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High-valent metal-fluoride complexes are currently being explored for concerted proton-electron transfer (CPET) reactions, the driving force being the high bond dissociation energy of H-F (BDEH-F = 135 kcal/mol) that is formed after the reaction. Ni(III)-fluoride-based complexes on the pyridine dicarboxamide pincer ligand framework have been utilized for CPET reactions toward phenols and hydrocarbons. We have replaced the central pyridine ligand with an N-heterocyclic carbene carbene to probe its effect in both stabilizing the high-valent Ni(III) state and its ability to initiate CPET reactions. We report a monomeric carbene-diamide-based Ni(II)-fluoride pincer complex that was characterized through 1H/19F NMR, mass spectrometry, UV-vis, and X-ray crystallography analysis. Although carbenes and deprotonated carboxamides in the Ni(II)-fluoride complex are expected to stabilize the Ni(III) state upon oxidation, the Ni(III)/Ni(II) redox process occurred at very high potential (0.87 V vs Fc+/Fc, dichloromethane) and was irreversible. Structural studies indicate significant distortion in the imidazolium "NCN" carbene plane of Ni(II)-fluoride caused by the formation of six-membered metallacycles. The high-valent NiIII-fluoride analogue was synthesized by the addition of 1.0 equiv CTAN (ceric tetrabutylammonium nitrate) in dichloromethane at -20 °C which was characterized by UV-vis, mass spectrometry, and EPR spectroscopy. Density functional theory studies indicate that the Ni-carbene bond elongated, while the Ni-F bond shortened upon oxidation to the Ni(III) species. The high-valent Ni(III)-fluoride was found to react with the substituted phenols. Analysis of the KIE and linear free energy relationship correlates well with the CPET nature of the reaction. Preliminary analysis indicates that the CPET is asynchronous and is primarily driven by the E0' of the Ni(III)-fluoride complex.
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Formation of G-quadruplex (G4) DNA structures in key regulatory regions in the genome has emerged as a secondary structure-based epigenetic mechanism for regulating multiple biological processes including transcription, replication, and telomere maintenance. G4 formation (folding), stabilization, and unfolding must be regulated to coordinate G4-mediated biological functions; however, how cells regulate the spatiotemporal formation of G4 structures in the genome is largely unknown. Here, we demonstrate that endogenous oxidized guanine bases in G4 sequences and the subsequent activation of the base excision repair (BER) pathway drive the spatiotemporal formation of G4 structures in the genome. Genome-wide mapping of occurrence of Apurinic/apyrimidinic (AP) site damage, binding of BER proteins, and G4 structures revealed that oxidized base-derived AP site damage and binding of OGG1 and APE1 are predominant in G4 sequences. Loss of APE1 abrogated G4 structure formation in cells, which suggests an essential role of APE1 in regulating the formation of G4 structures in the genome. Binding of APE1 to G4 sequences promotes G4 folding, and acetylation of APE1, which enhances its residence time, stabilizes G4 structures in cells. APE1 subsequently facilitates transcription factor loading to the promoter, providing mechanistic insight into the role of APE1 in G4-mediated gene expression. Our study unravels a role of endogenous oxidized DNA bases and APE1 in controlling the formation of higher-order DNA secondary structures to regulate transcription beyond its well-established role in safeguarding the genomic integrity.
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Dano ao DNA , Reparo do DNA/fisiologia , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Quadruplex G , Células A549 , Acetilação , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Expressão Gênica , Genes myc , Genoma Humano , Guanina/química , Guanina/metabolismo , Células HCT116 , Humanos , Oxirredução , Estresse Oxidativo/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
A high incidence of oral squamous cell carcinoma (OSCC) is observed in South-East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell-derived factor-1α (SDF-1 or SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco. Targeted immunohistochemical staining and Western blotting were performed on primary tumour and metastatic lymph node (LN) tissues in parallel. Overexpression of hepatocyte growth factor (HGF), activated form of its cognate receptor tyrosine kinase, c-Met (p-Met), GRB2-associated-binding protein 1 (Gab1), phospho-protein kinase B (pAkt), nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2) were observed in primary tumour and metastatic lymph nodes in both chewer and non-chewer cohorts. Variance analysis showed significant positive correlation between them (P < .0001) indicating upregulation of these biomarkers upon ligand-induced activation of c-Met in both tobacco chewers and non-chewers. Significantly higher expressions of SDF1α and CXCR4 were observed in both primary tumours and metastatic lymph nodes of tobacco chewers (P < .0001) and coincided with overexpressed HGF. In contrast, no significant correlation was observed between expression of HGF and that of SDF1α and CXCR4 in non-chewers. Together, our findings provide important insights into the association of HGF/c-Met and the SDF1α/CXCR4 axis in lymph node metastasis and to an aetiological link with the habit of chewing tobacco.
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Quimiocina CXCL12/metabolismo , Neoplasias Bucais/patologia , Receptores CXCR4/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Tabaco sem Fumaça/efeitos adversos , Adulto , Idoso , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismoRESUMO
Existing feedforward, or FF, controllers are based on differentially flat models. For double-acting single-rod cylinders, more compact than the double-rod ones, flat models could be constructed either under an incompressible-flow assumption for low-pressure, slow-response applications or for a matched valve-cylinder combination. Contrasting the existing models tackling only a single nonlinear aspect like valve leakage, oil compressibility or friction, a novel FF controller, generalized for different types of valve-cylinder-pump combinations, has been developed here. It is based on the highest-order assumption of incompressible flow that sustains the piston motion. An FFPI controller has been implemented in a laboratory setup for displacement tracking against sinusoidal demands up to 9 Hz frequency. The FF parameters has been estimated by minimizing the deviation of simulation prediction from an offline experimental time-varying response. The PI gains have been selected through a stability analysis by extending Routh criteria for linearized time-variant error dynamics. Comparison against a PI-only controller with identical gains has established the energy-saving potential of the FFPI controller both working with the same variable-displacement pump. In comparison to existing nonlinear adaptive controllers, more precise and smoother responses have been obtained over wider frequency range at lower control expenses, admittedly with occasional marginal penalty in the phase variation. The FFPI controller has exhibited the shortest transient and the highest resilience against measurement noise.
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Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.
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Closure of a circular tissue defect in the head-neck-face region is challenging because most transposition flaps are rhombic or triangular. For a tension-less closure, both rhombic transposition flap and the circular tissue defect need to be engineered maintaining strict geometric calculations. The present illustration demonstrates a modified rhombic transposition flap with greater freedom in rotation and mobility for closing a moderate-sized circular defect resulting from wide local excision of cutaneous squamous cell carcinoma in the mid-face. The circular shape of the primary tissue defect did not need to be altered. The authors revisited an earlier published technique in the process, adding their own modification to the rhombic transposition flap.
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Cu(II) complexes supported by tetradentate amido-quinoline acyclic ligands (L1 & L2) have been synthesized, characterized, and employed as catalysts for aromatic C-H hydroxylation using H2O2 as an oxidant in the absence of an external base with a high selectivity of around 90% for phenols via the non-radical pathway (TON ≥720). The KIE value, various spectroscopic studies and DFT calculation supported the involvement of Cu(II)-OOH species.
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Peróxido de Hidrogênio , Quinolinas , Peróxido de Hidrogênio/química , Modelos Moleculares , Hidroxilação , Oxidantes/química , LigantesRESUMO
Ni(II)-tetradentate amido-quinoline complexes effectively catalysed C-H chlorination of a series of hydrocarbons in the presence of NaOCl and acetic acid. The bond dissociation energy of the C(sp3)-H bond of the substrates varies from 99.3 kcal mol-1 (cyclohexane) to 87 kcal mol-1 (ethyl benzene). Exclusively chlorinated products (TON: 220 for cyclohexane) were obtained without any hydroxylated products, thus mimicking the activity of the halogenase enzyme.
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Níquel , Quinolinas , Catálise , Halogenação , Ligantes , Níquel/químicaRESUMO
Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition and cancer stem cell characteristics. Organoid cultures of ECDTg tumors showed ECD dependency for in vitro oncogenic phenotype and in vivo growth when implanted in mice. RNA sequencing (RNA-seq) analysis of ECDTg tumors showed a c-MYC signature, and alterations in ECD levels regulated c-MYC mRNA and protein levels as well as glucose metabolism. ECD knockdown-induced decrease in glucose uptake was rescued by overexpression of mouse ECD as well as c-MYC. Publicly available expression data analyses showed a significant correlation of ECD and c-MYC overexpression in breast cancer, and ECD and c-MYC coexpression exhibits worse survival in patients with breast cancer. Taken together, we establish a novel role of overexpressed ECD as an oncogenesis driver in the mouse mammary gland through upregulation of c-MYC-mediated glucose metabolism. IMPLICATIONS: We demonstrate ECD overexpression in the mammary gland of mice led to the development of a tumor progression model through upregulation of c-MYC signaling and glucose metabolism.
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Neoplasias da Mama , Carcinogênese , Carcinógenos , Proteínas de Transporte , Glucose , Proteínas Proto-Oncogênicas c-myc , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/patologia , Proteínas de Transporte/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Glucose/metabolismo , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Neoplasias Pulmonares/secundário , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro , Transdução de Sinais , Regulação para CimaRESUMO
INTRODUCTION: Distal radius physeal growth arrest in children secondary to trauma is a rare complication. Various modalities of surgical treatment exist. Correction of severe deformity by a single-stage surgery is rare in current literature. We describe a case of surgically treated posttraumatic manus valgus deformity in an adolescent female with a satisfactory surgical outcome. CASE REPORT: A 13-year-old right-hand dominant girl presented to us with a painless, gradually progressive left wrist deformity for the past 3 years. She sustained a left wrist injury 3.5 years back for which she received native treatment. She was able to do most of her daily activities and cosmetic disability was her primary concern. She had a 20° fixed radial deviation deformity with further radial deviation up to 60°. Forearm rotation was from 70° supination to 60° pronation. Her pre-operative Mayo Modified Wrist Score was 25/10/10/25/70 (Pain/Satisfaction/Range of motion/Grip strength/Total). Radiologically, there was the obliteration of lateral distal radial physis with overgrowth of medial physis. Distal ulnar physeal overgrowth led to positive ulnar variance. Radiologically, the magnitude of deformity was 43° manus valgus (+24° radial inclination). We performed dome osteotomy at distal radius metaphysis with distal radius plating through modified Henry approach. Simultaneous ulnar diaphyseal shortening osteotomy with plate fixation was done through a dorsal approach and distal ulnar epiphysiodesis was done by physeal drilling to prevent future overgrowth. At 13 months follow-up, the wrist has clinically no deformity and radiologically 5° manus valgus (+24° radial inclination). Both the osteotomy sites have united and ulnar variance is restored. Now, her ulnar deviation was 20° and radial deviation was 30°. Her forearm rotational arc was maintained. Mayo Modified Wrist Score was 25/25/10/25/85 (Pain/Satisfaction/Range of motion/Grip strength/Total) with no hindrance of daily activity. CONCLUSION: Correction of wrist deformity, restoration of ulnar variance, and normal wrist mechanics is possible in a single-stage surgery with judicious planning and can provide satisfactory result.
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BACKGROUND: Open excision remains the gold standard of treatment for posttraumatic heterotopic ossification (HO) of the elbow. The purpose of this study is to evaluate the functional outcome of early surgical excision done by adhering to a proposed surgical protocol with exclusive posttraumatic HO of the elbow. METHODS: A retrospective study was conducted with 31 patients (25 males and 6 females) with a mean follow-up of 40.5 ± 27.44 months. Excision was done according to our surgical protocol based on the location of HO, associated fractures, stability, need for ulnar nerve transposition, previous operative scar. Improvement in elbow function, Mayo elbow performance score (MEPS) preoperatively and at final follow-up was compared, and statistical analysis was done. RESULTS: Mean flexion-extension arc, supination-pronation arc and MEPS improved by 74.68° ± 29.32°, 26.13° ± 32.93°, 30.48 ± 11.57, respectively. Flexion arc deteriorated by 10.81° ± 10.42° from intraoperative to final follow-up. Improvement at final follow-up was significant in all the cases (P < 0.05). 19 patients had limited HO, and 12 had global HO. Their mean flexion-extension arc increase was 77.63° ± 29.12° and 70° ± 30.3° respectively, and the final mean MEPS score was 96.05 ± 5.16 and 88.75 ± 11.51, respectively. Nine patients had no initial fracture (Group 1), 13 had some fracture (Group 2), nine had a fracture-dislocation of the elbow (Group 3). Their flexion-extension improvement, final MEPS were 88.33° ± 30.82°, 98.33 ± 5, (Group 1); 81.15° ± 16.73°, 92.31 ± 9.27 (Group 2) and 51.67° ± 31.32°, 89.44 ± 9.5 (Group 3), respectively. We had two complications (6.45%). CONCLUSION: The surgical protocol described here enabled us to achieve good functional results and was in concordance with similar studies done previously. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-021-00381-x.
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The use of chewing tobacco is a severe risk factor for oral mucosa related diseases including cancer in India as well as USA, although its relationship with Oral Leukoplakia (OL) or related carcinogenicity is still not clear. This work chose two oncogenic pathway proteins- the Epidermal Growth Factor Receptor and the WNT pathway among leukoplakia patients and established their correlation with the individuals' tobacco chewing habit. 89 fresh patients with OL were selected for the work. The samples were classified based on the individual's tobacco chewing habit. The divided samples were then immunostained with antibodies for both of the EGFR as well as WNT pathway proteins. The samples were further classified based on their proliferation status and the expression of these oncoproteins was also observed. In order to compare the cytological data with histological data, 30 OL patients undergoing biopsy were chosen and immunohistological analysis was performed for the same pathways. Results showed overexpressing EGFR and WNT pathway proteins in all OL samples. Structurally atypic cells had a tendency to overexpress these oncoproteins. However the immunocytochemistry data could not confirm any positive effect of chewing tobacco on the OL's proliferative state. Statistical data from the immunfluorescence finally revealed the overexpression of both EGFR and WNT pathway proteins on the proliferative population establishing chewing tobacco as a positive risk factor for the onset of OL. Data from biopsy samples followed the same trend of protein expression seen in the cytological samples. Dysplastic zones showed huge overexpression of EGFR and WNT pathway proteins among tobacco chewers. In conclusion, this is the first time report showing the effect of chewing tobacco on the EGFR and WNT pathway in OL and its possible role as a potential risk factor for its proliferative type.
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Células Epiteliais/química , Imuno-Histoquímica , Leucoplasia Oral/etiologia , Mastigação , Mucosa Bucal/química , Tabaco sem Fumaça/efeitos adversos , Adulto , Biomarcadores/análise , Proliferação de Células , Células Epiteliais/patologia , Receptores ErbB/análise , Feminino , Imunofluorescência , Humanos , Leucoplasia Oral/metabolismo , Leucoplasia Oral/patologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Regulação para Cima , Proteínas Wnt/análise , Via de Sinalização Wnt , beta Catenina/análiseRESUMO
The mammalian orthologue of ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression, and mitigation of endoplasmic reticulum stress. Here, we identified key components of the mRNA export complexes as binding partners of ECD and characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A. We find that ECD is involved in RNA export through its interaction with DDX39A. ECD knockdown (KD) blocks mRNA export from the nucleus to the cytoplasm, which is rescued by expression of full-length ECD but not an ECD mutant that is defective in interaction with DDX39A. We have previously shown that ECD protein is overexpressed in ErbB2+ breast cancers (BC). In this study, we extended the analyses to two publicly available BC mRNA The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data sets. In both data sets, ECD mRNA overexpression correlated with short patient survival, specifically ErbB2+ BC. In the METABRIC data set, ECD overexpression also correlated with poor patient survival in triple-negative breast cancer (TNBC). Furthermore, ECD KD in ErbB2+ BC cells led to a decrease in ErbB2 mRNA level due to a block in its nuclear export and was associated with impairment of oncogenic traits. These findings provide novel mechanistic insight into the physiological and pathological functions of ECD.
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Transporte Ativo do Núcleo Celular/fisiologia , RNA Helicases DEAD-box/metabolismo , Transporte de RNA/fisiologia , RNA Mensageiro/metabolismo , Animais , Proteínas de Transporte/metabolismo , Citoplasma/metabolismo , Expressão Gênica/genética , Humanos , Splicing de RNA/genética , Transporte de RNA/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Our purpose of the study was to assess the knowledge and any gaps of early educators regarding hearing impairment, and to attempt to delineate the attitudes and perceptions of the educators regarding the outcomes of their students with hearing disabilities and their views on inclusive teaching, using a questionnaire based study. Only 71 respondents completed the questionnaire. The present questionnaire based study was conducted on 100 primary school teachers, undertaken on randomly selected schools from Gangtok, East Sikkim. Their knowledge and attitudes regarding hearing impairment in children in the areas of cause, diagnosis, investigations, treatment, prevention, special care and inclusion into mainstream schools were assessed. Our study showed that the knowledge of causes, investigation and treatment of hearing impairement [HI] among respondents/teachers was poor. The data was shown statistically significant with P < 0.001. However, responses testing behavior and attitudes towards HI was encouraging. 52.9% respondents disagreed that HI was a social handicap and 88.2% felt that teachers need special training before a HI child is admitted to the school. The results were statistically significant with P < 0.001. The biggest obstacle found for inclusive education of HI children was a lack of proper training to teachers (40.8%) and attitude of other students (29.5%).
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We aimed to improve the diagnostic accuracy of tumors by using immunocytochemistry (IHC) on destained smears to correlate the cytological findings with histopathology and/or IHC for final evaluation of results. We have done a randomized and prospective double-blind study. Forty-six clinically suspected patients of salivary gland tumor were enrolled for study. Those with non-neoplastic\ inflammatory salivary gland pathologies and swellings other than salivary gland origin were excluded from the study. The Fine needle aspiration cytological (FNAC) diagnosis of all the patients was compared with the corresponding histopathology. Sensitivity and specificity of FNAC in diagnosing malignancy were 91.3 and 100 %. Diagnostic accuracy of FNAC for malignant tumors was 95.65 %. In our study kappa value came out to be 0.88 (p value <0.00), which indicated an excellent agreement between histological and cytological typing of salivary gland tumors. FNAC is a highly sensitive and specific technique for diagnosis of salivary gland tumors. Histopathology however is the gold standard for diagnosis, classification and grading of tumors. Immuno-cytochemistry can act as adjuvant in diagnosing salivary gland tumors, however it did not help in improving the diagnostic accuracy of FNAC in our study. Considering an excellent agreement between cytology and histology, a type specific diagnosis can be reached on FNAC of salivary gland tumors.
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Mammalian Ecdysoneless (ECD) is a highly conserved ortholog of the DrosophilaEcd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects, but the mechanisms by which ECD functions are largely unknown. Here we present evidence that ECD regulates the endoplasmic reticulum (ER) stress response. ER stress induction led to a reduced ECD protein level, but this effect was not seen in PKR-like ER kinase knockout (PERK-KO) or phosphodeficient eukaryotic translation initiation factor 2α (eIF2α) mouse embryonic fibroblasts (MEFs); moreover, ECD mRNA levels were increased, suggesting impaired ECD translation as the mechanism for reduced protein levels. ECD colocalizes and coimmunoprecipitates with PERK and GRP78. ECD depletion increased the levels of both phospho-PERK (p-PERK) and p-eIF2α, and these effects were enhanced upon ER stress induction. Reciprocally, overexpression of ECD led to marked decreases in p-PERK, p-eIF2α, and ATF4 levels but robust increases in GRP78 protein levels. However, GRP78 mRNA levels were unchanged, suggesting a posttranscriptional event. Knockdown of GRP78 reversed the attenuating effect of ECD overexpression on PERK signaling. Significantly, overexpression of ECD provided a survival advantage to cells upon ER stress induction. Taken together, our data demonstrate that ECD promotes survival upon ER stress by increasing GRP78 protein levels to enhance the adaptive folding protein in the ER to attenuate PERK signaling.
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Proteínas de Transporte/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Proteínas de Choque Térmico/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/genética , Linhagem Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Proteínas de Choque Térmico/genética , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , eIF-2 Quinase/genéticaRESUMO
Cerebrospinal fluid (CSF) leak occurs due to an abnormal communication between the subarachnoid space and sinonasal tract. We reported a retrospective case series of five patients of spontaneous CSF rhinorrhea. These patients were undergone successful repair with a single transnasal endoscopic procedure. This is seen in anterior part of the cribriform plate of middle aged obese females. HRCT paranasal sinus (1 mm cuts) was an effective modality of investigation in our study with ancillary investigations been CT cisternography. Endoscopic repair of CSF rhinorrhea carries a high success rate with very low morbidity rate.
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Tuberculous osteomyelitis affecting long bones is a rare form of tuberculosis. Among infants born in endemic region, often it is difficult to diagnose owing to its subtle clinical features. Here, a case of tuberculous osteomyelitis affecting the distal radial metaphysis is reported, presenting as a cystic lesion in a nine-month-old male infant. Open biopsy with curettage was performed followed by filling of the cavity with synthetic bone substitute (beta tricalcium phosphate granules). The diagnosis was confirmed by histopathological examination and demonstration of acid fast bacilli. Further treatment with anti-tubercular drugs led to clinical and radiological improvement. This case report highlights the importance of keeping tuberculosis as a differential diagnosis while dealing with cases with similar presentation in an endemic region.
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INTRODUCTION: Without dissection of cadavers teaching and learning of anatomy is nearly difficult; there remains a gap between the practical knowledge and the gathered theoretical knowledge. But there is a scarcity in the availability of the donated bodies for the sake of medical education. On the other hand a large number of people in our country are in waiting list for organ transplantation which could be overcome by deceased organ donation. AIM: Aim of the study was to evaluate the awareness regarding body donation after death. MATERIALS AND METHODS: A cross-sectional study was conducted among medical students, engineering students and doctors in Indian population. Total 300 participants were answered the questionnaire providing information about the knowledge and attitude towards body and organ donation. RESULT: 46.33% of entire study group had strongly positive attitude about cadaveric organ donation and 17% had no idea about this. 18% of total participants were unwilling for body donation after death. CONCLUSION: The present study has been done elaborately to find out the different barriers for body or organ donation. It is clear from the study that though there is high level of awareness, nobody has filled up the pledge form till now. It indicates that there is a gap between the knowledge and motivation for organ and body donation after death which has to be overcome by proper guidance and education. Media and other voluntary organisations could take an important role for this purpose.
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INTRODUCTION: Various studies have been done regarding variations of circle of Willis, but few literatures are available about the detail configurations on Indian population. Posterior communicating artery is the main collateral channel between the vertebrobasilar and carotid system. It may act as a main source of blood flow via posterior cerebral artery if fetal configuration is present. Aim of the study is to see the bilateral configurations to compare the blood supply of both cerebral hemispheres via posterior cerebral artery in human cadavers. MATERIALS AND METHODS: Fifty six formalin fixed brains were used for study. The specimens were classified into 3 types and 21 subtypes according to the configuration of the vessel of both hemispheres. As hemodynamic balance is dependent on the calibre of the vessel, the diameter of the arteries were also taken into consideration. Pearson's correlation had been done. RESULT: In present study type I is 57.2%, type II is 37.5% and type III is 5.4%. Incidence of unilateral fetal type posterior cerebral artery is in high percentage (33.9%). Greatest diameter of posterior communicating artery is 3.8mm on right and 3.6mm on left side. Significant correlations also have been found between arterial segments of different types. CONCLUSION: It is expected that the study will help to enrich the knowledge about the arterial predominance of origin of posterior cerebral artery of both cerebral hemispheres in normal or variant cases and its effect on perfusion images.