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1.
Phys Chem Chem Phys ; 26(5): 4083-4090, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38226886

RESUMEN

N-heterocyclic carbene ligands (NHCs) are increasingly used to tune the properties of metal surfaces. The generally greater chemical and thermal robustness of NHCs on gold, as compared to thiolate surface ligands, underscores their potential for a range of applications. While much is now known about the adsorption geometry, overlayer structure, dynamics, and stability of NHCs on coinage elements, especially gold and copper, much less is known about their interaction with the surfaces of Pt-group metals, despite the importance of such metals in catalysis and electrochemistry. In this study, reflection absorption infrared spectroscopy (RAIRS) is used to probe the structure of benzimidazolylidene NHC ligands on Pt(111) and Ru(0001). The experiments exploit the intense absorption peaks of a CF3 substituent on the phenyl ring of the NHC backbone to provide unprecedented insight into adsorption geometry and chemical stability. The results also permit comparison with literature data for NHC ligands on Au(111) and to DFT predictions for NHCs on Pt(111) and Ru(0001), thereby greatly extending the known surface chemistry of NHCs and providing much needed molecular information for the design of metal-organic hybrid materials involving strongly reactive metals.

2.
Childs Nerv Syst ; 39(9): 2533-2536, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37209197

RESUMEN

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae.


Asunto(s)
Enfermedades del Nervio Abducens , Deficiencia de Vitamina B 12 , Masculino , Lactante , Humanos , Femenino , Embarazo , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/tratamiento farmacológico , Lactancia , Enfermedades del Nervio Abducens/complicaciones , Enfermedades del Nervio Abducens/tratamiento farmacológico , Atrofia , Hematoma Subdural/complicaciones , Vitamina B 12/uso terapéutico
3.
Pol J Radiol ; 88: e203-e215, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37234459

RESUMEN

Purpose: To determine the role of functional magnetic resonance imaging techniques (diffusion-weighted magnetic resonance imaging [DW-MRI] and dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]) in the differentiation of various salivary gland tumours. Material and methods: In this prospective study, we evaluated 32 patients with salivary gland tumours using functional MRI. Diffusion parameters (mean apparent diffusion coefficient [ADC], normalized ADC and homogeneity index [HI]),semiquantitative DCE parameters (time signal intensity curves [TICs]) and quantitative DCE parameters (Kep, Ktrans and Ve) were analysed. Diagnostic efficiencies of all these parameters were determined to differentiate benign and malignant tumours as well as to characterize 3 major subgroups of salivary gland tumours, namely pleomorphic adenoma, Warthin tumour, and malignant tumours. Results: Mean ADC, normalized ADC and HI were insignificant in differentiating benign and malignant tumours but were significant in differentiating pleomorphic adenomas, Warthin tumours, and malignant tumours. Mean ADC was the best parameter in predicting both pleomorphic adenomas and Warthin tumours (AUC: 0.95 and 0.89, respectively). Amongst DCE parameters, only TIC pattern could differentiate between benign and malignant tumours, with an accuracy of 93.75% (AUC: 0.94). The quantitative perfusion parameters aided greatly in characterizing pleomorphic adenomas, Warthin tumours and malignant tumours. For predicting pleomorphic adenomas, the accuracy of Kep and Ktrans was 96.77% (AUC: 0.98) and 93.55% (AUC: 0.95), respectively and for predicting Warthin tumours, the accuracy of both Kep and Ktrans was 96.77% (AUC: 0.97). Conclusions: DCE parameters (particularly TIC, Kep and Ktrans) had higher accuracy in characterizing various tumour subgroups (pleomorphic adenomas, Warthin tumours, and malignant tumours) than DWI parameters. Hence, dynamic contrast-enhanced imaging adds immense value with only a minimum time penalty to the examination.

4.
Am J Otolaryngol ; 43(1): 103220, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34547717

RESUMEN

BACKGROUND: It is an incontrovertible fact that the Rhino Orbital Cerebral Mucormycosis (ROCM) upsurge is being seen in the context of COVID-19 in India. Briefly presented is evidence that in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 and injudicious use of corticosteroids may be largely responsible for this malady. OBJECTIVE: To find the possible impact of COVID 19 infection and various co-morbidities on occurrence of ROCM and demonstrate the outcome based on medical and surgical interventions. METHODOLOGY: Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID-19 infection. Diagnostic nasal endoscopy (DNE) was performed on each patient and swabs were taken and sent for fungal KOH staining and microscopy. Medical management included Injection Liposomal Amphotericin B, Posaconazole and Voriconazole. Surgical treatment was restricted to patients with RT PCR negative results for COVID-19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow-up for survived patients was maintained regularly for the first postoperative month. RESULTS: Out of total 131 patients, 111 patients had prior history of SARS COVID 19 infection, confirmed with a positive RT-PCR report and the rest 20 patients had no such history. Steroids were received as a part of treatment in 67 patients infected with COVID 19. Among 131 patients, 124 recovered, 1 worsened and 6 died. Out of 101 known diabetics, 98 recovered and 3 had fatal outcomes. 7 patients with previous history of COVID infection did not have any evidence of Diabetes mellitus, steroid intake or any other comorbidity. CONCLUSION: It can be concluded that ROCM upsurge seen in the context of COVID-19 in India was mainly seen in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 infection and injudicious use of corticosteroids.


Asunto(s)
COVID-19/inmunología , Mucormicosis/inmunología , Corticoesteroides/efectos adversos , Antifúngicos/uso terapéutico , COVID-19/epidemiología , Complicaciones de la Diabetes/inmunología , Diagnóstico por Imagen , Endoscopía , Femenino , Humanos , India/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mucormicosis/tratamiento farmacológico , Mucormicosis/epidemiología , Pandemias , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2
5.
Physiol Mol Biol Plants ; 28(4): 885-898, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35592478

RESUMEN

The post green revolution agriculture is based on generous application of fertilizers and high-yielding genotypes that are suited for such high input regimes. Cereals, like maize (Zea mays L.) are capable of utilizing less than 20% of the applied inorganic phosphate (Pi) - a non-renewable fertilizer resource. A greater understanding of the molecular mechanisms underlying the acquisition, transportation and utilization of Pi may lead to engineering genotypes with high phosphorus use efficiency. In this study, we carried out functional domain similarity analysis, promoter analysis and comparative transcriptional expression profiling of 12 selected Pi responsive genes in the Pi stress tolerant maize inbred line HKI-163 under sufficient and deficient Pi conditions. Pi starvation led to significant increase in root length; marked proliferation of root hairs and lesser number of crown roots. Eleven genes were significantly up or down regulated in Pi deficient condition. The putative acid phosphatase, ZmACP5 expression was up regulated by 162.81 and 74.40 fold in root and leaf tissues, respectively. The RNase, ZmRNS1 showed 115 fold up regulation in roots under Pi deprivation. Among the two putative high affinity Pi transporters ZmPht1;4 was found specific to root, whereas ZmPht2 was found to be up regulated in both root and leaf tissues. The genes involved in Pi homeostasis pathway (ZmSIZ1, SPX1 and Pho2) were up regulated in root and leaf. In light of the expression profiling of selected regulatory genes, an updated model of transcriptional regulation under Pi starvation in maize has been presented. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01155-x.

6.
Chem Rev ; 119(8): 4986-5056, 2019 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-30938514

RESUMEN

N-Heterocyclic carbenes (NHCs) have become one of the most widely studied class of ligands in molecular chemistry and have found applications in fields as varied as catalysis, the stabilization of reactive molecular fragments, and biochemistry. More recently, NHCs have found applications in materials chemistry and have allowed for the functionalization of surfaces, polymers, nanoparticles, and discrete, well-defined clusters. In this review, we provide an in-depth look at recent advances in the use of NHCs for the development of functional materials.

7.
Indian J Med Res ; 153(4): 484-491, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34380795

RESUMEN

BACKGROUND & OBJECTIVES: Lingual squamous cell carcinomas (SCC) pose a major public health burden in India. Epithelial-mesenchymal transition (EMT) is the conversion of an epithelial cell to a mesenchymal phenotype at the invasive front (IF) enhancing invasiveness of these cells which may be studied using immunohistochemistry. The objective of this study was to assess the expression of E-cadherin and vimentin at the IF, and their correlation with the histological risk assessment score, clinicopathological parameters and lymph node metastasis. METHODS: Thirty consecutive untreated patients diagnosed as lingual SCC who underwent hemiglossectomy over one year formed the study group. The immunohistochemical expression of E-cadherin and vimentin in the periphery as well as the centre of tumour islands was correlated with clinicopathological parameters, Brandwein-Gensler risk assessment score and lymph node metastasis, along with a correlation between the coexpression of two markers at the IF. RESULTS: Loss of E-cadherin expression was seen at IF in 83.3 per cent (25/30) cases. Out of these, 20 per cent (5/25) showed a corresponding gain in vimentin expression (complete epithelial-mesenchymal transition) and 80 per cent (20/25) did not. Overall, 16.6 per cent (5/30) cases showed complete EMT. However, no correlation between E- cadherin and vimentin expression at the IF was found. No statistical significance was found between E-cadherin loss and vimentin gain at the IF, with the various parameters or the risk score. INTERPRETATION & CONCLUSIONS: The present study suggests that the cells at IF may metastasize even without a gain in vimentin expression (without classical EMT), as cohesive clusters showing incomplete EMT (E-cadh-/Vim-).


Asunto(s)
Cadherinas , Carcinoma de Células Escamosas , Transición Epitelial-Mesenquimal , Neoplasias de Cabeza y Cuello , Vimentina , Antígenos CD , Biomarcadores de Tumor/genética , Cadherinas/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/genética , Humanos , Pronóstico , Vimentina/genética
8.
Am J Otolaryngol ; 42(4): 102978, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33621762

RESUMEN

BACKGROUND AND OBJECTIVES: Butterfly cartilage myringoplasty has been widely practiced over two decades due to its simplicity and feasibility. The present study is aimed to compare the efficacy of endoscopic versus microscopic transcanal inlay butterfly cartilage myringoplasty. SUBJECTS AND METHODS: In this randomised control trial, fifty patients with small to medium sized perforation were included. The first group underwent butterfly cartilage myringoplasty using endoscope and the second group using microscope and, outcomes were compared. RESULTS: Graft success rates in the endoscopic group was 96% ±â€¯4% and in the microscopic group was 92% ±â€¯8%. The improvement in the Air-Bone Gap was 11.00 ±â€¯7.21 dB in the endoscopic group and 10.8 ±â€¯7.59 dB in the microscopic group. The difference was not statistically significant. CONCLUSIONS: The overall success rates and hearing outcomes were similar in the endoscopic and microscopic group with added advantages of less pain, shorter operative time and better field of vision in the endoscopic group.


Asunto(s)
Cartílago Auricular/cirugía , Endoscopía/métodos , Microscopía , Microcirugia/métodos , Miringoplastia/métodos , Perforación de la Membrana Timpánica/cirugía , Adulto , Femenino , Audición , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Resultado del Tratamiento , Perforación de la Membrana Timpánica/patología , Perforación de la Membrana Timpánica/fisiopatología
9.
Chemistry ; 26(50): 11431-11434, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32428330

RESUMEN

Benzimidazolium hydrogen carbonate salts have been shown to act as N-heterocyclic carbene precursors, which can remove oxide from copper oxide surfaces and functionalize the resulting metallic surfaces in a single pot. Both the surfaces and the etching products were fully characterized by spectroscopic methods. Analysis of surfaces before and after NHC treatment by X-ray photoelectron spectroscopy demonstrates the complete removal of copper(II) oxide. By using 13 C-labelling, we determined that the products of this transformation include a cyclic urea, a ring-opened formamide and a bis-carbene copper(I) complex. These results illustrate the potential of NHCs to functionalize a much broader class of metals, including those prone to oxidation, greatly facilitating the preparation of NHC-based films on metals other than gold.

10.
Physiol Mol Biol Plants ; 26(5): 921-929, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32377042

RESUMEN

In order to dissect the adaptation response of maize to heat-stress, we characterized and juxtaposed different physio-biochemical parameters for two contrasting genotypes, namely DTPYC9F119 (heat-stress tolerant) and K64R (heat-stress susceptible) under 6 days heat treatment (38/28 °C). Chlorophyll a and b content was found to be reduced under high temperature in both the genotypes, but, it was reduced more prominently in the susceptible genotype (K64R). Net photosynthetic rate was significantly reduced under high temperature in K64R but this reduction was relatively lower in case of DTPYC9F119. Stomatal conductance was increased under stress treatment in both the genotypes but the rate of increase was lower in tolerant one (DTPYC9F119). Activity of anti-oxidant enzymes (viz. catalase, peroxidase and superoxide dismutase) and their gene expression was increased in both the genotypes under heat-stress condition. Thus, the heat-stress tolerant genotype has evolved some strategies like modulation of anti-oxidant gene expression, lower transpiration rate, lower increase of internal CO2 concentration which could make sustain a basic level of photosynthesis even under high temperature stress, etc. that may contribute to its tolerance trait.

11.
J Biol Chem ; 293(34): 13073-13089, 2018 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-29929978

RESUMEN

Toll-like receptors (TLRs) are a family of pattern-recognition receptors involved in innate immunity. Previous studies have shown that TLR2 inhibition protects the heart from acute stress, including myocardial infarction and doxorubicin-induced cardiotoxicity in animal models. However, the role of TLR2 in the development of aging-associated heart failure is not known. In this work, we studied aging-associated changes in structure and function of TLR2-deficient mice hearts. Whereas young TLR2-KO mice did not develop marked cardiac dysfunction, 8- and 12-month-old TLR2-KO mice exhibited spontaneous adverse cardiac remodeling and cardiac dysfunction in an age-dependent manner. The hearts of the 8-month-old TLR2-KO mice had increased fibrosis, cell death, and reactivation of fetal genes. Moreover, TLR2-KO hearts displayed reduced infiltration by macrophages, increased numbers of myofibroblasts and atrophic cardiomyocytes, and higher levels of the atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Mechanistically, TLR2 deficiency impaired the PI3K/Akt signaling pathway, leading to hyperactivation of the transcription factor Forkhead box protein O1 (FoxO1) and, in turn, to elevated expression of FoxO target genes involved in the regulation of muscle wasting and cell death. AS1842856-mediated chemical inhibition of FoxO1 reduced the expression of the atrophy-related ubiquitin ligases and significantly reversed the adverse cardiac remodeling while improving the contractile functions in the TLR2-KO mice. Interestingly, TLR2 levels decreased in hearts of older mice, and the activation of TLR1/2 signaling improved cardiac functions in these mice. These findings suggest that TLR2 signaling is essential for protecting the heart against aging-associated adverse remodeling and contractile dysfunction in mice.


Asunto(s)
Envejecimiento/patología , Proteína Forkhead Box O1/metabolismo , Regulación de la Expresión Génica , Cardiopatías/etiología , Miocitos Cardíacos/patología , Receptor Toll-Like 2/fisiología , Envejecimiento/metabolismo , Animales , Células Cultivadas , Proteína Forkhead Box O1/genética , Cardiopatías/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal
12.
J Immunol ; 198(8): 3296-3306, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28298524

RESUMEN

The p38 MAPK family is composed of four kinases of which p38α/MAPK14 is the major proinflammatory member. These kinases contribute to many inflammatory diseases, but the currently available p38 catalytic inhibitors (e.g., SB203580) are poorly effective and cause toxicity. We reasoned that the failure of catalytic p38 inhibitors may derive from their activity against noninflammatory p38 isoforms (e.g., p38ß/MAPK11) and loss of all p38α-dependent responses, including anti-inflammatory, counterregulatory responses via mitogen- and stress-activated kinase (MSK) 1/2 and Smad3. We used computer-aided drug design to target small molecules to a pocket near the p38α glutamate-aspartate (ED) substrate-docking site rather than the catalytic site, the sequence of which had only modest homology among p38 isoforms. We identified a lead compound, UM101, that was at least as effective as SB203580 in stabilizing endothelial barrier function, reducing inflammation, and mitigating LPS-induced mouse lung injury. Differential scanning fluorimetry and saturation transfer difference-nuclear magnetic resonance demonstrated specific binding of UM101 to the computer-aided drug design-targeted pockets in p38α but not p38ß. RNA sequencing analysis of TNF-α-stimulated gene expression revealed that UM101 inhibited only 28 of 61 SB203580-inhibited genes and 7 of 15 SB203580-inhibited transcription factors, but spared the anti-inflammatory MSK1/2 pathway. We provide proof of principle that small molecules that target the ED substrate-docking site may exert anti-inflammatory effects similar to the catalytic p38 inhibitors, but their isoform specificity and substrate selectivity may confer inherent advantages over catalytic inhibitors for treating inflammatory diseases.


Asunto(s)
Antiinflamatorios/farmacología , Diseño Asistido por Computadora , Células Endoteliales/efectos de los fármacos , Proteína Quinasa 14 Activada por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Lesión Pulmonar Aguda/patología , Animales , Modelos Animales de Enfermedad , Diseño de Fármacos , Humanos , Ratones , Modelos Moleculares
13.
Orbit ; 38(4): 331-334, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30142013

RESUMEN

Tuberculosis is an airborne communicable disease primarily affecting lungs. Primary tuberculosis of the lacrimal sac is very rare. A 15-year-old girl presented with bilateral epiphora for 8 months. Examination revealed bilateral nasolacrimal duct obstruction. During dacryocystorhinostomy, bone over lacrimal sac was found partially eroded. Lacrimal sac was found filled with caseous white material. Biopsy from the lacrimal sac revealed tubercular granulomas. Patient improved after anti-tubercular therapy. Abbreviations: PCR: polymerase chain reaction; NAAT: nucleic acid amplification test.


Asunto(s)
Dacriocistitis/diagnóstico , Obstrucción del Conducto Lagrimal/diagnóstico , Conducto Nasolagrimal/patología , Tuberculosis Ocular/diagnóstico , Adolescente , Antituberculosos/uso terapéutico , Biopsia , Sedimentación Sanguínea , Enfermedad Crónica , Dacriocistitis/microbiología , Dacriocistitis/terapia , Dacriocistorrinostomía , Quimioterapia Combinada , Femenino , Humanos , Obstrucción del Conducto Lagrimal/microbiología , Obstrucción del Conducto Lagrimal/terapia , Mycobacterium tuberculosis/aislamiento & purificación , Conducto Nasolagrimal/efectos de los fármacos , Conducto Nasolagrimal/microbiología , Conducto Nasolagrimal/cirugía , Prueba de Tuberculina , Tuberculosis Ocular/microbiología , Tuberculosis Ocular/terapia
14.
Pol J Radiol ; 84: e598-e615, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32082459

RESUMEN

Temporomandibular joint disorders are a common cause of chronic musculoskeletal pain worldwide. Among these, internal disc derangement is the most frequent type of disorder. Internal derangement is defined as an abnormal positional and functional relationship between the disc and articulating surfaces. Common clinical symptoms include pain and clicking. Imaging plays a key role in diagnosing temporomandibular joint disorders. It is important for the radiologist to detect early imaging signs of internal derangement, thereby avoiding the evolution of this condition to degenerative joint disease. The aim of this article is to familiarise the reader with the spectrum of imaging findings that are encountered at different stages of the disease.

15.
Int J Hyperthermia ; 34(1): 1-10, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28540808

RESUMEN

BACKGROUND: As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (i) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (ii) HSF1 is activated at febrile temperatures (38-41 °C) and (iii) hypothermia (32 °C) activates and hyperthermia (39.5 °C) reduces expression of a subset of miRNAs that target protein kinase-Cα (PKCα) and enhance proliferation. METHODS: We analysed the effect of hypo- and hyperthermia exposure on Wnt signalling by exposing human small airway epithelial cells (SAECs) and HEK293T cells to 32, 37 or 39.5 °C for 24 h, then analysing Wnt-3a-induced epithelial-mesenchymal transition (EMT) gene expression by qRT-PCR and TOPFlash reporter plasmid activity. Effects of miRNA mimics and inhibitors and the HSF1 inhibitor, KNK437, were evaluated. RESULTS: Exposure to 39.5 °C for 24 h increased subsequent Wnt-3a-induced EMT gene expression in SAECs and Wnt-3a-induced TOPFlash activity in HEK293T cells. Increased Wnt responsiveness was associated with HSF1 activation and blocked by KNK437. Overexpressing temperature-responsive miRNA mimics reduced Wnt responsiveness in 39.5 °C-exposed HEK293T cells, but inhibitors of the same miRNAs failed to restore Wnt responsiveness in 32 °C-exposed HEK293T cells. CONCLUSIONS: Wnt responsiveness, including expression of genes associated with EMT, increases after exposure to febrile-range temperature through an HSF1-dependent mechanism that is independent of previously identified temperature-dependent miRNAs. This process may be relevant to febrile fibrosing lung diseases, including the fibroproliferative phase of acute respiratory distress syndrome (ARDS) and exacerbations of idiopathic pulmonary fibrosis (IPF).


Asunto(s)
Transición Epitelial-Mesenquimal/fisiología , Epitelio/metabolismo , Fiebre/genética , Fiebre/fisiopatología , Expresión Génica/genética , Pulmón/metabolismo , Adulto , Humanos , Masculino , Transducción de Señal
16.
Physiol Mol Biol Plants ; 24(2): 175-183, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29515313

RESUMEN

Maize is an important crop for billions of people as food, feed, and industrial raw material. It is a prime driver of the global agricultural economy as well as the livelihoods of millions of farmers. Genetic interventions, such as breeding, hybridization and transgenesis have led to increased productivity of this crop in the last 100 years. The technique of genome editing is the latest advancement in genetics. Genome editing can be used for targeted deletions, additions, and corrections in the genome, all aimed at genetic enhancement of crops. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 9 (CRISPR/Cas9) system is a recent genome editing technique that is considered simple, precise, robust and the most revolutionary. This review summarizes the current state of the art and predicts future directions in the use of the CRISPR/Cas9 tool in maize crop improvement.

17.
RNA ; 21(7): 1261-73, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26018549

RESUMEN

Previous studies have revealed that clinically relevant changes in temperature modify clinically relevant gene expression profiles through transcriptional regulation. Temperature dependence of post-transcriptional regulation, specifically, through expression of miRNAs has been less studied. We comprehensively analyzed the effect of 24 h exposure to 32°C or 39.5°C on miRNA expression profile in primary cultured human small airway epithelial cells (hSAECs) and its impact on expression of a targeted protein, protein kinase C α (PKCα). Using microarray, and solution hybridization-based nCounter assays, with confirmation by quantitative RT-PCR, we found significant temperature-dependent changes in expression level of only five mature human miRNAs, representing only 1% of detected miRNAs. Four of these five miRNAs are the less abundant passenger (star) strands. They exhibited a similar pattern of increased expression at 32°C and reduced expression at 39.5°C relative to 37°C. As PKCα mRNA has multiple potential binding sites for three of these miRNAs, we analyzed PKCα protein expression in HEK 293T cells and hSAECs. PKCα protein levels were lowest at 32°C and highest at 39.5°C and specific miRNA inhibitors reduced these effects. Finally, we analyzed cell-cycle progression in hSAECs and found 32°C cells exhibited the greatest G1 to S transition, a process known to be inhibited by PKCα, and the effect was mitigated by specific miRNA inhibitors. These results demonstrate that exposure to clinically relevant hypothermia or hyperthermia modifies expression of a narrow subset of miRNAs and impacts expression of at least one signaling protein involved in multiple important cellular processes.


Asunto(s)
Calor , MicroARNs/metabolismo , Humanos , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa
18.
Angew Chem Int Ed Engl ; 56(43): 13288-13292, 2017 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-28837256

RESUMEN

Homochirality in peptides is crucial in sustaining "like-like" intermolecular interactions that allow the formation of assemblies and aggregates and is ultimately responsible for the resulting material properties. With the help of a series of stereoisomers of the tripeptide F-F-L, we demonstrate the critical role that peptide stereochemistry plays in the self-assembly of peptides, guided by molecular recognition, and for self-sorting. Homochiral self-assemblies are thermally and mechanically more robust compared to heterochiral self-assemblies. Morphological studies of the multicomponent peptide systems showed that aggregates formed from homochiral peptides possessed a uniform nano-fibrous structure, whereas heterochiral systems resulted in self-sorted systems with a heterogeneous morphology. In essence, homochiral peptides form the stronger aggregates, which may be one of reasons why homochirality is preferred in living systems.


Asunto(s)
Péptidos/metabolismo , Compuestos Ferrosos/química , Geles/química , Metalocenos/química , Microscopía Electrónica de Transmisión , Resonancia Magnética Nuclear Biomolecular , Péptidos/química , Transición de Fase , Estereoisomerismo , Temperatura de Transición
19.
Am J Physiol Lung Cell Mol Physiol ; 311(5): L941-L955, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27638903

RESUMEN

We previously showed that coincident exposure to heat shock (HS; 42°C for 2 h) and TNF-α synergistically induces apoptosis in mouse lung epithelium. We extended this work by analyzing HS effects on human lung epithelial responses to clinically relevant injury. Cotreatment with TNF-α and HS induced little caspase-3 and poly(ADP-ribose) polymerase cleavage in human small airway epithelial cells, A549 cells, and BEAS2B cells. Scratch wound closure rates almost doubled when A549 and BEAS2B cells and air-liquid interface cultures of human bronchial epithelial cells were heat shocked immediately after wounding. Microarray, qRT-PCR, and immunoblotting showed fibroblast growth factor 1 (FGF1) to be synergistically induced by HS and wounding. Enhanced FGF1 expression in HS/wounded A549 was blocked by inhibitors of p38 MAPK (SB203580) or HS factor (HSF)-1 (KNK-437) and in HSF1 knockout BEAS2B cells. PCR demonstrated FGF1 to be expressed from the two most distal promoters in wounded/HS cells. Wound closure in HS A549 and BEAS2B cells was reduced by FGF receptor-1/3 inhibition (SU-5402) or FGF1 depletion. Exogenous FGF1 accelerated A549 wound closure in the absence but not presence of HS. In the presence of exogenous FGF1, HS slowed wound closure, suggesting that it increases FGF1 expression but impairs FGF1-stimulated wound closure. Frozen sections from normal and idiopathic pulmonary fibrosis (IPF) lung were analyzed for FGF1 and HSP70 by immunofluorescence confocal microscopy and qRT-PCR. FGF1 and HSP70 mRNA levels were 7.5- and 5.9-fold higher in IPF than normal lung, and the proteins colocalized to fibroblastic foci in IPF lung. We conclude that HS signaling may have an important impact on gene expression contributing to lung injury, healing, and fibrosis.


Asunto(s)
Epitelio/metabolismo , Epitelio/patología , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Respuesta al Choque Térmico , Lesión Pulmonar/patología , Animales , Apoptosis/genética , Sitios de Unión , Línea Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Factor 1 de Crecimiento de Fibroblastos/genética , Regulación de la Expresión Génica , Proteínas HSP70 de Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico , Respuesta al Choque Térmico/genética , Humanos , Fibrosis Pulmonar Idiopática/genética , Pulmón/metabolismo , Pulmón/patología , Lesión Pulmonar/genética , Ratones , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cicatrización de Heridas/genética
20.
Org Biomol Chem ; 14(4): 1359-62, 2016 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-26660647

RESUMEN

This manuscript describes the surface immobilization of a light-harvesting complex to prescribed locations directed by the sequence-selective recognition of duplex DNA. An engineered light-harvesting complex (RC-LH1) derived from Rhodopseudomonas (Rps.) palustris containing the zinc finger (ZF) domain zif268 was prepared. The zif268 domain directed the binding of zfRC-LH1 to target double-stranded DNA sequences both in solution and when immobilized on lithographically defined micro-patterns. Excitation energy transfer from the carotenoids to the bacteriochlorophyll pigments within zfRC-LH1 confirmed that the functional and structural integrity of the complex is retained after surface immobilization.


Asunto(s)
ADN/metabolismo , Complejos de Proteína Captadores de Luz/metabolismo , Rhodopseudomonas/química , Transferencia de Energía , Complejos de Proteína Captadores de Luz/química , Modelos Moleculares , Fotosíntesis , Rhodopseudomonas/metabolismo
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