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1.
BMC Plant Biol ; 24(1): 562, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38877425

ABSTRACT

BACKGROUND: On tropical regions, phosphorus (P) fixation onto aluminum and iron oxides in soil clays restricts P diffusion from the soil to the root surface, limiting crop yields. While increased root surface area favors P uptake under low-P availability, the relationship between the three-dimensional arrangement of the root system and P efficiency remains elusive. Here, we simultaneously assessed allelic effects of loci associated with a variety of root and P efficiency traits, in addition to grain yield under low-P availability, using multi-trait genome-wide association. We also set out to establish the relationship between root architectural traits assessed in hydroponics and in a low-P soil. Our goal was to better understand the influence of root morphology and architecture in sorghum performance under low-P availability. RESULT: In general, the same alleles of associated SNPs increased root and P efficiency traits including grain yield in a low-P soil. We found that sorghum P efficiency relies on pleiotropic loci affecting root traits, which enhance grain yield under low-P availability. Root systems with enhanced surface area stemming from lateral root proliferation mostly up to 40 cm soil depth are important for sorghum adaptation to low-P soils, indicating that differences in root morphology leading to enhanced P uptake occur exactly in the soil layer where P is found at the highest concentration. CONCLUSION: Integrated QTLs detected in different mapping populations now provide a comprehensive molecular genetic framework for P efficiency studies in sorghum. This indicated extensive conservation of P efficiency QTL across populations and emphasized the terminal portion of chromosome 3 as an important region for P efficiency in sorghum. Increases in root surface area via enhancement of lateral root development is a relevant trait for sorghum low-P soil adaptation, impacting the overall architecture of the sorghum root system. In turn, particularly concerning the critical trait for water and nutrient uptake, root surface area, root system development in deeper soil layers does not occur at the expense of shallow rooting, which may be a key reason leading to the distinctive sorghum adaptation to tropical soils with multiple abiotic stresses including low P availability and drought.


Subject(s)
Genome-Wide Association Study , Phosphorus , Plant Roots , Quantitative Trait Loci , Sorghum , Sorghum/genetics , Sorghum/metabolism , Sorghum/growth & development , Phosphorus/metabolism , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/genetics , Plant Roots/anatomy & histology , Chromosome Mapping , Polymorphism, Single Nucleotide , Soil/chemistry , Phenotype
2.
Am J Med Genet A ; : e63602, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38517102

ABSTRACT

Ramon syndrome (OMIM #266270) was first described in a patient with cherubism, gingival fibromatosis, epilepsy, intellectual disability, hypertrichosis, and stunted growth. In 2018, Mehawej et al. described a patient with Ramon syndrome in whom a homozygous variant in ELMO2 was identified, suggesting that this gene may be the causative for this syndrome. ELMO2 biallelic pathogenic variants were also described in patients with a primary intraosseous vascular malformation (PIVM; OMIM #606893). These patients presented gingival bleeding and cherubism phenotype. Herein, a patient with gingival hypertrophy, neurodevelopmental delay, and cherubism phenotype with a novel homozygous predicted loss-of-function (LOF) variant in the ELMO2 gene and family recurrence was reported. A surgical approach to treat gingival bleeding and mandible vascular malformation was also described. Furthermore, this study includes a comprehensive literature review of molecular data regarding the ELMO2 gene. All the variants, except one described in the ELMO2, were predicted as LOF, including our patient's variant. There is an overlapping between PIVM, also caused by LOF biallelic variants in the ELMO2 gene, and Ramon syndrome, which can suggest that they are not different entities. However, due to a limited number of cases described with molecular evaluation, it is hard to establish a genotype-phenotype correlation. Our study supports that LOF pathogenic biallelic variants in the ELMO2 gene cause a phenotype that has cherubism and gingival hypertrophy as main characteristics.

3.
Gerontology ; 69(1): 65-72, 2023.
Article in English | MEDLINE | ID: mdl-35584617

ABSTRACT

INTRODUCTION: Radiological indicators in head computed tomography (CT) scan have emerged as tools to evaluate sarcopenia using the sectional area and thickness of the temporal muscle. They can be obtained by standardized measurements in preoperative image assessment of patients with brain aneurysms. We aimed to evaluate the association between functional outcomes after interventions for intracranial aneurysms (IAs) and temporal muscle thickness (TMT) and area (TMA), as surrogates of sarcopenia. METHODS: This is a prospective observational cohort study in patients who underwent microsurgery or embolization for ruptured or unruptured IA between January 2018 and December 2019, with a 6-month follow-up. Preoperative CT scans were analyzed to measure TMT and TMA. The functional outcome was assessed by the modified Rankin Scale (mRS). The main outcome was the relationship between sarcopenia and the postoperative functional outcome. RESULTS: A total of 361 patients were included, of whom 199 (55.1%) had ruptured and 162 (44.9%) had unruptured lesions. Larger TMA significantly predicted better functional outcomes at discharge. TMT was associated with functional outcomes at both discharge and 6 months, adjusted for rupture and hypertension. Maximizing the sum sensitivity-specificity, an optimal TMT cutoff of 6.25 mm can predict unfavorable outcomes. Maximizing the positive predictive value × negative predictive value of a product, the cutpoint was 3.55 mm. CONCLUSIONS: Sarcopenia, represented by TMT and TMA, is associated with poorer functional results at discharge and 6-month follow-up in IA surgery. TMT below 6.25 mm was associated with unfavorable functional outcomes. These easily obtainable measurements may improve the decision-making process for patients with IAs.


Subject(s)
Intracranial Aneurysm , Sarcopenia , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Cohort Studies , Sarcopenia/diagnosis , Sarcopenia/diagnostic imaging , Retrospective Studies , Predictive Value of Tests , Treatment Outcome
4.
Pharmacogenet Genomics ; 32(9): 293-300, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36256702

ABSTRACT

OBJECTIVES: The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. METHODS: The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and ß2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. RESULTS: Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of ß2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). CONCLUSIONS: The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , Male , Humans , Middle Aged , Female , Tenofovir/adverse effects , Anti-HIV Agents/adverse effects , Acquired Immunodeficiency Syndrome/drug therapy , Pharmacogenomic Testing , Case-Control Studies , HIV Infections/drug therapy , HIV Infections/genetics , Multidrug Resistance-Associated Protein 2 , Phosphorus/therapeutic use
5.
J Clin Immunol ; 42(8): 1708-1720, 2022 11.
Article in English | MEDLINE | ID: mdl-35907101

ABSTRACT

OBJECTIVE: The Bacille Calmette-Guérin (BCG) vaccine is routinely applied in Brazil. Adverse events (AE) may occur in patients with inborn or acquired immunodeficiencies, varying between local (BCGitis) or disseminated (BCGosis) reactions. We evaluated 53 individuals with local or disseminated adverse events to BCG vaccination to assess if they had inborn errors of immunity (IEI). METHODS: Patients diagnosed with an adverse event following BCG vaccination between 2014 and 2017 were included in the study. We collected clinical data, immunophenotyped T and B lymphocytes, and natural killer cells (NK), assessed oxidative function of neutrophils through dihydrorhodamine (DHR) 123 testing, and genotyped 361 genes related to IEI through targeted (panel) sequencing. RESULTS: The median age of the 53 individuals was four months (IQ 1.5-12), and 52.8% were male. Forty-eight (90.6%) individuals presented only locoregional AE and five (9.4%) presented both locoregional and disseminated AE. Nine (16.9%) patients were diagnosed with an IEI. Four of them presented BCGitis and five presented BCGosis after BCG vaccination. Clinically, four presented chronic granulomatous disease (CGD), three Mendelian susceptibility to mycobacterial disease (MSMD), and two severe combined immunodeficiency (SCID). Patients with IEI had a higher frequency of systemic symptomatology (p = 0.002), history of other infections (p < 0.001), parental consanguinity (p = 0.01), familial history of sick siblings (p < 0.001), or early deaths in the family (p < 0.01). CONCLUSION: There is a high frequency of IEI in patients with locoregional and disseminated adverse events to BCG vaccination, revealing the need for the investigation of IEI accompanied by clinical and familial inquiry.


Subject(s)
BCG Vaccine , Severe Combined Immunodeficiency , Tuberculosis , Child, Preschool , Female , Humans , Male , BCG Vaccine/adverse effects , Brazil/epidemiology , Severe Combined Immunodeficiency/genetics , Tuberculosis/diagnosis , Vaccination/adverse effects
6.
Arch Microbiol ; 204(2): 143, 2022 Jan 19.
Article in English | MEDLINE | ID: mdl-35044594

ABSTRACT

Usage of Bacillus and Azospirillum as new eco-friendly microbial consortium inoculants is a promising strategy to increase plant growth and crop yield by improving nutrient availability in agricultural sustainable systems. In this study, we designed a multispecies inoculum containing B. thuringiensis (strain B116), B. subtillis (strain B2084) and Azospirillum sp. (strains A1626 and A2142) to investigate their individual or co-inoculated ability to solubilize and mineralize phosphate, produce indole acetic acid (IAA) and their effect on maize growth promotion in hydroponics and in a non-sterile soil. All strains showed significant IAA production, P mineralization (sodium phytate) and Ca-P, Fe-P (tricalcium phosphate and iron phosphate, respectively) solubilization. In hydroponics, co-inoculation with A1626 x A2142, B2084 x A2142, B2084 x A1626 resulted in higher root total length, total surface area, and surface area of roots with diameter between 0 and 1 mm than other treatments with single inoculant, except B2084. In a greenhouse experiment, maize inoculated with the two Azospirillum strains exhibited enhanced shoot dry weight, shoot P and K content, root dry weight, root N and K content and acid and alkaline phosphatase activities than the other treatments. There was a significant correlation between soil P and P shoot, alkaline phosphatase and P shoot and between acid phosphatase and root dry weight. It may be concluded that co-inoculations are most effective than single inoculants strains, mainly between two selected Azospirillum strains. Thus, they could have synergistic interactions during maize growth, and be useful in the formulation of new inoculants to improve the tropical cropping systems sustainability.


Subject(s)
Azospirillum , Bacillus , Nutrients , Plant Roots , Soil Microbiology , Zea mays
7.
An Acad Bras Cienc ; 93(3): e20201614, 2021.
Article in English | MEDLINE | ID: mdl-34406286

ABSTRACT

Magnesium is one of the essential elements for the plant growth. However, when the supply of magnesium is required exclusively, few economically feasible options are available. Serpentinite represents an alternative source of magnesium, although little is known about its potential and efficiency under tropical soil conditions. This work aimed to evaluate the use of serpentinite as a soil remineralizer, as well as magnesium fertilizer. The study was conducted in a greenhouse, using a completely randomized design, with seven treatments and four replications, as follows: three levels of serpentinite, mix of serpentinite and phonolite, and the controls with dolomitic limestone and without fertilization. Two plant species (Zea mays L. corn hybrid BRS - 1055 and Phaseolus vulgaris L. common bean variety BRS - Estilo) and two contrasting soils (clayey and sandy texture), were used in pots. Results showed that serpentinite's free silica and toxic element contents fitted the legal requirements. No statistically significant difference was observed for the plant dry matter weight production in the serpentinite and dolomitic limestone control, as well as in the pure serpentinite and the mix with phonolite treatments. The serpentinite was able to supply and to fullfil magnesium requirements for growth and development of corn and bean plants.


Subject(s)
Phaseolus , Soil , Agriculture , Fertilizers/analysis , Zea mays
8.
BMC Med Educ ; 21(1): 248, 2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33926437

ABSTRACT

BACKGROUND: With the emergence of the new coronavirus pandemic (COVID-19), distance learning, especially that mediated by information and digital communication technologies, has been adopted in all areas of knowledge and at all levels, including medical education. Imminently practical areas, such as pathology, have made traditional teaching based on conventional microscopy more flexible through the synergies of computational tools and image digitization, not only to improve teaching-learning but also to offer alternatives to repetitive and exhaustive histopathological analyzes. In this context, machine learning algorithms capable of recognizing histological patterns in kidney biopsy slides have been developed and validated with a view to building computational models capable of accurately identifying renal pathologies. In practice, the use of such algorithms can contribute to the universalization of teaching, allowing quality training even in regions where there is a lack of good nephropathologists. The purpose of this work is to describe and test the functionality of SmartPathk, a tool to support teaching of glomerulopathies using machine learning. The training for knowledge acquisition was performed automatically by machine learning methods using the J48 algorithm to create a computational model of an appropriate decision tree. RESULTS: An intelligent system, SmartPathk, was developed as a complementary remote tool in the teaching-learning process for pathology teachers and their students (undergraduate and graduate students), showing 89,47% accuracy using machine learning algorithms based on decision trees. CONCLUSION: This artificial intelligence system can assist in teaching renal pathology to increase the training capacity of new medical professionals in this area.


Subject(s)
COVID-19 , Education, Distance , Artificial Intelligence , Humans , Machine Learning , SARS-CoV-2 , Teaching
9.
Genet Mol Biol ; 42(2): 351-356, 2019.
Article in English | MEDLINE | ID: mdl-31259360

ABSTRACT

Vitamin D exerts an immuno-modulatory activity on several immune system cells through the vitamin D receptor (VDR). Herein, we verified that age and a therapeutic regimen containing protease inhibitors are associated with failures in antiretroviral therapies (ARVs). In addition, we assessed whether a VDR SNP (rs11568820: C allele and CC genotype) and GC (rs2228570-rs11568820) allelic combinations are associated with immunological failure (p < 0.05). Our findings suggest a possible role of VDR SNPs on immunological failure in HIV-1+ individuals undergoing regular ARVs.

10.
Phys Rev Lett ; 119(1): 013601, 2017 Jul 07.
Article in English | MEDLINE | ID: mdl-28731763

ABSTRACT

Strong nonlinearity at the single photon level represents a crucial enabling tool for optical quantum technologies. Here we report on experimental implementation of a strong Kerr nonlinearity by measurement-induced quantum operations on weak quantum states of light. Our scheme coherently combines two sequences of single photon addition and subtraction to induce a nonlinear phase shift at the single photon level. We probe the induced nonlinearity with weak coherent states and characterize the output non-Gaussian states with quantum state tomography. The strong nonlinearity is clearly witnessed as a change of sign of specific off-diagonal density matrix elements in the Fock basis.

11.
Int J Mol Sci ; 18(8)2017 Aug 05.
Article in English | MEDLINE | ID: mdl-28783051

ABSTRACT

Zika virus is an emergent flavivirus transmitted by Aedes genus mosquitoes that recently reached the Americas and was soon implicated in an increase of microcephaly incidence. The objective of the present study is to systematically review the published data and perform a meta-analysis to estimate the prevalence of microcephaly in babies born to Zika virus-infected women during pregnancy. We searched PubMed and Cochrane databases, included cohort studies, and excluded case reports and case series publications. We extracted sample sizes and the number of microcephaly cases from eight studies, which permitted a calculation of prevalence rates that are pooled in a random-effects model meta-analysis. We estimated the prevalence of microcephaly of 2.3% (95% CI = 1.0-5.3%) among all pregnancies. Limitations include mixed samples of women infected at different pregnancy times, since it is known that infection at the first trimester is associated with higher risk to congenital anomalies. The estimates are deceptively low, given the devastating impact the infection causes over children and their families. We hope our study contributes to public health knowledge to fight Zika virus epidemics to protect mothers and their newborns.


Subject(s)
Microcephaly/epidemiology , Microcephaly/virology , Zika Virus Infection/epidemiology , Zika Virus/physiology , Female , Humans , Infant , Infant, Newborn , Prevalence
12.
Int J Mol Sci ; 18(2)2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28212307

ABSTRACT

Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-"boosted" lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV-1 , Maternal Exposure , Mothers , Prenatal Exposure Delayed Effects , Animals , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Disease Management , Disease Models, Animal , Epigenesis, Genetic/drug effects , Female , HIV Infections/complications , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical/prevention & control , Meta-Analysis as Topic , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/prevention & control , Pregnancy
13.
Phys Rev Lett ; 116(11): 110501, 2016 Mar 18.
Article in English | MEDLINE | ID: mdl-27035292

ABSTRACT

We experimentally demonstrate a universal strategy for producing a quantum state that is orthogonal to an arbitrary, infinite-dimensional, pure input one, even if only a limited amount of information about the latter is available. Arbitrary coherent superpositions of the two mutually orthogonal states are then produced by a simple change in the experimental parameters. We use input coherent states of light to illustrate two variations of the method. However, we show that the scheme works equally well for arbitrary input fields and constitutes a universal procedure, which may thus prove a useful building block for quantum state engineering and quantum information processing with continuous-variable qubits.

14.
J Mater Sci Mater Med ; 27(8): 129, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27379627

ABSTRACT

The use of meshes for treatment of hernias continues to draw attention of surgeons and the industry in the search of an ideal prosthesis. The purpose of this work is to use meshes manufactured from bacterial cellulose, evaluate their organic tissue interaction and compare with an expanded polytetrafluorethylene (ePTFE's) prosthesis used to repair acute defect of muscle aponeurotic induced in rats. Forty-five male Wistar rats were classified using the following criteria: (1) surgical repair of acute muscle aponeurotic defect with perforated bacterial cellulose film (PBC; n = 18); (2) compact bacterial cellulose film (CBC; n = 12) and (3) ePTFE; (n = 15). After postoperative period, rectangles (2 × 3 cm) including prosthesis, muscles and peritoneum were collected for biomechanical, histological and stereological analysis. In all cases, the maximum acceptable error probability for rejecting the null hypothesis was 5 %. Between PBC and CBC samples, the variables of strain (P = 0.011) and elasticity (P = 0.035) were statistically different. The same was found between CBC and ePTFE (elasticity, P = 0.000; strain, P = 0.009). PBC differed from CBC for giant cells (P = 0.001) and new blood vessels (P = 0.000). In conclusion, there was biological integration and biomechanical elasticity of PBC; therefore, we think this option should be considered as a new alternative biomaterial for use as a bio prosthesis.


Subject(s)
Abdominal Muscles/pathology , Cellulose/chemistry , Hernia/therapy , Polytetrafluoroethylene/chemistry , Surgical Mesh , Tissue Adhesions/prevention & control , Animals , Bacteria/chemistry , Biocompatible Materials/chemistry , Hydrogels/chemistry , Inflammation , Male , Peritoneum/pathology , Rats , Rats, Wistar , Stress, Mechanical
15.
Ann Hum Biol ; 43(3): 261-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26079218

ABSTRACT

BACKGROUND: The Human Papillomavirus (HPV) predisposes 500 000 women to cervical cancer. Host genetic background may facilitate virus persistence in the uterine cervix. Polymorphisms in regulatory and coding regions of cytokine genes have been associated with susceptibility to some human diseases. AIM: This study aims at investigating whether TNFA -308 G/A and IL18 -137 G/C and -607 C/A polymorphisms are associated with susceptibility to HPV infection/progression to high-grade squamous intraepithelial lesion (HSIL). SUBJECTS AND METHODS: One hundred and twenty-two HPV infected and 132 HPV negative women (the latter used as healthy controls) were analysed. TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were analysed using specific sequence polymorphism PCR (SSP-PCR). Univariate statistical analysis and a logistic regression were performed. RESULTS: The TNFA -308A allele was associated with susceptibility to HPV infection (p = 0.0008), while the IL18 -607A allele conferred protection against HPV infection (p = 0.0043). TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were not associated with development of cervical lesions (p > 0.05). An association was also observed between smoking and susceptibility to the development of HSIL. CONCLUSION: The findings suggest an association between two TNFA SNPs and susceptibility to HPV infection in women from Northeast Brazil. The results need to be functionally validated and replicated in other populations with different ethnic backgrounds.


Subject(s)
Genetic Predisposition to Disease , Interleukin-18/genetics , Papillomaviridae/physiology , Papillomavirus Infections/genetics , Polymorphism, Single Nucleotide/genetics , Tumor Necrosis Factor-alpha/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/virology
16.
Int J Mol Sci ; 17(12)2016 Nov 26.
Article in English | MEDLINE | ID: mdl-27898045

ABSTRACT

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.


Subject(s)
AIDS Vaccines/therapeutic use , Dendritic Cells/immunology , HIV Infections/drug therapy , Immunotherapy/methods , Clinical Trials as Topic , HIV Infections/immunology , HIV Infections/prevention & control , Humans
17.
Am J Hum Biol ; 27(5): 674-80, 2015.
Article in English | MEDLINE | ID: mdl-25820814

ABSTRACT

OBJECTIVES: This study aims at performing a systematic review and meta-analysis with the studies of genetic admixture inference of Brazilian population and to compare these results with the genetic admixture levels in other Latin American countries. METHODS: We searched for articles regarding the estimation of Brazilian genetic admixture published between 1980 and 2014 that used autosomal markers. Then, conducted meta-analyses at the whole-country and regional level. Finally, we compared the results of Brazil with other estimates from other South, Central and North American countries. RESULTS: We analyzed data from 25 studies in 38 different Brazilian populations. European (EUR) ancestry is the major contributor to the genetic background of Brazilians, followed by African (AFR), and Amerindian (AMR) ancestries. The pooled ancestry contributions were 0.62 EUR, 0.21 AFR, and 0.17AMR. The Southern region had a greater EUR contribution (0.77) than other regions. Individuals from the Northeast (NE) region had the highest AFR contribution (0.27) whereas individuals from the North regions had more AMR contribution (0.32). In the Latin America context, Brazil has the 5th high EUR contribution, the 12th for the AFR component and the 10th for the AMR ancestry. CONCLUSIONS: Admixture proportions vary greatly among Brazilian populations and also through Latin America. More studies in the Center-West, North and NE regions are needed to capture a more complete picture of the genomic ancestry of Brazil.


Subject(s)
Gene Frequency , Genetic Variation , Brazil , Ethnicity , Humans
18.
Rheumatol Int ; 35(4): 657-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25146332

ABSTRACT

Mevalonate kinase deficiency (MKD) is a rare autosomal disease caused by mutations in the mevalonate kinase gene (MVK). The genotype-phenotype correlation is sometimes problematic due to the great genetic and clinical heterogeneity; so we hypothesize that genes other than MVK are able to modulate MKD clinical phenotypes. This hypothesis was tested by analyzing the exome of 22 patients with MKD all carrying MVK gene mutations, and 20 patients with recurrent fevers (RF) not carrying MVK mutations. Our preliminary findings suggest a possible role of GRID2 in the susceptibility to develop MKD. GRID2 gene (4q22.2), encoding for human glutamate receptor delta-2, associated with MKD: The rs1450500 SNP was differently distributed in patients with MKD with respect to those with RF. Being aware of the small number of patients analyzed, we hypothesized a possible role for GRID2 as possible phenotype modifier in MKD patients, especially in those with severe phenotypes.


Subject(s)
Alleles , Mevalonate Kinase Deficiency/genetics , Receptors, Glutamate/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Mutation , Phenotype
19.
Mem Inst Oswaldo Cruz ; 110(2): 222-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25946246

ABSTRACT

Lactotransferrin, also known as lactoferrin, is an iron binding glycoprotein that displays antiviral activity against many different infectious agents, including human immunodeficiency virus (HIV)-1. Lactotransferrin is present in the breast milk and in the female genitourinary mucosa and it has been hypothesised as a possible candidate to prevent mother-to-child HIV-1 transmission. To verify if two functional polymorphisms, Thr29Ala and Arg47Lys, in the lactotransferrin encoding gene (LTF) could affect HIV-1 infection and vertical transmission, a preliminary association study was performed in 238 HIV-1 positive and 99 HIV-1 negative children from Brazil, Italy, Africa and India. No statistically significant association for the Thr29Ala and Arg47Lys LTF polymorphisms and HIV-1 susceptibility in the studied populations was found. Additionally LTF polymorphisms frequencies were compared between the four different ethnic groups.


Subject(s)
Acquired Immunodeficiency Syndrome/transmission , Genetic Predisposition to Disease/genetics , HIV-1/genetics , Infectious Disease Transmission, Vertical , Lactoferrin/genetics , Polymorphism, Single Nucleotide/genetics , Acquired Immunodeficiency Syndrome/ethnology , Adolescent , Brazil/ethnology , Child , Cohort Studies , Ethnicity/genetics , Female , Gene Frequency/genetics , Genotyping Techniques , Humans , India/ethnology , Infant, Newborn , Italy/ethnology , Male , Real-Time Polymerase Chain Reaction , Retrospective Studies , Zimbabwe/ethnology
20.
Mem Inst Oswaldo Cruz ; 109(7): 918-22, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25410996

ABSTRACT

The human beta defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5'UTR and c.*5G>A and c.*87A>G in the 3'UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.


Subject(s)
Papillomavirus Infections/genetics , Polymorphism, Single Nucleotide/genetics , Reproductive Tract Infections/virology , beta-Defensins/genetics , Adolescent , Adult , Aged , Brazil/epidemiology , Case-Control Studies , Female , Genetic Predisposition to Disease , Haplotypes/genetics , Humans , Middle Aged , Papillomavirus Infections/epidemiology , Young Adult
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