Slow Dissociation of a Charged Ligand: Analysis of the Primary Quinone QA Site of Photosynthetic Bacterial Reaction Centers

Reaction centers (RCs) are integral membrane proteins that undergo a series of electron transfer reactions during the process of photosynthesis. In the QA site of RCs from Rhodobacter sphaeroides, ubiquinone-10 is reduced, by a single electron transfer, to its semiquinone. The neutral quinone and anionic semiquinone have similar affinities, which is required for correct in situ reaction thermodynamics. A previous study showed that despite similar affinities, anionic quinones associate and dissociate from the QA site at rates ≈104 times slower than neutral quinones indicating that anionic quinones encounter larger binding barriers (Madeo, J.; Gunner, M. R. Modeling binding kinetics at the QA site in bacterial reaction centers. Biochemistry2005, 44, 10994–11004). The present study investigates these barriers computationally, using steered molecular dynamics (SMD) to model the unbinding of neutral ground state ubiquinone (UQ) and its reduced anionic semiquinone (SQ–) from the QA site. In agreement with experiment, the SMD unbinding barrier for SQ– is larger than for UQ. Multi Conformational Continuum Electrostatics (MCCE), used here to calculate the binding energy, shows that SQ– and UQ have comparable affinities. In the QA site, there are stronger binding interactions for SQ– compared to UQ, especially electrostatic attraction to a bound non-heme Fe2+. These interactions compensate for the higher SQ– desolvation penalty, allowing both redox states to have similar affinities. These additional interactions also increase the dissociation barrier for SQ– relative to UQ. Thus, the slower SQ– dissociation rate is a direct physical consequence of the additional binding interactions required to achieve a QA site affinity similar to that of UQ. By a similar mechanism, the slower association rate is caused by stronger interactions between SQ– and the polar solvent. Thus, stronger interactions for both the unbound and bound states of charged and highly polar ligands can slow their binding kinetics without a conformational gate. Implications of this for other systems are discussed

TTV-INFECTION: CLINICAL, EPIDEMIOLOGICAL AND DIAGNOSTIC ASPECTS

Following article based on the literature and our own observations presents a brief analytical review covering clinical and epidemiological characteristics of hepatitis associated with TT virus, as well as modern methods of diagnosis and approach to the treatment of infectious diseases. The clinical observation showed symptoms of acute inflammation of the liver caused by TTV-infection. Characteristics of epidemiological anamnesis confirms that besides the main parenteral mechanism there is also a fecal-oral mechanism of infection TT virus. Following observation verifies a longterm persistence of TT virus in the body and complete absence of spontaneous elimination

Assessing student learning outcomes using mixed diagnostic tests and cognitive graphic tools

In this paper, we provide an approach to assessing student learning outcomes by using mixed diagnostic tests. These tests represent an optimal compromise between unconditional and conditional components and facilitate the development of individual learning paths, which, in turn, would provide students with the opportunity for self-guided learning. To construct individual learning paths, we apply an intelligent learning and testing system. Thus, each student becomes able to predict their learning outcomes following the respective learning path designed. In addition, we describe a cognitive graphic tool the 2-simplex prism to cognitively visualize the results of student learning assessment. We assume that our approach can be used when assessing student learning outcomes within any subject and propose applying this approach as a tool to enhance both student and teacher activity

New Coronavirus Infection (Covid-19): Clinical and Epidemiological Aspects

Environmental change, climate warming, population density increase, high migration activity of the population and other factors provoke the emergence and spread of new infections around the world. The emergence in December 2019 of diseases caused by the new coronavirus («coronavirus disease 2019») has already gone down in history as an emergency of international importance. It is known that the most common clinical manifestation of a new infection is pneumonia, and also in a significant part of patients — respiratory distress syndrome. Our article provides a brief analytical review of these temporary guidelines Ministry of Health of the Russian Federation «Prevention, Diagnosis and Treatment of a New Coronavirus Infection (COVID-19)», version 3 (03.03.20) and other published sources. The team of authors expresses the hope that these data will be useful to doctors in providing medical care to patients with a new coronary virus infection, as well as to teachers in preparing students and residents. Source: Ministry of Health of the Russian Federation. Temporary guidelines «Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)», version 4 (27.03.20). Available on: https://static-3.rosminzdrav.ru/system/attachments/attaches/000/049/881/original/COVID19_recomend_v4.pd

THE DIFFICULTIES OF EARLY DIAGNOSIS AND TREATMENT OF BOTULISM

The popularity of home canning contributes to a sufficiently high incidence of botulism worldwide. The canned products containing botulinum toxin do not change neither color, taste, nor smell of contents of canned food. The criteria for the severity of the course of botulism are considered a violation of swallowing liquid food and symptoms of difficulty breathing. A distinctive feature of the paralytic syndrome in botulism is its symmetry and the absence of a violation of sensitivity. The criteria of the severity of the course of botulism is considered a violation of swallowing liquid food and the severity of acute respiratory failure. The paper presents the features of the therapy of the patients with botulism in the intensive care unit. Clinical examples illustrate the difficulties in recognizing botulism at the early stage of the disease, which are due to the polymorphism of the clinical picture of botulism and the similarity of symptoms with other diseases. Most commonly, patients with botulism are diagnosed with acute intestinal infection or the neurological pathology. Patients are not hospitalized in a timely manner, which can affect the outcome of the disease. The ability to recognize botulism at the prehospital stage is necessary for all doctors

Epidemiological and Parasitological Aspects and Peculiarity Prevention of Infections Transmitted by Ixodid Ticks in Moscow

Following article represents an analysis of the epidemiological situation of tick-borne diseases in Moscow. The study presents incidence rates of Lyme borreliosis in Moscow city population and an estimation of Ixodid ticks abundance in «Sokolniki» park and its adjacent part «Losiniy Ostrov». We estimated the prevalence of tick-borne diseases in quested ticks collected from vegetation. We developed recommendations to prevent tick bites of «Sokolniki» park visitors. The article discussed the need to develop specific strategy and tactics for the metropolis to take preventive action against tick-borne diseases