bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer disease brains
Authors: Novotny Brenna C , Fernandez Maria Victoria , Wang Ciyang , Budde John P , Bergmann Kristy , Eteleeb Abdallah , Bradley Joseph , Webster Carol , Ebl Curtis , Norton Joanne , Gentsch Jen , Dube Umber , Wang Fengxian , Morris John C , Bateman Randall J , Perrin Richard J , McDade Eric , Xiong Chengjie , Chhatwal Jasmeer ,   Dominantly Inherited Alzheimer Network Study Group,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium, Goate Alison , Farlow Martin , Schofield Peter , Chui Helena , Karch Celeste M , Benitez Bruno A , Cruchaga Carlos , Harari Oscar 
Published: November 2021

AbstractThe identification of multiple genetic risk factors for Alzheimer Disease (AD) provides evidence to support that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain, including information on treatment targets. In this study, we interrogate the metabolomic and lipidomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE ε4 and TREM2 risk variant carriers, and non-carrier sporadic AD (sAD). We generated metabolomic and lipidomic data from parietal cortical tissue from 366 participants with AD pathology and 26 cognitively unimpaired controls using the Metabolon global metabolomics platform. We identified 133 metabolites associated with disease status (FDR q-value<0.05). In sAD brains these include tryptophan betaine (b=-0.57) and N-acetylputrescine (b=-0.14). Metabolites associated with sAD and ADAD include ergothioneine (b=-0.21 and -0.26 respectively) and serotonin (b=-0.34 and -0.58, respectively). TREM2 and ADAD showed association with α-tocopherol (b=-0.12 and -0.12) and CDP-ethanolamine (b=-0.13 and -0.10). β-citrylglutamate levels are associated with sAD, ADAD, and TREM2 compared to controls (b=-0.15; -0.22; and -0.29, respectively). Additionally, we identified a signature of 16 metabolites that is significantly altered between genetic groups (sAD vs. control p = 1.05×10-7, ADAD vs. sAD p = 3.21×10-5) and is associated with Braak tau stage and disease duration. These data are available to the scientific community through a public web browser (http://ngi.pub/Metabolomics). Our findings were replicated in an independent cohort of 327 individuals.
Sulfite preservatives effects on the mouth microbiome: changes in viability, diversity and composition of microbiota
Authors: Irwin Sally V , Deardorff Luz Maria , Deng Youping , Fisher Peter , Gould Michelle , June Junnie , Kent Rachael S. , Qin Yujia , Yadao Fracesca 
Published: November 2021

AbstractProcessed foods make up about 70 percent of the American diet. Sulfites and other food preservatives are added to these foods largely to limit bacterial contamination. The mouth microbiota and its associated enzymes are the first to encounter food and therefore likely to be the most affected.Eight saliva samples from ten individuals were exposed to two sulfite preservatives, sodium sulfite and sodium bisulfite. One sample set was evaluated for bacteria composition utilizing 16s rRNA sequencing, and the number of viable cells in all sample sets was determined utilizing ATP assays at 10 and 40-minute exposure times. All untreated samples were analyzed for baseline lysozyme activity, and possible correlations between the number of viable cells and lysozyme activity.Sequencing results indicated significant increases in alpha diversity with sodium bisulfite exposure and changes in relative abundance of 3 amplicon sequence variants (ASV). Sodium sulfite treated samples showed a significant decrease in the Firmicutes/Bacteroidetes ratio, a marginally significant change in alpha diversity, and a significant change in the relative abundance for Proteobacteria, Firmicutes, Bacteroidetes, and for 6 ASVs. Beta diversity didn’t show any separation between groups, however, all but one sample set was observed to be moving in the same direction under sodium sulfite treatment in a principal component analysis.ATP assays indicated a significant and consistent average decrease in activity ranging from 24 - 46% at both exposure times with both sulfites.Average initial rates of lysozyme activity between all individuals ranged from +/- 76% compared to individual variations of +/- 10 - 34%. No consistent, significant correlation was found between ATP and lysozyme activity in any sample sets.ConclusionsSulfite preservatives, at concentrations regarded as safe by the FDA, alter the relative abundance and richness of the microbiota found in saliva, and decrease the number of viable cells, within 10 minutes of exposure.
The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
Authors: Abdelnabi Rana , Foo Caroline S. , Jochmans Dirk , Vangeel Laura , De Jonghe Steven , Augustijns Patrick , Mols Raf , Weynand Birgit , Wattanakul Thanaporn , Hoglund Richard M. , Tarning Joel , Mowbray Charles E. , Sjö Peter , Escudié Fanny , Scandale Ivan , Chatelain Eric , Neyts Johan 
Published: November 2021

AbstractThere is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.
Absence of enterotypes in the human gut microbiomes reanalyzed with non-linear dimensionality reduction methods
Authors: Bulygin Ivan , Shatov Vladislav , Rykachevsky Anton , Rayko Arseny , Bernstein Alexander , Burnaev Evgeny , Gelfand Mikhail S. 
Published: November 2021

AbstractEnterotypes of the human gut microbiome have been proposed to be a powerful prognostic tool to evaluate the correlation between lifestyle, nutrition, and disease. However, the number of enterotypes suggested in the literature ranged from two to four. The growth of available metagenome data and the use of exact, non-linear methods of data analysis challenges the very concept of clusters in the multidimensional space of bacterial microbiomes. Using several published human gut microbiome datasets, we demonstrate the presence of a lower-dimensional structure in the microbiome space, with high-dimensional data concentrated near a low-dimensional non-linear submanifold, but the absence of distinct and stable clusters that could represent enterotypes. This observation is robust with regard to diverse combinations of dimensionality reduction techniques and clustering algorithms.
How low can you go: sex identification from low-quantity sequencing data despite lacking assembled sex chromosomes
Authors: Cabrera Andrea A. , Rey-Iglesia Alba , Louis Marie , Skovrind Mikkel , Westbury Michael V , Lorenzen Eline D 
Published: November 2021

AbstractAccurate sex identification is crucial for elucidating the biology of a species. In the absence of directly observable sexual characteristics, sex identification of wild fauna can be challenging, if not impossible. Molecular sexing offers a powerful alternative to morphological sexing approaches. Here, we present SeXY, a novel sex-identification pipeline, for very low-coverage shotgun sequencing data from a single individual. SeXY was designed to utilise low-effort screening data for sex identification and does not require a conspecific sex-chromosome assembly as reference. We assess the accuracy of our pipeline to data quantity by downsampling sequencing data from 100,000 to 1,000 mapped reads, and to reference genome selection by mapping to a variety of reference genomes of various qualities and phylogenetic distance. We show that our method is 100% accurate when mapping to a high-quality (highly contiguous N50 > 30 Mb) conspecific genome, even down to 1,000 mapped reads. For lower-quality reference assemblies (N50 < 30 Mb), our method is 100% accurate with 50,000 mapped reads, regardless of reference assembly quality or phylogenetic distance. The SeXY pipeline provides several advantages over previously implemented methods; SeXY (i) requires sequencing data from only a single individual, (ii) does not require assembled conspecific sex-chromosomes, or even a conspecific reference assembly, (iii) takes into account variation in coverage across the genome, and (iv) is accurate with only 1,000 mapped reads in many cases.
Age-Volume Associations in Cerebellar Regions by Sex and Reproductive Stage
Authors: Hicks Tracey H. , Ballard Hannah K. , Sang Huiyan , Bernard Jessica A. 
Published: November 2021

AbstractIntroductionThe cerebellum has established associations with motor function and a well- recognized role in cognition. In advanced age, cognitive and motor impairments contribute to reduced quality of life and are more common. Regional cerebellar volume is associated with performance across these domains and sex hormones may influence this volume. Examining sex differences in regional cerebellar volume in conjunction with age, and in the context of reproductive stage stands to improve our understanding of cerebellar aging and pathology.MethodsData from 530 healthy adults (ages 18-88; 49% female) from the Cambridge Centre for Ageing and Neuroscience database were used here. CERES was utilized to assess lobular volume in T1-weighted images. We examined sex differences in adjusted regional cerebellar volume while controlling for age. A subgroup (n = 354, 50% female) was used to assess group differences in female reproductive stages as compared to age-matched males.ResultsSex differences in adjusted volume were seen across most anterior and posterior cerebellar lobules. The majority of cerebellar regions had significant linear relationships with age in males and females. However, there were no interactions between sex and reproductive stage groups (i.e., female reproductive stage did not display a relationship with regional cerebellar volume).DiscussionWe found sex differences in volume across much of the cerebellum, linear associations with age, and did not find an effect of female reproductive stage on regional cerebellar volume. Longitudinal investigation into hormonal influences on cerebellar structure and function is warranted as hormonal changes with menopause may impact structure over time.
Increased Occurrence of Treponema spp. and Double-species Infections in Patients with Alzheimer’s Disease
Authors: Nemergut Michal , Batkova Tereza , Vigasova Dana , Bartos Milan , Hlozankova Martina , Schenkmayerova Andrea , Liskova Barbora , Sheardova Katerina , Vyhnalek Martin , Hort Jakub , Laczo Jan , Kovacova Ingrid , Sitina Michal , Matej Radoslav , Jancalek Radim , Marek Martin , Damborsky Jiri 
Published: November 2021

AbstractObjectiveAlthough the link between microbial infections and Alzheimer’s disease (AD) has been demonstrated in multiple studies, the involvement of pathogens in the development of AD remains unclear. Therefore, this theory beckons further systematic investigation. In this study, we have examined the association between the 10 most widely discussed viral and bacterial pathogens found in serum and cerebrospinal fluid (CSF) from patients with AD.MethodsWe have used an in-house developed multiplex PCR kit for simultaneous detection of five bacterial and five viral pathogens in serum and CSF from 50 AD patients and 53 healthy controls. Data analysis was performed with multiple statistical methods: Fisher’s exact test, chisquare goodness of fit test, and one-sample proportion test.ResultsWe observed an increased frequency of AD patients tested positive for Treponema spp. (AD: 62.2%; CTRL: 30.3%; p-value = 0.007). Furthermore, we confirmed a significantly higher prevalence of cases with two and more simultaneous infections in AD patients compared to controls (AD: 24%; CTRL 7.5%; p-value = 0.029). The studied pathogens were widespread equally in serum and CSF. Borrelia burgdorferi, human herpesvirus 7, and human cytomegalovirus were not detected in any of the studied samples.DiscussionAn increased prevalence of Treponema spp. and double-species infections in AD patients compared to the healthy controls provides further evidence of the association between microbial infections and AD. Paralleled analysis of multiple sample specimens provides complementary information and is advisable for future studies.
Multi-omics analysis for potential inflammation-related genes involved in tumor immune evasion via extended application of epigenetic data
Authors: Huang Chenshen , Wang Ning , Zhang Na , Ni Zhizhan , Liu Xiaohong , Xiong Hao , Xie Huahao , Lin Boxu , Ge Bujun , Huang Qi , Du Bing 
Published: November 2021

AbstractBackgroundAccumulating evidence suggests that inflammation-related genes may play key roles in tumor immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating antitumor immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression.MethodsThe open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments.ResultsWe identified chr9:5449463-5449962 and chr9:5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results.ConclusionOur study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumor immune evasion in cancers, suggesting the potential value for tumor treatment.
Plant-derived insulator-like sequences for control of transgene expression
Authors: Park Jubilee Y. , Kovar Lynsey , LaFayette Peter R. , Wallace Jason G. , Parrott Wayne A. 
Published: November 2021

AbstractStable and consistent transgene expression is necessary to advance plant biotechnology. Stable expression can be achieved by incorporating enhancer-blocking insulators, which are cis-regulatory elements that reduce enhancer interference in gene expression, into transgene constructs. Sufficient insulators for plant use are not available, and their discovery has remained elusive. In this work, we computationally mined the compact genome of Utricularia gibba for insulator sequences and identified short (<1 kb) sequences with potential insulator activity. Based on in vivo tests, three of these effectively mitigate the ectopic transgene expression caused by the Cauliflower Mosaic Virus 35S promoter and do so better than previously reported plant insulators. However, all sequences with apparent insulator activity also decrease the effectiveness of the CaMV 35S promoter, and thus may be more accurately classified as silencers. However, since the insulator effect is proportionately much higher than the silencing effect, these sequences are still useful for plant transformation.
Motor response vigour and fixations reflect subjective preferences during intertemporal choice
Authors: Smith Elke , Peters Jan 
Published: November 2021

AbstractValue-based decision-making is of central interest in cognitive neuroscience and psychology, as well as in the context of neuropsychiatric disorders characterised by decision-making impairments. Studies examining (neuro-)computational mechanisms underlying choice behaviour typically focus on participants’ decisions. However, there is increasing evidence that option valuation might also be reflected in motor response vigour and eye movements, implicit measures of subjective utility.To examine motor response vigour and visual fixation correlates of option valuation in intertemporal choice, we set up a task where the participants selected an option by pressing a grip force transducer, simultaneously tracking fixation shifts between options. As outlined in our preregistration (https://osf.io/k6jct), we used hierarchical Bayesian parameter estimation to model the choices assuming hyperbolic discounting, compared variants of the softmax and drift diffusion model, and assessed the relationship between response vigour and the estimated model parameters.The behavioural data were best explained by a drift diffusion model specifying a non-linear scaling of the drift rate by the subjective value differences. Replicating previous findings (Green et al., 1997; Wagner et al., 2020), we found a magnitude effect for temporal discounting, such that higher rewards were discounted less. This magnitude effect was further reflected in response vigour, such that stronger forces were exerted in the high vs. the low magnitude condition. Bayesian hierarchical linear regression further revealed higher grip forces, faster response times and a lower number of fixation shifts for trials with higher subjective value differences.Our data suggest that subjective utility or implicit valuation is reflected in response vigour during intertemporal choice. Taking into account response vigour might thus provide deeper insight into decision-making, reward valuation and maladaptive changes in these processes, e.g. in the context of neuropsychiatric disorders.
Complete genome sequence and Benzophenone-3 mineralisation potential of Rhodococcus sp. USK10, a bacterium isolated from riverbank sediment
Authors: Martin Joseph Donald , Krüger Urse Scheel , Zervas Athanasios , Schostag Morten Dencker , Nielsen Tue Kjærgaard , Aamand Jens , Hansen Lars Hestbjerg , Ellegaard-Jensen Lea 
Published: November 2021

AbstractBenzophenone-3 (BP3) is an organic UV filter whose presence in the aquatic environment has been linked to detrimental developmental impacts in aquatic organisms such as coral and fish. The genus Rhodococcus has been extensively studied and is known for possessing large genomes housing genes for biodegradation of a wide range of compounds, including aromatic carbons. Here, we present the genome sequence of Rhodococcus sp. USK10, which was isolated from Chinese riverbank sediment and is capable of utilising BP3 as the sole carbon source, resulting in full BP3 mineralisation. The genome consisted of 9,870,030 bp in 3 replicons, a G+C content of 67.2%, and 9,722 coding DNA sequences (CDSs). Annotation of the genome revealed that 179 of these CDSs are involved in metabolism of aromatic carbons. The complete genome of Rhodococcus sp. USK10 is the first complete, annotated genome sequence of a Benzophenone-3 degrading bacterium. Through radiolabelling, it is also the first bacterium proven to mineralise Benzophenone-3. Due to the widespread environmental prevalence of Benzophenone-3, coupled to its adverse impact on aquatic organisms, this characterisation provides an integral first step in better understanding the environmentally relevant degradation pathway of the commonly used UV filter. Given USK10’s ability to completely mineralise Benzophenone-3, it could prove to be a suitable candidate for bioremediation application.
Gene essentiality in cancer cell lines is modified by the sex chromosomes
Authors: Shohat Shahar , Vol Ethel , Shifman Sagiv 
Published: November 2021

AbstractHuman sex differences are thought to arise from gonadal hormones and genes on the sex chromosomes. Here we studied how sex and the sex chromosomes can modulate the outcome of mutations across the genome. We used the results of genome-wide CRISPR-based screens on 306 female and 396 male cancer cell lines to detect differences in gene essentiality between the sexes. By exploiting the tendency of cancer cells to lose or gain sex chromosomes, we were able to dissect the contribution of the Y and X chromosomes to variable gene essentiality. Using this approach, we identified 178 differentially essential genes that depend on the biological sex or the sex chromosomes. Integration with sex bias in gene expression and the rate of somatic mutations in human tumors highlighted genes that escape from X-inactivation, cancer-testis antigens, and Y-linked paralogs as central to the functional genetic differences between males and females.
Wild birds as reservoirs of multidrug-resistant enterobacteria in Mulungu, Brazil
Authors: Beleza Antonio Jackson Forte , Maciel William Cardoso , Carreira Arianne Silva , Marques Adson Ribeiro , Nogueira Carlos Henrique Guedes , Filho Neilton Monteiro Pascoal , Lima Bruno Pessoa , da Silva Isaac Neto Goes , Vasconcelos Ruben Horn , Ribeiro Leandro Rodrigues , de Castro Teixeira Régis Siqueira 
Published: November 2021

ABSTRACTCaatinga is a biome unique to Brazil that is degraded by anthropogenic actions, which lead to the loss of biodiversity putting many species at risk of extinction. The Ceará State is located in the Caatinga and has a rich avifauna comprised of 433 species including 13 species that are threatened with extinction, which are found in the Baturité Massif. The aim of this study was to investigate the frequency and diversity of enterobacteria in wild birds and to determine their susceptibility to antimicrobials. Cloacal swab samples were collected from 50 individuals of 28 different species, including the Ceara Gnatheter (Conopophaga cearae) and Red-necked Tanager (Tangara cyanocephala cearensis), which are classified as vulnerable (VU) by the Brazilian Ministry of the Environment. A total of 55 isolates belonging to 14 different species of Enterobacteriaceae were identified. Among these, Pantoea agglomerans and Escherichia coli were the most prevalent species with isolation rates of 36% and 26%, respectively. The highest rate of antimicrobial resistance found was to ampicillin (41.8%), followed by nalidixic Acid (36.3%) and amoxicillin associated with clavulanic acid (32.7%). The drugs with the best efficacy were tobramycin (96.4%), ciprofloxacin (92.6%) and tetracycline (90.9%). Multidrug resistance was observed in 23.5% of the analyzed strains. This research provides important information about the composition of the cloacal microbiota of wild birds in Mulungu, Brazil, as well as their health status. In addition, these results demonstrate that they harbor multidrug-resistant strains of Enterobacteriaceae.