Changes in electrolyte concentrations and hydration status in endurance horses following transport and an overnight stay prior to competition

OBJECTIVE To evaluate changes in electrolyte concentrations and hydration status that take place in endurance horses prior to the start of a competition and determine whether these changes would be associated with elimination. ANIMALS 19 horses entered in the 2016 Tevis Cup 100-Miles (160 km) One-Day Western States Trail Ride. PROCEDURES Heparinized blood samples were collected at 5 time points: prior to transport to the ride (T0), during check-in the day before the ride (T1), 1 to 2 hours before the start of the ride (T2), at the 15-km mark (T3), and at the 55-km mark (T4). Packed cell volume and plasma sodium, potassium, chloride, urea nitrogen, glucose, bicarbonate, and total protein concentrations were determined and compared across time points and between finishers and nonfinishers. RESULTS Signif icant differences were detected among plasma sodium, potassium, and urea nitrogen concentrations measured prior to the start of the ride (ie, T0, T1, and T2). For all variables except chloride and bicarbonate concentrations, significant differences were detected between values obtained prior to the start of the ride and values obtained during the ride (ie, T3 and T4). Only bicarbonate concentration at the 15-km mark of the ride was significantly associated with finishing status. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that significant changes in plasma sodium, potassium, and urea nitrogen concentrations can occur in endurance horses during transport to a competition and when horses are stabled overnight before an event. Additionally, a lower bicarbonate concentration following a steep climb early during the ride was associated with subsequent elimination.

Restriction of Wolbachia bacteria in early embryogenesis of neotropical Drosophila species via ER-mediated autophagy

Wolbachia bacteria are maternally transmitted intracellular microbes that are not only restricted to the reproductive organs but also found in various somatic tissues of their native hosts. The abundance of the endosymbiont in somatic tissues, usually a dead end for vertically transmitted bacteria, causes a multitude of effects on life history traits of their hosts, which are still not well understood. Thus, deciphering the host-symbiont interactions on a cellular level throughout a host’s lifecycle is of great importance to understand their homeostatic nature, persistence and spreading success. Using fluorescent and transmission electron microscopy, we conducted a comprehensive analysis of Wolbachia tropism in somatic and reproductive tissues of six Drosophila species at the intracellular level during host development. Our data uncovered diagnostic patterns of infections to embryonic primordial germ cells and to particular cells of somatic tissues in three different neotropical Drosophila species of the willistoni and saltans groups that have apparently evolved in both independently. We further found that restricted patterns of Wolbachia tropism are already determined in early fly embryogenesis. This is achieved via selective autophagy, and the restriction of infection is preserved through larval hatching and metamorphosis. We further uncovered tight interactions of Wolbachia with membranes of the endoplasmic reticulum, which might play a scaffolding role for autophagosome formation and subsequent elimination of the endosymbiont. Finally, by analyzing D. simulans lines transinfected with non-native Wolbachia, we uncovered that the host genetic background regulates tissue tropism of infection. Our data demonstrate a peculiar and novel mechanism to limit and spatially restrict bacterial infection in somatic tissues during a very early stage of host development.

Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1

Organic cation transporter 1 (OCT1) is a transporter that regulates the hepatic uptake and subsequent elimination of diverse cationic compounds. Although OCT1 has been involved in drug-drug interactions and causes pharmacokinetic variability of many prescription drugs, details of the molecular mechanisms that regulate the activity of OCT1 remain incompletely understood. Based on an unbiased phospho-proteomics screen, we identified OCT1 as a tyrosine-phosphorylated transporter, and functional validation studies using genetic and pharmacological approaches revealed that OCT1 is highly sensitive to small molecules that target the protein kinase YES1, such as dasatinib. In addition, we found that dasatinib can inhibit hepatic OCT1 function in mice as evidenced from its ability to modulate levels of isobutyryl L-carnitine, a hepatic OCT1 biomarker identified from a targeted metabolomics analysis. These findings provide novel insight into the post-translational regulation of OCT1 and suggest that caution is warranted with polypharmacy regimes involving the combined use of OCT1 substrates and kinase inhibitors that target YES1.

Regulation of MHC I Molecules in Glioblastoma Cells and the Sensitizing of NK Cells

Immunotherapy has been established as an important area in the therapy of malignant diseases. Immunogenicity sufficient for immune recognition and subsequent elimination can be bypassed by tumors through altered and/or reduced expression levels of major histocompatibility complex class I (MHC I) molecules. Natural killer (NK) cells can eliminate tumor cells in a MHC I antigen presentation-independent manner by an array of activating and inhibitory receptors, which are promising candidates for immunotherapy. Here we summarize the latest findings in recognizing and regulating MHC I molecules that affect NK cell surveillance of glioblastoma cells.

Iterative model of psychological support of special attention categories persons

Актуальность статьи обусловлена необходимостью совершенствования и приведения в соответствие с современными научными и социальными тенденциями модели ресоциализации личности лиц категории особого внимания. В статье показана необходимость интенсивного развития проблемы ресоциализации личности с учетом потребностей общества и государства на современном этапе ее развития. На основе данных психологической науки и анализа существующей системы психологического сопровождения представлена итерационная модель ресоциализации личности, подверженной идеологии терроризма и экстремизма. Ожидаемым результатом реализации итерационной модели ресоциализации личности является успешная профилактическая работа, направленная на изменение мышления (смягчение или отказ от определенных, опасных для общества, ценностей, установок и взглядов – то есть дерадикализация) или изменение поведения человека (отказ от практики насилия, выход из террористических структур, без изменения фундаментальных убеждений – то есть ресоциализация). Кроме того, предложена поэтапная схема процесса ресоциализации личности лиц категории особого внимания; проведено описание этапов ее прохождения и последующее устранение причин и условий, способствующих снижению вовлекаемости в его смысловое и деятельностное поле. Статья предназначена для педагогов-психологов, представителей коррекционных служб, руководителей образовательных организаций, представителей гуманитарного научного сообщества. The relevance of the article is due to the need to improve and bring into line with modern scientific and social trends the model of resocialization of the personality of persons of the category of special attention. The article shows the need for intensive development of the problem of the resocialization of the individual, taking into account the needs of society and the state at the modern stage of development. Based on the data of psychological science and analysis of the existing system of psychological support, an iterative model of the resocialization of a person exposed to the ideology of terrorism and extremism is presented. The expected result of the implementation of the iterative model of personality resocialization is successful preventive work aimed at changing the way of thinking (softening or abandoning certain values, attitudes and views that are dangerous to society – that is, deradicalization) or changing human behavior (abandoning the practice of violence, leaving terrorist structures, without changing fundamental beliefs – that is, resocialization). In addition, a step-by-step scheme has been proposed for the process of re-socialization of the identity of persons of special concern; description of stages of its passage and subsequent elimination of causes and conditions contributing to reduction of involvement in its semantic and activity field. The article is intended for teachers-psychologists, representatives of correctional services, heads of educational organizations, representatives of the humanitarian scientific community.

Senescent cells and macrophages: key players for regeneration?

Over the last decade, our understanding of the physiological role of senescent cells has drastically evolved, from merely indicators of cellular stress and ageing to having a central role in regeneration and repair. Increasingly, studies have identified senescent cells and the senescence-associated secretory phenotype (SASP) as being critical in the regenerative process following injury; however, the timing and context at which the senescence programme is activated can lead to distinct outcomes. For example, a transient induction of senescent cells followed by rapid clearance at the early stages following injury promotes repair, while the long-term accumulation of senescent cells impairs tissue function and can lead to organ failure. A key role of the SASP is the recruitment of immune cells to the site of injury and the subsequent elimination of senescent cells. Among these cell types are macrophages, which have well-documented regulatory roles in all stages of regeneration and repair. However, while the role of senescent cells and macrophages in this process is starting to be explored, the specific interactions between these cell types and how these are important in the different stages of injury/reparative response still require further investigation. In this review, we consider the current literature regarding the interaction of these cell types, how their cooperation is important for regeneration and repair, and what questions remain to be answered to advance the field.

On the Detection of Exploitation of Vulnerabilities Leading to the Execution of a Malicious Code

Software protection from exploitation of possible unknown vulnerabilities can be performed both by searching (for example, using symbolic execution) and subsequent elimination of the vulnerabilities and by using detection and / or intrusion prevention systems. In the latter case, this problem is usually solved by forming a profile of a normal behavior and deviation from normal behavior over a predetermined threshold is regarded as an anomaly or an attack. In this paper, the task is to protect a given software P from exploiting unknown vulnerabilities. For this aim a method is proposed for constructing a profile of the normal execution of the program P, in which, in addition to a set of legal chains of system and library functions, it is proposed to take into account the distances between adjacent function calls. At the same time, a profile is formed for each program. It is assumed that taking into account the distances between function calls will reveal shell code execution using system and / or library function calls. An algorithm and a system for detecting abnormal code execution are proposed. The work carried out experiments in the case when P is the FireFox browser. During the experiments the possibility of applying the developed algorithm to identify abnormal behavior when launching publicly available exploits was investigated.

CASSATION PROCEEDINGS UNDER THE DRAFT STATUTE OF CIVIL PROCEDURE OF 1863

Introduction. The creation of a system of cassation courts of general jurisdiction organized on an extraterritorial basis and other significant changes in modern cassation proceedings quite obviously mediate a new wave of scientific interest in the history of the development of a system for verifying judicial acts in the domestic tradition of civil procedure. In this regard, the experience in carrying out the Judicial Reform of 1864, in particular, enforcement of the Statute of Civil Procedure regularized the cassation institution for the first time, became relevant. At the same time, despite the fact that many modern scientific works are devoted to the study of the Statute of Civil Procedure of 1864 itself (including possibilities for appealing court decisions provided for thereby), the studies of foregoing drafts also stay relevant. The draft of 1863 is one such example. This article is devoted to the analysis of this draft in accordance with the declared topic. Purpose. The purpose of this study is to describe the draft Statute of Civil Procedure of 1863 in the context of its provisions defining the content of cassation institution. Methods. In the framework of the study, mainly historical-legal and comparative-legal methods were used. Results. The significance of the draft Statute of Civil Procedure of 1863, in the context of establishment and development of cassation institution in the civil procedure of the Russian Empire, was manifested, first of all, in a sufficiently clear consolidation in it of the very grounds for cassation of decisions. Its definitions are very similar to its provisions have been already consolidated in the Statute of Civil Procedure of 1864. At the same time, existing in that period distinction between terms “cassation” and “revision” promoted the consolidation of two basic tasks of cassation proceedings in the provisions of the Statute of Civil Procedure of 1863: verifying of the final decisions for judicial errors with the purpose of their subsequent elimination and ensuring uniform application and interpretation of the law. Conclusion. The draft Statute of Civil Procedure of 1863, having incorporated the ideas of many subsequent legislative works into itself, became some sort of provisional result of development of the necessity of cassation court in the Russian Empire of the 1800s – 1860s. At the same time, of course, the work on drafting the Statute of Civil Procedure did not end there, wherefore the draft was actively discussed and improved, and its main provisions regarding the regulation of the cassation proceedings formed the basis of the Statute of November 20, 1864.

Mannose-binding lectin gene polymorphisms in the East Siberia and Russian Arctic populations

ABSTRACTBackgroundMannose-binding lectin (MBL) encoded by MBL2 gene is a protein with the ability to form carbohydrate complexes with microbial wall promoting their subsequent elimination. Genetically determined levels of MBL can modify the risk and clinical characteristics of many infectious diseases. The frequency of MBL2 genotypes exhibits significant population differences. The data on the distribution of MBL2 genotypes among the aborigines of the Russian Arctic territories have not yet been published.MethodsA total of 880 specimens of dried blood spots of the newborns were genotyped. The newborns represented four populations: Nenets, Dolgan-Nganasans, Mixed aboriginal population, and Russians (Caucasians, Krasnoyarsk). Six polymorphisms of the MBL2 gene were studied: rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451.ResultsThe frequency of the combined rare O allele (composed of the coding region variants rs5030737, rs1800450, and rs1800451) in the homozygous state was significantly higher in Russians: 10% vs 2% in Nenets and 1% in Dolgan-Nganosans (p<0.001 for Russians vs other populations). The frequency of the high-producing haplotype (HYPA) was 35.4% in the Russian newborns, in keeping with European populations (27-33%); 64% for Nenets and 56% for Dolgan-Nganasans, similar to the estimates obtained for Eskimos and North Amerinds (64-81%).ConclusionOur study results are in line with the hypothesis that human evolution has been moving in the direction of accumulation of the genotypes associated with low activity of the lectin complement activation pathway because of the prevalence of some intracellular infections such as tuberculosis, whereby low MBL activity may have a protective effect.

Structure Prediction and Synthesis of a New Class of Macrocyclic Peptide Natural Products

<p>Owing to advances in genomic sequencing and bioinformatics, the breadth of natural product biosynthetic gene clusters (BGCs) has meteorically risen. This remains true for ribosomally synthesized and post-translationally modified peptides (RiPPs), where the rate of bioinformatically identifying clusters vastly outpaces characterization efforts. Uniting bioinformatics and enzymological knowledge to predict the chemical product(s) of a RiPP BGC with total chemical synthesis to obtain the natural compound is an effective platform for investigating cryptic gene clusters. Herein, we report the bioinformatic identification of a biosynthetically divergent class of RiPP bearing a subset of enzymes involved in thiopeptide biosynthesis. These natural products were predicted based on BGC architecture to undergo a formal, enzymatic [4+2]-cycloaddition with subsequent elimination of the leader peptide and water to produce a tri-substituted pyridine-based macrocycle. Bearing a pyridine similar to thiopeptides but lacking the ubiquitous thiazole heterocycles, these new RiPPs were termed pyritides. One of the predicted natural products was chemically synthesized using an 11-step synthesis. This structure was verified to be chemically identical by an orthogonal chemoenzymatic synthesis utilizing the precursor peptide and the cognate [4+2]-cycloaddition enzyme. The chemoenzymatic platform was used to synthesize a second in-cluster pyritide product as well as analogs from other bioinformatically identified pyritide BGCs. This work exemplifies complementary bioinformatic, enzymological, and synthetic techniques to characterize a structurally distinct class of RiPP natural product.</p>