An empirical test of Baker's law: Dispersal favors increased rates of self-fertilization.

Baker's law is the observation that recently dispersed populations are more likely to be self-fertilizing than populations at the range core. The explanatory hypothesis is that dispersal favors self-fertilization due to reproductive assurance. Caenorhabditis elegans nematodes reproduce via either self-fertilization or outcrossing and frequently disperse in small numbers to new bacterial food sources.

The clock-like accumulation of germline and somatic mutations can arise from the interplay of DNA damage and repair.

The rates at which mutations accumulate across human cell types vary. To identify causes of this variation, mutations are often decomposed into a combination of the single-base substitution (SBS) "signatures" observed in germline, soma, and tumors, with the idea that each signature corresponds to one or a small number of underlying mutagenic processes. Two such signatures turn out to be ubiquitous across cell types: SBS signature 1, which consists primarily of transitions at methylated CpG sites thought to be caused by spontaneous deamination, and the more diffuse SBS signature 5, which is of unknown etiology.

Contract development and manufacturing organization selection: critical considerations that can make or break your cell and gene therapy development.

Background Aims: With the increase in cell and gene therapy (CGT) clinical trials in recent years has come a subsequent increase in the number of contract development and manufacturing organizations (CDMOs). Successful transition from development and early-phase clinical trials to commercialization of a CGT product often depends on selecting the best-suited CDMO. However, many CGT companies are small biotech companies that lack expertise in the field or do not have experience selecting and transferring a process to a CDMO.

Disentangling sources of clock-like mutations in germline and soma.

The rates of mutations vary across cell types. To identify causes of this variation, mutations are often decomposed into a combination of the single base substitution (SBS) "signatures" observed in germline, soma and tumors, with the idea that each signature corresponds to one or a small number of underlying mutagenic processes. Two such signatures turn out to be ubiquitous across cell types: SBS signature 1, which consists primarily of transitions at methylated CpG sites caused by spontaneous deamination, and the more diffuse SBS signature 5, which is of unknown etiology.

The impact of genetic modifiers on variation in germline mutation rates within and among human populations.

Mutation rates and spectra differ among human populations. Here, we examine whether this variation could be explained by evolution at mutation modifiers. To this end, we consider genetic modifier sites at which mutations, "mutator alleles," increase genome-wide mutation rates and model their evolution under purifying selection due to the additional deleterious mutations that they cause, genetic drift, and demographic processes.

Impact of essential workers in the context of social distancing for epidemic control.

New emerging infectious diseases are identified every year, a subset of which become global pandemics like COVID-19. In the case of COVID-19, many governments have responded to the ongoing pandemic by imposing social policies that restrict contacts outside of the home, resulting in a large fraction of the workforce either working from home or not working. To ensure essential services, however, a substantial number of workers are not subject to these limitations, and maintain many of their pre-intervention contacts.

Cell and gene therapy: a snapshot of investor perspectives.

In a collaborative effort between the Commercialization Committee of the International Society for Cell & Gene Therapy (ISCT) and Bloomberg Intelligence, a broad survey of the investment community was executed in order to understand investor perceptions of companies that develop cell and gene therapies (CGTs) and gauge the trajectory of future investment. A broad spectrum of investors responded to the survey, including both health care specialists and generalist investors across a wide range of fund sizes and geographies. A majority of survey respondents have limited exposure to CGTs in their health care portfolios today, which highlights the opportunity to increase awareness of this burgeoning field in the investment community.

Scalable Production of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Under Serum-/Xeno-Free Conditions in a Microcarrier-Based Bioreactor Culture System.

Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases.

Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations.

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size.

Scalable Manufacturing of Human Mesenchymal Stromal Cells in the Vertical-Wheel Bioreactor System: An Experimental and Economic Approach.

Mesenchymal stromal cells (MSC) hold great promise for tissue engineering applications and cell-based therapies. Large cell doses (>1 × 10 cells kg ) and Good Manufacturing Practices (GMP)-compliant processes are however required for clinical purposes. Here, a serum- and xenogeneic-free (S/XF) microcarrier-based culture system is established for the expansion of human umbilical cord matrix (UCM)- and adipose tissue (AT)-derived MSC using the Vertical-Wheel system (PBS-0.

A roadmap for cost-of-goods planning to guide economic production of cell therapy products.

Cell therapy products are frequently developed and produced without incorporating cost considerations into process development, contributing to prohibitively costly products. Herein we contextualize individual process development decisions within a broad framework for cost-efficient therapeutic manufacturing. This roadmap guides the analysis of cost of goods (COG) arising from tissue procurement, material acquisition, facility operation, production, and storage.

A discrete stage-structured model of California newt population dynamics during a period of drought.

We introduce a mathematical model for studying the population dynamics under drought of the California newt (Taricha torosa), a species of special concern in the state of California. Since 2012, California has experienced a record-setting drought, and multiple studies predict drought conditions currently underway will persist and even increase in severity. Recent declines and local extinctions of California newt populations in Santa Monica Mountain streams motivate our study of the impact of drought on newt population sizes.

Integrated culture platform based on a human platelet lysate supplement for the isolation and scalable manufacturing of umbilical cord matrix-derived mesenchymal stem/stromal cells.

Umbilical cord matrix (UCM)-derived mesenchymal stem/stromal cells (MSCs) are promising therapeutic candidates for regenerative medicine settings. UCM MSCs have advantages over adult cells as these can be obtained through a non-invasive harvesting procedure and display a higher proliferative capacity. However, the high cell doses required in the clinical setting make large-scale manufacturing of UCM MSCs mandatory.