Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to ...form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease. In mice with high fat diet (HFD)-induced obesity, JBSNF-000088 treatment caused a reduction in body weight, improved insulin sensitivity and normalized glucose tolerance to the level of lean control mice. These effects were not seen in NNMT knockout mice on HFD, confirming specificity of JBSNF-000088. The compound also improved glucose handling in ob/ob and db/db mice albeit to a lesser extent and in the absence of weight loss. Co-crystal structure analysis revealed the presence of the N-methylated product of JBSNF-000088 bound to the NNMT protein. The N-methylated product was also detected in the plasma of mice treated with JBSNF-000088. Hence, JBSNF-000088 may act as a slow-turnover substrate analog, driving the observed metabolic benefits.
This manuscript presents a thorough review of unitized regenerative fuel cells (URFCs) and their importance in Remote Area Power Supply (RAPS). In RAPS systems that utilize solar and hydrogen power, ...which typically include photovoltaic modules, a proton exchange membrane (PEM) electrolyzer, hydrogen gas storage, and PEM fuel cells, the cost of these systems is currently higher compared to conventional RAPS systems that employ diesel generators or batteries. URFCs offer a potential solution to reduce the expenses of solar hydrogen renewable energy systems in RAPS by combining the functionalities of the electrolyzer and fuel cell into a single unit, thereby eliminating the need to purchase separate and costly electrolyzer and fuel cell units. URFCs are particularly well-suited for RAPS applications because the electrolyzer and fuel cell do not need to operate simultaneously. In electrolyzer mode, URFCs function similarly to stand-alone electrolyzers. However, in fuel cell mode, the performance of URFCs is inferior to that of stand-alone fuel cells. The presented review summarizes the past, present, and future of URFCs with details on the operating modes of URFCs, limitations and technical challenges, and applications. Solar hydrogen renewable energy applications in RAPS and challenges facing solar hydrogen renewable energy in the RAPS is discussed in detail.
This study comprises the combined effect of piezocatalytic and photocatalytic activity to obtain improved piezo-photocatalytic dye degradation efficiency in visible light. Single-phase Bi2VO5.5 ...powder was prepared through solid-state synthesis at 750 °C in 8 h. Time-dependent photocurrent responses were conducted to understand the phenomenon of charge carrier transport in visible light. Bi2VO5.5 powder sample demonstrated high photocatalytic efficiency and good reusability possessing a bandgap value of 2.13 eV. Bi2VO5.5 powder sample attained ∼70% and ∼58% degradation efficiency during photocatalysis and piezocatalysis respectively. The piezo-photocatalytic methylene blue dye attained ∼82% degradation efficiency in 240 min duration of visible light illumination. The scavenger test depicted holes (h+) as the principal active species in the piezo-photocatalytic dye degradation. There incurred no severe loss in photocatalytic efficiency even after 4 cycles which proclaims the reusability of the Bi2VO5.5 powder sample. A study on the kinetic rate constant with varying dye concentrations was conducted. With varied dye concentration of 5, 10, 15 mg/L, the kinetic rate constant obtained was 0.00528, 0.0030, and 0.00125 min−1, respectively. Germination index was found through a phytotoxicity test using vigna radiata seeds. Here visible light along with mechanical energy has been used to achieve higher MB dye degradation efficiency through piezo-photocatalysis.
Despite radiation forming the curative backbone of over 50% of malignancies, there are no genomically-driven radiosensitizers for clinical use. Herein we perform in vivo shRNA screening to identify ...targets generally associated with radiation response as well as those exhibiting a genomic dependency. This identifies the histone acetyltransferases CREBBP/EP300 as a target for radiosensitization in combination with radiation in cognate mutant tumors. Further in vitro and in vivo studies confirm this phenomenon to be due to repression of homologous recombination following DNA damage and reproducible using chemical inhibition of histone acetyltransferase (HAT), but not bromodomain function. Selected mutations in CREBBP lead to a hyperacetylated state that increases CBP and BRCA1 acetylation, representing a gain of function targeted by HAT inhibition. Additionally, mutations in CREBBP/EP300 are associated with recurrence following radiation in squamous cell carcinoma cohorts. These findings provide both a mechanism of resistance and the potential for genomically-driven treatment.
Abstract
Autism spectrum disorder (ASD) and Alzheimer’s disease (AD) are two different neurological disorders that share common clinical features, such as language impairment, executive functions, ...and motor problems. A genetic convergence has been proposed as well. However, the molecular mechanisms of these pathologies are still not well understood. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions. Previously, we have shown that NO and SNO are involved in the InsG3680(+/+) ASD and P301S AD mouse models. Here, we performed large-scale computational biology analysis of the SNO-proteome followed by biochemical validation to decipher the shared mechanisms between the pathologies. This analysis pointed to the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway as one of the shared molecular mechanisms. Activation of mTOR in the cortex of both mouse models was confirmed by western blots that showed increased phosphorylation of RPS6, a major substrate of mTORC1. Other molecular alterations affected by SNO and shared between the two mouse models, such as synaptic-associated processes, PKA signaling, and cytoskeleton-related processes were also detected. This is the first study to decipher the SNO-related shared mechanisms between
SHANK3
and
MAPT
mutations. Understanding the involvement of SNO in neurological disorders and its intersection between ASD and AD might help developing an effective novel therapy for both neuropathologies.
Household headship with decision-making power may have a positive influence on life satisfaction in older adults. This study examines the associations of several types of household headship with life ...satisfaction among older adults in India.
The study utilized the data from the Longitudinal Ageing Study in India (2017-18). The effective sample size for the study was 31,464 adults aged 60 years or older. Ordered logistic regression model was employed to find the association of life satisfaction with household headship status after adjusting for selected socioeconomic and demographic factors.
It was found that about 1.3% of older male and 1.5% of older females had nominal headship status in their household. Higher percentage of older males (42%) and females (48.3%) who had nominal headship status had low life satisfaction. In multivariable analysis, older adults who practiced nominal headship had significantly higher odds of low life satisfaction in reference to older adults who practiced functional headship Adjusted odds ratio (AOR): 1.87; confidence interval (CI): 1.45,2.42. Interaction model reveals that older men who practised nominal headship had significantly higher odds of low life satisfaction in reference to older men who practised functional headship AOR: 2.34; CI: 1.59,3.45. Similarly, older women who practised nominal headship had 55% significantly higher likelihood to have low life satisfaction in reference to older men who practised functional headship AOR: 1.55; CI: 1.09, 2.18.
The recognition of older individuals as active agents of the households they belong to, and giving them the value they deserve may help boosting their mental well-being. As a direct driver of subjective well-being, headship status and decision making power deserve a more prominent role and future studies are required on the mechanisms of functional and nominal headship statuses that have impact on successful aging.
Background: Rorschach test has been considered a well-known and most widely used projective test for the assessment of personality and diagnostic evaluation in various psychiatric disorders. ...Schizophrenia is considered to be the major psychiatric illness characterized by gross distortion of reality, the disorganization and fragmentation of perception, thought, emotion, and withdrawal from social interaction. Rorschach provides both specific and general knowledge about the different areas of personality functioning, such as coping style, emotions, managing stress, mediation, ideation, self-perception, and interpersonal relationships along with correlating with the psychopathology of the schizophrenia patients. Aim: The aim of the present study is to assess the relationship between Rorschach response pattern different symptoms in schizophrenia patients. Methodology: After having informed consent, 100 patients of schizophrenia group were included as per the International Classification of Diseases 10th Revision Diagnostic Criteria for Research (ICD-10 DCR) criteria. Information about sociodemographic data and clinical details was collected using the sociodemographic and clinical data sheet from the drawn sample. For the assessment of symptoms of schizophrenia patients, Scale for the Assessment of Positive Symptom and Scale for the Assessment of Negative Symptom have been used. After that Rorschach test was administered individually to all the participants to assess the personality structure of each schizophrenia patients. Results: The results showed that there is a significant positive and negative correlation among positive, negative schizophrenia symptoms, and different Rorschach variables. Conclusion: Schizophrenia patients having positive and negative symptoms would be giving Rorschach variables indicative of moderate level of cognitive distortions, poorly controlled and disorganized affect, less conventional form of responses, poor perception and loss with reality, poor interpersonal relationships, presence of anxiety, and aggression.
•Melatonin is an imperative signalling molecule produced endogenously in plants.•The exogenous application of melatonin has proven to be beneficial for plants against multiple abiotic stresses.•Seed ...priming with beneficial elements is an easy methodfor enhancing seed germination and plant vigor under normal as well as stress conditions.•This review discusses the mechanisms involved in beneficial effects of seed priming with melatonin under stress conditions.
Melatonin is an indolic compound derived from tryptophan and has an important role in the general processes of plants including germination, photosynthesis, circadian rhythms, flowering, senescence, and alleviating stress. Integrating melatonin application to agronomical practices reportedly provides numerous benefits. More particularly seed priming with melatonin has been shown to improve seed germination as well as improve resilience under adverse conditions. This review discusses in detail the studies showing elevated drought, salinity, heat, and heavy metal stress resistance as a result of melatonin seed priming. Differences in transcript and protein levels have been observed in plants/seedlings germinated via melatonin primed seeds, providing the foundation for further studies. Many pieces of research have also shown primed seeds possess a greater content of osmoprotectants, upregulation of energy-producing pathways, and an increase in protein content, which may lead to enhancing abiotic stress response in plants. The primary function attributed to melatonin is reactive oxygen species scavenging, which consequently leads to enhancing plant stress resistance against multiple stresses. Here, we highlight all the potential mechanisms involved in melatonin meditated induction of abiotic stress tolerance. We review the reports emphasizing the role played by melatonin under stress conditions in multiple crop species, the modification at genome, ribonucleic acid, and protein level involved, and the underlying mechanisms. Information provided here will be helpful to better understand the melatonin role in plants and its efficient exploration in the cropping system.
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