The indispensable role of time in autonomous development.

Advances in single-cell analysis have led to a picture of development largely in agreement with Waddington's eponymous epigenetic landscape, in which a cell's fate is determined by its basin of attraction in a high-dimensional gene-expression space. Yet conceptual gaps remain as to how a single progenitor can simultaneously generate multiple endpoints, and why time should be required of the process at all. We propose a theoretical model based on the Hamiltonian mechanics of n-dimensional rotational motion, which resolves these paradoxes.

ablation in skeletal muscle results in functional alterations.

, a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear.

Refining the genetic risk of breast cancer with rare haplotypes and pattern mining.

Hundreds of common variants have been found to confer small but significant differences in breast cancer risk, supporting the widely accepted polygenic model of inherited predisposition. Using a novel closed-pattern mining algorithm, we provide evidence that rare haplotypes may refine the association of breast cancer risk with common germline alleles. Our method, called Chromosome Overlap, consists in iteratively pairing chromosomes from affected individuals and looking for noncontiguous patterns of shared alleles.

Mustn1 ablation in skeletal muscle results in increased glucose tolerance concomitant with upregulated GLUT expression in male mice.

Glucose homeostasis is closely regulated to maintain energy requirements of vital organs and skeletal muscle plays a crucial role in this process. Mustn1 is expressed during embryonic and postnatal skeletal muscle development and its function has been implicated in myogenic differentiation and myofusion. Whether Mustn1 plays a role in glucose homeostasis in anyway remains largely unknown.

Inference on the Genetic Architecture of Breast Cancer Risk.

Background: What are the major determinants of women's breast cancer risk? Rare mutations such as those in the BRCA1/2 genes, polygenic scores of common alleles identified by genome-wide association studies, or nongenetic factors?

Methods: The population-based Nordic Twin Study of Cancer, with 3,933 breast cancer cases among 21,054 monozygotic (MZ) and 30,939 dizygotic (DZ) female twin pairs, provides three key clues to this question: (i) the average lifetime risk, approximately 8%, does not differ by twin zygosity; (ii) the mean time interval between diagnoses when both twins develop disease (i.e., disease concordance) also does not differ by zygosity; but, (iii) conditioning on one twin having developed disease, the incidence rate in the co-twin is approximately 1% per year if the pair is MZ and 0.

Genome-Wide Analysis of Rare Haplotypes Associated with Breast Cancer Risk.

Unlabelled: Numerous common genetic variants have been linked to breast cancer risk, but they only partially explain the total breast cancer heritability. Inference from Nordic population-based twin data indicates rare high-risk loci as the chief determinant of breast cancer risk. Here, we use haplotypes, rather than single variants, to identify rare high-risk loci for breast cancer.

Corrigendum: The Magnitude of Black/Hispanic Disparity in COVID-19 Mortality Across United States Counties During the First Waves of the COVID-19 Pandemic.

[This corrects the article DOI: 10.3389/ijph.2021.

The Magnitude of Black/Hispanic Disparity in COVID-19 Mortality Across United States Counties During the First Waves of the COVID-19 Pandemic.

To quantify the Black/Hispanic disparity in COVID-19 mortality in the United States (US). COVID-19 deaths in all US counties nationwide were analyzed to estimate COVID-19 mortality rate ratios by county-level proportions of Black/Hispanic residents, using mixed-effects Poisson regression. Excess COVID-19 mortality counts, relative to predicted under a counterfactual scenario of no racial/ethnic disparity gradient, were estimated.

Forgoing needed medical care among long-term survivors of childhood cancer: racial/ethnic-insurance disparities.

Purpose: To investigate racial/ethnic-related disparities by insurance status in "forgoing needed medical care in the last year due to finances" in childhood cancer survivors.

Methods: Our study included 3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx survivors from the St. Jude Lifetime Cohort Study.

Noncommutative Biology: Sequential Regulation of Complex Networks.

Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome.