Introduction: The safety and therapeutic effects of Gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking.
Methods: This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with major neurocognitive disorder due to Alzheimer's disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12-24.
The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II.
View Article and Find Full Text PDFIn this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor.
View Article and Find Full Text PDFA common mRNA modification is 5-methylcytosine (mC), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of mC and impaired SRSF2 mC binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in mC recognition and the impact of the prevalent leukemia-associated mutation SRSF2.
View Article and Find Full Text PDFThe most common and challenging chief complaint in the emergency department is abdominal pain. Intussusception, although rare in adults, is an important etiology to consider. The diagnosis is often delayed because of the nonspecific symptoms, especially in adults.
View Article and Find Full Text PDFBRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638-5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses expression of TATDN2, a poorly characterized member of the TATD nuclease family.
View Article and Find Full Text PDFIn diffuse large B-cell lymphoma (DLBCL), the transcription factor IRF8 is the target of a series of potentially oncogenic events, including, chromosomal translocation, focal amplification, and super-enhancer perturbations. IRF8 is also frequently mutant in DLBCL, but how these variants contribute to lymphomagenesis is unknown. We modeled IRF8 mutations in DLBCL and found that they did not meaningfully impact cell fitness.
View Article and Find Full Text PDFPlant nucleotide-binding leucine-rich repeat (NLRs) immune receptors directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley (Hordeum vulgare) NLR gene Mildew locus a (Mla) has undergone functional diversification, and the proteins encoded by different Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f.
View Article and Find Full Text PDFThe nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the of adenosine (A) in RNA to mA and in ssDNA to 6mA. mA marks are prevalent in eukaryotic mRNAs and lncRNAs and modulate their stability and fate in a context-dependent manner. The cytoplasmic METTL3 can act as a mA reader.
View Article and Find Full Text PDFInt J Environ Res Public Health
May 2023
The global economy has suffered losses as a result of the COVID-19 epidemic. Accurate and effective predictive models are necessary for the governance and readiness of the healthcare system and its resources and, ultimately, for the prevention of the spread of illness. The primary objective of the project is to build a robust, universal method for predicting COVID-19-positive cases.
View Article and Find Full Text PDFMonkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were reported globally, with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern.
View Article and Find Full Text PDFUnlabelled: Monkeypox virus (MPXV) infection in humans are historically restricted to endemic regions in Africa. However, in 2022, an alarming number of MPXV cases have been reported globally with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern.
View Article and Find Full Text PDFWith >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases.
View Article and Find Full Text PDFA free space optical module is used in laser communication to transport a signal from the transmitter to the receiver. Free Space Optical Communication (FSOC) is a Line of Sight connectivity that sends a highly narrow beamwidth. FSOC provides high bandwidth and data rates greater than 10 Gbps.
View Article and Find Full Text PDFPatients from countries, endemic with tuberculosis, who present with febrile lymphadenopathy refractory to first line antibiotics are often empirically treated for extra-pulmonary tuberculosis. However, Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitis, a self-limiting and benign condition, presents with similar clinical symptoms. We present an adolescent with febrile lymphadenopathy, who was initially treated for tubercular lymphadenopathy, before a diagnosis of KFD was made.
View Article and Find Full Text PDFBackground/aims: The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity.
Methods: A cross-sectional study was conducted between June 2021 and December 2021.
Background/aims: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India.
Methods: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India.
Fungal interactions with plant roots, either beneficial or detrimental, have a crucial impact on agriculture and ecosystems. The cosmopolitan plant pathogen Fusarium oxysporum (Fo) provokes vascular wilts in more than a hundred different crops. Isolates of this fungus exhibit host-specific pathogenicity, which is conferred by lineage-specific Secreted In Xylem (SIX) effectors encoded on accessory genomic regions.
View Article and Find Full Text PDFThe major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive.
View Article and Find Full Text PDFMethyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from -adenosyl-L-methionine to amino group of adenosine bases in RNA (mA) and DNA (mdA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear.
View Article and Find Full Text PDFhas emerged globally as a multi-drug resistant yeast and is commonly associated with nosocomial outbreaks in ICUs. We conducted a retrospective observational multicentre study to determine the epidemiology of infections, its management strategies, patient outcomes, and infection prevention and control practices across 10 centres from five countries. Significant risk factors for infection include the age group of 61-70 years (39%), recent history of ICU admission (63%), diabetes (63%), renal failure (52%), presence of CVC (91%) and previous history of antibiotic treatment (96%).
View Article and Find Full Text PDFPrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3'-terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti).
View Article and Find Full Text PDFThe SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1).
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