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1.
Nature ; 625(7995): 540-547, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38030719

RESUMO

The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent1-7. With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8. We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.


Assuntos
DNA Antigo , Emigração e Imigração , Genética Populacional , Idioma , Humanos , África Ocidental , Conjuntos de Dados como Assunto , República Democrática do Congo , DNA Antigo/análise , Emigração e Imigração/história , Efeito Fundador , Fluxo Gênico/genética , Variação Genética/genética , História Antiga , Idioma/história , Linguística/história , Zâmbia , Mapeamento Geográfico
2.
BMC Public Health ; 24(1): 1116, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654178

RESUMO

Diabetes poses a substantial disease burden, prompting preventive interventions. Physical inactivity, a major risk factor for type 2 diabetes, can potentially be mitigated by enhancing area-level walkability. Despite this, limited population-based studies have investigated the link between walkability and objective diabetes measures. Our study aims to estimate the association between area-level walkability and individual glycated haemoglobin levels in the Portuguese adult population without the diagnosis of diabetes. Data from the 2011 census and an updated street map were obtained to construct a walkability index based on residential density, land-use mix, and street connectivity. Individual health data were sourced from The National Health Examination Survey (INSEF) 2015, a representative survey of the Portuguese adult population. Gamma regression was employed for estimation of the main associations, revealing that residing in moderately walkable areas significantly reduced average glycated haemoglobin levels (Exp(ß) = 0.906; 95% CI: 0.821, 0.999) compared to the least walkable areas. The association was less pronounced and not statistically significant for the third tertile of walkability (Exp(ß) = 0.919; 95% CI: 0.822, 1.028). Our findings highlight a nonlinear protective association between walkability and glycated haemoglobin, emphasizing the potential policy implications for urban planning, diabetes prevention, and health promotion.


Assuntos
Planejamento Ambiental , Hemoglobinas Glicadas , Caminhada , Humanos , Portugal/epidemiologia , Hemoglobinas Glicadas/análise , Masculino , Feminino , Caminhada/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Planejamento Ambiental/estatística & dados numéricos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Idoso , Características de Residência/estatística & dados numéricos , Inquéritos Epidemiológicos , Adulto Jovem
3.
BMC Microbiol ; 23(1): 226, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596536

RESUMO

BACKGROUND: While the human oral microbiome is known to play an important role in systemic health, its average composition and diversity patterns are still poorly understood. To gain better insights into the general composition of the microbiome on a global scale, the characterization of microbiomes from a broad range of populations, including non-industrialized societies, is needed. Here, we used the portion of non-human reads obtained through an expanded exome capture sequencing approach to characterize the saliva microbiomes of 52 individuals from eight ethnolinguistically diverse southern African populations from Angola (Kuvale, Kwepe, Himba, Tjimba, Kwisi, Twa, !Xun) and Zimbabwe (Tshwa), including foragers, food-producers, and peripatetic groups (low-status communities who provide services to their dominant neighbors). RESULTS: Our results indicate that neither host genetics nor livelihood seem to influence the oral microbiome profile, with Neisseria, Streptococcus, Prevotella, Rothia, and Porphyromonas being the five most frequent genera in southern African groups, in line with what has been shown for other human populations. However, we found that some Tshwa and Twa individuals display an enrichment of pathogenic genera from the Enterobacteriaceae family (i.e. Enterobacter, Citrobacter, Salmonella) of the Proteobacteria phylum, probably reflecting deficient sanitation and poor health conditions associated with social marginalization. CONCLUSIONS: Taken together, our results suggest that socio-economic status, rather than ethnolinguistic affiliation or subsistence mode, is a key factor in shaping the salivary microbial profiles of human populations in southern Africa.


Assuntos
Citrobacter , Microbiota , Humanos , Zimbábue , Angola , África Austral , Microbiota/genética
4.
Analyst ; 148(22): 5762-5774, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37843562

RESUMO

Bacteria with antagonistic activity inhibit the growth of other bacteria through different mechanisms, including the production of antibiotics. As a result, these microorganisms are a prolific source of such compounds. However, searching for antibiotic-producing strains requires high-throughput techniques due to the vast diversity of microorganisms. Here, we screened and isolated bacteria with antagonistic activity against Escherichia coli expressing the green fluorescent protein (E. coli-GFP). We used microfluidics to co-encapsulate and co-culture single cells from different strains within picoliter gel beads and analyzed them using fluorescence-activated cell sorting (FACS). To test the methodology, we used three bacterial isolates obtained from Mexican maize, which exhibit high, moderate, or no antagonistic activity against E. coli-GFP, as determined previously using agar plate assays. Single cells from each strain were separately co-incubated into gel beads with E. coli-GFP. We monitored the development of the maize bacteria microcolonies and tracked the growth or inhibition of E. coli-GFP using bright-field and fluorescent microscopy. We correlated these images with distinctive light scatter and fluorescence signatures of each incubated bead type using FACS. This analysis enabled us to sort gel beads filled with an antagonistic strain, starting from a mixture of the three different types of maize bacteria and E. coli-GFP. Likewise, culturing the FACS-sorted beads on agar plates confirmed the isolation and recovery of the two antagonistic strains. In addition, enrichment assays demonstrated the methodology's effectiveness in isolating rare antibiotic-producer strains (0.01% abundance) present in a mixture of microorganisms. These results show that associating light side scatter and fluorescent flow cytometry signals with microscopy images provides valuable controls to establish successful high-throughput methods for sorting beads in which microbial interaction assays are performed.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Microfluídica , Ágar/metabolismo , Bactérias , Citometria de Fluxo/métodos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo
5.
Can J Microbiol ; 69(12): 488-500, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37815047

RESUMO

Uropathogenic Escherichia coli (UPEC) is classified as the major causative agent of urinary tract infections (UTIs). UPEC virulence and antibiotic resistance can lead to complications in pregnant women and (or) newborns. Therefore, the aim of this study was to determine the etiological agents of UTIs, as well as to identify genes related to virulence factors in bacteria isolated from pregnant and nonpregnant women. A total of 4506 urine samples were collected from pregnant and nonpregnant women. Urine cultures were performed, and PCR was used to identify phylogroups and virulence-related genes. Antibiotic resistance profiles were determined. The incidence of UTIs was 6.9% (pregnant women, n = 206 and nonpregnant women, n = 57), and UPEC belonging to phylogroup A was the most prevalent. The presence of genes related to capsular protection, adhesins, iron acquisition, and serum protection in UPEC was associated with not being pregnant, while the presence of genes related to adhesins was associated with pregnancy. Bacteria isolated from nonpregnant women were more resistant to antibiotics; 36.5% were multidrug resistant, and 34.9% were extensively drug resistant. Finally, UTIs were associated with neonatal sepsis risk, particularly in pregnant women who underwent cesarean section while having a UTI caused by E. coli. In conclusion, UPEC isolated from nonpregnant women carried more virulence factors than those isolated from pregnant women, and maternal UTIs were associated with neonatal sepsis risk.


Assuntos
Infecções por Escherichia coli , Sepse Neonatal , Infecções Urinárias , Escherichia coli Uropatogênica , Gravidez , Humanos , Feminino , Recém-Nascido , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Virulência/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Sepse Neonatal/tratamento farmacológico , Cesárea , Farmacorresistência Bacteriana/genética , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Fatores de Virulência/genética , Escherichia coli Uropatogênica/genética
6.
Environ Microbiol ; 24(11): 5583-5595, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36053914

RESUMO

Milpas are traditional Mesoamerican agroecosystems maintained with ancestral practices. Maize landraces are grown in polyculture, creating highly productive and diverse ecosystems. Recent studies suggest that milpas maintain beneficial plant-microbe interactions that are probably absent in modern agroecosystems; however, direct comparisons of the microbiome of plants between traditional and modern agroecosystems are still needed. Here, we studied seed-endophytic bacterial communities from native maize landraces from milpas and hybrid varieties. First, we quantified the abundance of culturable endophytic microbes; next, we assessed pairwise antagonistic interaction networks between bacterial isolates; finally, we compared bacterial community structure by 16S rRNA amplicon sequencing. We found that seeds from native maize landraces harbour a higher endophytic microbial load, including more bacterial strains with antagonistic activity against soil-borne bacteria, and overall harbour more diverse bacterial communities than the hybrid varieties. Noteworthy, most of the seed-endophytic strains with antagonistic activity corresponded to Burkholderia spp. that were only found in native maize seeds, through both culture-dependent and independent strategies. Altogether, our results support that crop modernization alters the functions and structure of plant-associated microbes; we propose native maize from milpas could serve as a model for understanding plant-microbe interactions and the effect of modernization.


Assuntos
Microbiota , Zea mays , RNA Ribossômico 16S/genética , Zea mays/microbiologia , Endófitos , Bactérias , Microbiota/genética , Sementes/microbiologia , Plantas/genética
7.
World J Microbiol Biotechnol ; 39(1): 12, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372802

RESUMO

Transcriptional factors are well studied in bacteria for their global interactions and the effects they produce at the phenotypic level. Particularly, Bacillus subtilis has been widely employed as a model Gram-positive microorganism used to characterize these network interactions. Bacillus species are currently used as efficient commercial microbial platforms to produce diverse metabolites such as extracellular enzymes, antibiotics, surfactants, industrial chemicals, heterologous proteins, among others. However, the pleiotropic effects caused by the genetic modification of specific genes that codify for global regulators (transcription factors) have not been implicated commonly from a bioprocess point of view. Recently, these strategies have attracted the attention in Bacillus species because they can have an application to increase production efficiency of certain commercial interest metabolites. In this review, we update the recent advances that involve this trend in the use of genetic engineering (mutations, deletion, or overexpression) performed to global regulators such as Spo0A, CcpA, CodY and AbrB, which can provide an advantage for the development or improvement of bioprocesses that involve Bacillus species as production platforms. Genetic networks, regulation pathways and their relationship to the development of growth stages are also discussed to correlate the interactions that occur between these regulators, which are important to consider for application in the improvement of commercial-interest metabolites. Reported yields from these products currently produced mostly under laboratory conditions and, in a lesser extent at bioreactor level, are also discussed to give valuable perspectives about their potential use and developmental level directed to process optimization at large-scale.


Assuntos
Bacillus , Fatores de Transcrição , Fatores de Transcrição/genética , Bacillus/genética , Bacillus/metabolismo , Bacillus subtilis/metabolismo , Engenharia Genética , Redes Reguladoras de Genes , Proteínas de Bactérias/metabolismo , Transcrição Gênica
8.
Mol Biol Evol ; 37(2): 406-416, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593238

RESUMO

The Bantu expansion, which started in West Central Africa around 5,000 BP, constitutes a major migratory movement involving the joint spread of peoples and languages across sub-Saharan Africa. Despite the rich linguistic and archaeological evidence available, the genetic relationships between different Bantu-speaking populations and the migratory routes they followed during various phases of the expansion remain poorly understood. Here, we analyze the genetic profiles of southwestern and southeastern Bantu-speaking peoples located at the edges of the Bantu expansion by generating genome-wide data for 200 individuals from 12 Mozambican and 3 Angolan populations using ∼1.9 million autosomal single nucleotide polymorphisms. Incorporating a wide range of available genetic data, our analyses confirm previous results favoring a "late split" between West and East Bantu speakers, following a joint passage through the rainforest. In addition, we find that Bantu speakers from eastern Africa display genetic substructure, with Mozambican populations forming a gradient of relatedness along a North-South cline stretching from the coastal border between Kenya and Tanzania to South Africa. This gradient is further associated with a southward increase in genetic homogeneity, and involved minimum admixture with resident populations. Together, our results provide the first genetic evidence in support of a rapid North-South dispersal of Bantu peoples along the Indian Ocean Coast, as inferred from the distribution and antiquity of Early Iron Age assemblages associated with the Kwale archaeological tradition.


Assuntos
População Negra/genética , Cromossomos Humanos/genética , Genômica/métodos , Polimorfismo de Nucleotídeo Único , Angola/etnologia , População Negra/etnologia , Emigração e Imigração , Evolução Molecular , Genética Populacional , Humanos , Índia/etnologia , Oceano Índico , Moçambique/etnologia , Filogeografia
9.
Mol Biol Evol ; 37(6): 1647-1656, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32128591

RESUMO

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.


Assuntos
População Negra/genética , Escravização/história , Pool Gênico , Genoma Humano , Migração Humana/história , África , América , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , Humanos , Filogeografia
10.
Pharmacogenomics J ; 21(6): 649-656, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34302047

RESUMO

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10-3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.


Assuntos
Tratamento Farmacológico da COVID-19 , Cloroquina/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Hidroxicloroquina/efeitos adversos , África Subsaariana/epidemiologia , COVID-19/epidemiologia , COVID-19/genética , Bases de Dados Genéticas , Variação Genética/genética , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Mutação de Sentido Incorreto/genética , Fatores de Risco
11.
PLoS Pathog ; 15(2): e1007571, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742693

RESUMO

Bacterial pathogens have evolved strategies that enable them to invade tissues and spread within the host. Enterococcus faecalis is a leading cause of local and disseminated multidrug-resistant hospital infections, but the molecular mechanisms used by this non-motile bacterium to penetrate surfaces and translocate through tissues remain largely unexplored. Here we present experimental evidence indicating that E. faecalis generates exopolysaccharides containing ß-1,6-linked poly-N-acetylglucosamine (polyGlcNAc) as a mechanism to successfully penetrate semisolid surfaces and translocate through human epithelial cell monolayers. Genetic screening and molecular analyses of mutant strains identified glnA, rpiA and epaX as genes critically required for optimal E. faecalis penetration and translocation. Mechanistically, GlnA and RpiA cooperated to generate uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) that was utilized by EpaX to synthesize polyGlcNAc-containing polymers. Notably, exogenous supplementation with polymeric N-acetylglucosamine (PNAG) restored surface penetration by E. faecalis mutants devoid of EpaX. Our study uncovers an unexpected mechanism whereby the RpiA-GlnA-EpaX metabolic axis enables production of polyGlcNAc-containing polysaccharides that endow E. faecalis with the ability to penetrate surfaces. Hence, targeting carbohydrate metabolism or inhibiting biosynthesis of polyGlcNAc-containing exopolymers may represent a new strategy to more effectively confront enterococcal infections in the clinic.


Assuntos
Enterococcus faecalis/metabolismo , Matriz Extracelular de Substâncias Poliméricas/fisiologia , Polissacarídeos Bacterianos/fisiologia , Proteínas de Bactérias , Enterococcus faecalis/patogenicidade , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Infecções por Bactérias Gram-Positivas , Humanos , Polissacarídeos Bacterianos/metabolismo
12.
Org Biomol Chem ; 19(15): 3404-3412, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33899881

RESUMO

We demonstrate here that the Ugi-Sonogashira protocol can be successfully used to obtain five new molecular rotors 10a-e with strong emission. They have been synthesized by combining multicomponent Ugi stators and several aromatic rotary components: phenylene, p-xylene, naphthalene and anthracene. The synthesized conjugated rotors are highly fluorescent (Φf = 0.39 to Φf = 0.10), and changes in their emission were observed upon variations of the surrounding media. Particularly, we found that they are sensitive to aggregation (THF/water) or high viscosity (methanol/glycerol) conditions. This work paves the way to develop new emissive rotors with exciting photophysical properties.

13.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360551

RESUMO

Pharmacogenomics aims to reveal variants associated with drug response phenotypes. Genes whose roles involve the absorption, distribution, metabolism, and excretion of drugs, are highly polymorphic between populations. High coverage whole genome sequencing showed that a large proportion of the variants for these genes are rare in African populations. This study investigated the impact of such variants on protein structure to assess their functional importance. We used genetic data of CYP3A5 from 458 individuals from sub-Saharan Africa to conduct a structural bioinformatics analysis. Five missense variants were modeled and microsecond scale molecular dynamics simulations were conducted for each, as well as for the CYP3A5 wildtype and the Y53C variant, which has a known deleterious impact on enzyme activity. The binding of ritonavir and artemether to CYP3A5 variant structures was also evaluated. Our results showed different conformational characteristics between all the variants. No significant structural changes were noticed. However, the genetic variability seemed to act on the plasticity of the protein. The impact on drug binding might be drug dependant. We concluded that rare variants hold relevance in determining the pharmacogenomics properties of populations. This could have a significant impact on precision medicine applications in sub-Saharan Africa.


Assuntos
Simulação por Computador , Citocromo P-450 CYP3A/genética , Genética Populacional , Genoma Humano , Fenótipo , Polimorfismo de Nucleotídeo Único , África Subsaariana , Genótipo , Humanos , Sequenciamento Completo do Genoma
14.
Environ Manage ; 68(4): 580-590, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34370090

RESUMO

Quantification of SARS-CoV-2 in urban wastewaters has emerged as a cheap, efficient strategy to follow trends of active COVID-19 cases in populations. Moreover, mathematical models have been developed that allow the prediction of active cases following the temporal patterns of viral loads in wastewaters. In Mexico, no systematic efforts have been reported in the use of these strategies. In this work, we quantified SARS-CoV-2 in rivers and irrigation canals in the Mezquital Valley, Hidalgo, an agricultural region where wastewater from Mexico City is distributed and used for irrigation. Using quantitative RT-PCR, we detected the virus in six out of eight water samples from rivers and five out of eight water samples from irrigation canals. Notably, samples showed a general consistent trend of having the highest viral loads in the sites closer to Mexico City, indicating that this is the main source that contributes to detection. Using the data for SARS-CoV-2 concentration in the river samples, we generated a simplified transport model that describes the spatial patterns of dispersion of virus in the river. We suggest that this model can be extrapolated to other wastewater systems where knowledge of spatial patterns of viral dispersion, at a geographic scale, is required. Our work highlights the need for improved practices and policies related to the use of wastewater for irrigation in Mexico and other countries.


Assuntos
COVID-19 , Águas Residuárias , Humanos , México , Rios , SARS-CoV-2
15.
Trop Anim Health Prod ; 53(2): 280, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885987

RESUMO

The aim of this study was to evaluate the correlation between the corpus luteum vascularization with the concentration of progesterone and the fertility of embryo recipient mares. Mangalarga Marchador mares (n = 33) were distributed into groups according to the days (D) after ovulation, as follows: D3 (n = 8), D4 (n = 8), D5 (n = 9), and D6 (n = 8). The evaluations of the corpus luteum, endometrium, and blood collection to quantify the progesterone concentration were carried out on D3, D4, D5, and D6. Among the parameters evaluated, only progesterone concentration on D6 differed from the other groups (P <0.05). A positive correlation (P <0.05) between the diameter and the area of the corpus luteum, and the objective and subjective methods of the corpus luteum vascular perfusion, was identified. Likewise, a positive correlation (P <0.05) was observed between the objective and subjective methods of the vascular perfusion in the corpus luteum and the progesterone concentration. The pregnancy rate obtained in this study (54.54%) was not affected (P> 0.05) by the day of embryo transfer, whose percentages were 37.50% (3/8) on D3, 50% (4/8) on D4, 66.70% (6/9) on D5, and 62.50% (5/8) on D6. It was estimated that with each increase on the day of embryo transfer, the pregnancy rate increases. The results allow to conclude that the corpus luteum vascularization in mares, evaluated by Doppler ultrasound, correlates with progesterone concentration and the embryo transfer day.


Assuntos
Corpo Lúteo , Progesterona , Animais , Transferência Embrionária/veterinária , Feminino , Fertilidade , Cavalos , Ovulação , Gravidez
16.
J Bacteriol ; 202(6)2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-31871034

RESUMO

Quorum sensing (QS) is a mechanism of synthesis and detection of signaling molecules to regulate gene expression and coordinate behaviors in bacterial populations. In Bacillus subtilis, multiple paralog Rap-Phr QS systems (receptor-signaling peptides) are highly redundant and multifunctional, interconnecting the regulation of differentiation processes such as sporulation and competence. However, their functions in the Bacillus cereus group are largely unknown. We evaluated the functions of Rap proteins in Bacillus thuringiensis Bt8741, which codes for eight Rap-Phr systems; these were individually overexpressed to study their participation in sporulation, biofilm formation, spreading, and extracellular proteolytic activity. Our results show that four Rap-Phr systems (RapC, RapK, RapF, and RapLike) inhibit sporulation, two of which (RapK and RapF) probably dephosphorylate Spo0F from the Spo0A phosphorelay; these two Rap proteins also inhibit biofilm formation. Four systems (RapC, RacF1, RacF2, and RapLike) participate in spreading inhibition; finally, six systems (RapC, -F, -F2, -I, and -I1 and RapLike) decrease extracellular proteolytic activity. We foresee that functions performed by Rap proteins of Bt8741 could also be carried out by Rap homologs in other strains within the B. cereus group. These results indicate that Rap-Phr systems constitute a highly multifunctional and redundant regulatory repertoire that enables B. thuringiensis and other species from the B. cereus group to efficiently regulate collective functions during their life cycle in the face of changing environments.IMPORTANCE The Bacillus cereus group of bacteria includes species of high economic, clinical, biological warfare, and biotechnological interest, e.g., B. anthracis in bioterrorism, B. cereus in food intoxications, and B. thuringiensis in biocontrol. Knowledge about the ecology of these bacteria is hindered by our limited understanding of the regulatory circuits that control differentiation and specialization processes. Here, we uncover the participation of eight Rap quorum-sensing receptors in collective functions of B. thuringiensis These proteins are highly multifunctional and redundant in their functions, linking ecologically relevant processes such as sporulation, biofilm formation, spreading, extracellular proteolytic activity, and probably other functions in species from the B. cereus group.


Assuntos
Bacillus thuringiensis/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Sequência de Aminoácidos , Proteínas de Bactérias/química , Biofilmes/crescimento & desenvolvimento , Sequência Conservada , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Percepção de Quorum , Esporos Bacterianos/genética
17.
J Bacteriol ; 202(10)2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32071096

RESUMO

In bacterial populations, quorum sensing (QS) systems participate in the regulation of specialization processes and regulate collective behaviors that mediate interactions and allow survival of the species. In Gram-positive bacteria, QS systems of the RRNPP family (Rgg, Rap, NprR, PlcR, and PrgX) consist of intracellular receptors and their cognate signaling peptides. Two of these receptors, Rap and NprR, have regained attention in Bacillus subtilis and the Bacillus cereus group. Some Rap proteins, such as RapH and Rap60, are multifunctional and/or redundant in function, linking the specialization processes of sporulation and competence, as well as global expression changes in the transition phase in B. subtilis NprR, an evolutionary intermediate between Rap and RRNPP transcriptional activators, is a bifunctional regulator that modulates sporulation initiation and activates nutrient scavenging genes. In this review, we discuss how these receptors switch between functions and connect distinct signaling pathways. Based on structural evidence, we propose that RapH and Rap60 should be considered moonlighting proteins. Additionally, we analyze an evolutionary and ecological perspective to understand the multifunctionality and functional redundancy of these regulators in both Bacillus spp. and non-Bacillus Firmicutes Understanding the mechanistic, structural, ecological, and evolutionary basis for the multifunctionality and redundancy of these QS systems is a key step for achieving the development of innovative technologies for health and agriculture.


Assuntos
Bacillus/fisiologia , Proteínas de Bactérias/metabolismo , Percepção de Quorum , Bacillus/genética , Bacillus/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Esporos Bacterianos/genética , Esporos Bacterianos/crescimento & desenvolvimento , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Hum Mutat ; 41(11): 1871-1876, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32827185

RESUMO

More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole-exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease-causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod-cone dystrophy, hearing loss, and Fanconi-type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.


Assuntos
Proteínas de Ciclo Celular/genética , Distrofias de Cones e Bastonetes/genética , Perda Auditiva Neurossensorial/genética , Nefropatias/genética , Ribonucleotídeo Redutases/genética , Feminino , Efeito Fundador , Haplótipos , Humanos , Masculino , Linhagem , África do Sul , Sequenciamento do Exoma
19.
J Mol Evol ; 88(1): 77-87, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31363820

RESUMO

Skin pigmentation is a complex, conspicuous, highly variable human trait that exhibits a remarkable correlation with latitude. The evolutionary history and genetic basis of skin color variation has been the subject of intense research in the last years. This article reviews the major hypotheses explaining skin color diversity and explores the implications of recent findings about the genes associated with skin pigmentation for understanding the evolutionary forces that have shaped the current patterns of skin color variation. A major aspect of these findings is that the genetic basis of skin color is less simple than previously thought and that geographic variation in skin pigmentation was influenced by the concerted action of different types of natural selection, rather than just by selective sweeps in a few key genes.


Assuntos
Pigmentação da Pele/genética , Pigmentação da Pele/fisiologia , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Evolução Biológica , Evolução Molecular , Variação Genética/genética , Humanos , Fenótipo , Seleção Genética/genética
20.
Biochem Biophys Res Commun ; 527(3): 702-708, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32410735

RESUMO

The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.


Assuntos
Betacoronavirus/química , Peptidil Dipeptidase A/química , Glicoproteína da Espícula de Coronavírus/química , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2 , Sítios de Ligação , COVID-19 , Infecções por Coronavirus , Humanos , Simulação de Acoplamento Molecular , Pandemias , Filogenia , Pneumonia Viral , Domínios Proteicos , Estrutura Terciária de Proteína , SARS-CoV-2
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