Three-Dimensional Ideal Gas Reference State based Energy Function

Energy functions are found to be a key of protein structure prediction. In this work, we propose a novel 3-dimensional energy function based on hydrophobic-hydrophilic properties of amino acid where we consider at least three different possible interaction of amino acid in a 3-dimensional sphere categorized as hydrophilic versus hydrophilic, hydrophobic versus hydrophobic and hydrophobic versus hydrophilic. Each of these interactions are governed by a 3-dimensional parameter alpha used to model the interaction and 3-dimensional parameter beta used to model weight of contribution. We use Genetic Algorithm (GA) to optimize the value of alpha, beta and Z-score. We obtain three energy scores libraries from a database of 4332 protein structures obtained from Protein Data Bank (PDB) server. Proposed energy function is found to outperform nearest competitor by 40.9% for the most challenging Rosetta decoy as well as better in terms of the Z-score based on Moulder and Rosetta decoy sets

STUDY OF CHARKOKTA ANGULA PRAMANA OF SHADANGA AND IT’S IMPACT ON PHYSICAL HEALTH

Body parts and their Pramana are specially described in Ayurveda which is an important part of Rachana Sharir. Description of Angula Pramana was found in Vedic Kala, Purana-Upanishad Kala. Samhita Kala like Vrahtai (Charaka Samhita, Sushruta Samhita, Ashtanga Sangraha, Astanga Hridya) Kashyapa Samhita, Bhela Samhita, Sharangadhara Samhita, Vangsena Samhita, and Kautilya Arthashastra. Pramanas are not useful only in Rog and Rogi Pariksha but also useful to know about his/her Ayu such as Hitaayu, Ahitaayu, Sukhayu and Dukhaayu. At the time of Acharya Charaka, the length and breadth of different Anga-Pratyanga was measured by using their own fingers. This technique of measurement is known as Anguli Pramana. Anguli Pramana which is based on Swa-Angula Pramana is used for measuring the dimensions (Ayam, Vistara and Parinaha etc.) of the different Anga Pratyanga of the body. The study was conducted on 200 volunteers in the age group of 16-40 years. One Angula as a unit of Angula Pramana was obtained by measuring the width of Madhyamparva of middle finger of working hand. The measurements were taken in centimetres for standardization as per metric system and then converted into Anguli Pramana based on individual. This article summarizes the facts related to Anguli Pramana from classical literature, Ayurvedic literature and modern literature along with result of our research work to identify the anatomical landmark of Shadanga to measure through Anguli Pramana and its impact on physical health in present era. At present, there are many physical anomalies either they are genetic disorders, endocrine disorders, traumatic injury which results as anatomical disfiguration of body parts that can distinguish from their Anguli pramana or anthropometry

CLINICAL STUDY OF LAGHUPANCHMOOLA SADHIT COW’S MILK IN COW’S MILK PROTEIN ALLERGY

In Ayurveda classics it is pointed out that cow’s milk have Vamaka, Virechaka, Sarama and Abhisyandi properties. In classics, it has been mentioned that cow milk should always be processed with Laghupanchmoola before it is consumed. Aims and Objectives of the study: To study Aetiopathogensis of cow milk protein allergy and to evaluate the efficacy of Laghupanchmoola sadhit cow milk in CMPA. Material & Methods: To fulfill the above Aims and Objectives: Total 35 patients were selected between the age group of 0-3 years of age with symptoms of CMPA. Hb%, complete history and elimination-challenge test were used for evaluation of the patients. Laghupanchmoola granules dose depend upon age and duration of trial was 60 days. Results: After analyzing the data statistically in 30 patients, statistically highly significant improvements were found in diarrhea, abdominal pain, respiratory difficulty and vomiting. Significant improvements were found in dermatitis. No improvement was found in anemia and nausea. Statistically highly significant improvement was found in weight, height, mid arm circumference, chest circumference and head circumference. After full observation of treatment modules, it was found that: Number of patient with complete improvement was 0, Number of patient unchanged was 2 (6.5%), Mild improvement was observed in 05 patients (16.6%), and Moderate improvement was observed in 21 patients (70%), where marked improvement was observed in 2 patients (6.7%). Conclusion: Laghupanchmoola proved quite effective in managing the patients of CMPA due to its Tridoṣahar, Deepana, Aamdoshanasaka, Balya and Brahmanna properties

Radial glia regulate vascular patterning around the developing spinal cord

Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial glia ablation in zebrafish embryos leads to excessive sprouting of the trunk vessels around the spinal cord, and exclusively those of venous identity. Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 overexpression rescues it. Genetic mosaic analyses show that sFlt1 function in trunk endothelial cells can limit their over-sprouting. Together, our findings identify CNS-resident progenitors as critical angiogenic regulators that determine the precise patterning of the vasculature around the spinal cord, providing novel insights into vascular network formation around developing organs

Rectal migration of Ventriculo-peritonial shunt: A rare case report

Colonic perforation following ventriculoperitoneal shunt is a rare complication. The common treatment is to remove the perforating catheter and replace with new one. In this case report we reported a rare case of colonic perforation following VP shunt and its anal migration. We have discussed its pathogenesis, management strategy and review of literature

Vitamin A Deficiency after Gastric Bypass Surgery: An Underreported Postoperative Complication

Introduction. Few data are available on vitamin A deficiency in the gastric bypass population. Methods. We performed a retrospective chart review of gastric bypass patients (n = 69, 74% female). The relationship between serum vitamin A concentration and markers of protein metabolism at 6-weeks and 1-year post-operative were assessed. Results. The average weight loss at 6-weeks and 1-year following surgery was 20.1 ± 9.1 kg and 44.1 ± 17.1 kg, respectively. At 6 weeks and 1 year after surgery, 35% and 18% of patients were vitamin A deficient, (<325 mcg/L). Similarly, 34% and 19% had low pre-albumin levels (<18 mg/dL), at these time intervals. Vitamin A directly correlated with pre-albumin levels at 6 weeks (r = 0.67, P < 0.001) and 1-year (r = 0.67,  P < 0.0001). There was no correlation between the roux limb length measurement and pre-albumin or vitamin A serum concentrations at these post-operative follow-ups. Vitamin A levels and markers of liver function testing were also unrelated. Conclusion. Vitamin A deficiency is common after bariatric surgery and is associated with a low serum concentration of pre-albumin. This fat-soluble vitamin should be measured in patients who have undergone gastric bypass surgery and deficiency should be suspected in those with evidence of protein-calorie malnutrition

Illuminating oncology research by bioluminescent imaging

Bioluminescent imaging (BLI) has emerged as a powerful tool in cancer research, allowing for non-invasive, real-time monitoring of various aspects of cancer biology in vivo. This technique relies on the expression of bioluminescent reporter genes in cancer cells, enabling the visualization of tumor growth, metastasis, and response to treatment. In this review, we provide an overview of the principles underlying BLI, its applications in cancer research, and the potential advantages and limitations of this technology

The Influence of Behavioral, Social, and Environmental Factors on Reproducibility and Replicability in Aquatic Animal Models

The publication of reproducible, replicable, and translatable data in studies utilizing animal models is a scientific, practical, and ethical necessity. This requires careful planning and execution of experiments and accurate reporting of results. Recognition that numerous developmental, environmental, and test-related factors can affect experimental outcomes is essential for a quality study design. Factors commonly considered when designing studies utilizing aquatic animal species include strain, sex, or age of the animal; water quality; temperature; and acoustic and light conditions. However, in the aquatic environment, it is equally important to consider normal species behavior, group dynamics, stocking density, and environmental complexity, including tank design and structural enrichment. Here, we will outline normal species and social behavior of 2 commonly used aquatic species: zebrafish (Danio rerio) and Xenopus (X. laevis and X. tropicalis). We also provide examples as to how these behaviors and the complexity of the tank environment can influence research results and provide general recommendations to assist with improvement of reproducibility and replicability, particularly as it pertains to behavior and environmental complexity, when utilizing these popular aquatic models. © The Author(s) 2020. Published by Oxford University Press on behalf of the National Academies of Sciences, Engineering, and Medicine. All rights reserved.A.V.K. research was supported by the Russian Science Foundation grant 19-15-00053. He is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC). This collaboration was supported, in part, through the NIH/NCI Cancer Center Support Grant P30 CA008748. The authors would like to thank Gregory Paull for sharing his photographs and insight into the natural habitat of zebrafish in Bangladesh

Pharmacological modulation of learning and memory in mice and zebrafish: Implications for Alzheimer’s disease animal models

Learning and memory impairments are the clinical manifestations of several neurodegenerative disorders including Alzheimer’s disease (AD), the most common form of dementia affecting millions of people worldwide. Current AD treatments target cognitive decline or failure and provide only minor benefits across the array of clinical symptoms. The development of numerous treatment strategies have been trailed in pre-clinical, or human clinical trials. One of the potential candidates to be used for cognitive enhancement is CB1 cannabinoid receptor antagonist. CB1 cannabinoid receptor antagonists have been shown to improve learning and memory in rodents, whereas CB1 cannabinoid receptor agonists have been shown to impair memory. The project has overall aims of (1) investigating the role of CB1 receptors in learning and memory, and assessing the potential of a CB1 receptor antagonist (SR141716A) as a novel cognitive enhancer in mice models; (2) Assessing the potential of zebrafish as an alternative in vivo model for the high-through put assessment of learning and memory. The involvement of cannabinoid CB1 (CB1) receptors in associative learning in two strains of mice (i.e., C57BL/6J and C3H/HeJ) were first investigated. Here, the effects of the cannabinoid CB1 receptor agonist (i.e., CP55940) and antagonist (i.e., SR141716A) on associative learning were assessed in mice using eight-arm radial maze. The results showed that the CB1 receptor agonist impaired reference memory in C57BL/6J but not in C3H/HeJ strains, and the former effect was probably mediated by CB1 receptors since the selective antagonist, SR141716A, reversed these effects. The CP55940 agonist also impaired working memory selectively in the C57BL/6J mice, which was not affected by SR141716A. This study provided evidence for a strain- specific effect of CP55940 on working memory that is likely to be independent of the CB1 receptors. Cannabinoid receptor effects were also evaluated on non-associative learning in mice by measuring habituation of acoustic startle reflex (ASR). CB1 receptor agonist and antagonist\u27s effects were assessed in two different strains of mice (i.e., C57BL/6J and C3H/HeJ). The findings further supported the strain-specific effects of CP55940. This agonist decreased habituation of the ASR in C57BL/6J, but increased habituation in C3H/HeJ. Both of these measures were reversed by SR141716A. This indicates that the cannabinoid agonist exerts its effects on non-associative learning and memory in both strains of mice via CB1 receptors. The advantages of zebrafish in comparison to other common vertebrate models including high fecundity, low maintenance cost, transparent embryos, and rapid development are some reasons for its popularity in genetics, pharmacological and behavioural research. As vertebrates, zebrafish share considerable sequence similarity with humans and are being used as an animal model for various human disease conditions. Here a video and written protocol is presented for the regular care and maintenance of a zebrafish laboratory and the optimisation of breeding conditions to enable efficient embryo production. In order to establish learning and memory procedures for a novel animal model, it is also important to assess potential confounds that may affect the results of the experiments. One such confound is the natural preference of zebrafish towards a particular colour if zebrafish are to be trained for a colour discrimination learning task. Therefore, the natural colour preference of zebrafish towards specific colours was evaluated using a place preference procedure and a T-maze with coloured sleeves. The results from this study showed a strong aversion towards blue colour compared to red, green, and yellow, with yellow being less preferred relative to red and green. Hence, the findings from this study may underpin any further designing of colour-based associative learning and memory paradigms in the zebrafish. The potential of zebrafish to be used for non-associative learning in a high-throughput manner was also evaluated in a 96-well plate by measuring habituation of the acoustic startle reflex in zebrafish larvae. It was found that larvae can be used for assessing non-associative learning and memory in a 96-well plate because zebrafish larvae startled significantly after the presentation of acoustic stimuli and this response decreased when the stimuli were presented continuously over a period of time. The reduction in response over time was consistent with the phenomenon of habituation, a form of non-associative learning. The non-associative learning and memory in zebrafish larvae was further validated by modulating with several pharmacological agents that are known to alter learning and memory in rodents and in humans such as donepezil and scopolamine. Donepezil was found to reduce the ASR and habituation of ASR in zebrafish larvae, consistent with some reports in rodents. Scopolamine treatment of zebrafish larvae produced a biphasic effect on non-cognitive measures such as ASR and locomotion such that lower doses decreased locomotion and ASR whereas the highest dose showed no effects. Similarly, scopolamine impaired non-associative learning with a lower dose but not with the higher dose. Therefore, the use of this drug for cognitive deficits model cannot be supported in this animal model before the reasons for the biphasic dose effect of scopolamine are elucidated. One hypothesis is suggested, that the differences in the effects of scopolamine are due to different affinities of scopolamine for different muscarinic acetylcholine receptor subtypes. The biphasic dose effect of the antagonist may be related to differential activation of these receptors by the endogenous agonist, rather than pharmacological properties of scopolamine itself. Finally, the effect of CP55940 was evaluated on non-associative learning and non-cognitive measures such as locomotor activity in zebrafish larvae. The solubility of CP55940 is a pragmatic issue when used for zebrafish research, as frequently used solvents are toxic to zebrafish. Therefore, CP55940 was dissolved in several different solvents and studied for its toxicity, locomotion effects, ASR and finally habituation of ASR. It was found that CP55940 was successfully dissolved in two solvents (i.e., ethanol + PBS and captisol) that were not toxic to zebrafish larvae, so CP55940 dissolved in these two solvents was tested for its effects on ASR and habituation of ASR. The results of these experiments showed that CP55940 dissolved in these two solvents produced differing effects on ASR and habituation. For instance, CP dissolved in ethanol+PBS had no effects on ASR but impaired habituation; however, CP dissolved in captisol reduced ASR but had no effects on habituation. CP dissolved in both these solvents decreased locomotor activity in zebrafish larvae, a well known effect of CP in rodents. In conclusion, the cannabinoid CB1 agonist may be used as a pharmacological model for inducing memory impairments with a caveat that effects can be strongly influenced by mouse strain. This project also validated the use of zebrafish for high-throughput screening of the effects of pharmacological agents on non-associative learning and showed potential confounds that may impact on zebrafish behaviour. Furthermore, similar to mice, cannabinoid CB1 agonist can induce habituation deficits in zebrafish. Overall, this project has evaluated novel CB1 receptor agonists and antagonists in modulating learning and memory in mice, and has established and validated non-associative memory tasks in zebrafish that can now be utilised in high-throughput screening for modulators of memory