Search results for: evolutionary bioinformatics

Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva

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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.

Keywords: totiviridae, killer virus, proteomics, transcriptomics

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Authors: Peng Hou

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Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

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Authors: Umairah Natasya Binti Mohd Omeershffudin, Suresh Kumar

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Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. Particular concern is the global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae. Characterization of antibiotic resistance determinants at the genomic level plays a critical role in understanding, and potentially controlling, the spread of multidrug-resistant (MDR) pathogens. In this study, drug-resistant Klebsiella pneumoniae strain 825795-1 was investigated with extensive computational approaches aimed at identifying novel drug targets among hypothetical proteins. We have analyzed 1099 hypothetical proteins available in genome. We have used in-silico genome subtraction methodology to design potential and pathogen-specific drug targets against Klebsiella pneumoniae. We employed bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted 645 proteins were further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We found 135 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we identified 49 cytoplasmic protein as potential drug targets through sub-cellular localization prediction. Further, we investigated these proteins in the DrugBank databases, and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. The results of this study will facilitate discovery of new drugs against Klebsiella pneumoniae.

Keywords: pneumonia, drug target, hypothetical protein, subtractive genomics

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Authors: Tei Kim, Brooklynn McNeil, Kathryn Dunn, Douglas I. Walker

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To better characterize the relationship between complex chemical exposures and disease, our laboratory uses an approach that combines low-cost, polydimethylsiloxane (silicone) wristband samplers that absorb many of the chemicals we are exposed to with untargeted high-resolution mass spectrometry (HRMS) to characterize 1000’s of chemicals at a time. In studies with human populations, these wristbands can provide an important measure of our environment: however, there is a need to use this approach in large cohorts to study exposures associated with the disease. To facilitate the use of silicone samplers in large scale population studies, the goal of this research project was to establish automated sample preparation methods that improve throughput, robustness, and scalability of analytical methods for silicone wristbands. Using the Opentron OT2 automated liquid platform, which provides a low-cost and opensource framework for automated pipetting, we created two separate workflows that translate the manual wristband preparation method to a fully automated protocol that requires minor intervention by the operator. These protocols include a sequence generation step, which defines the location of all plates and labware according to user-specified settings, and a transfer protocol that includes all necessary instrument parameters and instructions for automated solvent extraction of wristband samplers. These protocols were written in Python and uploaded to GitHub for use by others in the research community. Results from this project show it is possible to establish automated and open source methods for the preparation of silicone wristband samplers to support profiling of many environmental exposures. Ongoing studies include deployment in longitudinal cohort studies to investigate the relationship between personal chemical exposure and disease.

Keywords: bioinformatics, automation, opentrons, research

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Authors: Elham Fariborzi, Hoda Anvari Kazemabad

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Today, ICT plays an important role in all matters and it affects the development of creative cities. According to virtual space in this technology, it use especially for expand terms like smart schools, Virtual University, web-based training and virtual classrooms that is in parallel with the traditional teaching. Nowadays, the educational systems in different countries such as Iran are changing and start increasing creativity in the learning environment. It will contribute to the development of innovative ideas and thinking of the people in this environment; such opportunities might be cause scientific discovery and development issues. The creativity means the ability to generate ideas and numerous, new and suitable solutions for solving the problems of real and virtual individuals and society, which can play a significant role in the development of creative current physical cities or virtual borders ones in the future. The purpose of this paper is to study strategies to increase creativity in a virtual learning to develop a creative city. In this paper, citation/ library study was used. The full description given in the text, including how to create and enhance learning creativity in a virtual classroom by reflecting on performance and progress; attention to self-directed learning guidelines, efficient use of social networks, systematic discussion groups and non-intuitive targeted controls them by involved factors and it may be effective in the teaching process regarding to creativity. Meanwhile, creating a virtual classroom the style of class recognizes formally the creativity. Also the use of a common model of creative thinking between student/teacher is effective to solve problems of virtual classroom. It is recommended to virtual education’ authorities in Iran to have a special review to the virtual curriculum for increasing creativity in educational content and such classes to be witnesses more creative in Iran's cities.

Keywords: virtual learning, creativity, e-learning, bioinformatics, biomedicine

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Authors: M. S. Matlala, I. Ignatious

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Environmental sustainability has taken the center stage in human life all over the world. Energy is the most essential component of our life. The conventional sources of energy are non-renewable and have a detrimental environmental impact. Therefore, there is a need to move from conventional to non-conventional renewable energy sources to satisfy the world’s energy demands. The study aimed at screening for microbial cellulolytic enzymes using a proteomic approach. The objectives were to screen for microbial cellulases with high specific activity and separate the cellulolytic enzymes using a combination of zymography and two-dimensional (2-D) gel electrophoresis followed by tryptic digestion, Matrix-assisted Laser Desorption Ionisation-Time of Flight (MALDI-TOF) and bioinformatics analysis. Fungal and bacterial isolates were cultured in M9 minimal and Mandel media for a period of 168 hours at 60°C and 30°C with cellobiose and Avicel as carbon sources. Microbial cells were separated from supernatants through centrifugation, and the crude enzyme from the cultures was used for the determination of cellulase activity, zymography, SDS-PAGE, and two-dimensional gel electrophoresis. Five isolates, with lytic action on carbon sources studied, were a bacterial strain (BARK) and fungal strains (VCFF1, VCFF14, VCFF17, and VCFF18). Peak cellulase production by the selected isolates was found to be 3.8U/ml, 2.09U/ml, 3.38U/ml, 3.18U/ml, and 1.95U/ml, respectively. Two-dimensional gel protein maps resulted in the separation and quantitative expression of different proteins by the microbial isolates. MALDI-TOF analysis and database search showed that the expressed proteins in this study closely relate to different glycoside hydrolases produced by other microbial species with an acceptable confidence level of 100%.

Keywords: cellulases, energy, two-dimensional gel electrophoresis, matrix-assisted laser desorption ionisation-time of flight, MALDI-TOF MS

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Authors: Victor Prevost, Solene Landerneau, Michel Duhamel, Joel Sternheimer, Olivier Gallet, Pedro Ferrandiz, Marwa Mokni

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The search for homologous proteins is one of the ongoing challenges in biology and bioinformatics. Traditionally, a pair of proteins is thought to be homologous when they originate from the same ancestral protein. In such a case, their sequences share similarities, and advanced scientific research effort is spent to investigate this question. On this basis, we propose the Protein-Wave Alignment Tool (”P-WAT”) developed within the framework of the France Relance 2030 plan. Our work takes into consideration the mass-related wave aspect of protein biosynthesis, by associating specific frequencies to each amino acid according to its mass. Amino acids are then regrouped within their mass category. This way, our algorithm produces specific alignments in addition to those obtained with a common amino acid coding system. For this purpose, we develop the ”P-WAT” original algorithm, able to address large protein databases, with different attributes such as species, protein names, etc. that allow us to align user’s requests with a set of specific protein sequences. The primary intent of this algorithm is to achieve efficient alignments, in this specific conceptual frame, by minimizing execution costs and information loss. Our algorithm identifies sequence similarities by searching for matches of sub-sequences of different sizes, referred to as primers. Our algorithm relies on Boolean operations upon a dot plot matrix to identify primer amino acids common to both proteins which are likely to be part of a significant alignment of peptides. From those primers, dynamic programming-like traceback operations generate alignments and alignment scores based on an adjusted PAM250 matrix.

Keywords: protein, alignment, homologous, Genodic

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Authors: Benjamin A. Ha, Marco Morselli, Xinhui Paige Zhang, Elizabeth A. C. Heath-Heckman, Jonathan B. Puritz, David K. Jacobs

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Next-generation sequencing has enhanced the ability to acquire massive amounts of sequence data to address classic population genetic questions for non-model organisms. Targeted approaches allow for cost effective or more precise analyses of relevant sequences; although, many such techniques require a known genome and it can be costly to purchase probes from a company. This is challenging for non-model organisms with no published genome and can be expensive for large population genetic studies. Expressed exome capture sequencing (EecSeq) synthesizes probes in the lab from expressed mRNA, which is used to capture and sequence the coding regions of genomic DNA from a pooled suite of samples. A normalization step produces probes to recover transcripts from a wide range of expression levels. This approach offers low cost recovery of a broad range of genes in the genome. This research project expands on EecSeq to investigate if mRNA from one taxon may be used to capture relevant sequences from a series of increasingly less closely related taxa. For this purpose, we propose to use the endangered Northern Tidewater goby, Eucyclogobius newberryi, a non-model organism that inhabits California coastal lagoons. mRNA will be extracted from E. newberryi to create probes and capture exomes from eight other taxa, including the more at-risk Southern Tidewater goby, E. kristinae, and more divergent species. Captured exomes will be sequenced, analyzed bioinformatically and phylogenetically, then compared to previously generated phylogenies across this group of gobies. This will provide an assessment of the utility of the technique in cross-species studies and for analyzing low genetic variation within species as is the case for E. kristinae. This method has potential applications to provide economical ways to expand population genetic and evolutionary biology studies for non-model organisms.

Keywords: coastal lagoons, endangered species, non-model organism, target capture method

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Authors: Tamara Zappaterra

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The Learning Difficulties have an evolutionary nature. The international research has focused its analysis on the characteristics of Learning Difficulties in childhood, but we are still far from a thorough understanding of the nature of such disorders in adolescence and adulthood. Such issues become even more urgent in the university context. Spelling, meaning, and appropriate use of the specific vocabulary of the various disciplines represent an additional challenge for the dyslexic student. This paper explores the characteristics of Learning Difficulties in adulthood and the impact with the university teaching. It presents the results of an interdisciplinary project (educational, medical and engineering area) at University of Florence. The purpose of project is to design of a protocol for usability of teaching and individual study at university level. The project, after a first reconnaissance of user needs that have been reached with the participation of the very same protagonists, is at the stage of guidelines drafting for inclusion and education, to be used by teachers, students and administrative staff. The methodologies used are a questionnaire built on purpose and a series of focus groups with users. For collecting data during the focus groups it was decided to use a method typical of the Quality Function Deployment, a tool originally used for quality management, whose versatility makes it easy to use in a number of different context. The paper presents furthermore the findings of the project, the most significant elements of the guidelines for teaching, i.e. the section for teachers, whose aim is to implement a Learning Difficulties-friendly teaching, even at the university level, in compliance with italian Law 170/2010. The Guidelines for the didactic and inclusion of Learning Difficulties students of the University of Florence are articulated around a global and systemic plan of action, meant to accompany and protect the students during their study career, even before enrolling at the University, with different declination: the logistical, relational, educational, and didactic levels have been considered. These guidelines in Italy received the endorsement of the CNUDD. It is a systemic intervention plan for Learning Difficulties students, which roused and keeps rousing the interest of all the university system, with a radical consideration on academic teaching. Since while we try to provide the best Learning Difficulties-friendly didactic in compliance with the rules, no one can be exempted from a wider consideration on the nature and the quality of university teaching offered to all students.

Keywords: didactic tools, learning difficulties, special and inclusive education, university teaching

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Authors: Manju Kanu, Subrata Sinha, Surabhi Johari

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Viral proteins of Ebola viruses belong to one of the best studied viruses; however no effective prevention against EBOV has been developed. Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with Ebola virus as a model system. Hence great challenge in the field of ebola virus research is to design universal vaccine. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertypes Human Leukocyte Antigen (HLA) alleles. MUSCLE and MOTIF tools were used to find out most conserved peptide sequences of viral proteins. Immunoinformatics tools were used for prediction of immunogenic peptides of viral proteins in zaire strains of Ebola virus. Putative epitopes for viral proteins (VP) were predicted from conserved peptide sequences of VP. Three tools NetCTL 1.2, BIMAS and Syfpeithi were used to predict the Class I putative epitopes while three tools, ProPred, IEDB-SMM-align and NetMHCII 2.2 were used to predict the Class II putative epitopes. B cell epitopes were predicted by BCPREDS 1.0. Immunogenic peptides were identified and selected manually by putative epitopes predicted from online tools individually for both MHC classes. Finally sequences of predicted peptides for both MHC classes were looked for common region which was selected as common immunogenic peptide. The immunogenic peptides were found for viral proteins of Ebola virus: epitopes FLESGAVKY, SSLAKHGEY. These predicted peptides could be promising candidates to be used as target for vaccine design.

Keywords: epitope, b cell, immunogenicity, ebola

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Authors: David Nogueiras Blanco, Amir Alwash, Arnaud Gaudinat, René Schneider

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At a time when the access to and the sharing of information are crucial in the world of research, the use of technologies such as persistent identifiers (PIDs), Current Research Information Systems (CRIS), and ontologies may create platforms for information sharing if they respond to the need of disambiguation of their data by assuring interoperability inside and between other systems. INCIPIT-CRIS is a continuation of the former INCIPIT project, whose goal was to set up an infrastructure for a low-cost attribution of PIDs with high granularity based on Archival Resource Keys (ARKs). INCIPIT-CRIS can be interpreted as a logical consequence and propose a research information management system developed from scratch. The system has been created on and around the Schema.org ontology with a further articulation of the use of ARKs. It is thus built upon the infrastructure previously implemented (i.e., INCIPIT) in order to enhance the persistence of URIs. As a consequence, INCIPIT-CRIS aims to be the hinge between previously separated aspects such as CRIS, ontologies and PIDs in order to produce a powerful system allowing the resolution of disambiguation problems using a combination of an ontology such as Schema.org and unique persistent identifiers such as ARK, allowing the sharing of information through a dedicated platform, but also the interoperability of the system by representing the entirety of the data as RDF triplets. This paper aims to present the implemented solution as well as its simulation in real life. We will describe the underlying ideas and inspirations while going through the logic and the different functionalities implemented and their links with ARKs and Schema.org. Finally, we will discuss the tests performed with our project partner, the Swiss Institute of Bioinformatics (SIB), by the use of large and real-world data sets.

Keywords: current research information systems, linked data, ontologies, persistent identifier, schema.org, semantic web

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Authors: Monisha Isaac

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Biotechnology is a discipline which explains the use of living organisms and systems to construct a product, or we can define it as an application or technology developed to use biological systems and organisms processes for a specific use. Particularly, it includes cells and its components use for new technologies and inventions. The tools developed can be further used in diverse fields such as agriculture, industry, research and hospitals etc. The 21^st century has seen a drastic development and advancement in biotechnology in India. Significant increase in Government of India’s outlays for biotechnology over the past decade has been observed. A sectoral break up of biotechnology-based companies in India shows that most of the companies are agriculture-based companies having interests ranging from tissue culture to biopesticides. Major attention has been given by the companies in health related activities and in environmental biotechnology. The biopharmaceutical, which comprises of vaccines, diagnostic, and recombinant products is the most reliable and largest segment of the Indian Biotech industry. India has developed its vaccine markets and supplies them to various countries. Then there are the bio-services, which mainly comprise of contract researches and manufacturing services. India has made noticeable developments in the field of bio industries including manufacturing of enzymes, biofuels and biopolymers. Biotechnology is also playing a crucial and significant role in the field of agriculture. Traditional methods have been replaced by new technologies that mainly focus on GM crops, marker assisted technologies and the use of biotechnological tools to improve the quality of fertilizers and soil. It may only be a small contributor but has shown to have huge potential for growth. Bioinformatics is a computational method which helps to store, manage, arrange and design tools to interpret the extensive data gathered through experimental trials, making it important in the design of drugs.

Keywords: biotechnology, advancement, agriculture, bio-services, bio-industries, bio-pharmaceuticals

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Authors: Huang Hao, Li Weiwen

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Global biodiversity continues to decline as a result of global climate change and various human activities, such as habitat destruction, pollution, introduction of alien species and overfishing. Although there are connections between global marine organisms more or less, it is better to have clear geographical boundaries in order to facilitate the assessment and management of different biogeographical zones. And so area based management tools (ABMT) are considered as the most effective means for the conservation and sustainable use of marine biodiversity. On a large scale, the geographical gap (or barrier) is the main factor to influence the connectivity, diffusion, ecological and evolutionary process of marine organisms, which results in different distribution patterns. On a small scale, these factors include geographical location, geology, and geomorphology, water depth, current, temperature, salinity, etc. Therefore, the analysis on geographic and environmental factors is of great significance in the study of biodiversity characteristics. This paper summarizes the marine spatial classification and ABMTs used in coastal area, open oceans and deep sea. And analysis principles and methods of marine spatial classification based on biogeographic related factors, and take China Near Sea (CNS) area as case study, and select key biogeographic related factors, carry out marine spatial classification at biological region scale, ecological regionals scale and biogeographical scale. The research shows that CNS is divided into 5 biological regions by climate and geographical differences, the Yellow Sea, the Bohai Sea, the East China Sea, the Taiwan Straits, and the South China Sea. And the bioregions are then divided into 12 ecological regions according to the typical ecological and administrative factors, and finally the eco-regions are divided into 98 biogeographical units according to the benthic substrate types, depth, coastal types, water temperature, and salinity, given the integrity of biological and ecological process, the area of the biogeographical units is not less than 1,000 km². This research is of great use to the coastal management and biodiversity conservation for local and central government, and provide important scientific support for future spatial planning and management of coastal waters and sustainable use of marine biodiversity.

Keywords: spatial classification, marine biodiversity, bio-geographical, conservation

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Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

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The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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Authors: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik

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Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).

Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Husham Bayazed

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Purpose of presentation: Pregnancy represents the most important period for the conservation of the species. The immune system is one of the most important systems protecting the mother against the environment and preventing damage to the fetus. This presentation aims to review and discuss the role of the immune system during pregnancy, the evolutionary inflammatory process through pregnancy, infectious and environmental exposure influences on the mother and the fetus, and the impacts of sexual dimorphism of the placenta on offspring susceptibility to different disorders. Recent Findings: In 1960, Peter Medawar (Nobel Prize Winner) proposed that the fetus, a semi-allograft, is similar to a tissue graft that escapes rejection through a mechanism involving systemic immune suppression (Graft –Host response). However, recent researchers and studies have documented that implantation means inflammation, and the inflammatory process is considered a breach of tolerance in pregnancy with immune induction, which is necessary for the protection of the mother and the fetus against infections and environmental triggers. This inflammatory process should be maintained during different pregnancy phases till parturition, and any block at any phase will be associated with pregnancy complications, including pregnancy failure or loss, miscarriage, and preterm birth subsequently. Maternal immune activation following any trigger can have a positive effect on the fetus. The old concept of the placenta being asexual is inaccurate, and being with sexual dimorphism with clear differences in susceptibility to different factors that stimulate maternal immunity. Summary: The presence of different immune cells ((i.e., T cells, B cells, NK cells, etc.) at the implantation site is considered proof of a strong maternal immune response to the fetus. Therefore, human pregnancy is considered a unique immunological paradigm requiring maternal immune modulation rather than suppression. So Medawar's postulation of maternal systemic immunosuppression is wrong. Maternal immune system activation triggered by infections, stress, diet, and pollution can have a positive effect on the fetus, with the development of fetal-trained immunity necessary for survival. The sexual dimorphism of the placenta seems to have an impact on the differences in sex susceptible to the environment maternal risk stimuli. This link to why the incidence of autism is increasing more among boys than girls.

Keywords: pregnancy, maternal immunity, implantation and inflammation, placenta sexual dimorphism

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Authors: Deddi Nordiawan

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Effective public policy creation required a strong budget system, both in terms of design and implementation. Performance-based Budget is an evolutionary approach with two substantial characteristics; first, the strong integration between budgeting and planning, and second, its existence as guidance so that all activities and expenditures refer to measurable performance targets. There are four processes in the government that should be followed in order to make the budget become performance-based. These four processes consist of the preparation of a vision according to the bold aspiration, the formulation of outcome, the determination of output based on the analysis of organizational resources, and the formulation of Value Creation Map that contains a series of programs and activities. This is consistent with the concept of logic model which revealed that the budget performance should be placed within a relational framework of resources, activities, outputs, outcomes and impacts. Through the issuance of Law 17/2003 regarding State Finance, local governments in Indonesia have to implement performance-based budget. Central Government then issued Government Regulation 58/2005 which contains the detail guidelines how to prepare local governments budget. After a decade, implementation of performance budgeting in local government is still not fully meet expectations, though the guidance is completed, socialization routinely performed, and trainings have also been carried out at all levels. Accordingly, this study views the practice of performance-based budget at local governments as a problematic situation. This condition must be approached with a system approach that allows the solutions from many point of views. Based on the fact that the infrastructure of budgeting has already settled, the study then considering the situation as complexity. Therefore, the intervention needs to be done in the area of human activity system. Using Soft Systems Methodology, this research will reconstruct the process of performance-based budget at local governments is area of human activity system. Through conceptual models, this study will invite all actors (central government, local government, and the parliament) for dialogue and formulate interventions in human activity systems that systematically desirable and culturally feasible. The result will direct central government in revise the guidance to local government budgeting process as well as a reference to build the capacity building strategy.

Keywords: soft systems methodology, performance-based budgeting, Indonesia, public policy

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Authors: John McDowall, Lucy Lightfoot

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Stigma constitutes a significant barrier to the recovery and social integration of individuals affected by mental illness. Although there is some debate in the literature regarding the definition and utility of stigma as a concept, it is widely accepted that it comprises three components: stereotypical beliefs, prejudicial reactions, and discrimination. Stereotypical beliefs describe the cognitive knowledge-based component of stigma, referring to beliefs (often negative) about members of a group that is based on cultural and societal norms (e.g. ‘People with anxiety are just weak’). Prejudice refers to the affective/evaluative component of stigma and describes the endorsement of negative stereotypes and the resulting negative emotional reactions (e.g. ‘People with anxiety are just weak, and they frustrate me’). Discrimination refers to the behavioural component of stigma, which is arguably the most problematic, as it exerts a direct effect on the stigmatized person and may lead people to behave in a hostile or avoidant way towards them (i.e. refusal to hire them). Research exploring anti-stigma initiatives focus primarily on an educational approach, with the view that accurate information will replace misconceptions and decrease stigma. Many approaches take a biogenetic stance, emphasising brain and biochemical deficits - the idea being that ‘mental illness is an illness like any other.' While this approach tends to effectively reduce blame, it has also demonstrated negative effects such as increasing prognostic pessimism, the desire for social distance and perceptions of stereotypes. In the present study 144 participants were split into three groups and read one of three vignettes presenting causal explanations for Generalised Anxiety Disorder (GAD): One explanation emphasized biogenetic factors as being important in the etiology of GAD, another emphasised psychosocial factors (e.g. aversive life events, poverty, etc.), and a third stressed the adaptive features of the disorder from an evolutionary viewpoint. A variety of measures tapping the various components of stigma were administered following the vignettes. No difference in stigma measures as a function of causal explanation was found. People who had contact with mental illness in the past were significantly less stigmatising across a wide range of measures, but this did not interact with the type of causal explanation.

Keywords: generalised anxiety disorder, discrimination, prejudice, stigma

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Debamitra Chakravorty, Pratap K. Parida

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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.

Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design

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Authors: Mohammad Faheem, M. Tabish Rehman, Mohd Danishuddin, Asad U. Khan

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The worldwide dissemination of CTX-M type β-lactamases is a threat to human health. Previously, we have reported the spread of blaCTX-M-15 gene in different clinical strains of Enterobacteriaceae from the hospital settings of Aligarh in north India. In view of the varying resistance pattern against cephalosporins and other β-lactam antibiotics, we intended to understand the correlation between MICs and catalytic activity of CTX-M-15. In this study, steady-state kinetic parameters and MICs were determined on E. coli DH5α transformed with blaCTX-M-15 gene that was cloned from Enterobacter cloacae (EC-15) strain of clinical background. The effect of conventional β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) on CTX-M-15 was also studied. We have found that tazobactam is the best among these inhibitors against CTX-M-15. The inhibition characteristic of tazobactam is defined by its very low IC50 value (6 nM), high affinity (Ki = 0.017 µM) and better acylation efficiency (k+2/K9 = 0.44 µM-1s-1). It forms an acyl-enzyme covalent complex, which is quite stable (k+3 = 0.0057 s-1). Since increasing resistance has been reported against conventional b-lactam antibiotic-inhibitor combinations, we aspire to design a non-b-lactam core containing b-lactamase inhibitor. For this, we screened ZINC database and performed molecular docking to identify a potential non-β-lactam based inhibitor (ZINC03787097). The MICs of cephalosporin antibiotics in combination with this inhibitor gave promising results. Steady-state kinetics and molecular docking studies showed that ZINC03787097 is a reversible inhibitor which binds non-covalently to the active site of the enzyme through hydrogen bonds and hydrophobic interactions. Though, it’s IC50 (180 nM) is much higher than tazobactam, it has good affinity for CTX-M-15 (Ki = 0.388 µM). This study concludes that ZINC03787097 compound can be used as seed molecule to design more efficient non-b-lactam containing b-lactamase inhibitor that could evade pre-existing bacterial resistance mechanisms.

Keywords: ESBL, non-b-lactam-b-lactamase inhibitor, bioinformatics, biomedicine

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Authors: Perizat Balkhimbekova

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Evolutionary changes in cognitive world view taking place in the last decades are followed by changes in perception of the key concepts which are related to the certain lingua-cultural sphere. Also, such concepts reflect the person’s attitude to essential processes in the sphere of concepts, e.g. the opposite operations like creation and destruction. These changes in people’s life and thinking are displayed in a language world view. In order to open the maintenance of mental structures and concepts we should use language means as observable results of people’s cognitive activity. Semantics of words, free phrases and idioms should be considered as an authoritative source of information concerning concepts. The regularized set of concepts in people consciousness forms the sphere of concepts. Cognitive linguistics widely discusses the sphere of concepts as its crucial category defining it as the field of knowledge which is made of concepts. It is considered that a sphere of concepts comprises the various types of association and forms conceptual fields. As a material for the given research, the data from Russian National Corpus and British National Corpus were used. In is necessary to point out that data provided by computational studies, are intrinsic and verifiable; so that we have used them in order to get the reliable results. The procedure of study was based on such techniques as extracting of the context containing concepts of creation|destruction from the Russian National Corpus (RNC), and British National Corpus (BNC); analyzing and interpreting of those context on the basis of cognitive approach; finding of correspondence between the given concepts in the Russian and English world view. The key problem of our study is to find the correspondence between the elements of world view represented by opposite concepts such as creation and destruction. Findings: The concept of "destruction" indicates a process which leads to full or partial destruction of an object. In other words, it is a loss of the object primary essence: structures, properties, distinctive signs and its initial integrity. The concept of "creation", on the contrary, comprises positive characteristics, represents the activity aimed at improvement of the certain object, at the creation of ideal models of the world. On the other hand, destruction is represented much more widely in RNC than creation (1254 cases of the first concept by comparison to 192 cases for the second one). Our hypothesis consists in the antinomy represented by the aforementioned concepts. Being opposite both in respect of semantics and pragmatics, and from the point of view of axiology, they are at the same time complementary and interrelated concepts.

Keywords: creation, destruction, concept, world view

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Authors: Asif Mahmood, Yousef Alzeghayer

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The size effects of a precursor Y2BaCuO5 (Y211) powder on the microstructure and critical current density (Jc) of liquid infiltration growth (LIG)-processed YBa2Cu3O7-y (Y123) bulk superconductors were investigated in terms of milling time (t). YBCO bulk samples having high Jc values have been selected for the flywheel energy storage system. Y211 powders were attrition-milled for 0-10 h in 2 h increments at a fixed rotation speed of 400 RPM. Y211 pre-forms were made by pelletizing the milled Y211 powders followed by subsequent sintering, after which an LIG process with top seeding was applied to the Y211/Ba3Cu5O8 (Y035) pre-forms. Spherical pores were observed in all LIG-processed Y123 samples, and the pore density gradually decreased as t increased from 0 h to 8 h. In addition to the reduced pore density, the Y211 particle size in the final Y123 products also decreased with increasing t. As t increased further to 10 h, unexpected Y211 coarsening and large pore evolutions were observed. The magnetic susceptibility-temperature curves showed that the onset superconducting transition temperature (Tc, onset) of all samples was the same (91.5 K), but the transition width became greater as t increased. The Jc of the Y123 bulk superconductors fabricated in this study was observed to correlate well with t of the Y211 precursor powder. The maximum Jc of 1.0×105 A cm-2 (at 77 K, 0 T) was achieved at t = 8 h, which is attributed to the reduction in pore density and Y211 particle size. The prolonged milling time of t = 10 h decreased the Jc of the LIG-processed Y123 superconductor owing to the evolution of large pores and exaggerated Y211 growth. YBCO bulk samples having high Jc (samples prepared using 8 h milled powders) have been used for the energy storage system in flywheel energy storage system.

Keywords: critical current, bulk superconductor, liquid infiltration, bioinformatics

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Authors: Scott Andersen

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Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

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Authors: Renata Martins Pacheco, João Claro

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Wildfires are becoming an increasing concern worldwide, causing substantial social, economic, and environmental disruptions. This situation is especially relevant in Mediterranean-climate regions, present in all the five continents of the world, in which fire is not only a natural component of the environment but also perhaps one of the most important evolutionary forces. The rise in wildfire occurrences and their associated impacts suggests the need for identifying knowledge gaps and enhancing the basis of scientific evidence on how managers and policymakers may act effectively to address them. Considering that the main goal of a systematic map is to collate and catalog a body of evidence to describe the state of knowledge for a specific topic, it is a suitable approach to be used for this purpose. In this context, the aim of this study is to systematically map the research trends in wildfire management practices in Mediterranean-climate regions. A total of 201 wildfire management studies were analyzed and systematically mapped in terms of their: Year of publication; Place of study; Scientific outlet; Research area (Web of Science) or Research field (Scopus); Wildfire phase; Central research topic; Main objective of the study; Research methods; and Main conclusions or contributions. The results indicate that there is an increasing number of studies being developed on the topic (most from the last 10 years), but more than half of them are conducted in few Mediterranean countries (60% of the analyzed studies were conducted in Spain, Portugal, Greece, Italy or France), and more than 50% are focused on pre-fire issues, such as prevention and fuel management. In contrast, only 12% of the studies focused on “Economic modeling” or “Human factors and issues,” which suggests that the triple bottom line of the sustainability argument (social, environmental, and economic) is not being fully addressed by fire management research. More than one-fourth of the studies had their objective related to testing new approaches in fire or forest management, suggesting that new knowledge is being produced on the field. Nevertheless, the results indicate that most studies (about 84%) employed quantitative research methods, and only 3% of the studies used research methods that tackled social issues or addressed expert and practitioner’s knowledge. Perhaps this lack of multidisciplinary studies is one of the factors hindering more progress from being made in terms of reducing wildfire occurrences and their impacts.

Keywords: wildfire, Mediterranean-climate regions, management, policy

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Authors: Fatemeh Zeinali Sehrig

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Background: miRNAs play an important role in the post-transcriptional regulation of genes, including genes involved in DNA methylation (DNMTs), and are also important regulators of oncogenic pathways. The study of microRNAs and DNMTs in breast cancer allows the development of targeted treatments and early detection of this cancer. Methods and Materials: Clinical Patients and Samples: Institutional guidelines, including ethical approval and informed consent, were followed by the Ethics Committee (Ethics code: IR.IAU.TABRIZ.REC.1401.063) of Tabriz Azad University, Tabriz, Iran. In this study, tissues of 100 patients with breast cancer and tissues of 100 healthy women were collected from Noor Nejat Hospital in Tabriz. The basic characteristics of the patients with breast cancer included: 1)Tumor grade(Grade 3 = 5%, Grade 2 = 87.5%, Grade 1 = 7.5%), 2)Lymph node(Yes = 87.5%, No = 12.5%), 3)Family cancer history(Yes = 47.5%, No = 41.3%, Unknown = 11.2%), 4) Abortion history(Yes = 36.2%).In silico methods (data gathering, process, and build networks): Gene Expression Omnibus (GEO), a high-throughput genomic database, was queried for miRNAs expression profiles in breast cancer. For Experimental protocol Tissue Processing, Total RNA isolation, complementary DNA(cDNA) synthesis, and quantitative real time PCR (QRT-PCR) analysis were performed. Results: In the present study, we found significant (p.value<0.05) changes in the expression level of miRNAs and DNMTs in patients with breast cancer. In bioinformatics studies, the GEO microarray data set, similar to qPCR results, showed a decreased expression of miRNAs and increased expression of DNMTs in breast cancer. Conclusion: According to the results of the present study, which showed a decrease in the expression of miRNAs and DNMTs in breast cancer, it can be said that these genes can be used as important diagnostic and therapeutic biomarkers in breast cancer.

Keywords: gene expression omnibus, microarray dataset, breast cancer, miRNA, DNMT (DNA methyltransferases)

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Authors: Ziv Kassner, Gal Ribak

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Members of the Odonata order (dragonflies and damselflies) stand out for their maneuverability and superb flight control, which allow them to catch flying prey in the air. These outstanding aerial abilities were fine-tuned during millions of years of an evolutionary arms race between Odonata and their prey, providing an attractive research model for studying the relationship between sensory input – and aerodynamic output in a flying insect. The ability to catch a maneuvering target in air is interesting not just for insect behavioral ecology and neuroethology but also for designing small and efficient robotic air vehicles. While the aerial prey interception of dragonflies (suborder: Anisoptera) have been studied before, little is known about how damselflies (suborder: Zygoptera) intercept prey. Here, high-speed cameras (filming at 1000 frames per second) were used to explore how damselflies catch unpredictable targets that move through air. Blue-tailed damselflies - Ischnura elegans (family: Coenagrionidae) were introduced to a flight arena and filmed while landing on moving targets that were oscillated harmonically. The insects succeeded in capturing targets that were moved with an amplitude of 6 cm and frequencies of 0-2.5 Hz (fastest mean target speed of 0.3 m s⁻¹) and targets that were moved in 1 Hz (an average speed of 0.3 m s⁻¹) but with an amplitude of 15 cm. To land on stationary or slow targets, damselflies either flew directly to the target, or flew sideways, up to a point in which the target was fixed in the center of the field of view, followed by direct flight path towards the target. As the target moved in increased frequency, damselflies demonstrated an ability to track the targets while flying sideways and minimizing the changes of their body direction on the yaw axis. This was likely an attempt to keep the targets at the center of the visual field while minimizing rotational optic flow of the surrounding visual panorama. Stabilizing rotational optic flow helps in estimation of the velocity and distance of the target. These results illustrate how dynamic visual information is used by damselflies to guide them towards a maneuvering target, enabling the superb aerial hunting abilities of these insects. They also exemplifies the plasticity of the damselfly flight apparatus which enables flight in any direction, irrespective of the direction of the body.

Keywords: bio-mechanics, insect flight, target fixation, tracking and interception

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Authors: D. Anderlini, G. Wallis

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Background: The number of people experiencing stroke is steadily increasing due to changes in diet and lifestyle, to longer life expectancy resulting in older population, to higher survival rates as a consequence of improvements during the acute phase. This study considers what risk factors might contribute to delayed entry to hospital for treatment. Methods: We analyzed data from 2472 patients admitted to the Stroke Unit of the Royal Brisbane Women's Hospital, Australia, between 2002 to 2011. Results: Previous studies have reported that factors which can contribute to delay include the patient’s age, the time of day, physical location, visit the GP instead of going to the emergency, means of transport, severity of symptoms and type of stroke. Contrary to findings of other studies, we found a strong correlation between side of lesion and delay in admission: patients with right hemisphere lesions had an average delay of 3.78 days, while patients with left hemisphere lesions had an average delay of 1.49 days. Damage to the right hemisphere generally ends in motor impairment in the non-dominant hand and no speech impediment. In contrast, left hemisphere lesions can result in deficit to; dominant hand function and aphasia which will be noticed even if their impact on performance is relatively minor. A finding which goes against many previous studies, is the fact that women get to the hospital much sooner than men, showing an average delay of 0.92 days in women vs. 3.36 days in men. Conclusion: Acute surgical-pharmacological therapies are most effective if applied immediately after stroke. Hence delays to admission can be crucial to the degree of recovery. The tendency of patients to overlook symptoms of right hemisphere lesion should be the target of information campaigns both for the general public and GPs. Why do men go to hospital so late? We don't know yet! Nevertheless an awareness plan specifically direct to male population should be on the agenda of Health Departments.

Keywords: gender, admission delay, stroke location, bioinformatics, biomedicine

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

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The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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