Biology subjects

Dodd, E.

Publications and source records attributed to Dodd, E..

3 recordsLinked to original sources

bioRxiv2025

Exercise serum promotes DNA damage repair and upregulates DNA repair gene PNKP in colon cancer cells

Exercise protects against colon cancer progression, but the underlying biological mechanisms remain incompletely understood. One proposed mechanism is the release of bioactive molecules into the interstitium and systemic circulation during exercise, which may act directly on precancerous or tumour cells to suppress DNA damage, inhibit proliferation, and preserve genomic stability. Here, we evaluated the effects of exercise-conditioned human serum on DNA damage kinetics and transcriptomic signatures in colon cancer cells. Blood samples were collected from 30 participants (age 50-78 years, body mass index [≥]25 kg/m2) before and immediately after a maximal incremental cycling test. LoVo cells were exposed to pre- or post-exercise serum, treated with 2 Gy irradiation, and assessed for {gamma}-H2AX foci over 24 hours. Compared to pre-exercise serum, post-exercise serum significantly reduced {gamma}-H2AX foci at 6 hours (p=0.024) and decreased the area under the curve (AUC, p=0.014), indicating accelerated DNA repair. Post-exercise serum also increased expression of the DNA repair protein PNKP in LoVo cells, both with and without irradiation (p=0.007 and p=0.029, respectively). Transcriptomic analysis revealed upregulation of mitochondrial energy metabolism and downregulation of cell cycle and proteasome-related pathways. These findings suggest that acute exercise elicits systemic responses that enhance DNA repair and shift colon cancer cells towards a less proliferative transcriptomic state under sublethal genotoxic stress, offering a potential mechanistic explanation for the protective effects of exercise against colorectal carcinogenesis.

cancer biology↗

bioRxiv2025

Probabilistic projections of distributions of kin over the life course

BACKGROUNDMathematical kinship demography is an expanding area of research. Recent papers have explored the expected number of kin a typical individual should experience. Despite the uncertainty of the future number and distributions of kin, just one paper investigates it. OBJECTIVETo develop a new method for obtaining the probability that a typical population member experiences one or more of some kin at any age through the life course. METHODSWe use combinatorics and matrix algebra to construct and project a discrete probability distribution of kin. Our model requires as inputs, age-specific mortality and fertility. CONCLUSIONSWe derive probabilities of kin-number for fixed age of kin and over all possible ages of kin. We derive expected numbers and variance of kin. We demonstrate how kinship structures are conditional on familial events. CONTRIBUTIONThe paper presents the first analytic approach allowing the projection of a full probability distribution of the number of kin of arbitrary type that a population member has over the life course.

ecology↗

bioRxiv2019

Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses. An accurate estimation of the penetrance of different cancer types in LFS is crucial to improve the clinical characterization and management of high-risk individuals of LFS. Our competing risk-based statistical model incorporates the pedigree structure efficiently into the penetrance estimation and corrects for the ascertainment bias. A set of TP53 penetrance for three cancer types (breast, BR/sarcoma, SA/others, OT) involved in LFS is then estimated from 186 pediatric-sarcoma families collected at MD Anderson Cancer Center. The penetrance was then validated on a mixed cohort of clinically ascertained families with cancer (total number of families=668). The age-dependent onset probability distributions of specific cancer types are different. For breast cancer, the TP53 penetrance goes up at an earlier age than the reported BRCA1/2 penetrance. We validated the prediction performance of the penetrance estimates via two independent cohorts combined (BR=85, SA=540, OT=158). We obtained areas under the ROC curves (AUCs) of 0.92 (BR), 0.75 (SA), and 0.81 (OT). Our R package, LFSPRO, provides risk estimates for the diagnosis of breast cancer, sarcoma, other cancers or death before cancer diagnosis in future.\n\nSignificanceCancer-specific penetrance can facilitate clinical characterization of LFS and will contribute to the management of families at high risk of LFS.

genetics↗