A Phylogenetic Approach to the Uneven Global Distribution of the COVID-19 Pandemic

A possible role of Y chromosomal haplogroups in COVID-19 mortality is discussed without claiming causality. The mortality of COVID-19 seems unequally distributed in different populations and statistically significant regional covariation is presented between COVID-19 mortality and the haplogroup Y-R1b. Y-R1b is suggested as a possible marker for mortality in the first wave of the pandemic affecting the Western Europe. September 2020 the pandemic involved also Eastern Europe severely in a second wave, while South East Asia, with a very high frequency of Y-0, had strikingly low COVID-19 mortality rate. Eastern Europe is dominated by Y-haplogroups (i.e., Y-R1a), with close ancestry to Y-R1b. Molecular mechanisms mediated by the Y chromosome involved in COVID-19 mortality are discussed, presenting a possible role of KDM5D in androgen receptor modulation and regulation of TMPRSS2 known to enable SARS-CoV-2 binding to ACE2 and facilitating virus entrance into the cell and virus replication. Sex bias and comorbidities point at the role of variations in the Y-chromosomal phylogeny.

Considerations and Challenges for Sex-Aware Drug Repurposing

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

A Report of Chigger Mites on the Striped Field Mouse, Apodemus agrarius, in Southwest China

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

Sex bias evaluation of classic and novel Housekeeping Genes in adipose tissue through the massive analysis of transcriptomics data

ABSTRACTHousekeeping genes (HKG), those involved in the maintenance of basic cell functions, are considered to have constant expression levels in all cell types, and are therefore commonly used as internal controls in gene expression studies. Nevertheless, multiple studies have shown that not all of them have stable expression levels across different cells, tissues, and conditions, introducing a systematic error in the experimental results. The proper selection and validation of control housekeeping genes in the specific studied conditions is crucial for the validity of the obtained results, although, up to date, sex has never been taken into account as a biological variable.In this work, we evaluate the expression profiles of six classical housekeeping genes, (four metabolic: HPRT, GAPDH, PPIA and UBC, and two ribosomal: 18S and RPL19) used as controls in several tissues, to determine the stability of their expression in adipose tissue of Homo sapiens and Mus musculus and asses sex bias and control suitability. We also evaluated gene expression stability of the genes included in different whole transcriptome microarrays available at the Gene Expression Omnibus database (GEO), to identify new genes suitable to be used as sex-unbiased controls. We perform a sex-based analysis to test for/reveal sexual dimorphism of mRNA expression stability.We use a novel computational strategy based on meta-analysis techniques which evidence that some classical housekeeping genes do not fit to analyze human adipose tissue when sex variable is included. For instance, the extensively used 18S has shown to be variable in this tissue, while PPIA and RPL19 have shown to be good HKG targets. Further, we propose new sex-unbiased human and mouse housekeeping genes, derived from sex-specific expression profiles, including, RPS8 or UBB. All the results generated in this work are available in an open web resource (https://bioinfo.cipf.es/metafun-HKG), so that they can be consulted and used in further studies.

Sex Bias in Differentiated Thyroid Cancer

Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient’s behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.

Stronger net selection on males across animals

Sexual selection is considered the major driver for the evolution of sex differences. However, the eco-evolutionary dynamics of sexual selection and their role for a population’s adaptive potential to respond to environmental change have only recently been explored. Theory predicts that sexual selection promotes adaptation at a low demographic cost only if sexual selection is aligned with natural selection and if net selection is stronger on males compared to females. We used a comparative approach to show that net selection is indeed stronger in males and provide preliminary support that this sex bias is associated with sexual selection. Given that both sexes share the vast majority of their genes, our findings corroborate the notion that the genome is often confronted with a more stressful environment when expressed in males. Collectively, our study supports one of the long-standing key assumptions required for sexual selection to bolster adaptation, and sexual selection may therefore enable some species to track environmental change more efficiently.

Sex Allocation, Diet, and Small Population Management of African Rhinoceros

<p>The application of sex allocation theory can provide useful insight into endangered rhinoceros biology to improve in situ and ex situ conservation efforts by understanding the factors that cause a female to produce one sex of calf. By decreasing the birth sex ratio (number of males born per number of females born) in a population it may be possible to increase population growth rates. The first aim was to determine if an environmentally cued sex allocation response occurred in black rhinos. By examining rainfall and calf sex records in a wild black rhino population, I identified that birth sex ratios increase in rainy seasons and rainy years. Mothers were more likely to be observed with male calves if they conceived during the wet season (57.3% male) than during the dry season (42.9% male). Mothers were more likely to raise male calves if they conceived during wet years (60.2% male) than during dry years (46.1% male). Next, I examined whether pulsatile or random variation in sex ratios of different magnitudes, as might occur under changes in climate patterns, would be detrimental to rhinoceros population growth. Results demonstrated that while random increases in the magnitude of birth sex ratio variation, in either direction, increased population survival probability up to 0.907, sequential pulsed years of birth sex ratio bias had the opposite effect on population performance down to a survival probability of 0.619. Furthermore, for both scenarios, populations of less than 50 animals are particularly vulnerable to extinction. Since the sex biases observed in the captive rhinoceros population were attributed to several factors, I used an information theoretic approach to evaluate the relative importance of different hypotheses for birth sex bias for predicting calf sex. The results demonstrated that none of the models tested were greatly predictive of calf sex. Suspecting that the mechanisms that were cueing calf sex occur close to the time of conception and were nutritionally cued, in the final experiment, I measured changes in blood glucose in white rhinos after they ate different meals. At 90 minutes, serum glucose levels in rhinos eating the 10 % lucerne hay diet were significantly lower than the 5% glucose and 10% glucose diets but not the 10% pellet nor 10% grass hay diets. This is the first time such an experiment has been published in a wildlife species and not only demonstrates the feasibility of training rhinos for successive blood draws but also that captive diets are low glycemic for white rhinos. Overall, my research confirmed that an environmentally cued sex allocation response does occur in African rhinos, and changes in the duration and magnitude of sex ratio patterns can decrease population growth and increase potential for extinction. Additionally, none of the previous hypotheses for the suspected male-sex bias in captive born rhinos were influential on calf sex, which shifts the focus of sex allocation research in rhinos to more acute signals around the time of conception, such as changes in diet and body condition.</p>

Sex Allocation, Diet, and Small Population Management of African Rhinoceros

<p>The application of sex allocation theory can provide useful insight into endangered rhinoceros biology to improve in situ and ex situ conservation efforts by understanding the factors that cause a female to produce one sex of calf. By decreasing the birth sex ratio (number of males born per number of females born) in a population it may be possible to increase population growth rates. The first aim was to determine if an environmentally cued sex allocation response occurred in black rhinos. By examining rainfall and calf sex records in a wild black rhino population, I identified that birth sex ratios increase in rainy seasons and rainy years. Mothers were more likely to be observed with male calves if they conceived during the wet season (57.3% male) than during the dry season (42.9% male). Mothers were more likely to raise male calves if they conceived during wet years (60.2% male) than during dry years (46.1% male). Next, I examined whether pulsatile or random variation in sex ratios of different magnitudes, as might occur under changes in climate patterns, would be detrimental to rhinoceros population growth. Results demonstrated that while random increases in the magnitude of birth sex ratio variation, in either direction, increased population survival probability up to 0.907, sequential pulsed years of birth sex ratio bias had the opposite effect on population performance down to a survival probability of 0.619. Furthermore, for both scenarios, populations of less than 50 animals are particularly vulnerable to extinction. Since the sex biases observed in the captive rhinoceros population were attributed to several factors, I used an information theoretic approach to evaluate the relative importance of different hypotheses for birth sex bias for predicting calf sex. The results demonstrated that none of the models tested were greatly predictive of calf sex. Suspecting that the mechanisms that were cueing calf sex occur close to the time of conception and were nutritionally cued, in the final experiment, I measured changes in blood glucose in white rhinos after they ate different meals. At 90 minutes, serum glucose levels in rhinos eating the 10 % lucerne hay diet were significantly lower than the 5% glucose and 10% glucose diets but not the 10% pellet nor 10% grass hay diets. This is the first time such an experiment has been published in a wildlife species and not only demonstrates the feasibility of training rhinos for successive blood draws but also that captive diets are low glycemic for white rhinos. Overall, my research confirmed that an environmentally cued sex allocation response does occur in African rhinos, and changes in the duration and magnitude of sex ratio patterns can decrease population growth and increase potential for extinction. Additionally, none of the previous hypotheses for the suspected male-sex bias in captive born rhinos were influential on calf sex, which shifts the focus of sex allocation research in rhinos to more acute signals around the time of conception, such as changes in diet and body condition.</p>