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1.
Br J Sociol ; 74(3): 310-323, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36694107

RESUMO

Julian Go's 'Thinking Against Empire' identifies the corpus of 'anticolonial thought' as being instructive for a wider rethinking of how sociology might rally its key conceptualisations of social relations. He insightfully identifies the marginalisation of such thinking from Sociology as an institutionalised discipline. In our response we take up some of the warnings Go provides in the closing sections of his essay-which concern the expanse of intellectual engagement being currently bracketed under or connected to the 'anti-colonial', not least vis-à-vis the 'decolonising/decolonial' turn-to further unpack how the 'anti-colonial' might be adapted for thinking through contemporary socio-political dynamics. Offering, first, a precis of some particularities of British Sociology vis-a-vis the contributions of anticolonial social theory, this article then expands upon the dilemmas arising when anticolonial theory contemporaneous to the pre-decolonisation era is transposed to contingencies of the present 21st century. Namely, whilst the anticolonial archive has proved invaluable to upending the omissions but also complicities of European social theory canons, allowing for a much more expansive sense of how the modern world and its violences were conjured and how we might accordingly escape its miseries, it is also clear that much of the postcolonial world has undergone sufficient shifts to warrant an adapted sense of how we consider the anti-colonial for our current politics. We suggest that the important deviations which anti-colonial theorisations might heed include the dangers of conflating the anticolonial with an affirmation of Global South, non-white nativist identity; the need to recognise some key conjunctural premises by which the anticolonial is no longer geographically indexed to a straightforward Global North-Global South distinction; and the need to acknowledge that, at its most radical, anticolonial thought is itself still invested in traversing both the dreams but also corruptions of those dreams as intrinsic to modernity.


Assuntos
Política , Sociologia , Humanos , Sociologia/história , Teoria Social
3.
Am J Transl Res ; 15(11): 6476-6485, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074818

RESUMO

BACKGROUND AND OBJECTIVES: Cadherin13 (CDH13) is an uncommon cadherin family member, lacking a transmembrane domain, and attaches via a glycosylphosphatidylinositol anchor to the peripheral surface of the cell membrane. CDH13 plays an important role in the development and maintenance of axonal growth cones, synapse morphogenesis, and the embryonic neural tube. Cadherin superfamily genes have been associated with many neuropsychiatric diseases. Studies have shown the Cadherin13 gene as a risk locus for Schizophrenia (SCZ). In this study, we investigated CDH13 gene variants rs7204454 in the promotor region and rs9940180 in the intronic region of the gene with susceptibility to SCZ risk in the population of Jammu region of J&K, India. METHODS: The genotyping was performed using TaqMan assay, where 560 individuals, comprising 164 patients and 396 healthy controls, were genotyped. RESULTS: The result of the study suggested rs9940180 was significantly found to be associated with Schizophrenia and the "C" allele of rs9940180 was associated with increased risk for SCZ (P = 0.03817; OR = 1.527; 95% CI, 1.022-2.28) whereas the other variant rs7204454 of CDH13 gene did not show significant association with schizophrenia risk with P = 0.8827, OR = 0.582-1.33 at 95% CI. CONCLUSION: This is the first report suggesting a significant association of polymorphism at CDH13 rs9940180 with Schizophrenia in the Dogra population group of the Jammu region. The current study offers a piece of important information on the genetic reason for CDH13 in the Jammu population of J&K. Also, it supports the GWAS findings on the correlation of CDH13 in schizophrenia.

4.
Bioresour Technol ; 375: 128791, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36871702

RESUMO

Current study is the first report of the combined application of chemical (deep eutectic solvent), physical (microwave irradiation) and biological (laccase) pretreatment strategies for enhancing the enzymatic digestibility of rice straw biomass. Pretreated rice straw biomass was saccharified by cellulase/xylanase from Aspergillus japonicus DSB2 to get a sugar yield of 252.36 mg/g biomass. Design of Experiment based optimization of pretreatment and saccharification variables increased the total sugar yield by 1.67 times (421.5 mg/g biomass, saccharification efficiency 72.6%). Sugary hydrolysate was ethanol-fermented by Saccharomyces cerevisiae and Pichia stipitis to achieve an ethanol yield of 214 mg/g biomass (bioconversion efficiency 72.5%). Structural/chemical aberrations induced in the biomass due to pretreatment were elucidated by X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, and 1H nuclear magnetic resonance techniques to unravel the pretreatment mechanisms. Combined application of various physico-chemical/biological pretreatment may be a promising approach for proficient bioconversion of rice straw biomass.


Assuntos
Oryza , Solventes , Oryza/química , Lacase , Solventes Eutéticos Profundos , Biomassa , Micro-Ondas , Etanol , Saccharomyces cerevisiae , Açúcares , Hidrólise
5.
J Immunol ; 184(6): 3117-26, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20147635

RESUMO

Pathogenic mycobacteria have evolved unique strategies to survive within the hostile environment of macrophages. Modulation of key signaling cascades by NO, generated by the host during infection, assumes critical importance in overall cell-fate decisions. We show that NO is a critical factor in Mycobacterium bovis bacillus Calmette-Guérin-mediated Notch1 activation, as the generation of activated Notch1 or expression of Notch1 target genes matrix metalloproteinase-9 (MMP-9) or Hes1 was abrogated in macrophages derived from inducible NO synthase (iNOS) knockout (iNOS(-/-)), but not from wild-type, mice. Interestingly, expression of the Notch1 ligand Jagged1 was compromised in M. bovis bacillus Calmette-Guérin-stimulated iNOS(-/-) macrophages, and loss of Jagged1 expression or Notch1 signaling could be rescued by NO donors. Signaling perturbations or genetic approaches implicated that robust expression of MMP-9 or Hes1 required synergy and cross talk between TLR2 and canonical Notch1-PI3K cascade. Further, CSL/RBP-Jk contributed to TLR2-mediated expression of MMP-9 or Hes1. Correlative evidence shows that, in a murine model for CNS tuberculosis, this mechanism operates in vivo only in brains derived from WT but not from iNOS(-/-) mice. Importantly, we demonstrate the activation of Notch1 signaling in vivo in granulomatous lesions in the brains of Mycobacterium tuberculosis-infected human patients with tuberculous meningitis. Current investigation identifies NO as a pathological link that modulates direct cooperation of TLR2 with Notch1-PI3K signaling or Jagged1 to regulate specific components of TLR2 responses. These findings provide new insights into mechanisms by which Notch1, TLR2, and NO signals are integrated in a cross talk that modulates a defined set of effector functions in macrophages.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas de Membrana/fisiologia , Mycobacterium bovis/imunologia , Óxido Nítrico/fisiologia , Receptor Notch1/fisiologia , Transdução de Sinais/imunologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular , Ativação Enzimática/genética , Ativação Enzimática/imunologia , Regulação da Expressão Gênica/imunologia , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-1 , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/deficiência , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/fisiologia , Estrutura Terciária de Proteína/genética , Receptor Cross-Talk/imunologia , Receptor Notch1/biossíntese , Receptor Notch1/genética , Proteínas Serrate-Jagged , Transdução de Sinais/genética , Receptor 2 Toll-Like/fisiologia , Fatores de Transcrição HES-1 , Tuberculose Meníngea/genética , Tuberculose Meníngea/imunologia , Tuberculose Meníngea/patologia
6.
JOP ; 13(3): 292-5, 2012 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22572135

RESUMO

CONTEXT: Pancreatic fistulae are uncommon and usually follow acute or chronic pancreatitis. While most of these are treated conservatively, some require surgery. Recently endoscopic therapy has emerged as an effective alternative treatment modality. CASE REPORT: We present a patient with internal pancreatic fistula due to alcohol related chronic pancreatitis. Endotherapy using glue resulted in resolution of the fistula. CONCLUSION: The use of endoscopic glue injection may be a safe and effective method for the successful therapy of internal pancreatic fistula.


Assuntos
Adesivos/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/métodos , Embucrilato/uso terapêutico , Cirrose Hepática Alcoólica/complicações , Fístula Pancreática/etiologia , Fístula Pancreática/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
J Emerg Med ; 43(4): 637-40, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20580518

RESUMO

BACKGROUND: Acute abdominal pain is commonly encountered in the emergency department (ED), but a diagnosis of gall bladder perforation (GBP) is rarely considered in the absence of predisposing factors. OBJECTIVES: This article will highlight the risk factors, diagnosis, and management of GBP, a rare but potentially life-threatening biliary pathology. CASE REPORT: A 73-year-old diabetic man presented to the ED with a 12-h history of severe upper abdominal pain. He was hemodynamically stable, but abdominal examination showed distention, guarding, and diffuse tenderness. Abdominal X-ray study showed mildly distended small bowel loops without any air-fluid levels. Abdominal sonography revealed mild ascites and pericholecystic fluid collection but no gall bladder calculi. Laboratory reports documented a white blood cell count of 13,700/mm(3) and elevated serum amylase of 484 IU/L. A contrast-enhanced computed tomography (CT) scan of the abdomen suggested discontinuity of the gall bladder wall along with fluid accumulation in the pericholecystic, perihepatic, right subphrenic, and right paracolic spaces. In view of the possibility of spontaneous GBP developing as a complication of acute acalculous cholecystitis, laparotomy was planned. At surgery, several liters of bile-stained peritoneal fluid were aspirated and inspection of the gall bladder revealed a perforation at the fundus. After cholecystectomy, the patient had an uneventful recovery. CONCLUSION: The diagnosis of spontaneous gall bladder perforation should be considered in elderly patients presenting to the ED with symptoms and signs of peritonitis even in the absence of pre-existing gall bladder disease. Abdominal CT scan is an invaluable tool for the diagnosis, and early surgical intervention is usually life-saving.


Assuntos
Abdome Agudo/etiologia , Colecistite Acalculosa/diagnóstico por imagem , Colecistite Acalculosa/complicações , Colecistite Acalculosa/cirurgia , Idoso , Colecistectomia , Humanos , Masculino , Radiografia , Ruptura Espontânea/complicações , Ruptura Espontânea/diagnóstico por imagem , Ruptura Espontânea/cirurgia
8.
J Biosci ; 472022.
Artigo em Inglês | MEDLINE | ID: mdl-36477022

RESUMO

Viola odorata L., known for its pharmacological properties, produces a plethora of structurally stable peptides called cyclotides. Cyclotides are macrocyclic peptides with a unique topology containing a cyclic cystine knot motif. The objective of the present study was to identify the precursor sequences and respective cyclotide domains from the petiole tissue of V. odorata. The study is based on the isolation, identification, and characterization of the cyclic peptides using LC-MS/MS followed by database searching and processing. Our study detected 47 precursor sequences encoded for 15 reported cyclotides, 4 putative novel cyclotides, and 3 acyclotides from the petiole tissue. The novel sequences identified were based on the hydrophobic nature, disulfide bonds, conserved cysteine residues, and presence of cyclic peptide backbone. Four putative novel and three acyclotides were also characterized for their sequence and subfamilies. A protein diversity wheel was used to reveal the variation in the amino acid sequence and cysteine residue conservation in the isolated cyclotides. The results provide information about the number of cyclotides and acyclotides from the petiole tissue and their sequence diversity, which may constitute novel tools for future research on this plant species.


Assuntos
Ciclotídeos , Viola , Ciclotídeos/genética , Viola/genética , Cromatografia Líquida , Cisteína , Espectrometria de Massas em Tandem
9.
Indian J Psychiatry ; 64(6): 567-571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714673

RESUMO

Background: Neurogenic locus notch homolog 4 (NOTCH4) regulates signaling pathways associated with neuronal maturation, a process involved in the development and patterning of the central nervous system. The NOTCH4 gene has also been identified as a possible susceptibility gene for schizophrenia (SCZ). Aim: The study aimed to determine the association of NOTCH4 polymorphisms with the risk of SCZ in the North Indian population of the Jammu region. Methods: The single nucleotide polymorphism genotyping for NOTCH4 variant rs2071287 was done by Sanger's sequencing method, and the other variant rs3131296 was done by TaqMan assay method for 207 SCZ cases and 304 healthy controls of North Indian origin. Results: This association study suggested that the rs2071287 was found to be significantly associated with SCZ. Moreover, the GG genotype of rs2071287 was observed to be associated with a higher risk for SCZ (P-value = 6.45 × 10 - 5; OR = 1.71; 95% CI, 1.31-2.24). Conclusion: To establish the potential biomarker role of this variant, large-scale association analyses in other populations is required.

10.
J Biol Chem ; 285(40): 30389-403, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20558725

RESUMO

Mycobacterium tuberculosis utilizes unique strategies to survive amid the hostile environment of infected host cells. Infection-specific expression of a unique mycobacterial cell surface antigen that could modulate key signaling cascades can act as a key survival strategy in curtailing host effector responses like oxidative stress. We demonstrate here that hypothetical PE_PGRS11 ORF encodes a functional phosphoglycerate mutase. The transcriptional analysis revealed that PE_PGRS11 is a hypoxia-responsive gene, and enforced expression of PE_PGRS11 by recombinant adenovirus or Mycobacterium smegmatis imparted resistance to alveolar epithelial cells against oxidative stress. PE_PGRS11-induced resistance to oxidative stress necessitated the modulation of genetic signatures like induced expression of Bcl2 or COX-2. This modulation of specific antiapoptotic molecular signatures involved recognition of PE_PGRS11 by TLR2 and subsequent activation of the PI3K-ERK1/2-NF-κB signaling axis. Furthermore, PE_PGRS11 markedly diminished H(2)O(2)-induced p38 MAPK activation. Interestingly, PE_PGRS11 protein was exposed at the mycobacterial cell surface and was involved in survival of mycobacteria under oxidative stress. Furthermore, PE_PGRS11 displayed differential B cell responses during tuberculosis infection. Taken together, our investigation identified PE_PGRS11 as an in vivo expressed immunodominant antigen that plays a crucial role in modulating cellular life span restrictions imposed during oxidative stress by triggering TLR2-dependent expression of COX-2 and Bcl2. These observations clearly provide a mechanistic basis for the rescue of pathogenic Mycobacterium-infected lung epithelial cells from oxidative stress.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Células Epiteliais/metabolismo , Proteínas de Membrana/metabolismo , Mycobacterium tuberculosis/enzimologia , Estresse Oxidativo , Fosfoglicerato Mutase/metabolismo , Alvéolos Pulmonares/metabolismo , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Ciclo-Oxigenase 2/biossíntese , Células Epiteliais/microbiologia , Humanos , Peróxido de Hidrogênio/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mycobacterium smegmatis/enzimologia , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/imunologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Oxidantes/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoglicerato Mutase/genética , Fosfoglicerato Mutase/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Alvéolos Pulmonares/microbiologia , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/metabolismo , Tuberculose/enzimologia , Tuberculose/genética , Tuberculose/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
3 Biotech ; 11(5): 211, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33927999

RESUMO

Cyclotides are true gene products characterized by the presence of six conserved cysteine residues and knotted arrangement of three disulfide bonds. These macrocyclic peptides show exceptional resistance to thermal, chemical and enzymatic degradation which is defined due to their three-dimensional folding. The current study describes an efficient strategy involving reduction, enzymatic digestion and mass spectroscopy sequencing for the identification of the precursor sequences and the cyclotide domains present in the leaf tissue of Viola odorata. We observed 122 partial peptide sequences containing 31 cyclotide domains along with 19 unique sequences consisting of putative novel cyclotides and acyclotides. Four precursor sequences consisting of putative new and already reported domains were further characterized for cyclotide domains, their structure and subfamilies. The sequences revealed the presence of classic knotted cyclotide folds with similar six characteristic loops but different amino acid residues. Molecular modeling indicated that the secondary structures present in the cyclotides are mainly α-helix and random coils. Variation in the sequences and conservation in cysteine residues in the cyclotides was revealed by protein diversity wheel. The significant information observed in the current study expands our knowledge about the structure and type of cyclic peptides in V. odorata leaves. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02763-2.

12.
Bioresour Technol ; 333: 125191, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33951579

RESUMO

This work aimed to study the hydrolysis of ionic liquid (IL) pretreated sugarcane tops (SCT) biomass with in-house developed IL-stable enzyme preparation, from a fungal isolate Aspergillus flavus PN3. Maximum reducing sugar yield (181.18 mg/g biomass) was obtained from tris (2-hydroxyethyl) methylammonium-methylsulfate ([TMA]MeSO4) pretreated biomass. Pretreatment parameters were optimized to attain enhanced sugar yield (1.57-fold). Functional mechanism of IL mediated pretreatment of SCT biomass was elucidated by SEM, XRD, FTIR and 1H NMR studies. Furthermore, nanobiocatalysts prepared by immobilization of enzyme preparation by covalent coupling on magnetic nanoparticles functionalized with amino-propyl triethoxysilane, were assessed for their hydrolytic efficacy and reusability. Nanobiocatalysts were examined by SEM and FTIR analysis for substantiation of immobilization. This is the first ever report of application of magnetic nanobiocatalysts for saccharification of IL-pretreated sugarcane tops biomass.


Assuntos
Líquidos Iônicos , Saccharum , Biocombustíveis , Biomassa , Hidrólise
13.
J Genet ; 982019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31767815

RESUMO

The diversity on fruit colouration in plants directly depends on the flavonoids that explain the development of different pigmentation patterns. Anthocyanins are the major class of flavonoid pigments that are synthesized through flavonoid biosynthetic pathway. In the present study, two genes: PgUFGT gene and R2R3-PgMYB gene, involved in anthocyanin biosynthesis were analysed in four tissues of wild pomegranate. The structural genes, UDP-glucose: flavonoid-3-O-glucosyl transferase (PgUFGT; GenBank accession number: MK058491) and its myeloblastosis transcription factor (R2R3-PgMYB; GenBank accession number: MK092063) were isolated and their expression pattern were studied. Molecular modelling indicated that the main secondary structures of PgUFGT and R2R3-PgMYB genes are α-helix and random coil. In addition, expression profiling of PgUFGT and R2R3-PgMYB by quantitative-real time PCR indicated a positive correlation between anthocyanin content and their expression in leaves, flowers, green and red fruits of wild pomegranate. Among all the tissues, the red fruit exhibited high transcripts levels of PgUFGT as well as R2R3-PgMYB transcription factor. An extensive homology with UFGTs from other plants was revealed on comparative and bioinformatic analyses. Present study reveals that PgUFGT plays a predominant role in anthocyanin content in wild pomegranate fruits. Further, it is strongly suggested that R2R3-PgMYB transcription factor regulates the anthocyanin biosynthesis in wild pomegranate via expression of PgUFGT gene. This is the first study which provides an insight on expression profile of PgUFGT and R2R3-PgMYB that are involved in colour development and fruit ripening in wild pomegranate.


Assuntos
Flavonoides/biossíntese , Flavonoides/genética , Genes de Plantas/genética , Proteínas de Plantas/genética , Punica granatum/genética , Punica granatum/metabolismo , Fatores de Transcrição/genética , Antocianinas/biossíntese , Antocianinas/genética , Vias Biossintéticas/genética , Clonagem Molecular , Bases de Dados de Ácidos Nucleicos , Flores/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Índia , Pigmentação/genética , Folhas de Planta/genética
14.
PLoS One ; 5(12): e15466, 2010 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-21151933

RESUMO

Cationic amino acid transporters (mCAT1 and mCAT2B) regulate the arginine availability in macrophages. How in the infected cell a pathogen can alter the arginine metabolism of the host remains to be understood. We reveal here a novel mechanism by which Salmonella exploit mCAT1 and mCAT2B to acquire host arginine towards its own intracellular growth within antigen presenting cells. We demonstrate that Salmonella infected bone marrow derived macrophages and dendritic cells show enhanced arginine uptake and increased expression of mCAT1 and mCAT2B. We show that the mCAT1 transporter is in close proximity to Salmonella containing vacuole (SCV) specifically by live intracellular Salmonella in order to access the macrophage cytosolic arginine pool. Further, Lysosome associated membrane protein 1, a marker of SCV, also was found to colocalize with mCAT1 in the Salmonella infected cell. The intra vacuolar Salmonella then acquire the host arginine via its own arginine transporter, ArgT for growth. The argT knockout strain was unable to acquire host arginine and was attenuated in growth in both macrophages and in mice model of infection. Together, these data reveal survival strategies by which virulent Salmonella adapt to the harsh conditions prevailing in the infected host cells.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos/fisiologia , Arginina/química , Salmonella typhimurium/metabolismo , Animais , Arginina/metabolismo , Proteínas de Bactérias/metabolismo , Células Cultivadas , Citosol/metabolismo , Teste de Complementação Genética , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/metabolismo , Nitritos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Salmonella/metabolismo , Virulência
15.
PLoS One ; 4(3): e4911, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19290049

RESUMO

Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor -kappaB (NF-kappaB) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of Suppressor of Hairless (CSL) and NF-kappaB to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Macrófagos/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptor Notch1/metabolismo , Transdução de Sinais/fisiologia , Animais , Células Cultivadas , Ativação Enzimática , Receptores de Hialuronatos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo
16.
Mol Immunol ; 46(15): 2947-54, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19608279

RESUMO

Initiation of proinflammatory host immunity in response to infection represents as a key event in effective control and containment of the pathogen at the site of infection as well as in elicitation of robust immune memory responses. In the current investigation, we demonstrate that an integral cell wall antigen of the mycobacterial envelope, Phosphatidyl-myo-inositol dimannosides (PIM2) triggers Suppressor of cytokine signaling (SOCS) 3 expression in macrophages in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Data derived from signaling perturbations suggest the involvement of phosphoinositide-3 kinase (PI3K) and protein kinase C (PKC) signaling pathways during PIM2 induced SOCS3 expression. Further, pharmacological inhibition of ERK1/2, but not of p38 MAP kinase or JNK abrogated the induced expression of SOCS3. The PIM2 induced activation of ERK1/2 was dependent on the activation of PI3K or PKC signaling which in turn regulated p65 nuclear factor -kappaB (NF-kappaB) nuclear translocation. Overall, current study delineates the role for PI3K-PKC axis and ERK1/2 signaling as key signaling events during PIM2 induced SOCS3 expression in macrophages.


Assuntos
Macrófagos/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis/imunologia , Proteína Quinase C/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Animais , Linhagem Celular , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Técnicas de Silenciamento de Genes , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/imunologia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/imunologia , Fosfatidilinositóis/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/imunologia , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/imunologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/agonistas , Proteínas Supressoras da Sinalização de Citocina/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo
17.
Curr Opin Obstet Gynecol ; 19(6): 586-90, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18007138

RESUMO

PURPOSE OF REVIEW: There is controversy about the best approach to screening and management for gestational diabetes. In the recent Confidential Enquiry in Maternal and Child Health (CEMACH) the outcome of women with diabetes compared with women without diabetes. The results were exceptionally poor, suggesting the need for a new management approach. The aim of this review is to address these findings and our suggested care pathways. RECENT FINDINGS: The CEMACH report showed the congenital malformation rate was four to 10-fold higher, the perinatal mortality rate was four to seven-fold higher, stillbirth was five times more common, and babies were three times more likely to die in the first 3 months of life. Only 39% of women with established diabetes took folic acid and only 37% had some documentation of glycaemic control before pregnancy. Overall, less than a fifth of NHS trusts in the UK had any kind of multidisciplinary preconception services. The results for women with type 2 diabetes were as bad as those for type 1. Caesarean delivery rates were very high (67%). SUMMARY: Prepregnancy counselling and multidisciplinary team management is the key in achieving good pregnancy outcomes. There is emerging evidence about the safety and efficacy of oral hypoglycaemics like metformin in pregnancy.


Assuntos
Anormalidades Congênitas/epidemiologia , Diabetes Gestacional/fisiopatologia , Hipoglicemiantes/uso terapêutico , Mortalidade Infantil , Gravidez em Diabéticas/fisiopatologia , Cuidado Pré-Natal/métodos , Cesárea/métodos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/terapia , Dieta , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Administração dos Cuidados ao Paciente , Gravidez , Resultado da Gravidez , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/terapia , Fatores de Risco
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