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1.
BMC Genomics ; 25(1): 341, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575858

RESUMO

BACKGROUND: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems. RESULTS: Here, using novel single-cell transcriptomics datasets, we delineate cellular diversity within the intestine of adult female Ascaris suum, a parasitic nematode species that infects animals and people. Gene transcripts expressed in individual nuclei of untreated intestinal cells resolved three phenotypic clusters, while lower stringency resolved additional subclusters and more potential diversity. Clusters 1 and 3 phenotypes displayed variable congruence with scRNA phenotypes of C. elegans intestinal cells, whereas the A. suum cluster 2 phenotype was markedly unique. Distinct functional pathway enrichment characterized each A. suum intestinal cell cluster. Cluster 2 was distinctly enriched for Clade III-associated genes, suggesting it evolved within clade III nematodes. Clusters also demonstrated differential transcriptional responsiveness to nematode intestinal toxic treatments, with Cluster 2 displaying the least responses to short-term intra-pseudocoelomic nematode intestinal toxin treatments. CONCLUSIONS: This investigation presents advances in knowledge related to biological differences among major cell populations of adult A. suum intestinal cells. For the first time, diverse nematode intestinal cell populations were characterized, and associated biological markers of these cells were identified to support tracking of constituent cells under experimental conditions. These advances will promote better understanding of this and other parasitic nematodes of global importance, and will help to guide future anthelmintic treatments.


Assuntos
Anti-Helmínticos , Nematoides , Humanos , Animais , Caenorhabditis elegans , Intestinos , Nematoides/genética , Perfilação da Expressão Gênica , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico
2.
Int Arch Allergy Immunol ; 185(4): 370-381, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38194943

RESUMO

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.


Assuntos
Agamaglobulinemia , Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Linfo-Histiocitose Hemofagocítica , Transtornos Linfoproliferativos , Criança , Humanos , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/terapia , Prednisolona
3.
Clin Exp Dermatol ; 49(3): 226-234, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37815217

RESUMO

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.


Assuntos
Eczema , Infecções por Vírus Epstein-Barr , Hipersensibilidade , Síndrome de Job , Neoplasias , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Síndrome de Job/genética , Citocinese , Centros de Atenção Terciária , Homozigoto , Deleção de Sequência , Herpesvirus Humano 4 , Eczema/genética , Fatores de Troca do Nucleotídeo Guanina/genética
4.
Clin Exp Dermatol ; 49(4): 368-374, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38039144

RESUMO

BACKGROUND: Hereditary angio-oedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of nonpruritic subcutaneous and/or submucosal oedema. Laryngeal oedema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for the management of HAE, mortality was as high as 30%. Mortality has significantly declined in countries where first-line treatment options are available and patients can access these therapies. There is a paucity of literature on the outcomes of patients with HAE in developing countries where availability of and access to first-line treatment options are still a challenge. OBJECTIVES: To report our experience on mortality in patients with HAE and to report factors associated with the death of these patients. METHODS: We carried out a record review of all patients diagnosed with HAE between January 1996 and August 2022. Families with HAE who had reported the death of at least one family member/relative from laryngeal oedema were studied in detail. RESULTS: Of the 65 families (170 patients) registered in the clinic, 16 families reported the death of at least one family member/relative from laryngeal oedema (total of 36 deaths). Of these 16 families, 14 reported that 1 or more family members had experienced at least 1 attack of laryngeal oedema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid, while the remaining 35 patients were not diagnosed with HAE at the time of their death. At the time of death of all 36 patients, at least 1 other family member had symptoms suggestive of HAE, but the diagnosis was not established for the family. CONCLUSIONS: To our knowledge, this is the largest single-centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. The delay in diagnosis is the most important reason for mortality.


Assuntos
Angioedemas Hereditários , Edema Laríngeo , Feminino , Humanos , Edema Laríngeo/complicações , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Diagnóstico Tardio , Índia/epidemiologia , Edema , Proteína Inibidora do Complemento C1/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-37325971

RESUMO

The COVID-19 pandemic has affected the world, leading to significant morbidity and mortality. Various meteorological parameters are considered essential for the viability and transmission of the virus. Multiple reports from various parts of the world suggest a correlation between the disease spread and air pollution severity. This study was carried out to identify the relationship between meteorological parameters, air pollution, and COVID-19 in New Delhi, one of the worst-affected states in India. We studied air pollution and meteorological parameters in New Delhi, India. We obtained data about COVID-19 occurrence, meteorological parameters, and air pollution indicators from various sources from Apr 1, 2020, till Nov 12, 2020. We performed correlational analysis and employed autoregressive distributed lag models (ARDLM) for identifying the relationship between COVID-19 cases with air pollution and meteorological parameters. We found a significant impact of PM 2.5, PM 10, and meteorological parameters on COVID-19. There was a significant positive correlation between daily COVID-19 cases and COVID-19-related deaths with PM2.5 and PM10 levels. Increasing temperature and windspeed were associated with a reduction in the number of cases while increasing humidity was associated with increased cases. This study demonstrated a significant association of PM2.5 and PM10 with daily COVID-19 cases and COVID-19-related mortality. This knowledge will likely help us prepare well for the future and implement air pollution control measures for other airborne disease epidemics.

6.
Med J Armed Forces India ; 78(1): 103-105, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35035052

RESUMO

Peripheral eosinophilia can have a myriad of causes and presents a diagnostic challenge in everyday practice. Tropical pulmonary eosinophilia (TPE), seen commonly in tropics, is an immunological reaction to filarial parasites. This disease can present with clinical features that closely mimic asthma, eosinophilic pneumonia, and Loffler's syndrome. Differentiating between these diseases is essential owing to marked differences in treatment. This can be further challenging in pregnancy as any wrong treatment is likely to affect both the mother and the child. We report a case of a pregnant lady who presented with eosinophilia and of how she was worked up to the correct diagnosis. There are only few reported cases of TPE in pregnancy, and there are no reported cases from India. The case also underlines the approach required in these patients to reach the correct diagnosis.

7.
Med J Armed Forces India ; 78(4): 485-488, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36267517

RESUMO

Swimming-induced pulmonary edema (SIPE) is a rare form of non-cardiogenic pulmonary edema occurring in swimmers. It is important to consider the diagnosis of SIPE and differentiate it from aspiration pneumonitis in patients presenting with respiratory distress after swimming. We report a case of military recruit who developed SIPE. This is the first reported case of SIPE from India. Owing to the paucity of reported cases, the treatment of this entity in the literature is anecdotal, and we present successful management of SIPE with non-invasive ventilation and diuretics. A review of literature is made to understand the diagnosis, pathophysiology, and management of SIPE.

8.
Med J Armed Forces India ; 78(4): 481-484, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36267520

RESUMO

We report a rare case of congenital pulmonary airway malformation (CPAM) in a middle-aged female patient with bilateral involvement. In view of its presentation in adulthood, it presents a rare picture of a disease often diagnosed in early childhood. Until now, 65 cases of this disease have been reported in adults, including 3 cases with bilateral involvement. A classical radiological picture of CPAM can often be confused with bronchiectasis or pulmonary sequestration. A definite treatment with surgical resection poses a challenge in bilateral involvement. We highlight a rare case with its challenges in diagnosis and management. A review of literature of cases of CPAM with bilateral involvement is conducted in an effort to better understand this entity in adulthood.

9.
Monaldi Arch Chest Dis ; 91(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33501822

RESUMO

COVID 19 pandemic has brought about a sea change in health care practices across the globe. All specialities have changed their way of working during the pandemic. In this study, we evaluated the impact of COVID-19 on the practice of interventional pulmonology at our centre. All interventional pulmonology procedures done during the three months after implementation of lockdown were evaluated retrospectively for patient demographics, clinical diagnosis, indication for procedure and diagnostic accuracy. The changes in practices, additional human resources requirement, the additional cost per procedure and impact on resident training were also assessed. Procedures done during the month of January 2020 were used as controls for comparison. Twenty-two flexible bronchoscopies (75.8%), four semirigid thoracoscopies (13.7%) and three EBUS-TBNAs (10.3%) were carried out during three month lockdown period as compared to 174 during January 2020. Twenty-three of the procedures were for the diagnostic indication (79%), and six were therapeutic (20.6%). The diagnostic yield in suspected neoplasm was 100% while for suspected infections was 58.3%. The percentage of independent procedures being done by residents reduced from 45.4% to 0%. The workforce required per procedure increased from 0.75 to 4-8, and the additional cost per procedure came out to be 135 USD. To conclude, COVID 19 has impacted the interventional pulmonology services in various ways and brought about a need to reorganize the services, while also thinking of innovative ideas to reduce cost without compromising patient safety.


Assuntos
Broncoscopia , COVID-19 , Atenção à Saúde , Controle de Infecções , Pneumopatias , Broncoscopia/métodos , Broncoscopia/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Atenção à Saúde/organização & administração , Atenção à Saúde/tendências , Técnicas de Diagnóstico do Sistema Respiratório/estatística & dados numéricos , Feminino , Humanos , Índia/epidemiologia , Controle de Infecções/instrumentação , Controle de Infecções/métodos , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Inovação Organizacional , Estudos Retrospectivos , SARS-CoV-2 , Centros de Atenção Terciária/estatística & dados numéricos
10.
Gastroenterology ; 157(4): 1109-1122, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31255652

RESUMO

BACKGROUND & AIMS: The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD. METHODS: We performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis. RESULTS: Fecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87). CONCLUSIONS: In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.


Assuntos
Bactérias/genética , DNA Bacteriano/genética , Microbioma Gastrointestinal , Intestinos/microbiologia , Cirrose Hepática/microbiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , RNA Ribossômico 16S/genética , Adolescente , Bactérias/classificação , Bactérias/patogenicidade , Estudos de Casos e Controles , Criança , Estudos Transversais , Disbiose , Fezes/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Metagenoma , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Prospectivos , Ribotipagem , Índice de Gravidade de Doença
11.
Muscle Nerve ; 62(4): 528-533, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32696574

RESUMO

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Proteínas de Ciclo Celular/líquido cefalorraquidiano , Quimiocina CCL2/líquido cefalorraquidiano , Proteínas de Ligação a DNA/líquido cefalorraquidiano , Proteínas de Membrana Transportadoras/líquido cefalorraquidiano , Ribonuclease Pancreático/líquido cefalorraquidiano , Fator A de Crescimento do Endotélio Vascular/líquido cefalorraquidiano , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/líquido cefalorraquidiano , Adulto , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade
12.
PLoS Genet ; 13(1): e1006537, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28060841

RESUMO

Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. hepatica Oregon and related food-borne trematodes are metabolically less constrained than schistosomes and cestodes, taking advantage of the richer millieux offered by the hepatobiliary organs. Protease families differentially expanded between diverse trematodes may facilitate migration and survival within the heterogeneous environments and niches within the mammalian host. Surprisingly, the sequencing of Oregon and Uruguay F. hepatica isolates led to the first discovery of an endobacteria in this species. Two contigs from the F. hepatica Oregon assembly were joined to complete the 859,205 bp genome of a novel Neorickettsia endobacterium (nFh) closely related to the etiological agents of human Sennetsu and Potomac horse fevers. Immunohistochemical studies targeting a Neorickettsia surface protein found nFh in specific organs and tissues of the adult trematode including the female reproductive tract, eggs, the Mehlis' gland, seminal vesicle, and oral suckers, suggesting putative routes for fluke-to-fluke and fluke-to-host transmission. The genomes of F. hepatica and nFh will serve as a resource for further exploration of the biology of F. hepatica, and specifically its newly discovered trans-kingdom interaction with nFh and the impact of both species on disease in ruminants and humans.


Assuntos
Fasciola hepatica/genética , Genoma Bacteriano , Genoma Helmíntico , Neorickettsia sennetsu/genética , Animais , Proteínas da Membrana Bacteriana Externa/genética , Ehrlichiose/microbiologia , Ehrlichiose/transmissão , Ehrlichiose/veterinária , Fasciola hepatica/isolamento & purificação , Fasciola hepatica/microbiologia , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/transmissão , Cavalos , Humanos , Neorickettsia sennetsu/patogenicidade , Oregon , Ovinos/parasitologia , Uruguai
13.
Med J Armed Forces India ; 76(4): 462-465, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33162658

RESUMO

Primary pulmonary Hodgkins lymphoma is a rare and enigmatic neoplasm commonly seen in females. The aim of this case report is to emphasize that pulmonary lymphoma should be considered as a differential diagnosis in a young patient presenting with a lung mass and B symptoms. Extensive clinical details, imaging should be done to rule out the secondary involvement of lung by other lymphomas.

14.
Curr Genomics ; 20(7): 519-530, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32655290

RESUMO

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a progressive, fatal neuromuscular disorder caused by mutations in the DMD gene. Emerging antisense oligomer based exon skipping therapy provides hope for the restoration of the reading frame. OBJECTIVES: Population-based DMD mutation database may enable exon skipping to be used for the benefit of patients. Hence, we planned this study to identify DMD gene variants in North Indian DMD cases. METHODS: A total of 100 DMD cases were recruited and Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to obtain the deletion and duplication profile. RESULTS: Copy number variations (deletion/duplication) were found in 80.85% of unrelated DMD cases. Sixty-eight percent of cases were found to have variations in the distal hotspot region (Exon 45-55) of the DMD gene. Exon 44/45 variations were found to be the most prominent among single exon variations, whereas exon 49/50 was found to be the most frequently mutated locations in single/multiple exon variations. As per Leiden databases, 86.84% cases harboured out-of-frame mutations. Domain wise investigation revealed that 68% of mutations were localized in the region of spectrin repeats. Dp140 isoform was predicted to be absent in 62/76 (81.57%) cases. A total of 45/80 (56.25%) and 23/80 (28.70%) DMD subjects were predicted to be amenable to exon 51 and exon 45 skipping trials, respectively. CONCLUSION: A major proportion of DMD subjects (80%) could be diagnosed by the MLPA technique. The data generated from our study may be beneficial for strengthening of mutation database in the North Indian population.

15.
J Infect Dis ; 216(6): 736-743, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28934436

RESUMO

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides derived from 8 of 10 proteins tested: OVOC1192(1-15), OVOC9988(28-42), OVOC9225(320-334), OVOC7453(22-36), OVOC11517(14-28), OVOC3177(283-297), OVOC7911(594-608), and OVOC12628(174-188). Our data show that differences in immunoreactivity to variant antigenic peptides may be used to characterize Ov populations, thereby elucidating features of Ov population biology previously inaccessible because of the limited availability of parasite material.


Assuntos
Genética Populacional , Proteínas de Helminto/genética , Imunofenotipagem , Onchocerca volvulus/genética , Oncocercose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Anti-Helmínticos/sangue , Formação de Anticorpos , Antígenos de Helmintos/sangue , Criança , DNA de Protozoário/genética , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Onchocerca volvulus/isolamento & purificação , Oncocercose/imunologia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Adulto Jovem
16.
J Cell Biochem ; 118(8): 2087-2095, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27966779

RESUMO

AMD is a complex eye disease predominantly occurring in aged population. Till now about 53 genetic loci have been found to be associated with the AMD pathology. AMD pathogenesis is being increasingly known to progress through mechanisms independent of the CFH mediated pathway. Therefore, our aim for current study was to examine the genes by analyzing their expression levels in AMD. We recruited about 50 AMD and same number of age matched controls. We analyzed the CFH duplication and deletion by multiplex ligation probe amplification (MLPA) and found no duplication and deletion in CFH gene in AMD patients. We also estimated the IER-3, SLC16A8, LIPC, and TIMP-3 expression levels in both CFH-negative AMD cases (i.e. no duplication and deletion in CFH gene) besides examining these in AMD and controls. We found that the expression level of LIPC, SLC16A8, and TIMP-3 was significantly associated with AMD pathology in both groups (LIPC: P = 0.008, SLC16A8: P < 0.001, TIMP-3: P < 0.001, respectively). However, we did not find any significant difference in IER-3 levels in AMD and controls. Therefore, the evidence from current study, suggests that AMD pathology may be mediated through mechanistic pathways linked to other genetic loci. J. Cell. Biochem. 118: 2087-2095, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Lipase/genética , Degeneração Macular/genética , Transportadores de Ácidos Monocarboxílicos/genética , Inibidor Tecidual de Metaloproteinase-3/genética , Idoso , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Estudos de Casos e Controles , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Feminino , Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Lipase/metabolismo , Degeneração Macular/sangue , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Transportadores de Ácidos Monocarboxílicos/metabolismo , Simportadores , Inibidor Tecidual de Metaloproteinase-3/metabolismo
17.
RNA Biol ; 14(10): 1335-1352, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-27002534

RESUMO

The intestine of parasitic nematodes has proven an important target for therapies aimed at prevention and treatment of diseases caused by these pathogens in humans, animals and plants. We have developed a unique research model with the intestine of Ascaris suum, the large round worm of swine and humans, that will enhance biological research on this tissue. To expand utility of this model, we quantitatively compared expression of 15,382 coding RNAs and 277 noncoding, micro RNAs (miRNAs) among 3 contiguous regions of the adult A. suum intestine. Differentially expressed transcripts were identified among regions, with the largest number expressed at significantly higher levels in the anterior region, identifying this region as the most functionally unique compared to middle and posterior regions. We further identified 64 exon splice variants (from 47 genes) that are differentially expressed among these regions. A total of 2,063 intestinal mRNA transcripts were predicted to be targeted by intestinal miRNA, and negative correlation coefficients for miRNA:mRNA abundances predicted 22 likely influential miRNAs and 503 likely associated miRNA:mRNA pairs. A. suum intestinal miRNAs were identified that are conserved with intestinal miRNAs from C. elegans (10 mature sequences and 13 seed sequences conserved), and prospective intestinal miRNAs from the murine gastrointestinal nematode, Heligmosomoides polygyrus (5 mature and 11 seeds). Most of the conserved intestinal miRNAs were also high abundance miRNAs. The data provide the most comprehensive compilation of constitutively and differentially expressed genes along the length of the intestine for any nematode species. The information will guide prospective development of many hypotheses on nematode intestinal functions encoded by mRNAs, miRNAs and interactions between these RNA populations.


Assuntos
Ascaris suum/genética , Perfilação da Expressão Gênica/métodos , Intestinos/química , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Sequência de Bases , Sequência Conservada , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , Especificidade de Órgãos , RNA de Helmintos/genética
19.
Nucleic Acids Res ; 43(Database issue): D698-706, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25392426

RESUMO

Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases' interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species' omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net.


Assuntos
Bases de Dados Genéticas , Genoma Helmíntico , Nematoides/genética , Trematódeos/genética , Animais , Genômica , Humanos , Internet , Microbiota , Nematoides/metabolismo , Trematódeos/metabolismo , Infecções por Trematódeos/microbiologia
20.
Chemistry ; 22(16): 5629-36, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26961861

RESUMO

Chiral head groups have been introduced into water-soluble hydroxyl-terminated nonionic amphiphiles and the impact of the head group stereochemistry on the supramolecular ultrastructures has been studied. Enantiomeric isomers were compared with the achiral meso form and the racemic mixture by means of cryogenic transmission electron microscopy and circular dichroism spectroscopy. Structurally, all amphiphiles are composed of the first-generation hydrophilic polyglycerol head group coupled to a single hydrophobic hexadecyl chain through an amide linkage and diaromatic spacer. The enantiomers aggregate to form twisted ribbons with uniform handedness, whereas the meso stereoisomer and racemic mixture produce elongated assemblies, namely, tubules and platelets, but without a chiral ultrastructure. Simulations on the molecular packing geometries of the stereoisomers indicate different preferential assembly routes that explain the individual supramolecular aggregation behavior.

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