The functionalization of C-H bonds is one of the most challenging transformations in synthetic chemistry. In biology, these processes are well-known and are achieved with a variety of metalloenzymes, many of which contain a single metal center within their active sites. The most well studied are those with Fe centers, and the emerging experimental data show that high-valent iron oxido species are the intermediates responsible for cleaving the C-H bond.
View Article and Find Full Text PDFThe site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein-protein interactions both and . Herein, we engineer a bromodomain to introduce 4-benzoyl-L-phenylalanine (BzF) using amber suppressor mutagenesis without compromising its ability to recognize the acetylated histone proteins. We demonstrate the high crosslinking efficiency of the engineered reader towards the interacting partners and its suitability for profiling the transient bromodomain interactome.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2021
The oxidation of substrates via the cleavage of thermodynamically strong C-H bonds is an essential part of mammalian metabolism. These reactions are predominantly carried out by enzymes that produce high-valent metal-oxido species, which are directly responsible for cleaving the C-H bonds. While much is known about the identity of these transient intermediates, the mechanistic factors that enable metal-oxido species to accomplish such difficult reactions are still incomplete.
View Article and Find Full Text PDFBromodomains are evolutionarily conserved reader modules that recognize acetylated lysine residues on the histone tails to facilitate gene transcription. The bromodomain and PHD finger containing protein 3 (BRPF3) is a scaffolding protein that forms a tetrameric complex with HBO1 histone acetyltransferase (HAT) and two other subunits, which is known to regulate the HAT activity and substrate specificity. However, its molecular mechanism, histone ligands, and biological functions remain unknown.
View Article and Find Full Text PDFMigratory birds play a major role in spreading influenza viruses over long distances. We report highly pathogenic avian influenza A(H5N6) viruses in migratory and resident ducks in Bangladesh. The viruses were genetically similar to viruses detected in wild birds in China and Mongolia, suggesting migration-associated dissemination of these zoonotic pathogens.
View Article and Find Full Text PDFThe potential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) escape mutants is a threat to the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutation landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site.
View Article and Find Full Text PDFThe escalating rise in the population of multidrug-resistant (MDR) pathogens coupled with their biofilm forming ability has struck the global health as nightmare. Alongwith the threat of aforementioned menace, the sluggish development of new antibiotics and the continuous deterioration of the antibiotic pipeline has stimulated the scientific community toward the search of smart and innovative alternatives. In near future, membrane targeting antimicrobial polymers, inspired from antimicrobial peptides, can stand out significantly to combat against the MDR superbugs.
View Article and Find Full Text PDFJ Oral Maxillofac Pathol
May 2021
Angiomyxomas are a group of rare myxoid benign mesenchymal tumors prone to local recurrences. Two types of angiomyxomas are well recognized in the literature: superficial and aggressive angiomyxoma. Aggressive angiomyxomas are relatively uncommon, poorly circumscribed, locally infiltrative myofibroblastic tumors with a specific predilection for the perineal regions and exceedingly rare in the head and neck region.
View Article and Find Full Text PDFIndia came under the grip of the coronavirus disease-2019 (COVID-19) pandemic and is now seeing rising graph. Cancer patients are specially in the high-risk group because of their immunocompromised status on one hand and progressive disease on the other hand. Hence, cancer care facility needs to prepare a clear strategy to manage their space, staff and supplies so that optimum patient care can be continued in the face of COVID-19 pandemic.
View Article and Find Full Text PDFPancreatic cancer (PC) remains a major cause of cancer-related deaths primarily due to its inherent potential of therapy resistance. Checkpoint inhibitors have emerged as promising anti-cancer agents when used in combination with conventional anti-cancer therapies. Recent studies have highlighted a critical role of the Greatwall kinase (microtubule-associated serine/threonine-protein kinase-like (MASTL)) in promoting oncogenic malignancy and resistance to anti-cancer therapies; however, its role in PC remains unknown.
View Article and Find Full Text PDFThe microtubule is regarded as the key target for designing anticancer and neurotherapeutic drugs due to its functional importance in eukaryotic cells including neurons. The microtubule is a dynamic hollow polymer tube consisting of α,β-tubulin heterodimer. Polymerization of α,β-tubulin heterodimer resulted in microtubule formation.
View Article and Find Full Text PDFIatrogenic displacement of a tooth or tooth fragment is a rare but well-recognized complication that occurs during exodontia. The most common sites of dislodgment of a mandibular third molar fragment are the sublingual, submandibular, and pterygomandibular and lateral pharyngeal spaces. Removal of a displaced tooth from these spaces may be complex due to poor visualization and limited access.
View Article and Find Full Text PDFInfantile myofibromas (IM) are benign soft tissue lesions of childhood and represent a significant portion of the benign spectrum of fibroblastic-myofibroblastic tumors. Cytological diagnosis of these tumors can be challenging because of overlapping morphology and limited case report descriptions. We describe the cytological features and the cytological differential diagnoses.
View Article and Find Full Text PDFArtificial spin ice systems have seen burgeoning interest due to their intriguing physics and potential applications in reprogrammable memory, logic, and magnonics. Integration of artificial spin ice with functional magnonics is a relatively recent research direction, with a host of promising results. As the field progresses, direct in-depth comparisons of distinct artificial spin systems are crucial to advancing the field.
View Article and Find Full Text PDFBackground: Substance use disorders have become a widespread public health problem, especially in the northeastern states, and limited studies have been undertaken to reflect the picture of the same.
Aims: The aim of the study was to study the sociodemographic and clinical profile of drug treatment seekers attending a State Psychiatric Hospital and De-addiction Center of Northeastern India.
Materials And Methods: It was a cross-sectional hospital-based study conducted from October 2018 to August 2019.
Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis.
View Article and Find Full Text PDFThis review presents new findings on Wnt signaling in endometrial carcinoma and implications for possible future treatments. The Wnt proteins are essential mediators in cell signaling during vertebrate embryo development. Recent biochemical and genetic studies have provided significant insight into Wnt signaling, in particular in cell cycle regulation, inflammation, and cancer.
View Article and Find Full Text PDFUsing time-resolved magneto-optical Kerr effect (TR-MOKE) microscopy, we demonstrate surface-acoustic-wave (SAW) induced resonant amplification of intrinsic spin-wave (SW) modes, as well as generation of new extrinsic or driven modes at the SAW frequency, in a densely packed two-dimensional array of elliptical Co nanomagnets fabricated on a piezoelectric LiNbO substrate. This system can efficiently serve as a magnonic crystal (MC), where the intrinsic shape anisotropy and the strong inter-element magnetostatic interaction trigger the incoherent precession of the nanomagnets' magnetization in the absence of any bias magnetic field, giving rise to the 'intrinsic' SW modes. The magnetoelastic coupling leads to a rich variety of SW phenomena when the SAW is launched along the major axis of the nanomagnets, such as 4-7 times amplification of intrinsic modes (at 3, 4, 7 and 10 GHz) when the applied SAW frequencies are resonant with these frequencies, and the generation of new extrinsic modes at non-resonant SAW frequencies.
View Article and Find Full Text PDFA significant gap in the knowledge of zinc homeostasis exists for breast cancer cells. In this study, we investigated the transcriptomic response of the luminal breast cancer cells (MCF-7) to the exposure of extracellular zinc using next-generation RNA sequencing. The dataset was collected for three time points (T0, T30, and T120) in the time course of zinc treatment, which revealed the dramatic increase, up to 869-fold, of the gene expression for metallothioneins (MT1B, MT1F, MT1X, and MT2A) and the zinc exporter ZnT1 (SLC30A1) at T30, continuingly through to T120.
View Article and Find Full Text PDFDespite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs.
View Article and Find Full Text PDFCrit Rev Food Sci Nutr
February 2022
Zinc present in the islet cells of the pancreas is crucial for the synthesis, storage, and secretion of insulin. The excretion of large amounts of zinc from the body is reported in diabetic situations. Zinc depletion and increased oxidative stress have a major impact on the pathogenesis of diabetic complications.
View Article and Find Full Text PDFCoronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses.
View Article and Find Full Text PDFIn the present investigation, a novel Fe-TiO composite was fabricated by mixing fly ash (FA), foundry sand (FS), and bentonite clay for the degradation of paracetamol (PCM). This composite acts as a surface for immobilizing the TiO catalyst (using the dip-coating method) besides facilitating the leaching of iron (FA and FS) in acidic conditions. Leached iron (in the form of Fe(II), Fe(III), and total iron) promotes the photo-Fenton (with the addition of HO in the system) while the surface-active TiO layer leads to photocatalysis, thus leading to in situ dual process combining photocatalysis and photo-Fenton in one system.
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