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Neoechinorhynchus (Neoechinorhynchus) johnii Yamaguti, 1939 is redescribed from Eleutheronema tetradactylum (Polynemidae), Johnius carouna (Sciaenidae), Johnius sp., and Otolithes ruber (Sciaenidae) along the north and south coasts of Vietnam. Our description completes missing and inadequate information in the original descriptions and line drawings from Johnius goma in Japan and from Pseudosciaena diacanthus in the Indian Ocean. We add new information documented by scanning electron microscopy (SEM) and photomicroscopy, and explore the wide morphological diversity attributed to host species. The redescription includes: worms cylindrical with round proboscis with prominent apical organ, and large anterior hooks distant from small middle and posterior hooks; neck longer than the proboscis, nucleated lemnisci subequal, and receptacle with large basal triangulate cephalic ganglion and attached para-receptacle structure (PRS); male reproductive system in posterior half of trunk; adult females with introvert genital vestibule; and eggs spherical or rectangular. Gallium cuts and X-ray scans of hooks show high concentrations of sulfur on edge layer aiding in forming hardened calcium phosphate apatite of that layer with calcium and phosphorus in higher concentration in central part of hook. Molecular results consistently yielded a strongly supported distinct clade for the Neoechinorhynchus species from Vietnam for both 18S gene and the ITS1-5.8S-ITS2 region of ribosomal RNA. Phylogenetic analysis demonstrated that N. johnii occupies a separate position in the trees, probably indicating an Asian origin of this species.

A novel series of 7-(trifluoromethyl)indolizine derivatives (4a-4n) was synthesized using a 1,3-Dipolar cycloaddition reaction. Structure elucidation of the synthesized compounds was done using various spectroscopic techniques. Compounds were assessed for their larvicidal activity against Anopheles arabiensis. Exposure of Anopheles arabiensis larvae to a series of 7-(trifluoromethyl)indolizine at 4 µg/mL for 24 and 48 h resulted in moderate to high larval mortality rates. Among them, compounds 4b, 4a, 4g, and 4m exhibited the most promising larvicidal activities, with mortality rates of 94.4%, 93.3%, 80.00%, and 85.6%, respectively, compared to controls, Acetone and Temephos. The structural activity relationship analysis of the evaluated compounds revealed that substitution with halogens or electron-withdrawing groups (CN, F, Cl, Br) at the para position of the benzoyl group is crucial for achieving promising larvicidal activity. Molecular docking studies were carried out involving six potential larvicidal target proteins to predict how the tested compounds might work. Compounds 4a and 4b showed strong binding to the Mosquito Juvenile Hormone-Binding Protein (5V13). Molecular dynamics (MD) simulations confirmed the stability of the protein-ligand complexes over the simulation period, reinforcing the reliability of the docking results. Compounds 4a and 4b also exhibited favourable ADMET profiles, showing high oral bioavailability, good permeability, moderate distribution, low plasma protein binding, sufficient metabolic stability, efficient renal clearance and low toxicity. Given the crucial role of Juvenile Hormone in regulating gene expression and developmental pathways through receptor interactions, compounds 4a and 4b show promise as inhibitors of this protein. Inhibiting this process could hinder larval growth and reproduction, presenting a promising approach for early-stage mosquito larvicidal activity. Therefore, compounds 4a and 4b represent lead candidates for further optimization and the development of new larvicidal agents., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Series of 7-(Trifluoromethyl) substituted indolizine 4a-g was synthesized using the one-pot method. Spectroscopic techniques such as IR, 1 H-NMR, 13 C-NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a-g compounds were tested for their anti-inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a-g selectively targeting COX-2 enzyme, tumor necrosis factor-α (TNF-α) and, interleukin-6 (IL-6). The in silico docking studies of 4a-g showed that these compounds have a higher affinity for COX-2 enzyme, TNF- α, and IL-6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood-brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX-2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF-α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL-6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti-inflammatory activities of these novel 7-(Trifluoromethyl) substituted indolizine derivatives., (© 2024 John Wiley & Sons Ltd.)

Background: Fontan baffle punctures and creation of Fontan fenestration for cardiac catheterisation procedures remain challenging especially due to the heavy calcification of prosthetic material and complex anatomy., Objectives: We sought to evaluate our experience using radiofrequency current via surgical electrocautery needle for Fontan baffle puncture to facilitate diagnostic, electrophysiology, and interventional procedures., Methods: A retrospective chart review of all Fontan patients (pts) who underwent Fontan baffle puncture using radiofrequency energy via surgical electrocautery from three centres were performed from January 2011 to July 2021., Results: A total of 19 pts underwent 22 successful Fontan baffle puncture. The median age and weight were 17 (3-36 years) and 55 (14-88) kg, respectively. The procedural indications for Fontan fenestration creation included: diagnostic study (n = 1), atrial septostomy and stenting (n = 1), electrophysiology study and ablation procedures (n = 8), Fontan baffle stenting for Fontan failure including protein-losing enteropathy (n = 7), and occlusion of veno-venous collaterals (n = 2) for cyanosis. The type of Fontan baffles included: extra-cardiac conduits (n = 12), lateral tunnel (n = 5), classic atrio-pulmonary connection (n = 1), and intra-cardiac baffle (n = 1). A Fontan baffle puncture was initially attempted using traditional method in 6 pts and Baylis radiofrequency trans-septal system in 2 pts unsuccessfully. In all pts, Fontan baffle puncture using radiofrequency energy via electrocautery needle was successful. The radiofrequency energy utilised was (10-50 W) and required 1-5 attempts for 2-5 seconds. There were no vascular or neurological complications., Conclusions: Radiofrequency current delivery using surgical electrocautery facilitates Fontan baffle puncture in patients with complex and calcified Fontan baffles for diagnostic, interventional, and electrophysiology procedures.

According to the WHO (World Health Organization), lung cancer is the leading cause of cancer deaths globally. In the future, more than 2.2 million people will be diagnosed with lung cancer worldwide, making up 11.4% of every primary cause of cancer. Furthermore, lung cancer is expected to be the biggest driver of cancer-related mortality worldwide in 2020, with an estimated 1.8 million fatalities. Statistics on lung cancer rates are not uniform among geographic areas, demographic subgroups, or age groups. The chance of an effective treatment outcome and the likelihood of patient survival can be greatly improved with the early identification of lung cancer. Lung cancer identification in medical pictures like CT scans and MRIs is an area where deep learning (DL) algorithms have shown a lot of potential. This study uses the Hybridized Faster R-CNN (HFRCNN) to identify lung cancer at an early stage. Among the numerous uses for which faster R-CNN has been put to good use is identifying critical entities in medical imagery, such as MRIs and CT scans. Many research investigations in recent years have examined the use of various techniques to detect lung nodules (possible indicators of lung cancer) in scanned images, which may help in the early identification of lung cancer. One such model is HFRCNN, a two-stage, region-based entity detector. It begins by generating a collection of proposed regions, which are subsequently classified and refined with the aid of a convolutional neural network (CNN). A distinct dataset is used in the model's training process, producing valuable outcomes. More than a 97% detection accuracy was achieved with the suggested model, making it far more accurate than several previously announced methods.

Three-dimensional (3D) reconstruction of human organs has gained attention in recent years due to advances in the Internet and graphics processing units. In the coming years, most patient care will shift toward this new paradigm. However, development of fast and accurate 3D models from medical images or a set of medical scans remains a daunting task due to the number of pre-processing steps involved, most of which are dependent on human expertise. In this review, a survey of pre-processing steps was conducted, and reconstruction techniques for several organs in medical diagnosis were studied. Various methods and principles related to 3D reconstruction were highlighted. The usefulness of 3D reconstruction of organs in medical diagnosis was also highlighted., (© 2023. The Author(s).)

Climate change is a critical yield-limiting factor that has threatened the entire global crop production system in the present scenario. The use of biostimulants in agriculture has shown tremendous potential in combating climate change-induced stresses such as drought, salinity, temperature stress, etc. Biostimulants are organic compounds, microbes, or amalgamation of both that could regulate plant growth behavior through molecular alteration and physiological, biochemical, and anatomical modulations. Their nature is diverse due to the varying composition of bioactive compounds, and they function through various modes of action. To generate a successful biostimulatory action on crops under different parameters, a multi- omics approach would be beneficial to identify or predict its outcome comprehensively. The ' omics' approach has greatly helped us to understand the mode of action of biostimulants on plants at cellular levels. Biostimulants acting as a messenger in signal transduction resembling phytohormones and other chemical compounds and their cross-talk in various abiotic stresses help us design future crop management under changing climate, thus, sustaining food security with finite natural resources. This review article elucidates the strategic potential and prospects of biostimulants in mitigating the adverse impacts of harsh environmental conditions on plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhupenchandra, Chongtham, Devi, R, Choudhary, Salam, Sahoo, Bhutia, Devi, Thounaojam, Behera, MN, Kumar, Dasgupta, Devi, Singh, Bhagowati, Devi, Singh and Khaba.)

The effects of radiation on patients and the providers are dose-dependent and cumulative. Pediatric patients are not only more sensitive to radiation but also may undergo more procedures and diagnostic tests throughout their lifetime. As providers, the endeavor is to cause no harm and it behooves us to either eliminate or minimize the radiation exposure to patients without affecting the efficacy and outcomes of the diagnostic or therapeutic modalities. Pediatric electrophysiologists have taken the lead in attempting to minimize the radiation exposure to patients and staff with innovative and advanced techniques. The techniques range from minimizing the exposure to radiation with better understanding and applications of the physics associated with fluoroscopic imaging to using alternative imaging modalities that do not use radiation.

The propensity of cells to align in particular directions is relevant to a number of areas, including tissue engineering and biohybrid robotics. Cell alignment is modulated through various extracellular conditions including surface topographies, mechanical cues from cell-matrix interactions, and cell-cell interactions. Understanding of these conditions provides guidance for desirable cellular structure constructions. In this study, we examine the roles of surface topographies and cell-cell interactions in inducing cell alignment. We employed wavy surface topographies at the nanometer scale as a model extracellular environment for cell culture. The results show that, within a certain range of wavelengths and amplitudes of the surface topographies, cell alignment is dependent on cell confluency. This dependence on both topology and confluency suggests interplay between cell-cell and cell-matrix interactions in inducing cell alignment. Images of sparsely distributed and confluent cells also demonstrated clear differences in the structures of their focal adhesion complexes. To understand this effect, we introduced anti-N-cadherin to cell culture to inhibit cell-cell interactions. The results show that, when anti-N-cadherin was applied, cells on wavy surfaces required greater confluency to achieve the same alignment compared to that in the absence of anti-N-cadherin. The understanding of the cell alignment mechanisms will be important in numerous potential applications such as scaffold design, tissue repair, and development of biohybrid robotic systems. STATEMENT OF SIGNIFICANCE: Cell alignment plays a critical role in numerous biological functions. Advances in tissue engineering utilizes cell alignment to restore, maintain, or even replace different types of biological tissues. The clinical impact that tissue engineering has made is facilitated by advancements in the understanding of interactions between scaffolds, biological factors, and cells. This work further elucidates the role of cell-cell interactions in promoting the organization of biological tissues., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial interests or personal relationships that could influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Heterotaxy is a rare syndrome associated with cardiac complexity, anatomic variability and high morbidity and mortality. It is often challenging to visualize and provide an accurate diagnosis of the cardiac anatomy prior to surgery with the use of conventional imaging techniques. We report a unique case demonstrating how the use of three-dimensional (3D) cardiac printed model allowed us to better understand the anatomical complexity and plan a tailored surgical approach for successful biventricular repair in a patient with heterotaxy syndrome.

L -DOPA, a precursor of dopamine, is the drug of choice for Parkinson's disease, which persists due to decreased levels of dopamine in the brain. Present study emphasis the microbial production of L -DOPA rather than the biotransformation of L -DOPA by L-tyrosine. The production of L -DOPA by bacterial isolates had gained more acceptance due to its more straightforward extraction and downstream processes. Pseudomonas fluorescens was used to produce the L -DOPA in a bioreactor system under submerged condition. The design of experiment-based Taguchi orthogonal array method was adopted for the optimization of production. L-9 orthogonal array using the analysis of mean approach was used to study the effect of different factors viz NaCl, lactose, tryptone, and inducer on the microbial production of L -DOPA. The method mentioned above is less time consuming and does not require any harsh chemicals, proving it to be an eco-friendly process. After optimizing selected factors, i.e., NaCl (1.2 g/l), lactose (1.5 g/l), tryptone (4 g/l), and inducer (0.1 g/l), 16.9 % of enhancement in L -DOPA production with 66.6% of process cost saving was observed. The production of L -DOPA was increased from 3.426 ± 0.08 g/l to 4.123 ± 0.05 g/l after optimization. Subsequently, unstructured kinetic models were adopted to simulate the fermentation kinetics and understand the metabolic process. Fisher' F test and determination coefficients ( R 2 ) confirmed that the Velhurst-Pearl logistic equation, Luedeking-Piret equation, and modified Luedeking-Piret equation was best fitted with the biomass production, product formation, and substrate utilization, respectively.

For the past two decades, slide-based presentation has been the method of content delivery in medical education. In recent years, other teaching modalities involving three-dimensional (3D) visualization such as 3D printed anatomical models, virtual reality (VR), and augmented reality (AR) have been explored to augment the education experience. This review article will analyze the use of slide-based presentation, 3D printed anatomical models, AR, and VR technologies in medical education, including their benefits and limitations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bui, Bhattacharya, Wong, Singh and Agarwal.)

Camellia sinensis (green tea leaves) which acts as a reducing agent was used for the reduction of graphene oxide (GO) to obtain reduced graphene oxide (RGO). Anionic surfactant SDS was used to enhance the stability of synthesized reduced graphene oxide nanoparticles. Characterized reduced graphene oxide nanoparticle grain size was calculated to be 3.92 nm from the X-ray diffraction method, whereas zeta potential was measured - 35.23 ± 5.45 mV at room temperature. Antioxidant and cell cytotoxicity against A-549 lung carcinoma cells were also studied. Phytochemical content of Camellia sinensis imparts feasible DPPH activity of 85.98 ± 2.49% against RGO, whereas ABTS scavenging activity was found to be 88.87 ± 1.74% followed by measurement of the total phenolic content of 842 ± 13.33 µg/gm. RGO at concentration 400 µg/ml showed an optimum level of hemolysis at pH 7.4 (4.92 ± 1.20%) than pH 5.6 (11.15 ± 0.03%). Cytotoxicity activity studied by MTT assay of RGO on A-549 lung carcinomas cells was compared with drug doxorubicin. The bandgap energy of RGO was calculated to be 3.97 eV from absorption data, hence reveals the generation of oxidative stress in the A-549 lung cancer cell line. Thus, the surfactant and phytochemicals found in Camellia sinensis enhanced the stability of RGO, thereby providing enough energy to destabilize the target cells without affecting healthy cells, hence suggests its role in therapeutics application., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03015-z., Competing Interests: Conflict of interestThe authors Farkhunda Fatima, Santosh Kumar Jha and Hare Ram Singh declare that they have no conflicts of interest regarding the publication of this article., (© King Abdulaziz City for Science and Technology 2021.)

Bioflocculant-producing bacteria were isolated from various water reservoirs and sediments of the water treatment plant. Four promising strains were identified by standard biochemical methods and 16s rRNA gene sequencing. Bioflocculants were produced in a batch bioreactor of 3 L under optimized conditions. Fourier transformed infrared spectroscopy and scanning electron microscopy (SEM) were used to confirm the chemical and morphological nature of bioflocculants. Anionic and cationic textile dyes congo red (CR) and rhodamine-B (RB) decolourization efficiency by ethanol precipitated bioflocculants were accessed under different values of pH, temperature, dose of flocculant and presence of monovalent, divalent and trivalent cations. Bioflocculants of all the four isolates were found to be highly efficient in decolourization of dye from an aqueous medium with the removal rate up to 99.56%. The removal rate of CR and RB from aqueous medium was largely influenced by the physiochemical condition of the solution viz. pH, temperature, concentration of ions and dose of flocculants. The microbial bioflocculants are biodegradable and highly stable as well as possess abroad range of pH, temperature and ions tolerance range. So, they may be economical and can be greener substitutes for the present harsh chemical-based wastewater effluent treatment methods.

Polymer science offers a great insight and a new research dimension for biomedical applications. The synthesis of polymeric materials by the physical ways provides several advantages over the conventional chemical methods. It is though expansive but less toxic, stable, and efficiently reproducible. In the present report, electrospinning was used for bio-composite preparation. The bio-composite was developed using polyvinyl alcohol (PVA) and curcumin. The electrospun fiber bio-composite were analyzed for antibacterial activity, bacterial filtration capability, and endotoxin elimination. The bio-composite was analyzed for physical structure and properties using Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX), and Fourier Transform Infra-Red spectroscopy (FT-IR). PVA solely was not able to exhibit any of the antibacterial or endotoxin removal properties. However, the curcumin-based bio-composite was found to be bactericidal and endotoxin eliminator. The bio-composite was able to remove 100% of endotoxin and nearly 100% of the bacterial cells. The endotoxin removal properties of bio-composite were found to be excellent fit under Langmuir curve with a R 2 value of 0.98. Additionally, the effect of bio-composite was also studied over protein content in the sample and L-asparaginase activity. However, the effect observed was negligible.

Anti-leukemic enzyme L-asparaginase despite having significant applicability in medicine, holds side effects attributed to glutaminase activity and endotoxin content. Glutaminase activity proves to be toxic to non-tumor cells as glutamine is an essential amino acid. Endotoxin illicit the production of vasoactive amines and induce septic shock. Hence there is a need for glutaminase free L-asparaginase with minimum endotoxin level. The report aims at the development of a downstream process for purification of glutaminase free L-asparaginase and subsequent endotoxin removal. Producing bacteria were isolated from various soil samples and screened initially for asparaginase and glutaminase activity. The glutaminase free L-asparaginase producing bacteria were identified as Bacillus altitudinis . Production of L-asparaginase was optimized. The optimum medium comprised of comprising Lactose (1.5 g/L), NaCl (1.2 g/L), Yeast extract (5 g/L), L-asparagine (20 g/L) with pH 7.0 and incubation time of 18 h. Kinetic parameters Km and Vmax were computed to be 9.09x10 -2 M and 0.09 M/S. L-asparaginase Purification was achieved with a specific activity of 800 U/mg of enzyme. Molecular weight of the purified L-asparaginase was determined to be around 35 KDa using SDS-PAGE. The developed process also brought down the endotoxin content below the FDA recommended level. The endotoxin content of the purified enzyme was determined to be 0.015EU/mL.

Several soil isolates from 1 g of soil sample were isolated and screened for the production of L-asparaginase. Primary screening was performed using rapid plate assay; dye indicator studies were conducted, and phenol red with 0.005% concentration was found to be optimum. The secondary screening was carried out using the Nesslerization method. The bacteria screened for L-asparaginase production with no glutaminase activity was identified as Bacillus subtilis . Crude L-asparaginase enzyme was partially purified 1.57 folds of purity and 110 U/mg of specific activity. The glutaminase-free L-asparaginase activity was also confirmed using LC-MS analysis. The presence of mass peaks at 147.0 in the reaction mixture suggested an absence of glutaminase activity. An optimized medium obtained comprised of Dextrose 1.5 g/L, K 2 HPO 4 1.2 g/L, L-asparagine 15 g/L, and Tryptone 5 g/L. The highest L-asparaginase activity was observed at 6.0 pH and 30 °C. Kinetic parameters associated with biomass and L-asparaginase production were also studied. The computed values were µ m 0.104 h -1 , X m 6g/L P 0 1.7U/mL P m 8.2 U/mL Y X/S 4 g-cell/g-glucose µ P m 0.35 h -1 q p 5.46 U/g/h Y P/x 13.6667 U/g-cell. The novel bacterial isolates showed promise as a potential glutaminase-free L-asparaginase producer, which can prove to be of industrial applications.

Background: Predictors of risk of lethal arrhythmic events (LAE) is poorly understood and may differ from adults in children with hypertrophic cardiomyopathy (HCM)., Objective: The purpose of this study was to determine predictors of LAE in children with HCM., Methods: A retrospective data collection was performed on 446 children and teenagers 20 years and younger (290 [65%] male; mean age 10.1 ± 5.7 years) with idiopathic HCM from 35 centers. Patients were classified as group 1 (HCM with LAE) if having a secondary prevention implantable cardioverter-defibrillator (ICD) or primary prevention ICD with appropriate interventions or group 2 (HCM without LAE) if having a primary prevention ICD without appropriate interventions., Results: There were 152 children (34%) in group 1 and 294 (66%) in group 2. Risk factors for group 1 by univariate analysis were septal thickness, posterior left ventricular (LV) wall thickness, lower LV outflow gradient, and Q wave > 3 mm in inferior electrocardiographic leads. Factors not associated with LAE were family history of SCD, abnormal blood pressure response to exercise, and ventricular tachycardia on ambulatory electrocardiographic monitoring. Risk factors for SCD by multivariate analysis were age at ICD placement (hazard ratio [HR] 0.9; P = .0025), LV posterior wall thickness z score (HR 1.02; P < .005), and LV outflow gradient < 30 mm Hg (HR 2.0; P < .006). LV posterior wall thickness z score ≥ 5 was associated with LAE., Conclusion: Risk factors for LAE appear different in children compared to adults. Conventional adult risk factors were not significant in children. Further prospective studies are needed to improve risk stratification for LAE in children with HCM., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied.

Dynamic DNA nanotechnology, a subfield of DNA nanotechnology, is concerned with the study and application of nucleic acid strand-displacement reactions. Strand-displacement reactions generally proceed by three-way or four-way branch migration and initially were investigated for their relevance to genetic recombination. Through the use of toeholds, which are single-stranded segments of DNA to which an invader strand can bind to initiate branch migration, the rate with which strand displacement reactions proceed can be varied by more than 6 orders of magnitude. In addition, the use of toeholds enables the construction of enzyme-free DNA reaction networks exhibiting complex dynamical behavior. A demonstration of this was provided in the year 2000, in which strand displacement reactions were employed to drive a DNA-based nanomachine (Yurke, B.; et al. Nature 2000, 406, 605-608). Since then, toehold-mediated strand displacement reactions have been used with ever increasing sophistication and the field of dynamic DNA nanotechnology has grown exponentially. Besides molecular machines, the field has produced enzyme-free catalytic systems, all DNA chemical oscillators and the most complex molecular computers yet devised. Enzyme-free catalytic systems can function as chemical amplifiers and as such have received considerable attention for sensing and detection applications in chemistry and medical diagnostics. Strand-displacement reactions have been combined with other enzymatically driven processes and have also been employed within living cells (Groves, B.; et al. Nat. Nanotechnol. 2015, 11, 287-294). Strand-displacement principles have also been applied in synthetic biology to enable artificial gene regulation and computation in bacteria. Given the enormous progress of dynamic DNA nanotechnology over the past years, the field now seems poised for practical application.

A few recent reports reveal fundamental new insights into the intricate regulatory mechanisms that govern RNA polymerase II (Pol II)-mediated gene transcription. Whereas a histidine-rich domain (HRD) triggers phase separation, promoting transcription elongation, a phosphatase switch promotes transcription termination. A paradigm that might govern the underlying mechanisms leading to robust gene transcription is now starting to emerge., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The epigenome editing framework provides an engineering approach to explore chromatin-based gene expression mechanisms. However, therapeutic utility of epigenetic editing-based systems has been lacking. A report in Cell (Liu et. al., 2018) shows that epigenetic editors can revert abnormal heterochromatin formation at the gene promoter leading to restoration of FMR1 gene expression, functionally rescuing fragile X syndrome (FXS), an otherwise unamenable genetic disorder., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

DNA-based nanorobots have been shown to sense and respond to molecular triggers, such as intracellular pH and cell surface receptors. A recent report describes DNA nanorobots as potential cancer therapeutic agents that can be programmed to trigger coagulation inside blood vessels at the tumor site, starving tumor cells to death., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain's interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD + -metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Atrial transseptal puncture (TSP) for cardiac catheterization procedures remain challenging in children and adults with complex congenital heart disease (CHD)., Objectives: We sought to evaluate our experience using radiofrequency (RF) current via surgical electrocautery needle for TSP to facilitate diagnostic and interventional procedures., Methods: Retrospective chart review of all patients (pts) who underwent TSP using RF energy (10-25 W) via surgical electrocautery from three centers from January 2011 to January 2017 were evaluated. Echocardiograms were reviewed to define the atrial septum as normal and complex (thin aneurysmal, thick/fibrotic, synthetic patch material, and extra cardiac conduit)., Results: A total of 54 pts underwent 55 successful TSP. Median age was 12.5 years (1 day-54 years) and weight was 52.7 kg (2-162). Indications for TSP included; EP study and ablation procedures in structurally normal hearts (n = 24) and in complex atrial septum/CHD and structural heart disease pts (n = 30): Electrophysiology study and ablation in 4, diagnostic catheterization in 9, and interventional procedures in 17 pts were performed. Atrial TSP was successful in 54/55 (98%). Atrial perforation with tiny-small pericardial effusion not requiring intervention was noted in 2 pts. TSP was unsuccessful in one critically ill neonate with unobstructed TAPVR and restricted atrial septum who experienced cardiac arrest requiring CPR, ECMO, and emergent surgery., Conclusions: RF current delivery using surgical electrocautery for TSP is a feasible and an effective option in patients with complex CHD for diagnostic, interventional, and electrophysiology procedures., (© 2017 Wiley Periodicals, Inc.)

Anomalous origin of the left main coronary artery from the noncoronary sinus (LCANS) is a rare variant of anomalous aortic origin of a coronary artery that is not characterized by an interarterial course. Despite the absence of an interarterial course, there are rare reports of LCANS presenting with sudden death, life-threatening arrhythmia, exercise-induced myocardial ischemia, premature ventricular contractions, and syncope. We report a patient with LCANS presenting with acute myocardial infarction who recovered completely with emergent surgical unroofing of the coronary artery.

Background: The medicinal legume Mucuna pruriens (L.) DC. has attracted attention worldwide as a source of the anti-Parkinson's drug L-Dopa. It is also a popular green manure cover crop that offers many agronomic benefits including high protein content, nitrogen fixation and soil nutrients. The plant currently lacks genomic resources and there is limited knowledge on gene expression, metabolic pathways, and genetics of secondary metabolite production. Here, we present transcriptomic resources for M. pruriens, including a de novo transcriptome assembly and annotation, as well as differential transcript expression analyses between root, leaf, and pod tissues. We also develop microsatellite markers and analyze genetic diversity and population structure within a set of Indian germplasm accessions., Results: One-hundred ninety-one million two hundred thirty-three thousand two hundred forty-two bp cleaned reads were assembled into 67,561 transcripts with mean length of 626 bp and N50 of 987 bp. Assembled sequences were annotated using BLASTX against public databases with over 80% of transcripts annotated. We identified 7,493 simple sequence repeat (SSR) motifs, including 787 polymorphic repeats between the parents of a mapping population. 134 SSRs from expressed sequenced tags (ESTs) were screened against 23 M. pruriens accessions from India, with 52 EST-SSRs retained after quality control. Population structure analysis using a Bayesian framework implemented in fastSTRUCTURE showed nearly similar groupings as with distance-based (neighbor-joining) and principal component analyses, with most of the accessions clustering per geographical origins. Pair-wise comparison of transcript expression in leaves, roots and pods identified 4,387 differentially expressed transcripts with the highest number occurring between roots and leaves. Differentially expressed transcripts were enriched with transcription factors and transcripts annotated as belonging to secondary metabolite pathways., Conclusions: The M. pruriens transcriptomic resources generated in this study provide foundational resources for gene discovery and development of molecular markers. Polymorphic SSRs identified can be used for genetic diversity, marker-trait analyses, and development of functional markers for crop improvement. The results of differential expression studies can be used to investigate genes involved in L-Dopa synthesis and other key metabolic pathways in M. pruriens.

Hyposidra talaca is a major defoliating pest of tea plants in north-eastern part of India. In this study, we look for variations (if any) in the attacking virus. Viral samples were collected from different regions of the northern part of West Bengal in India and were analyzed by PCR technique to study the variations across the region. The partial segment of the HytaNPV polyhedrin gene was cloned and sequenced. A 527 bp nucleotide sequence containing highly conserved region from polyhedrin gene of HytaNPV was observed. The blast homology search for studied polyhedrin gene showed 98% sequence identity with the sequence of previous reported NPV of H. talaca, H. infixaria and Buzura suppressaria. Pathogenicity study against second instar H. talaca indicated that the LC 50 values ranged from 4.61 × 10 5 to 7.57 × 10 5 polyhedral occlusion bodies per ml (POBs/ml) and the LT 50 values ranged from 4.2 to 6.66 days. Sequencing result reveals that the same HytaNPV strain dominates across this area and the pathogenicity indicates its potential as an alternative to chemical insecticides to control H. talaca.

Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl)ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)- and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD + - and ATP-dependent chromatin relaxation upon DNA damage in vivo., (© 2016 Sellou, Lebeaupin, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Plant-fungal associations have been explored by routine cultivation based approaches and cultivation based approaches cannot catalogue more than 5% of fungal diversity associated with any niche. In the present study, an attempt has been made to catalogue fungal diversity associated with belowground parts i.e. rhizosphere and cormosphere, of Crocus sativus (an economically important herb) during two growth stages, using cultivation independent ITS gene targeted approach, taking bulk soil as reference. The 454 pyrosequencing sequence data analysis suggests that the fungal diversity was niche and growth stage specific. Fungi diversity, in the present case, was not only different between the two organs (roots and corm) but the dominance pattern varies between the cormosphere during two growth stages. Zygomycota was dominant fungal phylum in the rhizosphere whereas Basidiomycota was dominant in cormosphere during flowering stage. However in cormosphere though Basidiomycota was dominant phylum during flowering stage but Zygomycota was dominant during dormant stage. Interestingly, in cormosphere, the phyla which was dominant at dormant stage was rare at flowering stage and vice-versa (Basidiomycota: Flowering = 93.2% Dormant = 0.05% and Zygomycota: Flowering = 0.8% Dormant = 99.7%). At genus level, Rhizopus was dominant in dormant stage but was rare in flowering stage (Rhizopus: Dormant = 99.7% Flowering = 0.55%). This dynamics is not followed by the bulk soil fungi which was dominated by Ascomycota during both stages under study. The genus Fusarium, whose species F. oxysporum causes corm rot in C. sativus, was present during both stages with slightly higher abundance in roots. Interestingly, the abundance of Rhizopus varied a great deal in two stages in cormosphere but the abundance of Fusarium was comparable in two growth stages (Bulk soil Flowering = 0.05%, Rhizosphere Flowering = 1.4%, Cormosphere Flowering = 0.06%, Bulk soil Dormant = 2.47% and cormosphere dormant = 0.05%). This is the first report on the fungal diversity associated with the root of Crocus sativus and first report on the fungi associated with corm of any plant with the temporal and spatial variation in the fungal community structure., Competing Interests: The authors have declared that no competing interests exist.

Background: Use of nonfluoroscopic 3-dimensional electroanatomic mapping (NF-3DEAM) in patients with congenital heart defects (CHDs) is not well reported., Objective: The purpose of this study was to evaluate the feasibility, accuracy, and safety of NF-3DEAM in patients with CHDs., Methods: Retrospective review of electrophysiologic study (EPS) in patients with CHD from 2009 to 2013 was conducted. Patients undergoing EPS with NF-3DEAM using the EnSite NavX system (St. Jude Medical) were included and those with fluoroscopy were excluded. Cardiac angiography performed in close proximity was matched with 3DEAM by proper aspect ratio using manual alignment by overlay images and comparing distances between cardiac landmarks using Pearson correlation coefficient and intraclass correlation. Success and complications were reviewed., Results: Three-dimensional electroanatomic mapping and angiograms were compared in 48 EPS (45 patients); 13 patients with intracardiac leads, quiescent chambers indicating significant scarring, and who required transseptal puncture were excluded. Indications for EPS included documented tachyarrhythmia and preoperative mapping. Mean age was 25.3 ± 9.8 years. Simple CHDs (isolated shunt lesions or valvular lesions) were identified in 13 studies (27%) and complex CHDs (others) were identified in 35 studies (73%). Ablations were performed in 25 studies (52%). Average time to obtain right atrial geometry was 25.3 minutes (range 14-47 minutes) and right ventricular geometry was 22.8 minutes (range 12-35 minutes). Pearson correlation coefficient and intraclass correlation of cardiac landmarks were 0.90 and 0.80, respectively. Anatomic landmarks, mapping, and ablation were accurate in all 3DEAMs. No complications were recorded., Conclusion: NF-3DEAM is feasible, safe, and accurate in CHD patients without extensive scarring, intracardiac leads, and need for transseptal puncture., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Eukaryotic chromatin is a complex yet dynamic structure, which is regulated in part by the assembly and disassembly of nucleosomes. Key to this process is a group of proteins termed histone chaperones that guide the thermodynamic assembly of nucleosomes by interacting with soluble histones. Here we investigate the interaction between the histone chaperone sNASP and its histone H3 substrate. We find that sNASP binds with nanomolar affinity to a conserved heptapeptide motif in the globular domain of H3, close to the C-terminus. Through functional analysis of sNASP homologues we identified point mutations in surface residues within the TPR domain of sNASP that disrupt H3 peptide interaction, but do not completely disrupt binding to full length H3 in cells, suggesting that sNASP interacts with H3 through additional contacts. Furthermore, chemical shift perturbations from(1)H-(15)N HSQC experiments show that H3 peptide binding maps to the helical groove formed by the stacked TPR motifs of sNASP. Our findings reveal a new mode of interaction between a TPR repeat domain and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants, including CenpA and have implications for the mechanism of histone chaperoning within the cell., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of DNA topoisomerase I and has applications in treating ovarian, small lung and refractory ovarian cancers. Stem wood tissue of Nothapodytes nimmoniana (Graham) Mabb. (family Icacinaceae) is one of the richest sources of CPT. Since there is no genomic or transcriptome data available for the species, the present work sequenced and analysed transcriptome of stem wood tissue on an Illumina platform. From a total of 77,55,978 reads, 9,187 transcripts were assembled with an average length of 255 bp. Functional annotation and categorization of these assembled transcripts unraveled the transcriptome architecture and also a total of 13 genes associated with CPT biosynthetic pathway were identified in the stem wood tissue. Four genes of the pathway were cloned to full length by RACE to validate the transcriptome data. Expression analysis of 13 genes associated with CPT biosynthetic pathway in 11 different tissues vis-a-vis CPT content analysis suggested an important role of NnPG10H, NnPSLS and NnPSTR genes in the biosynthesis of CPT. These results indicated that CPT might be synthesized in the leaves and then perhaps exported to stem wood tissue for storage.