Unravelling how the biosynthesis of sphingolipids impacts stress responses in Aspergillus nidulans

"For the past years filamentous fungi have been emerging as critical human-pathogens and have been increasingly provoking deadly invasive infections. The currently available antifungal drugs are inadequate to fight this global threat and the discovery of new antifungal targets are urgently needed. In this context, fungal sphingolipids have come up as potential targets for the development of new antifungal agents; however, knowledge on sphingolipid biosynthetic pathways in filamentous fungi, such as Aspergillus nidulans, is still rather limited. Previous observations demonstrated that some ionic liquids can trigger the accumulation of sphingolipid intermediates of the glucosylceramide biosynthetic pathway, that in response to the induced stress are probably acting as second messengers. In the present thesis we wanted to assess how sphingolipid biosynthesis can impact stress responses in A. nidulans.(...)

Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs

<p>Abstract</p> <p>Background</p> <p>Epitope vaccines have been suggested as a strategy to counteract viral escape and development of drug resistance. Multiple studies have shown that Cytotoxic T-Lymphocyte (CTL) and T-Helper (Th) epitopes can generate strong immune responses in Human Immunodeficiency Virus (HIV-1). However, not much is known about the relationship among different types of HIV epitopes, particularly those epitopes that can be considered potential candidates for inclusion in the multi-epitope vaccines.</p> <p>Results</p> <p>In this study we used association rule mining to examine relationship between different types of epitopes (CTL, Th and antibody epitopes) from nine protein-coding HIV-1 genes to identify strong associations as potent multi-epitope vaccine candidates. Our results revealed 137 association rules that were consistently present in the majority of reference and non-reference HIV-1 genomes and included epitopes of two different types (CTL and Th) from three different genes (<it>Gag, Pol </it>and <it>Nef</it>). These rules involved 14 non-overlapping epitope regions that frequently co-occurred despite high mutation and recombination rates, including in genomes of circulating recombinant forms. These epitope regions were also highly conserved at both the amino acid and nucleotide levels indicating strong purifying selection driven by functional and/or structural constraints and hence, the diminished likelihood of successful escape mutations.</p> <p>Conclusions</p> <p>Our results provide a comprehensive systematic survey of CTL, Th and Ab epitopes that are both highly conserved and co-occur together among all subtypes of HIV-1, including circulating recombinant forms. Several co-occurring epitope combinations were identified as potent candidates for inclusion in multi-epitope vaccines, including epitopes that are immuno-responsive to different arms of the host immune machinery and can enable stronger and more efficient immune responses, similar to responses achieved with adjuvant therapies. Signature of strong purifying selection acting at the nucleotide level of the associated epitopes indicates that these regions are functionally critical, although the exact reasons behind such sequence conservation remain to be elucidated.</p

Molecular phylogenetics of Trypanosomatidae: contrasting results from 18S rRNA and protein phylogenies

Phylogenetic analyses of the family Trypanosomatidae have been conducted using both 18S rRNA gene sequences and a variety of protein sequences. Using a variety of phylogenetic methods, 18S rRNA phylogenies indicate that the genus Trypanosoma is not monophyletic. Rather, they suggest that the American and African trypanosomes constitute distinct clades. By contrast, phylogenetic analyses of available sequences in 42 protein families gene generally supported monophyly of the genus Trypanosoma. One possible explanation for these conflicting results is poor taxon sampling in the case of protein coding genes, most of which have been sequenced for only a few species of Trypanosomatidae

DNA repeat arrays in chicken and human genomes and the adaptive evolution of avian genome size

BACKGROUND: Birds have smaller average genome sizes than other tetrapod classes, and it has been proposed that a relatively low frequency of repeating DNA is one factor in reduction of avian genome sizes. RESULTS: DNA repeat arrays in the sequenced portion of the chicken (Gallus gallus) autosomes were quantified and compared with those in human autosomes. In the chicken 10.3% of the genome was occupied by DNA repeats, in contrast to 44.9% in human. In the chicken, the percentage of a chromosome occupied by repeats was positively correlated with chromosome length, but even the largest chicken chromosomes had repeat densities much lower than those in human, indicating that avoidance of repeats in the chicken is not confined to minichromosomes. When 294 simple sequence repeat types shared between chicken and human genomes were compared, mean repeat array length and maximum repeat array length were significantly lower in the chicken than in human. CONCLUSIONS: The fact that the chicken simple sequence repeat arrays were consistently smaller than arrays of the same type in human is evidence that the reduction in repeat array length in the chicken has involved numerous independent evolutionary events. This implies that reduction of DNA repeats in birds is the result of adaptive evolution. Reduction of DNA repeats on minichromosomes may be an adaptation to permit chiasma formation and alignment of small chromosomes. However, the fact that repeat array lengths are consistently reduced on the largest chicken chromosomes supports the hypothesis that other selective factors are at work, presumably related to the reduction of cell size and consequent advantages for the energetic demands of flight

Identification of novel light-induced genes in the suprachiasmatic nucleus

<p>Abstract</p> <p>Background</p> <p>The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice.</p> <p>Results</p> <p>The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose) polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements.</p> <p>Conclusion</p> <p>The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders.</p

Cross-species mapping of bidirectional promoters enables prediction of unannotated 5' UTRs and identification of species-specific transcripts

BACKGROUND: Bidirectional promoters are shared regulatory regions that influence the expression of two oppositely oriented genes. This type of regulatory architecture is found more frequently than expected by chance in the human genome, yet many specifics underlying the regulatory design are unknown. Given that the function of most orthologous genes is similar across species, we hypothesized that the architecture and regulation of bidirectional promoters might also be similar across species, representing a core regulatory structure and enabling annotation of these regions in additional mammalian genomes. RESULTS: By mapping the intergenic distances of genes in human, chimpanzee, bovine, murine, and rat, we show an enrichment for pairs of genes equal to or less than 1,000 bp between their adjacent 5' ends ("head-to-head") compared to pairs of genes that fall in the same orientation ("head-to-tail") or whose 3' ends are side-by-side ("tail-to-tail"). A representative set of 1,369 human bidirectional promoters was mapped to orthologous sequences in other mammals. We confirmed predictions for 5' UTRs in nine of ten manual picks in bovine based on comparison to the orthologous human promoter set and in six of seven predictions in human based on comparison to the bovine dataset. The two predictions that did not have orthology as bidirectional promoters in the other species resulted from unique events that initiated transcription in the opposite direction in only those species. We found evidence supporting the independent emergence of bidirectional promoters from the family of five RecQ helicase genes, which gained their bidirectional promoters and partner genes independently rather than through a duplication process. Furthermore, by expanding our comparisons from pairwise to multispecies analyses we developed a map representing a core set of bidirectional promoters in mammals. CONCLUSION: We show that the orthologous positions of bidirectional promoters provide a reliable guide to directly annotate over one thousand regulatory regions in sequences of mammalian genomes, while also serving as a useful tool to predict 5' UTR positions and identify genes that are novel to a single species

Информационно-образовательная среда подготовки специалистов социономических профессий в высшей школе

The presented study examines the issues of ensuring the quality of training of future specialists in socionomic professions in institutions of higher education nstitutions. The relevance of studying the specifics of training for professional activities of the socionomic type and the importance of such researches are due to the increasing importance and, accordingly, the spread of socio-forming activities in modern society. Based on the analysis of the goals of education in various countries, the authors show that such goals are aimed not only at assimilating the amount of subject knowledge, but primarily provide for the harmonious development of the individual, the achievement of personal well-being. The authors emphasize that socionomic professions, that is, professions in the “person ↔ person” system, differ in specific conditions, means, as well as in the specifics of the subject and product of labor. The main distinguishing feature, from the authors' point of view, is that socionomic professions are characterized by the absence of unique and strict requirements for the very process of professional activity, organized for a high-quality socially significant result (product of labor). That's why, high requirements are imposed on representatives of such professions, in accordance with the level of their responsibility, since other people are the object of labor for them. The authors submit that professions of the socionomic type require specialists to intensify the development of a number of specific psychological qualities and abilities, including the ability to communicate; emotional stability, empathy, organizational qualities, etc. It is important that it is the purposeful formation and development of professional competence, which has these abilities in the core, should be a priority in the implementation of an information and educational environment for the training of specialists in socionomic professions in higher education institutions. Also, according to the authors'conviction, the main component of the educational process of training future specialists in this area is the socio-psychological organization of the loyalty of pedagogical workers, who, in the trend of modern challenges, effectively carry out activities to increase motivation, ensure emotional satisfaction, develop skills to prevent professional burnout, etc. in future specialists of socionomic professions. The research presents a complex of structural and organizing components of the information and educational environment aimed at the development and self-improvement of the mentioned above qualities, which acts as a means of increasing the competitiveness of future specialists of socionomic professions in the labor market.У представленому дослідженні розглядаються питання забезпечення якості підготовки майбутніх спеціалістів соціономічних професій у закладах вищої освіти. Актуальність вивчення специфіки підготовки до професійної діяльності соціономічного типу та важливість таких досліджень зумовлені зростанням значення та, відповідно, поширенням соціоформуючої діяльності в сучасному суспільстві. На основі аналізу цілей освіти в різних країнах показано, що такі цілі спрямовані не тільки на засвоєння обсягу предметних знань, а передусім передбачають гармонійний розвиток особистості, досягнення особистого благополуччя. Автори наголошують, що соціономічні професії, тобто професії в системі «людина ↔ людина», відрізняються конкретними умовами, засобами, а також специфікою предмета і продукту праці. Основною відмінною рисою, на думку авторів, є те, що соціономічні професії характеризуються відсутністю єдиних і жорстких вимог до самого процесу професійної діяльності, організованої для отримання якісного суспільно значущого результату (продукту праці). Тому до представників таких професій пред'являються високі вимоги відповідно до рівня їхньої відповідальності, оскільки предметом праці для них є інші люди. Автори стверджують, що професії соціономічного типу вимагають від спеціалістів інтенсифікації розвитку низки специфічних психологічних якостей та здібностей, у т.ч. вміння спілкуватися; емоційної стійкості, емпатії, організаторськіх якостей тощо. Важливо, що саме цілеспрямоване формування та розвиток професійної компетентності, в основу якої покладено ці здібності, мають бути пріоритетними у реалізації інформаційно-освітнього середовища для підготовки фахівців соціономічних професій у закладах вищої освіти. Також, на переконання авторів, основною складовою освітнього процесу з підготовки майбутніх фахівців у цьому спрямуванні є соціально-психологічна організація лояльності педагогічних працівників, які в тенденції сучасних викликів ефективно здійснюють діяльність щодо підвищення мотивації, забезпечення емоційного задоволення, формування навичок запобігання професійному вигоранню тощо у майбутніх спеціалістів соціономічних професій. У дослідженні представлено комплекс структурно-організуючих компонентів інформаційно-освітнього середовища, спрямованих на розвиток та самовдосконалення зазначених вище якостей, що виступають засобами підвищення конкурентоздатності майбутніх фахівців соціономічних професій на ринку праці.В представленном исследовании рассматриваются вопросы обеспечения качества подготовки будущих специалистов социономических профессий в учреждениях высшего образования. Актуальность изучения специфики подготовки к профессиональной деятельности социономического типа и значимость таких исследований обусловлены возрастающим значением и, соответственно, распространением социально-формирующей деятельности в современном обществе. На основе анализа целей образования в различных странах авторы показывают, что такие цели направлены не только на усвоение объема предметных знаний, но в первую очередь предусматривают гармоничное развитие личности, достижение личного благополучия. Авторы подчеркивают, что cоциономические профессии, то есть профессии в системе «человек ↔ человек», различаются специфическими условиями, средствами, а также спецификой предмета и продукта труда. Главной отличительной чертой, с точки зрения авторов, является то, что для социономических профессий характерно отсутствие однозначных и жестких требований к самому процессу профессиональной деятельности, организованной для получения качественного общественно значимого результата (продукта труда). Вот почему, к представителям таких профессий предъявляются высокие требования в соответствии с уровнем их ответственности, так как предметом труда для них являются другие люди. Авторы утверждают, что профессии социономического типа требуют от специалистов интенсификации развитие ряда специфических психологических качеств и способностей, в том числе умения общаться; эмоциональной устойчивости, эмпатии, организаторские качества и др. Важно, что именно целенаправленное формирование и развитие профессиональной компетентности, в основе которой лежат эти способности, должно быть приоритетным направлением в реализации информационно-образовательной среды подготовки специалистов социономических профессий в высших учебных заведениях. Также, по убеждению авторов, основной составляющей образовательного процесса подготовки будущих специалистов в данной области является социально-психологическая организация лояльности педагогических работников, которые в тренде современных вызовов эффективно осуществляют деятельность по повышению мотивации, обеспечению эмоционального удовлетворения, развитию навыков профилактики профессионального выгорания и т.д. у будущих специалистов социономических профессий. В исследовании представлен комплекс структурно-организующих компонентов информационно-образовательной среды, направленных на развитие и самосовершенствование указанных выше качеств, которые выступают средством повышения конкурентоспособности будущих специалистов социономических профессий на рынке труда

COVID-19 and emerging viral infections: The case for interferon lambda

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections

Discovery of novel targets for multi-epitope vaccines: Screening of HIV-1 genomes using association rule mining

© 2009 Paul and Piontkivska; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Mouse Dfa Is a Repressor of TATA-box Promoters and Interacts with the Abt1 Activator of Basal Transcription

Our study of the mouse Ate1 arginyltransferase, a component of the N-end rule pathway, has shown that Ate1 pre-mRNA is produced from a bidirectional promoter that also expresses, in the opposite direction, a previously uncharacterized gene (Hu, R. G., Brower, C. S., Wang, H., Davydov, I. V., Sheng, J., Zhou, J., Kwon, Y. T., and Varshavsky, A. (2006) J. Biol. Chem. 281, 32559–32573). In this work, we began analyzing this gene, termed Dfa (divergent from Ate1). Mouse Dfa was found to be transcribed from both the bidirectional P_(Ate1/Dfa) promoter and other nearby promoters. The resulting transcripts are alternatively spliced, yielding a complex set of Dfa mRNAs that are present largely, although not exclusively, in the testis. A specific Dfa mRNA encodes, via its 3′-terminal exon, a 217-residue protein termed Dfa^A. Other Dfa mRNAs also contain this exon. DfaA is sequelogous (similar in sequence) to a region of the human/mouse HTEX4 protein, whose physiological function is unknown. We produced an affinity-purified antibody to recombinant mouse DfaA that detected a 35-kDa protein in the mouse testis and in several cell lines. Experiments in which RNA interference was used to down-regulate Dfa indicated that the 35-kDa protein was indeed Dfa^A. Furthermore, Dfa^A was present in the interchromatin granule clusters and was also found to bind to the Ggnbp1 gametogenetin-binding protein-1 and to the Abt1 activator of basal transcription that interacts with the TATA-binding protein. Given these results, RNA interference was used to probe the influence of Dfa levels in luciferase reporter assays. We found that Dfa^A acts as a repressor of TATA-box transcriptional promoters