Biology subjects

Toman, J.

Publications and source records attributed to Toman, J..

4 recordsLinked to original sources

bioRxiv2026

HIV remodels germinal centers through T follicular helper cell loss

T follicular helper cells (Tfh) within germinal centers are among the most permissive cells for HIV infection and serve as a critical part of the viral reservoir. Given the key role of Tfh in affinity maturation and the production of plasma cells and memory B cells, an understanding of this critical viral reservoir is fundamental not only for cure strategies but also for understanding immunodeficiency in people living with HIV (PLWH). Using rare clinical specimens from PLWH, we demonstrate that HIV causes both a change in the cellular composition of germinal centers and changes in their overall architecture in ways that are consistent with the immunodeficiency seen in PLWH, independent of their CD4 count. We note a significant decrease in the number of GC Tfh cells and an increase in the number of follicular CD8 T cells in lymphoid tissues obtained from PLWH. Our data further show that GC size is decreased both by HIV and with increased age. Single-cell RNA sequencing data demonstrate that HIV acutely decreases the expression of Tfh B-cell support pathways and disrupts Tfh expression of cell trafficking receptors. Additionally, in a lymphoid organoid model of acute infection that forms GC-like structures, these findings are recapitulated, suggesting that New Approach Methodologies could be germane to understanding the impact of HIV on the reservoir and immunodeficiency. This study describes previously undocumented remodeling of the germinal center niche in PLWH, providing insight into the immune microenvironment of a key HIV reservoir that may help inform future cure strategies.

microbiology↗

bioRxiv2019

Maternal RhD heterozygous genotype is associated with male biased secondary sex ratio

The results of previous studies overwhelmingly suggest that RhD positive heterozygotes express better health status than Rh positive homozygous, especially in RhD negative subjects. This also applies to pregnant women. According to the Trivers-Willard hypothesis, women in better physical condition should have a male-skewed sex ratio. The aim of the present study was to test the hypothesis that RhD positive heterozygous mothers give birth to more sons than daughters. In the present cross-sectional study, we analysed data from 5,655 women who have given birth in the General University Hospital in Prague, Czech Republic between 2008-2012. Clinical records comprised maternal weight before pregnancy, number of previous deliveries, sex of the newborn, maternal RhD phenotype, and RhD phenotype of the newborn. Secondary sex ratio was significantly higher (P=0.028) in RhD positive mothers who had RhD negative newborns, i.e. in heterozygotes (SR=1.23), than in RhD positive mothers who had RhD positive newborns, i.e. in a mixed population of heterozygotes and homozygotes (SR=1.00), especially in primiparous women (P=0.013; SR=1.37 and 0.99 resp.). In line with the Trivers-Willard effect, RhD maternal heterozygous genotype is associated with male biased secondary sex ratio. The results supported the hypothesis that RhD polymorphism may be maintained due to heterozygote health advantages.

evolutionary biology↗

bioRxiv2017

Stability-based sorting: The forgotten process behind (not only) biological evolution

Natural selection is considered to be the main process that drives biological evolution. It requires selected entities to originate dependent upon one another by the means of reproduction or copying, and for the progeny to inherit the qualities of their ancestors. However, natural selection is a manifestation of a more general persistence principle, whose temporal consequences we propose to name \"stability-based sorting\" (SBS). Sorting based on static stability, i.e., SBS in its strict sense and usual conception, favours characters that increase the persistence of their holders and act on all material and immaterial entities. Sorted entities could originate independently from each other, are not required to propagate and need not exhibit heredity. Natural selection is a specific form of SBS--sorting based on dynamic stability. It requires some form of heredity and is based on competition for the largest difference between the speed of generating its own copies and their expiration. SBS in its strict sense and selection thus have markedly different evolutionary consequences that are stressed in this paper. In contrast to selection, which is opportunistic, SBS is able to accumulate even momentarily detrimental characters that are advantageous for the long-term persistence of sorted entities. However, it lacks the amplification effect based on the preferential propagation of holders of advantageous characters. Thus, it works slower than selection and normally is unable to create complex adaptations. From a long-term perspective, SBS is a decisive force in evolution--especially macroevolution. SBS offers a new explanation for numerous evolutionary phenomena, including broad distribution and persistence of sexuality, altruistic behaviour, horizontal gene transfer, patterns of evolutionary stasis, planetary homeostasis, increasing ecosystem resistance to disturbances, and the universal decline of disparity in the evolution of metazoan lineages. SBS acts on all levels in all biotic and abiotic systems. It could be the only truly universal evolutionary process, and an explanatory framework based on SBS could provide new insight into the evolution of complex abiotic and biotic systems.

evolutionary biology↗

bioRxiv2017

General Environmental Heterogeneity As The Explanation Of Sexuality? Comparative Study Shows That Ancient Asexual Taxa Are Associated With Both Biotically And Abiotically Homogeneous Environments

Ecological theories of sexual reproduction assume that sexuality is advantageous in certain conditions, for example, in biotically or abiotically more heterogeneous environments. Such theories thus could be tested by comparative studies. However, the published results of these studies are rather unconvincing. Here we present the results of a new comparative study based solely on the ancient asexual clades. The association with biotically or abiotically homogeneous environments in these asexual clades was compared with the same association in their sister, or closely related, sexual clades. Using the conservative definition of ancient asexuals (i.e. age > 1 million years), we found six pairs for which relevant ecological data are available. The difference between the homogeneity type of environment associated with the sexual and asexual species was then compared in an exact binomial test. Based on available literature, the results showed that the vast majority of ancient asexual clades tend to be associated with biotically or abiotically, biotically, and abiotically more homogeneous environments than their sexual controls. In the exploratory part of the study, we found that the ancient asexuals often have durable resting stages, enabling life in subjectively homogeneous environments, live in the absence of intense biotic interactions, and are very often sedentary, inhabiting benthos and soil. The consequences of these findings for the ecological theories of sexual reproduction are discussed.

evolutionary biology↗