Identification and genome-wide analysis provide insights into the genetic diversity and biotechnological potentials of novel cold-adapted Acinetobacter strain.

Extreme cold environments, such as polar regions or high-altitude mountains, are known for their challenging conditions including low temperatures, high salinity, and limited nutrient availability. Microbes that thrive in these environments have evolved specialized strategies to survive and function under such harsh conditions. The study aims to identify, sequence the genome, perform genome assembly, and conduct a comparative genome-wide analysis of Acinetobacter sp. strain P1, which was isolated from the Batura glacier regions of Pakistan. A basic local alignment search tool of NCBI using 16 s RNA gene sequence confirmed the strain Acinetobacter following phylogenetic analysis revealed that strain P1 clustered with Acinetobacter sp. strain AcBz01. The high-throughput Genome sequencing was done by the NovaSeq 6000 sequencing system following de novo genome assembly reported 23 contigs, a genome size of 3,732,502 bp containing approximately 3489 genes and 63 RNAs (60 tRNA, 3 rRNA). The comparative genome analysis revealed that Acinetobacter sp. strain P1 exhibited the highest homology with the Acinetobacter baumannii ATCC 17978 genome and encompassed 1668 indispensable genes, 1280 conserved genes 1821 specific genes suggesting high genomic plasticity and evolutionary diversity. The genes with functional assignments include exopolysaccharide phosphotransferase enzyme, cold-shock proteins, T6SS, membrane modifications, antibiotic resistance, and set of genes related to a wide range of metabolic characteristics such as exopolysaccharides were also present. Moreover, the structural prediction analysis of EPS proteins reveals that structural flexibility allows for conformational modifications during catalysis, which boosts or increases the catalytic effectiveness at lower temperatures. Overall, the identification of Acinetobacter, a cold-adapted bacterium, offers promising applications in bioremediation, enzyme production, food preservation, pharmaceutical development, and astrobiology. Further research and exploration of these microorganisms can unlock their full biotechnological potential and contribute to various industries and scientific endeavors.

BMT: Bioinformatics mini toolbox for comprehensive DNA and protein analysis.

Background Bioinformatics tools are of great significance and are used in different spheres of life sciences. There are wide variety of tools available to perform primary analysis of DNA and protein but most of them are available on different platforms and many remain undetected. Accessing these tools separately to perform individual task is uneconomical and inefficient. Objective Our aim is to bring different bioinformatics models on a single platform to ameliorate scientific research. Hence, our objective is to make a tool for comprehensive DNA and protein analysis. Methods To develop a reliable, straight-forward and standalone desktop application we used state of the art python packages and libraries. Bioinformatics Mini Toolbox (BMT) is combination of seven tools including FastqTrimmer, Gene Prediction, DNA Analysis, Translation, Protein analysis and Pairwise and Multiple alignment. Results FastqTrimmer assists in quality assurance of NGS data. Gene prediction predicts the genes by homology from novel genome on the basis of reference sequence. Protein analysis and DNA analysis calculates physiochemical properties of nucleotide and protein sequences, respectively. Translation translates the DNA sequence into six open reading frames. Pairwise alignment performs pairwise global and local alignment of DNA and protein sequences on the basis or multiple matrices. Multiple alignment aligns multiple sequences and generates a phylogenetic tree. Conclusion We developed a tool for comprehensive DNA and protein analysis. The link to download BMT is https://github.com/nasiriqbal012/BMT_SETUP.git.

Progresses on bacterial secretomes enlighten research on Mycoplasma secretome.

Bacterial secretome is a comprehensive catalog of bacterial proteins that are released or secreted outside the cells. They offer a number of factors that possess several significant roles in virulence as well as cell to cell communication and hence play a core role in bacterial pathogenesis. Sometimes these proteins are bounded with membranes giving them the shape of vesicles called extracellular vesicles (EVs) or outer membrane vesicles (OMVs). Bacteria secrete these proteins via Sec and Tat pathways into the periplasm. Secreted proteins have found to be important as diagnostic markers as well as antigenic factors for the development of an effective candidate vaccine. Recently, the research in the field of secretomics is growing up and getting more interesting due to their direct involvement in the pathogenesis of the microorganisms leading to the infection. Many pathogenic bacteria have been studied for their secretome and the results illustrated novel antigens. This review highlights the secretome studies of different pathogenic bacteria in humans and animals, general secretion mechanisms, different approaches and challenges in the secretome of Mycoplasma sp.

Identification of 60 secreted proteins for Mycoplasma bovis with secretome assay.

Mycoplasma bovis is a risky pathogen mainly responsible for pneumonia and mastitis in cattle. Up to date, its pathogenesis is not clear. Since secreted proteins have a tricky role in M. bovis pathogenesis, this study was designed to systematically reveal M. bovis secretome and potential role in virulence of the pathogen. By using bioinformatics tools, a total of 246 secreted proteins were predicted based on M. bovis genome. Among them, 14 were classical, 154 non-classical and 78 both pathways. Then by using 2-dimensional gel electrophoresis (2-DE) and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF- MS), 169 proteins were revealed. Of them, 60 were predicted to be secreted including 3 classical, 43 non-classical, and 14 both classical and non-classical. Further 8 proteins (MbovP0038, MbovP0338, MbovP0341, MbovP0520, MbovP0581, MbovP0674, MbovP0693, MbovP0845) were predicted to be virulence-related factors with VFDB. In addition, MbovP0581 (ABC transporter protein) was validated experimentally as secreted in nature and highly immunogenic reacting with sera of cattle experimentally infected with M. bovis. In conclusion, this study might be a crucial step towards a better understanding of pathogenesis and leading to the development of novel diagnostic marker and potent vaccine against M. bovis.

Analysis of the conformational changes caused by the mutations in mitofusin2 gene by Insilico approach.

OBJECTIVE: To find the effect of pathogenic Mitofusin 2 mutations, responsible for Charcot-Marie-Tooth hereditary neuropathy type 2A, on protein structure. METHODS: The study was conducted at department of biosciences COMSATS University Islamabad, Sahiwal campus from September 2016 to July 2017, and comprised patients with Charcot Marie-Tooth hereditary neuropathy type 2A who were divided into early-onset severe group A and late-onset mild group B. Bioinformatics and molecular analysis was done to find the changes in the protein structure caused by the mutation. Three mutations were selected in two domains of the gene. These were: p. Arg94Trp, p. His165Arg and p. Thr362Met. RESULTS: Of the 10 patients, 5(50%) were in each of the two groups. Change in the structure was predicted in the mutated protein at position p. Arg94Trp, and, due to the mutation, an extra alpha helix was formed in the mutated protein. CONCLUSIONS: Change in the structure of protein can be in a critical position that is involved in the mitochondrial fusion process. However, further studies are required to validate and explain the findings.

In silico analysis of four structural proteins of aphthovirus serotypes revealed significant B and T cell epitopes.

Foot and Mouth disease (FMD) is economically devastating, highly contagious transboundry viral disease of livestock with 100% morbidity, rapid spread and severe production losses in animals. The FMDV has seven different serotypes. There is no vaccine that can protect animals from all serotypes. Hence, it is need of the day to develop a vaccine that protects animals from hetrologous challenge. In this study, we used immunoinformatics approach to find T and B-cell epitopes that will help to construct a universal vaccine for FMDV. For this purpose, first we constructed a consensus sequence for four structural proteins (VP1, VP2, VP3 and VP4) of aphthovirus for seven serotypes (A, O, C, Asia1, SAT1, SAT2 and SAT3). Various computational tools were used to perform multiple sequence alignment to identify the conserved regions, generation of consensus sequence through conserved regions, structures prediction and finally prediction of B and T cell epitopes. We predicted 5 B cell and 18 T cell epitopes. Finally a GPGPG spacer was used to join these epitopes to decrease binding affinity around the core binding regions. Hence, our study identified the epitopes which can be used to develop cross protective vaccines against all the fatal strains of Aphthovirus which can easily protect all the serotypes. Though, successful In vivo and In vitro studies are required to determine the genuine strength of our predicted epitopes against the fatal strains of Aphthovirus.

Prediction of conserved sites and domains in glycoproteins B, C and D of herpes viruses.

Glycoprotein B (gB), C (gC) and D (gD) of herpes simplex virus are implicated in virus adsorption and penetration. The gB, gC and gD are glycoproteins for different processes of virus binding and attachment to the host cells. Moreover, their expression is necessary and sufficient to induce cell fusion in the absence of other glycoproteins. Egress of herpes simplex virus (HSV) and other herpes viruses from cells involves extensive modification of cellular membranes and sequential envelopment, de-envelopment and re-envelopment steps. Viral glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Hence, we target the 3 important glycoproteins (B, C and D) of eight different herpes viruses of different species. These species include human (HSV1 and 2), bovine (BHV1), equine (EHV1 and 4), chicken (ILT1 and MDV2) and pig (PRV1). By applying different bioinformatics tools, we highlighted the conserved sites in these glycoproteins which might be most significant regarding attachment and infection of the viruses. Moreover the conserved domains in these glycoproteins are also highlighted. From this study, we will able to analyze the role of different viral glycoproteins of different species during herpes virus adsorption and penetration. Moreover, this study will help to construct the antivirals that target the glycoproteins of different herpes viruses.

Proteomics analysis and its role in elucidation of functionally significant proteins in Mycoplasma bovis.

Mycoplasma bovis (M. bovis) is an emerging devastating cause of pneumonia in dairy and feedlot calves around the world, largely due to its increasing resistance to new generation effective antibiotics and lack of efficient vaccine. Failure of protective measures against M. bovis is mainly due to nonspecific targets. Most of the virulent factors of M. bovis and their underlying mechanisms are obscure to devise an effective control strategy. Full genome sequences of M. bovis strains basically provided a useful platform for the accurate identification of novel proteins and understanding their biological value using proteomics tools. Most of the previously documented proteins of M. bovis are involved in adhesion to host cells and are antigenic in nature. However, host immune response to some antigens proved to be non-protective. For the diagnosis of M. bovis infection, a serological assay based on whole cell proteins of M. bovis is commercially available but the specificity is likely to be improved by identifying and targeting the specific proteins. Many of the predicted proteins of M. bovis remain hypothetical, as their functions are yet to be confirmed experimentally. This review mainly focuses on the proteomics analysis of M. bovis and its role in identification of the virulence related factors and antigenic proteins of M. bovis. Future research directions have also been highlighted in this script for the application of important antigenic factors of M. bovis.

Genotype distribution of Chinese Mycoplasma bovis isolates and their evolutionary relationship to strains from other countries.

This study was undertaken to determine the genotypic distribution of Chinese M. bovis strains and their similarity to isolates from other countries. Two multilocus sequence typing (MLST) schemes (MLST-1 and MLST-2) and pulsed field gel electrophoresis (PFGE) were used to compare 44 Chinese strains and the M. bovis type strain PG45. The results showed a high genetic homogeneity of Chinese isolates; 43 of 44 (97.7%) Chinese isolates were identified as ST-10 and as ST-34 by MLST-1, while for MLST-2 42 of 44 (95.5%) were identified as ST-10 with the two remaining isolates of ST-32 and ST43. PFGE clustered 42 of 44 (95.5%) of the Chinese isolates into PT-I. The overall agreement rate between the three typing methods was 97.8% (95% CI:86.8-99.9%). The type strain PG45 was identified as a unique type by all three methods. When the MLST-2 scheme was further used to analyze 16 isolates of Australian and Israeli origin ST-10 was more dominant among Australian isolates (7/8), compared with those from Israel (3/8). The evolutionary relationship of the 60 isolates typed in this study assessed together with 206 additional isolates retrieved from pubmlst/mbovis database analyzed by geoBURST Minimum spanning tree (MST) confirmed that the Chinese, Israeli and Australian M. bovis isolates typed in this study that were predominantly ST-10, were clustered in CC3 with isolates originating from the USA. Our results suggest that ST-10 is an emerging clone of M. bovis population. We hypothesized that the widespread distribution of this type is a result of global livestock movements. These findings will help further the understanding of the global evolution of M. bovis and development of novel vaccines against M. bovis.

In silico analysis of fragile histidine triad involved in regression of carcinoma.

Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many different proteins are involved in HCCa including insulin growth factor (IGF) II , signal transducers and activators of transcription (STAT) 3, STAT4, mothers against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and selective internal radiation therapy (SIRT) etc. The present study is based on the bioinformatics analysis of FHIT protein in order to understand the proteomics aspect and improvement of the diagnosis of the disease based on the protein. Different information related to protein were gathered from different databases, including National Centre for Biotechnology Information (NCBI) Gene, Protein and Online Mendelian Inheritance in Man (OMIM) databases, Uniprot database, String database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Moreover, the structure of the protein and evaluation of the quality of the structure were included from Easy modeler programme. Hence, this analysis not only helped to gather information related to the protein at one place, but also analysed the structure and quality of the protein to conclude that the protein has a role in carcinoma.

Role Of Clamping Tube Thoracostomy Prior To Removal In Non-Cardiac Thoracic Trauma.

BACKGROUND: The frequently encountered thoracic trauma in surgical emergencies is a major cause of mortality and morbidity. Eighty percent of thoracic trauma can be managed by simple insertion of tube thoracostomy. Though guidelines for insertion are comprehensively explained in literature, an ideal algorithm for discontinuation is not available. A standard and safe defined protocol would eliminate hesitancy in confident removal among general surgeons. The objective of this study was to determine role of clamping trial prior to removal in terms of frequency of recurrent pneumothorax. METHODS: This study was conducted in department of Surgery Combined military hospital/Military Hospital Rawalpindi from April 2013 to March 2014. Total 180 patients with blunt or penetrating thoracic trauma were included in the study. Chest tube (28-36 Fr) was inserted in Trauma centre under strict asepsis. Tubes were then connected to under water seal for minimum six hours. Patients were randomly divided in two equal groups (90 in each). In Group A, Clamping trial was given before attempting removal while in Group B, tube was removed immediately without clamping trial. Patients of both groups were observed two hourly for development of recurrent pneumothorax. Data was analysed using SPSS-18. RESULTS: The comparison of frequency of recurrent pneumothorax in Group A (9 patients, 10%) and in Group B (4 patients, 4.5%) was not found to be statistically significant. (p-value 2.073). CONCLUSIONS: Clamping trial is unnecessary prior to removal of tube thoracostomy in blunt and penetrating non-cardiac thoracic trauma in terms of recurrent pneumothorax.

Role of Anteromedial Cortical Support for Unstable Intertrochanteric Fractures Being Treated With Cephalomedullary Nails.

INTRODUCTION: Reduction quality is of paramount importance for an optimal outcome in unstable pertrochanteric fractures. The non-anatomical functional anteromedial buttress is proposed to prevent impending mechanical complications. We aimed to evaluate the role of anteromedial cortical support in preventing mechanical complications following fixation with the cephalomedullary nail. MATERIALS AND METHODS: A prospective, single-arm interventional study was conducted in the Orthopaedics Department of a Combined Military Hospital (CMH) in Rawalpindi. The duration of the study was 24 months. Patients were recruited by the purposive sampling technique as per inclusion/exclusion criteria. Preoperatively, the reduction was categorized as per Baumgartner's and Chang's criteria. Post-operatively, weight bearing as tolerated was advised. Radiographs prior to discharge for loss of reduction were evaluated. Follow-up radiographic measurements of neck length, neck shaft angle, and their loss as per protocol were done at three and six months. RESULTS: A total of 202 patients were operated on from October 21 until August 23. Mortality at six months in 39 patients (19.3%) and loss to follow-up in 31 patients (15.3%) resulted in 132 patients with complete follow-up and having developed complications in 12 patients (9.09%). The mean age was 76.3 ± 7.98 years; males were 105 (79.5%), and females were 27 (20.5%). Closed reduction was 58 (43.9%), and additional manoeuvres were required in 74 (56.1%). The mean tip apex distance (TAD) was 24.56 ± 2.76, and the Calcar gap was 5.16 ± 1.27. Cleveland zone centre-centre in 54 (40.9%), inferior-centre in 65 (49.2%), and inferior-posterior (9.9%) were statistically significant for mechanical complications (p≤0.001). There was a significant association between the grading of Chang's and Baumgartner's poor groups for the development of mechanical complications (p≤0.001). The mean time to full weight bearing without support was 21 ± 1.22 weeks. The mean Hip Harris score at six months was 69.27 ± 7.68. CONCLUSION: Results suggest that anteromedial cortical support can lead to fewer potential mechanical complications at six months. A higher Chang's grade drives surgeons to engage in additional manoeuvres. Anteromedial cortical support is worth consideration for unstable pertrochanteric fractures.

Identification of Natural Lead Compounds against Hemagglutinin-Esterase Surface Glycoprotein in Human Coronaviruses Investigated via MD Simulation, Principal Component Analysis, Cross-Correlation, H-Bond Plot and MMGBSA.

The pandemic outbreak of human coronavirus is a global health concern that affects people of all ages and genders, but there is currently still no effective, approved and potential drug against human coronavirus, as many other coronavirus vaccines have serious side effects while the development of small antiviral inhibitors has gained tremendous attention. For this research, HE was used as a therapeutic target, as the spike protein displays a high binding affinity for both host ACE2 and viral HE glycoprotein. Molecular docking, pharmacophore modelling and virtual screening of 38,000 natural compounds were employed to find out the best natural inhibitor against human coronaviruses with more efficiency and fewer side effects and further evaluated via MD simulation, PCA, DCCR and MMGBSA. The lead compound 'Calceolarioside B' was identified on the basis of pharmacophoric features which depict favorable binding (ΔGbind -37.6799 kcal/mol) with the HE(5N11) receptor that describes positive correlation movements in active site residues with better stability, a robust H-bond network, compactness and reliable ADMET properties. The Fraxinus sieboldiana Blume plant containing the Calceolarioside B compound could be used as a potential inhibitor that shows a higher efficacy and potency with fewer side effects. This research work will aid investigators in the testing and identification of chemicals that are effective and useful against human coronavirus.

Conserved Domains in Variable Surface Lipoproteins A-G of Mycoplasma hyorhinis May Serve as Probable Multi-Epitope Candidate Vaccine: Computational Reverse Vaccinology Approach.

Mycoplasma hyorhinis (M. hyorhinis) is responsible for infections in the swine population. Such infections are usually cured by using antimicrobials and lead to develop resistance. Until now, there has been no effective vaccine to eradicate the disease. This study used conserved domains found in seven members of the variable lipoprotein (VlpA-G) family in order to design a multi-epitope candidate vaccine (MEV) against M. hyorhinis. The immunoinformatics approach was followed to predict epitopes, and a vaccine construct consisting of an adjuvant, two B cell epitopes, two HTL epitopes, and one CTL epitope was designed. The suitability of the vaccine construct was identified by its non-allergen, non-toxic, and antigenic nature. A molecular dynamic simulation was executed to assess the stability of the TLR2 docked structure. An immune simulation showed a high immune response toward the antigen. The protein sequence was reverse-translated, and codons were optimized to gain a high expression level in E. coli. The proposed vaccine construct may be a candidate for a multi-epitope vaccine. Experimental validation is required in future to test the safety and efficacy of the hypothetical candidate vaccine.

Design and Assessment of a Novel In Silico Approach for Developing a Next-Generation Multi-Epitope Universal Vaccine Targeting Coronaviruses.

In the past two decades, there have been three coronavirus outbreaks that have caused significant economic and health crises. Biologists predict that more coronaviruses may emerge in the near future. Therefore, it is crucial to develop preventive vaccines that can effectively combat multiple coronaviruses. In this study, we employed computational approaches to analyze genetically related coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, focusing on the spike glycoprotein as a potential vaccine candidate. By predicting common epitopes, we identified the top epitopes and combined them to create a multi-epitope candidate vaccine. The overall quality of the candidate vaccine was validated through in silico analyses, confirming its antigenicity, immunogenicity, and stability. In silico docking and simulation studies suggested a stable interaction between the multi-epitope candidate vaccine and human toll-like receptor 2 (TLR2). In silico codon optimization and cloning were used to further explore the successful expression of the designed candidate vaccine in a prokaryotic expression system. Based on computational analysis, the designed candidate vaccine was found to be stable and non-allergenic in the human body. The efficiency of the multi-epitope vaccine in triggering effective cellular and humoral immune responses was assessed through immune stimulation, demonstrating that the designed candidate vaccine can elicit specific immune responses against multiple coronaviruses. Therefore, it holds promise as a potential candidate vaccine against existing and future coronaviruses.

An In silico study of derivative of Newcastle disease virus epitopes based vaccine against Hemagglutunin neuraminidase protein.

The causative agent of Newcastle disease (ND) is Newcastle disease virus. It belongs to avian species of Orthoavulavirus, Avulavirinae subfamily and if left untreated it may cause epidemic in poultry. Many vaccines have been made against Newcastle disease based on inactivated and attenuated viruses but become useless due to the genetic changes in the virus. We have recently reported epitope based vaccine by using immunoinformatics approaches. The vaccine was previously constructed against Hemagglutunin neuraminidase protein of Newcastle disease virus. Here we extended our work to develop several chimera of the proposed vaccine to design a new multi-epitope vaccine by shuffling the cytotoxic T lymphocytes (CTL) segments of the vaccine. Total 5040 constructs have been analyzed by shuffling 7 CTL epitopes. Highest antigenic multi-epitope construct was selected for the further study. Our new multi-epitope vaccine (MEV) construct contains 259 amino acids and is immunogenic, more antigenic and non-allergen. The refinement of the structure of MEV construct was performed. Molecular docking analyses showed its maximum binding with avian Toll-like 4 receptor. Subsequently, immune simulations showed its predicted ability to induce the host primary and secondary responses. Study suggests that our new multi-epitope vaccine chimera is more effective and stable protein against Newcastle disease virus strains in Pakistan. However, further studies are required to validate the vaccine through In vitro and In vivo studies.

Identification of Lead Compounds against Scm (fms10) in Enterococcus faecium Using Computer Aided Drug Designing.

(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance in E. faecium. The focus of this research work is to identify a novel compound against this pathogen by using bioinformatics tools and technology. (2) Methods: We screened the proteome (accession No. PRJNA55353) information from the genome database of the National Centre for Biotechnology Information (NCBI) and suggested a potential drug target. I-TASSER was used to predict the three-dimensional structure of the protein, and the structure was optimized and minimized by different tools. PubChem and ChEBI were used to retrieve the inhibitors. Pharmacophore modeling and virtual screening were performed to identify novel compounds. Binding interactions of compounds with target protein were checked using LigPlot. pkCSM, SwissADME, and ProTox-II were used for adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. (3) Results: Novel selected compounds have improved absorption and have better ADMET properties. Based on our results, the chemically identified inhibitor ZINC48942 targeted the receptor that can inhibit the activity of infection in E. faecium. This research work will be beneficial for the scientific community and could aid in the design of a new drug against E. faecium infections. (4) Conclusions: It was observed that novel compounds are potential inhibitors with more efficacy and fewer side effects. This research work will help researchers in testing and identification of these chemicals useful against E. faecium.

Genome-wide Analysis of Four Enterobacter cloacae complex type strains: Insights into Virulence and Niche Adaptation.

Enterobacter cloacae complex (Ecc) species are widely distributed opportunistic pathogens mainly associated with humans and plants. In this study, the genomes of clinical isolates including E. hormaechei, E. kobei, and E. ludwigii and non-clinical isolate including E. nimipressuralis were analysed in combination with the genome of E. asburiae by using the reference strain E. cloacae subsp. cloacae ATCC 13047; the Ecc strains were tested on artificial sputum media (ASM), which mimics the host, to evaluate T6SS genes as a case study. All five Ecc strains were sequenced in our lab. Comparative genome analysis of the Ecc strains revealed that genes associated with the survival of Ecc strains, including genes of metal-requiring proteins, defence-associated genes and genes associated with general physiology, were highly conserved in the genomes. However, the genes involved in virulence and drug resistance, specifically those involved in bacterial secretion, host determination and colonization of different strains, were present in different genomic regions. For example, T6SS accessory and core components, T4SS, and multidrug resistance genes/efflux system genes seemed vital for the survival of Ecc strains in various environmental niches, such as humans and plants. Moreover, the ASM host-mimicking growth medium revealed significantly high expression of T6SS genes, including PrpC, which is a regulatory gene of the T6SS, in all tested Ecc strains compared to the control medium. The variations in T6SS gene expression in ASM vs. control showed that the ASM system represents a simple, reproducible and economical alternative to animal models for studies such as those aimed at understanding the divergence of Ecc populations. In summary, genome sequencing of clinical and environmental Ecc genomes will assist in understanding the epidemiology of Ecc strains, including the isolation, virulence characteristics, prevention and treatment of infectious disease caused by these broad-host-range niche-associated species.

In Silico Identification of Novel Apolipoprotein E4 Inhibitor for Alzheimer's Disease Therapy.

INTRODUCTION: Apolipoprotein E4 (ApoE) is a major genetic factor for developing Alzheimer's disease (AD). It plays a vital role in brain to maintain a constant supply of neuronal lipids for rapid and dynamic membrane synthesis. Aggregation of beta amyloid plaques (Aß) and neurofibrillary tangles in brain are responsible for onset of AD. The current study is designed to predict a drug against over activity of apoE4. 22 natural compounds (marine, microorganism and plant derivative) were used in current study. METHODS: These compounds were used as inhibitors to target apoE4 protein activity. Moreover, six synthetic compounds were docked with target protein to compare and analyze the docking results with natural compounds. S-Allyl-L-Cysteine, Epicatechin Gallate and Fulvic acid showed highest binding affinity (-7.1, - 7 and -7 kcal /mol respectively). Analysis of the docked complex showed that Epicatechin Gallate bonded with Gln156 and Asp35. Furthermore, Fulvic Acid showed hydrogen bonding with Glu27. Among synthetic compound, Tideglusib had highest binding affinity with target protein but did not show hydrogen bonding with any amino acid residue. Moreover, a natural compound S-Allyl-LCysteine also showed highest binding affinity but did not show hydrogen bonding with any amino acid residue. RESULTS AND CONCLUSION: Our study highlighted Epicatechin Gallate as a potential lead compound on the basis of binding affinity and hydrogen bonding to inhibit the progression of AD.

Accidental Ingestion Of Toothbrush: An Unusual Foreign Body.

Toothbrush is a rare foreign body to be ingested accidentally. The unusual shape of the toothbrush with no theoretical possibility of spontaneous passage mandates an interventional approach. If left untreated, it can lead to pressure necrosis, bleeding, perforation and ulceration. An endoscopic attempt in an expert clinic if available is the ideal approach. If failed, surgical management by laparoscope or mini laparotomy should be done. The evaluation for underlying psychiatric disorders like bulimia, schizophrenia or generalized eating disorder should be considered to prevent such recurrence. Here, we present a case of 55 years of age, male living a normal life with no known comorbid, who ingested accidentally a toothbrush two weeks prior to presentation and was managed at our surgical department after a failed endoscopic attempt.