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Background: AKT1 is a serine/threonine kinase necessary for the mediation of apoptosis, angiogenesis, metabolism, and cell proliferation in both normal and cancerous cells. The mutations in the AKT1 gene have been associated with different types of cancer. Further, the AKT1 gene mutations are also reported to be associated with other diseases such as Proteus syndrome and Cowden syndromes. Hence, this study aims to identify the deleterious AKT1 missense SNPs and predict their effect on the function and structure of the AKT1 protein using various computational tools. Methods: Extensive in silico approaches were applied to identify deleterious SNPs of the human AKT1 gene and assessment of their impact on the function and structure of the AKT1 protein. The association of these highly deleterious missense SNPs with different forms of cancers was also analyzed. The in silico approach can help in reducing the cost and time required to identify SNPs associated with diseases. Results: In this study, 12 highly deleterious SNPs were identified which could affect the structure and function of the AKT1 protein. Out of the 12, four SNPs—namely, G157R, G159V, G336D, and H265Y—were predicted to be located at highly conserved residues. G157R could affect the ligand binding to the AKT1 protein. Another highly deleterious SNP, R273Q, was predicted to be associated with liver cancer. Conclusions: This study can be useful for pharmacogenomics, molecular diagnosis of diseases, and developing inhibitors of the AKT1 oncogene. [ABSTRACT FROM AUTHOR]

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network. [ABSTRACT FROM AUTHOR]

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four T-cytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV-MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments. [ABSTRACT FROM AUTHOR]

Dark septate endophytes (DSE) exert a plethora of effects in regulating plant growth, signalling and stress tolerance. The advent of metagenomics has led to the identification of various species of DSE to be associated with plant organs. They are known to modulate growth, nutrient uptake, phytohormone biosynthesis and production of active bioconstituents in several plants. The interactions between the DSE and host plants are mostly mutualistic but they can also be neutral or exhibit negative interactions. The DSE has beneficial role in removal/sequestration of toxic heavy metals from various environmental sites. Here, we discuss the beneficial role of DSE in enhancing plant tolerance to heavy metal stress, drought conditions, high salinity and protection from various plant pathogens. Furthermore, the underlying mechanism of stress resilience facilitated by DSE-plant interaction has also been discussed. The article also provides insights to some important future perspectives associated with DSE-mediated phytoremediation and reclamation of polluted land worldwide thus facilitating sustainable agriculture. [ABSTRACT FROM AUTHOR]

Microorganisms are ubiquitous on Earth and can inhabit almost every environment. In a complex heterogeneous environment or in face of ecological disturbance, the microbes adjust to fluctuating environmental conditions through a cascade of cellular and molecular systems. Their habitats differ from cold microcosms of Antarctica to the geothermal volcanic areas, terrestrial to marine, highly alkaline zones to the extremely acidic areas and freshwater to brackish water sources. The diverse ecological microbial niches are attributed to the versatile, adaptable nature under fluctuating temperature, nutrient availability and pH of the microorganisms. These organisms have developed a series of mechanisms to face the environmental changes and thereby keep their role in mediate important ecosystem functions. The underlying mechanisms of adaptable microbial nature are thoroughly investigated at the cellular, genetic and molecular levels. The adaptation is mediated by a spectrum of processes like natural selection, genetic recombination, horizontal gene transfer, DNA damage repair and pleiotropy-like events. This review paper provides the fundamentals insight into the microbial adaptability besides highlighting the molecular network of microbial adaptation under different environmental conditions. [ABSTRACT FROM AUTHOR]

Microbial exopolysaccharides (EPSs) have emerged as a fascinating area of research in the field of pharmacology due to their diverse and potent biological activities. This review paper aims to provide a comprehensive overview of the pharmacological properties exhibited by EPSs, shedding light on their potential applications in various therapeutic areas. The review begins by introducing EPSs, exploring their various sources, significance in microbial growth and survival, and their applications across different industries. Subsequently, a thorough examination of the pharmaceutical properties of microbial EPSs unveils their antioxidant, immunomodulatory, antimicrobial, antidepressant, antidiabetic, antiviral, antihyperlipidemic, hepatoprotective, anti-inflammatory, and anticancer activities. Mechanistic insights into how different EPSs exert these therapeutic effects have also been discussed in this review. The review also provides comprehensive information about the monosaccharide composition, backbone, branches, glycosidic bonds, and molecular weight of pharmacologically active EPSs from various microbial sources. Furthermore, the factors that can affect the pharmacological activities of EPSs and approaches to improve the EPSs' pharmacological activity have also been discussed. In conclusion, this review illuminates the immense pharmaceutical promise of microbial EPS as versatile bioactive compounds with wide-ranging therapeutic applications. By elucidating their structural features, biological activities, and potential applications, this review aims to catalyze further research and development efforts in leveraging the pharmaceutical potential of microbial EPS for the advancement of human health and well-being, while also contributing to sustainable and environmentally friendly practices in the pharmaceutical industry. [Display omitted] • Microbial EPSs are captivating area of research in pharmacology due to their potent biological activities. • EPSs show variety in their structure, composition and physiochemical properties. • Monosaccharide composition, and glycosidic linkage of EPSs play significant role in determining biological activities. • Various methods have been used to enhance the biological activities of the EPSs. [ABSTRACT FROM AUTHOR]

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health. [ABSTRACT FROM AUTHOR]

Human chondrocytes accumulate an ECM-rich matrix by secreting matrix macromolecules during monolayer culture, which makes them difficult to transfect efficiently. Here we report a non-viral based protocol to transfect the primary human chondrocytes with high efficiency in suspension. Chondrocyte cultures were digested using Pronase and Collagenase and transfected in suspension. Transfection efficiencies of more than 80% were achieved routinely using the protocol described. The viability of siRNA transfected or un-transfected chondrocytes was not affected and resulted in 80–90% knockdown of the target mRNA levels. This protocol may be useful in gene knockdown, and ectopic overexpression studies in chondrocytes. [ABSTRACT FROM AUTHOR]

This study aims at the assessing and improvising the services - digital library, books, journals, newspapers, Tumitin software for plagiarism, indexing.and abstracting and PhD theses - rendered by the Higher Education Commission (HEC) Library. User's satisfaction is considered as key element to assess the current status of the services in the world. In order to evaluate the services of library from the students' vintage point, the researchers sought feedback from the visitors of the HEC library using a survey research method. The research measured the users' satisfaction level about library ambience, behavior of supporting staff, number and variety of data bases, digital library, availability of journals, indexing services, access of PhD theses and plagiarism detecting facility in 2015. Sample of the study comprised of 128 library visitors. A three point Likert Scale was used from 1 (least satisfied) to 3 (most satisfied). The study expressed that the mostly users were moderately satisfied with the current services offered in the HEC library. The study will help the HEC administration to improve the HEC Library resources and services based on findings of this research. [ABSTRACT FROM AUTHOR]

TNF-α is a major cytokine implicated in rheumatoid arthritis (RA), and its expression is regulated at the transcriptional and posttranscriptional levels. However, the impact of changes in microRNA expression on posttranslational processes involved in TNF-α signaling networks is not well defined in RA. In this study, we evaluated the effect of miR-17, a member of the miR-17--92 cluster, on the TNF-α signaling pathway in human RA synovial fibroblasts (SFs). We demonstrated that miR-17 expression was significantly low in RA serum, SFs, and synovial tissues, as well as in the serum and joints of adjuvant-induced arthritis rats. RNA-sequencing analysis showed modulation of 664 genes by pre--miR-17 in human RA SFs. Ingenuity pathway analysis of RNA-sequencing data identified the ubiquitin proteasome system in the TNF-α signaling pathway as a primary target of miR-17. Western blot analysis confirmed the reduction in TRAF2, cIAP1, cIAP2, USP2, and PSMD13 expression by miR-17 in TNF-α--stimulated RA SFs. Immunoprecipitation assays showed that miR-17 restoration increased the K48-linked polyubiquitination of TRAF2, cIAP1, and cIAP2 in TNF-α--stimulated RA SFs. Thus, destabilization of TRAF2 by miR-17 reduced the ability of TRAF2 to associate with cIAP2, resulting in the downregulation of TNF-α--induced NF-κBp65, c-Jun, and STAT3 nuclear translocation and the production of IL-6, IL-8, MMP-1, and MMP-13 in human RA SFs. In conclusion, this study provides evidence for the role of miR-17 as a negative regulator of TNF-α signaling by modulating the protein ubiquitin processes in RA SFs. [ABSTRACT FROM AUTHOR]

• Plant synthesized hormones are essential to counteract stress conditions. • Strigolactones (SLs), a novel phytohormones, regulate plant development and interactions. • SLs crosstalk with other phytohormones is vital for plant health. • SLs fights both biotic and abiotic stress by increasing tolerance level in plants. Plants respond to a range of abiotic stimuli in nature involving anatomical, cellular, morphological, and physiological changes. The adaptability of plants to acclimatize to different environments is greatly influenced by phytohormones, which mediate growth, development and nutrient partitioning. These signal molecules are biosynthesized by plant itself and are often known as plant growth regulators. Strigolactones (SLs) are a unique class of phytohormones that have an ecological role in overcoming multiple stress circumstances. SLs are originally found in the germinating seeds of parasitic weeds, biosynthesized from precursor carotenoids and perform widespread physiological functions in bud outgrowth, shoot branching, nodulation, and photomorphogenesis. SLs correspondingly persuade arbuscular mycorrhizal fungi's hyphal branching in germinating spores. Lately, SLs have been drawn to attention as of their role in molecular and physiological adaptations in response to abiotic stresses. The SLs demonstrate crosstalk with other phytohormones and function in mitigating stress conditions through diverse molecular pathways. The present review addresses comprehensive information about the molecular signaling, biosynthesis, and importance of SLs in providing resilience towards stress conditions in diverse plants. [ABSTRACT FROM AUTHOR]

Objective Hedgehog (HH) signaling has recently been associated with cartilage degradation in osteoarthritis (OA). Because interleukin-1β (IL-1β) has been implicated as a principal instigator of OA, we sought to determine whether IL-1β induces the expression of sonic HH (SHH) and its regulation by microRNAs (miRNAs) in human chondrocytes. Methods Expression of SHH protein in human OA cartilage and in an animal model of OA was determined by immunohistochemical analysis and immunofluorescence analysis, respectively. Gene and protein expression in IL-1β- or SHH-stimulated OA chondrocytes was determined by TaqMan assays and Western blotting, respectively. The effect of overexpression of miRNA-602 (miR-602) and miR-608 or their antagomirs on SHH expression was evaluated by transient transfection of human chondrocytes and HEK 293 cells. The role of signaling pathways was evaluated using small molecule inhibitors. Binding of miRNAs with the putative seed sequence in SHH messenger RNA (mRNA) was validated using a luciferase reporter assay. Results Expression of SHH, patched 1, Gli-1, HH-interacting protein, matrix metalloproteinase 13 (MMP-13), and Colα1(X) was high in damaged OA cartilage. In damaged cartilage and in IL-1β-stimulated OA chondrocytes, expression of SHH was inversely correlated with expression of miR-608. Cotransfection of OA chondrocytes with miR-608 or miR-602 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. Overexpression of miR-602 or miR-608 inhibited the expression of SHH mRNA and protein, and this was abrogated by antagomirs. Stimulation with recombinant human SHH protein up-regulated MMP-13 expression, and inhibition of HH signaling blocked MMP-13 expression in OA chondrocytes. Conclusion MiR-602 and miR-608 are important posttranscription regulators of SHH expression in OA chondrocytes, and their suppression by IL-1β may contribute to the enhanced expression of SHH and MMP-13 in OA. [ABSTRACT FROM AUTHOR]

Quantitative measurement is an effective technique to improve the services in the field of Library and Information Science. It provides a framework to the Library professionals to practice new concepts of quantitative forms in the area of Library and Information Science. This paper highlights the measurement practices adopted in the Special Library of Higher Education Commission of Pakistan in a form of case study. It examines how a traditional library is switching over to a modem library extending benefits of research and information to students, scholars and professionals. Facilitation to the visitors and rapid access to information are the basic pillars of new strategy. Quantitative monthly progress reports as main measuring instruments cover areas of journals received, newspapers received, library visitors, internet/digital library users, visitors helped, acquisition and issuing of books, books/journals shelved, photocopies arranged for users, PhD theses received, digitized and processed for shifting and reference services. In addition to that, readers and visitors are provided spacious environment to consult books, journals, research reports, HEC's monographs, manuals, annual reports and theses of different universities. This quantitative measurement of library services serves as the mirror of performance for the library management. They review and analyze this measurement to improve the library services continuously. [ABSTRACT FROM AUTHOR]

Context: Vitiligo is a chronic, benign, but emotionally frustrating autoimmune disorder of depigmentation, with an incidence of 0.25-2.5% in India, the treatment of which is equally frustrating to the patient, as well as the doctor. Phototherapy is the first line treatment in many cases, which needs to be given at frequent sittings for long periods of time. As there is no satisfactory, short term treatment, many vitiligo patients, though enthusiastic in the beginning, become defaulters after a few weeks or months. Aims: This study was conducted to assess the compliance to phototherapy (PUVA and NB-UVB), determine the reasons for non-compliance, to calculate the overall response to phototherapy and to know about the patients' perception about improvement of lesions. Materials and Methods: All files of the patients who attended phototherapy for Vitiligo in the department for a period of 4 years from January 2007 were analyzed and the patients were contacted via mail or telephone and were made to answer questionnaire regarding their disease. Conclusions: At the end of this retrospective questionnaire based study we concluded that only a quarter of the patients underwent regular phototherapy, among which the younger patients and those with widespread disease and facial lesions were more compliant. Educational status and sex had no impact on default status. [ABSTRACT FROM AUTHOR]

To solve the inverse gravimetric problem, i.e. to reconstruct the Earth's mass density distribution by using the gravitational potential, we introduce a spline interpolation method for the ellipsoidal Earth model, where the ellipsoid has a rotational symmetry. This problem is ill-posed in the sense of Hadamard as the solution may not exist, it is not unique and it is not stable. Since the anharmonic part (orthogonal complement) of the density function produces a zero potential, we restrict our attention only to reconstruct the harmonic part of the density function by using the gravitational potential. This spline interpolation method gives the existence and uniqueness of the unknown solution. Moreover, this method represents a regularization, i.e. every spline continuously depends on the given gravitational potential. These splines are also combined with a multiresolution concept, i.e. we get closer and closer to the unknown solution by increasing the scale and adding more and more data at each step. [ABSTRACT FROM AUTHOR]

Objective. To investigate whether advanced glycation end products (AGEs) induce the expression of IL-6 and IL-8 through the receptor for AGEs (RAGE)-activated pathways in human OA chondrocytes.Methods. OA chondrocytes were stimulated with AGE-modified BSA (AGE-BSA). Gene expression of IL-6 and IL-8 was quantified by TaqMan assays and the production was determined using ELISAs. Immunoblotting was used to analyse the activation of mitogen-activated protein kinases (MAPKs) and the degradation of IκBα. Activation of NF-κB was determined using an ELISA. Pharmacological studies to elucidate the involved pathways were executed using transfection with small interfering RNAs (siRNAs), inhibitors of MAPKs and NF-κB.Results. AGE-BSA induced the expression of IL-6 and IL-8 in OA chondrocytes, which was inhibited by pre-treatment with soluble RAGE (sRAGE) or RAGE knockdown by siRNAs. Treatment with SB202190 (p38-MAPK inhibitor) or PD98059 (ERK inhibitor) inhibited AGE-BSA-induced IL-6 and IL-8 expression. However, SP600125 (JNK inhibitor) had no effect on AGE-BSA-induced IL-6 expression but inhibited the expression of IL-8. Treatment with NF-κB inhibitors suppressed AGE-BSA-induced IL-6 and IL-8 expression.Conclusions. This is the first study to demonstrate that AGEs induce the expression of IL-6 and IL-8 in OA chondrocytes. A novel finding of our studies is that in OA chondrocytes, AGE-BSA-induced expression of IL-6, but not of IL-8, was independent of the JNK pathway. Activation of NF-κB was an absolute requirement for both IL-6 and IL-8 expression. These results demonstrate that AGE-BSA-induced expression of IL-6 and IL-8 via RAGE is mediated through different MAPK signalling pathways in OA and possibly in other degenerative diseases. [ABSTRACT FROM PUBLISHER]

Abstract: A number of factors including inflammation and oxidative stress are believed to play a role in the development of chronic joint diseases. Green tea has become a popular drink and is consumed throughout the world. Extracts of green tea and polyphenols present therein have been shown to inhibit the inflammatory responses in vitro in different cell types and the development of arthritis in animal model studies. There is considerable evidence that (−)-epigallocatechin-3-gallate (EGCG), the predominant green tea polyphenol which mimic its effects, inhibits enzyme activities and signal transduction pathways that play important roles in inflammation and joint destruction in arthritis. After oral consumption EGCG become bioavailable and proteomic studies suggest that EGCG may directly interact with a large set of protein targets and alter the physiological response of the cells. Taken together these and other studies identify and support the use of EGCG as a possible chemopreventive agent with a potential to inhibit the development of arthritis. Here we review the biological effects of EGCG in an attempt to understand its pivotal molecular targets that directly affect the inflammation and joint destruction process for prevention and/or for the development of new therapeutics for arthritis in humans. [Copyright &y& Elsevier]

The article presents a study regarding the regulation of microRNA on the matrix metalloproteinases (MMPs) expression in human osteoarthritis (OA) chondrocytes. It states that interleukin-1β (IL-1β) in vitro was used to stimulate chondrocytes while TaqMan for quantifying gene expression. The results show that 2 microRNA were up-regulated while 42 microRNA were down-regulated in IL-β—stimulated OA chondrocytes.

[Display omitted] • Anepitope vaccine was designed against Human Cytomegalovirus by in silico method. • The vaccine consists of T-cell epitopes and adjuvants joined by GGS linker. • The vaccine is non-allergic, antigenic , and has good physiochemical properties. • Molecular docking and simulation showed the vaccine interacts with stability to Toll like receptor. • In silico cloning shows that the vaccine can be cloned in E. coli K12 strain. Human Cytomegalovirus (HCMV) is one of the most common causes of congenital infections globally. They infect the fetus and cause severe birth defects such as hearing loss, complications in the eyes, epilepsy, autism, and various other neurological disorders. They are also the leading cause of death in patients with compromised immunity. Due to the prevalence and severity of the virus, the United States National Academy of Medicine has announced the development of the HCMV vaccine as a matter of high priority for public health. Hence, this study is focused on designing a novel potent multi-epitope HCMV vaccine. The envelope glycoproteins B, H, L and M of HCMV were targeted to predict T cell (both Helper and Cytotoxic) epitopes that were non-toxic, highly antigenic, and non-allergenic and could induce interferon-γ production. Further, the selected epitopes were subjected to molecular docking and population coverage analysis. Eventually, using the two best epitopes and adjuvants like RS09, flagellin protein and PADRE sequence a 283 amino acid long vaccine was designed. The vaccine is antigenic, non-allergenic, stable, and soluble. The 3D model of the vaccine was developed and validated using the Ramachandran plot. Docking with Toll-like receptor 5 (TLR5) molecule and molecular dynamics simulation confirmed the stability of the vaccine. In silico cloning simulation using pET28a (+) vector showed that the vaccine can be successfully cloned and expressed in E. coli K12 strain. However, the efficacy and the safety of the vaccine need to be further validated by in vivo studies. [ABSTRACT FROM AUTHOR]

Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-γ synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies. • Candida auris is a rapidly emerging human pathogenic fungus with high mortality rate. • A multi-epitope subunit-based vaccine against C. auris is designed using in-silico tools. • The vaccine was constructed using 8 highly antigenic epitopes, PADRE sequence, and adjuvant linked together by GGS linker. • The results show that the vaccine construct is highly antigenic but at the same time non-toxic, and non-allergenic. [ABSTRACT FROM AUTHOR]

The association of microorganisms with livestock as endosymbionts, opportunists, and pathogens has been a matter of debate for a long time. Several livestock-associated bacterial and other microbial species have been identified and characterized through traditional culture-dependent genomic approaches. However, it is imperative to understand the comprehensive microbial network of domestic animals for their wellness, disease management, and disease transmission control. Since it is strenuous to provide a niche replica to any microorganisms while culturing them, thus a substantial number of microbial communities remain obscure. Metagenomics has laid out a powerful lens for gaining insight into the hidden microbial diversity by allowing the direct sequencing of the DNA isolated from any livestock sample like the gastrointestinal tract, udder, or genital system. Through metatranscriptomics and metabolomics, understanding gene expression profiles of the microorganisms and their molecular phenotype has become unchallenging. With large data sets emerging out of the genomic, metagenomic, and other meta-omics methods, several computational tools have also been developed for curation, assembly, gene prediction, and taxonomic profiling of the microorganisms. This review provides a detailed account of the beneficial and pathogenic organisms that dwell within or on farm animals. Besides, it highlights the role of meta-omics and computational tools in a comprehensive analysis of livestock-associated microorganisms. [ABSTRACT FROM AUTHOR]

Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four mammalian syndecans, SDC‐1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. SDCs modulate disease progression by interacting with a diverse array of ligands, receptors, and other proteins, including extracellular matrix, glycoproteins, integrins, morphogens, and various growth factors and chemokines, along with their receptors and kinases. Specifically, SDCs present on cell surface can bind directly to chemokines to enhance their binding to receptors, downstream signaling, and migration. Alternatively, SDCs can be cleaved and shed to mediate negative regulation of chemokine and growth factor signaling pathways and ligand sequestration. Importantly, SDC shedding may be a biomarker of inflammation, especially in chronic inflammatory diseases. While the current therapies for cancer and several autoimmune disorders have revolutionized treatment outcomes, understanding the pathophysiological role of SDCs and the use of HSPG mimetic or antagonists on cytokine signaling networks may uncover potentially novel targeted therapeutic approaches. This review mainly summarizes the current findings on the role of individual SDCs in disease processes, mechanisms through which SDCs mediate their biological functions, and the possibility of targeting SDCs as future potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Digital Libraries are the recent gateway of modem knowledge and information. In order to make progress in the academic field, it is essential that quality digital library services be provided by the Universities. Higher Education Commission has endeavored to provide access to the most recent digital data bases in the last decade. Access to information and scientific data bases has increased in the universities of Pakistan on a large scale. [ABSTRACT FROM AUTHOR]

Rhizosphere is a dynamic and complex environment shaped by intricate interactions between plants and a diverse microbial community. The rhizosphere microbiome is crucial for plant growth, nutrition, and health in agro-ecosystems. Recent advancements in metagenomics, especially through shotgun sequencing, offer unprecedented opportunities to unravel the complexities of rhizosphere microbial dynamics. Sequence and function-based metagenomic approaches enhance our understanding of plant-microbe relationships and serve as transformative tools for sustainable agriculture. They offer insights into precision microbiome engineering and ecosystem management by capturing the genomic landscape of microbial communities, revealing their taxonomic composition and functional potential. The integration of computational tools and machine learning approaches provides a powerful analytical framework to interpret vast and intricate metagenomic datasets. This paper comprehensively explores the rhizosphere using cutting-edge shotgun sequencing techniques to capture a holistic view of microbial communities in this crucial zone. Additionally, it delves into the emerging domain of virus-rhizosphere interactions, elucidating the impact of viral dynamics on rhizosphere microbial composition. To date, significant achievements in rhizosphere biology through metagenomics include detailed characterizations of microbial diversity, functional profiling of microbial communities, and identification of key microbial players in plant health and nutrient cycling. These advances underscore the critical role of metagenomics in advancing our understanding of rhizosphere biology and its applications in sustainable agriculture. The novel application of these advanced metagenomic techniques presents both opportunities and challenges, offering deeper insights into the rhizosphere while highlighting the need for improved data integration and interpretation methods. [Display omitted] • Metagenomics is a tool for studying rhizosphere microbial community genetics. • Shotgun sequencing is a common high-throughput method in metagenomics. • Metagenomics explores plant-microbe ecological interactions, including viruses. • Computational tools process and analyze large metagenomic data sets. • Metagenomics reveals insights into metabolic pathways, nutrient cycling, and plant interactions. [ABSTRACT FROM AUTHOR]

For many years, scientists have aspired to edit any DNA segment of living organisms precisely, and with the discovery of CRISPR/Cas9, they have moved closer to achieving their objective. Using this tool, researchers can knock out or knock-in a gene into or from any part of the genome. The CRISPR-Cas9 system is a highly effective and accurate tool and has replaced previous genome editing technologies such as ZFN and TALEN having lesser precision and accuracy. Advances in CRISPR/Cas technology have been remarkable in recent years, with significant applications in various fields of life sciences research. Despite the diverse applications of the CRISPR system, this tool also poses a threat to living organisms and the environment. The intentional misuse of CRISPR could be a disaster to society and the environment. Different countries have imposed laws and guidelines to regulate genome editing through multiple agencies. However, in some countries, these rules and regulations are still under development or don't exist, leading to higher chances of the technology getting misused. Dual-use of this technology could be a threat to biosecurity and biodefense. This article summarizes the potential applications of the CRISPR system in human and plants, and also evaluate the laws and regulations imposed by different countries to keep genome editing technology under check. [ABSTRACT FROM AUTHOR]

To clarify the relationship between cultivar difference in the sensitivity of net photosynthesis to ozone (O3) and the reactive oxygen species (ROS) scavenging system in wheat ( Triticum aestivum), we investigated the effects of chronic exposure to ambient levels of O3 on gas exchange rates, activity and concentration of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), activity of ROS scavenging enzymes and concentration of antioxidants of the flag leaf in two Japanese winter wheat cultivars (Norin 61 and Shirogane-komugi). Although the net photosynthetic rate of the flag leaf in Norin 61 was not significantly reduced by exposure to O3, that in Shirogane-komugi was significantly reduced by the exposure to O3 during the anthesis and early grain-filling stages. In the two cultivars, stomatal diffusive conductance to H2O of the flag leaf was not significantly affected by the exposure to O3. The exposure to O3 induced significant reductions in the activity and concentration of Rubisco, activities of catalase (CAT) and monodehydroascorbate reductase (MDAR) and concentrations of reduced form of ascorbate and total glutathione of the flag leaf in Shirogane-komugi. It was concluded that the sensitivity of net photosynthesis of flag leaf to O3 is higher in Shirogane-komugi than in Norin 61, and the difference in the sensitivity to O3 between the two cultivars is mainly due to that in the effects of O3 on the detoxification ability of ROS, mainly determined by the activity of ROS scavenging enzymes, such as CAT and MDAR. [ABSTRACT FROM AUTHOR]

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful. • This study focused on designing a multi-epitope vaccine against HCV. • The conserved regions of the E2 protein were used to predict epitopes. • A vaccine was constructed by joining epitopes, linkers, and an adjuvant. • The vaccine was found to be antigenic, non-toxic, and non-allergenic. • The vaccine revealed a stable molecular interaction with innate immune receptors. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) have emerged as a promising frontier in plant science owing to their unique physicochemical properties and versatile applications. CNTs enhance stress tolerance by improving water dynamics and nutrient uptake and activating defence mechanisms against abiotic and biotic stresses. They can be taken up by roots and translocated within the plant, impacting water retention, nutrient assimilation, and photosynthesis. CNTs have shown promise in modulating plant-microbe interactions, influencing symbiotic relationships and mitigating the detrimental effects of phytopathogens. CNTs have demonstrated the ability to modulate gene expression in plants, offering a powerful tool for targeted genetic modifications. The integration of CNTs as sensing elements in plants has opened new avenues for real-time monitoring of environmental conditions and early detection of stress-induced changes. In the realm of agrochemicals, CNTs have been explored for their potential as carriers for targeted delivery of nutrients, pesticides, and other bioactive compounds. CNTs have the potential to demonstrate phytotoxic effects, detrimentally influencing both the growth and developmental processes of plants. Phytotoxicity is characterized by induction of oxidative stress, impairment of cellular integrity, disruption of photosynthetic processes, perturbation of nutrient homeostasis, and alterations in gene expression. This review aims to provide a comprehensive overview of the current state of knowledge regarding the multifaceted roles of CNTs in plant physiology, emphasizing their potential applications and addressing the existing challenges in translating this knowledge into sustainable agricultural practices. • Carbon nanotubes (CNTs) exhibit a promising ability to enhance stress tolerance in plants. • CNTs modulate gene expression, offering a powerful tool for targeted genetic modifications. • Multifaceted role of CNTs in shaping plant-microbe dynamics. • Integration of CNTs as sensing elements for real-time monitoring of environmental conditions. • CNT toxicity is characterized by oxidative stress and, disruption of photosynthesis. [ABSTRACT FROM AUTHOR]

Rare cancers (RCs), which account for over 20% of cancer cases, face significant research and treatment challenges due to their limited prevalence. This results in suboptimal outcomes compared to more common malignancies. Rare bone tumors (RBTs) constitute 5–10% of rare cancer cases and pose unique diagnostic complexities. The therapeutic potential of anti-cancer drugs for RBTs remains largely unexplored. Identifying molecular alterations in cancer-related genes and their associated pathways is essential for precision medicine in RBTs. Small molecule inhibitors and monoclonal antibodies targeting specific RBT-associated proteins show promise. Ongoing clinical trials aim to define RBT biomarkers, subtypes, and optimal treatment contexts, including combination therapies and immunotherapeutic agents. This review addresses the challenges in diagnosing, treating, and studying RBTs, shedding light on the current state of RBT biomarkers, potential therapeutic targets, and promising inhibitors. Rare cancers demand attention and innovative solutions to improve clinical outcomes. • 20% of cancer cases fall into the category of rare cancers. • Rare bone tumors (RBTs) comprise chordoma, adamantinoma, chondromyxoid fibroma, and periosteal osteosarcoma. • The therapeutic potential of anti-cancer drugs for RBTs remains underexplored. • Clinical trials and case studies define biomarkers, subtypes, and therapeutic contexts of RBTs. [ABSTRACT FROM AUTHOR]

Dengue viral disease has been reported as an Aedes aegypti mosquito-borne human disease and causing a severe global public health concern. In this study, immunoinformatics methods was deployed for crafting CTL T-cell epitopes as dengue vaccine candidates. The NS1 protein sequence of dengue serotype 1 strain retrieved from the protein database and T-cell epitopes (n = 85) were predicted by the artificial neural network. The conserved epitopes (n = 10) were predicted and selected for intensive computational analysis. The machine learning technique and quantitative matrix-based toxicity analysis assured nontoxic peptide selection. Hidden Markov Model derived Structural Alphabet (SA) based algorithm predicted the 3D molecular structure and all-atom structure of peptide ligand validated by Ramachandran-plot. Three-tier molecular docking approaches were used to predictthe peptide - HLA docking complex. Molecular dynamics (MD) simulation study confirmed the docking complex was stable in the time frame of 100ns. Population coverage analysis predicted the interaction epitope interaction with a particular population of HLA. These results concluded that the computationally designed HTLWSNGVL and FTTNIWLKL epitope peptides could be used as putative agents for the multi CTL T cell epitope vaccine. The vaccine protein sequence expression and translation were analyzed in the prokaryotic vector adapted by codon usage. Such in silico formulated CTL T-cell-based prophylactic vaccines could encourage the commercial development of dengue vaccines. Image 1 • DENV Serotype 1 proteome was screened to design epitope for vaccine candidate. • Designed epitope's toxicity, antigenicity, MHC I interaction and population coverage analyzed. • On the basis of molecular docking and simulation, the epitopes HTLWSNGVL and FTTNIWLKL were found to be most stable. • Based on the analysis of various parameters, epitope based vaccines that can elicit a robust immune response against DENV Serotypes. • Vaccine formulation, codon adaptation and Insilico cloning expression analysis was done to establish our claim. [ABSTRACT FROM AUTHOR]

Zoonotic viral infections continue to pose significant threats to global public health, as highlighted by the COVID-19 pandemic caused by the SARS-CoV-2 virus. The emergence of SARS-CoV-2 served as a stark reminder of the potential for zoonotic transmission of viruses from animals to humans. Understanding the origins and dynamics of zoonotic viruses is critical for early detection, prevention, and effective management of future outbreaks. Metagenomics has emerged as a powerful tool for investigating the virome of diverse ecosystems, shedding light on the diversity of viral populations, their hosts, and potential zoonotic spillover events. We provide an in-depth examination of metagenomic approaches, including, NGS metagenomics, shotgun metagenomics, viral metagenomics, and single-virus metagenomics, highlighting their strengths and limitations in identifying and characterizing zoonotic viral pathogens. This review underscores the pivotal role of metagenomics in enhancing our ability to detect, monitor, and mitigate zoonotic viral infections, using SARS-CoV-2 analogues as a case study. We emphasize the need for continued interdisciplinary collaboration among virologists, ecologists, and bioinformaticians to harness the full potential of metagenomic approaches in safeguarding public health against emerging zoonotic threats. [Display omitted] • zoonotic viral infection spillover from animals to humans is global health concern. • Metagenomics allows comprehensive analysis of genetic material for early detection. • NGS and shotgun metagenome sequencing ensure early virome analysis in complex biological samples. • The development of advanced bioinformatics tools can help in pandemic preparedness and response. [ABSTRACT FROM AUTHOR]

The base excision repair (BER) pathway is an important DNA repair pathway and is essential for immune responses. In fact, it regulates both the antigen-stimulated somatic hypermutation (SHM) process and plays a central function in the process of class switch recombination (CSR). For both processes, a central role for apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated. APE1 acts also as a master regulator of gene expression through its redox activity. APE1's redox activity stimulates the DNA-binding activity of several transcription factors, including NF-κB and a few others involved in inflammation and in immune responses. Therefore, it is possible that APE1 has a role in regulating the CSR through its function as a redox coactivator. The present study was undertaken to address this question. Using the CSR-competent mouse B-cell line CH12F3 and a combination of specific inhibitors of APE1's redox (APX3330) and repair (compound 3) activities, APE1- deficient or -reconstituted cell lines expressing redox-deficient or endonuclease-deficient proteins, and APX3330- treated mice, we determined the contributions of both endonuclease and redox functions of APE1 in CSR. We found that APE1's endonuclease activity is essential for IgA-class switch recombination. We provide evidence that the redox function of APE1 appears to play a role in regulating CSR through the interleukin-6 signaling pathway and in proper IgA expression. Our results shed light on APE1's redox function in the control of cancer growth through modulation of the IgA CSR process. [ABSTRACT FROM AUTHOR]