Evolutionary dynamics of the cytoskeletal profilin gene family in Brassica juncea L. reveal its roles in silique development and stress resilience.

Essential to plant adaptation, cell wall (CW) integrity is maintained by CW-biosynthesis genes. Cytoskeletal actin-(de)polymerizing, phospholipid-binding profilin (PRF) proteins play important roles in maintaining cellular homeostasis across kingdoms. However, evolutionary selection of PRF genes and their systematic characterization in family Brassicaceae, especially in Brassica juncea remain unexplored. Here, a comprehensive analysis of genome-wide identification of BjPRFs, their phylogenetic association, genomic localization, gene structure, and transcriptional profiling were performed in an evolutionary framework. Identification of 23 BjPRFs in B. juncea indicated an evolutionary conservation within Brassicaceae. The BjPRFs evolved through paralogous and orthologous gene formation in Brassica genomes. Evolutionary divergence of BjPRFs indicated purifying selection, with nonsynonymous (dN)/synonymous (dS) value of 0.090 for orthologous gene-pairs. Hybrid homology-modeling identified evolutionary distinct and conserved domains in BjPRFs which suggested that these proteins evolved following the divergence of monocot and eudicot plants. RNA-seq profiles of BjPRFs revealed their functional evolution in spatiotemporal manner during plant-development and stress-conditions in diploid/amphidiploid Brassica species. Real-Time PCR experiments in seedling, vegetative, floral and silique tissues of B. juncea suggested their essential roles in systematic plant development. These observations underscore the expansion of BjPRFs in B. juncea, and offer valuable evolutionary insights for exploring cellular mechanisms, and stress resilience.

Blocking µ-opioid receptor by naltrexone exaggerates oxidative stress and airway inflammation via the MAPkinase pathway in a murine model of asthma.

Opioids regulate various physiological and pathophysiological functions, including cell proliferation, immune function, obesity, and neurodegenerative disorders. They have been used for centuries as a treatment for severe pain, binding to opioid receptors a specific G protein-coupled receptor. Common opioids, like ß-endorphin, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), and dynorphins, have analgesic effects. The use of a potent antagonist, like naltrexone hydrochloride, to block the effects of mu Opioid Receptor (µOR) may result in the withdrawal of physiological effects and could potentially impact immune responses in many diseases including respiratory disease. Asthma is a respiratory disease characterized by airway hyperresponsiveness, inflammation, bronchoconstriction, chest tightness, stress generation and release of various cytokines. Airway inflammation leads recruitment and activation of immune cells releasing mediators, including opioids, which may modulate inflammatory response by binding to their respective receptors. The study aims to explore the role of µOR antagonist (naltrexone) in regulating asthma pathophysiology, as the regulation of immune and inflammatory responses in asthma remains unclear. Balb/c mice were sensitized intranasally by 1% TDI and challenged with 2.5% TDI. Naltrexone hydrochloride (1 mg/kg body weight) was administered through intraperitoneal route 1 h before TDI induction. Blocking µOR by naltrexone exacerbates airway inflammation by recruiting inflammatory cells (lymphocytes and neutrophils), enhancing intracellular Reactive oxygen species in bronchoalveolar lavage fluid (BALF), and inflammatory mediator (histamine, Eosinophil peroxidase and neutrophil elastase) in lungs. Naltrexone administration modulated inflammatory cytokines (TNF-α, IL-4, IL-5, IL-6, IL-10, and IL-17A), and enhanced IgE and CRP levels. Naltrexone administration also increased the expression of NF-κB, and phosphorylated p-P38, p-Erk, p-JNK and NF-κB by inhibiting the µOR. Docking study revealed good binding affinity of naltrexone with µOR compared to δ and κ receptors. In future it might elucidate potential therapeutic against many respiratory pathological disorders. In conclusion, µOR blocking by naltrexone regulates and implicates inflammation, bronchoconstriction, and lung physiology.

Pharmacological inhibition of SIRT-2 by AK-7 modulates redox status and apoptosis via regulating Nrf2 in an experimental model of chronic obstructive pulmonary disease: an invivo and insilico study.

Chronic obstructive pulmonary disease (COPD) is defined by inflammation and emphysema. Sirtuins (SIRT) are NAD+-dependent histone deacetylases that regulate oxidative stress and inflammation. The present work investigates the modulatory role of SIRT-2 in experimental COPD model. Insilico comparative assessment of SIRT-2 inhibitors (AK-7 and AGK-2) by ADMET and molecular docking revealed AK-7 as suitable candidate for invivo application. COPD in mice was established by cigarette smoke (CS) exposure for 2 months. AK-7 (100 µg/kg and 200 µg/kg body weight) was administered intranasally one hour before CS exposure. The present investigation demonstrates that CS exposure increases total cell count, and free radical production (total reactive oxygen species, total oxidant status, myeloperoxidase, and nitric oxide), which were decreased by AK-7. It also altered antioxidant enzymatic activity (total antioxidant status, catalase, superoxide dismutase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase, and reduced glutathione), hence preserving the redox balance. AK-7 significantly decreases apoptosis, protein carbonylation, lipid peroxidation, TNF-α and IFN-ï»» levels represent COPD generation in mice and were dramatically decreased by AK-7. Histopathological studies shows that CS exposure damages alveoli and produces peribronchiolar inflammation; both of these events were reduced by AK-7. The antioxidative potency of AK-7 was confirmed by observing Nrf2 and Keap1 proteins. Keap-dependent Nrf2 regulation was observed, with cytosolic Nrf2 and Keap1 expression elevated in COPD and reduced in the AK-7 group while nuclear Nrf2 was reduced in COPD and increased in the AK-7 group. The present study concludes that inhibition of SIRT-2 minimizes COPD severity and mediates therapeutic effects in the lungs.

The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results.

BACKGROUND: The pathfinder6 (NCT02137850) international phase 3 trial examined immunogenicity, safety, and efficacy of the extended half-life factor VIII (FVIII) replacement product N8-GP (turoctocog alfa pegol; Esperoct) in previously untreated patients (PUPs) with hemophilia A. OBJECTIVES: We present end-of trial results for extended PUP N8-GP treatment for up to a median (range) 2.5 (0.0; 7.4) years. PATIENTS/METHODS: Longer-term N8-GP treatment in PUPs with hemophilia A was examined. The prophylaxis regimen was ∼60 IU/kg N8-GP i.v. twice weekly, or every 3 or 7 days. The primary endpoint was the incidence of FVIII inhibitors. RESULTS: Overall, 81 patients received N8-GP and were included in this analysis. The inhibitor incidence was 30.0% (15.7% high-titer [>5 BU]) for the extension phase. Patients had a median (range) 2.9 (0.1; 7.2) years of prophylaxis following the pre-prophylaxis period. During prophylaxis, the median annualized bleeding rate (ABR) (interquartile range) was 1.4 (0.6; 3.5), 13% of patients experienced no bleeding episodes, and 55.1% of patients experienced no spontaneous bleeds. The proportion of patients without any spontaneous bleeding episodes increased after the first year of prophylaxis. The hemostatic success rate in the treatment of bleeding episodes was 87.6%. No additional safety concerns were observed in patients with previously reported observation of temporarily decreased incremental recovery (IR). CONCLUSION: Long-term end-of-trial PUP N8-GP prophylaxis data indicate that PUPs respond well to long-term N8-GP treatment. The inhibitor incidence was consistent with previous results. Median ABR during prophylaxis was 1.4. There were no lasting clinical impacts or safety concerns for patients with an observation of temporarily decreased IR.

ß-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model.

Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. ß-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including ß-Endorphin as an anti­inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of ß-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. ß-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of ß-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of ß-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of ß-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, ß-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of ß-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of ß-Endorphin in regulating asthma.

Comparison of thermal and athermal dynamics of the cell membrane slope fluctuations in the presence and absence of Latrunculin-B.

Conventionally, only the normal cell membrane fluctuations have been studied and used to ascertain membrane properties like the bending rigidity. A new concept, the membrane local slope fluctuations was introduced recently (Vaippullyet al2020Soft Matter167606), which can be modelled as a gradient of the normal fluctuations. It has been found that the power spectral density (PSD) of slope fluctuations behave as (frequency)-1while the normal fluctuations yields (frequency)-5/3even on the apical cell membrane in the high frequency region. In this manuscript, we explore a different situation where the cell is applied with the drug Latrunculin-B which inhibits actin polymerization and find the effect on membrane fluctuations. We find that even as the normal fluctuations show a power law (frequency)-5/3as is the case for a free membrane, the slope fluctuations PSD remains (frequency)-1, with exactly the same coefficient as the case when the drug was not applied. Moreover, while sometimes, when the normal fluctuations at high frequency yield a power law of (frequency)-4/3, the pitch PSD still yields (frequency)-1. Thus, this presents a convenient opportunity to study membrane parameters like bending rigidity as a function of time after application of the drug, while the membrane softens. We also investigate the active athermal fluctuations of the membrane appearing in the PSD at low frequencies and find active timescales of slower than 1 s.

Genetic group and swim-up processing affect SYBR Green real-time PCR-based porcine semen sex ratio in Landrace and its crossbred boars.

Determination of factors affecting sex ratio is important while considering application of sex ratio enrichment approach. Present study aimed to design a SYBR Green qPCR-based method for measurement of primary sex ratio and to evaluate different factors (genetic group, sire, spermiogenic cycle and processing layer) affecting boar sperm sex ratio. The qPCR was based on relative copy number analysis of sex chromosome-specific single copy gene fragments with an autosomal gene as reference and was evaluated using DNA dilution series from pigs with numerically normal karyotype. The sex ratio was estimated from genomic DNA samples isolated from boar semen collected from different genetic groups at different time points and different processing layers. The X chromosome frequencies of semen samples revealed significant effect of genetic group. However, significant variation was observed neither within same genetic group nor between ejaculates of different spermatogenic cycles. Among the processing techniques studied, swim-up technique produced a significant X sperm enrichment in comparison to control whereas, Percoll density gradient failed to show any significant difference among layers. The lower layer in swim-up technique was found to contain higher proportion of X sperms. The designed qPCR is found to be an easy, less time-consuming method and does not require high end laboratory facilities or the specialized expertise. The lower layer of swim-up processing has a scope for X sperm enrichment in boar semen with proper validation.

Potential of hydroethanolic leaf extract of Ocimum sanctum in ameliorating redox status and lung injury in COPD: an in vivo and in silico study.

Oxidative stress and inflammation are hypothesised as the main contributor for Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS), a major cause of COPD leads to inflammation resulting in recruitment of neutrophils and macrophages which are rich sources of oxidants. Activation of these cells produces excess oxidants and depletes antioxidants resulting in stress. Presently, effective drug for COPD is limited; therefore, novel compounds from natural sources, including plants are under exploration. The present study aims to investigate the protective effect of Ocimum sanctum leaf extract (OLE) in CS - induced model of COPD. Exposure to CS was performed thrice a week for 8 weeks and OLE (200 mg/kg and 400 mg/kg) was administered an hour before CS exposure. Control group (negative control) were exposed to ambient air while COPD group was exposed to CS (positive control). Administration of OLE doses reduced inflammation, decreased oxidant concentration and increased antioxidant concentration (p < 0.01). Molecular docking studies between the major phytocompounds of OLE (Eugenol, Cyclohexane and Caryophyllene) and antioxidant enzymes Superoxide dismutase (SOD), Catalase, Glutathione peroxidase (GPx), Glutathione reductase (GR) and Glutathione S Transferase (GST) showed strong binding interaction in terms of binding energy. In vivo and in silico findings for the first time indicates that OLE extract significantly alleviates oxidative stress by its potent free radical scavenging property and strong interaction with antioxidant enzymes. OLE extract may prove to be a therapeutic option for COPD prevention and treatment.

Selection of a stable reference gene for relative copy number profiling of porcine chromosomal genes using SYBR green qPCR.

Reference gene with stable copy number is essential for normalization in qPCR based copy number assay. Present study aims to identify a suitable reference gene in pigs for qPCR based relative copy number profiling of chromosomal genes. A total of 30 crossbred pigs of both sexes were cyto-screened and gDNA was extracted from the pigs having numerically normal karyotypes. The copy number stability was studied for 7 genes (FSHB, IL4, IGF1R, TCF24, BRMS1L, ARMC1 and SRSF4) selected on the basis of the chromosomal location, reports of single copy and lack of involvement in structural chromosomal abnormalities. The copy number was estimated from Ct values in 3 technical replicates using 6 animals from either sex for each gene. The stability was evaluated from the variations in Ct values using different (Delta Ct, geNorm, BestKeeper and normFinder) algorithms. While the moderate variation was observed among relative copy number stabilities among the genes, comprehensive ranking revealed the most stable gene for normalization (IGF1R > FSHB > TCF24 > IL4 > ARMC1> SRSF4 > BRMS1L) across the samples. The selected reference gene was validated using DNA of cyto-screened pigs to find out ratio of X and Y chromosome fragments using qPCR based copy number analysis.

Pseudoxanthomatous Mastocytosis in a 2-Month Female Infant.

Mastocytosis is a rare disease characterized by infiltration of mast cells in various tissues like skin, bone marrow, liver, spleen, and gastrointestinal tract. Here, we present a case report of diffuse cutaneous mastocytosis (pseudoxanthomatous type) in a neonate which is a rare presentation.

Comparison Between QT and Corrected QT Interval Assessment by an Apple Watch With the AccurBeat Platform and by a 12­Lead Electrocardiogram With Manual Annotation: Prospective Observational Study.

BACKGROUND: Abnormal prolongation or shortening of the QT interval is associated with increased risk for ventricular arrhythmias and sudden cardiac death. For continuous monitoring, widespread use, and prevention of cardiac events, advanced wearable technologies are emerging as promising surrogates for conventional 12­lead electrocardiogram (ECG) QT interval assessment. Previous studies have shown a good agreement between QT and corrected QT (QTc) intervals measured on a smartwatch ECG and a 12-lead ECG, but the clinical accuracy of computerized algorithms for QT and QTc interval measurement from smartwatch ECGs is unclear. OBJECTIVE: The prospective observational study compared the smartwatch-recorded QT and QTc assessed using AccurKardia's AccurBeat platform with the conventional 12­lead ECG annotated manually by a cardiologist. METHODS: ECGs were collected from healthy participants (without any known cardiovascular disease) aged >22 years. Two consecutive 30-second ECG readings followed by (within 15 minutes) a 10-second standard 12-lead ECG were recorded for each participant. Characteristics of the participants were compared by sex using a 2-sample t test and Wilcoxon rank sum test. Statistical comparisons of heart rate (HR), QT interval, and QTc interval between the platform and the 12-lead ECG, ECG lead I, and ECG lead II were done using the Wilcoxon sign rank test. Linear regression was used to predict QTc and QT intervals from the ECG based on the platform's QTc/QT intervals with adjustment for age, sex, and difference in HR measurement. The Bland-Altman method was used to check agreement between various QT and QTc interval measurements. RESULTS: A total of 50 participants (32 female, mean age 46 years, SD 1 year) were included in the study. The result of the regression model using the platform measurements to predict the 12-lead ECG measurements indicated that, in univariate analysis, QT/QTc intervals from the platform significantly predicted QT/QTc intervals from the 12-lead ECG, ECG lead I, and ECG lead II, and this remained significant after adjustment for sex, age, and change in HR. The Bland-Altman plot results found that 96% of the average QTc interval measurements between the platform and QTc intervals from the 12-lead ECG were within the 95% confidence limit of the average difference between the two measurements, with a mean difference of -10.5 (95% limits of agreement -71.43, 50.43). A total of 94% of the average QT interval measurements between the platform and the 12-lead ECG were within the 95% CI of the average difference between the two measurements, with a mean difference of -6.3 (95% limits of agreement -54.54, 41.94). CONCLUSIONS: QT and QTc intervals obtained by a smartwatch coupled with the platform's assessment were comparable to those from a 12-lead ECG. Accordingly, with further refinements, remote monitoring using this technology holds promise for the identification of QT interval prolongation.

Force-velocity relation and load-sharing in the linear polymerization ratchet revisited: the effects of barrier diffusion.

We study the velocity-force (V-F) relation for a Brownian ratchet consisting of a linear rigid polymer growing against a diffusing barrier, acted upon by a opposing constant force (F). Using a careful mathematical analysis, we derive the V-F relations in the extreme limits of fast and slow barrier diffusion. In the first case, V depends exponentially on the load F, in agreement with the well-known formula proposed by Peskin, Odell and Oster (1993), while the relationship becomes linear in the second case. For a bundle of two filaments growing against a common barrier, equal sharing of load in the corresponding V-F relation is predicted by a mean-field argument in both limits. However, the scaling behaviour of velocity with the number of filaments is different for the two cases. In the limit of large D, the validity of the mean-field approach is tested, and partially supported by a detailed and rigorous analysis. Our principal predictions are also verified in numerical simulations.

Pregabalin Induced Maculopapular Eruption in an Elderly Male.

BACKGROUND: Pregabalin is used in the treatment of neuropathic pain of various etiologies and as an adjuvant in epilepsy. Blockade of the α2δ subunit of L and N-type Ca-channels is its main mechanism of neurotropic action. Compared to other antiepileptics like phenytoin, valproate and lamotrigine, and other neuropathic pain medications such as amitriptyline and duloxetine, pregabalin has a relatively favorable safety profile and hence is a drug of choice for many geriatricians. CASE PRESENTATION: Here we describe a case of maculopapular rash induced by pregabalin in an older man, which resolved with withdrawal of the offending drug and conservative management. CONCLUSION: We have also conducted a literature review of similar cases and highlighted the clinical patterns and management strategies for pregabalin-induced skin rashes.

A Comparative Evaluation of Measurement-Based Psychiatric Care Delivered via Specialized Telemental Health Platform Versus Treatment As Usual: A Retrospective Analysis.

Background and objective A significant proportion of the adult population in the United States (US) live with some form of mental illness. The more prevalent conditions of depression and anxiety are typically managed in primary care settings rather than specialty care. The aim of this study was to determine the efficacy of a novel, measurement-driven psychiatric treatment platform delivered via an online telemental health platform as compared to treatment as usual (TAU). Methods The TAU dataset and the telemental health platform (Brightside) dataset were constructed based on the total populations of adult patients receiving care for depression from January 2018 through December 2020 (November 2018 through March 2021 for the Brightside group). Patients in both groups had a primary mental health diagnosis of depression and the presence of a positive screen for depression as measured by the Patient Health Questionnaire-9 (PHQ-9) upon initiation of treatment. HITLAB, an independent digital health verification and testing lab, conducted comparative analyses of the two groups using the Chi-square test of independence. Results Close to 80% of telemental health platform patients experienced a reduction of 5 or more points from their baseline PHQ-9 score as compared to 52% of TAU patients. The mean reduction in PHQ-9 score was slightly higher in the Brightside group (-11.5) versus the TAU group (-10.1). Chi-square tests of independence [x2 (1, n=6281) = 256.75, p≤0.001] for meaningful reduction and for remission [x2 (1, n=6281) = 105.50 p≤0.001] were highly significant. Conclusion The telemental health platform patients performed significantly better than those under psychiatric TAU in terms of reduction in symptoms of depression in adults.

Unravelling the molecular mechanism of mutagenic factors impacting human health.

Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate multiple physiological, biochemical, and genetic modifications in humans. Most mutagens are having genotoxic effects on the following generation through germ cells. The influence of germinal mutations on health will be determined by their frequency, nature, and the mechanisms that keep a specific mutation in the population. Early prenatal lethal mutations have less public health consequences than genetic illnesses linked with long-term medical and social difficulties. Physical and chemical mutagens are common mutagens found in the environment. These two environmental mutagens have been associated with multiple neurological disorders and carcinogenesis in humans. Thus in this study, we aim to unravel the molecular mechanism of physical mutagens (UV rays, X-rays, gamma rays), chemical mutagens (dimethyl sulfate (DMS), bisphenol A (BPA), polycyclic aromatic hydrocarbons (PAHs), 5-chlorocytosine (5ClC)), and several heavy metals (Ar, Pb, Al, Hg, Cd, Cr) implicated in DNA damage, carcinogenesis, chromosomal abnormalities, and oxidative stress which leads to multiple disorders and impacting human health. Biological tests for mutagen detection are crucial; therefore, we also discuss several approaches (Ames test and Mutatox test) to estimate mutagenic factors in the environment. The potential risks of environmental mutagens impacting humans require a deeper basic knowledge of human genetics as well as ongoing research on humans, animals, and their tissues and fluids.

Pleiotropic role of PARP1: an overview.

Poly (ADP-ribose) polymerase 1 (PARP1) protein is encoded by the PARP1 gene located on chromosome 1 (1q42.12) in human cells. It plays a crucial role in post-translational modification by adding poly (ADP-ribose) (PAR) groups to various proteins and PARP1 itself by utilizing nicotinamide adenine dinucleotide (NAD +) as a substrate. Since the discovery of PARP1, its role in DNA repair and cell death has been its identity. This is evident from an overwhelmingly high number of scientific reports in this regard. However, PARP1 also plays critical roles in inflammation, metabolism, tumor development and progression, chromatin modification and transcription, mRNA stability, and alternative splicing. In the present study, we attempted to compile all the scattered scientific information about this molecule, including the structure and multifunctional role of PARP1 in cancer and non-cancer diseases, along with PARP1 inhibitors (PARPis). Furthermore, for the first time, we have classified PARP1-mediated cell death for ease of understanding its role in cell death pathways.

Understanding the genomic architecture of clinical mastitis in Bos indicus.

This study elucidated potential genetic variants and QTLs associated with clinical mastitis incidence traits in Bos indicus breed, Sahiwal. Estimated breeding values for the traits (calculated using Bayesian inference) were used as pseudo-phenotypes for association with genome-wide SNPs and further QTL regions underlying the traits were identified. In all, 25 SNPs were found to be associated with the traits at the genome-wide suggestive threshold (p ≤ 5 × 10-4) and these SNPs were used to define QTL boundaries based on the linkage disequilibrium structure. A total of 16 QTLs were associated with the trait EBVs including seven each for clinical mastitis incidence (CMI) in first and second lactations and two for CMI in third lactation. Nine out of sixteen QTLs overlapped with the already reported QTLs for mastitis traits, whereas seven were adjudged as novel ones. Important candidates for clinical mastitis in the identified QTL regions included DNAJB9, ELMO1, ARHGAP26, NR3C1, CACNB2, RAB4A, GRB2, NUP85, SUMO2, RBPJ, and RAB33B genes. These findings shed light on the genetic architecture of the disease in Bos indicus, and present potential regions for fine mapping and downstream analysis in future.

First report of 16SrII group (Peanut witches' Broom) Phytoplasmas associated with the Leucas aspera Phyllody in India.

Leucas aspera (Wild.) Linn. (Family: Lamiaceae) is a commonly found weed throughout India, known for its pharmacological properties. Its white flowers and leaves are used in many Ayurvedic formulations for the treatment of chronic rheumatism, psoriasis, snake bites and skin eruptions (Prajapathi et al., 2010). During a survey of commercial flower crop fields in May 2018, a few L. aspera plants, growing as unwanted weeds in the fields and surrounding agricultural wastelands with the symptoms of phyllody, virescence and little leaves were observed in Emmekoppalu (12.2106, 76.2511; n= 1/26 plants) and Beerihundi (12.1630, 76.3225; n= 2/59 plants) localities of Mysuru district, and Srirangapatna in Mandya district (12.2541, 76.411; 1/67 plants), Karnataka- India(Figure 1). 'n' denotes the symptomatic/ asymptomatic samples observed. The disease incidence in the surveyed localities ranged less than four per cent. The total genomic DNA was extracted from the leaf midrib tissues of three representative symptomatic and two asymptomatic samples using the CTAB method. The phytoplasma 16S rRNA gene was amplified in nested PCR assay by P1/P7 followed by R16F2n/R16R2 primers using Long Amplification (LA) Taq polymerase (Takara, Japan). Additionally, the PCR assays were performed for the amplification of phytoplasma secA gene using the primers SecAfor1/SecArev3 and SecAfor2/SecArev3 (Hodgetts et al., 2008). The DNA templates from all the symptomatic samples generated amplicons of approximately 1.25kb (16S rRNA gene) and 480 bp (secA gene) revealing the association of phytoplasma strains. No amplifications were observed for the asymptomatic L. aspera samples. The obtained 16S rRNA gene sequences (MN223676, MT807111 and MZ093053) showed 97.96, 98.37 and 98.18 % sequence identity, respectively; with the 'Candidatus Phytoplasma aurantifolia', strain 'WBDL (U15442) using EzBiocloud database. The NCBI-BLAST analysis revealed maximum identity to various Peanut witches' Broom (PWB) phytoplasma strains. The virtual RFLP tool, iPhyClassifier delineated the Leucas phyllody phytoplasma strains (MN223676, MT807111 and MZ093053) to group 16SrII (PWB, Peanut Witches' broom group) subgroup D with the similarity coefficient 1.0 (Zhao et al. 2009). The obtained secA gene sequences (MZ151944, MZ151945 and MZ151946) were 98.15 to 100 % similar to the strain sequences of PWB phytoplasma strains. Further, the clustering pattern in the phylogenetic trees (16S rRNA and secA genes) constructed using MEGA 7 confirmed that the Leucas phyllody phytoplasma sequences were closely related to PWB strains. To the best of our knowledge, this is the first report on the association of 16SrII-D subgroup phytoplasma with the phyllody disease of L. aspera. In India, many weeds and wild plants serve as alternative hosts of PWB phytoplasmas and aid in the emergence of related diseases in economically important crops (Thorat et al., 2016; Thorat et al., 2017). The close genetic association of phytoplasma strains found in L. aspera and many other crops indicates the presence of common insect vector(s) transmitting these phytoplasmas (Yadav et al. 2015). This report is an addition to the catalogue of the weed species harboring phytoplasma strains associated with economically important crop plants (Rao et al., 2017). The screening of phytoplasma strains in weeds, alternate hosts and known/ unknown insect vectors is therefore essential to develop management strategies and effective management of phytophagous insect vectors feeding on both weeds and crop plants.

Quantitative Modeling of Protein Synthesis Using Ribosome Profiling Data.

Quantitative prediction on protein synthesis requires accurate translation initiation and codon translation rates. Ribosome profiling data, which provide steady-state distribution of relative ribosome occupancies along a transcript, can be used to extract these rate parameters. Various methods have been developed in the past few years to measure translation-initiation and codon translation rates from ribosome profiling data. In the review, we provide a detailed analysis of the key methods employed to extract the translation rate parameters from ribosome profiling data. We further discuss how these approaches were used to decipher the role of various structural and sequence-based features of mRNA molecules in the regulation of gene expression. The utilization of these accurate rate parameters in computational modeling of protein synthesis may provide new insights into the kinetic control of the process of gene expression.