Publications by authors named "Shakya B"

Article Synopsis
  • The nuclear export receptor XPO1 is commonly overexpressed in cancer cells, leading to mislocalization of important proteins; the inhibitor selinexor reverses this effect by blocking XPO1-cargo binding.
  • Selinexor triggers the degradation of XPO1 through a specific mechanism involving the cullin-RING E3 ubiquitin ligase (CRL) system and its substrate receptor ASB8.
  • Research using cryogenic electron microscopy revealed that selinexor stabilizes XPO1 in a unique conformation, allowing ASB8 to bind effectively and facilitate ubiquitination, showcasing a new method of protein degradation that differs from previously known molecular glue strategies.
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Gene expression in response to environmental stimuli is dependent on nuclear localization of key signaling components, which can be tightly regulated by phosphorylation. This is exemplified by the phosphate-sensing transcription factor Pho4, which requires phosphorylation for nuclear export by the yeast exportin Msn5. Unlike the traditional hydrophobic nuclear export signal (NES) utilized by the Exportin-1/XPO1 system, cryogenic-electron microscopy structures reveal that Pho4 presents a novel, phosphorylated 35-residue NES that interacts with the concave surface of Msn5 through two Pho4 phospho-serines that align with two Msn5 basic patches, unveiling a previously unknown mechanism of phosphate-specific recognition.

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Article Synopsis
  • The study aimed to explore meniscal calcifications in individuals with and without knee osteoarthritis (OA), focusing on two types: basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP).
  • The researchers analyzed 82 meniscal samples from 41 subjects, comparing those with OA (who had knee replacements) to deceased donors without OA, using histological methods and Raman spectroscopy for detailed analysis.
  • Results showed that all OA participants had some calcifications, primarily BCP, while CPP was more common in donor samples, indicating that BCP may play a key role in the OA process deserving further study.
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The national-level land cover database is essential to sustainable landscape management, environmental protection, and food security. In Afghanistan, the existing national-level land cover data from 1972, 1993, and 2010 relied on satellite data from diverse sensors adopted three different land cover classification systems. This inconsistent land cover map across the various years leads to the challenge of assessing landscape changes that are crucial for management efforts.

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Ephedrine, metaraminol, epinephrine and maneuvers like carotid sinus stimulation used during intraoperative period have been postulated to cause temporary spasm of the coronary vessels leading to decrease supply to the myocardium and precipitating myocardial infraction in non-obstructive coronary arteries (MINOCA). As an anaesthesiologists, we should be aware that even a dose as small as 25 mcg epinephrine infiltrated along with local anaesthetic in the subcutaneous plane may be responsible for coronary vessel spasm and thus myocardial infraction in nonobstructive coronary arteries. We report a case of 45 years old female with papillary carcinoma of thyroid who developed features of non-ST elevation myocardial infarction 5 minutes after the subcutaneous infiltration of 5 ml of 2% Xylocaine with 1:200000 Epinephrine.

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Genetic code expansion (GCE) offers many exciting opportunities for the creation of synthetic organisms and for drug discovery methods that utilize in vitro translation. One type of GCE, sense codon reassignment (SCR), focuses on breaking the degeneracy of the 61 sense codons which encode for only 20 amino acids. SCR has great potential for genetic code expansion, but extensive SCR is limited by the post-transcriptional modifications on tRNAs and wobble reading of these tRNAs by the ribosome.

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Background: There are mainly two types of blood donor in Nepal i.e., Voluntary Non-Remunerated Donor and Replacement Donor.

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Objective: This study aimed to translate the DN4 questionnaire into Nepalese version and assess its psychometric properties: diagnostic accuracy, internal consistency, and test-retest reliability.

Methods: An observational study was conducted in a tertiary level teaching hospital of Kathmandu, Nepal. We included 166 patients with chronic pain visiting a pain clinic over a period of one year.

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Article Synopsis
  • Integrating ecosystem services into development strategies can enhance understanding of how nature benefits human societies, particularly in the biodiverse Hindu Kush Himalaya region, which is crucial for a significant portion of the global population.
  • The analysis shows that prioritizing relationships between ecosystems and socio-economic factors can help tackle challenges like poverty, cultural preservation, and holistic development within the area.
  • The Nature Futures Framework from the IPBES outlines three key pathways—Prevention, Restoration, and Development innovation—that promote sustainability by aligning societal values with ecosystem service management and policy decisions.
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Fungi are morphologically and ecologically diverse kingdom but less explored in the global perspective. This systematic review of mainly higher fungi (mushrooms) and lichenized fungi (lichens) was aimed to convey comprehensive knowledge on these understudied taxa, especially considering diversity, research trends, taxonomic/geographic knowledge gaps, and their contribution to ecosystem services. We investigated literature from the Far Eastern Himalayas and adjacent areas.

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Agents that suppress the toxic effect of arecoline (a chemical present in the Areca nut fruit) have become a need of the hour owing to its several harmful effects on human beings. Although some drug molecules have been developed for this purpose, yet, simple, easy to prepare, and economical molecules with remarkable potency are still a challenge to design. The present work thus becomes important as it involves the synthesis of a new charge transfer complex (CTC) material, which has, for the first time, been screened to investigate its effect on the toxic effects of arecoline.

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Background Musculoskeletal disorders (MSDs) and Computer vision syndrome (CVS) are workrelated health problems affecting people of working-age, which result in loss of productivity and quality of life. Objective To assess the prevalence of musculoskeletal disorders and computer vision syndrome and their association with quality of life among the banking staff of Nepal. Method A cross-sectional questionnaire survey was conducted among 207 banking staff of the banks of Kathmandu.

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The novel Mannich base benzimidazole derivative (), 1-((1H-benzo[d]imidazol-1-yl)(3-chlorophenyl)methyl)-3-phenylurea) has been designed and synthesized by reacting benzimidazole, 3-chloro benzaldehyde, and N-Phenyl urea. has been characterized by UV- Visible, FTIR, and H NMR. was explored to study the interaction with the most abundant blood protein which involved in the role of transport of molecules (drugs), human serum albumin (HSA).

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Background: The incidence of antibiotic resistance in commensal bacteria is increasing with the production of extended-spectrum beta-lactamase. Therefore, this study was conducted to understand the status of fecal carriage of such enzyme producing Escherichia coli among health science students of seven different faculties of Institute of Medicine, Tribhuvan University.

Methods: This was a cross-sectional study conducted over six months among the health science students.

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Background: Pregnant women with cardiac disease pose a unique challenge to both the anaesthesiologists and obstetrician because of high morbidity affecting the maternal and fetal outcomes. Our research aims to provide an overview of pregnant women with heart disease coming for delivery in Tribhuvan University Teaching Hospital over one year, the occurrence of adverse maternal and neonatal outcome (mortality and morbidity) and correlation of certain maternal factors associated with adverse outcome.

Methods: This is an observational cross-sectional study conducted in Tribhuvan University Teaching Hospital from 2075/11/01 to 2076/10/30 where data of pregnant women beyond 28 wks period of gestation with diagnosed cardiac disease was recorded from secondary sources.

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proteins are exported to the erythrocyte cytoplasm to create an environment that supports parasite replication. Although hundreds of proteins are predicted to be exported through export element (PEXEL)-dependent and -independent mechanisms, the functions of exported proteins are largely uncharacterized. In this study, we used a biochemical screening approach to identify putative exported proteins that bound to inside-out vesicles prepared from erythrocytes.

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The reprogramming of the genetic code through the introduction of noncanonical amino acids (ncAAs) has enabled exciting advances in synthetic biology and peptide drug discovery. Ribosomes that function with high efficiency and fidelity are necessary for all of these efforts, but for challenging ncAAs, the competing processes of near-cognate readthrough and peptidyl-tRNA dropoff can be issues. Here we uncover the surprising extent of these competing pathways in the PURE translation system using mRNAs encoding peptides with affinity tags at the N- and C-termini.

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Article Synopsis
  • The study examines the presence and reduction of SARS-CoV-2 in various water samples from two wastewater treatment plants in Nepal between July 2020 and February 2021, finding significant detection rates.
  • SARS-CoV-2 RNA was found in a high percentage of samples from wastewater treatment plants, river water, hospital wastewater, and sewer lines, indicating the biological treatments used are insufficient for complete RNA elimination.
  • The research suggests wastewater-based epidemiology (WBE) can be an effective tool for monitoring COVID-19 trends, especially in developing countries, despite some limitations in correlating RNA concentrations with new COVID-19 cases.
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The use of Fourier Transform Infrared (FTIR) microspectroscopy to study cancerous cells and tissues has gained popularity due to its ability to provide spatially resolved information at the molecular level. Transmission and transflection are the commonly used measurement modes for FTIR microspectroscopy, and the tissue samples measured in these modes are often paraffinized or deparaffinized. Previous studies have shown that variability in the spectra acquired using different measurement modes and sample processing methods affect the result of the analysis.

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Setting: Tribhuvan University Teaching Tertiary Care Hospital, Kathmandu, Nepal, May-October 2019.

Objective: 1) To describe the bacteriological profile, 2) to identify the antimicrobial resistance (AMR) pattern, and 3) to find the demographic characteristics associated with the presence of bacterial growth and multidrug resistance (MDR) in adult urine samples undergoing culture and drug susceptibility testing.

Design: This was a hospital-based, cross-sectional study using routine laboratory records.

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The mitochondrial antiviral signaling protein (MAVS) is part of the cell's innate immune mechanism of defense. MAVS mRNA is bicistronic and can give rise to a full length-MAVS and a shorter isoform termed miniMAVS. In response to viral infections, viral RNA can be sensed by the cytosolic RNA sensors retinoic acid-inducible gene I (RIG-I) and/or melanoma differentiation-associated protein 5 (MDA5) and activate NF-κB through interaction with MAVS.

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Biophysical separation promises label-free, less-invasive methods to manipulate the diverse properties of live cells, such as density, magnetic susceptibility, and morphological characteristics. However, some cellular changes are so minute that they are undetectable by current methods. We developed a multiparametric cell-separation approach to profile cells with simultaneously changing density and magnetic susceptibility.

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Invasion of human erythrocytes by the malaria parasite is a multi-step process. Previously, a forward genetic screen for host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization.

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Among skin cancers, melanoma is the lethal form and the leading cause of death in humans. Melanoma begins in melanocytes and is curable at early stages. Thus, early detection and evaluation of its metastatic potential are crucial for effective clinical intervention.

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