This review provides a comprehensive survey relating to the synthesis and biological applications of pyrazolines and related heterocycles in the last five years (2007–2011). These compounds are ...usually prepared from the cyclization of chalcones with hydrazine and its derivatives under the alcoholic conditions. The major incentive behind the synthesis of these compounds was the immense biological activities associated to these heterocyclic derivatives. The aim of this review is to find out different methods for the synthesis of pyrazoline derivatives.
The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We ...characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.
The Polycomb-like protein PHF19/PCL3 associates with PRC2 and mediates its recruitment to chromatin in embryonic stem cells. PHF19 is also overexpressed in many cancers. However, neither PHF19 ...targets nor misregulated pathways involving PHF19 are known. Here, we investigate the role of PHF19 in prostate cancer cells. We find that PHF19 interacts with PRC2 and binds to PRC2 targets on chromatin. PHF19 target genes are involved in proliferation, differentiation, angiogenesis, and extracellular matrix organization. Depletion of PHF19 triggers an increase in MTF2/PCL2 chromatin recruitment, with a genome-wide gain in PRC2 occupancy and H3K27me3 deposition. Transcriptome analysis shows that PHF19 loss promotes deregulation of key genes involved in growth, metastasis, invasion, and of factors that stimulate blood vessels formation. Consistent with this,
silencing reduces cell proliferation, while promotes invasive growth and angiogenesis. Our findings reveal a role for PHF19 in controlling the balance between cell proliferation and invasiveness in prostate cancer.
Although telemedicine has been used spottily in Indian health care so far, the 2020 Covid-19 pandemic provided the nation's health systems an unprecedented opportunity to make a concerted effort to ...increase access and coverage. Health-care providers can incorporate telemedicine systems to reduce doctor-patient visits and help in breaking the chain of transmission of infections. Anticipating the increased need of telemedicine by health-care providers, the Medical Council of India released practice guidelines in March 2020. In this article, the literature pertinent to telemedicine and its applications with special reference to recently released practice guidelines were reviewed and summarized in a historical and current context. Telemedicine is bound to grow and be adopted by more health-care practitioners and patients in a wide variety of forms due to ease and availability. At the same time, it cannot replace in-person consultation or emergency medicine.
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant ...disorder characterized by genetically driven heterotopic ossification, and in 20–25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. We highlight our current knowledge of ACVR1 in both diseases, and then describe the growing opportunities and barriers to effectively investigate ACVR1 in DIPG. Importantly, learning from other seemingly unrelated diseases harboring similar mutations may uncover novel mechanisms or processes for future investigation.
•Fibrodysplasia Ossificans Progressiva (FOP) and Diffuse Intrinsic Pontine Gliomas (DIPGs) share ACVR1 mutations.•While ACVR1 mutations underlie FOP, their functional role in DIPG remains unclear.•Developmental biology provides a context of shared biology among diverse diseases.•Intersecting Mendelian disorders and cancer genomics can elucidate potential cancer genes.
Despite public/private/third sector organisations creating and demonstrating the social value of their interventions, they face challenges in understanding and executing the process of social value ...creation, due to both the lack of definition and theoretically embedded explanatory models of social value. This article seeks to fill this gap by defining social value and identifying the process involved in social value creation from a Weberian standpoint of social action, class and power. Nine resource capitals were identified that contribute to the creation of social value in society: social, ethical, cultural, human/intellectual, physical, economic/financial, environmental/natural, religious, and political. The research utilises Q-methodology to develop a typology of social value and semi-structured interviews to understand the process of social value creation. The results reveal four-types of social value: action-driven, outcomes-driven, sustainability-driven and pluralism-driven, which can be derived through individual/collaborative and resource capitals-driven processes. An integrated framework for social value creation, embedded within a Weberian theoretical framework, is presented to assist policy-makers to commission social value, and public/private/third sector organisations to deliver social value.
Abstract
Dysembryoplastic neuroepithelial tumors (DNT) lacking key diagnostic criteria are challenging to diagnose and sometimes fall into the broader category of mixed neuronal-glial tumors (MNGT) ...or the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY). We examined 41 patients with DNT, MNGT, or PLNTY for histologic features, genomic findings, and progression-free survival (PFS). Genomic analysis included sequence and copy number variants and RNA-sequencing. Classic DNT (n = 26) was compared with those with diffuse growth without cortical nodules (n = 15), 6 of which exhibited impressive CD34 staining classifying them as PLNTY. Genomic analysis was complete in 33, with sequence alterations recurrently identified in BRAF, FGFR1, NF1, and PDGFRA, as well as 7 fusion genes involving FGFR2, FGFR1, NTRK2, and BRAF. Genetic alterations did not distinguish between MNGTs, DNTs, or PLNTYs; however, FGFR1 alterations were confined to DNT, and PLNTYs contained BRAF V600E or FGFR2 fusion genes. Analysis of PFS showed no significant difference by histology or genetic alteration; however, numbers were small and follow-up time short. Further molecular characterization of a PLNTY-related gene fusion, FGFR2-CTNNA3, demonstrated oncogenic potential via MAPK/PI3K/mTOR pathway activation. Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations.
Photochemical reaction is a chemical reaction initiated by the absorption of energy in the form of light resulting in different types of reaction. Chromones, bischromones and anthraquinones are the ...bichromophoric molecules which contain the carbonyl group and double bond in conjugation. Photochemical reactions of these compounds result in the formation of such molecules which are not obtained via conventional methods. This review article describes the photochemical transformations of chromones, bischromones and anthraquinone derivatives and here main emphasis has been laid upon the intramolecular photochemical H-abstraction reactions that provide many exotic heterocyclics as the final photoproducts.
This review article describes the survey of literature regarding the variety of synthetic methods of 1,3,4-thiadiazoline and related compounds in the last seven years (2004–2010). The aim of the ...review is to find out different methods for the synthesis of thiadiazolines. These heterocyclics are majorly obtained from the cyclization reactions of thiosemicarbazone under the various conditions. From the literature studies it was found that major importance was given to their pharmaceutical significance i.e., regarding their biological activity against different fungal and bacterial strains.
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