Prioritization of genes associated with the pathogenesis of leukosis in cattle

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), which can affect the sensitivity/resistance of cattle to leukemia

Evaluation of rat brain morphology following the induction of acute meningitis treated with Ceftriaxone

The present study aimed to assess the histological and immunohistochemical characteristics of the brain of rats that underwent induced acute purulent pneumococcal meningitis after antibiotic therapy with Ceftriaxon

Single nucleotide polymorphism rs110861313 in the intergenic region of chromosome 23 is associated with the development of leukosis in the Russian Black Pied cattle

In recent years, using a genome-wide association study (GWAS), a number of single nucleotide polymorphisms (SNPs) have been suggested to be associated with susceptibility to leukemia in cattle. However, all studies have been done with purebred Holstein cows and their hybrids. In this regard, it is important to confirm the functional role of polymorphisms previously identified in a GWAS study in Russian cattle breeds. The aim of this study was to verify the association between rs110861313 in the intergenic region of bovine chromosome 23 and leukemia in the Russian Black Pied cattle. Based on the levels of bovine leukemia virus (BLV)-specific antibodies detected in serum using serodiagnostic techniques, animals were divided into three groups: healthy animals (n = 115), asymptomatic virus carriers (n = 145) and animals with leukemia (n = 107). Genotyping of rs110861313 was carried out using polymerase chain reaction followed by analysis of restriction fragment length polymorphisms. A significant decrease in the frequency of the A/A genotype (11.2 %) was revealed in animals with persistent lymphocytosis compared to virus carriers (27.6 %) (p < 0.002). At the same time, the frequency of animals with the C/C genotype in animals with persistent lymphocytosis (41.1 %) was significantly higher than that of virus carriers (21.4 %) (p < 0.001). In this case, asymptomatic virus carriers can be considered a more suitable control than healthy animals that have not been in contact with the virus. According to bioinformatics analysis, resistance to BLV can be due to the presence of the transcription factor FOXM1 binding site in the region of rs110861313. FOXM1 is expressed in immune cells and can potentially affect the expression of the neighboring genes (LY6G5B, GPANK1, ABHD16A, LY6G6F, LY6G6E, CSNK2B, ApoM). Thus, we found that SNP rs110861313 in the intergenic region of bovine chromosome 23 is associated with the development of leukemia following BLV infection in the Russian Black Pied cattle

Making Muscle Elastic: The Structural Basis of Myomesin Stretching

The muscle M-band protein myomesin comprises a 36-nm long filament made of repetitive immunoglobulin–helix modules that can stretch to 2.5-fold this length, demonstrating substantial molecular elasticity

Structural Organization of DNA in Chlorella Viruses

Chlorella viruses have icosahedral capsids with an internal membrane enclosing their large dsDNA genomes and associated proteins. Their genomes are packaged in the particles with a predicted DNA density of ca. 0.2 bp nm−3. Occasionally infection of an algal cell by an individual particle fails and the viral DNA is dynamically ejected from the capsid. This shows that the release of the DNA generates a force, which can aid in the transfer of the genome into the host in a successful infection. Imaging of ejected viral DNA indicates that it is intimately associated with proteins in a periodic fashion. The bulk of the protein particles detected by atomic force microscopy have a size of ∼60 kDa and two proteins (A278L and A282L) of about this size are among 6 basic putative DNA binding proteins found in a proteomic analysis of DNA binding proteins packaged in the virion. A combination of fluorescence images of ejected DNA and a bioinformatics analysis of the DNA reveal periodic patterns in the viral DNA. The periodic distribution of GC rich regions in the genome provides potential binding sites for basic proteins. This DNA/protein aggregation could be responsible for the periodic concentration of fluorescently labeled DNA observed in ejected viral DNA. Collectively the data indicate that the large chlorella viruses have a DNA packaging strategy that differs from bacteriophages; it involves proteins and share similarities to that of chromatin structure in eukaryotes

Отдаленные последствия недоношенности: нарушения физического развития и пищевого поведения детей и подростков

Aim. To characterize the physical development (PD) and eating behavior (EB) of children and adolescents born prematurely.Materials and methods. The study involved 123 people born in the period 1997-2008, 58 children born prematurely, age (12 ± 1.3) years, gestation period (33.07 ± 1.9) weeks (main group). The control group consisted of 65 full-term peers, age (12.7 ± 2.2) years, gestational age (39.5 ± 0.8) weeks. Participants were evaluated by PD (height, weight, body mass index (BMI), waist circumference (WC), throat circumference (TC)) under the WHO AnthroPlus program, and EB using the Dutch DEBQ questionnaire.Results. Growth and Z-score growth of boys and girls of the main group is lower than that of their fullterm peers, p = 0.04; 0.004 (p < 0.0001 for Z-score growth). Z-score BMI in boys and girls of the main group is higher than in full-term, p = 0.04; 0.01. WC/TC the girls of the main group is higher than in fullterm peers, p < 0.0001. In premature boys, the restrictive type is 13.3%, emotional and external – 50%, the combination of emotional and external – 33.3%. In the control restrictive – 5,7%, emotional – 28,6%, external – 32,3%, the combination of emotional and external – 10,8%, the combination of all three types – 5,7%. In the group of premature girls restrictive –7.1% against 36.7% in the control, (p = 0.007), emotsiogenic – 10.7% against 36.6% of the control (p = 0.02), external – 10.3% against 60% of the control (p = 0.003). In the control group the combination of external and emotiogenic – 16.7% (in the primary group is 0, p = 0.02). Preterm boys emotiogenic and external and their combination more often than girls (p = 0.001; 0.02; 0.001).Conclusion. Children and adolescents born prematurely are below full-term peers and have a high z-score of BMI. Boys realize violations of external and emotional types, and their combination. Цель. Охарактеризовать физическое развития (ФР) и пищевое поведение (ПП) детей и подростков, родившихся недоношенными.Материалы и методы. В исследовании приняли участие 123 человека, родившихся в 1997–2008 гг., в том числе 58 недоношенных детей, возраст (12 ± 1,3) лет, срок гестации (33,07 ± 1,9) нед (основная группа). Группу контроля составили 65 доношенных сверстников, возраст (12,7 ± 2,2) лет, срок гестации (39,5 ± 0,8) нед. Участникам проведена оценка ФР (рост, вес, индекс массы тела (ИМТ), окружность талии (ОТ), окружность бедер (ОБ)) по программе WHO AnthroPlus и ПП с помощью голландского опросника DEBQ.Результаты. В исследовании показано, что рост и z-score роста мальчиков и девочек основной группы ниже, чем у их доношенных сверстников, р = 0,04; р = 0,004 соответственно (р < 0,0001 для z-score роста). Отмечено, что z-score ИМТ у мальчиков и девочек основной группы выше, чем у доношенных, р = 0,04; р = 0,01; ОТ/ОБ у девочек основной группы выше, чем у доношенных сверстниц, р < 0,0001. У недоношенных мальчиков выявлены следующие типы ПП: ограничительный (13,3%), эмоциогенный и экстернальный (по 50%), сочетание эмоциогенного и экстернального (33,3%). В контрольной группе обнаружены следующие типы ПП: ограничительный (5,7%), эмоциогенный (28,6%), экстернальный (32,3%), сочетание эмоциогенного и экстернального (10,8%), сочетание всех трех типов (5,7%). У девочек наблюдались следующие типы ПП: ограничительный в основной группе (7,1%) и контрольной (36,7%), р = 0,007; эмоциогенный – 10,7% против 36,6% из контроля (р = 0,02); экстернальный – 10,3% против 60% из контроля (р = 0,003). В контрольной группе отмечено сочетание эмоциогенного и экстернального (16,7%), в основной группе – 0, р = 0,02. У недоношенных мальчиков эмоциогенный и экстернальный тип ПП и их сочетание наблюдались чаще, чем у девочек (р = 0,001; р = 0,02; р = 0,001).Заключение. Дети и подростки, родившиеся недоношенными, ниже доношенных сверстников и имеют высокие z-score ИМТ. Мальчики реализуют нарушения экстернального и эмоциогенного типов и их сочетание.

Cytoskeletal protein kinases: titin and its relations in mechanosensing

Titin, the giant elastic ruler protein of striated muscle sarcomeres, contains a catalytic kinase domain related to a family of intrasterically regulated protein kinases. The most extensively studied member of this branch of the human kinome is the Ca2+–calmodulin (CaM)-regulated myosin light-chain kinases (MLCK). However, not all kinases of the MLCK branch are functional MLCKs, and about half lack a CaM binding site in their C-terminal autoinhibitory tail (AI). A unifying feature is their association with the cytoskeleton, mostly via actin and myosin filaments. Titin kinase, similar to its invertebrate analogue twitchin kinase and likely other “MLCKs”, is not Ca2+–calmodulin-activated. Recently, local protein unfolding of the C-terminal AI has emerged as a common mechanism in the activation of CaM kinases. Single-molecule data suggested that opening of the TK active site could also be achieved by mechanical unfolding of the AI. Mechanical modulation of catalytic activity might thus allow cytoskeletal signalling proteins to act as mechanosensors, creating feedback mechanisms between cytoskeletal tension and tension generation or cellular remodelling. Similar to other MLCK-like kinases like DRAK2 and DAPK1, TK is linked to protein turnover regulation via the autophagy/lysosomal system, suggesting the MLCK-like kinases have common functions beyond contraction regulation

Conformation-regulated mechanosensory control via titin domains in cardiac muscle

The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

Life-Cycle and Genome of OtV5, a Large DNA Virus of the Pelagic Marine Unicellular Green Alga Ostreococcus tauri

Large DNA viruses are ubiquitous, infecting diverse organisms ranging from algae to man, and have probably evolved from an ancient common ancestor. In aquatic environments, such algal viruses control blooms and shape the evolution of biodiversity in phytoplankton, but little is known about their biological functions. We show that Ostreococcus tauri, the smallest known marine photosynthetic eukaryote, whose genome is completely characterized, is a host for large DNA viruses, and present an analysis of the life-cycle and 186,234 bp long linear genome of OtV5. OtV5 is a lytic phycodnavirus which unexpectedly does not degrade its host chromosomes before the host cell bursts. Analysis of its complete genome sequence confirmed that it lacks expected site-specific endonucleases, and revealed the presence of 16 genes whose predicted functions are novel to this group of viruses. OtV5 carries at least one predicted gene whose protein closely resembles its host counterpart and several other host-like sequences, suggesting that horizontal gene transfers between host and viral genomes may occur frequently on an evolutionary scale. Fifty seven percent of the 268 predicted proteins present no similarities with any known protein in Genbank, underlining the wealth of undiscovered biological diversity present in oceanic viruses, which are estimated to harbour 200Mt of carbon