Systemic inflammatory response to cardiac surgery: does female sex really protect?

Sex hormones have important interactions with the immune system and modulate the inflammatory response. In this regard, oestrogen inhibits the transcription of proinflammatory cytokines and confers tissue protection in experimental models. On the basis of this evidence, Trotter et al. in this issue of Critical Care addressed the question of whether, in children, female sex would protect against the deleterious effects of cardiac operations with cardiopulmonary bypass by providing a favourable anti-inflammatory cytokine balance. The observations made in that study suggest sex-related immunomodulation and organ protection during cardiac surgery in the paediatric population. Prospective trials conducted in large series, including sex hormone determination in neonates, infants and children with congenital cardiac defects, are necessary to test this hypothesis. The verification of sex-related intraoperative organ protection would provide new opportunities for preventing the uncontrolled systemic inflammatory response that may occur during cardiac surgery

Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling

Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin

Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?

INTRODUCTION: Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis. METHODS: We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity. RESULTS: The ex vivo production of TNF-α and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity. CONCLUSION: Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-α and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction

WHIRLY1 is a major organizer of chloroplast nucleoids

WHIRLY1 is an abundant protein of chloroplast nucleoids, which has also been named pTAC-1 with regard to its detection in the proteome of transcriptionally active chromosomes (TAC). In barley primary foliage leaves, expression of the WHIRLY1 gene is highest at the base whereas protein accumulation is highest in the middle of the leaf where young developing chloroplasts are found. In order to elucidate the function of WHIRLY1 in chloroplast nucleoids, transgenic barley plants with an RNAi-mediated knock-down of the HvWHIRLY1 gene (RNAi-W1) were generated. The homozygous RNAi-W1-7 plants, barely containing traces of the WHIRLY1 protein, were chosen for detailed analyses of nucleoids. Nucleic acid specific-staining with YO-PRO®-1 revealed that in comparison to wild type chloroplasts, which have multiple small nucleoids attached to thylakoids, chloroplasts of the transgenic plants contain large irregularly formed patches of DNA besides nucleoids that are similar in size and shape to those of wild type chloroplasts. In large electron lucent areas, filamentous structures were detected by conventional transmission electron microscopy. Analyses of ptDNA levels by both DNA dot-blot hybridization and quantitative PCR showed that leaves of the transgenic plants have a two- to three-fold higher level of ptDNA than the wild type. The higher ptDNA level in RNAi-W1 plants coincided with an enhanced expression of the gene encoding a putative organelle targeted DNA polymerase in the mid part of primary foliage leaves. Furthermore, overexpression of the barley WHIRLY1 gene in E. coli cells revealed a higher compaction of bacterial nucleoids. These results suggest that WHIRLY1 belongs to the group of plastid nucleoid associated proteins (ptNAP) having a function in compacting a subpopulation of chloroplast nucleoids thereby affecting DNA replication

First record of Dothistroma needle blight (Dothistroma septosporum) in the northeast German lowlands

Im April 2015 wurde in einem brandenburgischen Arboretum eine rötliche Bänderung an vorjährigen Nadeln von Pinus jeffreyi Balf. (Jeffrey-Kiefer) und Pinus ponderosa Douglas ex C. Lawson (Gelb-Kiefer) festgestellt. Später konnte diese Symptomatik bei systematischen Kon­trollen auch an Pinus attenuata Lemmon (Höcker-Kiefer) und Pinus thunbergii Parl. (Japanische Schwarz-Kiefer) beobachtet werden. Anhand von mikromorphologischen Untersuchungen und laborativen Analysen bestätigte sich der Verdacht auf eine Infektion durch den Quarantäneschadpilz Dothistroma septosporum (Dorogin) M. More­let (Erreger der Dothistroma-Nadelbräune). Erkrankt waren ausschließlich jüngere Bäume in einem Geländebereich mit anhaltend hoher Luftfeuchtigkeit. Der weltweit vorkommende Krankheitserreger befällt überwiegend Kiefern-Arten (Pinus spp.). Gravierende Schäden verursachte er bislang speziell auf der Südhalbkugel. In letzter Zeit konnte Dothistroma septosporum allerdings auch in einigen europäischen Ländern bemerkenswert oft nachgewiesen werden. Möglicherweise geht die verstärkte Präsenz des Pilzes nördlich des Äquators auf die sich seit einigen Jahrzehnten abzeichnende Klimaveränderung zurück. Da der Krankheitserreger imstande ist, auch an der in Europa heimischen Schwarz-Kiefer (Pinus nigra J.F. Arnold) umfangreiche Schäden hervorzurufen, resultieren aus dem Vorkommen forstwirtschaftliche Risi­ken. Zudem ist unklar, welche Intensität ein Befall von Reinbeständen der Gemeinen Kiefer (Pinus sylvestris L.) erreichen würde.In April 2015, reddish banding at last year's needles of Pinus jeffreyi Balf. (Jeffrey pine) and Pinus ponderosa Douglas ex C. Lawson (Ponderosa Pine) was found in an Arboretum in the federal state of Brandenburg (Germany). These symptoms were observed in systematic controls at Pinus attenuata Lemmon (Knobcone pine) and Pinus thunbergii Parl. (Japanese black pine) later too. Based on micromorphological investigations and laborative tests, the suspected infection by the quarantine fungus Dothi­stroma septosporum (Dorogin) M. Morelet (causative agent of Dothistroma needle blight) was confirmed. Only younger trees in an area with persistently high air humidity were diseased.The worldwide occurring pathogen infects mainly pine species (Pinus spp.). It caused serious damage especially in the southern hemisphere until now. Lately however Dothistroma septosporum was remarkably often detected in several European countries. The increased presence of the fungus north of the Equator is supposed to originate in the recognizable climate change of the last few deca­des. The pathogen is capable of damaging the native to Europe Black pine (Pinus nigra J.F. Arnold) considerably. Therefore forestry risks result. In addition, it is unclear, what intensity an infestation of pure stands of Scots pine (Pinus sylvestris L.) would reach

Non-canonical shedding of TNFα by SPPL2a is determined by the conformational flexibility of its transmembrane helix

Ectodomain (EC) shedding defines the proteolytic removal of a membrane protein EC and acts as an important molecular switch in signaling and other cellular processes. Using tumor necrosis factor (TNF)α as a model substrate, we identify a non-canonical shedding activity of SPPL2a, an intramembrane cleaving aspartyl protease of the GxGD type. Proline insertions in the TNFα transmembrane (TM) helix strongly increased SPPL2a non-canonical shedding, while leucine mutations decreased this cleavage. Using biophysical and structural analysis, as well as molecular dynamic simulations, we identified a flexible region in the center of the TNFα wildtype TM domain, which plays an important role in the processing of TNFα by SPPL2a. This study combines molecular biology, biochemistry, and biophysics to provide insights into the dynamic architecture of a substrate\u27s TM helix and its impact on non-canonical shedding. Thus, these data will provide the basis to identify further physiological substrates of non-canonical shedding in the future

Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix

Ectodomain (EC) shedding defines the proteolytic removal of a membrane protein EC and acts as an important molecular switch in signaling and other cellular processes. Using tumor necrosis factor (TNF)α as a model substrate, we identify a non-canonical shedding activity of SPPL2a, an intramembrane cleaving aspartyl protease of the GxGD type. Proline insertions in the TNFα transmembrane (TM) helix strongly increased SPPL2a non-canonical shedding, while leucine mutations decreased this cleavage. Using biophysical and structural analysis, as well as molecular dynamic simulations, we identified a flexible region in the center of the TNFα wildtype TM domain, which plays an important role in the processing of TNFα by SPPL2a. This study combines molecular biology, biochemistry, and biophysics to provide insights into the dynamic architecture of a substrate\u27s TM helix and its impact on non-canonical shedding. Thus, these data will provide the basis to identify further physiological substrates of non-canonical shedding in the future

Разработка технологии сборки и сварки стыкового соединения труба-лист из низколегированной стали

Соединение вида труба-лист является одним из распространенных типов сварных соединений. К примеру, оно часто применяется при изготовлении металлических колонн и несущих опор каркасов зданий. Применение низколегированных сталей взамен углеродистых при изготовлении данных металлоконструкций обеспечивает существенное снижение металлоемкости, а также позволяет повысить различные прочностные характеристики соединения. Цель работы – разработка технологии сборки и сварки стыкового соединения труба-лист из стали 09Г2С. В процессе работы был выбран способ сварки, сварочное оборудование и сварочные материалы. Произведены расчеты параметров режима сварки, рассчитаны оптимальные геометрические характеристики шва, а также его ожидаемый химический состав.Pipe-to-sheet joint is one of common welded joints. For example it is used to make of metal columns and load-bearing supports of building frames. The use of low alloy steels instead of carbon steels in the manufacture of metal structures reduces metal consumption and allows to increase the strength characteristics of joint. Purpose of the work is development of fitting up and welding technology of a butt pipe-to-sheet joint steel 09G2S. In the progress, a welding method, welding equipment and welding materials were selected. The parameters of the welding mode, geometric characteristics and chemical composition are calculated

Нанесение антифрикционных покрытий порошком Б-83 методом холодного газодинамического напыления

Работа направлена на развитие технологии холодного газодинамического напыления антифрикционного покрытия порошком Б-83 на подшипники скольжения судовые. Как альтернатива традиционному методу баббитозаливки судовых подшипников скольжения.The work is aimed at the development of technology of cold gas-dynamic spraying of antifriction coating with powder B-83 on ship bearings. As an alternative to the traditional method of babiogorski marine bearings