpression of an autosomal, long non-coding RNA (OVCH1-AS1) was seen in all 45,X tissues. In the placenta, lower expression ofCSF2RAwas demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide novel insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome.
Molecular Signatures of Normal Pressure Hydrocephalus: A Large-scale Proteomic Analysis of Cerebrospinal Fluid
Authors: Kamalian Aida , Barough Siavash Shirzadeh , Ho Sara G. , Albert Marilyn , Luciano Mark G. , Yasar Sevil , Moghekar Abhay 
Published: March 2024

AbstractGiven the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.
Aroma compounds profile is affected by the initial yeast ratio in wort co-fermentations
Authors: Aguiar-Cervera Jose , Visinoni Federico , Zhang Penghan , Hollywood Katherine , Vrhovsek Urska , Severn Oliver , Delneri Daniela 
Published: March 2024

ABSTRACTIn recent years, the boom of the craft beer industry refocused the biotech interest from ethanol production to diversification of beer aroma profiles. This study analyses the fermentative phenotype of a collection of non-conventional yeasts and examines their role in creating new flavours, particularly through co-fermentation with industrialSaccharomyces cerevisiae. High-throughput solid and liquid media fitness screening compared the ability of eightSaccharomycesand four non-Saccharomycesyeast strains to grow in wort. We determined the volatile profile of these yeast strains and found thatHanseniaspora vineaedisplayed a particularly high production of the desirable aroma compounds ethyl acetate and 2-phenethyl acetate. Given thatH. vineaeon its own was a poor fermenter, we carried out mixed wort co-fermentations with aS. cerevisiaebrewing strain at different ratios. The two yeast strains were able to co-exist throughout the experiment, regardless of their initial inoculum, and the increase in the production of the esters observed in theH. vineaemonoculture was maintained, alongside with a high ethanol production. Moreover, different inoculum ratios yielded different aroma profiles: the 50/50S. cerevisiae/H. vineaeratio produced a more balanced profile, while the 10/90 ratio generated stronger floral aromas. Our findings show the potential of using different yeasts and different inoculum combinations to tailor the final aroma, thus offering new possibilities for a broader range of beer flavours and styles.IMPORTANCECraft brewing underwent an unprecedented growth in the last years due to customer demand for more unique and complex beverages. Brewers started to explore innovative fermentation methods using new ingredients, different brewing conditions, and new yeasts to explore a larger flavour landscape. The use of non-Saccharomycesyeasts has emerged as an effective strategy to produce novel distinct flavour profiles, however, knowledge regarding their fermentation performance and volatiles production is still limited, which hinders their industrial application. In this study, we expand on the knowledge of several non-Saccharomycesyeasts in terms of their brewing application and highlight the potential ofH. vineaein co-fermentation withS. cerevisiaefor producing unique fruity beers with a standard ethanol content. Our findings provide the craft beer industry with a new strategy to produce distinctive fruity beers.
The global β-lactam resistome revealed by comprehensive sequence analysis
Authors: Gholipour Sevan , Chen John , Lee Dongkyu , Tokuriki Nobuhiko 
Published: March 2024

AbstractMost antibiotic-resistance genes (ARGs) evolved in environmental microbes long before humanity’s antibiotic breakthrough, and widespread antibiotic use expedited the dissemination of ARGs among clinical pathogens. While widely discussed, the investigation of environmental ARG distributions lacks the scalability and taxonomic information necessary for a comprehensive analysis. Here, we present a global distribution of all five classes of β-lactamases among microbes and environments. We generated a β-lactamase taxonomy-environment map by identifying >113,000 β-lactamases across diverse bacterial phyla and environmental ecosystems. Remarkably abundant, their occurrence is only ∼2.6-fold lower than the essentialrecAgene in various environmental ecosystems, with particularly strong enrichment in wastewater and plant samples. The enrichment in plant samples implies an environment where the arms race of β-lactam producers and resistant bacteria occurred over millions of years. We uncover the origins of clinically relevant β-lactamases (mainly in ɣ-Proteobacteria) and expand beyond the previously suggested wastewater samples in plant, terrestrial, and other aquatic settings.
The TD drive - A parametric, open-source implant for multi-area electrophysiological recordings in behaving and sleeping rats
Authors: Schröder Tim , van der Meij Jacqueline , van Heumen Paul , Samanta Anumita , Genzel Lisa 
Published: March 2024

ABSTRACTIntricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as formation and consolidation of memories are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and medio-lateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze (HexMaze 9×5 m) using two different commercial recording systems and headstages.In sum, presented here is the adaptable design and assembly of a new electrophysiological implant facilitating fast preparation and implantation.
Multi-condition and multi-modal temporal profile inference during mouse embryonic development
Authors: Zhang Ran , Qiu Chengxiang , Filippova Gala , Li Gang , Shendure Jay , Vert Jean-Philippe , Deng Xinxian , Disteche Christine , Noble William Stafford 
Published: March 2024

AbstractThe emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of a particular cell. Furthermore, single-cell profiles can be collected at mismatched time points across different conditions (e.g., sex, batch, disease) and data modalities (e.g., scRNA-seq, scATAC-seq), which makes modeling challenging. Here we propose a joint modeling framework, Sunbear, for integrating multi-condition and multi-modal single-cell profiles across time. Sunbear can be used to impute single-cell temporal profile changes, align multi-dataset and multi-modal profiles across time, and extrapolate single-cell profiles in a missing modality. We applied Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multi-modal profiles are unavailable. Sunbear thus enables the projection of single-cell time-series snapshots to multi-modal and multi-condition views of cellular trajectories.
A Methodology for Specific Disruption of Microtubules in Dendritic Spines
Authors: Holland Elizabeth D. , Miller Hannah L. , Millette Matthew M. , Taylor Russell J. , Drucker Gabrielle L. , Dent Erik W. 
Published: March 2024

AbstractDendritic spines, the mushroom-shaped extensions along dendritic shafts of excitatory neurons, are critical for synaptic function and are one of the first neuronal structures disrupted in neurodevelopmental and neurodegenerative diseases. Microtubule (MT) polymerization into dendritic spines is an activity-dependent process capable of affecting spine shape and function. Studies have shown that MT polymerization into spines occurs specifically in spines undergoing plastic changes. However, discerning the function of MT invasion of dendritic spines requires the specific inhibition of MT polymerization into spines, while leaving MT dynamics in the dendritic shaft, synaptically connected axons and associated glial cells intact. This is not possible with the unrestricted, bath application of pharmacological compounds. To specifically disrupt MT entry into spines we coupled a MT elimination domain (MTED) from the Efa6 protein to the actin filament-binding peptide LifeAct. LifeAct was chosen because actin filaments are highly concentrated in spines and are necessary for MT invasions. Temporally controlled expression of this LifeAct-MTED construct inhibits MT entry into dendritic spines, while preserving typical MT dynamics in the dendrite shaft. Expression of this construct will allow for the determination of the function of MT invasion of spines and more broadly, to discern how MT-actin interactions affect cellular processes.Significance StatementThe LifeAct-MTED construct provides spatial and temporal control of microtubule depolymerization within individual cellsTargeting this construct directly to spines allows for the specific inhibition of microtubule dynamics into dendritic spines, without affecting microtubule dynamics in the dendritic shaftImplementation of the construct will allow for the testing of microtubule contributions to specific biological processes, without global disruption of microtubule dynamics