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1.
Ocul Immunol Inflamm ; : 1-7, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160084

RESUMO

Purpose: To evaluate the role of angiogenic growth factors in the pathogenesis of intraocular tuberculosis.Methods: Retinal Pigment Epithelium (RPE) cells were infected with varying dilution of Mycobacterium tuberculosis (MTB), ranging from several thousand to a few MTB bacilli to replicate paucibacillary conditions. Angiogenesis growth factors were evaluated using multiplex fluorescent bead based flow cytometry in the culture supernatant of RPE cells infected with MTB, vitreous fluids and tear samples of uveitis patients visiting retina clinic.Results: Vascular endothelial growth factor (VEGF) levels were elevated and fibroblast growth factors (FGFs) were down regulated in RPE-infected MTB cells. Similar pattern of VEGF and FGF was observed in the vitreous of IOTB patients. However, no changes were observed in tear samples.Conclusions: MTB exploits the angiogenesis growth factors for pathogenesis by decreasing FGF with concomitant surge of VEGF in MTB infected RPE as well in the vitreous of IOTB patients.

3.
Gene ; 739: 144498, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32097694

RESUMO

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is one of the deadly diseases with poor metastatic disease prognosis. There is an urgent need to explore the potential molecular markers which can improve the prognosis of the disease. Histone demethylases have emerged as a powerful tool for cancer prognosis and therapeutics during the last decade. The implications of demethylases of histone 3 lysine 4 (H3K4) in ccRCC are however unrevealed. We therefore evaluated the expression of H3K4 demethylases in ccRCC, with emphasis on their clinical significance as a prognostic marker. METHODS: Total 50 histopathological confirmed cases of ccRCC were enrolled in the study. The expression of seven H3K4 demethylases was determined by Real-Time PCR using gene specific primers and correlated with tumor stage, grade and metastasis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognostic significance of H3K4 demethylases. RESULTS: The median age of the patients was 54 years with predominance of male patients by 2.6-fold. Among seven genes viz FBXL10, LSD1, LSD2, KDM5A, KDM5B, KDM5C and KDM5D analyzed, LSD2 was found to be significantly associated with tumor stage and metastasis. The optimal cut-off value for LSD2 was 3.2 as calculated from ROC curve analysis for metastasis as well as TNM stage with area under curve of 0.74 and 0.78 respectively. In addition, LSD2 expression showed significant positive correlation with LSD1 expression in tumor metastasis. CONCLUSION: The expression of LSD2 was associated with higher TNM stage and metastasis of the tumor and thus, might serve as a useful marker for ccRCC progression.

4.
Bioresour Technol ; 301: 122778, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31983580

RESUMO

With the inevitable rise in human population, resource recovery from waste stream is becoming important for a sustainable economy, conservation of the ecosystem as well as for reducing the dependence on the finite natural resources. In this regard, a bio-based circular economy considers organic wastes and residues as potential resources that can be utilized to supply chemicals, nutrients, and fuels needed by mankind. This review explored the role of aerobic and anaerobic digestion technologies for the advancement of a bio-based circular society. The developed routes within the anaerobic digestion domain, such as the production of biogas and other high-value chemicals (volatile fatty acids) were discussed. The potential to recover important nutrients, such as nitrogen through composting, was also addressed. An emphasis was made on the innovative models for improved economics and process performance, which include co-digestion of various organic solid wastes, recovery of multiple bio-products, and integrated bioprocesses.


Assuntos
Compostagem , Resíduos Sólidos , Anaerobiose , Biocombustíveis , Reatores Biológicos , Ecossistema
5.
Ocul Immunol Inflamm ; : 1-7, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940227

RESUMO

Purpose: To evaluate the cytokine levels in tear samples of human leukocyte antigen B27 (HLA-B27)-associated uveitis.Methods: Twenty HLA-B27-associated uveitis patients and 10 non-HLA-B27 uveitis controls were enrolled for the estimation of interleukin-6 (IL-6) and IL-10 levels in the tear samples. The cytokine levels were determined by flow cytometry using a bead-based assay.Results: IL-6, and IL-10 levels and IL-6/IL-10 ratio were found to be higher in the tear samples of HLA-B27-associated uveitis patients as compared to controls. IL-6 levels were also elevated in the active disease as compared to the quiescent group; likewise, IL-6 levels were higher even in the quiescent phase in comparison to non-HLA-B27 disease control. Additionally, levels of IL-6 were significantly correlated with multiple disease episodes. Moreover, IL-6 showed a good area under the curve in receiver operating characteristic analysis.Conclusions: Elevated tear IL-6 levels were associated with active disease and multiple disease episodes and thus could be used as putative markers for disease episodes.

6.
Clin Exp Ophthalmol ; 48(1): 69-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31587479

RESUMO

BACKGROUND: Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra-pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known. METHODS: We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel-based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real-time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non-tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology. RESULTS: The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl-Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology. CONCLUSIONS: MTB could not be detected in human ocular tissues in latent state in India, a TB-endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.

7.
Ophthalmology ; 127(3): 296-302, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31543349

RESUMO

PURPOSE: To characterize surgical confusions in ophthalmology to determine their incidence, root causes, and impact on patients and physicians. DESIGN: Retrospective cohort study of errors in ophthalmic surgical procedures between January 1, 2006, and December 31, 2017. PARTICIPANTS: One hundred forty-three cases involving surgical confusions. METHODS: Cases were identified by the Ophthalmic Mutual Insurance Company from closed case files and by the New York State Health Department from the New York Patient Occurrence Reporting and Tracking program that identified the surgical confusions. MAIN OUTCOME MEASURES: Incidence and impact by intended surgery, error type, and root cause as well as preventability by the Universal Protocol. RESULTS: Of the 143 cases of surgical confusions identified, 92 cases (64.3%) were deemed preventable by the Universal Protocol. Approximately two thirds, 95 cases (66.4%), were cases of incorrect implants being used during cataract surgery (cataract extraction and intraocular lens implantation), of which 33 cases (34.7%) were not preventable by the Universal Protocol. Wrong eye blocks or anesthesia accounted for 20 cases (14.0%), incorrect eye procedures accounted for 10 cases (7.00%), incorrect refractive surgery measurements accounted for 6 cases (4.20%), incorrect patient or procedure accounted for 5 cases (3.50%), incorrect intraocular gas concentration accounted for 4 cases (2.80%), and incorrect medication in surgery accounted for 3 cases (2.10%). The most common root cause of confusion was an inadequately performed time out, which was responsible for nearly one third of all surgical confusions, 46 cases (32.2%). Incorrect lens orders or calculations before surgery (so-called upstream errors) were the second most common cause of surgical confusion, involving 31 cases (21.7%). The average legal indemnity for incorrect implant during cataract surgery was $57 514 (United States dollars). The average indemnity for incorrect refractive surgery measurement was $123 125, that for incorrect eye procedure was $50 000, and that for incorrect gas concentration was $220 844. CONCLUSIONS: Most surgical confusions could have been prevented by following the Universal Protocol properly. However, upstream errors, originating in the clinic or office before surgery, and ineffective communication during time outs suggest a need for modification of the Universal Protocol.

8.
Bioresour Technol ; 297: 122469, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787517

RESUMO

This work dealt with the determination of the suitability of sorption of Volatile Organic Compounds (VOCs) on biochars prepared from neem, sugarcane and bamboo feedstocks. Six different VOCs namely benzene, toluene, methyl chloride, xylene, chloroform and carbon tetrachloride were used in a laboratory-scale set-up on non-activated biochars prepared via slow pyrolysis (350-550 °C). Although all the chars showed considerable sorption but amongst them N3 (neem-based biochar) showed the maximum removal efficiency (65.5 mg g-1 for toluene). Variation in pyrolysis temperature and feedstock type showed significant change in the porosity and specific surface area of the biochar, which is favorable for VOC sorption efficiency. With higher surface area and contact time, the sorption capacity of char enhanced. However, the extent of sorption capacity of biochars differed with changing VOC type. Pseudo-Second-Order model fitted well with the results obtained from VOC sorption kinetics.


Assuntos
Compostos Orgânicos Voláteis , Adsorção , Carvão Vegetal , Tolueno
9.
Ocul Immunol Inflamm ; 28(1): 111-115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31157988

RESUMO

A 25-year-old male presented with unilateral panuveitis with multiple voluminous elevated retinal lesions along with subretinal fluid and exudation. An extensive laboratory work-up was done, and a clinical suspicion of viral retinitis was considered. The patient was initiated on antiviral therapy and, subsequently, oral corticosteroids. As the corticosteroids were tapered, the patient developed worsening lesions and vitreous inflammation. Pars plana vitrectomy (diagnostic and therapeutic) was performed and cytology sample revealed a highly eosinophilic infiltrate suggestive of parasitic infection. The real-time polymerase chain reaction was positive for Toxocara cati. The diagnosis of ocular toxocariasis was made. This case highlights a highly unusual presentation where multiple retinal granulomas of ocular toxocariasis were observed in an immunocompetent male.

11.
Infect Immun ; 87(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31262983

RESUMO

The overuse of antibiotics has led to the evolution of drug-resistant bacteria that are becoming increasingly dangerous to human health. According to the Centers for Disease Control and Prevention, antibiotic-resistant bacteria cause at least 2 million illnesses and 23,000 deaths in the United States annually. Traditionally, antibiotics are bactericidal or bacteriostatic agents that place selective pressure on bacteria, leading to the expansion of antibiotic-resistant strains. In addition, antibiotics that are effective against some pathogens can also exacerbate their pathogenesis and may lead to severe progression of the disease. Therefore, alternative strategies are needed to treat antibiotic-resistant bacterial infections. One novel approach is to target bacterial virulence to prevent or limit pathogen colonization, while also minimizing tissue damage and disease comorbidities in the host. This review focuses on the interactions between enteric pathogens and naturally occurring small molecules in the human gut as potential therapeutic targets for antivirulence strategies. Individual small molecules in the intestines modulate enteric pathogen virulence and subsequent intestinal fitness and colonization. Targeted interruption of pathogen sensing of these small molecules could therefore attenuate their virulence. This review highlights the paths of discovery for new classes of antimicrobials that could potentially mitigate the urgent problem of antibiotic resistance.


Assuntos
Bactérias/patogenicidade , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Anti-Infecciosos/metabolismo , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos
12.
mBio ; 10(3)2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164470

RESUMO

Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host- or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lumen compared to the intestinal tissue. This difference in indole concentration plays a key role in modulating virulence gene expression of the enteric pathogens enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium Indole decreases expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form attaching and effacing (AE) lesions on enterocytes. We synthetically altered the concentration of indole in the GI tracts of mice by employing mice treated with antibiotics to deplete the microbiota and reconstituted with indole-producing commensal Bacteroides thetaiotaomicron (B. theta) or a B. theta ΔtnaA mutant (does not produce indole) or by engineering an indole-producing C. rodentium strain. This allowed us to assess the role of self-produced versus microbiota-produced indole, and the results show that decreased indole concentrations promote bacterial pathogenesis, while increased levels of indole decrease bacterial virulence gene expression. Moreover, we identified the bacterial membrane-bound histidine sensor kinase (HK) CpxA as an indole sensor. Enteric pathogens sense a gradient of indole concentrations in the gut to probe different niches and successfully establish an infection.IMPORTANCE Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize.


Assuntos
Bactérias/patogenicidade , Microbioma Gastrointestinal , Trato Gastrointestinal/química , Interações Hospedeiro-Patógeno , Indóis/metabolismo , Transdução de Sinais , Animais , Bactérias/genética , Proteínas de Bactérias/genética , Citrobacter rodentium/genética , Citrobacter rodentium/patogenicidade , Enterócitos/microbiologia , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Êntero-Hemorrágica/patogenicidade , Feminino , Trato Gastrointestinal/microbiologia , Regulação Bacteriana da Expressão Gênica , Camundongos , Proteínas Quinases/genética , Virulência , Fatores de Virulência/genética
13.
Sci Rep ; 9(1): 8189, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160694

RESUMO

Renal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological cancers, which results in response to combination of genetic and epigenetic factors. Histone methylations have been implicated in renal tumorigenesis but their clinical significance and underlying pathology are unexplored. Here, we elucidated the histone 3 lysine 4 (H3K4) methylation patterns in clear cell RCC and its underlying pathology. Lower cellular levels of H3K4 mono-methylation, -dimethylation and -tri-methylation were fraternized with higher TNM staging and Fuhrman grading as well as tumor metastasis. Further, the expression profile of 20 H3K4 modifiers revealed the significant over-expression of histone demethylases compared to methyltransferases, indicating their role in the reduction of H3K4 methylation levels. In view of above facts, the role of LSD2 and KDM5A demethylases in RCC pathogenesis were explored using respective siRNAs. The RCC cells exhibited reduced cell viability after knockdown of LSD2 and KDM5A genes with concomitant induction of apoptosis. In addition, propidium iodide staining demonstrated an arrest of RCC cells at S-phase and sub-G1 phase of the cell cycle. Taken together, these observations provide new pathological insights behind the alterations of H3K4 methylation patterns in ccRCC with their prognostic and therapeutic implications.

14.
Indian J Clin Biochem ; 34(2): 123-132, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31092985

RESUMO

Histone modifications occupy an essential position in the epigenetic landscape of the cell, and their alterations have been linked to cancers. Histone 3 lysine 4 (H3K4) methylation has emerged as a critical epigenetic cue for the regulation of gene transcription through dynamic modulation by several H3K4 methyltransferases (writers) and demethylases (erasers). Any disturbance in the delicate balance of writers and erasers can result in the mis-regulation of H3K4 methylation, which has been demonstrated in several human cancers. Therefore, H3K4 methylation has been recognized as a putative therapeutic or prognostic tool and drug trials of different inhibitors of this process have demonstrated promising results. Henceforth, more detailed knowledge of H3K4 methylation is utmost important for elucidating the complex cellular processes, which might help in improving the disease outcome. The primary focus of this review will be directed on deciphering the role of H3K4 methylation along with its writers/erasers in different cancers.

15.
Front Plant Sci ; 10: 308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936886

RESUMO

Wheat is one of the most important staple crops in the world and good source of calories and nutrition. Its flour and dough have unique physical properties and can be processed to make unique products like bread, cakes, biscuits, pasta, noodles etc., which is not possible from other staple crops. Due to domestication, the genetic variability of the genes coding for different economically important traits in wheat is narrow. This genetic variability can be increased by utilizing its wild relatives. Its closest relative, genus Aegilops can be an important source of new alleles. Aegilops has played a very important role in evolution of tetraploid and hexaploid wheat. It consists of 22 species with C, D, M, N, S, T and U genomes with high allelic diversity relative to wheat. Its utilization for wheat improvement for various abiotic and biotic stresses has been reported by various scientific publications. Here in, for the first time, we review the potential of Aegilops for improvement of processing and nutritional traits in wheat. Among processing quality related gluten proteins; high molecular weight glutenins (HMW GS), being easiest to study have been explored in highest number of accessions or lines i.e., 681 belonging to 13 species and selected ones like Ae. searsii, Ae. geniculata and Ae. longissima have been linked with improved bread making quality of wheat. Gliadins and low molecular weight glutenins (LMW GS) have also been extensively explored for wheat improvement and Ae. umbellulata specific LMW GS have been linked with wheat bread making quality improvement. Aegilops has been explored for seed texture diversity and proteins like puroindolins (Pin) and grain softness proteins (GSP). For nutrition quality improvement, it has been screened for essential micronutrients like Fe, Zn, phytochemicals like carotenoids and dietary fibers like arabinoxylan and ß-glucan. Ae. kotschyi and Ae. biuncialis transfer in wheat have been associated with higher Fe, Zn content. In this article we have tried to compile information available on exploration of nutritional and processing quality related traits in Aegilops section and their utilization for wheat improvement by different approaches.

16.
Ophthalmol Retina ; 3(2): 170-177, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31014768

RESUMO

PURPOSE: Dengue maculopathy can present with a unique constellation of features resulting in significant central visual morbidity. We aim to describe various findings of dengue-induced inflammatory, ischemic foveolitis, and outer maculopathy (DIII-FOM) and assess the serial changes in vitreous inflammation, retinal structure, and vascularity using swept-source OCT (SS-OCT) and OCT angiography (OCTA). DESIGN: Retrospective case series. PARTICIPANTS: A total of 32 eyes (16 patients; 7 male) with dengue fever (positive serology for NS1 antigen) were enrolled in the study. METHODS: In this study, serial assessments of ocular findings and imaging using fundus photography, SS-OCT, and SS-OCTA were performed. All the patients received 0.5 to 1 mg/kg/day oral prednisolone that was tapered over 4 to 6 weeks. MAIN OUTCOME MEASURES: Outcome measures included functional change, that is, improvement in best-corrected visual acuity (BCVA), structural changes in the vitreous and retinal layers on SS-OCT, and retinal perfusion on OCTA. RESULTS: The mean age of the patients was 29.17±10.91 years. Swept-source OCT showed vitreous cells (32 eyes; 100%), disruption of outer retinal layers (foveolitis) (24 eyes; 75%), and conical foveal elevation (22 eyes; 68.75%). After initiation of systemic corticosteroids, all the eyes showed resolution of vitreous cells and improvement in the integrity of retinal layers. Mean BCVA improved from an initial 0.80±0.33 logarithm of the minimum angle of resolution (logMAR) to 0.23±0.36 logMAR. Retinal plexus flow deficit (superficial plexus: 0.10±0.12 mm2; deep plexus: 0.29±0.13 mm2) persisted in all eyes and correlated well with initial BCVA (P < 0.05). CONCLUSIONS: The pathophysiology of dengue maculopathy involves both ischemic and inflammatory components. Early institution of corticosteroid therapy may help in resolution of the inflammation-driven vitreoretinal alterations, but ischemia of the deep retinal plexuses may persist and may be the cause of permanent structural and functional changes.


Assuntos
Dengue/complicações , Fóvea Central/patologia , Macula Lutea/patologia , Doenças Retinianas/patologia , Adolescente , Adulto , Feminino , Fóvea Central/irrigação sanguínea , Humanos , Isquemia , Masculino , Doenças Retinianas/etiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
17.
Mol Biol Rep ; 46(3): 3307-3313, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30980273

RESUMO

Clinical heterogeneity is commonly observed in Wilson disease (WD), including cases with identical ATP7B mutations. It is thought to be an outcome of impairment in other genes involved in cellular copper homeostasis in addition to the mutations in the ATP7B gene. ATOX1, a copper chaperone that delivers copper to ATP7B, is a potential genetic modifier of WD. In the present study, we analyzed the genetic variations in the ATOX1 gene in 50 WD patients and 60 controls. We identified four novel variants, of which, the coding region variant c.40G > A, p.(Gly14Ser) was observed in 2% alleles. Interestingly, p.(Gly14Ser) was seen with an early onset age, reduced serum ceruloplasmin level and manifestations of liver and brain in a WD patient unlike the other having identical ATP7B mutation but normal ATOX1 alleles. Further, computational analysis predicted that p.(Gly14Ser) substitution, in the critical copper binding motif (MXCXG14C) of the protein, affects the protein-protein interaction involved in copper sharing and transfer between ATOX1 and ATP7B-MBD4. Our findings suggest that p.(Gly14Ser) variant of ATOX1 might play a role as a genetic modifier leading to phenotypic variation in WD.


Assuntos
ATPases Transportadoras de Cobre/genética , Metalochaperonas/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/genética , Criança , Pré-Escolar , Simulação por Computador , Cobre/metabolismo , ATPases Transportadoras de Cobre/metabolismo , ATPases Transportadoras de Cobre/ultraestrutura , Feminino , Frequência do Gene/genética , Degeneração Hepatolenticular/genética , Humanos , Índia , Fígado/metabolismo , Masculino , Metalochaperonas/metabolismo , Metalochaperonas/ultraestrutura , Chaperonas Moleculares/genética , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único/genética
18.
BMJ Case Rep ; 12(1)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30674497

RESUMO

Idiopathic gingival fibromatosis (GF), also known as gingivomatosis, is a rare condition in childhood, with an unknown aetiology. The oral manifestations of the condition are varied and depend on the severity and age of involvement. This paper describe the case of a 5-year-old male child with extensive gingival enlargement covering almost all the maxillary and mandibular teeth resulted in difficulty with speech, mastication and poor aesthetics. Clinical and radiographic examination along with haematological investigations ruled out any systemic association. The case was managed with conventional scalpel blade surgery along with electrocautery under general anaesthesia yielding good results without any recurrence after a 12-month follow-up. The results revealed that the oral manifestations of GF depend on its severity and the age of onset. Timely intervention can help to prevent associated complications in a growing child.


Assuntos
Fibromatose Gengival/patologia , Gengivectomia/métodos , Distúrbios da Fala/etiologia , Assistência ao Convalescente , Pré-Escolar , Diagnóstico Diferencial , Fibromatose Gengival/cirurgia , Doenças da Gengiva/patologia , Doenças da Gengiva/cirurgia , Hiperplasia Gengival/patologia , Hiperplasia Gengival/cirurgia , Humanos , Masculino , Mastigação/fisiologia , Distúrbios da Fala/diagnóstico , Resultado do Tratamento
19.
mBio ; 9(6)2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514785

RESUMO

Enteric pathogens have complex interactions with the gut microbiota. Most of what is known about them has focused on microbiota-derived metabolites or small molecules that serve as nutrients and/or signals to aid in growth or transcriptionally regulate virulence gene expression. A common virulence strategy is to express a type III secretion system (T3SS), which is a molecular syringe deployed by many Gram-negative pathogens to hijack host cell function. Enterohemorrhagic Escherichia coli (EHEC) requires its T3SS to colonize the intestinal tract and cause disease. Here we report that a prominent member of the intestinal microbiota, Bacteroides thetaiotamicron (Bt), secretes proteases that cleave the translocon of the T3SS of EHEC to enhance effector translocation into host cells. This is in contrast from an endogenous protease from EHEC itself (namely, EspP) that cleaves the translocon protein EspB in a different site to limit effector translocation. The EspB protein forms the T3SS pore in mammalian cells, and pore proteins are conserved in the T3SSs from several pathogens. This is the first demonstration of a commensal species directly processing a pathogen's T3SS, posing a new paradigm for how the microbiota can influence the severity of disease caused by bacterial pathogens. Because T3SSs are employed by many pathogens, this phenomenon has broad implications to commensal-pathogen relationships.IMPORTANCE The gut microbiota is usually regarded as providing colonization resistance against enteric pathogens. However, some pathogens evolved to thrive with the aid of certain members of the microbiota. Several Gram-negative bacteria employ type three secretion systems (T3SSs), which are molecular syringes that deliver effector proteins to host cells, hijacking host cell function. Here we show that the T3SS of enterohemorrhagic E. coli (EHEC) is cleaved by self and microbiota-derived proteases. Self-cleavage limits effector translocation, while cleavage by the microbiota member Bacteroides thetaiotamicron (Bt) exacerbates effector translocation and lesion formation on epithelial cells.


Assuntos
Bacteroides/enzimologia , Escherichia coli Êntero-Hemorrágica/metabolismo , Microbiota , Peptídeo Hidrolases/metabolismo , Sistemas de Secreção Tipo III/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Escherichia coli Êntero-Hemorrágica/genética , Células Epiteliais/microbiologia , Proteínas de Escherichia coli/metabolismo , Células HeLa , Humanos , Transporte Proteico , Proteólise , Proteoma/metabolismo , Virulência , Fatores de Virulência/metabolismo
20.
Anim Reprod Sci ; 199: 51-59, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30384994

RESUMO

The water buffalo have a seasonal pattern of reproduction with decreased sexual activity during the longer photoperiod. The present study was designed to identify a single nucleotide polymorphism (SNP) in the MTNR1 A gene and its association with seasonal reproduction and reproductive characteristics in Murrah buffalo cows. The 812 bp fragment encompassing exon II of the MTNR1 A gene was amplified from genomic DNA of 190 pluriparous Murrah buffalo cows. Amplified PCR products from 12 samples were subjected to custom sequencing of both ends (5' and 3' ends). A synonymous mutation was identified at position 72 in exon II of MTNR1 A gene. Digestion of PCR products with HpaI enzyme indicated there was one polymorphic site caused by the presence of nucleotide C at position 72 in place of T that resulted in three genotypes: T/T (812bp), C/T (812, 743 and 69 bp) and C/C (743 and 69 bp). There was an association (P < 0.05) between the MTNR1 A genotype and reproductive activity in Murrah buffalo cows such that buffalo cows with T/T genotype had less seasonal reproductive activity as compared with those with the C/C genotype. The period of greatest mating activity of buffalo cows with the C/C genotype was from November to December whereas buffalo cows with the T/T genotype mated mainly between May and July. Thus, the polymorphism of the MTNR1 A gene might be considered as a genetic marker to identify Murrah buffalo, which are able to reproduce during periods that are not a part of the typical breeding season for these buffalo.


Assuntos
Búfalos/genética , Polimorfismo de Nucleotídeo Único , Receptores de Melatonina/genética , Reprodução , Animais , Cruzamento , Feminino , Genótipo , Masculino , Fotoperíodo , Estações do Ano
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