がんモデルマウスにおけるリンパ節標的治療の前臨床的評価

Tohoku University博士（医工学）要約のみthesi

Characterization of Protein Residue Surface Accessibility Using Sequence Homology

Residues present on the surface of the proteins are involved in a number of functions, especially in ligand-protein interactions, that are important for drug design. The residues present in the core of the protein provide stability to the protein and help in maintaining protein structure. Hence, there is a need for a binary characterization of protein residues based on their surface accessibility (surface accessible or buried). Such a classification can aid in the directed study of either residue type. A number of methods for the prediction of surface accessible protein residues have been proposed in the past. However, most of these methods are computationally complex and time consuming. In this thesis, we propose a simple method based on protein sequence homology parameters for the binary classification of protein residues as surface accessible or “buried”. To aid in the classification of protein residues, we chose three highly conservative homology-based parameter filter thresholds. The filter thresholds predicted and evaluated are: residue sequence entropy ≥0:15, fraction of strongly hydrophobic residues \u3c0:5 and fraction of small residues \u3c 0:15. The application of these filter thresholds to the residues, is expected to predict the “buried residues” with a better percentage accuracy than that of the surface accessible residues. These filter thresholds were selected from the frequency distributions and the aggregate correlation plots of the various homology-based parameters. An analysis of the plots suggests the presence of a strongly hydrophobic core between packing density 14 –22 where the presence of strongly hydrophobic residues is maximum and the presence of small and non-strongly hydrophobic residues is minimum. However, the densest portion of the protein (density 26 – 35) is indicated to be occupied by a combination of small and non-strongly hydrophobic residues with a negligible presence of strongly hydrophobic residues

A Comparative Study of Approved Drugs for SARS-CoV-2 by Molecular Docking

SARS-CoV-2, a new type of Coronavirus, has affected more millions of people worldwide. From the spread of this infection, many studies related to this virus and drug designing for the treatment have been started. Most of the studies target the SARS-CoV-2 main protease, spike protein of SASR-CoV-2, and some are targeting the human furin protease. In the current work, we chose the clinically used drug molecules remdesivir, favipiravir, lopinavir, hydroxychloroquine, and chloroquine onto the target protein SARS-CoV-2 main protease. Docking studies were performed using Arguslab, while Discovery Studio collected 2D and 3D pose views with the crystal structure of COVID-19 main protease in complex with an inhibitor N3 with PDB ID 6LU7. Computational studies reveal that all ligands provided good binding affinities towards the target protein. Among all the chosen drugs, lopinavir showed the highest docking score of -11.75 kcal/mol. The results from this molecular docking study encourage the use of lopinavir as the first-line treatment drug due to its highest binding affinity

Utilization of Fruit Peel Wastes for the Management of Chikungunya Vector, Aedes aegypti

Chikungunya, a widely spread viral disease transmitted to human beings by Aedes aegypti, is on rise in India, Africa and Asian subcontinent since last decade. Although chemical insecticides are used at a large scale for the control of Chikungunya vector, their applications have led to several undesirable effects including insecticide resistance, revival of pests species, appearance of secondary pests, environmental pollution, noxious hazards to human beings and non-target organisms forcing investigators to explore unconventional alternate strategies. As an environment-friendly approach, there is increased attention to devise and adopt suitable methods to utilize wastes as value-added products to reduce the problem of environmental pollution. Consequently, the larvicidal and adult irritant potential of hexane and petroleum ether peel extracts of three different Citrus species, C. limetta, C. sinensis and C. Limon, were assessed against Ae. aegypti. The results showed the larvicidal potential of all the three peels, C. limetta peel extracts exhibiting the least activity. Furthermore, hexane extracts were more effective than petroleum ether extracts, C. sinensis peels hexane extract being most effectual (LC50, 39.51 ppm) while petroleum ether peels extract of C. limon was the most effective larvicide with LC50 value of 51.25 ppm. All the extracts also exhibited significant elicit response and irritant potential against adults signifying their potential role in reduced mosquito bites and disease transmission. The qualitative phytochemical analysis of the extracts showed presence of certain components suggesting their probable role in bioefficacy of extracts. Further studies are needed to isolate and identify the active ingredient to formulate strategies for mosquito control

Evaluation of 15 Local Plant Species as Larvicidal Agents Against an Indian Strain of Dengue Fever Mosquito, Aedes aegypti L. (Diptera: Culicidae)

The adverse effects of chemical insecticides-based intervention measures for the control of mosquito vectors have received wide public apprehension because of several problems like insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans, and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly, environmentally safe, bio-degradable plant products which are non-toxic to non-target organisms too. In view of this, 15 plant species were collected from local areas in New Delhi, India. Different parts of these plants were separated, dried, mechanically grinded, and sieved to get fine powder. The 200 g of each part was soaked in 1000 mL of different solvents separately and the crude extracts, thus formed, were concentrated using a vacuum evaporator at 45°C under low pressure. Each extract was screened to explore its potential as a mosquito larvicidal agent against early fourth instars of dengue vector, Aedes aegypti using WHO protocol. The preliminary screening showed that only 10 plants possessed larvicidal potential as they could result in 100% mortality at 1000 ppm. Further evaluation of the potential larvicidal extracts established the hexane leaf extract of Lantana camara to be most effective extract exhibiting a significant LC50 value of 30.71 ppm while the Phyllanthus emblica fruit extract was found to be least effective with an LC50 value of 298.93 ppm. The extracts made from different parts of other five plants; Achyranthes aspera, Zingiber officinalis, Ricinus communis, Trachyspermum ammi, and Cassia occidentalis also possessed significant larvicidal potential with LC50 values ranging from 55.0 to 74.67 ppm. Other three extracts showed moderate toxicity against A. aegypti larvae. Further investigations would be needed to isolate and identify the primary component responsible for the larvicidal efficiency of the effective plants

Electromyographical Analysis of The Thigh Muscle During Four Yogasana

The goal of the study was to examine the peak EMG at four lower body muscles during four different yoga poses performed by yoga practitioners. Materials and methods: Male Yoga practitioners (n= 11) were assessed for peak electromyography (EMG) of VM-Vastus Medialis, VL- Vastus lateralis, BF- Biceps femoris, ST- Semitendinosus, while performing four Yogasana: UK- Utkatasana, VB- Virabhadrasana II, UPE- Urdhva prasarita ekapadasana six, DOL- Dolasana (pendulum pose). Results: The UK induced the highest EMG for VM (124.5000 ± 25.36088), VL(124.2364 ± 27.35410), ST (106.6091 ± 32.77619),BF (96.6909 ± 29.34824),The VB II induced the highest EMG for the VL (102.0727 ± 32.96262), VM (100.4091± 16.30960), BF (84.5727 ± 28.63844), ST (86.2818 ± 26.07239).The UPE-Six induced the highest EMG for the VM (42.4364 ± 17.09025), BF (45.0636 ± 21.33440),ST (39.3727 ± 17.03315),VL (38.3636 ± 20.73612).The DOL induced the highest EMG for the VM (88.7455 ± 56.13069), BF (65.2545 ± 36.53172), ST (62.6455 ± 19.28302),VL (43.2545 ± 24.14255). However, between Yogasana, only the VM showed a significant (P < .000) * different EMG. Specifically, the UK induced greater VM EMG compared to UPE (82.064, P < .000), VB (57.973, P < .000) * Conclusions: Peak muscular activation in the four lowerbody muscles can change depending on how the yoga players treat the four differences. A declining pattern of peak EMG for the UK > VB II > DOL and UPE six Yogasana, however, indicates that variations between poses appear to be minimal, with the exception of the VM muscle

Risk factors for myocardial infarction among low socioeconomic status South Indian population

<p>Abstract</p> <p>Background</p> <p>As longevity increases, cases of myocardial infarction (MI) are likely to be more. Cardiovascular disease (CVD) is a major global health problem reaching epidemic proportions in the Indian subcontinent, also among low socio-economic status (SES) and thin individuals.</p> <p>Objectives</p> <p>The present study was undertaken to elicit risk factors for MI among low SES Southern Indians and to find out its association with body mass index (BMI).</p> <p>Materials and methods</p> <p>A case-control study of patients with MI matched against healthy control subjects was carried out in a tertiary care teaching hospital. Standard methods were followed to elicit risk factors and BMI. Chi-square and Fishers exact test for categorical versus categorical, to show relationship with risk factors were analyzed.</p> <p>Results</p> <p>A total of 949 patients (male (M) = 692 and post menopausal female (F) = 257) and 611 age and sex matched healthy controls were included. In our study, BMI was below 23 in 48.2% of patients and below 21 in 22.5%. The risk of developing MI was significantly more in males (odds ratio (OR) = 3.3, 95% confidence interval (C.I.) = 2.69-4.13), among females with post-menopausal duration (PMD) of more than or equal to 3 years (OR = 9.27, 95% C.I. = 6.36-13.50) and in those with BMI less than 23 with one or other risk factors (P = 0.002, OR = 1.38, 95% C.I. = 1.13-1.70).</p> <p>Conclusion</p> <p>BMI cannot be considered as a lone independent risk factor, as the study population had low BMI but had one or more modifiable risk factors. It would be advisable to keep BMI at least 21 kg/m²for screening program. Health education on life style modification and programs to diagnose and control diabetes and hypertension have to be initiated at community level in order to reduce the occurrence.</p

"Mother-weights" and lost fathers: parents in South Asian American literature

That parent-child relationships should play a significant role within South Asian American literature is perhaps no surprise, since this is crucial material for any writer. But the particular forms they so often take – a dysfunctional mother-daughter dynamic, leading to the search for maternal surrogates; and the figure of the prematurely deceased father – are more perplexing. Why do families adhere to these patterns in so many South Asian American texts and what does that tell us about this œuvre? More precisely, why are mothers subjected to a harsher critique than fathers and what purpose does this critique serve? How might we interpret the trope of the untimely paternal death? In this article I will seek to answer these questions – arguably key to an understanding of this growing body of writing – by considering works produced between the 1990s and the early twenty-first century by a range of South Asian American writers

Preclinical Evaluation of Lymph Node Targeted Therapy in Mouse Models of Cancer

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