Plant-derived antimicrobials to fight against multi-drug-resistant human pathogens

Antibiotic resistance is becoming a pivotal concern for public health that has accelerated the search for new antimicrobial molecules from nature. Numbers of human pathogens have inevitably evolved to become resistant to various currently available drugs causing considerable mortality and morbidity worldwide. It is apparent that novel antibiotics are urgently warranted to combat these life-threatening pathogens. In recent years, there have been an increasing number of studies to discover new bioactive compounds from plant origin with the hope to control antibiotic-resistant bacteria. This review attempts to focus and record the plant-derived compounds and plant extracts against multi-drug-resistant (MDR) pathogens including methicillin-resistant Staphylococcus aureus (MRSA), MDR-Mycobacterium tuberculosis and malarial parasites Plasmodium spp. reported between 2005 and 2015. During this period, a total of 110 purified compounds and 60 plant extracts were obtained from 112 different plants. The plants reviewed in this study belong to 70 different families reported from 36 countries around the world. The present review also discusses the drug resistance in bacteria and emphasizes the urge for new drugs

An Obsevational study on the Human Acetabulum in South Indian Fetuses and Adult Population

Acetabulum (acetum - vinegar, abulum - saucer or cup) is a bony component of hip bone. Anatomical, evolutionary, Anthropological, Histopathological, Forensic, Orthopedic and Radiological significance of Acetabulum were analysed and the dissertation plot was designed based on the acetabulum. In 100 dry hip bones, the acetabular diameter, acetabular depth, capacity of acetabulum and types of anterior acetabular ridge were observed. On statistical analysis ,there was significant difference observed in the morphometric parameters when it is based on gender , there was no significance when based on sides. In 30 cadaveric hip bones the acetabular diameter, acetabular depth and capacity of the acetabulum were analysed.There was significant difference observed in the morphometric parameters when it is based on gender, there was no significance when based on sides. In 105 Xray pelvis (AP view), the CE angle, AD, AA, AIA, RA, ARO, EI, LS, DTW, JSW and PED were measured.CE angle, AD , RA , LS , PED and JSW were the parameters observed to have statistically significant difference with respect to gender but not with sides. In CT abdomen and pelvis (50) (100 acetabula) (24 males, 26 females) (50 right and 50 left) CE angle, AD, AA, AIA, RA, ARO, EI, LS, DTW, AV, JSW, PED, AASA and PASA were measured.When statistically analyzed AD, RA, AA, LS, PED and JSW were the parameters observed to have significant difference with respect to gender but not with sides. In 30 (15 males and 15 females) fetuses (12 to 40 weeks), the acetabular diameter, acetabular depth and shape of the acetabulum were measured. The diameter and depth of the acetabulum increased with the age of the fetuses and the shape of the acetabulum became less hemispherical as the age advanced, thereby the socket was converted into a shallow cavity. The results were statistically apprehended

Business Strategies Influences in global Business for sustainable growth in Economic development

Communications and transportation technologies constantly change the world. The ease of interactions and transactions they afford has given rise to global business. However, just because being a global business is more possible doesn't necessarily make it easy. Business leaders and managers have many business strategies to create success in international markets,Technology which is the inevitable two tendency of the last century becomes a very effective especially in the business arena and reshapes the phenomenon of business competition. Ä°ncreasing the pressure competition day by day when world is shrinking continuously plays a role as the driving force in the Business competition which is the primary purpose of profit maximization of enterprises. A business process is composed of implementing various strategies onthe assetsand liabilities in a common pool.The process of transformation occurring in business structures is investigated by explaining the changing face of competition in the first part of the study within the framework of globalization and Business growth concept is described in detail that is fundamental dynamics of this transformationto process the business successful. Theoretical information that related to take business mergers and acquisitions are given as Business strategy on the second part

Effect of Awris Traditional Dances on Health-Related Physical Fitness Traits among High School Students in Ethiopia

The purpose of this study was to evaluate the effect of Awris traditional dance Tigray regional state on health related physical fitness traits among high school students. To achieve the purpose of this study, 40 high school students were selected randomly. And their age ranged between 15 and 17 years. The selected participants were categorized into experimental and control group with twenty (n=20) subjects in each. The experimental group performed traditional dances for a period of 16 weeks three days per week whereas participants in the control group were informed to follow their usual daily activity. All participants were tested on selected criterion measures on muscular strength, flexibility, cardiovascular endurance and body composition prior to and after the 16 weeks of the training period. The data pertaining to the variables in this study were statistically examined by using SPSS statistical software version 25. Descriptive statistics such as mean and standard deviation were found in order to get the basic idea of the data distribution. Independent t- test was employed for finding whether there was any statistically significant pre-test to post-test mean differences in their respective variables of each group. Level of significant was set at 0.05. Following the 16-weeks traditional dance training, significant change was observed on muscular strength and cardiovascular endurance, but there was no significant improvement in flexibility and body composition as compare the experimental groups with the control group. Therefore it can be concluded that Awris traditional dance training program can notably improve muscular strength and cardiovascular endurance of high school students

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles

Large oncosomes (LO) are atypically large (1-10 mu m diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease. We report that 25% of the proteins, identified by a quantitative proteomics analysis, are differentially represented in large and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs included enzymes involved in glucose, glutamine and amino acid metabolism, all metabolic processes relevant to cancer. Glutamine metabolism was altered in cancer cells exposed to large EVs, an effect that was not observed upon treatment with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol (OptiPrep (TM)) gradients. Fluorescent microscopy of large EVs revealed an appearance consistent with LO morphology, indicating that these structures can be categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was one of the most abundant (within the top 5th percentile) and was used to develop an assay to detect LO in the circulation and tissues of mice and patients with prostate cancer. These observations indicate that LO represent a discrete EV type that may play a distinct role in tumor progression and that may be a source of cancer-specific markers.1182Ysciescopu

SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design

Rule-based modeling of biochemical systems with BioNetGen

Totowa, NJ. Please cite this article when referencing BioNetGen in future publications. Rule-based modeling involves the representation of molecules as structured objects and molecular interactions as rules for transforming the attributes of these objects. The approach is notable in that it allows one to systematically incorporate site-specific details about proteinprotein interactions into a model for the dynamics of a signal-transduction system, but the method has other applications as well, such as following the fates of individual carbon atoms in metabolic reactions. The consequences of protein-protein interactions are difficult to specify and track with a conventional modeling approach because of the large number of protein phosphoforms and protein complexes that these interactions potentially generate. Here, we focus on how a rule-based model is specified in the BioNetGen language (BNGL) and how a model specification is analyzed using the BioNetGen software tool. We also discuss new developments in rule-based modeling that should enable the construction and analyses of comprehensive models for signal transduction pathways and similarly large-scale models for other biochemical systems. Key Words: Computational systems biology; mathematical modeling; combinatorial complexity; software; formal languages; stochastic simulation; ordinary differential equations; protein-protein interactions; signal transduction; metabolic networks. 1

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON