Zinc finger (ZF) protein Kaiso mediates the transcription repression by binding with methylated DNA through ZF domains and recruiting the nuclear receptor co-repressor (NCoR) complex via its BTB/POZ ...(Broad complex, Tramtrack, Bric-à-brac/Pox virus and Zinc finger) domain. Investigating the molecular mechanism of interactions of Kaiso with the NCoR protein is essential to understand the role of Kaiso in the transcription repression process. A detailed study on the binding mechanism of Kaiso with the NCoR complex is still lacking due to the intrinsically disordered nature of the NCoR protein. In this work, we employed molecular modeling, docking, and molecular dynamics simulation to investigate the formation of the Kaiso–NCoR complex. We modeled the complex and predicted the key interacting residues as well as the interfacial interaction involved in the binding of Kaiso with NCoR. Our results reveal that various inter-protein interactions, such as salt bridges, hydrogen bonds, and hydrophobic interactions between the interfacial residues, play crucial roles in forming and stabilizing the Kaiso–NCoR complex. Our investigations provide molecular insights into how Kaiso recruits the NCoR complex via its BTB/POZ domain and mediates transcription repression.
Methyl CpG binding proteins (MBPs) are transcription factors that recognize the methylated CpG sites in DNA and mediate the DNA methylation signal into various downstream cellular processes. The C2H2 ...zinc finger (ZF) protein, Kaiso, also an MBP, preferentially binds to two symmetrically methylated CpG sites in DNA sequences via C-terminal C2H2 ZF domains and mediates the transcription regulation process. Investigation of the molecular mechanism of the recognition of methylated DNA (meDNA) by Kaiso is important to understand how this protein reads and translates this methylation signal into downstream transcription outcomes. Despite previous studies in Kaiso-meDNA interactions, detailed structural investigations on the sequence-specific interaction of Kaiso with the meDNA sequence are still lacking. In this work, we used molecular modeling and molecular dynamics (MD) simulation-based computational approaches to investigate the recognition of various methylated DNA sequences by Kaiso. Our MD simulation results show that the Kaiso-meDNA interaction is sequence specific. The recognition of meDNA by Kaiso is enhanced in the MeECad sequence compared to the MeCG2 sequence. Compared to the 5′-flanking T/A pair in MeCG2, both MeCG2_mutCG and MeECad sequences show that a C/G base pair allows GLU535 of Kaiso to preferably recognize and bind the core mCpG site. The core mCGmCG site is crucial for the recognition process and formation of a stable complex. Our results reveal that the 5′-flanking nucleotides are also important for the enhanced binding and recognition of methylated sites.
The emergence of new variants of the novel coronavirus SARS-CoV-2 with increased infectivity, superior virulence, high transmissibility, and unmatched immune escape has demonstrated the adaptability ...and evolutionary fitness of the virus. The subject of relative order of the binding affinity of SARS-CoV-2 variants with the human ACE2 (hACE2) receptor is hotly debated and its resolution has implications for drug design and development. In this work, we have investigated the energetics of the binding of receptor binding domain (RBD) of SARS-CoV-2 variants of concern (VOCs): Beta (B.1.351), Delta (B.1.617.2), Omicron (B.1.1.529), variant of interest (VOI): Kappa (B.1.617.1), and Delta Plus (B.1.617.2.1) variant with the human ACE2 receptor by using the umbrella sampling (US) method. Our work indicates that Delta and Delta Plus variants have greater values of the US binding free energy than Wild-type (WT), whereas Beta, Kappa, and Omicron variants have lower values. Further analysis of hydrogen bonding, salt bridges, non-bonded interaction energy, and contact surface area at the RBD-hACE2 interface establish Delta as the variant with the highest binding affinity among these variants.
Around the world, cereal grains provide a significant source of dietary nutrients. Since prehistoric times, cereal-based food products have formed the foundation of the human diet. Fermented foods ...made from cereals account for a significant portion of the calorie intake in developing nations. Worldwide dietary recommendations are urging the consumption of whole grains due to mounting evidence that these grains and food products made from them can improve health in ways other than just giving energy and minerals. The creation of novel food items with qualities that improve health will be aided by the understanding gained from the functional qualities of the many chemical components found in whole grains.
Therefore, the main aim of this study is to illuminate the varied application of cereals like rice, maize, wheat, and barley in preparing a wide range of delightful dishes like (Aila, Dhindo, Yomari, Selroti, Chatamari, Khurma, Chiura, and Lakhamari) which holds immense significance in shaping the cultural identity of the Newari community. In this study, the nutritional advantages of cereals highlight their crucial role in maintaining the health and well-being of the Newar community. Cereals are abundant in essential vitamins, fibers, minerals, and carbohydrates as a fundamental component of a well-balanced diet that promotes overall well-being
Abstract
SARS-CoV-2 virus is the serious health concern throughout the world. A comprehensive investigation of binding of SARS-CoV-2 active site with host receptor protein hACE2 is important in ...designing effective drugs. In the present work, the major amino acid binding partners between the virus CTD and host receptor have been studied and are compared with SARS-CoV RBD binding with hACE2. Our investigation show that some unique hydrogen bond pairs which were not reported in previous work. Along with hydrogen bonding, salt-bridges, hydrophobic interactions and contributions of electrostatic and van der Waals contacts play significant role in binding mechanism. The binding affinity of SARS-CoV-2 CTD/hACE2 is greater than SARS-CoV RBD/hACE2. This outcome is also verified from the free energy estimation by using umbrella sampling.
A wound gets infected when the organism gets invaded through the breached skin, proliferated and production of various enzymes, toxins, etc. In order to treat the wound infection, antibiotic ...susceptibility pattern of organism should be determined before the prescription of the medicine. The present study was conducted from September 2017 to March 2018 with an aim to determine antibiotic susceptibility pattern of Staphylococcus aureus identified from the pus/wound swab among the patients visiting the International Friendship Children's Hospital, Kathmandu, Nepal. Total 270 sample were processed, isolated and identified using standard microbiological procedure and biochemical test. Antibiotic susceptibility test was carried out by using Modified Kirby Bauer's Disc Diffusion Method. Out of total sample, 51.48% (139) showed growth. The growth distribution was found to be high in out-patient department 84.9% (118) than in-patient department 15.1% (21). Among 139 positive growth, 83.5% were gram positive and 16.5% were gram negative. All together 12 different organisms were identified, among which S. aureus was found to be predominant organism 105 (75.5%). S. aureus was found to be sensitive towards Linezolid followed by Doxycycline whereas it was found resistant towards Ciprofloxacin. Among S. aureus identified, 50% were Multidrug resistant (MDR) S. aureus and 55% were Methicillin resistance S. aureus (MRSA). MRSA was found to be sensitive towards Linezolid followed by Doxycycline and resistant towards Ciprofloxacin. The association between MDR and MRSA was found positively significant (i.e. p-value = 0.000). All strains of S. aureus were found to be sensitive towards Vancomycin. 22.86% were double disk diffusion test (D-test) positive. The prevalence of D-test was found to be high in MRSA (75%). The relationship between D-test and MRSA was found to be significantly correlated with each other (r = 0.39). Linezolid, Chloramphenicol, Vancomycin and Doxycycline is a drug of a choice for both S. aureus and MRSA infection.
This cross-sectional study was conducted to describe the socio-demographic characteristics, assess the utilization of HIV testing and counselling services, and to explore the reasons for the ...non-utilization of HIV testing and counselling services among the key populations at the Bhutanese refugee camps in eastern Nepal.
The HIV testing and counselling services are utilized by less than a third (29%) of the key population among the Bhutanese Refugees. The prime source of information about the HIV testing and counselling sites has been health workers followed by peer/outreach educators and neighbors. Common self-reported barriers for utilization of HIV testing and counselling services by the Bhutanese refugees were self-perceived stigma about HIV, the fear of being discriminated and the lack of knowledge about HIV testing and counselling services. There is a need to analyze the gap between availability and utilization through more qualitative approaches in order to identify interventions to increase the uptake of the HIV testing and counselling services.
Apple production is a vital sector of agriculture in Nepal, significantly impacting local livelihoods and the regional economy. This study, conducted in Jumla District, Nepal, from January to July ...2022, aims to comprehensively assess apple production, including its existing conditions, economic implications, marketing and challenges. The research hypothesizes that while apple production in Jumla District contributes significantly to the local economy, it faces challenges related to pest and disease management, marketing, and adoption of modern practices. Using Statistical Package for Social Science (SPSS), descriptive statistics were computed based on data collected from a sample of 80 respondents selected through simple random sampling. The result revealed that agriculture constituted the primary source of income for 73.75% of the population, with an average landholding size of 0.3428 ha and an apple-growing land area of 0.3164 ha. Income from apple production, along with vegetables and fruits, was a major income source. The average annual sales of apple production were 7.291 t/ha. Labor costs accounted for 45.67% of the total cost of apple production, with an average total production cost of NPR 238,097.2 and average gross returns of NPR 485,500. Apple productivity was 9.71 t/ha, demonstrating its economic viability with net returns of NPR 247,402.80 per ha and benefit cost ratio of 2.039. However, the study found that farm produce only sufficed for 6-9 months, with pest and disease incidence and marketing issues as major challenges. Interventions should address pest and disease management, marketing strategies, and modern practices adoption to enhance sustainable and profitable apple production in Jumla. Efforts to extend farm produce sufficiency should also be explored, highlighting apple production's potential and the need for targeted support to overcome challenges and foster sector development.
PDF
