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Chickpea is a crucial leguminous crop and India is the leading producer, with an average yield of 1.18 tons/ha. It is renowned for its specific nodulation with rhizobia. Despite its significance, studies on chickpea-nodulating rhizobia often focused on small-scale investigations within restricted geographical areas. This study delves into the population, genetic diversity, and symbiotic efficiency of chickpea-nodulating rhizobia in the Indo-Gangetic Plains (IGP) of India. The study revealed a low population of chickpea rhizobia (ranging from 11 to 565 cells/g dry soil) across the examined area. Only three samples exhibited a population exceeding 300 cells/g, emphasizing the potential need for inoculation of rhizobia with efficient and competitive strains. Correlation analysis highlighted a significant positive correlation between rhizobial population and organic carbon content, among various soil parameters like pH, electrical conductivity, available nitrogen (N), phosphorus (P), potassium (K), and organic carbon content. Among the 79 presumptive rhizobia isolated from 24 IGP locations, 61 successfully nodulated chickpea cultivar Pusa 362. 16S rRNA gene sequencing categorized 54 isolates as Mesorhizobium, four as Rhizobium, and three as Ensifer. Genetic diversity assessed by BOX-PCR revealed sixteen distinct banding patterns, underscoring substantial variability among the strains. The strains exhibited plant growth-promoting activities, salt tolerance up to 3% NaCl, and pH tolerance between 4 and 10. Six symbiotically efficient strains were identified based on their positive impact on nodulation and dry biomass. This study provides crucial insights into the diversity, genetic makeup, and symbiotic efficiency of chickpea rhizobia in the IGP, supporting the potential use of indigenous rhizobia for sustainable chickpea productivity in the region.
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PURPOSE: To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). METHODS: This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein-protein interaction network and functional enrichment analysis were performed using the STRING database. RESULTS: The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p < .0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p < .0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). CONCLUSION: The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval.
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Variações do Número de Cópias de DNA , Reserva Ovariana , Ubiquitina Tiolesterase , Humanos , Feminino , Reserva Ovariana/genética , Adulto , Variações do Número de Cópias de DNA/genética , Ubiquitina Tiolesterase/genética , Estudos de Casos e Controles , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Recuperação de Oócitos , Proteínas Repressoras/genética , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oócitos/patologiaRESUMO
Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.
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Variações do Número de Cópias de DNA , Sequenciamento Completo do Genoma , Humanos , Variações do Número de Cópias de DNA/genética , Sequenciamento Completo do Genoma/economia , Sequenciamento Completo do Genoma/métodos , Brasil , Masculino , Feminino , Criança , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Análise Custo-Benefício , Análise em Microsséries/economia , Análise em Microsséries/métodos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/diagnóstico , Pré-Escolar , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Países em Desenvolvimento , Adolescente , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/diagnóstico , Testes Genéticos/economia , Testes Genéticos/métodosRESUMO
Alphabaculoviruses are lethal dsDNA viruses of Lepidoptera that have high genetic diversity and are transmitted in aggregates within proteinaceous occlusion bodies. This mode of transmission has implications for their efficacy as biological insecticides. A Nicaraguan isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV-NIC) comprising nine genotypic variants has been the subject of considerable study due to the influence of variant interactions on the insecticidal properties of mixed-variant occlusion bodies. As part of a systematic study on the replication and transmission of variant mixtures, a tool for the accurate quantification of a selection of genotypic variants was developed based on the quantitative PCR technique (qPCR). First, primer pairs were designed around a region of high variability in four variants named SfNic-A, SfNic-B, SfNic-C and SfNic-E to produce amplicons of 103-150 bp. Then, using cloned purified amplicons as standards, amplification was demonstrated over a dynamic range of 108-101 copies of each target. The assay was efficient (mean ± SD: 98.5 ± 0.8%), reproducible, as shown by low inter- and intra-assay coefficients of variation (<5%), and specific to the target variants (99.7-100% specificity across variants). The quantification method was validated on mixtures of genotype-specific amplicons and demonstrated accurate quantification. Finally, mixtures of the four variants were quantified based on mixtures of budded virions and mixtures of DNA extracted from occlusion-derived virions. In both cases, mixed-variant preparations compared favorably to total viral genome numbers by quantification of the polyhedrin (polh) gene that is present in all variants. This technique should prove invaluable in elucidating the influence of variant diversity on the transmission and insecticidal characteristics of this pathogen.
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Variação Genética , Genótipo , Nucleopoliedrovírus , Reação em Cadeia da Polimerase em Tempo Real , Spodoptera , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/classificação , Nucleopoliedrovírus/isolamento & purificação , Animais , Spodoptera/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , DNA Viral/genéticaRESUMO
A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein-creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034-0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119-0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.
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Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.
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BACKGROUND: In prostate cancer (PCa), well-established biomarkers such as MSI status, TMB high, and PDL1 expression serve as reliable indicators for favorable responses to immunotherapy. Recent studies have suggested a potential association between CDK12 mutations and immunotherapy response; however, the precise mechanisms through which CDK12 mutation may influence immune response remain unclear. A plausible explanation for immune evasion in this subset of CDK12-mutated PCa may be reduced MHC expression. RESULTS: Using genomic data of CDK12-mutated PCa from 48 primary and 10 metastatic public domain samples and a retrospective cohort of 53 low-intermediate risk primary PCa, we investigated how variation in the expression of the MHC genes affected associated downstream pathways. We classified the patients based on gene expression quartiles of MHC-related genes and categorized the tumors into "High" and "Low" expression levels. CDK12-mutated tumors with higher MHC-expressed pathways were associated with the immune system and elevated PD-L1, IDO1, and TIM3 expression. Consistent with an inflamed tumor microenvironment (TME) phenotype, digital cytometric analyses identified increased CD8 + T cells, B cells, γδ T cells, and M1 Macrophages in this group. In contrast, CDK12-mutated tumors with lower MHC expression exhibited features consistent with an immune cold TME phenotype and immunoediting. Significantly, low MHC expression was also associated with chromosome 6 loss of heterozygosity (LOH) affecting the entire HLA gene cluster. These LOH events were observed in both major clonal and minor subclonal populations of tumor cells. In our retrospective study of 53 primary PCa cases from this Institute, we found a 4% (2/53) prevalence of CDK12 mutations, with the confirmation of this defect in one tumor through Sanger sequencing. In keeping with our analysis of public domain data this tumor exhibited low MHC expression at the RNA level. More extensive studies will be required to determine whether reduced HLA expression is generally associated with primary tumors or is a specific feature of CDK12 mutated PCa. CONCLUSIONS: These data show that analysis of CDK12 alteration, in the context of MHC expression levels, and LOH status may offer improved predictive value for outcomes in this potentially actionable genomic subgroup of PCa. In addition, these findings highlight the need to explore novel therapeutic strategies to enhance MHC expression in CDK12-defective PCa to improve immunotherapy responses.
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Due to substantial differences between studies, the understanding of avian taste perception remains incomplete. Also, studies on chicken taste preferences have mainly focused on measuring consumption differences, neglecting consumption behaviour patterns. This study investigated how age, the compound delivery matrix, and the number of birds per pen affect broiler chicken preferences and consumption behaviour, and established their preference values for four taste compounds. Ninety-six one-day-old male broiler chickens (Ross 308) were divided into two age groups (initial: days 7-23; final: days 26-42), with two compound delivery matrices (water or ground wheat) and two numbers of birds (one or two chickens per pen), following a 2 × 2 × 2 factorial design. Four taste compounds (sucrose, monosodium glutamate (MSG), L-lysine, and calcium carbonate) were tested at different concentrations. Preferences were assessed at 2, 4, and 8 h post-test, along with recording various behavioural parameters. Initial-stage birds showed higher (p < 0.001) preference values, time of approach (TA), number of bouts (NB), duration of bouts (DB), and number of pecks (NP) than final-stage birds. Birds exposed to a water matrix also exhibited higher (p < 0.001) preference and NB, while those exposed to a ground wheat matrix showed a higher (p < 0.001) NP. Pens with a pair of birds had a higher (p < 0.003) 2 h preference, TA, NB, DB, and NP, than pens with a single chicken. Chickens showed significant preference values for 100 mM sucrose at 2 h (p = 0.025), 150 mM MSG at 4 h (p = 0.026) and 8 h (p = 0.013), and 300 mM MSG at 2 h (p = 0.013). We concluded that all the variables evaluated influence broilers' taste preferences and consumption behaviour during selection tests. Future studies should prioritize including chickens in the initial stage of the production cycle, testing them in pairs or groups, and delivering compounds via a liquid matrix.
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A comprehensive mathematical model is proposed to study two strains of dengue virus with saturated incidence rates and quarantine measures. Imperfect dengue vaccination is also assumed in the model. Existence, uniqueness and stability of the proposed model are proved using the results from fixed point and degree theory. Additionally, well constructed Lyapunov function candidates are also applied to prove the global stability of infection-free equilibria. It is also demonstrated that the model is generalized Ulam-Hyers stable under some appropriate conditions. The model is fitted to the real data of dengue epidemic taken from the city of Espirito Santo in Brazil. For the approximate solution of the model, a non-standard finite difference(NSFD) approach is applied. Sensitivity analysis is also carried out to show the influence of different parameters involved in the model. The behaviour of the NSFD is also assessed under different denominator functions and it is observed that the choice of the denominator function could influence the solution trajectories. Different scenario analysis are also assessed when the reproduction number is below or above one. Furthermore, simulations are also presented to assess the epidemiological impact of dengue vaccination and quarantine measures for infected individuals.
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Dengue , Quarentena , Vacinação , Dengue/transmissão , Dengue/prevenção & controle , Dengue/epidemiologia , Humanos , Brasil/epidemiologia , Vírus da Dengue/imunologia , Modelos Teóricos , Vacinas contra DengueRESUMO
Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaß pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaß pathway in predisposition to endometriosis.
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Variações do Número de Cópias de DNA , Endometriose , Humanos , Endometriose/genética , Feminino , Adulto , Cromossomos Humanos Par 3/genética , Predisposição Genética para Doença , Polimorfismo GenéticoRESUMO
Copy number variation is a common contributor to phenotypic diversity, yet its involvement in ecological adaptation is not easily discerned. Instances of parallelly evolving populations of the same species in a similar environment marked by strong selective pressures present opportunities to study the role of copy number variants (CNVs) in adaptation. By identifying CNVs that repeatedly occur in multiple populations of the derived ecotype and are not (or are rarely) present in the populations of the ancestral ecotype, the association of such CNVs with adaptation to the novel environment can be inferred. We used this paradigm to identify CNVs associated with recurrent adaptation of the Mexican tetra (Astyanax mexicanus) to cave environment. Using a read-depth approach, we detected CNVs from previously re-sequenced genomes of 44 individuals belonging to two ancestral surfaces and three derived cave populations. We identified 102 genes and 292 genomic regions that repeatedly diverge in copy number between the two ecotypes and occupy 0.8% of the reference genome. Functional analysis revealed their association with processes previously recognized to be relevant for adaptation, such as vision, immunity, oxygen consumption, metabolism, and neural function and we propose that these variants have been selected for in the cave or surface waters. The majority of the ecotype-divergent CNVs are multiallelic and display copy number increases in cavefish compared to surface fish. Our findings suggest that multiallelic CNVs - including gene duplications - and divergence in copy number provide a fast route to produce novel phenotypes associated with adaptation to subterranean life.
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Cavernas , Characidae , Variações do Número de Cópias de DNA , Variações do Número de Cópias de DNA/genética , Animais , Characidae/genética , Genética Populacional , Adaptação Fisiológica/genética , Ecótipo , MéxicoRESUMO
Pressure fluctuations in a mixing tank can provide valuable information about the existing flow regime within the tank, which in turn influences the degree of mixing that can be achieved. In the present work, we propose a prototype for identifying the flow regime in mechanically stirred tanks equipped with four vertical baffles through the characterization of pressure fluctuations. Our innovative proposal is based on force sensors strategically placed in the baffles of the mixing tank. The signals coming from the sensors are transmitted to an electronic module based on an Arduino UNO development board. In the electronic module, the pressure signals are conditioned, amplified and sent via Bluetooth to a computer. In the computer, the signals can be plotted or stored in an Excel file. In addition, the proposed system includes a moving average filtering and a hierarchical bottom-up clustering analysis that can determine the real-time flow regime (i.e., the Reynolds number, Re) in which the tank was operated during the mixing process. Finally, to demonstrate the versatility of the proposed prototype, experiments were conducted to identify the Reynolds number for different flow regimes (static, laminar, transition and turbulent), i.e., 0≤Re≤ 42,955. Obtained results were in agreement with the prevailing consensus on the onset and developed from different flow regimes in mechanically stirred tanks.
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PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases. METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC. RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed. CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.
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Ciclina E , Variações do Número de Cópias de DNA , Neoplasias do Endométrio , Amplificação de Genes , Gradação de Tumores , Proteínas Oncogênicas , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Humanos , Ciclina E/genética , Proteínas Oncogênicas/genética , Variações do Número de Cópias de DNA/genética , Carcinogênese/genética , Pessoa de Meia-Idade , Sequenciamento do Exoma , Replicação do DNA/genética , Prognóstico , IdosoRESUMO
In late March 2020, SARS-CoV-2 arrived in Manaus, Brazil, and rapidly developed into a large-scale epidemic that collapsed the local health system and resulted in extreme death rates. Several key studies reported that â¼76% of residents of Manaus were infected (attack rate AR≃76%) by October 2020, suggesting protective herd immunity had been reached. Despite this, an unexpected second wave of COVID-19 struck again in November and proved to be larger than the first, creating a catastrophe for the unprepared population. It has been suggested that this could be possible if the second wave was driven by reinfections. However, it is widely reported that reinfections were at a low rate (before the emergence of Omicron), and reinfections tend to be mild. Here, we use novel methods to model the epidemic from mortality data without considering reinfection-caused deaths and evaluate the impact of interventions to explain why the second wave appeared. The method fits a "flexible" reproductive number R0(t) that changes over the epidemic, and it is demonstrated that the method can successfully reconstruct R0(t) from simulated data. For Manaus, the method finds AR≃34% by October 2020 for the first wave, which is far less than required for herd immunity yet in-line with seroprevalence estimates. The work is complemented by a two-strain model. Using genomic data, the model estimates transmissibility of the new P.1 virus lineage as 1.9 times higher than that of the non-P.1. Moreover, an age class model variant that considers the high mortality rates of older adults show very similar results. These models thus provide a reasonable explanation for the two-wave dynamics in Manaus without the need to rely on large reinfection rates, which until now have only been found in negligible to moderate numbers in recent surveillance efforts.
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OBJECTIVE: This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). MATERIALS AND METHODS: We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. RESULTS: Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways. CONCLUSION: This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.
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Adenocarcinoma , Adenoma Pleomorfo , MicroRNAs , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/patologia , Variações do Número de Cópias de DNA , Neoplasias das Glândulas Salivares/patologia , MicroRNAs/genética , Hibridização Genômica Comparativa , Transformação Celular Neoplásica/patologia , Adenocarcinoma/patologiaRESUMO
The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015-2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection.
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Aedes , Epidemias , Infecção por Zika virus , Zika virus , Animais , Humanos , Brasil/epidemiologia , EsgotosRESUMO
Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression.
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Variações do Número de Cópias de DNA , DNA Mitocondrial , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , DNA Mitocondrial/genética , Feminino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Biomarcadores Tumorais/genética , PrognósticoRESUMO
In this paper we discuss the details, limitations, and difficulties of the implementation in hardware of a memristor-based random number generator that exhibits monofractal/multifractal behavior. To do so, the components and selection criteria of a reference memristor and one proposed by the authors, the chaotic circuit leveraging them, and the processing that is performed on the chaotic signals to achieve the random discrete sequences are described. After applying the estimation tools, findings indicate that more than 60% of the proposed combinations allow generating random discrete sequences, with long-range dependence, and that both monofractal and multifractal behaviors can also be obtained. Consequently, a hardware system was achieved that can be used as a source of entropy in future synthetic biological signal generators.
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Today, safeguarding sensitive content through encryption is crucial. This work presents a hybrid cryptosystem for images that employs both asymmetric and symmetric encryption. The asymmetric component involves applying the Diffie-Hellman protocol and the ElGamal cryptosystem to securely transmit two constants. These constants are necessary for the symmetrical aspect to generate dynamic permutations, substitution boxes, and round keys. Following an encryption process with fourteen rounds, the encrypted images are processed by an algorithm proposed to enhance entropy, a critical metric for assessing encryption quality. It increases the frequencies of the basic colors to achieve a histogram closely resembling a uniform distribution, but it increases the image size by approximately 8%. This improves the entropy values achieved by the hybrid cryptosystem, bringing them remarkably close to the ideal value of 8.0. In specific instances, the entropy values were elevated from 7.99926 to 8.0. The proposed method exhibits resilience against various attacks, including differential, linear, brute force, and algebraic attacks, as evaluated through the entropy, correlation, goodness of fit, Discrete Fourier Transform (DFT), Number of Pixels Change Rate (NPCR), Unified Average Changing Intensity (UACI), Avalanche Criteria (AC), contrast, energy, and homogeneity. Further, encrypted images are subjected to noise attacks ranging from 20% to 50% noise, including additive, multiplicative, occlusion noise, as well as the newly introduced χ2 noise. The noise damage is quantified using the proposed Similarity Parameter (SP), and a 3 × 3 median filter is employed to enhance the visual quality.
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Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3-4% of the world's population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8-21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for "isolated" ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.