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1.
medRxiv ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39252912

RESUMO

Large-scale genome-wide association studies of schizophrenia have uncovered hundreds of associated loci but with extremely limited representation of African diaspora populations. We surveyed electronic health records of 200,000 individuals of African ancestry in the Million Veteran and All of Us Research Programs, and, coupled with genotype-level data from four case-control studies, realized a combined sample size of 13,012 affected and 54,266 unaffected persons. Three genome-wide significant signals - near PLXNA4, PMAIP1, and TRPA1 - are the first to be independently identified in populations of predominantly African ancestry. Joint analyses of African, European, and East Asian ancestries across 86,981 cases and 303,771 controls, yielded 376 distinct autosomal loci, which were refined to 708 putatively causal variants via multi-ancestry fine-mapping. Utilizing single-cell functional genomic data from human brain tissue and two complementary approaches, transcriptome-wide association studies and enhancer-promoter contact mapping, we identified a consensus set of 94 genes across ancestries and pinpointed the specific cell types in which they act. We identified reproducible associations of schizophrenia polygenic risk scores with schizophrenia diagnoses and a range of other mental and physical health problems. Our study addresses a longstanding gap in the generalizability of research findings for schizophrenia across ancestral populations, underlining shared biological underpinnings of schizophrenia across global populations in the presence of broadly divergent risk allele frequencies.

2.
Lancet Microbe ; : 100946, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39284331

RESUMO

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. Transmission of T cruzi by triatomine vectors is dependent on diverse environmental and socioeconomic factors. Climate change, which is disrupting patterns of human habitation and land use, can affect the epidemiology of Chagas disease by influencing the distribution of vector and host species. We conducted a review using triatomine distribution as a proxy for T cruzi transmission in North America (Canada, Mexico, and the USA) and central America (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama) and investigated the association of T cruzi transmission with climate change, identifying 12 relevant studies. Most studies (n=9) modelled the effect of the scenario of climate change on the distribution of relevant vector species and found that global warming could sometimes favour and sometimes hinder triatomine distribution. There is a need for more research in parasite biology and social sciences to further understand how climate change and socioeconomic factors can affect the epidemiology of this neglected tropical disease.

3.
Stem Cell Reports ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39270650

RESUMO

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPDs) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop codons (iSTOP) that lead to mRNA nonsense-mediated decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 genes. Using RNA sequencing (RNA-seq), we confirmed their pluripotency, absence of chromosomal abnormalities, and NMD. Despite high editing efficiency, three schizophrenia risk genes (SETD1A, TRIO, and CUL1) only had heterozygous LoF alleles, suggesting their essential roles for cell growth. We found that CUL1-LoF reduced neurite branches and synaptic puncta density. This iSTOP pipeline enables a scaled and efficient LoF mutagenesis of NPD genes, yielding an invaluable shareable resource.

4.
Oper Dent ; 49(5): 564-573, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39169512

RESUMO

This study evaluated the mechanical properties of demineralized dentin matrix submitted to different bleaching treatments, as well as the changes in mass and collagen biodegradation brought about by endogenous protease. Dentin collagen matrices were prepared to receive the following treatments (n=12): no bleaching treatment (C-control), 10% carbamide peroxide (CP-Opalescence PF, Ultradent, South Jordan, UT, USA) 10%/8 hours/ day/14 days, and 40% hydrogen peroxide (HP-Opalescence Boost, Ultradent), 40 minutes per session/3 sessions. The dentin matrices were evaluated for elastic modulus and mass before and after treatments and ultimate tensile strength after treatments. The solution collected during storage was evaluated for hydroxyproline release. There was no statistically significant difference between CP and C in terms of the elastic modulus (p=0.3697) or mass variation (p=0.1333). Dentin beams treated with HP and C presented significant mass loss after the first session (p=0.0003). HP treatment led to complete degradation of collagen matrices after the second bleaching session. After the second session, CP showed higher hydroxyproline concentration than C (p<0.0001). Ultimate tensile strength was lower for CP than C (p=0.0097). CP did not affect the elastic modulus or the dentin collagen matrix mass but did promote hydroxyproline release by endogenous protease and reduce the ultimate tensile strength. HP significantly affected the mechanical properties of dentin and promoted complete degradation of the demineralized dentin collagen matrix.


Assuntos
Peróxido de Carbamida , Colágeno , Dentina , Módulo de Elasticidade , Peróxido de Hidrogênio , Resistência à Tração , Clareadores Dentários , Clareamento Dental , Dentina/metabolismo , Dentina/efeitos dos fármacos , Colágeno/metabolismo , Humanos , Clareadores Dentários/farmacologia , Peróxido de Carbamida/farmacologia , Clareamento Dental/métodos , Peptídeo Hidrolases/metabolismo , Peróxidos , Ureia/análogos & derivados , Ureia/farmacologia , Hidroxiprolina/metabolismo , Técnicas In Vitro
5.
Front Pediatr ; 12: 1386082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144471

RESUMO

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

6.
MethodsX ; 13: 102880, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39185461

RESUMO

This paper presents a novel information generation methodology to support safer cycling patterns in urban environments, leveraging for that Large Language Models (LLMs), AI-based agents, and open geospatial data. By processing multiple files containing previously computed urban risk levels and existing mobility infrastructure, which are generated by exploiting open data sources, our method exploits multi-layer data preprocessing procedures and prompt engineering to create easy-to-use, user-friendly assistive systems that are able to provide useful information concerning cycling safety. Through a well-defined processing pipeline based on Data Ingestion and Preparation, Agents Orchestration, and Decision Execution methodological steps, our method shows how to integrate open-source tools and datasets, ensuring reproducibility and accessibility for urban planners and cyclists. Moreover, an AI agent is also provided, which fully implements our method and acts as a proof-of-concept implementation. This paper demonstrates the effectiveness of our method in enhancing cycling safety and urban mobility planning.•A novel method that combines LLMs and AI agents is defined to enhance the processing of multi-domain open geospatial data, potentially promoting cycling safety.•It integrates urban risk data and cycling infrastructure for a more comprehensive understanding of cycling resources, which become accessible by textual or audio prompts.

7.
Front Psychol ; 15: 1346732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39118847

RESUMO

Introduction: This meta-analytic review surveyed previous empirical studies that examined links between moral identity and indicators of emotional well-being. Additionally, this meta-analysis examined cultural origin as a moderator, testing if links between moral identity and emotional well-being differ in collectivistic vs. individualistic countries. Methods: A systematic literature review was conducted through ProQuest's 65 databases and PubMed. A random-effect meta-analysis and subgroup analyses were conducted using Comprehensive Meta-Analysis 4.0 (CMA) software. Results: Drawing on 27 eligible studies, moral identity was associated with greater emotional well-being (r = 0.27, p < 0.001). Follow up analyses on individual dimensions showed medium effect sizes in links between moral identity and greater happiness or positive affect (r = 0.28, p < 0.001), greater sense of purpose or meaning in life (r = 0.29, p < 0.001), and higher self-esteem (r = 0.25, p < 0.001). Moreover, moral identity was associated with greater life satisfaction showing a small effect size (r = 0.15, p = 0.011). Results showed that effect sizes of links between moral identity and overall emotional well-being did not significantly differ by cultural origin. However, effect sizes tended to be larger in the nine studies that were conducted in collectivistic countries (r = 0.30, p < 0.001) as compared to the 15 studies that were conducted in individualistic countries (r = 0.27, p < 0.001). Discussion: The results of this meta-analysis indicate a robust empirical relationship between moral identity and emotional well-being that is present across various dimensions of emotional well-being and in both individualistic and collectivistic cultures. Systematic review registration: https://osf.io/94f8b/?view_only=6db54da0fa304c83993d0438ecb5c637.

9.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38874164

RESUMO

The role of antagonistic secondary metabolites produced by Pseudomonas protegens in suppression of soil-borne phytopathogens has been clearly documented. However, their contribution to the ability of P. protegens to establish in soil and rhizosphere microbiomes remains less clear. Here, we use a four-species synthetic community (SynCom) in which individual members are sensitive towards key P. protegens antimicrobial metabolites (DAPG, pyoluteorin, and orfamide A) to determine how antibiotic production contributes to P. protegens community invasion and to identify community traits that counteract the antimicrobial effects. We show that P. protegens readily invades and alters the SynCom composition over time, and that P. protegens establishment requires production of DAPG and pyoluteorin. An orfamide A-deficient mutant of P. protegens invades the community as efficiently as wildtype, and both cause similar perturbations to community composition. Here, we identify the microbial interactions underlying the absence of an orfamide A mediated impact on the otherwise antibiotic-sensitive SynCom member, and show that the cyclic lipopeptide is inactivated and degraded by the combined action of Rhodococcus globerulus D757 and Stenotrophomonas indicatrix D763. Altogether, the demonstration that the synthetic community constrains P. protegens invasion by detoxifying its antibiotics may provide a mechanistic explanation to inconsistencies in biocontrol effectiveness in situ.


Assuntos
Biotransformação , Pseudomonas , Metabolismo Secundário , Microbiologia do Solo , Pseudomonas/metabolismo , Pseudomonas/genética , Rizosfera , Microbiota , Interações Microbianas , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Fenóis , Floroglucinol/análogos & derivados , Pirróis
10.
J Res Adolesc ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38817080

RESUMO

Witnessing inter-parental conflict is associated with dating violence perpetration in late adolescence and adulthood. This relationship may be moderated by adolescents' empathy, with more empathic youth viewing their parents' conflict behavior as less acceptable, and thus refraining from dating violence perpetration. This study sought to determine if empathy buffers the effects of inter-parental conflict in early adolescence on expected dating violence perpetration in early adolescence and actual dating violence perpetration in late adolescence and adulthood. Moreover, this study tested if expected dating violence perpetration in early adolescence and dating violence perpetration in late adolescence mediate the effects of inter-parental conflict and empathy on dating violence perpetration in adulthood. Sex differences in these relationships were also examined. The sample included 412 adolescents (52% male, 73% Black, 25% White, 2% Other) who participated at three time points between 2006 and 2022 (T1-T3, Mean age = 13, 18, 28 years). Results indicated that higher inter-parental conflict and lower empathy were associated with higher expected dating violence perpetration at T1 in both males and females. Inter-parental conflict at T1 predicted higher dating violence perpetration at T3 through expected dating violence perpetration at T1 and dating violence perpetration at T2. Empathy at T1 predicted lower dating violence perpetration at T3 directly and also indirectly through lower expected dating violence at T1 and lower dating violence perpetration at T2 in both sexes. There were no interaction effects of inter-parental conflict and empathy on expected or actual dating violence perpetration at any age.

11.
Nat Commun ; 15(1): 4486, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802389

RESUMO

Bacterial-fungal interactions influence microbial community performance of most ecosystems and elicit specific microbial behaviours, including stimulating specialised metabolite production. Here, we use a co-culture experimental evolution approach to investigate bacterial adaptation to the presence of a fungus, using a simple model of bacterial-fungal interactions encompassing the bacterium Bacillus subtilis and the fungus Aspergillus niger. We find in one evolving population that B. subtilis was selected for enhanced production of the lipopeptide surfactin and accelerated surface spreading ability, leading to inhibition of fungal expansion and acidification of the environment. These phenotypes were explained by specific mutations in the DegS-DegU two-component system. In the presence of surfactin, fungal hyphae exhibited bulging cells with delocalised secretory vesicles possibly provoking an RlmA-dependent cell wall stress. Thus, our results indicate that the presence of the fungus selects for increased surfactin production, which inhibits fungal growth and facilitates the competitive success of the bacterium.


Assuntos
Adaptação Fisiológica , Aspergillus niger , Bacillus subtilis , Lipopeptídeos , Bacillus subtilis/fisiologia , Bacillus subtilis/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Aspergillus niger/metabolismo , Aspergillus niger/fisiologia , Aspergillus niger/crescimento & desenvolvimento , Lipopeptídeos/metabolismo , Peptídeos Cíclicos/metabolismo , Hifas/crescimento & desenvolvimento , Hifas/metabolismo , Interações Microbianas/fisiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Técnicas de Cocultura , Mutação , Parede Celular/metabolismo
12.
Acta Trop ; 256: 107262, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38801912

RESUMO

Chagas disease is a zoonosis caused by the protozoan Trypanosoma cruzi and transmitted through the feces of triatomines, mainly in Latin America. Since the 1950s, chemical insecticides have been the primary method for controlling these triatomines, yet resistance has emerged, prompting the exploration of alternative approaches. The objective of this research was to test the capacity of the entomopathogenic nematodes Heterorhabditis indica and its symbiotic bacteria Photorhabdus luminescens, to produce mortality of Triatoma dimidiata a key vector of T. cruzi in Mexico under laboratory conditions. Two bioassays were conducted. In the first bioassay, the experimental unit was a 250 ml plastic jar with 100 g of sterile soil and three adult T. dimidiata. Three nematode quantities were tested: 2250, 4500, and 9000 nematodes per 100 g of sterile soil (n/100 g) per jar, with 3 replicates for each concentration and 1 control per concentration (1 jar with 100 g of sterile soil and 3 T. dimidiata without nematodes). The experimental unit of the second bioassay was a 500 ml plastic jar with 100 g of sterile soil and 4 adult T. dimidiata. This bioassay included 5, 50, 500, and 5000 n/100 g of sterile soil per jar, with 3 replicates of each quantity and 1 control per quantity. Data were analyzed using Kaplan-Meyer survival analysis. Electron microscopy was used to assess the presence of nematodes and tissue damage in T. dimidiata. The results of the first bioassay demonstrated that the nematode induced an accumulated average mortality ranging from 55.5 % (2250 n/100 g) to 100 % (4500 and 9000 n/100 g) within 144 h. In the second bioassay, the 5000 n/100 g concentration yielded 87.5 % mortality at 86 h, but a concentration as small as 500 n/100 g caused 75 % mortality from 84 h onwards. Survival analysis indicated higher T. dimidiata mortality with increased nematode quantities, with significant differences between the 4500, 5000, and 9000 n/100 g and controls. Electron microscopy revealed the presence of nematodes and its presumably symbiotic bacteria in the digestive system of T. dimidiata. Based on these analyses, we assert that the H. indica and P. luminescens complex causes mortality in adult T. dimidiata under laboratory conditions.


Assuntos
Doença de Chagas , Photorhabdus , Triatoma , Animais , Doença de Chagas/parasitologia , Doença de Chagas/prevenção & controle , Triatoma/parasitologia , México , Análise de Sobrevida , Rabditídios/fisiologia , Agentes de Controle Biológico , Controle Biológico de Vetores/métodos , Rhabditoidea/fisiologia , Vetores de Doenças , Trypanosoma cruzi/fisiologia
13.
Phytochem Anal ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693046

RESUMO

INTRODUCTION: Pectin-oligosaccharides (POS) serve diverse purposes as a food ingredient, antimicrobial and biostimulant in plants, and their functionality is linked to the degree of esterification. Grape and broccoli wastes emerge as environmentally friendly alternatives to obtaining pectin, serving as a sustainable source to producing POS. For example, microwaves have proven to be an effective and sustainable method to extract polysaccharides from plant matrices. OBJECTIVE: This work aims to use grape and broccoli wastes as alternative sources for obtaining pectin by microwave-assisted extraction and biotransformation into POS, which possess biological properties. MATERIAL AND METHODS: The extraction conditions were identified at a power of 400 W, 300 s for the extraction of pectin from grape pomace and broccoli waste. Biotransformation of pectins into POS, using commercial enzyme preparations (Viscozyme L and Pectinase). Characterisation was carried out by Fourier-transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. RESULTS: Physicochemical analysis indicated grape pomace and broccoli waste pectins had galacturonic acid content of 63.81 ± 1.67 and 40.83 ± 2.85 mg 100 mg-1, low degree of esterification of 34.89% and 16.22%, respectively. Biotransformation of pectins into POS resulted in a 20% hydrolysis rate. The main enzymatic activity was polygalacturonase for the degradation of the main structure of the pectin. CONCLUSION: Production of POS from agro-industrial wastes by emerging technologies, such as the combined use of microwave-assisted extraction and enzymatic processes, represents an alternative method for the generation of bioactive compounds with distinctive properties suitable for different applications of interest.

14.
Oper Dent ; 49(3): 262-272, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38632866

RESUMO

OBJECTIVES: This study evaluated the influence of hydrogen peroxide (HP) with or without titanium dioxide nanotubes (TiO2) associated with violet LED (VL) regarding: a) the temperature change in the pulp chamber and facial surface; b) the decomposition of HP; and c) the cytotoxicity of the gels on pulp cells. METHODS AND MATERIALS: The experimental groups were: HP35 (35% HP/Whiteness HP, FGM); HP35+VL; HP35T (HP35+TiO2); HP35T+VL; HP7 (7.5% HP/White Class 7.5%, FGM); HP7+VL; HP7T (HP7+TiO2); and HP7T+VL. TiO2 was incorporated into the bleaching gels at 1%. Eighty bovine incisors were evaluated to determine temperature change in 8 experimental groups (n=10/group). A k-type thermocouple was used to evaluate the temperatures of the facial surface and in the pulp chamber, achieved by enabling endodontic access to the palatal surface, throughout the 30-minute session. HP decomposition (n=3) of gels was evaluated by using an automatic potentiometric titrator at the initial and 30-minute time points. Trans-enamel and trans-dentinal cell viability were assessed with a pulp chamber device as well as enamel and dentin discs (n=6), and the treatment extracts (culture medium + diffused components) were collected and applied to MDPC-23 odontoblast cells to evaluate cell viability according to the MTT test. RESULTS: A temperature increase in the pulp chamber was observed in the presence of VL at 30 minutes (p<0.05) (Mann-Whitney test). Also at 30 minutes, HP35 showed greater decomposition in the presence of VL rather than in its absence (p<0.05) (mixed linear models and the Tukey-Kramer test). HP7 provided greater cell viability than the groups treated with HP35 (p<0.05) (generalized linear models test). Cell viability was significantly lower for HP7 in the presence of VL (p<0.05). CONCLUSION: Pulpal temperature increased with VL (maximum of 1.9°C), but did not exceed the critical limit to cause pulp damage. Less concentrated HP resulted in higher cell viability, even when associated with VL.


Assuntos
Polpa Dentária , Peróxido de Hidrogênio , Clareamento Dental , Animais , Clareamento Dental/métodos , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Bovinos , Peróxido de Hidrogênio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Clareadores Dentários/farmacologia , Titânio , Temperatura Corporal , Cavidade Pulpar/efeitos dos fármacos
15.
bioRxiv ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38562852

RESUMO

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPD) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, here we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop-codons (iSTOP) that lead to mRNA nonsense-mediated-decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 NPD genes. Using RNAseq, we confirmed their pluripotency, absence of chromosomal abnormalities, and NMD. Interestingly, for three schizophrenia risk genes (SETD1A, TRIO, CUL1), despite the high efficiency of base editing, we only obtained heterozygous LoF alleles, suggesting their essential roles for cell growth. We replicated the reported neural phenotypes of SHANK3-haploinsufficiency and found CUL1-LoF reduced neurite branches and synaptic puncta density. This iSTOP pipeline enables a scaled and efficient LoF mutagenesis of NPD genes, yielding an invaluable shareable resource.

16.
Neotrop Entomol ; 53(2): 439-454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38530618

RESUMO

In Mexico, few studies have explored how environmental conditions in tropical dry forests (TDF) influence bat fly load even though, according to climate change scenarios, this ecosystem will experience a drier and warmer climate. Such an extension of the dry season in these ecosystems could have dramatic consequences for biodiversity, particularly in regions with plains where animals do not have elevational climate shifts. The present study therefore evaluates the effect of prevailing environmental conditions during 2015-2019, as well as host body conditions, on the infestation and abundance of bat-specific ectoparasites and the composition and bat fly load in the dry season of a TDF in Yucatan. Since Yucatan has an essentially flat and low-lying topography, organisms cannot escape from the predicted extreme conditions with elevational shifts. This region is therefore an excellent location for assessment of the potential effects of warming. We collected 270 bat flies from 12 species. Three streblid species (Nycterophilia parnelli Wenzel, Trichobius johnsonae Wenzel, and Trichobius sparsus Kessel) are new records for Yucatan. Our overview of the dry season bat ectoparasite loads reveals low values of richness and prevalence, but high aggregation. Our models detected significant differences in ectoparasite infestation and abundance over the years, but the environmental and body host condition variables were unrelated to these. We report that pregnant females are parasitized to a greater extent by bat flies during the dry season, which generally represents the season of most significant nutritional stress.


Assuntos
Quirópteros , Dípteros , Animais , Feminino , Ecossistema , Florestas , México , Estações do Ano , Gravidez , Masculino
17.
medRxiv ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410442

RESUMO

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

18.
PLoS Negl Trop Dis ; 18(2): e0011981, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38377140

RESUMO

BACKGROUND: Chagas disease, affecting approximately eight million individuals in tropical regions, is primarily transmitted by vectors. Rhodnius prolixus, a triatomine vector, commonly inhabits in ecotopes with diverse palm tree species, creating optimal conditions for vector proliferation. This study aims to explore the transmission ecology of Trypanosoma cruzi, the causative parasite of Chagas disease, by investigating the feeding patterns and natural infection rates of R. prolixus specimens collected from various wild palm species in the Colombian Orinoco region. MATERIALS AND METHODS: To achieve this objective, we sampled 35 individuals from three palm species (Attalea butyracea, Acrocomia aculeata, and Mauritia flexuosa) in a riparian forest in the Casanare department of eastern Colombia, totaling 105 sampled palm trees. DNA was extracted and analyzed from 115 R. prolixus specimens at different developmental stages using quantitative PCR (qPCR) for T. cruzi detection and identification of discrete typing units. Feeding preferences were determined by sequencing the 12S rRNA gene amplicon through next-generation sequencing. RESULTS: A total of 676 R. prolixus specimens were collected from the sampled palms. The study revealed variation in population densities and developmental stages of R. prolixus among palm tree species, with higher densities observed in A. butyracea and lower densities in M. flexuosa. TcI was the exclusive T. cruzi discrete typing unit (DTU) found, with infection frequency positively correlated with R. prolixus abundance. Insects captured in A. butyracea exhibited higher abundance and infection rates than those from other palm species. The feeding sources comprised 13 mammal species, showing no significant differences between palm species in terms of blood sources. However, Didelphis marsupialis and Homo sapiens were present in all examined R. prolixus, and Dasypus novemcinctus was found in 89.47% of the insects. CONCLUSION: This study highlights the significance of wild palms, particularly A. butyracea, as a substantial risk factor for T. cruzi transmission to humans in these environments. High population densities and infection rates of R. prolixus were observed in each examined palm tree species.


Assuntos
Doença de Chagas , Rhodnius , Triatominae , Trypanosoma cruzi , Animais , Humanos , Árvores , Trypanosoma cruzi/genética , Colômbia/epidemiologia , Doença de Chagas/epidemiologia , Tatus
19.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38365234

RESUMO

Siderophores have long been implicated in sociomicrobiology as determinants of bacterial interrelations. For plant-associated genera, like Bacillus and Pseudomonas, siderophores are well known for their biocontrol functions. Here, we explored the functional role of the Bacillus subtilis siderophore bacillibactin (BB) in an antagonistic interaction with Pseudomonas marginalis. The presence of BB strongly influenced the outcome of the interaction in an iron-dependent manner. The BB producer B. subtilis restricts colony spreading of P. marginalis by repressing the transcription of histidine kinase-encoding gene gacS, thereby abolishing production of secondary metabolites such as pyoverdine and viscosin. By contrast, lack of BB restricted B. subtilis colony growth. To explore the specificity of the antagonism, we cocultured B. subtilis with a collection of fluorescent Pseudomonas spp. and found that the Bacillus-Pseudomonas interaction is conserved, expanding our understanding of the interplay between two of the most well-studied genera of soil bacteria.


Assuntos
Bacillus subtilis , Ferro , Ferro/metabolismo , Bacillus subtilis/genética , Sideróforos/metabolismo , Pseudomonas/genética , Pseudomonas/metabolismo
20.
J Adolesc ; 96(4): 710-719, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38196145

RESUMO

INTRODUCTION: Exposure to interpersonal violence at school has been linked with lower empathy, but less is known about factors that may moderate this relationship. Positive parent-child communication has been associated with higher empathy during adolescence and children of parents that communicate their disapproval of violent behavior respond more peacefully in situations involving violence. Mother-child communication about violence may therefore reduce the risk of desensitization to violent behavior and promote empathy in youth that are frequently exposed to violence. Thus, this study examines whether mother-child communication about violence mitigates the association between exposure to interpersonal school violence and adolescents' empathy. METHODS: This study addressed this question using a diverse sample of early adolescents from the Southeastern United States in 2003 (N = 642; mean age 11.3 years; 52% male; 76% Black, 22% non-Hispanic White). Adolescents reported on how often they witness or experience interpersonal violence at school and how often they communicate with their mother about violence and how to avoid it. Adolescents also self-reported on their level of empathy. RESULTS: Results from a hierarchical regression model showed that exposure to interpersonal school violence and lower mother-child communication about violence were uniquely associated with lower empathy, but communication about violence did not moderate the link between interpersonal school violence exposure and empathy. There were no sex differences in these relationships. CONCLUSIONS: Contrary to the hypothesis, youth who experience and witness interpersonal violence at school show lower empathy independent of whether youth communicate with their mother about violence and responding to violent situations.


Assuntos
Comunicação , Empatia , Relações Mãe-Filho , Instituições Acadêmicas , Violência , Humanos , Feminino , Masculino , Criança , Adolescente , Violência/psicologia , Violência/prevenção & controle , Sudeste dos Estados Unidos
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