Substantial Overlap Research Articles

Historical and morphological evidence for a remnant population of Lake Erie cisco Coregonus artedi (albus) in Crystal Lake, Pennsylvania

The cisco (Coregonus artedi) population in Crystal Lake, Pennsylvania, is of great scientific interest as it either originated from Lake Erie or Lake Ontario. Cisco in Lake Erie once supported the largest freshwater fishery in the world, but populations were extirpated by 1960. We conducted a morphological analysis of Crystal Lake cisco to determine whether it was consistent with a distinctive Lake Erie form (albus), which was also historically documented, albeit rarely, in western Lake Ontario. Using principal component analysis, we compared eight morphometric ratios and one meristic from our Crystal Lake cisco collection with historical and contemporary collections of cisco from Lakes Erie and Ontario. Maximum likelihood ellipse overlaps between Crystal Lake cisco and presumed albus (the dominant Lake Erie form prior to extirpation) collections averaged 54%. For all groups, the greatest morphological overlap (73.9%) occurred between Crystal Lake and 1957 Lake Erie cisco, which only differed from Crystal Lake cisco in dorsal fin length. Alternatively, overlap between Crystal Lake cisco and all other Lake Ontario collections averaged 3.2%. Our results demonstrate that Crystal Lake cisco are likely an albus form; furthermore, historical documentation and our morphological results suggest a Lake Erie origin. Substantial overlap between Crystal Lake cisco and Lake Ontario albus collected in 1917 is likely explained by continuous entrainment of Lake Erie larvae into Lake Ontario. We suspect this created an albus metapopulation spanning Lakes Erie and Ontario, yet albus are no longer observed in either lake today.

Multivariate, Multi-omic Analysis in 799,429 Individuals Identifies 134 Loci Associated with Somatoform Traits.

Somatoform traits, which manifest as persistent physical symptoms without a clear medical cause, are prevalent and pose challenges to clinical practice. Understanding the genetic basis of these disorders could improve diagnostic and therapeutic approaches. With publicly available summary statistics, we conducted a multivariate genome-wide association study (GWAS) and multi-omic analysis of four somatoform traits-fatigue, irritable bowel syndrome, pain intensity, and health satisfaction-in 799,429 individuals genetically similar to Europeans. Using genomic structural equation modeling, GWAS identified 134 loci significantly associated with a somatoform common factor, including 44 loci not significant in the input GWAS and 8 novel loci for somatoform traits. Gene-property analyses highlighted an enrichment of genes involved in synaptic transmission and enriched gene expression in 12 brain tissues. Six genes, including members of the CD300 family, had putatively causal effects mediated by protein abundance. There was substantial polygenic overlap (76-83%) between the somatoform and externalizing, internalizing, and general psychopathology factors. Somatoform polygenic scores were associated most strongly with obesity, Type 2 diabetes, tobacco use disorder, and mood/anxiety disorders in independent biobanks. Drug repurposing analyses suggested potential therapeutic targets, including MEK inhibitors. Mendelian randomization indicated potentially protective effects of gut microbiota, including Ruminococcus bromii. These biological insights provide promising avenues for treatment development.

Prospective One-Health investigation into low-abundant extended-spectrum β-lactamase producing Enterobacterales enables detection of potential dissemination events and persistence

BackgroundFollowing a one-health approach, we sought to determine reservoirs of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles. MethodsFrom 06/2017–05/2019, ESBL-PE isolates were recovered from clinical samples routinely collected at the University Hospital Basel (Basel, Switzerland), as well as from wastewater and foodstuffs collected monthly at predefined locations throughout the city of Basel. Whole-genome sequencing was performed for characterization of ESBL-PE isolates. ResultsAmong 1634 isolates recovered, 114 (7%) belonged to 17 low-abundant ESBL-PE species.Seven species originated from more than one compartment, mainly from clinical and wastewater samples (6/17). Sixteen different ESBL genes were identified, with blaCTX-M-15 (27%), blaFONA-6 (23%) and blaSHV-12 (16%) being most frequent. The blaCTX-M-1 gene was the only ESBL gene recovered from all three compartments. Putative plasmids constituted 60% of ESBL gene-containing contigs, while chromosomes comprised 40%. Foodstuff isolates showed the highest proportion (91%, 41/45) of ESBL genes located on chromosomes, whereas wastewater isolates had the highest proportion (95%, 37/39) of putative plasmids. Multi-replicon combinations were identified in 81% of the isolates. Epidemiological links were found among some clinical and wastewater isolates. ConclusionsThe dominance of blaCTX-M-15 among low-abundant ESBL-PE species supports its species-independent transmission potential beyond the E. coli and K. pneumoniae complex, and blaCTX-M-1 may be transmitted between strains recovered from different compartments. The substantial overlap between low-abundant ESBL-PE present in wastewater and clinical samples supports the utility of wastewater surveillance for antibiotic resistance monitoring.

"Comparative Analysis of Glycoproteomic Software Using a Tailored Glycan Database".

Glycoproteomics is a rapidly developing field, and data analysis has been stimulated by several technological innovations. As a result, there are many software tools from which to choose; and each comes with unique features that can be difficult to compare. This work presents a head-to-head comparison of five modern analytical software: Byonic, Protein Prospector, MSFraggerGlyco, pGlyco3, and GlycoDecipher. To enable a meaningful comparison, parameter variables were minimized. One potential confounding variable is the glycan database that informs glycoproteomic searches. We performed glycomic profiling of the samples and used the output to construct matched glycan databases for each software. Up to 19,000 glycopeptide spectra were identified across three replicates of wild-type SH-SY5Y cells. There was substantial overlap among most software for glycoproteins identified, locations of glycosites, and glycans, although Byonic reported a suspiciously large number of glycoproteins and glycosites of questionable reliability. We show that Protein Prospector identified the most glycopeptide spectrum matches with high agreement to known glycosites in UniProt. Overall, our results indicate that glycoproteomic searches should involve more than one software to generate confidence. It may be useful to consider software with peptide-first approaches and with glycan-first approaches.

Is the Norwegian stepped care model for allocation of patients with mental health problems working as intended? A cross-sectional study

ABSTRACT Objective Stepped care models are frameworks for mental health care systems in several countries. According to Norwegian guidelines, individuals with mental health problems of mild severity should be treated in community mental health services, moderate severity in specialist mental health services, while complex/severe problems are often a shared responsibility. This study investigated whether patients are allocated as intended. Methods In a cross-sectional study, 4061 outpatients recruited from community- and specialist mental health services reported demographic variables, symptoms of anxiety/depression, functional impairment, health status, and sick leave status. The community sample consisted of two subsamples: mild/moderate problems and complex problems. Results There was substantial overlap (80%–99%) of symptoms, impairment, and health between community- and specialist mental health services. More impairment, worse health, lower age, and being male were associated with treatment at specialist level compared to community mild/moderate. Better health, being in a relationship, and lower age were associated with specialized treatment compared to community complex group. Conclusion The limited association between treatment level and symptoms and functional impairment reveals inconsistencies between treatment guidelines and clinical practice. How the existing organization affects patient outcomes and satisfaction should be investigated further.

Connectome predictive modeling of trait mindfulness.

Trait mindfulness refers to one's disposition or tendency to pay attention to their experiences in the present moment, in a non-judgmental and accepting way. Trait mindfulness has been robustly associated with positive mental health outcomes, but its neural underpinnings are poorly understood. Prior resting-state fMRI studies have associated trait mindfulness with within- and between-network connectivity of the default-mode (DMN), fronto-parietal (FPN), and salience networks. However, it is unclear how generalizable the findings are, how they relate to different components of trait mindfulness, and how other networks and brain areas may be involved. To address these gaps, we conducted the largest resting-state fMRI study of trait mindfulness to-date, consisting of a pre-registered connectome predictive modeling analysis in 367 adults across three samples collected at different sites. In the model-training dataset, we did not find connections that predicted overall trait mindfulness, but we identified neural models of two mindfulness subscales, Acting with Awareness and Non-judging. Models included both positive networks (sets of pairwise connections that positively predicted mindfulness with increasing connectivity) and negative networks, which showed the inverse relationship. The Acting with Awareness and Non-judging positive network models showed distinct network representations involving FPN and DMN, respectively. The negative network models, which overlapped significantly across subscales, involved connections across the whole brain with prominent involvement of somatomotor, visual and DMN networks. Only the negative networks generalized to predict subscale scores out-of-sample, and not across both test datasets. Predictions from both models were also negatively correlated with predictions from a well-established mind-wandering connectome model. We present preliminary neural evidence for a generalizable connectivity models of trait mindfulness based on specific affective and cognitive facets. However, the incomplete generalization of the models across all sites and scanners, limited stability of the models, as well as the substantial overlap between the models, underscores the difficulty of finding robust brain markers of mindfulness facets.

Cognitive and sociolectal constraints on the theme-recipient alternation: evidence from Mandarin

Abstract We explore the cognitive and sociolectal constraints that probabilistically regulate the theme-recipient (or “dative”) alternation in modern varieties of Mandarin and how these constraints interact with each other. Based on an extensively annotated corpus dataset and regression modeling, we found that the probabilistic grammar that shapes the theme-recipient alternation is fundamentally stable across regional and genre varieties of Mandarin. This general stability notwithstanding, significant variation regarding the importance of cognitive constraints across different sociolectal constraints is detected. Crucially, the analysis revealed that recipient syntactic complexity has a much greater effect in Taiwan Mandarin than in Mainland Mandarin. The effect of theme concreteness is also found to be significantly reduced in telephone conversations compared to broadcast news. Corpus-based findings were cross-validated using a psycholinguistic rating task experiment. While the results of the two approaches demonstrate substantial overlap, they also exhibit diverging patterns at the level of interaction between regional variety and recipient complexity, potentially indicating nuanced differences between the two approaches. The findings provide evidence that interactional patterns between cognitive and sociolectal constraints on probabilistic grammatical alternations may be shared across languages, despite their distinct socio-cultural factors that shape variation in human interaction.

Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

Standardized risk levels for violent recidivism risk assessed with the HCR-20: an exploration

ABSTRACT Risk assessment plays an important role in forensic mental health care. The way the conclusions of those risk assessments are communicated varies considerably across instruments. In an effort to make them more comparable, Hanson, R. K., Bourgon, G., McGrath, R., Kroner, D. D., Amora, D. A., Thomas, S. S., & Tavarez, L. P. [2017. A five-level risk and needs system: Maximizing assessment results in corrections through the development of a common language. The Council of State Governments Justice Center. https://csgjusticecenter.org/wp-content/uploads/2017/01/A-Five-Level-Risk-and-Needs-System_Report.pdf] developed the Five-Level Risk and Needs System, placing the conclusions of different instruments along five theoretically meaningful levels. The current study explores a Five-Level Risk and Needs system for violent recidivism to which the numerical codings of the HCR-20 Version 2 and its successor, the HCR-20V3 are calibrated, using a combined sample from six previous studies for the HCR-20 Version 2 (n = 411 males with a violent index offence) and a pilot sample for the HCR-20V3 (n = 66 males with a violent index offence). Baselines for the five levels were defined by a combination of theoretical (e.g. expert meetings) and empirical (e.g. literature review) considerations. The calibration of the HCR-20 Version 2 was able to detect four levels, from a combined level I/II to an adjusted level V. The provisional calibration of the HCR-20V3 showed a substantial overlap with the HCR-20 Version 2, with each level boundary having a 2-point difference. Implications for practice and future research are discussed.

Promoting Self-Management in Adults with Type 2 Diabetes: Development of the Impact of Glucose Monitoring on Self-Management Scale

ObjectivesType 2 diabetes (T2D) management requires behavioural engagement to achieve optimal outcomes and continuous glucose monitoring (CGM) technologies may facilitate self-management. In this study we describe the development and validation of a self-report instrument, the Impact of Glucose Monitoring on Self-Management Scale (IGMSS), assessing the impact of device use (primarily CGM but also self-monitored blood glucose [SMBG]) on the capability, motivation, and opportunity to engage in self-management. MethodsPotential items were generated from 3 sources: themes and quotes from 13 adults with T2D motivated by CGM use who participated in a qualitative study; behaviour change theory identifying capability, opportunity, and motivation to self-manage; and expert committee review of items. An initial pool of 42 items were generated describing CGM as promoting personalized knowledge, improved health (Capability), improved relationships, having positive device characteristics (Opportunity), and improved engagement in self-management (Motivation). Based on expert committee consensus, items were written so as to be completed by those using any glucose-sensing device (SMBG and CGM). Psychometric evaluation was conducted with 514 English-speaking Canadians. Scale reduction (22 final items) was completed using item-response distribution, internal consistency, factor analysis, and expert opinion. Construct and convergent validity were evaluated using the Impact of Glucose Monitoring Satisfaction Scale, the Diabetes Self-Management Questionnaire, the Diabetes Distress Scale, the 5-item World Health Organization Well-Being Index, and the Centre for Epidemiology Depression Scale. Test–retest reliability was determined for 130 participants. ResultsInternal consistency was high for all scales, ranging from 0.73 to 0.91. Test–retest reliability ranged from 0.58 to 0.79, except for Device Characteristics. Construct and convergent validity indices were acceptable. There was substantial overlap between the IGMSS and established measures of CGM satisfaction. IGMSS findings were also predictive of self-management behaviour and emotional functioning. ConclusionsThe IGMSS has positive psychometric characteristics and has the potential to screen people with T2D for engagement in diabetes self-management using CGM or any sensing device. Scores can be determined for various aspects of Capability (Personalized Knowledge, Improved Health), Opportunity (Relationships and Device Characteristics), and Motivation.

Controlled Noise: Evidence of epigenetic regulation of Single-Cell expression variability.

Understanding single-cell expression variability (scEV) or gene expression noise among cells of the same type and state is crucial for delineating population-level cellular function. While epigenetic mechanisms are widely implicated in gene expression regulation, a definitive link between chromatin accessibility and scEV remains elusive. Recent advances in single-cell techniques enable the study of single-cell multiomics data that include the simultaneous measurement of scATAC-seq and scRNA-seq within individual cells, presenting an unprecedented opportunity to address this gap. This paper introduces an innovative testing pipeline to investigate the association between chromatin accessibility and scEV. With single-cell multiomics data of scATAC-seq and scRNA-seq, the pipeline hinges on comparing the prediction performance of scATAC-seq data on gene expression levels between highly variable genes (HVGs) and non-highly variable genes (non-HVGs). Applying this pipeline to paired scATAC-seq and scRNA-seq data from human hematopoietic stem and progenitor cells, we observed a significantly superior prediction performance of scATAC-seq data for HVGs compared to non-HVGs. Notably, there was substantial overlap between well-predicted genes and HVGs. The gene pathways enriched from well-predicted genes are highly pertinent to cell type-specific functions. Our findings support the notion that scEV largely stems from cell-to-cell variability in chromatin accessibility, providing compelling evidence for the epigenetic regulation of scEV and offering promising avenues for investigating gene regulation mechanisms at the single-cell level. The source code and data used in this paper can be found at https://github.com/SiweiCui/EpigeneticControlOfSingle-CellExpressionVariability. Supplementary data are available at Bioinformatics online.

Peripheral Microvascular Dysfunction in Children and Adults with Congenital Heart Disease: A Literature Review.

Although there is a continually growing number of patients with congenital heart disease (CHD) due to medical and surgical advances, these patients still have a poorer prognosis compared to healthy individuals of similar age. In patients with heart failure, microvascular dysfunction (MVD) has recently emerged as a crucial modulator of disease initiation and progression. Because of the substantial pathophysiological overlap between CHD and heart failure induced by other etiologies, MVD could be important in the pathophysiology of CHD as well. MVD is believed to be a systemic disease and may be manifested in several vascular beds. This review will focus on what is currently known about MVD in the peripheral vasculature in CHD. Therefore, a search on the direct assessment of the vasodilatory capacity of the peripheral microcirculation in patients with CHD was conducted in the PubMed database. Since there is little data available and the reported studies are also very heterogeneous, peripheral MVD in CHD is not sufficiently understood to date. Its exact extent and pathophysiological relevance remain to be elucidated in further research.

Integration of citizen science and eDNA reveals novel ecological insights for marine fish conservation

AbstractIn the face of climate change, the accelerating nature crisis, and other anthropogenic impacts, conserving biodiversity demands effective monitoring. While innovative approaches have emerged to enhance biodiversity assessment, significant data gaps persist, particularly within marine ecosystems. In this study, we assess the utility of combining citizen (community) science with environmental DNA (eDNA) metabarcoding for characterizing and quantifying marine fish biodiversity. Over the summer of 2022, 32 volunteers conducted extensive water sampling in a large Norwegian fjord, yielding 96 samples. Contrasting eDNA findings with conventional observational surveys (such as a national species registration database and beach seine surveys) unveiled a substantial overlap in recorded species inventories. The eDNA citizen science initiative identified previously undocumented species and rediscovered others emphasizing an increase in warm‐water species within the study area. Additionally, eDNA data unveiled reduced diversity within the inner fjord relative to the outer fjord. To conclude, our study demonstrates the successful integration of eDNA within a citizen science framework, facilitating comprehensive biodiversity tracking across coastal marine regions. These findings hold promise for advancing marine conservation efforts by providing valuable data to inform critical decision‐making processes.

Disruption of liquid/liquid phase separation in asymmetric GUVs prepared by hemifusion.

Model asymmetric bilayers are useful for studying the coupling between lateral and transverse lipid organization. Here, we used calcium-induced hemifusion to create asymmetric giant unilamellar vesicles (aGUVs) for exploring the phase behavior of 16:0-PC/16:1-PC/Cholesterol, a simplified model for the mammalian plasma membrane. Symmetric GUVs (sGUVs) were first prepared using a composition that produced coexisting liquid-disordered and liquid-ordered phases visible by confocal fluorescence microscopy. The sGUVs were then hemifused to a supported lipid bilayer (SLB) composed of uniformly mixed 16:1-PC/Cholesterol. The extent of outer leaflet exchange was quantified in aGUVs in two ways: (1) from the reduction in fluorescence intensity of a lipid probe initially in the sGUV ("probe exit"); or (2) from the gain in intensity of a probe initially in the SLB ("probe entry"). These measurements revealed a large variability in the extent of outer leaflet exchange in aGUVs within a given preparation, and two populations with respect to their phase behavior: a subset of vesicles that remained phase separated, and a second subset that appeared uniformly mixed. Moreover, a correlation between phase behavior and extent of asymmetry was observed, with more strongly asymmetric vesicles having a greater probability of being uniformly mixed. We also observed substantial overlap between these populations, an indication that the uncertainty in measured exchange fraction is high. We developed models to determine the position of the phase boundary (i.e., the fraction of outer leaflet exchange above which domain formation is suppressed) and found that the phase boundaries determined separately from probe-entry and probe-exit data are in good agreement. Our models also provide improved estimates of the compositional uncertainty of individual aGUVs. We discuss several potential sources of uncertainty in the determination of lipid exchange from fluorescence measurements.

Leveraging BIM for Enhanced Camera Allocation Planning at Construction Job Sites: A Voxel-Based Site Coverage and Overlapping Analysis

In the construction industry, the imperative for visual surveillance mechanisms is underscored by the need for safety monitoring, resources, and progress tracking, especially with the adoption of vision intelligence technology. Traditional camera installation plans often move toward coverage and cost objectives without considering substantial coverage overlap, inflating processing and storage requirements, and complicating subsequent analyses. To address these issues, this research proposes a voxel-based site coverage and overlapping analysis for camera allocation planning in parametric BIM environments, called the PBA approach. The first step is to collect information from the BIM model, which is the input for the parametric modeling step. After that, the PBA approach simulates the virtual devices and the construction layout by employing visual language programming and then generates a coverage area. Lastly, the performance simulation and evaluation of various placement scenarios against predefined criteria are conducted, including visual coverage and overlapping optimization for eliminating data redundancy purposes. The proposed approach is evaluated through its application to construction projects. The results from these various implementations indicate a marked decrease in data overlap and an overall enhancement in surveillance efficacy. This research contributes a novel, BIM-centric solution to visual information adoption in the construction industry, offering a scalable approach to optimize camera placement while mitigating overlapping areas.

Five amino acid mismatches in the zinc-finger domains of Cellulose Synthase 5 and Cellulose Synthase 6 cooperatively modulate their functional properties by controlling homodimerization in Arabidopsis.

Cellulose synthase 5 (CESA5) and CESA6 are known to share substantial functional overlap. In the zinc-finger domain (ZN) of CESA5, there are five amino acid (AA) mismatches when compared to CESA6. These mismatches in CESA5 were replaced with their CESA6 counterparts one by one until all were replaced, generating nine engineered CESA5s. Each N-terminal enhanced yellow fluorescent protein-tagged engineered CESA5 was introduced to prc1-1, a cesa6 null mutant, and resulting mutants were subjected to phenotypic analyses. We found that five single AA-replaced CESA5 proteins partially rescue the prc1-1 mutant phenotypes to different extents. Multi-AA replaced CESA5s further rescued the mutant phenotypes in an additive manner, culminating in full recovery by CESA5G43R + S49T+S54P+S80A+Y88F. Investigations in cellulose content, cellulose synthase complex (CSC) motility, and cellulose microfibril organization in the same mutants support the results of the phenotypic analyses. Bimolecular fluorescence complementation assays demonstrated that the level of homodimerization in every engineered CESA5 is substantially higher than CESA5. The mean fluorescence intensity of CSCs carrying each engineered CESA5 fluctuates with the degree to which the prc1-1 mutant phenotypes are rescued by introducing a corresponding engineered CESA5. Taken together, these five AA mismatches in the ZNs of CESA5 and CESA6 cooperatively modulate the functional properties of these CESAs by controlling their homodimerization capacity, which in turn imposes proportional changes on the incorporation of these CESAs into CSCs.

Accurate identification of individuals with subjective cognitive decline using 3D regional fractal dimensions on structural magnetic resonance imaging

Background and ObjectiveAccurate identification of individuals with subjective cognitive decline (SCD) is crucial for early intervention and prevention of neurodegenerative diseases. Fractal dimensionality (FD) has emerged as a robust and replicable measure, surpassing traditional geometric metrics, in characterizing the intricate fractal geometrical properties of brain structure. Nevertheless, the effectiveness of FD in identifying individuals with SCD remains largely unclear. A 3D regional FD method can be suggested to characterize and quantify the spatial complexity of the precise gray matter, providing insights into cognitive aging and aiding in the automated identification of individuals with SCD. MethodsThis study introduces a novel integer ratio based 3D box-counting fractal analysis (IRBCFA) to quantify regional fractal dimensions (FDs) in structural magnetic resonance imaging (MRI) data. The innovative method overcomes limitations of conventional box-counting techniques by accommodating arbitrary box sizes, thereby enhancing the precision of FD estimation in small, yet neurologically significant, brain regions. ResultsThe application of IRBCFA to two publicly available datasets, OASIS-3 and ADNI, consisting of 520 and 180 subjects, respectively. The method identified discriminative regions of interest (ROIs) predominantly within the limbic system, fronto-parietal region, occipito-temporal region, and basal ganglia-thalamus region. These ROIs exhibited significant correlations with cognitive functions, including executive functioning, memory, social cognition, and sensory perception, suggesting their potential as neuroimaging markers for SCD. The identification model trained on these ROIs demonstrated exceptional performance achieving over 93 % accuracy on the discovery dataset and exceeding 87 % on the independent testing dataset. Furthermore, an exchange experiment between datasets revealed a substantial overlap in discriminative ROIs, highlighting the robustness of our method across diverse populations. ConclusionOur findings indicate that IRBCFA can serve as a valuable tool for quantifying the spatial complexity of gray matter, providing insights into cognitive aging and aiding in the automated identification of individuals with SCD. The demonstrated generalizability and robustness of this method position it as a promising tool for neurodegenerative disease research and offer potential for clinical applications.

Dietary sucrose determines the regulatory activity of lithium on gene expression and lifespan in Drosophila melanogaster.

The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly Drosophila melanogaster. It is noteworthy that lithium is attributed with insulin-like activity as it stimulates protein kinase B/Akt and suppresses the activity of glycogen synthase kinase-3 (GSK-3). However, its interaction with dietary sugar has largely remained unexplored. Therefore, we investigated the effects of lithium supplementation on known lithium-sensitive parameters in fruit flies, such as lifespan, body composition, GSK-3 phosphorylation, and the transcriptome, while varying the dietary sugar concentration. For all these parameters, we observed that the efficacy of lithium was significantly influenced by the sucrose content in the diet. Overall, we found that lithium was most effective in enhancing longevity and altering body composition when added to a low-sucrose diet. Whole-body RNA sequencing revealed a remarkably similar transcriptional response when either increasing dietary sucrose from 1% to 10% or adding 1 mM LiCl to a 1% sucrose diet, characterized by a substantial overlap of nearly 500 differentially expressed genes. Hence, dietary sugar supply is suggested as a key factor in understanding lithium bioactivity, which could hold relevance for its therapeutic applications.

AuriDESI: mock catalogues for the DESI Milky Way Survey

ABSTRACT The Dark Energy Spectroscopic Instrument Milky Way Survey (DESI MWS) will explore the assembly history of the Milky Way by characterizing remnants of ancient dwarf galaxy accretion events and improving constraints on the distribution of dark matter in the outer halo. We present mock catalogues that reproduce the selection criteria of MWS and the format of the final MWS data set. These catalogues can be used to test methods for quantifying the properties of stellar halo substructure and reconstructing the Milky Way’s accretion history with the MWS data, including the effects of halo-to-halo variance. The mock catalogues are based on a phase-space kernel expansion technique applied to star particles in the Auriga suite of six high-resolution lambda-cold dark matter magnetohydrodynamic zoom-in simulations. They include photometric properties (and associated errors) used in DESI target selection and the outputs of the MWS spectral analysis pipeline (radial velocity, metallicity, surface gravity, and temperature). They also include information from the underlying simulation, such as the total gravitational potential and information on the progenitors of accreted halo stars. We discuss how the subset of halo stars observable by MWS in these simulations corresponds to their true content and properties. These mock Milky Ways have rich accretion histories, resulting in a large number of substructures that span the whole stellar halo out to large distances and have substantial overlap in the space of orbital energy and angular momentum.

Using expression data to fine map QTL associated with fertility in dairy cattle

BackgroundFemale fertility is an important trait in dairy cattle. Identifying putative causal variants associated with fertility may help to improve the accuracy of genomic prediction of fertility. Combining expression data (eQTL) of genes, exons, gene splicing and allele specific expression is a promising approach to fine map QTL to get closer to the causal mutations. Another approach is to identify genomic differences between cows selected for high and low fertility and a selection experiment in New Zealand has created exactly this resource. Our objective was to combine multiple types of expression data, fertility traits and allele frequency in high- (POS) and low-fertility (NEG) cows with a genome-wide association study (GWAS) on calving interval in Australian cows to fine-map QTL associated with fertility in both Australia and New Zealand dairy cattle populations.ResultsVariants that were significantly associated with calving interval (CI) were strongly enriched for variants associated with gene, exon, gene splicing and allele-specific expression, indicating that there is substantial overlap between QTL associated with CI and eQTL. We identified 671 genes with significant differential expression between POS and NEG cows, with the largest fold change detected for the CCDC196 gene on chromosome 10. Our results provide numerous candidate genes associated with female fertility in dairy cattle, including GYS2 and TIGAR on chromosome 5 and SYT3 and HSD17B14 on chromosome 18. Multiple QTL regions were located in regions with large numbers of copy number variants (CNV). To identify the causal mutations for these variants, long read sequencing may be useful.ConclusionsVariants that were significantly associated with CI were highly enriched for eQTL. We detected 671 genes that were differentially expressed between POS and NEG cows. Several QTL detected for CI overlapped with eQTL, providing candidate genes for fertility in dairy cattle.