Sales Management Portal

In the organizations managing the sales and client’s information plays a key role so for managing that information we are going to develop a Sales Management Portal. Sales Management portal is used to manage all the products and the services sales details and customer details in the organization. By using this portal, the sales information in the organization can be managed easily and in a secured way. This web portal is very scalable which can be used for the small and also for the large organizations. With this portal manager can see the employee’s progress and can also share the important messages with the employees by using announcements. This portal is also used by the employees to save and manage all the clients and prospects details. Employees can also manage the client’s general information, contact, opportunities, proposals and projects details. Modules: When coming to the modules of this portal, it contains 3 main modules like Administrator, Manager and Employee. Administrator: In this module the administrator can add and authorize the manager for accessing the appropriate operations and he can also view the current projects, proposals, prospects and clients details. Administrator can also post any important information like the meeting timings. Manager: In this module the manager can add and authorize the employees for doing necessary actions to store the clients and prospects general information, opportunities, proposals and projects details. By using this module, the manager can also track the employee’s progress and can also send the messages to the employees. In this module the manager can also view and update prospects, opportunities and proposals details and the manager can also manage the project details. Employee: In this module the employees can add and save the new clients and prospects details with their general information, contact information and their proposals, opportunities and projects information. The sales management employees can also update the clients and prospects information and they can also search the client or a prospect through their names or by using the client or prospect filters to search the appropriate details

CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD). However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB) activation, and activity-regulated cytoskeleton-associated protein (Arc) expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP), spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD

riboviz 2:A flexible and robust ribosome profiling data analysis and visualization workflow

MOTIVATION: Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. RESULTS: We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline. AVAILABILITY AND IMPLEMENTATION: riboviz 2 is freely available at github.com/riboviz/riboviz

Implications of tolerance to iron toxicity on root system architecture changes in rice (Oryza sativa L.)

IntroductionToxicity due to excess soil iron (Fe) is a significant concern for rice cultivation in lowland areas with acidic soils. Toxic levels of Fe adversely affect plant growth by disrupting the absorption of essential macronutrients, and by causing cellular damage. To understand the responses to excess Fe, particularly on seedling root system, this study evaluated rice genotypes under varying Fe levels.MethodsSixteen diverse rice genotypes were hydroponically screened under induced Fe levels, ranging from normal to excess. Morphological and root system characteristics were observed. The onset of leaf bronzing was monitored to identify the toxic response to the excess Fe. Additionally, agronomic and root characteristics were measured to classify genotypes into tolerant and sensitive categories by computing a response stability index.ResultsOur results revealed that 460 ppm of Fe in the nutrient solution served as a critical threshold for screening genotypes during the seedling stage. Fe toxicity significantly affected root system traits, emphasizing the consequential impact on aerial biomass and nutrient deprivation. To classify genotypes into tolerant and sensitive categories, leaf bronzing score was used as a major indicator of Fe stress. However, the response stability index provided a robust basis for classification for the growth performance. Apart from the established tolerant varieties, we could identify a previously unrecognized tolerant variety, ILS 12–5 in this study. Some of the popular mega varieties, including BPT 5204 and Pusa 44, were found to be highly sensitive.DiscussionOur findings suggest that root system damage, particularly in root length, surface area, and root volume, is the key factor contributing to the sensitivity responses under Fe toxicity. Tolerant genotypes were found to retain more healthy roots than the sensitive ones. Fe exclusion, by reducing Fe2+ uptake, may be a major mechanism for tolerance among these genotypes. Further field evaluations are necessary to confirm the behavior of identified tolerant and sensitive lines under natural conditions. Insights from the study provide potential scope for enhancement of tolerance through breeding programs as well as throw light on the role root system in conferring tolerance

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

SNP2SIM: a modular workflow for standardizing molecular simulation and functional analysis of protein variants

Abstract Background Molecular simulations are used to provide insight into protein structure and dynamics, and have the potential to provide important context when predicting the impact of sequence variation on protein function. In addition to understanding molecular mechanisms and interactions on the atomic scale, translational applications of those approaches include drug screening, development of novel molecular therapies, and targeted treatment planning. Supporting the continued development of these applications, we have developed the SNP2SIM workflow that generates reproducible molecular dynamics and molecular docking simulations for downstream functional variant analysis. The Python workflow utilizes molecular dynamics software (NAMD (Phillips et al., J Comput Chem 26(16):1781-802, 2005), VMD (Humphrey et al., J Mol Graph 14(1):33-8, 27-8, 1996)) to generate variant specific scaffolds for simulated small molecule docking (AutoDock Vina (Trott and Olson, J Comput Chem 31(2):455-61, 2010)). Results SNP2SIM is composed of three independent modules that can be used sequentially to generate the variant scaffolds of missense protein variants from the wildtype protein structure. The workflow first generates the mutant structure and configuration files required to execute molecular dynamics simulations of solvated protein variant structures. The resulting trajectories are clustered based on the structural diversity of residues involved in ligand binding to produce one or more variant scaffolds of the protein structure. Finally, these unique structural conformations are bound to small molecule ligand libraries to predict variant induced changes to drug binding relative to the wildtype protein structure. Conclusions SNP2SIM provides a platform to apply molecular simulation based functional analysis of sequence variation in the protein targets of small molecule therapies. In addition to simplifying the simulation of variant specific drug interactions, the workflow enables large scale computational mutagenesis by controlling the parameterization of molecular simulations across multiple users or distributed computing infrastructures. This enables the parallelization of the computationally intensive molecular simulations to be aggregated for downstream functional analysis, and facilitates comparing various simulation options, such as the specific residues used to define structural variant clusters. The Python scripts that implement the SNP2SIM workflow are available (SNP2SIM Repository. https://github.com/mccoymd/SNP2SIM, Accessed 2019 February ), and individual SNP2SIM modules are available as apps on the Seven Bridges Cancer Genomics Cloud (Lau et al., Cancer Res 77(21):e3-e6, 2017; Cancer Genomics Cloud [www.cancergenomicscloud.org; Accessed 2018 November])

The Diagnostic Dilemma of Ruptured Liver Metastasis in a Patient with Lung Cancer: A case report

Spontaneous rupture of a metastatic liver tumour is rarely documented in the literature when compared to hepatocellular carcinoma and other liver lesions, especially from a lung primary. We report a case of ruptured liver metastasis from an adenocarcinoma of the lung mimicking ruptured liver abscess, challenging the clinical diagnosis. A 42-year-female patient presented to a tertiary care institute in 2020 with complaints of abdominal pain, breathlessness and fever. On examination, the patient was tachypnoeic with a right hypochondriac mass. A contrast-enhanced computed tomography of abdomen and thorax revealed an ill-defined heterogeneously enhancing lesion in the liver with a communicating subcapsular collection and hypo-enhancing lesions in the left lobe and heterogeneously enhancing lesion in the left lung. Adenocarcinoma of the lung with hepatic metastasis was confirmed with a core needle biopsy. The patient was managed conservatively with intravenous antibiotics, intercostal drainage tube and gefitinib. However, despite best efforts, the patient succumbed to the disease. Keywords: Metastasis; Spontaneous Rupture; Hepatocellular Carcinoma; Thyroid Transcription Factor; Liver Abscess; Case Report; India

Leaf Transcriptome Assembly of Protium copal (Burseraceae) and Annotation of Terpene Biosynthetic Genes

Plants in the Burseraceae are globally recognized for producing resins and essential oils with medicinal properties and have economic value. In addition, most of the aromatic and non-aromatic components of Burseraceae resins are derived from a variety of terpene and terpenoid chemicals. Although terpene genes have been identified in model plant crops (e.g., Citrus, Arabidopsis), very few genomic resources are available for non-model groups, including the highly diverse Burseraceae family. Here we report the assembly of a leaf transcriptome of Protium copal, an aromatic tree that has a large distribution in Central America, describe the functional annotation of putative terpene biosynthetic genes and compare terpene biosynthetic genes found in P. copal with those identified in other Burseraceae taxa. The genomic resources of Protium copal can be used to generate novel sequencing markers for population genetics and comparative phylogenetic studies, and to investigate the diversity and evolution of terpene genes in the Burseraceae

Leaf Transcriptome Assembly of Protium copal (Burseraceae) and Annotation of Terpene Biosynthetic Genes

Plants in the Burseraceae are globally recognized for producing resins and essential oils with medicinal properties and have economic value. In addition, most of the aromatic and non-aromatic components of Burseraceae resins are derived from a variety of terpene and terpenoid chemicals. Although terpene genes have been identified in model plant crops (e.g., Citrus, Arabidopsis), very few genomic resources are available for non-model groups, including the highly diverse Burseraceae family. Here we report the assembly of a leaf transcriptome of Protium copal, an aromatic tree that has a large distribution in Central America, describe the functional annotation of putative terpene biosynthetic genes and compare terpene biosynthetic genes found in P. copal with those identified in other Burseraceae taxa. The genomic resources of Protium copal can be used to generate novel sequencing markers for population genetics and comparative phylogenetic studies, and to investigate the diversity and evolution of terpene genes in the Burseraceae