Structure and mechanical characterization of DNA i-motif nanowires by molecular dynamics simulation

We studied the structure and mechanical properties of DNA i-motif nanowires by means of molecular dynamics computer simulations. We built up to 230 nm long nanowires, based on a repeated TC5 sequence from crystallographic data, fully relaxed and equilibrated in water. The unusual stacked C*C+ stacked structure, formed by four ssDNA strands arranged in an intercalated tetramer, is here fully characterized both statically and dynamically. By applying stretching, compression and bending deformation with the steered molecular dynamics and umbrella sampling methods, we extract the apparent Young's and bending moduli of the nanowire, as wel as estimates for the tensile strength and persistence length. According to our results, the i-motif nanowire shares similarities with structural proteins, as far as its tensile stiffness, but is closer to nucleic acids and flexible proteins, as far as its bending rigidity is concerned. Furthermore, thanks to its very thin cross section, the apparent tensile toughness is close to that of a metal. Besides their yet to be clarified biological significance, i-motif nanowires may qualify as interesting candidates for nanotechnology templates, due to such outstanding mechanical properties.Comment: 25 pages, 1 table, 7 figures; preprint submitted to Biophysical Journa

(R1511) Numerical Solution of Differential Difference Equations Having Boundary Layers at Both the Ends

In this paper, numerical solution of differential-difference equation having boundary layers at both ends is discussed. Using Taylor’s series, the given second order differential-difference equation is replaced by an asymptotically equivalent first order differential equation and solved by suitable choice of integrating factor and finite differences. The numerical results for several test examples are presented to demonstrate the applicability of the method

Efficacy of Ayurved based therapy on global longitudinal strain in ischemic heart disease: a retrospective analysis

Background: The current study aimed to investigate the efficacy of the Ischemia Reversal program (IRP) as an Ayurveda based therapy to standard anti-ischemic therapy in patients with ischemic heart disease (IHD). Methods: A retrospective, single centre, observational study was conducted from January 2022 to May 2023. A total of 39 patients diagnosed with ischemic heart disease and global longitudinal strain (GLS) <15, regardless of underlying co-morbidities such as diabetes mellitus, hypertension, obesity, hyperlipidemia, low ejection fraction, history of myocardial infarction were included in this study. The primary endpoint was improvement in GLS from baseline to the 90-day follow-up in various different categories. Secondary endpoints were improvement in EF, abdominal girth, weight and reduction in dependency on allopathic medication from baseline to the 90-day follow-up. Results: The mean age of the study population was 59.23±9.01 years. Weight (day 1: 67.29±13.16 kg and day 90: 61.39±11.11 kg; p=0.00), body mass index (day 1: 25.75±4.03 and day 90: 23.79±3.50; p=0.00), abdominal girth (day 1: 95.31±10.75 cm and day 90: 85.67±17.02 cm p=0.00), EF (day 1: 40.74±10.30% and day 90: 53.91±11.87%; p=0.00), and GLS (day 1: -10.99±2.72 and day 90: -13.17±3.75; p=0.00) improved at the 90 day follow-up. Conclusions: The study showed notable improvements in weight, body mass index, abdominal girth, EF, and GLS after 90 days. These results suggest that IRP is beneficial treatment for IHD, but more extensive research is needed to confirm its effectiveness

Identifying complaints from product reviews: a case study on Hindi

When an expectation does not meet reality in a real-world situation, the difference is usually expressed and communicated via an act which is complaint. Customers often post reviews on the products or services they purchase on the retailer websites and different social media platforms, and the reviews may reflect complaints about the products or services. Automatic recognition of customers’ complaints on products or services that they purchase can be crucial for the organizations, multinationals and online retailers since they can exploit this information to fulfil the customers’ expectations including managing and resolving the complaints. In this work, we present the supervised and semi-supervised learning strategies to identify users’ complaints from the language they use to post their reviews. In other words, we automatically identify complaints from the opinionated texts (reviews) about products posted in Hindi. For this, first we automatically crawled the Hindi reviews on different products from the the websites of the retail giant Amazon and the popular social media platform YouTube, and prepared a gold-standard data set via a systematic manual annotation process. We use state-of-the-art classification algorithms for the complaints identification task and our classification models achieve reasonable classification accuracy (F1 = 68.38%) on a gold-standard evaluation test set

Identifying complaints from product reviews in low-resource scenarios via neural machine translation

Automatic recognition of customer complaints on products or services that they purchase can be crucial for the organizations, multinationals and online retailers since they can exploit this information to fulfil their customers’ expectations including managing and resolving the complaints. Recently, researchers have applied supervised learning strategies to automatically identify users’ complaints expressed in English on Twitter. The downside of these approaches is that they require labeled training data for learning, which is expensive to create. This poses a barrier for them being applied to low-resource languages and domains for which task-specific data is not available. Machine translation (MT) can be used as an alternative to the tools that require such task-specific data. In this work, we use state-of-the-art neural MT (NMT) models for translating Hindi reviews into English and investigate performance of the downstream classification task (complaints identification) on their English translations

ROLE OF MRI IN EVALUATION OF EPILEPSY IN PEDIATRIC AGE GROUP IN A TERTIARY CARE CENTRE OF JHARKHAND, INDIA- A PROSPECTIVE STUDY.

Background: Childhood epilepsy is a prevalent neurological disorder. Imaging, especially MRI of the brain, plays a pivotal role in diagnosing the underlying cause. This study aimed to assess the frequency of causative factors of epilepsy detected in MRI. Materials and Methods: This hospital-based prospective observational study was conducted in the Radiology Department at Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India from November 2021 to October 2022 in 100 children of 0 to 12 years of age referred from Pediatrics department for an MRI brain scan. MRI of the brain was performed in all cases and findings were analyzed and causes of epilepsy were assessed. Magnetic resonance spectroscopy (MRS) was also done when required for confirmation of diagnosis. Results: Positive findings in MRI were detected in 87% of children, and no abnormalities were detected in 13%. The majority of children belonged to the age group of 10-12 years (37%) and were predominantly males (66%). The most common cause of epilepsy was infections (27%) followed by hypoxic ischemic encephalopathy (22%). Tuberculoma was the most common infective cause of epilepsy in 59.3%. These were further followed by temporal lobe epilepsy and congenital malformations (11% each). The rest were other miscellaneous and idiopathic causes. Conclusion: MRI findings were specific to various conditions, helping in the localization and characterization of etiologies and playing a significant role in the evaluation of children who were newly diagnosed with epilepsy, especially those with partial seizures. Recommendation: Further research with a larger sample size and meta-analysis is recommended for more conclusive results

Modélisation numérique de l'application de forces mécaniques aux biomolécules

Dans les derniers 20 ans, les expériences de traction sur molécule unique par l’action d’une force mécanique ont donné plein d’informations autour des propriétés mécaniques des biomolécules, des modifications structurelles induites par des contraintes mécaniques, ainsi qu’éclaircir les mécanismes d’adhésion et décohésion des paires ligand-recepteur. Suivant cette analyse microscopique, outre que révéler des propriétés biologiques intéressantes, plusieurs de ces systèmes ont montré une nouvelle face, celle de nouveaux matériaux aux propriétés parfois uniques, et ont notamment induit des spéculations sur leur possibles utilisations dans des dispositif de nanotechnologie. Dans cette thèse, par le biais de simulations de dynamique moléculaire, notamment avec les méthodes dites “steered molecular dynamics” et “umbrella sampling”, nous avons réalisé des études concernant : (a) la caractérisation structurelle et mécanique de fragments d’ADN atypiques, comme le tétramère dénommé i-motif, ainsi que (b) la reconstruction des profils d’énergie libre de la liaison et dissociation entre des paires bromodomaine – queues d’histone acétylés (H3 et H4). Nous avons ainsi étudié la structure moléculaire de ces nanostructures particulières d’ADN, formées par l’intercalation de quatre brins d’ADN en un tétramère, et nous en avons déterminé pour la première fois les propriétés mécaniques de base : module de Young, module de flexion, longueur de persistance, et résistance mécanique. Dans la dernière partie du travail, nous avons étudié la manière d’appliquer ces mêmes méthodes à l’étude de paires ligand-recepteur dans le processus de transcription de l’ADN. Nous avons montré que les expériences simulées de traction, dans lesquelles la paire ligand-recepteur est séparée de manière contrôlée par une force mécanique aux extrémités, peuvent donner des informations sur l’hypersurface d’énergie libre. Nous avons essayé, avec un partiel succès, l’application au cas de l’interaction entre bromodomaines et queues d’histones, dans des conditions comparables aux expériences.In the past 20 years, single-molecule pulling experiments of biomolecules under mechanical forces provided a wealth of information about the mechanical properties of such molecules, and the structural changes that may happen under stress in mechanical proteins, as well as shedding light upon many receptor-ligand binding and unbinding mechanism. Upon such microscopic analysis, besides revealing interesting biological properties, many such systems appeared as unique novel materials, and suggested routes to include such materials in nanotechnology assembly processes. This thesis reports on our studies of the structural and mechanical characterization of DNA i-motif and free-energy based profiling of bromodomain and acetylated histone tails (H3 and H4) binding and dissociation, by using molecular dynamics simulations, and in particular steered “molecular dynamics” and “umbrella sampling” methods. We studied the molecular structure of a peculiar class of DNA-based nanostructures, the i-motif, resulting from the intercalation of four DNA strands into a tetramer, and obtained for the first time its basic mechanical properties: Young’s modulus, bending modulus, persistence length and mechanical toughness. In a final part of the work, we also studied the applicability of the same computational methods to ligand-binding interactions in DNA trasncription. We showed that simulated pulling experiments on ligand-binding pairs, in which the pair is taken apart in a controlled way, can give informations about its free-energy landscape. We attempted, with mixed success, the application to the case of bromodomain-histone tail interactions under conditions comparable to the experiments

Deciphering the Factors for Nodulation and Symbiosis of Mesorhizobium Associated with Cicer arietinum in Northwest India

The compatibility between rhizobia and legumes for nitrogen-fixing nodules and the stages of root hair curling, formation of infection thread, and nodulation initiation have been vitally studied, but the factors for the sustainable root surface colonization and efficient symbiosis within chickpea and rhizobia have been poorly investigated. Hence, we aimed to analyze phenotypic properties and phylogenetic relationships of root-nodule bacteria associated with chickpea (Cicer arietinum) in the north-west Indo Gangetic Plains (NW-IGP) region of Uttar Pradesh, India. In this study, 54 isolates were recovered from five agricultural locations. Strains exhibited high exopolysaccharide production and were capable of survival at 15–42 °C. Assays for phosphate solubilization, catalase, oxidase, Indole acetic acid (IAA) production, and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity revealed that all the tested isolates possessed plant growth-promoting potential. Metabolic profiling using Biolog plates indicated that patterns of substrate utilization differed considerably among isolates. A biofilm formation assay showed that isolates displayed a nearly four-fold range in their capacity for biofilm development. Inoculation experiments indicated that all isolates formed nodules on chickpea, but they exhibited more than a two-fold range in symbiotic efficiency. No nodules were observed on four other legumes (Phaseolus vulgaris, Pisum sativum, Lens culinaris, and Vigna mungo). Concatenated sequences from six loci (gap, edD, glnD, gnD, rpoB, and nodC) supported the assignment of all isolates to the species Mesorhizobium ciceri, with strain M. ciceri Ca181 as their closest relative

DNA I-motif provides steel-like tough ends to chromosomes

Symposium C : Advances in Mechanics of Biological and Bioinspired MaterialsInternational audienceWe studied the structure and mechanical properties of DNA i-motif nanowires by means of molecular dynamics computer simulations. We built up to 230 nm-long nanowires, based on a repeated TC5 sequence from crystallographic data, fully relaxed and equilibrated in water. The unusual C●C+ stacked structure, formed by four ssDNA strands arranged in an intercalated tetramer, is here fully characterized both statically and dynamically. By applying stretching, compression and bending deformations with the steered molecular dynamics and umbrella sampling methods, we extract the apparent Young's and bending moduli of the nanowire, as well as estimates for the tensile strength and persistence length. According to our results, i-motif nanowires share similarities with structural proteins, as far as their tensile stiffness, but are closer to nucleic acids and flexible proteins, as far as their bending rigidity is concerned. Curiously enough, their tensile strength makes such DNA fragments tough as a mild steel or a nickel alloy. Besides their yet to be clarified biological significance, i-motif nanowires may qualify as interesting candidates for nanotechnology templates, due to such outstanding mechanical properties