Biology subjects

O'Connell, M.

Publications and source records attributed to O'Connell, M..

5 recordsLinked to original sources

bioRxiv2024

Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study

Puberty is a critical developmental process that is associated with changes in steroid hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes) and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92 - 13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive DevelopmentSM (ABCD(R)) Study. We used elastic-net regression with cross- validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, were among the most important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.

neuroscience↗

bioRxiv2024

Global Analysis by LC-MS/MS of N6-Methyladenosine and Inosine in mRNA Reveals Complex Incidence

The precise and unambiguous detection and quantification of internal RNA modifications represents a critical step for understanding their physiological functions. The methods of direct RNA sequencing are quickly developing allowing for the precise location of internal RNA marks. This detection is however not quantitative and still presents detection limits. One of the biggest remaining challenges in the field is still the detection and quantification of m6A, m6Am and m1A modifications. The second intriguing and timely question remaining to be addressed is the extent to which individual marks are coregulated or potentially can affect each other. Here we present a methodological approach to detect and quantify several key mRNA modifications in human total RNA and in mRNA, which is difficult to purify way from contaminating tRNA. We show that the adenosine demethylase FTO primarily targets m6Am marks in noncoding RNAs in HEK293T cells. Surprisingly, we observe little effect of FTO or ALKBH5 depletion on the m6A mRNA levels. Interestingly, upregulation of ALKBH5 is accompanied by an increase in inosine level in overall mRNA.

molecular biology↗

bioRxiv2024

Enhancing Photosynthesis under Salt Stress via Directed Evolution in Cyanobacteria

A key aspect of enhancing photosynthesis is improving its recycling kinetics, enabling swift resumption of photochemical quenching following environmental disruptions or stress. Salt stress exacerbates high light stress in cyanobacteria and leads to severe yield losses in crop plants. Genetic traits that confer salt tolerance without compromising photosynthetic performance are essential for improving photosynthesis under these conditions. Here we applied accelerated evolution in Synechococcus elongatus PCC 7942 by conditionally suppressing its methyl-directed mismatch repair system to obtain beneficial genetic traits for enhanced photosynthesis under salt stress. Screening over 10,000 mutants, we isolated eight strains with increased biomass or sucrose productivity under salt stress. Genome sequencing revealed an average of 8-20 single nucleotide polymorphisms (SNPs) or indels per genome. Notably, mutations in the photosystem II (PSII) reaction center D1 gene, resulting in the amino acid changes L353F, I358N, and H359N at the carboxyl terminus of the pre-D1 (pD1) protein, improve photosynthesis under salt and combined salt and light stress by potentially accelerating D1 maturation during PSII repair. Phylogenetic analysis of pD1 across cyanobacteria and red algae highlights the broad significance of these adaptive genetic traits, underscoring the importance of leveraging evolutionary insights to improve photosynthesis under stress or fluctuating environments.

plant biology↗

bioRxiv2023

KOMPUTE: Imputing summary statistics of missing phenotypes in high-throughput model organism data

MotivationThe International Mouse Phenotyping Consortium (IMPC) is striving to build a comprehensive functional catalog of mammalian protein-coding genes by systematically producing and phenotyping gene-knockout mice for almost every protein-coding gene in the mouse genome and by testing associations between gene loss-of-function and phenotype. To date, the IMPC has identified over 90,000 gene-phenotype associations, but many phenotypes have not yet been measured for each gene, resulting in largely incomplete data; about 75.6% of association summary statistics are still missing in the latest IMPC summary statistics dataset (IMPC release version 16). ResultsTo overcome these challenges, we propose KOMPUTE, a novel method for imputing missing summary statistics in the IMPC dataset. Using conditional distribution properties of multivariate normal, KOMPUTE estimates association Z-scores of unmeasured phenotypes for a particular gene as a conditional expectation given the Z-scores of measured phenotypes. We evaluate the efficacy of the proposed method for recovering missing Z-scores using simulated and real-world data sets and compare it to a singular value decomposition (SVD) matrix completion method. Our results show that KOMPUTE outperforms the comparison method across different scenarios. Availability and implementationAn R package for KOMPUTE is publicly available at https://github.com/statsleelab/kompute, along with usage examples and results for different phenotype domains at https://statsleelab.github.io/komputeExamples. Contactleed13@miamioh.edu Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2017

Tropomyosin and a-actinin cooperation inhibits fimbrin association with actin filament networks in fission yeast

We previously discovered that competition between fission yeast actin binding proteins (ABPs) for association with F-actin helps facilitate their sorting to different F-actin networks. Specifically, competition between actin patch ABPs fimbrin Fim1 and cofilin Adf1 enhances each others activities, and rapidly displaces tropomyosin Cdc8 from the F-actin network. However, these interactions dont explain how Fim1, a robust competitor, is prevented from associating equally well with other F-actin networks. Here, with a combination of fission yeast genetics, live cell fluorescent imaging, and in vitro TIRF microscopy, we identified the contractile ring ABP -actinin Ain1 as a key sorting factor. Fim1 competes with Ain1 for association with F-actin, which is dependent upon their residence time on F-actin. Remarkably, although Fim1 outcompetes both contractile ring ABPs Ain1 and Cdc8 individually, Cdc8 enhances the bundling activity of Ain1 10-fold, allowing the combination of Ain1 and Cdc8 to inhibit Fim1 association with contractile ring F-actin.

cell biology↗