Origins of specificity in protein-DNA recognition.

Specific interactions between proteins and DNA are fundamental to many biological processes. In this review, we provide a revised view of protein-DNA interactions that emphasizes the importance of the three-dimensional structures of both macromolecules. We divide protein-DNA interactions into two categories: those when the protein recognizes the unique chemical signatures of the DNA bases (base readout) and those when the protein recognizes a sequence-dependent DNA shape (shape readout). We further divide base readout into those interactions that occur in the major groove from those that occur in the minor groove. Analogously, the readout of the DNA shape is subdivided into global shape recognition (for example, when the DNA helix exhibits an overall bend) and local shape recognition (for example, when a base pair step is kinked or a region of the minor groove is narrow). Based on the >1500 structures of protein-DNA complexes now available in the Protein Data Bank, we argue that individual DNA-binding proteins combine multiple readout mechanisms to achieve DNA-binding specificity. Specificity that distinguishes between families frequently involves base readout in the major groove, whereas shape readout is often exploited for higher resolution specificity, to distinguish between members within the same DNA-binding protein family.

Impact of individual, combined and sequential stress on photosynthesis machinery in rice (Oryza sativa L).

Abiotic stresses such as heat, drought and submergence are major threats to global food security. Despite simultaneous or sequential occurrence of these stresses being recurrent under field conditions, crop response to such stress combinations is poorly understood. Rice is a staple food crop for the majority of human beings. Exploitation of existing genetic diversity in rice for combined and/or sequential stress is a useful approach for developing climate-resilient cultivars. We phenotyped ~400 rice accessions under high temperature, drought, or submergence and their combinations. A cumulative performance index revealed Lomello as the best performer across stress and stress combinations at the seedling stage. Lomello showed a remarkable ability to maintain a higher quantum yield of photosystem (PS) II photochemistry. Moreover, the structural integrity of the photosystems, electron flow through both PSI and PSII and the ability to protect photosystems against photoinhibition were identified as the key traits of Lomello across the stress environments. A higher membrane stability and an increased amount of leaf chlorophyll under stress may be due to an efficient management of reactive oxygen species (ROS) at the cellular level. Further, an efficient electron flow through the photosystems and, thus, a higher photosynthetic rate in Lomello is expected to act as a sink for ROS by reducing the rate of electron transport to the high amount of molecular oxygen present in the chloroplast. However, further studies are needed to identify the molecular mechanism(s) involved in the stability of photosynthetic machinery and stress management in Lomello during stress conditions.

Sequential activation of Notch and Grainyhead gives apoptotic competence to Abdominal-B expressing larval neuroblasts in Drosophila Central nervous system.

Neural circuitry for mating and reproduction resides within the terminal segments of central nervous system (CNS) which express Hox paralogous group 9-13 (in vertebrates) or Abdominal-B (Abd-B) in Drosophila. Terminal neuroblasts (NBs) in A8-A10 segments of Drosophila larval CNS are subdivided into two groups based on expression of transcription factor Doublesex (Dsx). While the sex specific fate of Dsx-positive NBs is well investigated, the fate of Dsx-negative NBs is not known so far. Our studies with Dsx-negative NBs suggests that these cells, like their abdominal counterparts (in A3-A7 segments) use Hox, Grainyhead (Grh) and Notch to undergo cell death during larval development. This cell death also happens by transcriptionally activating RHG family of apoptotic genes through a common apoptotic enhancer in early to mid L3 stages. However, unlike abdominal NBs (in A3-A7 segments) which use increasing levels of resident Hox factor Abdominal-A (Abd-A) as an apoptosis trigger, Dsx-negative NBs (in A8-A10 segments) keep the levels of resident Hox factor Abd-B constant. These cells instead utilize increasing levels of the temporal transcription factor Grh and a rise in Notch activity to gain apoptotic competence. Biochemical and in vivo analysis suggest that Abdominal-A and Grh binding motifs in the common apoptotic enhancer also function as Abdominal-B and Grh binding motifs and maintains the enhancer activity in A8-A10 NBs. Finally, the deletion of this enhancer by the CRISPR-Cas9 method blocks the apoptosis of Dsx-negative NBs. These results highlight the fact that Hox dependent NB apoptosis in abdominal and terminal regions utilizes common molecular players (Hox, Grh and Notch), but seems to have evolved different molecular strategies to pattern CNS.

Classification of reviews of e-healthcare services to improve patient satisfaction: Insights from an emerging economy.

The COVID-19 pandemic has brought in many unique challenges and opportunities for patient care, and one is online healthcare practices. Patient satisfaction with online consultation is primary importance as online healthcare practices are evolving with time. Although previous research has examined how patient satisfaction with online doctor services can be further improved, there has been scant research on the satisfaction with online doctor services concerning Indian patients. Within the framework of service science theories, this study examines satisfaction and sentiments of Indian patients with online doctor services from multiple perspectives. A total of 38019 patient online feedback for 343 doctors was used for understanding patient sentiments. The sentiment analysis classified the reviews of the patients on online doctor consultation services. The finding suggests that healthcare service providers consider a systemic approach that includes core health services along with technical and marketing factors to proactively improve online patient satisfaction.

Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains.

Neural precursor cells expressed developmentally downregulated protein 4-2 (Nedd4-2), a homologous to the E6-AP carboxyl terminus (HECT) ubiquitin ligase, triggers the endocytosis and degradation of its downstream target molecules by regulating signal transduction through interactions with other targets, including 14-3-3 proteins. In our previous study, we found that 14-3-3 binding induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains. Here, we used time-resolved fluorescence intensity and anisotropy decay measurements, together with fluorescence quenching and mass spectrometry, to further characterize interactions between Nedd4-2 and 14-3-3 proteins. The results showed that 14-3-3 binding affects the emission properties of AEDANS-labeled WW3, WW4, and, to a lesser extent, WW2 domains, and reduces their mobility, but not those of the WW1 domain, which remains mobile. In contrast, 14-3-3 binding has the opposite effect on the active site of the HECT domain, which is more solvent exposed and mobile in the complexed form than in the apo form of Nedd4-2. Overall, our results suggest that steric hindrance of the WW3 and WW4 domains combined with conformational changes in the catalytic domain may account for the 14-3-3 binding-mediated regulation of Nedd4-2.

The Hox gene Abdominal-B uses DoublesexF as a cofactor to promote neuroblast apoptosis in the Drosophila central nervous system.

Highly conserved DM domain-containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In the Drosophila central nervous system, a set of Doublesex (Dsx)-expressing neuroblasts undergo apoptosis in females whereas their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that the female-specific isoform of Dsx collaborates with Hox gene Abdominal-B (Abd-B) to bring about this apoptosis. Biochemical results suggest that proteins AbdB and Dsx interact through their highly conserved homeodomain and DM domain, respectively. This interaction is translated into a cooperative binding of the two proteins on the apoptotic enhancer in the case of females but not in the case of males, resulting in female-specific activation of apoptotic genes. The capacity of AbdB to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species.

DTH8 overexpression induces early flowering, boosts yield, and improves stress recovery in rice cv IR64.

Rice yield and heading date are the two discrete traits controlled by quantitative trait loci (QTLs). Both traits are influenced by the genetic make-up of the plant as well as the environmental factors where it thrives. Drought and salinity adversely affect crop productivity in many parts of the world. Tolerance to these stresses is multigenic and complex in nature. In this study, we have characterized a QTL, DTH8 (days to heading) from Oryza sativa L. cv IR64 that encodes a putative HAP3/NF-YB/CBF subunit of CCAAT-box binding protein (HAP complex). We demonstrate DTH8 to be positively influencing the yield, heading date, and stress tolerance in IR64. DTH8 up-regulates the transcription of RFT1, Hd3a, GHD7, MOC1, and RCN1 in IR64 at the pre-flowering stage and plays a role in early flowering, increased number of tillers, enhanced panicle branching, and improved tolerance towards drought and salinity stress at the reproductive stage. The presence of DTH8 binding elements (CCAAT) in the promoter regions of all of these genes, predicted by in silico analysis of the promoter region, indicates the regulation of their expression by DTH8. In addition, DTH8 overexpressing transgenic lines showed favorable physiological parameters causing less yield penalty under stress than the WT plants. Taken together, DTH8 is a positive regulator of the network of genes related to early flowering/heading, higher yield, as well as salinity and drought stress tolerance, thus, enabling the crops to adapt to a wide range of climatic conditions.

Ion transporters and their regulatory signal transduction mechanisms for salinity tolerance in plants.

Soil salinity is one of the most serious threats to plant growth and productivity. Due to global climate change, burgeoning population and shrinking arable land, there is an urgent need to develop crops with minimum reduction in yield when cultivated in salt-affected areas. Salinity stress imposes osmotic stress as well as ion toxicity, which impairs major plant processes such as photosynthesis, cellular metabolism, and plant nutrition. One of the major effects of salinity stress in plants includes the disturbance of ion homeostasis in various tissues. In the present study, we aimed to review the regulation of uptake, transport, storage, efflux, influx, and accumulation of various ions in plants under salinity stress. We have summarized major research advancements towards understanding the ion homeostasis at both cellular and whole-plant level under salinity stress. We have also discussed various factors regulating the function of ion transporters and channels in maintaining ion homeostasis and ionic interactions under salt stress, including plant antioxidative defense, osmo-protection, and osmoregulation. We further elaborated on stress perception at extracellular and intracellular levels, which triggers downstream intracellular-signaling cascade, including secondary messenger molecules generation. Various signaling and signal transduction mechanisms under salinity stress and their role in improving ion homeostasis in plants are also discussed. Taken together, the present review focuses on recent advancements in understanding the regulation and function of different ion channels and transporters under salt stress, which may pave the way for crop improvement.

Investigating the breast cancer screening-treatment-mortality pathway of women diagnosed with invasive breast cancer: Results from linked health data.

OBJECTIVE: To examine the screening-treatment-mortality pathway among women with invasive breast cancer in 2006-2014 using linked data. METHODS: BreastScreen histories of South Australian women diagnosed with breast cancer (n = 8453) were investigated. Treatments recorded within 12 months from diagnosis were obtained from linked registry and administrative data. Associations of screening history with treatment were investigated using logistic regression and with cancer mortality outcomes using competing risk analyses, adjusting for socio-demographic, cancer and comorbidity characteristics. RESULTS AND CONCLUSION: For screening ages of 50-69 years, 70% had participated in BreastScreen SA ≤ 5 years and 53% ≤ 2 years of diagnosis. Five-year disease-specific survival post-diagnosis was 90%. Compared with those not screened ≤5 years, women screened ≤2 years had higher odds, adjusted for socio-demographic, cancer and comorbidity characteristics, and diagnostic period, of breast-conserving surgery (aOR 2.5, 95% CI 1.9-3.2) and radiotherapy (aOR 1.2, 95% CI 1.1-1.3). These women had a lower unadjusted risk of post-diagnostic cancer mortality (SHR 0.33, 95% CI 0.27-0.41), partly mediated by stage (aSHR 0.65, 95% CI 0.51-0.81), and less breast surgery (aSHR 0.78, 95% CI 0.62-0.99). Screening ≤2 years and conserving surgery appeared to have a greater than additive association with lower post-diagnostic mortality (interaction term SHR 0.42, 95% CI 0.23-0.78). The screening-treatment-mortality pathway was investigated using linked data.

Towards Developing a Robust Intrusion Detection Model Using Hadoop-Spark and Data Augmentation for IoT Networks.

In recent years, anomaly detection and machine learning for intrusion detection systems have been used to detect anomalies on Internet of Things networks. These systems rely on machine and deep learning to improve the detection accuracy. However, the robustness of the model depends on the number of datasamples available, quality of the data, and the distribution of the data classes. In the present paper, we focused specifically on the amount of data and class imbalanced since both parameters are key in IoT due to the fact that network traffic is increasing exponentially. For this reason, we propose a framework that uses a big data methodology with Hadoop-Spark to train and test multi-class and binary classification with one-vs-rest strategy for intrusion detection using the entire BoT IoT dataset. Thus, we evaluate all the algorithms available in Hadoop-Spark in terms of accuracy and processing time. In addition, since the BoT IoT dataset used is highly imbalanced, we also improve the accuracy for detecting minority classes by generating more datasamples using a Conditional Tabular Generative Adversarial Network (CTGAN). In general, our proposed model outperforms other published models including our previous model. Using our proposed methodology, the F1-score of one of the minority class, i.e., Theft attack was improved from 42% to 99%.

Stacking for future: Pyramiding genes to improve drought and salinity tolerance in rice.

Abiotic stresses, such as drought and salinity, adversely affect rice production and cause a severe threat to food security. Conventional crop breeding techniques alone are inadequate for achieving drought stress tolerance in crop plants. Using transgenic technology, incremental improvements in tolerance to drought and salinity have been successfully attained via manipulation of gene(s) in several crop species. However, achieving the goal via pyramiding multiple genes from the same or different tolerance mechanisms has received little attention. Pyramiding of multiple genes can be achieved either through breeding, by using marker-assisted selection, or by genetic engineering through molecular stacking co-transformation or re-transformation. Transgene stacking into a single locus has added advantages over breeding or re-transformation since the former assures co-inheritance of genes, contributing to more effective tolerance in transgenic plants for generations. Drought, being a polygenic trait, the potential candidate genes for gene stacking are those contributing to cellular detoxification, osmolyte accumulation, antioxidant machinery, and signaling pathways. Since cellular dehydration is inbuilt in salinity stress, manipulation of these genes results in improving tolerance to salinity along with drought in most of the cases. In this review, attempts have been made to provide a critical assessment of transgenic plants developed through transgene stacking and approaches to achieve the same. Identification and functional validation of more such candidate genes is needed for research programs targeting the gene stacking for developing crop plants with high precision in the shortest possible time to ensure sustainable crop productivity under marginal lands.

WRKY transcription factors and plant defense responses: latest discoveries and future prospects.

KEY MESSAGE: WRKY transcription factors are among the largest families of transcriptional regulators. In this review, their pivotal role in modulating various signal transduction pathways during biotic and abiotic stresses is discussed. Transcription factors (TFs) are important constituents of plant signaling pathways that define plant responses against biotic and abiotic stimuli besides playing a role in response to internal signals which coordinate different interacting partners during developmental processes. WRKY TFs, deriving their nomenclature from their signature DNA-binding sequence, represent one of the largest families of transcriptional regulators found exclusively in plants. By modulating different signal transduction pathways, these TFs contribute to various plant processes including nutrient deprivation, embryogenesis, seed and trichome development, senescence as well as other developmental and hormone-regulated processes. A growing body of research suggests transcriptional regulation of WRKY TFs in adapting plant to a variety of stressed environments. WRKY TFs can regulate diverse biological functions from receptors for pathogen triggered immunity, modulator of chromatin for specific interaction and signal transfer through a complicated network of genes. Latest discoveries illustrate the interaction of WRKY proteins with other TFs to form an integral part of signaling webs that regulate several seemingly disparate processes and defense-related genes, thus establishing their significant contributions to plant immune response. The present review starts with a brief description on the structural characteristics of WRKY TFs followed by the sections that present recent evidence on their roles in diverse biological processes in plants. We provide a comprehensive overview on regulatory crosstalks involving WRKY TFs during multiple stress responses in plants and future prospects of WRKY TFs as promising molecular diagnostics for enhancing crop improvement.

Female breast cancer treatment and survival in South Australia: Results from linked health data.

OBJECTIVE: We investigated treatment and survival by clinical and sociodemographic characteristics for service evaluation using linked data. METHOD: Data on invasive female breast cancers (n = 13,494) from the South Australian Cancer Registry (2000-2014 diagnoses) were linked to hospital inpatient, radiotherapy and universal health insurance data. Treatments ≤12 months from diagnosis and survival were analysed, using adjusted odds ratios (aORs) from logistic regression, and adjusted sub-hazard ratios (aSHRs) from competing risk regression. RESULTS AND CONCLUSION: Five-year disease-specific survival increased to 91% for 2010-2014. Most women had breast surgery (90%), systemic therapy (72%) and radiotherapy (60%). Less treatment applied for ages 80+ vs <50 years (aOR 0.10, 95% CI 0.05-0.20) and TNM stage IV vs stage I (aOR 0.13, 95% CI 0.08-0.22). Surgical treatment increased during the study period and strongly predicted higher survival. Compared with no surgery, aSHRs were 0.31 (95% CI 0.26-0.36) for women having breast-conserving surgery, 0.49 (95% CI 0.41-0.57) for mastectomy and 0.42 (95% CI 0.33-0.52) when both surgery types were received. Patients aged 80+ years had lower survival and less treatment. More trial evidence is needed to optimise trade-offs between benefits and harms in these older women. Survival differences were not found by residential remoteness and were marginal by socioeconomic status.

Elucidating the Response of Crop Plants towards Individual, Combined and Sequentially Occurring Abiotic Stresses.

In nature, plants are exposed to an ever-changing environment with increasing frequencies of multiple abiotic stresses. These abiotic stresses act either in combination or sequentially, thereby driving vegetation dynamics and limiting plant growth and productivity worldwide. Plants' responses against these combined and sequential stresses clearly differ from that triggered by an individual stress. Until now, experimental studies were mainly focused on plant responses to individual stress, but have overlooked the complex stress response generated in plants against combined or sequential abiotic stresses, as well as their interaction with each other. However, recent studies have demonstrated that the combined and sequential abiotic stresses overlap with respect to the central nodes of their interacting signaling pathways, and their impact cannot be modelled by swimming in an individual extreme event. Taken together, deciphering the regulatory networks operative between various abiotic stresses in agronomically important crops will contribute towards designing strategies for the development of plants with tolerance to multiple stress combinations. This review provides a brief overview of the recent developments in the interactive effects of combined and sequentially occurring stresses on crop plants. We believe that this study may improve our understanding of the molecular and physiological mechanisms in untangling the combined stress tolerance in plants, and may also provide a promising venue for agronomists, physiologists, as well as molecular biologists.

Novel Application of Hot Melt Extrusion Technology for Preparation and Evaluation of Valacyclovir Hydrochloride Ocular Inserts.

The objective of this study was to investigate the processability of hot-melt extrusion (HME) to formulate ocular inserts of valacyclovir hydrochloride and evaluate the in vivo bioavailability of the formulation. To optimize the formulation of this drug, different physical mixtures of the polymers and plasticizer were prepared. The physical mixture was extruded through a co-rotating twin-screw extruder, and the obtained ocular inserts were cut with dimensions of 4 mm × 2 mm × 1 mm to enhance the formulation instillation in the eye. Ocular inserts were evaluated for drug content, weight variation, uniformity of thickness, in vitro drug release, and in vivo drug bioavailability. The ocular inserts were thermally characterized using differential scanning calorimetry (DSC). The attributes observed for the ocular inserts were within the target specifications. The ocular inserts of valacyclovir hydrochloride were successfully prepared using the HME. They provided sustained drug release along with enhanced drug permeation when compared with the eyedrop solution and dissolve completely in 8 h. Additionally, the obtained results demonstrated that the formulation of ocular inserts of valacyclovir hydrochloride using HME was reproducible, robust, and effective method.

Methylglyoxal-glyoxalase system as a possible selection module for raising marker-safe plants in rice.

Methylglyoxal (MG) is ubiquitously produced in all living organisms as a byproduct of glycolysis, higher levels of which are cytotoxic, leading to oxidative stress and apoptosis in the living systems. Though its generation is spontaneous but its detoxification involves glyoxalase pathway genes. Based on this understanding, the present study describes the possible role of MG as a novel non-antibiotic-based selection agent in rice. Further, by metabolizing MG, the glyoxalase pathway genes viz. glyoxalase I (GLYI) and glyoxalase II (GLYII), may serve as selection markers. Therefore, herein, transgenic rice harboring GLYI-GLYII genes (as selection markers) were developed and the effect of MG as a selection agent was assessed. The 3 mM MG concentration was observed as optimum for the selection of transformed calli, allowing efficient callus induction and proliferation along with high regeneration frequency (55 ± 2%) of the transgenic calli. Since the transformed calli exhibited constitutively higher activity of GLYI and GLYII enzymes compared to the wild type calli, the rise in MG levels was restricted even upon exogenous addition of MG during the selection process, resulting in efficient selection of the transformed calli. Therefore, MG-based selection method is a useful and efficient system for selection of transformed plants without significantly compromising the transformation efficiency. Further, this MG-based selection system is bio-safe and can pave way towards better public acceptance of transgenic plants.

Enhancing trehalose biosynthesis improves yield potential in marker-free transgenic rice under drought, saline, and sodic conditions.

Edaphic factors such as salinity, sodicity, and drought adversely affect crop productivity, either alone or in combination. Despite soil sodicity being reported as an increasing problem worldwide, limited efforts have been made to address this issue. In the present study, we aimed to generate rice with tolerance to sodicity in conjunction with tolerance to salinity and drought. Using a fusion gene from E. coli coding for trehalose-6-phosphate synthase/phosphatase (TPSP) under the control of an ABA-inducible promoter, we generated marker-free, high-yielding transgenic rice (in the IR64 background) that can tolerate high pH (~9.9), high EC (~10.0 dS m-1), and severe drought (30-35% soil moisture content). The transgenic plants retained higher relative water content (RWC), chlorophyll content, K+/Na+ ratio, stomatal conductance, and photosynthetic efficiency compared to the wild-type under these stresses. Positive correlations between trehalose overproduction and high-yield parameters were observed under drought, saline, and sodic conditions. Metabolic profiling using GC-MS indicated that overproduction of trehalose in leaves differently modulated other metabolic switches, leading to significant changes in the levels of sugars, amino acids, and organic acids in transgenic plants under control and stress conditions. Our findings reveal a novel potential technological solution to tackle multiple stresses under changing climatic conditions.

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide.

BACKGROUND: This analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial. METHODS: Adults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm. RESULTS: One hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p < 0.01; placebo p = 0.02) and pain scores (octreotide p < 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores. CONCLUSION: The HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008).

Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS.

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.

Novel ß-Coronavirus (SARS-CoV-2): Current and future aspects of pharmacological treatments.

The novel coronavirus outbreak has reported to be rapidly spreading across the countries and becomes a foremost community health alarm. At present, no vaccine or specific drug is on hand for the treatment of this infectious disease. This review investigates the drugs, which are being evaluated and found to be effective against nCOVID-19 infection. A thorough literature search was performedon the recently published research papers in between January 2020 to May 2020, through various databases like "Science Direct", "Google Scholar", "PubMed","Medline", "Web of Science", and "World Health Organization (WHO)". We reviewed and documented the information related with the current and future aspects for the management and cure of COVID-19. As of 21st July 2020 a total of 14,562,550 confirmed cases of coronavirus and 607,781 deaths have been reported world-wide. The main clinical feature of COVID-19 ranges from asymptomatic disease to mild lower respiratory tract illness to severe pneumonia, acute lung injury, acute respiratory distress syndrome (ARDS), multiple organ dysfunction, and death. The drugs at present used in COVID-19 patients and ongoing clinical trials focusing on drug repurposing of various therapeutic classes of drug e.g. antiviral, anti-inflammatory and/or immunomodulatory drugs along with adjuvant/supportive care. Many drugs on clinical trials shows effective results on preliminary scale and now used currently in patients. Adjuvant/supportive care therapy are used in patients to get the best results in order to minimize the short and long-term complications. However, further studies and clinical trials are needed on large scale of population to reach any firm conclusion in terms of its efficacy and safety.