The start of commercial exploitation of soybean in India is nearly four decades old. In this period, the crop has shown unparallel growth in area and production. Soybean has established itself as a major rainy season crop in the rainfed agro-ecosystem of central and peninsular India. Introduction of soybean has resulted in an enhancement in the cropping intensity and resultant increase in the profitability per unit land area. In India, soybean will continue to remain a major rainfed oilseed crop. A number of varieties that have been bred have resulted in this unprecedented growth. The simulation studies and on-farm demonstrations indicate that with current varieties, the rainfed potential of soybean in India is about 2.1 t/ha against the national average productivity of just 1.2 t/ha. Hence, large yield gaps exist between the potential and the actual yields harvested by the farmers. Narrowing of this yield gap may lead to doubling of soybean production. National Agricultural Research System has so far been successful in meeting the research demands of agrarian and industrial community. Further improvements in the yield of soybean grain and quality of soybean oil are possible by use of new research methodologies and by exploitation of recent advances in biology.

Boronic acids have been successfully employed as inhibitors of hydrolytic enzymes. Typically, an enzymatic nucleophile catalyzing hydrolysis adds to the electrophilic boron atom forming a tetrahedral species that mimics the intermediate(s)/transition state(s) for the hydrolysis reaction. We show that para-substituted phenylboronic acids (PBAs) are potent competitive inhibitors of mandelate racemase (MR), an enzyme that catalyzes a 1,1-proton transfer rather than a hydrolysis reaction. The K i value for PBA was 1.8 ± 0.1 μM, and p-Cl-PBA exhibited the most potent inhibition (K i = 81 ± 4 nM), exceeding the binding affinity of the substrate by ∼4 orders of magnitude. Isothermal titration calorimetric studies with the wild-type, K166M, and H297N MR variants indicated that, of the two Brønsted acid−base catalysts Lys 166 and His 297, the former made the greater contribution to inhibitor binding. The X-ray crystal structure of the MR•PBA complex revealed the presence of multiple H-bonds between the boronic acid hydroxyl groups and the side chains of active site residues, as well as formation of a His 297 N ε2 −B dative bond. The dramatic upfield change in chemical shift of 27.2 ppm in the solution-phase 11 B nuclear magnetic resonance spectrum accompanying binding of PBA by MR was consistent with an sp 3 -hybridized boron, which was also supported by density-functional theory calculations. These unprecedented findings suggest that, beyond substituting boron at carbon centers participating in hydrolysis reactions, substitution of boron at the acidic carbon center of a substrate furnishes a new approach for generating inhibitors of enzymes catalyzing the deprotonation of carbon acid substrates.

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation. Methods and results We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%). Conclusion The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.

Sarcoidosis is an inflammatory granulomatous disease that can affect any organ. Up to one-quarter of patients with systemic sarcoidosis may have evidence of cardiac involvement. The clinical manifestations of cardiac sarcoidosis (CS) include heart block, atrial arrhythmias, ventricular arrhythmias and heart failure. The diagnosis of CS can be challenging given the patchy infiltration of the myocardium but, with the increased availability of advanced cardiac imaging, more cases of CS are being identified. Immunosuppression with corticosteroids remains the standard therapy for the acute inflammatory phase of CS, but there is an evolving role of steroid-sparing agents. In this article, the authors provide an update on the diagnosis of CS, including the role of imaging; review the clinical manifestations of CS, namely heart block, atrial and ventricular arrhythmias and heart failure; discuss updated management strategies, including immunosuppression, electrophysiological and heart failure therapies; and identify the current gaps in knowledge and future directions for cardiac sarcoidosis.

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BACKGROUND AND PURPOSERecently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action. EXPERIMENTAL APPROACHJurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry. KEY RESULTSCaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21 CIP1/WAF1 . The effect of CaeA on cell proliferation was reversible. CONCLUSIONS AND IMPLICATIONSCaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron. AbbreviationsCaeA, caerulomycin A; DCFDA, 2′,7′-dichlorofluorescin diacetate; DFO, desferoxamine; dNTP, deoxyribonucleoside triphosphate; ISD, immunosuppressive drug; PI, propidium iodide; RNR, ribonucleotide reductase BJP British Journal of Pharmacology

Seizures and epilepsy in children are common. They are caused by a variety of causes ranging from genetic to neuro -infections. History and actual observation or/video are very important to differentiate true seizure from non-epileptic event. A correct classification of seizure and epilepsy helps to decide need to treat, choice of anti-epileptic drugs (AED) and prognostication. Except for few seizure types, in majority of seizure types regular AED are started after second confirmed seizure. Goal of treatment is seizure control with minimal side effects and ensuring quality of life. With appropriate mono - therapy, about 70 % patients become seizure free and can be easily treated in community. An orderly approach to classify seizure type, holistic management and timely referral of intractable epilepsy will help in improving care of children with epilepsy.