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In response to oxidative stress cells reprogram gene expression to enhance levels of antioxidant enzymes and promote survival. In Saccharomyces cerevisiae the polysome-interacting La-related proteins (LARPs) Slf1 and Sro9 aid adaptation of protein synthesis during stress by undetermined means. To gain insight in their mechanisms of action in stress responses, we determined LARP mRNA binding positions in stressed and unstressed cells. Both proteins bind within coding regions of stress-regulated antioxidant enzyme and other highly translated mRNAs in both optimal and stressed conditions. LARP interaction sites are framed and enriched with ribosome footprints suggesting ribosome-LARP-mRNA complexes are identified. Although stress-induced translation of antioxidant enzyme mRNAs is attenuated in slf1Δ, these mRNAs remain on polysomes. Focusing further on Slf1, we find it binds to both monosomes and disomes following RNase treatment. slf1Δ reduces disome enrichment during stress and alters programmed ribosome frameshifting rates. We propose that Slf1 is a ribosome-associated translational modulator that stabilises stalled/collided ribosomes, prevents ribosome frameshifting and so promotes translation of a set of highly-translated mRNAs that together facilitate cell survival and adaptation to stress.
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Antioxidantes , Biossíntese de Proteínas , Saccharomyces cerevisiae , Antioxidantes/metabolismo , Estresse Oxidativo/genética , Ribossomos/genética , Ribossomos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMO
Electrochemical impedance spectroscopy (EIS) has been extensively used for the detailed investigation and understanding of the plethora of physical properties of variegated electrochemical and solid-state systems. Over the past few years, EIS has revealed many significant findings in hybrid halide perovskite (HHP)-based optoelectronic devices too. Photoinduced ion-migration, negative capacitance, anomalous mid-frequency capacitance, hysteresis, and instability to heat, light and moisture in HHP-based devices are among the few issues addressed by the IS technique. However, performing EIS in perovskite devices presents new challenges related to multilayer solid-state device geometry and complicated material properties. The ions in the perovskite behave in a specified manner, which is dictated by the energy-levels of the transport layer. Electronic-ionic coupling is one of the major challenges to understand ion transport kinetics in solid-state devices. In this work, we have performed impedance measurements in both solid-state (S-S) and liquid-electrolyte (L-E) device geometry to unfold the effect of charge transport layers on the ac ionic conductivity in perovskite materials. We have modelled the impedance spectra using the electrical equivalent circuit (EEC) and compared the behaviour of ions in different controlling environments. It was concluded that the AC as well as dc ionic conductivity and the accumulation of ions in the perovskite material are highly influenced by the nature of the interface in different device geometry. Charge accumulation in the S-S device gives rise to large polarisation, thereby negative capacitance or any inductive loop can be observed in the Nyquist plot while in the L-E device the presence of an electric double layer at the perovskite/electrolyte interface reduces the surface polarisation effect. Ionic conductivity is hopping limited in the low field regime and diffusion limited in the high field regime in the S-S device. Moreover, the perovskite/electrolyte based devices are promising candidates for electrolyte gated field-effect transistors, perovskite-based supercapacitors and electrochemical cells for water splitting or CO2 reduction.
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Ion migration in hybrid halide perovskites is ubiquitous in all conditions. However, the ionic conductivity can be manipulated by changing the material composition, operating temperature, light illumination, and applied bias as well as the nature of the interfaces of the devices. There have been various reports on electron ion coupling in hybrid perovskite semiconductors which gives rise to anomalous charge transport behavior in these devices under an applied bias. In this investigation, we have synthesized a mixture of 2D/3D perovskites by incorporating sulphur-doped graphene quantum dots (SGQDs) and demonstrated that the optical and electrical properties of the hybrid system can be tuned by controlling the ion conductivity through the active layer. It has been observed that the recombination resistance in undoped CH3NH3PbBr3 perovskites follows an anomalous behavior while the doped CH3NH3PbBr3 perovskite shows a monotonic increase with increasing applied bias due to reduced ionic conductivity. SGQDs at the grain boundaries of 2D/3D perovskites prohibit ion migration through the active layer, and therefore the electronic-ionic coupling is reduced. This results in increased recombination resistance with increasing applied bias.
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Charge transport through lead trihalide based perovskites is more complex than through any other semiconducting materials due to their mixed electronic-ionic conductivity as well as ambipolarity. Here we have investigated charge transport through a perovskite/electrolyte interface using electrochemical impedance spectroscopy (EIS) under illumination and applied bias conditions. Similar trends in EIS were observed with positively biased as well as negatively biased working electrodes, indicating ambipolar charge transport through the perovskite layer. Ionic conductivity upon photo-illumination plays a significant role in modulating charge transport at the interface by creating an additional built-in field which flips its polarity at a moderate applied bias voltage. Therefore, anomalous charge transport resistance is observed under illumination at around 400 to 600 mV applied bias. Electric field induced UV-Vis absorption spectroscopy shows a decrease in absorption when both positive and negative bias voltages are applied to a perovskite coated ITO working electrode, indicating the occurrence of excited state charge transfer at the electrolyte interface. Two distinct electric field induced bleaching bands have been observed at around 480 nm and 750 nm, similar to the two photobleaching bands due to the dual nature of the excited states in lead halide perovskites.
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BACKGROUND: Periodontal diseases are of microbial etiology and are globally causing loss of teeth in adult population. Many severe oral diseases have been recently associated to Herpes viruses, of which Epstein Barr Virus (EBV) and human cytomegalovirus (HCMV) have been indicated in the etiology of periodontal diseases. AIM: The purpose of the study was to compare the effect of EBV in different types of periodontal diseases namely acute gingivitis, chronic gingivitis, acute and chronic, localized and generalized aggressive (juvenile) periodontitis and apical periodontitis. MATERIAL AND METHOD: 70 individuals were included in this study. Supragingival plaque and plaque from two deepest sites of the periodontal pockets were collected then stored at 70° c and prepared for nucleic acid extraction. For EBV detection, DNA were extracted from the plaque samples with the QIAamp DNA mini kit. Q-PCR was performed by targeting the non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene using Corbett Research 6000 Q-PCR instrument and Rotor gene 6000 software. RESULTS: Overall prevalence of EBV in the disease group was 60% (27/45 patients) as compared to only 8% (4/25 people) in the normal population. The mean copy number of EBV DNA was found to be significantly higher in periodontitis (2234 ± 1811.34) when compared to gingivitis (554 ± 537.64, p = .001) and normal patients (370 ± 161.03, p < .001). CONCLUSION: Here, we found that the prevalence of EBV as well as copy number of EBV was significantly higher in periodontitis patients as compared to gingivitis patients or normal population.
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Gengivite , Herpesvirus Humano 4 , Periodontite , Adulto , Citomegalovirus , Gengivite/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Bolsa Periodontal , Periodontite/virologiaRESUMO
Context: Loneliness is a psychosocial problem that can affect anyone at any age in any circumstances, but it has become a serious issue of concern among the elderly. Aim: The present study aims to examine the overall and state and union-territories-wise prevalence of loneliness among India's elderly population and exploring the correlates of loneliness in old age. Method: The study is based on secondary data from Longitudinal Ageing Study in India (LASI) Wave-1 (2017-2018) data collected from a total of 30,394 older adults aged 60 and above excluding missing responses. Frequent loneliness was measured using a single question asking how often you feel alone. Statistical Analysis Used: Descriptive statistics, the Chi-square test, and bivariate logistic regression were used to meet the objectives. The statistical significance was set at <0.05. Results: 13.4% of elderly reported frequent loneliness. The prevalence of loneliness among elderly was found to be maximum in Andaman and Nicobar Island and minimum in Tripura. Age, current marital status, region, religion, MPCE quintile, number of chronic conditions, number of Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) difficulties, involvement in physical activity, involvement in yoga/meditation, number of social networks, participation in social activities, and involvement in leisure activities like reading books, watching TV, or using computer were found to be significantly associated with loneliness. Conclusion: Not being in a marital union, having more than two chronic conditions, more than two ADL and IADL difficulties, being physically inactive, non-involvement in Yoga/Meditation, and small social network are associated with higher loneliness.
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OBJECTIVE: Hypospadias is a common congenital abnormality that has been increasing in prevalence over the last decades. Historically, 46, XY patients with severe hypospadias and descended scrotal testes at birth have frequently lacked a genetic diagnosis. Platforms for molecular genetic testing have become more readily available and can offer an insight into underlying genetic causes of severe hypospadias. The goal of this study was to define the anatomical characteristics of severe hypospadias that can accurately define patients with 46, XY severe hypospadias and determine the practical utility of performing molecular genetic testing in this group of patients. METHODS: Patients who met the criteria for 46, XY severe hypospadias were offered a molecular genetic work-up in consultation with pediatric genetics. Patients were identified through chart review. Data extracted included karyotype, hypospadias phenotype including stretched penile length at diagnosis, age at genetic diagnosis, molecular genetic testing, pathogenic gene variant(s), gender identity, and clinical course. All patients underwent clinical genetic testing via 46, XY Disorders of Sexual Development (DSD) panels offered by Invitae®, GeneDx®, or Blueprint Genetics®. RESULTS: Of the 14 patients that underwent genetic testing, there were 5 previously published and 3 novel pathogenic or likely pathogenic variants in genes associated with 46, XY severe hypospadias (Table). Pathogenic variants were identified in AR (3), SRD5A2 [1], NR5A1 [2], WT1 [1], and ARTX [1]. Two patients had a variant of unknown significance, one in FREM2 and another in CEP41. Four had negative gene panels. The patient with the WT1 pathogenic variant was subsequently found to have developed a Wilms tumor and the patients with NR5A1 pathogenic variants are now undergoing adrenal insufficiency surveillance. DISCUSSION/CONCLUSION: Patients with 46,XY severe hypospadias and descended testes in the scrotum at birth can benefit from molecular genetic testing as their underlying disorders may reveal pathogenic variants that could have potentially life-altering consequences and change surveillance and monitoring.
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Hipospadia , Neoplasias Renais , Tumor de Wilms , Humanos , Masculino , Feminino , Hipospadia/diagnóstico , Hipospadia/genética , Mutação , Identidade de Gênero , Testes Genéticos , Neoplasias Renais/genética , Proteínas/genética , Proteínas de Membrana/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genéticaRESUMO
The numerous assorted accounts of the fundamental questions of ion migration in hybrid perovskites are making the picture further intricate. The review of photo-induced ion migration using small perturbation frequency domain techniques other than impedance spectroscopy is more crucial now. Herein, we probe into this by investigating perovskite-electrolyte (Pe-E) and polymer-aqueous electrolyte (Po-aqE) interface using intensity modulated photocurrent spectroscopy (IMPS) in addition to photoelectrochemical impedance spectroscopy (PEIS). We reported that the electronic-ionic interaction in hybrid perovskites including the low-frequency ion/charge transfer and recombination kinetics at the interface leads to the spiral feature in IMPS Nyquist plot of perovskite-based devices. This spiral trajectory for the perovskite-electrolyte interface depicts three distinct ion kinetics going on at the different time scales which can be more easily unveiled by IMPS rather than PEIS. Hence, IMPS is a promising alternative to PEIS. We used Peter's method of interpretation of IMPS plot in photoelectrochemistry to estimate charge transfer efficiency [Formula: see text] from the Rate Constant Model. The [Formula: see text] at low-frequency for Pe-E interface exceeds unity due to ion migration induced modified potential across the perovskite active layer. Hence, ion migration and mixed electronic-ionic conductivity of hybrid perovskites are responsible for the extraordinary properties of this material.
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Remarkable improvement in the perovskite solar cell efficiency from 3.8% in 2009 to 25.5% today has not been a cakewalk. The credit goes to various device fabrication and designing techniques employed by the researchers worldwide. Even after tremendous research in the field, phenomena such as ion migration, phase segregation, and spectral instability are not clearly understood to date. One of the widely used techniques for the mitigation of ion migration is to reduce the defect density by fabricating the high-quality perovskite thin films. Therefore, understanding and controlling the perovskite crystallization and growth have become inevitably crucial. Some of the latest methods attracting attention are controlling perovskite film morphology by modulating the coating substrate temperature, antisolvent treatment, and solvent engineering. Here, the latest techniques of morphology optimization are discussed, focusing on the process of nucleation and growth. It can be noted that during the process of nucleation, the supersaturation stage can be induced faster by modifying the chemical potential of the system. The tailoring of Gibbs free energy and, hence, the chemical potential using the highly utilized techniques is summarized in this minireview. The thermodynamics of the crystal growth, design, and orientation by changing several parameters is highlighted.
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Type 1 diabetes is associated with complications affecting muscle and bone, with diabetic bone disease and diabetic myopathy becoming increasingly reported in the past few decades. This review is aimed at succinctly reviewing the literature on the current knowledge regarding these increasingly identified and possibly interconnected complications on the musculoskeletal system. Furthermore, this review summarizes several nonmechanical factors that could be mediating the development and progression of premature musculoskeletal decline in this population and discusses preventative measures to reduce the burden of diabetes on the musculoskeletal system.
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Doenças Ósseas , Diabetes Mellitus Tipo 1 , Doenças Musculares , Doenças Ósseas/complicações , Osso e Ossos , Diabetes Mellitus Tipo 1/complicações , Humanos , Músculos , Doenças Musculares/etiologiaRESUMO
Perovskite light-emitting diodes have almost reached the threshold for potential commercialization within a few years of research. However, there are still some unsolved puzzles such as large ideality factor and the presence of large negative capacitance especially at the low-frequency regime yet to be addressed. Here, we have fabricated a methylammonium lead tri-bromide perovskite n-i-p structure for light-emitting diodes from a smooth and textured emissive layer and demonstrated for the first time that these two factors are strongly dependent on the perovskite film morphology. Bias-dependent capacitance measurement also reveals the transition between negative to positive capacitance in textured films at the low-frequency regime. We have observed an anomalous capacitive behavior at the mid-frequency regime in smooth perovskite films but not in textured films. The relatively large ideality factor and anomalous capacitive behavior observed in perovskite light-emitting diodes are due to the presence of strong coupling between ions and electrons near the electrode interface. Therefore, the ideality factor and anomalous capacitance at the mid-frequency regime can be decreased by minimizing electronic-ionic coupling in textured perovskite films, while light outcoupling can be improved significantly.
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It is known from earlier studies that the heat shock (HS) response in Malpighian tubules (MTs) of Drosophila larvae is different from that in other tissues because instead of the Hsp70 and other common heat shock proteins, Hsp64 and certain other new proteins are induced immediately after HS. In the present study, we examined the kinetics of the synthesis of Hsp70 and Hsp64 immediately after HS and during recovery from HS by 35S-methionine labeling and Western blotting. In addition, we also examined the transcriptional activity of hsp70 genes in larval MT cells at different times after HS by in situ hybridization and Northern blotting. The HS-induced synthesis of Hsp64 ceased by 1 hour of recovery from the HS when synthesis of the Hsp70 commenced. Our results revealed that the induced synthesis of Hsp64 immediately after HS was dependent on new transcription. Although the levels of Hsp70 in MT cells rapidly increased after its synthesis began during recovery, the levels of Hsp64 remained unaltered irrespective of its new synthesis occurring during or after HS. Inhibition of new Hsp64 synthesis by transcriptional or translational inhibitors also did not affect the total amount of this protein in MTs. The Hsp64 polypeptides synthesized in response to HS are degraded rapidly. Apparently, the cells in MTs maintain a balance between new synthesis of Hsp64 and its turnover so that under all conditions a more or less constant level of this protein is maintained. Although the Hsp70 synthesis started only after 1 hour of recovery, the hsp70 genes were transcriptionally activated immediately after HS and they continued to transcribe till at least 4 hours after the HS. The hsp70 transcripts in MT cells that recovered for 2 hours or longer did not contain the 3' untranslated regions (UTRs), which may allow their longer stability and translatability at normal temperature. Synthesis of Hsp70 during recovery period was dependent on continuing transcription. Assessment of the beta-galactosidase activity in 2 transgenic lines carrying the LacZ reporter gene under hsp70 promoter and different lengths of the 5'UTR suggested that the delayed translation of hsp70 transcripts in MTs is probably regulated by some elements in the 5'UTR.
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Proteínas de Drosophila/biossíntese , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico/biossíntese , Resposta ao Choque Térmico/fisiologia , Larva/metabolismo , Túbulos de Malpighi/metabolismo , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Genes Reporter/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Cinética , Larva/citologia , Túbulos de Malpighi/citologia , Dados de Sequência Molecular , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/fisiologia , Inibidores da Síntese de Proteínas/farmacologia , Homologia de Sequência de Aminoácidos , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , beta-Galactosidase/genéticaRESUMO
BACKGROUND/AIM: Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley. PATIENTS AND METHODS: The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant. RESULTS: The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea. CONCLUSION: These results suggest that variation in PLCE1 may be associated with GC risk in Kashmir Valley.
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DNA de Neoplasias/genética , Predisposição Genética para Doença , Fosfoinositídeo Fosfolipase C/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Feminino , Seguimentos , Genótipo , Haplótipos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fosfoinositídeo Fosfolipase C/metabolismo , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/epidemiologiaRESUMO
Context. Usnea ghattensis G. Awasthi (Usneaceae) endemic fruticose lichen found growing luxuriantly in Northern Western Ghats of India, it also contains Usnic acid as a major chemical and tested against some human pathogenic bacteria. Objective. To explore antimicrobial properties of Usnea ghattensis against some human pathogenic bacteria. Materials and Methods. The lichen was extracted in acetone, methanol, and ethanol. In vitro antimicrobial activity was tested initially by Kirby-Bauer technique of disc diffusion method and was confirmed by minimum inhibitory concentration using Broth microdilution method according to the NCCLS guidelines. Results. Ethanol extract was most effective against Bacillus cereus and Pseudomonas aeruginosa with a zone of inhibition 29.8 ± 0.6 mm and 12.3 ± 0.5 mm diameters at a concentration of 0.2 mg/mL. Acetone and methanol extract demonstrated almost similar activity against Staphylococcus aureus and the zone of inhibition was 24.6 ± 0.5 and 24.7 ± 0.4 mm. Only methanol extract was showing activity against Streptococcus faecalis with a 13.5 ± 0.8 mm zone. MIC value noted against Staphylococcus aureus and Streptococcus faecalis was 6.25 µ g/mL and 25 µ g/mL, whereas against Bacillus cereus and Pseudomonas aeruginosa, MIC calculated was 3.125 µ g/mL and 200 µ g/mL, respectively. Conclusion. The present study demonstrates the relatively higher activity of this lichen against not only gram (+) but significantly also against gram (-) bacteria. This indicates that this lichen might be a rich source of effective antimicrobial agents.
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BACKGROUND: Overuse of blood products is common, but prior efforts to improve transfusion decisions have met with limited success. STUDY DESIGN AND METHODS: This study examines transfusion practices before and after a conventional educational intervention followed by a randomized controlled trial of a decision support (DS) intervention with computerized physician order entry (CPOE) for red blood cell, platelet, and fresh-frozen plasma orders. The study was conducted in an academic medical center between April 2003 and June 2004. Orders originating from units not using CPOE with DS (e.g., the emergency department) were excluded. Junior housestaff were randomly assigned into a control group and an intervention group who received DS for transfusion orders. Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree. Chart reviews assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders. The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate. RESULTS: The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and randomly assigned junior housestaff were 72.6 percent (2154/2967) and 71.9 percent (1259/1752) and improved after conventional education to 63.8 percent (1699/2663; p < 0.0001) and 63.3 percent (1263/1996; p < 0.0001), respectively. The percentage of inappropriate orders in the DS intervention group continued to improve (59.6%, 804/1350; p < 0.0001). Physicians accepted 14 percent (133/939) of new DS-recommended orders, especially recommendations to increase transfusion doses (73%). CONCLUSIONS: Education and computerized DS both decreased the percentage of inappropriate transfusions, although the residual amount of inappropriate transfusions remained high.