Role of a two-component ResD-ResE system in regulating the expression of guanyl-specific ribonuclease genes in Bacilli

The role of the two-component ResD-ResE signal transduction system in regulating the expression of guanyl-specific ribonuclease genes in bacilli has been studied. Proteins with homologies to the ResD and ResE regulatory proteins of Bacillus subtilis have been found in all sequenced genomes of Bacillus. It has been shown using the B. subtilis strains defective in genes of these proteins that the ResD-ResE signal transduction system positively regulates the expression of ribonuclease genes of B. intermedius, B. pumilus, and B. thuringiensis in cells of B. subtilis. The data obtained in this work speak for the fact that regulatory system similar to the two-component ResD-ResE signal transduction system of B. subtilis also functions in other representatives of the Bacillus genus. © 2008 Allerton Press, Inc

Prospects for Drugs Based on the Mitochondria-Targeting Antioxidant SkQ1 in Treatment of Wounds with Impaired Healing

Chronic wounds with impared wound healing that require prolong time for healing remain unsolved problem of modern medicine. Excessive oxidative stress plays an important role in the pathogenesis of chronic wounds caused by aging, diabetes and other pathologies. This review is aimed at the role of mitochondria in oxidative stress and to the future prospects for using the innovative mitochondria targeted antioxidants for treatment of impaired wounds. Recent studies in old mice and mice with type 2 diabetes showed that the mitochondrial antioxidant SkQ1 [10- (6'- plastoquinonyl) decyltriphenylphosphonium] stimulates healing of full-thickness dermal wounds. SkQ1 accelerates inflammatory stage of wound healing, maturation of granulation tissue, angiogenesis and epithelization of wounds. The anti-inflammatory effect of SkQ1 is possibly connected to decreased inflammatory activation of the vascular endothelium, which is typical for aging, diabetes and other pathologies. Local administration of SkQ1 also accelerates wound healing and provides strong anti-inflammatory effect in the model of acute aseptic inflammation. In addition, SkQ1 to stimulate apoptosis of neutrophils and suppresses their activation, as well as suppresses inflammatory activation of mast cells. In the wound model in vitro, SkQ1 accelerates movement of epithelial cells and fibroblasts into the «wound» and stimulates differentiation of human subcutaneous fibroblasts to myofibroblasts. Reviewed data suggest that SkQ1-based topical drugs have a great potential to treat wounds that exhibit impaired healing also in patients suffering from chronic critical illness

Purification of a subtilisin-like serine proteinase from recombinant Bacillus subtilis during different phases of growth

Subtilisin-like proteinase Bacillus intermedius which is secreted at different stages of bacterial growth (at 28 h and 48 h) were purified from the culture media of recombinant strain Bacillus subtilis JB 20-36(pCS9) by chromatography on CM-cellulose and MonoS columns. MALDI-TOF mass spectroscopy of purified enzymes demonstrated that they were identical in regard to amino acid sequence. The molecular weights of both proteins were 27 kDa. Biochemical analysis revealed differences in Km values for proteinase isolated at different growth stages (1.85 and 0.86 mM for first and second fractions respectively), and in substrate specificity and sensitiveness to Ca2+ ions. Gel-filtration experiments demonstrated that subtilisin-like proteinase B. intermedius was produced as an active monomer (27 kDa) during early stationary phase (28 h of growth) and as a dimer (54 kDa) during the late stationary phase (48 h)

A novel secreted metzincin metalloproteinase from Bacillus intermedius

The mprBi gene from Bacillus intermedius 3-19 encoding a novel secreted metalloproteinase was identified. The mpriBi gene was expressed in an extracellular proteinase-deficient Bacillus subtilis BG 2036 strain and the corresponding protein was characterized biochemically. The 19. kDa MprBi protein was purified to homogeneity and sequenced by mass spectroscopy and Edman degradation methods. Amino acid sequence analysis of MprBi identified an active site motif HEYGHNFGLPHD and a conserved structural component Met-turn, both of which are unique features of the metzincin clan. Furthermore, MprBi harbors a number of distinct sequence elements characteristic of proteinase domains in eukaryotic adamalysins. We conclude that MprBi and similar proteins from other Bacillus species form a novel group of metzincin metalloproteinases in prokaryotes. © 2010 Federation of European Biochemical Societies

ИЗУЧЕНИЕ ДИНАМИКИ ОПУХОЛЕВОГО КРОВОТОКА ДЛЯ ОЦЕНКИ РАННЕГО ОТВЕТА РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ НА НЕОАДЪЮВАНТНУЮ ХИМИОТЕРАПИЮ

Background. Over the past 20 years, there has been a change in approaches to the treatment of breast cancer, in particular, a significant increase in the role of drug therapy. Breast cancer response to neoadjuvant chemotherapy is currently considered as a surrogate biomarker, which allows evaluation of the clinical course and prognosis of the disease. To solve this problem, it is necessary to assess the functional and metabolic changes in tumor tissue during treatment. Doppler ultrasound is a non-invasive, affordable, and low-cost imaging technique that can be safely used for repeated measurements.The purpose of the study was to study vascular changes in the tumor by power Doppler ultrasound for the evaluation of the early breast cancer response to neoadjuvant chemotherapy.Material and Methods. From May 2017 to August 2019, 63 patients with breast cancer received neoadjuvant chemotherapy. Changes in the tumor blood flow were assessed before starting the treatment and prior to the second course of neoadjuvant chemotherapy using Doppler scanning. Changes in tumor blood floor after chemotherapy were compared with the pathological tumor response after surgical treatment.Results. In the vast majority of cases (78 %), there was a decrease in the number of tumor vessels after the first cycle of neoadjuvant chemotherapy independent of the grade of pathological response. In 8 cases with increased vascularization after the first cycle of neoadjuvant chemotherapy, histological examination of the removed tumor showed no response / weak response to treatment in the absence of peritumoral inflammation. In 5 cases, a sharp increase in the number of vessels around large areas of intranodular necrosis and peritumoral inflammation was observed. In general, a comparison of changes in tumor vascularization and pathological response revealed a weak, although statistically significant, negative correlation between changes in the tumor blood flow after neoadjuvant chemotherapy and pathological response.Conclusion. It was not possible to establish an unambiguous relationship between the reaction of the vascular bed and the tumor response to the cytostatic effect. An increase in the number of tumor vessels in the absence of peritumoral inflammation was the only situation when changes in tumor blood flow during chemotherapy can be unambiguously interpreted as a predictive criterion for the absence / weak response of the tumor to treatment.Введение. В течение последних 20 лет произошло изменение подходов к лечению рака молочной железы, в частности существенное повышение роли лекарственной терапии. Ответ на неоадъювантную химиотерапию рассматривается в настоящее время как суррогатный биомаркер, который позволяет оценить течение и прогноз заболевания. Для решения данной задачи необходимо проводить оценку функциональных и метаболических изменений опухолевой ткани в процессе лечения. Ультразвуковая допплерография – это неинвазивный, доступный и недорогой метод визуализации, который можно безопасно использовать для повторных измерений. Цель исследования – изучение динамики васкуляризации опухоли ультразвуковым  методом в режиме энергетического допплера для оценки раннего ответа рака молочной железы на неоадъювантную химиотерапию. Материал и методы. Исследование проводилось на базе ФБУЗ ПОМЦ ФМБА России с мая 2017 по август 2019 г. В исследование были включены 63 больных раком молочной железы, которым проводилась неоадъювантная химиотерапия. Оценка кровотока опухоли с использованием допплеровского сканирования проводилась до начала и перед вторым курсом неоадъювантной химиотерапии. Изменения кровоснабжения опухоли на фоне химиотерапии сопоставлялись с патоморфологическим ответом опухоли после оперативного лечения.Результаты. В подавляющем большинстве случаев (78 %) наблюдалось не зависящее от степени лечебного патоморфоза уменьшение количества опухолевых сосудов после первого курса химиотерапии. В 8 случаях повышения васкуляризации после первого  курса неоадъювантной химиотерапии при гистологическом исследовании удаленной опухоли наблюдалось отсутствие ответа/слабый ответ на лечение при отсутствии перитуморального воспаления, в 5 случаях – резкое увеличение количества сосудов вокруг обширных зон интранодулярного некроза и обусловленного им перитуморального воспаления. В целом сопоставление динамики васкуляризации опухоли и  патоморфологического ответа выявило слабую, хотя и статистически значимую отрицательную корреляцию между изменениями кровоснабжения опухоли на фоне химиотерапии и степенью лечебного патоморфоза. Выводы. Не удалось установить однозначной зависимости между реакцией сосудистого русла и ответом опухоли на цитостатическое воздействие. Повышение количества  опухолевых сосудов при отсутствии перитуморального воспаления оказалось  единственной ситуацией, когда изменения опухолевого кровотока на фоне проведения химиотерапии могут быть однозначно интерпретированы как предиктивный критерий отсутствия/слабого ответа опухоли на лечение

Low voltage control of exchange coupling in aferromagnet-semiconductor quantum well hybridstructure

Voltage control of ferromagnetism on the nanometer scale is highly appealing for the development of novel electronic devices with low power consumption, high operation speed, reliable reversibility and compatibility with semiconductor technology. Hybrid structures based on the assembly of ferromagnetic and semiconducting building blocks are expected to show magnetic order as a ferromagnet and to be electrically tunable as a semiconductor. Here, we demonstrate the electrical control of the exchange coupling in a hybrid consisting of a ferromagnetic Co layer and a semiconductor CdTe quantum well, separated by a thin non-magnetic (Cd,Mg)Te barrier. The electric field controls the phononic ac Stark effect—the indirect exchange mechanism that is mediated by elliptically polarized phonons emitted from the ferromagnet. The effective magnetic field of the exchange interaction reaches up to 2.5 Tesla and can be turned on and off by application of 1V bias across the heterostructure

Rapid shifting of a deep magmatic source at Fagradalsfjall volcano, Iceland

Recent Icelandic rifting events have illuminated the roles of centralized crustal magma reservoirs and lateral magma transport1,2,3,4, important characteristics of mid-ocean ridge magmatism1,5. A consequence of such shallow crustal processing of magmas4,5 is the overprinting of signatures that trace the origin, evolution and transport of melts in the uppermost mantle and lowermost crust6,7. Here we present unique insights into processes occurring in this zone from integrated petrologic and geochemical studies of the 2021 Fagradalsfjall eruption on the Reykjanes Peninsula in Iceland. Geochemical analyses of basalts erupted during the first 50 days of the eruption, combined with associated gas emissions, reveal direct sourcing from a near-Moho magma storage zone. Geochemical proxies, which signify different mantle compositions and melting conditions, changed at a rate unparalleled for individual basaltic eruptions globally. Initially, the erupted lava was dominated by melts sourced from the shallowest mantle but over the following three weeks became increasingly dominated by magmas generated at a greater depth. This exceptionally rapid trend in erupted compositions provides an unprecedented temporal record of magma mixing that filters the mantle signal, consistent with processing in near-Moho melt lenses containing 107–108 m3 of basaltic magma. Exposing previously inaccessible parts of this key magma processing zone to near-real-time investigations provides new insights into the timescales and operational mode of basaltic magma systems