RESUMO
Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2's depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2's PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2's functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.
Assuntos
Proliferação de Células , Heterocromatina , Histonas , Células-Tronco Neurais , Neurogênese , Animais , Humanos , Camundongos , Instabilidade Genômica , Heterocromatina/metabolismo , Heterocromatina/genética , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Histonas/metabolismo , Metilação , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologiaRESUMO
Histone H1, a vital component in chromatin structure, binds to linker DNA and regulates nuclear processes. We have investigated the distribution of histone H1 variants in a breast cancer cell line using ChIP-Seq. Two major groups of variants are identified: H1.2, H1.3, H1.5 and H1.0 are abundant in low GC regions (B compartment), while H1.4 and H1X preferentially localize in high GC regions (A compartment). Examining their abundance within transposable elements (TEs) reveals that H1X and H1.4 are enriched in recently-incorporated TEs (SVA and SINE-Alu), while H1.0/H1.2/H1.3/H1.5 are more abundant in older elements. Notably, H1X is particularly enriched in SVA families, while H1.4 shows the highest abundance in young AluY elements. Although low GC variants are generally enriched in LINE, LTR and DNA repeats, H1X and H1.4 are also abundant in a subset of recent LINE-L1 and LTR repeats. H1X enrichment at SVA and Alu is consistent across multiple cell lines. Further, H1X depletion leads to TE derepression, suggesting its role in maintaining TE repression. Overall, this study provides novel insights into the differential distribution of histone H1 variants among repetitive elements, highlighting the potential involvement of H1X in repressing TEs recently incorporated within the human genome.
Assuntos
Elementos de DNA Transponíveis , Histonas , Humanos , Linhagem Celular , Elementos de DNA Transponíveis/genética , Genômica , Histonas/genética , Histonas/metabolismoRESUMO
Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1.2/H1.4 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local GC content and that their distribution is robust with respect to H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of topologically associating domains (TADs). Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.
Assuntos
Cromatina , Histonas , Composição de Bases , Cromatina/genética , Montagem e Desmontagem da Cromatina , Expressão Gênica , Histonas/genética , Histonas/metabolismo , HumanosRESUMO
When humans make decisions, objective rewards are mainly discounted by delay, risk and effort. Whereas recent research has demonstrated that several brain areas process costs and code subjective value in effort-based decision making, it remains obscure how neural activity patterns change when effort costs are reduced due to the acquisition of healthy habits, such as moving from sedentary to active lifestyles. Here, a sample of sedentary volunteers was behaviorally assessed and fMRI-scanned before and after completing a 3-month fitness plan. The impact of effort cost on decisions, measured as the constant defining a hyperbolic decaying function, was reduced after the plan. A logistic mixed model demonstrated that the explanatory power of effort decreased with time. At a neural level, there was a marginally significant disruption of effort-cost related functional activity in the anterior cingulate after the plan. Functional connectivity between the amygdala and anterior cingulate cortex was strengthened after habit acquisition. In turn, this interaction was stronger in those participants with lower effort discounting. Thus, we show for the first time changes in value-based decision making after moving from a sedentary to an active lifestyle, which points to the relevance of the amygdala-cingulate interplay when the impact of effort on decisions fades away.
Assuntos
Tonsila do Cerebelo/fisiologia , Tomada de Decisões/fisiologia , Exercício Físico/psicologia , Giro do Cíngulo/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Esforço Físico , Comportamento Sedentário , Adulto JovemRESUMO
In fungal cells cytokinesis requires coordinated closure of a contractile actomyosin ring (CAR) and synthesis of a special cell wall structure known as the division septum. Many CAR proteins have been identified and characterized, but how these molecules interact with the septum synthesis enzymes to form the septum remains unclear. Our genetic study using fission yeast shows that cooperation between the paxillin homolog Pxl1, required for ring integrity, and Bgs1, the enzyme responsible for linear ß(1,3)glucan synthesis and primary septum formation, is required for stable anchorage of the CAR to the plasma membrane before septation onset, and for cleavage furrow formation. Thus, lack of Pxl1 in combination with Bgs1 depletion, causes failure of ring contraction and lateral cell wall overgrowth towards the cell lumen without septum formation. We also describe here that Pxl1 concentration at the CAR increases during cytokinesis and that this increase depends on the SH3 domain of the F-BAR protein Cdc15. In consequence, Bgs1 depletion in cells carrying a cdc15ΔSH3 allele causes ring disassembly and septation blockage, as it does in cells lacking Pxl1. On the other hand, the absence of Pxl1 is lethal when Cdc15 function is affected, generating a large sliding of the CAR with deposition of septum wall material along the cell cortex, and suggesting additional functions for both Pxl1 and Cdc15 proteins. In conclusion, our findings indicate that CAR anchorage to the plasma membrane through Cdc15 and Pxl1, and concomitant Bgs1 activity, are necessary for CAR maintenance and septum formation in fission yeast.
Assuntos
Actomiosina/metabolismo , Extensões da Superfície Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Glucosiltransferases/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/genética , Citoesqueleto de Actina/metabolismo , Actomiosina/química , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Membrana Celular/metabolismo , Parede Celular/metabolismo , Citocinese/genética , Citocinese/fisiologia , Proteínas do Citoesqueleto/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Glucosiltransferases/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Paxilina/metabolismo , Estrutura Terciária de Proteína , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , beta-Glucanas/metabolismoRESUMO
Mermithidae is a family of endoparasitic nematodes known to cause intersexuality in arthropods. Intersexes of the genus Culicoides parasitized by mermithids have been the object of several studies aiming to describe their particular morphology. Culicoides intersexes are specimens with male genitalia and feminized sexually dimorphic structures, i.e. antennae, mouthparts and wings. To date, these specimens have only been described qualitatively and a quantitative approach supported by statistical analysis is lacking. Here we conduct morphometric analyses of sexually dimorphic structures in a sample of Culicoides circumscriptus that includes 34 intersexes with the aim of describing precisely the intersexual morphology. The morphology of antennae and the mouthparts was studied by multivariate statistical analysis of linear measures, and wing form by implementing geometric morphometrics techniques. While intersex wings proved to have a similar size to male wings, their shape was intermediate between males and females. However, when allometric shape variation was removed, the wing shape of intersexes was almost identical to that of females. The intersex antennae were morphometrically of the female type, especially when size variation was considered. In contrast, the measured mouthparts (the labrum and the third palpal segment) were halfway between males and females, even when body size was considered. Overall, the antennae and the wings showed a higher degree of feminization than the mouthparts. These findings indicate that the degree of feminization depends both on the morphological structure and on body size. Moreover, we propose that the feminization of the wings and antennae has an adaptive meaning for the parasite, which would favor female-like traits in order to access more easily its breeding sites, where the parasite has plenty of new hosts to infect. Female-like antennae would be beneficial to detect these sites, while having female-like wings would favor the host's capacity of dispersal to these sites.
Assuntos
Ceratopogonidae/anatomia & histologia , Ceratopogonidae/parasitologia , Mermithoidea/fisiologia , Adaptação Fisiológica , Análise de Variância , Animais , Antenas de Artrópodes/anatomia & histologia , Transtornos do Desenvolvimento Sexual , Feminino , Masculino , Análise de Componente Principal , Asas de Animais/anatomia & histologiaRESUMO
Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.
Assuntos
Neoplasias Colorretais/genética , Genes Supressores de Tumor , Dissomia Uniparental/genética , Aberrações Cromossômicas , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Humanos , Perda de Heterozigosidade , Dissomia Uniparental/patologiaRESUMO
BACKGROUND: Observations from different fields of research coincide in indicating that a defective gamma-aminobutyric acid (GABA) interneuron system may be among the primary factors accounting for the varied clinical expression of schizophrenia. GABA interneuron deficiency is locally expressed in the form of neural activity desynchronization. We mapped the functional anatomy of local synchrony in the cerebral cortex in schizophrenia using functional connectivity MRI. METHODS: Data from 86 patients with schizophrenia and 137 control subjects were obtained from publicly available repositories. Resting-state functional connectivity maps based on Iso-Distant Average Correlation measures across three distances were estimated detailing the local functional structure of the cerebral cortex. RESULTS: Patients with schizophrenia showed weaker local functional connectivity (i.e., lower MRI signal synchrony) in (i) prefrontal lobe areas, (ii) somatosensory, auditory, visual, and motor cortices, (iii) paralimbic system at the anterior insula and anterior cingulate cortex, and (iv) hippocampus. The distribution of the defect in cortical area synchrony largely coincided with the synchronization effect of the GABA agonist alprazolam previously observed using identical functional connectivity measures. There was also a notable resemblance between the anatomy of our findings and cortical areas showing higher density of parvalbumin (prefrontal lobe and sensory cortices) and somatostatin (anterior insula and anterior cingulate cortex) GABA interneurons in humans. CONCLUSIONS: Our results thus provide detail of the functional anatomy of synchrony changes in the cerebral cortex in schizophrenia and suggest which elements of the interneuron system are affected. Such information could ultimately be relevant in the search for specific treatments.
Assuntos
Esquizofrenia , Humanos , Córtex Cerebral , Córtex Pré-Frontal , Giro do Cíngulo , Ácido gama-Aminobutírico/análise , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Every year, more than 700,000 people die from vector-borne diseases, mainly transmitted by mosquitoes. Vector surveillance plays a major role in the control of these diseases and requires accurate and rapid taxonomical identification. New approaches to mosquito surveillance include the use of acoustic and optical sensors in combination with machine learning techniques to provide an automatic classification of mosquitoes based on their flight characteristics, including wingbeat frequency. The development and application of these methods could enable the remote monitoring of mosquito populations in the field, which could lead to significant improvements in vector surveillance. METHODS: A novel optical sensor prototype coupled to a commercial mosquito trap was tested in laboratory conditions for the automatic classification of mosquitoes by genus and sex. Recordings of > 4300 laboratory-reared mosquitoes of Aedes and Culex genera were made using the sensor. The chosen genera include mosquito species that have a major impact on public health in many parts of the world. Five features were extracted from each recording to form balanced datasets and used for the training and evaluation of five different machine learning algorithms to achieve the best model for mosquito classification. RESULTS: The best accuracy results achieved using machine learning were: 94.2% for genus classification, 99.4% for sex classification of Aedes, and 100% for sex classification of Culex. The best algorithms and features were deep neural network with spectrogram for genus classification and gradient boosting with Mel Frequency Cepstrum Coefficients among others for sex classification of either genus. CONCLUSIONS: To our knowledge, this is the first time that a sensor coupled to a standard mosquito suction trap has provided automatic classification of mosquito genus and sex with high accuracy using a large number of unique samples with class balance. This system represents an improvement of the state of the art in mosquito surveillance and encourages future use of the sensor for remote, real-time characterization of mosquito populations.
Assuntos
Aedes , Culex , Animais , Vetores de Doenças , Humanos , Aprendizado de Máquina , Mosquitos VetoresRESUMO
To explore the influence of cardiovascular risk factors (CVRFs) on cognitive symptoms, functional impairment, and systemic inflammatory markers in first-episode psychosis (FEP) patients at baseline and 2-year follow-up. Method: In a sample of 70 FEP patients and 85 age- and sex-matched healthy controls, we assessed nine modifiable CVRFs. All participants were classified into two subgroups according to their CVRF profile: lower (0-1 CVRFs) or higher (≥2 CVRFs). The following outcomes were measured at baseline and 2-year follow-up: cognition; functional outcomes; and white blood cell (WBC) subtype. Adjusted general linear models were conducted to study the effect of diagnosis and CVRF profile on cognition, functioning, WBC, and longitudinal changes in these variables. At baseline, FEP patients with a higher CVRF profile showed a significantly slower performance on the TMT-A test for psychomotor speed and higher lymphocyte levels than patients with a lower CVRF profile. No longitudinal changes were observed in primary outcomes at 2-year follow-up. Among FEP patients with a higher CVRF profile, slower psychomotor speed performance did not correlate with increased lymphocyte levels. Our findings suggest that the cognitive effects of CVRFs manifest early in the course of psychosis, thus highlighting the importance of targeting both CVRFs and cognitive deficits in FEP.
Assuntos
Doenças Cardiovasculares , Transtornos Psicóticos , Biomarcadores , Cognição , Seguimentos , Fatores de Risco de Doenças Cardíacas , Humanos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Fatores de RiscoRESUMO
Giemsa staining of metaphase chromosomes results in a characteristic banding useful for identification of chromosomes and its alterations. We have investigated in silico whether Giemsa bands (G bands) correlate with epigenetic and topological features of the interphase genome. Staining of G-positive bands decreases with GC content; nonetheless, G-negative bands are GC heterogeneous. High GC bands are enriched in active histone marks, RNA polymerase II, and SINEs and associate with gene richness, gene expression, and early replication. Low GC bands are enriched in repressive marks, lamina-associated domains, and LINEs. Histone H1 variants distribute heterogeneously among G bands: H1X is enriched at high GC bands and H1.2 is abundant at low GC, compacted bands. According to epigenetic features and H1 content, G bands can be organized in clusters useful to compartmentalize the genome. Indeed, we have obtained Hi-C chromosome interaction maps and compared topologically associating domains (TADs) and A/B compartments to G banding. TADs with high H1.2/H1X ratio strongly overlap with B compartment, late replicating, and inaccessible chromatin and low GC bands. We propose that GC content is a strong driver of chromatin compaction and 3D genome organization, that Giemsa staining recapitulates this organization denoted by high-throughput techniques, and that H1 variants distribute at distinct chromatin domains. DATABASES: Hi-C data on T47D breast cancer cells have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE147627.
Assuntos
Corantes Azur , Composição de Bases/genética , Montagem e Desmontagem da Cromatina/genética , Cromatina/genética , Histonas/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Cromatina/metabolismo , Epigênese Genética , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , HumanosRESUMO
STUDY TYPE: Prognosis (case series) Level of Evidence 4. OBJECTIVE: To estimate the relative risk of developing a second primary neoplasm, in particular lung cancer, after having non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients were included in the study if they had developed NMIBC between 1995 and 2003. All clinical data were extracted from the medical records of our institution's database. The interval between neoplasms, smoking habits, histological subtypes and survival were also analysed. Patient follow-up was >or=5 years. RESULTS: We found 231 patients with NMIBC, 39 of which had a second primary neoplasm: 10 lung cancer, one pancreas, one gastric, one pharynx, one liver, one parathyroid, one oesophageal, five basal cell carcinoma, three larynx, two colon, three rectal and 10 prostate. In patients with lung cancer, NMIBC was the first primary tumour. Overall, the median (range) interval between occurrence of NMIBC and lung cancer was 54.2 (8-168) months. For the relationship between the observed and expected cases of lung cancer, after normalizing our frequencies to the sex ratio and age of our group of patients, the risk of lung cancer was 10.27-fold higher in patients with NMIBC as compared with the general population of Catalonia (95% confidence interval 4.92-18.88). CONCLUSION: We consider that an annual examination for the detection and prevention of lung cancer must be included in clinical guides for patients with NMIBC. This proposal is reinforced by the finding that death in our group of patients with both tumours was always derived from lung cancer and not from bladder cancer.
Assuntos
Carcinoma de Células de Transição , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Segunda Neoplasia Primária/mortalidade , Fatores de Risco , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.
Assuntos
Transtornos Cognitivos/terapia , Terapia Cognitivo-Comportamental/métodos , Função Executiva/fisiologia , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Atividades Cotidianas , Adulto , Afeto/fisiologia , Transtornos Cognitivos/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Memória/fisiologia , Modelos Biológicos , Testes Neuropsicológicos , Esquizofrenia/complicações , Índice de Gravidade de Doença , Aprendizagem Verbal/fisiologiaRESUMO
Aedes albopictus mosquitoes have been experimentally demonstrated to be a competent vector for Zika virus (ZIKV) in different countries, but there are still some gaps related to the importance of Ae. albopictus in ZIKV transmission. Recent studies on Spanish Ae. albopictus populations showed controversial results for ZIKV transmission and no studies have been performed yet to detect infectious ZIKV in saliva of progeny of infected female mosquitoes. Herein, the horizontal transmission (HT) and vertical transmission (VT) of ZIKV in field-collected Ae. albopictus mosquitoes from Spain were evaluated for ZIKV strains (African I and Asian lineages) to better estimate the risk of ZIKV transmission by Ae. albopictus. The two field-collected Ae. albopictus populations assayed were infected by all tested ZIKV strains, however differences in terms of vector competence were detected depending on strain-population combination. Moreover, a higher susceptibility to the African I lineage strain than to the Asian lineage strain was observed in both mosquito populations. On the other hand, VT was demonstrated for both ZIKV lineages, detecting the virus in both males and females of the progeny of infected females, although importantly ZIKV dissemination and transmission were not detected in the infected females from the offspring. The results of the present study demonstrate that Spanish Ae. albopictus populations could sustain virus transmission in case of ZIKV introduction, but VT would play a poor role in the ZIKV epidemiology. Overall, our results provide helpful information to health authorities to establish efficient surveillance and vector control programmes for ZIKV.
Assuntos
Aedes/virologia , Transmissão de Doença Infecciosa/veterinária , Transmissão Vertical de Doenças Infecciosas/veterinária , Infecção por Zika virus/transmissão , Zika virus/isolamento & purificação , África , Animais , Ásia , Feminino , Masculino , Filogenia , Vigilância da População , Saliva/virologia , Espanha , Zika virus/classificação , Infecção por Zika virus/veterináriaRESUMO
[This corrects the article DOI: 10.3389/fpsyt.2019.01023.].
RESUMO
BACKGROUND: The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP). METHOD: Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses. RESULTS: After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEPâ¯<â¯HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype. CONCLUSIONS: Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Fator Neurotrófico Derivado do Encéfalo/genética , Estudos de Casos e Controles , Genótipo , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único/genética , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/genética , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genéticaRESUMO
In this work, we show that the proteins Pkc1 and Pfy1 play a role in the repolarization of the actin cytoskeleton and in cell survival in response to oxidative stress. We have also developed an assay to determine the actin polymerization capacity of total protein extracts using fluorescence recovery after photobleaching techniques and actin purified from rabbit muscle. This assay allowed us to demonstrate that Pfy1 promotes actin polymerization under conditions of oxidative stress, while Pkc1 induces actin polymerization and cell survival under all the conditions tested. Our assay also points to a relationship between Pkc1 and Pfy1 in the actin cytoskeleton polymerization that is required to adapt to oxidative stress.
Assuntos
Actinas/metabolismo , Viabilidade Microbiana , Estresse Oxidativo , Profilinas/fisiologia , Proteína Quinase C/fisiologia , Multimerização Proteica , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/fisiologia , Estresse Fisiológico , Proteínas FúngicasRESUMO
BACKGROUND: Aedes caspius (Pallas, 1771) is a floodwater mosquito species widely distributed in the Western Palaearctic. As an anthropophilic species, its role as an arbovirus vector may be the key for understanding the transmission cycle of certain diseases in Europe such as Zika virus (ZIKV). Concerning vector competence for ZIKV, studies related to Ae. caspius are still scarce. ZIKV is an arbovirus that has provoked a widespread epidemic in the Pacific region (2007-2013) and in the Americas (2015-2016). ZIKV is associated with serious neurological injuries (e.g. microcephaly) and Guillain-Barré syndrome. Due to the ZIKV epidemics in the American continent, some viraemic travellers coming from endemic countries have been reported in Europe. More knowledge is therefore required to define the susceptibility of autochthonous mosquito species such as Ae. caspius for ZIKV in order to improve arbovirus surveillance and control programmes. In the present study, the vector competence of a European population of Ae. caspius was evaluated for two ZIKV lineages, the Suriname ZIKV strain (Asian lineage) and the MR766 ZIKV strain (African I lineage). Females were tested at 7, 14 and 21 days post-exposure (dpe) to infectious blood meals. An Ae. aegypti PAEA strain was used as a positive control. RESULTS: Aedes caspius presented low susceptibility to ZIKV infection and the virus was only detected by RT-qPCR in body samples. Low viral loads were detected for the MR766 strain at 7 dpe and for the Suriname strain at 14 and 21 dpe. Aedes caspius was unable to produce a disseminated infection and virus transmission at any of the tested time points. Using Ae. aegypti PAEA strain, infection, dissemination and transmission rates were calculated for the Suriname ZIKV strain (Asian lineage) at each time point. For the MR766 ZIKV strain (African I lineage), while only infection rates were estimated at each time point, no dissemination or transmission were detected in either species. CONCLUSIONS: The results of the present study reveal that the tested Ae. caspius population has a strong midgut escape barrier that limits the dissemination or transmission of the virus. As such, it seems unlikely that European Ae. caspius mosquitoes could be involved in ZIKV transmission if ZIKV was introduced into Europe. This information may help in designing a better strategy to European surveillance and control programmes for ZIKV.
Assuntos
Aedes/classificação , Aedes/virologia , Mosquitos Vetores/virologia , Infecção por Zika virus/transmissão , Animais , Europa (Continente) , Feminino , Saliva/virologia , Carga Viral , Zika virusRESUMO
According to the theory of value-based decision making, subjects tend to choose the most valuable among a set of options. However, agents may not be consistent when facing the same decision several times. In this paper, Shannon's entropy (H) is employed as a measure of behavioral inconsistency: it is a central measure of information theory that, applied to decision making, allows the estimation of behavioral preferences among a set of options. We scanned (functional magnetic resonance imaging, fMRI) 24 young (18-25 year) subjects (14 female) while performing a decision-making task, where monetary rewards were devalued by physical effort (minutes running in the treadmill) and risk. Twenty different pairs of options were presented nine times each, and H was calculated for each pair and subject. Behavioral analyses showed that subjective value (SV) significantly explained agents' preferences only in pairs with a low inconsistent response. Averaged response time positively correlated with H, confirming entropy as an indicator of choice difficulty. Group analyses on fMRI data revealed a cluster in the paracingulate cortex as the neural correlate of H. Besides, BOLD signal in the posterior cingulate correlated with the SV of the pair only in consistent decisions, confirming that SV loses its explanatory power on highly inconsistent decisions. Finally, the anterior and central cingulate were especially recruited when predicting a secured effortless reward, compared with a secured reward that involved a maximum effort. Our study shows that different regions of the cingulate cortex are involved in choice inconsistency, SV and processing effort costs.
Assuntos
Encéfalo/diagnóstico por imagem , Comportamento de Escolha/fisiologia , Esforço Físico/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Tomada de Decisões/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tempo de Reação/fisiologia , Adulto JovemRESUMO
Background: Patients with a first episode psychosis (FEP) who are admitted for the first time to a psychiatric hospital frequently have experienced prior psychological trauma. Additionally, 40-80% develop posttraumatic stress symptoms, which are summarized as a post-psychotic post-traumatic syndrome (PPS). Eye Movement Desensitization and reprocessing (EMDR) therapy could be an effective psychotherapy to treat a PPS and prior psychological traumas in this population. Objectives: To assess if EMDR therapy leads to: 1) a reduction of relapses after intervention, 2) an improvement of trauma-related, psychotic and affective symptoms, 3) an improvement of overall functioning, and 4) an improvement in quality of life. Methods: This is a multicenter phase II rater-blinded randomized controlled trial in which 80 FEP patients with a history of psychological trauma will be randomly assigned to EMDR (n = 40) or to TAU (n = 40). Traumatic events will be measured by the Global Assessment of Posttraumatic Stress Questionnaire, the Cumulative Trauma Screening, the Impact of Event Scale-Revised, the Dissociative Experiences Scale, the Childhood Trauma Scale, the Holmes-Rahe Life Stress Inventory, and the Dissociative Experiences Questionnaire. Clinical symptomatology will be evaluated using the Suicide and Drug Consumption module of the International Neuropsychiatric Interview, Structured Clinical Interview for Positive and Negative Syndrome Scale, Young's Scale for Mania Evaluation, and Beck Depression II Questionnaire. Functionality will be assessed with the Global Assessment of Functioning and the Quality of Life with the Standardized Instrument developed by the EuroQol Group. The cognitive insight and adherence to the treatment will be assessed with the Beck Cognitive Insight Scale and the Drug Attitude Inventory. All variables will be measured at baseline, post-treatment and at 12-month follow-up. Conclusion: This study will provide evidence of whether EMDR therapy is effective in reducing trauma and clinical symptoms, reducing relapses and in improving functionality and quality of life in patients with FEP and a history of trauma. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03991377.