AIMS: Liver cytochromes (CYPs) play an important role in drug metabolism but display a large interindividual variability resulting both from genetic and environmental factors. Most drug dose adjustment guidelines are based on genetics performed in healthy volunteers. However, hospitalized patients are not only more likely to be the target of new prescriptions and drug treatment modifications than healthy volunteers, but will also be more subject to polypharmacy, drug-drug interactions, or to suffer from disease or inflammation affecting CYP activities. METHODS: We compared predicted phenotype based on genetic data and measured phenotype using the Geneva cocktail to determine the extent of drug metabolizing enzyme variability in a large population of hospitalized patients (>500) and healthy young volunteers (>300). We aimed to assess the correlation between predicted and measured phenotype in the two populations. RESULTS: We found that, even in cases where the genetically predicted metabolizer group correlates well with measured CYP activity at group level, this prediction lacks accuracy for the determination of individual metabolizer capacities. Drugs can have a profound impact on CYP activity, but even after combining genetic and drug treatment information, the activity of a significant proportion of extreme metabolizers could not be explained. CONCLUSIONS: Our results support the use of measured metabolic ratios in addition to genotyping for accurate determination of individual metabolic capacities to guide personalized drug prescription.
- Klíčová slova
- cytochrome P450, drug metabolism, genotyping, phenotyping,
- MeSH
- dospělí MeSH
- fenotyp MeSH
- genotyp MeSH
- hospitalizace MeSH
- léčivé přípravky metabolismus MeSH
- lékové interakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři MeSH
- systém (enzymů) cytochromů P-450 * genetika metabolismus MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- léčivé přípravky MeSH
- systém (enzymů) cytochromů P-450 * MeSH
It has been suggested that in threatening environments, both women and men should prefer more masculine men as romantic and coalition partners, respectively. Empirical evidence for this hypothesis has been weak or inconsistent, primarily because most experimental research has focused on elevating the perceived danger from other men through virtual threats. This study investigates whether personal experience with violence predicts the preference for masculine features in 326 Senegalese participants presented with pairs of manipulated facial photographs of West African men (one more feminine, one more masculine) and asked to indicate which face is more attractive (to women) or more trustworthy (to men). The findings reveal a strong association between violence exposure and facial feature preferences. Those who experienced (particularly physical) violence showed a higher preference for masculinized faces (up to 95% in women, 82% in men) compared to the baseline (57% in women, 63% in men). This difference is proposed to reflect an adaptive strategy of prioritizing physical protection in settings with a higher incidence of violent confrontations. Much of the variance can be found between groups. The direct effect of experienced violence diminishes over time, which suggests a dynamic interplay between innate predispositions and environmental influences on aesthetic preferences.
- Klíčová slova
- attractiveness, contextual preferences, evolutionary psychology, facial masculinity, trustworthiness, violence exposure,
- MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužskost MeSH
- násilí MeSH
- obličej * MeSH
- výběrové chování MeSH
- vystavení násilí psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Senegal MeSH
The Fulani people, one of the most important pastoralist groups in sub-Saharan Africa, are still largely underrepresented in population genomic research. They speak a Niger-Congo language called Fulfulde or Pulaar and live in scattered locations across the Sahel/Savannah belt, from the Atlantic Ocean to Lake Chad. According to historical records, their ancestors spread from Futa Toro in the Middle Senegal Valley to Futa-Jallon in Guinea and then eastward into the Sahel belt over the past 1,500 years. However, the earlier history of this traditionally pastoral population has not been well studied. To uncover the genetic structure and ancestry of this widespread population, we gathered genome-wide genotype data from 460 individuals across 18 local Fulani populations, along with comparative data from both modern and ancient worldwide populations. This represents a comprehensive geographically wide-scaled genome-wide study of the Fulani. We revealed a genetic component closely associated with all local Fulani populations, suggesting a shared ancestral component possibly linked to the beginning of African pastoralism in the Green Sahara. Comparison to ancient DNA results also identified the presence of an ancient Iberomaurusian-associated component across all Fulani groups, providing additional insights into their deep genetic history. Additionally, our genetic data indicate a later Fulani expansion from the western to the eastern Sahel, characterized by a clinal pattern and admixture with several other African populations north of the equator.
- Klíčová slova
- Africa, Fulani, Sahel, admixture, ancient DNA, genomics, migration, population structure,
- MeSH
- černoši * genetika MeSH
- etnicita genetika MeSH
- genetická variace MeSH
- genom lidský MeSH
- lidé MeSH
- populační genetika * MeSH
- Středoafričané MeSH
- Východoafričané MeSH
- Západoafričané MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- subsaharská Afrika MeSH
African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount importance in a continent such as Africa, where the burden of infectious diseases is a major public health challenge. In this study, we investigated the molecular variation of four Human Leukocyte Antigens (HLA) class II genes (DRB1, DQA1, DQB1 and DPB1), directly involved in the immune response to parasitic infections, in more than 1000 individuals from 23 populations across North, East, Central and West Africa. By analyzing the HLA molecular diversity of these populations in relation to various geographical, cultural and environmental factors, we identified divergent genetic profiles for several (semi-)nomadic populations of the Sahel belt as a signature of their unique demography. In addition, we observed significant genetic structuring supporting both substantial geographic and linguistic differentiations within West Africa. Furthermore, neutrality tests suggest balancing selection has been shaping the diversity of these four HLA class II genes, which is consistent with molecular comparisons between HLA genes and their orthologs in chimpanzees (Patr). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of Plasmodium falciparum, the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the DPB1 gene. DPB1*01:01, a highly frequent allele in Burkinabé populations, is identified as a potential protective allele against malaria, suggesting that strong pathogen-driven positive selection at this gene has shaped HLA variation in Africa. Additionally, two low-frequency DRB1 alleles, DRB1*08:06 and DRB1*11:02, also show significant associations with P. falciparum prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects.
- Klíčová slova
- Africa, HLA, human molecular diversity, malaria, pathogen‐driven selection, plasmodium falciparum,
- Publikační typ
- časopisecké články MeSH
This report summarizes the ASEV-CzeSEV Joint Meeting on Extracellular Vesicles (EVs), held at the Medical University of Vienna in September 2024. The conference focused on introducing and expanding EV research and infrastructure within the Czech Republic and Austria, highlighting areas for collaboration. Key sessions featured research on EV-based diagnostics, tissue regeneration, interspecies communication and therapeutic applications, with an emphasis on shared resources and cross-border partnerships. The program included oral and poster presentations on EV engineering, new isolation techniques, and potential clinical applications, as well as industry updates on the latest EV technologies. The meeting concluded with awards for outstanding presentations reflecting the quality of work presented. Following the conference, a dedicated workshop was held on flow cytometry analysis of EVs, allowing participants to deepen their technical expertise in EV characterization. This report captures the main discussions, findings, and collaborative opportunities explored at the ASEV-CzeSEV meeting, signaling strong regional support for advancing EV research.
Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro- and anti-inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83-EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83-EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83-EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83-EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83-EVs interact with nasal-associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83-EVs activate the NF-κΒ signalling pathway, resulting in the nitric oxide production. EcO83-EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies.
- Klíčová slova
- EVs, Ec083, NF‐κΒ signalling, bacterial extracellular vesicles, macrophage, nitric oxide, postbiotics, probiotic,
- MeSH
- aplikace intranazální * MeSH
- epitelové buňky metabolismus MeSH
- Escherichia coli * metabolismus MeSH
- extracelulární vezikuly * metabolismus MeSH
- lidé MeSH
- lymfoidní tkáň metabolismus MeSH
- makrofágy metabolismus MeSH
- myši MeSH
- NF-kappa B metabolismus MeSH
- oxidační stres MeSH
- plíce mikrobiologie metabolismus MeSH
- probiotika * aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- NF-kappa B MeSH
OBJECTIVES: Previous research revealed that in some African populations, food-production strategies are associated with facial shape. Nomadic pastoralists living in the African Sahel/Savannah belt have a different facial morphology than their sedentary neighbors. We investigated whether the lifestyle associated with a subsistence pattern has an impact on sexual dimorphism in the facial structure. METHODS: We employed several methods from geometric morphometrics and demonstrated such effect in four ethnically distinct populations that share the same geographic space. RESULTS: We show that the facial traits which correlate with a subsistence strategy are systematically associated with levels of facial sex-typicality. In particular, we found that faces with more pronounced pastoralist features have on average more masculine facial traits and that this effect is more pronounced in men than in women. CONCLUSIONS: In general, though, the magnitude of overall facial dimorphism does not differ between pastoralists and farmers. Pastoralists (in contrast to farmers) tend to have a more masculine facial morphology but facial differences between the sexes are in both groups the same.
- MeSH
- černoši MeSH
- fenotyp MeSH
- lidé MeSH
- mitochondriální DNA MeSH
- obličej * anatomie a histologie MeSH
- pohlavní dimorfismus * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mitochondriální DNA MeSH
INTRODUCTION: The immune systems of both the mother and the newborn face significant challenges during birth. Proper immune regulation after birth is essential for the survival of neonates. Numerous studies have demonstrated that the neonatal immune system is relatively immature, particularly in its adaptive arm, placing the primary responsibility for immune surveillance on innate immunity. METHODS: Given the significant role of neutrophils in protecting the neonate after birth, we conducted a study investigating the properties of neutrophils in newborn cord blood using various methodological approaches. RESULTS: Our findings demonstrate the presence of immature low-density neutrophils in the cord blood, which are likely responsible for the observed elevated expression of genes coding for proteins essential to antimicrobial response, including myeloperoxidase, neutrophils elastase, and defensins. DISCUSSION: We propose that these cells function normally and support the protection of newborns early after birth. Furthermore, our results suggest that the mode of delivery might significantly influence the programming of neutrophil function. The presented findings emphasize the importance of distinct neutrophil subpopulations in neonatal immunity and their potential impact on early postnatal health.
- Klíčová slova
- cord blood, defensins, myeloperoxidase, neutrophils, oxidative burst,
- MeSH
- antiinfekční látky * metabolismus MeSH
- fetální krev MeSH
- lidé MeSH
- neutrofily * MeSH
- novorozenec MeSH
- přirozená imunita MeSH
- proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- antiinfekční látky * MeSH
- proteiny MeSH
This review focuses on the Sahel/Savannah belt, a large region of Africa where two alternative subsistence systems (pastoralism and agriculture), nowadays, interact. It is a long-standing question whether the pastoralists became isolated here from other populations after cattle began to spread into Africa (~8 thousand years ago, kya) or, rather, began to merge with other populations, such as agropastoralists, after the domestication of sorghum and pearl millet (~5 kya) and with the subsequent spread of agriculture. If we look at lactase persistence, a trait closely associated with pastoral lifestyle, we see that its variants in current pastoralists distinguish them from their farmer neighbours. Most other (mostly neutral) genetic polymorphisms do not, however, indicate such clear differentiation between these groups; they suggest a common origin and/or an extensive gene flow. Genetic affinity and ecological symbiosis between the two subsistence systems can help us better understand the population history of this African region. In this review, we show that genomic datasets of modern Sahel/Savannah belt populations properly collected in local populations can complement the still insufficient archaeological research of this region, especially when dealing with the prehistory of mobile populations with perishable material culture and therefore precarious archaeological visibility.
- Klíčová slova
- Africa, Sahel/Savannah belt, archaeogenetics, pastoralism, population genetics, selection,
- MeSH
- archeologie MeSH
- lidé MeSH
- polymorfismus genetický * MeSH
- populační genetika * MeSH
- skot MeSH
- zemědělství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Afrika MeSH
