The circadian system of the cockroach Leucophaea maderae: The role of the neuropeptide orcokinin and light entrainment

Das circadiane system der Schabe Leucophaea maderae: Die Rolle des Neuropetides Orcokinin und die Synchronisation der Inneren Uhr durch Licht

The circadian system of the cockroach Leucophaea maderae: The role of the neuropeptide orcokinin and light entrainment

Das circadiane system der Schabe Leucophaea maderae: Die Rolle des Neuropetides Orcokinin und die Synchronisation der Inneren Uhr durch Licht

Reconstruction and Dissection of the Entire Human Visual Pathway Using Diffusion Tensor MRI

The human visual system comprises elongated fiber pathways that represent a serious challenge for diffusion tensor imaging (DTI) and fiber tractography: while tracking of frontal fiber bundles may be compromised by the nearby presence of air-filled cavities, nerves, and eye muscles, the anatomic courses of the three main fiber bundles of the optic radiation are subject to pronounced inter-subject variability. Here, tractography of the entire visual pathway was achieved in six healthy subjects at high spatial accuracy, that is, at 1.8 mm isotropic spatial resolution, without susceptibility-induced distortions, and in direct correspondence to anatomic MRI structures. Using a newly developed diffusion-weighted single-shot STEAM MRI sequence, we were able to track the thin optic nerve including the nasal optic nerve fibers, which cross the optic chiasm, and to dissect the optic radiation into the anterior ventral bundle (Meyer's loop), the central bundle, and the dorsal bundle. Apart from scientific applications these results in single subjects promise advances in the planning of neurosurgical procedures to avoid unnecessary damage to the visual fiber system

Der Einfluss einer Steroidvorbehandlung von Spenderorganen auf die initiale Transplantatfunktion nach allogener Nierentransplantation

Fragestellung In verschiedenen Studien wurde nach Transplantation von Organen älterer Spender eine erhöhte Transplantatimmunogenität und eine verstärkte Immunantwort im Empfänger beobachtet, mit der Konsequenz einer reduzierten Transplantatfunktion und erhöhten Abstoßungsraten. Zusätzlich wird die Transplanatfunktion durch weitere Alloantigen-unabhängige Faktoren wie Empfängeralter, Hirntod und kalte Ischämiezeit beeinflusst. Frühere klinische und experimentelle Studien zeigten den anti-inflammatorischen Effekt einer Spendervorbehandlung mit Steroiden auf die Immunogenität des Transplantats. Ziel der vorliegenden klinischen Studie war es zu untersuchen, ob eine Methylprednisolonvorbehandlung hirntoter Nierentransplantatspender zu einer Reduktion der Rejektionsraten und einer verbesserten initialen Transplantatfunktion bei Patienten des „European Senior Program“ (ESP) im Vergleich zum Normalkollektiv führt. Zusätzlich sollte der Einfluss der kalten Ischämiezeit in den verschiedenen Kollektiven untersucht werden. Methoden Untersucht wurden 134 Empfänger von Transplantaten verstorbener Spender sowie 35 Empfänger von Lebendspenden. Mit Ausnahme der Lebendspenden, erhielten alle randomisiert Nieren von Methylprednisolon-vorbehandelten (n=64) oder unbehandelten (n=70) hirntoten Spendern. Bei erfolgter Vorbehandlung erhielt der Nierenspender 12h vor Organentnahme 500 mg Methylprednisolon i.v. als Bolusgabe, nachfolgend 100 mg/h bis zur Organentnahme. Das Studienkollektiv wurde in verschiedene Altersgruppen unterteilt. Nach Transplantation wurden die einzelnen Gruppen hinsichtlich aufgetretener Abstoßungsreaktionen, initialer Transplantatfunktion und kalter Ischämiezeit verglichen. Ergebnisse Im Vergleich vorbehandelter vs. unbehandelter Spenderorgane zeigte sich in keiner der gewählten Gruppen ein signifikanter Unterschied bezüglich der Gesamtrejektionsraten, wenngleich die Rejektionsraten in den vorbehandelten Gruppen um durchschnittlich 15,2% niedriger lagen als in den Vergleichsgruppen. Innerhalb der Subgruppen zeigten sich im Vergleich frühe gegen späte Rejektionen (< bzw. ≥ 7 Tage; studienspezifische Einteilung) in allen Gruppen altersunabhängig signifikant höhere Raten später Rejektionen nach Transplantation unbehandelter Spenderorgane. Bezüglich der initialen Transplantatfunktion wurden keine signifikanten Unterschiede beobachtet. Erwartungsgemäß fiel eine tendenziell schlechtere Initialfunktion marginaler Spenderorgane auf, Unterschiede im Vergleich ESP vs. Normalkollektiv waren jedoch nicht signifikant. Die kalte Ischämiezeit war im ESP-Kollektiv im Vergleich zum Normalkollektiv signifikant verkürzt, so dass ein Ziel des ESP, die kalte Ischämiezeit zu reduzieren, in unserem Patientenkollektiv erreicht wurde. Überraschend waren die hohen Rejektionsraten der Lebendspender-Gruppe, welche denen der verstorbenen Spender vergleichbar waren. Andererseits zeigten Organe von Lebendspendern gute initiale Transplantatfunktionen, die mit verkürzten kalten Ischämiezeiten assoziiert waren. Zusammenfassung Eine Vorbehandlung mit Methylprednisolon scheint einen altersunabhängigen inhibitorischen Effekt auf die immunologischen Rejektionsprozesse nach Transplantation zu haben. Alle vorbehandelten Gruppen wiesen prozentual niedrigere Rejektionsraten als die Vergleichsgruppen auf. Über den Einfluss der Steroide auf die initiale Transplantatfunktion lässt sich kein eindeutiger Schluss ziehen, hierfür wären weitere Studien mit höherer Fallzahl erforderlich.Background Increasing donor age is associated with elevated graft immunogenicity and an intensified recipient immune response, leading to increased rates of allograft rejection episodes and delayed graft function (DGF). Additional alloantigen-independent factors such as increased recipient age, donor brain death and prolonged cold storage time (CIT) may amplify these effects. Recent clinical and experimental studies demonstrated the beneficial effect of donor pretreatment with steroids resulting in lower rates of rejection episodes and DGF. The aim of this study was to evaluate whether patients, especially those of the European Senior Program (ESP) may benefit from donor pretreatment with methylprednisolone. Moreover, we wanted to examine the agedependent impact of CIT on graft function. Methods 134 recipients of organs from brain dead donors and 35 recipients from living donors were analysed. Except in case of living donor grafts, kidneys from donors with (n=64) or without (n=70) methylprednisolone treatment were randomly allocated to transplant recipients. Steroid pretreated donors received 500 mg methylprednisolone intravenously as a bolus 12 hours before explantation and consecutively 100 mg/h until explantation. The classification of each group occurred from age. After transplantation each group was analysed with regard to rejection and DGF. CIT was compared between all study groups. Results There was no significant difference regarding rejection rates between control and steroid pretreated groups, although rejection rates were up to 15,2% lower on average in the pretreated groups. Furthermore, we observed a significant higher number of late acute rejections (after > 7 days) in all untreated groups, regardless of age. Initial graft function was comparable in both, recipients of pretreated or untreated grafts. As expected, DGF was more pronounced in older organs, although there was no significant difference between the ESP and the normal cohort. According to the objective of the ESP, CIT was indeed significantly reduced in the ESP group. Surprisingly, we observed a high number of rejections in the living donor cohort, comparable to those in the brain dead donor group. However, the initial function in the living donor group was excellent and was associated with a very short CIT. Conclusion Donor pretreatment with methylprednisolone seems to have an inhibitory effect on the immune response after transplantation, independent of age. All pretreated groups showed reduced rejection rates when compared to the respective controls. To further clarify the impact of steroid pretreatment on the initial graft function, higher number of patients have to be included in further studies

Ponašanje termički modificiranog drva u vanjskim uvjetima primjene – trajnost, abrazija i izgled

Thermally modified timber (TMT) is increasingly offered in Europe as an alternative to preservative treated timber. TMT durability in field tests as well as its moisture sorption behaviour in façade application was determined so as to consider its suitability for outdoor use. Additionally, abrasion and crack-formation of TMT deckings were examined and the optical appearance of a TMT façade was evaluated after 5 years of service. After 7.5 years exposure in ground contact, the various TMT materials tested were classed as “slightly durable” to “not durable” whereas the classification in above ground exposure was “very durable” to “moderately durable”, which was in line with the reduced moisture sorption of TMT in weathered application. Moreover, the TMT-decking showed less abrasion and crack-formation compared to references, though the TMT façade revealed considerable discoloration by weathering. Hence, the suitability of TMT for above ground use is suggested, but a surface treatment is obligatory if discoloration is objectionable.Termički modificirano drvo (TMT) sve se više nudi u Europi kao alternativa kemijski zaštićenom drvu. Za ocjenu prikladnosti TMT-a za vanjsku upotrebu ispitivana je biološka trajnost u vanjskim uvjetima, kao i sorpcija vode u elementima fasade. Dodatno je ispitivana otpornost na abraziju i nastajanje pukotina u TMT podovima, te je napravljen vizualni pregled TMT fasade nakon petogodišnje upotrebe. Nakon 7,5 godina izloženosti u dodiru s tlom, različiti TMT materijali ocijenjeni su kao "slabo otporni" do "neotporni" dok su ocjene tog istog materijala za izlaganje iznad tla bile "vrlo otporno" do "srednje otporno". Dobivene su ocjene, u skladu sa smanjenom sorpcijom vode TMT materijala u vanjskoj upotrebi. Štoviše, TMT podovi pokazali su manju abraziju i pukotine od referentnog drva, iako su TMT elementi fasade pokazali veću diskoloraciju uzrokovanu abiološkom razgradnjom. Dakle, TMT je u vanjskim uvjetima i iznad tla preporučljiv za upotrebu, ali uz obveznu površinsku obradu ako se želi izbjeći diskoloracija

Performance of thermally modified timber (TMT) in outdoor application - durability, abrasion and optical appearance

Thermally modified timber (TMT) is increasingly offered in Europe as an alternative to preservative treated timber. TMT durability, infield tests as well as its moisture sorption behaviour in facade application was determined so as to consider its suitability for outdoor use. Additionally, abrasion and crack-formation of TMT deckings were examined and the optical appearance of a TMT facade was evaluated after 5 years of service. After 7.5 years exposure in ground contact, the various TMT materials tested were classed as "slightly durable" to "not durable" whereas the classification in above ground exposure was "very durable" to "moderately, durable", which was in line with the reduced moisture sorption of TMT in weathered application. Moreover, the TMT-decking showed less abrasion and crack-formation compared to references, though the TMT facade revealed considerable discoloration by weathering. Hence, the suitability of TMT for above ground use is suggested, but a surface treatment is obligatory if discoloration is objectionable

Predictors of increasing BMI during the course of diabetes in children and adolescents with type 1 diabetes: data from the German/Austrian DPV multicentre survey

Objective: Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey. Design: Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53 108 patients with T1D, aged <20 years, were recorded in 248 centres. 12 774 patients (53% male, mean age 13.4+/-3.9, mean diabetes duration 4.7+/-3.0 years and mean age at diabetes onset 8.7+/-4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity. Results: 12.5% of T1D patients were overweight and 2.8% were obese. Multiple longitudinal regression analysis revealed that female gender, low BMI at diabetes onset, intensified insulin therapy and higher insulin dose, as well as pubertal diabetes onset, long diabetes duration and onset in earlier calendar years among girls, were related to higher BMI-SDS increase during the course of diabetes (p<0.01; all). Conclusions: Intensified insulin regimen is associated with weight gain during T1D treatment, in addition to demographic variables. Optimisation of diabetes management, especially in females, might limit weight gain in order to reduce overweight and obesity together with comorbidities among paediatric T1D patients

МИРГОРОДСЬКИЙ ПОЛК В РОСІЙСЬКО-ТУРЕЦЬКІЙ ВІЙНІ 1735-1739 РР.

Тема пропонованої шановному читачеві статті знаходиться на перетині воєнної історії та краєзнавства. Після тривалої неуваги, зараз воєнна історія, зокрема козаччини, розробляється досить динамічно. Варто згадати хоча б роботи І.Стороженка [1], В.Заруби [2], О.Сокирка [3], Г.Шпитальова [4]. Одночасно все ще не розроблена докладно воєнна історія полків, які складали Гетьманщину. Хоча спроби такого роду є [5], але вони зосереджені не стільки на воєнній історії, скільки на історії полку загалом і, на жаль, не представлені у вигляді монографічних досліджень та не викладені в Інтернеті, що суттєво ускладнює доступ до результатів таких досліджень. Сюжет, пов’язаний із участю Миргородського полку в російсько-турецькій війні 1735-1739 років, не знайшов висвітлення в історіографії, хоча деякі факти містять дослідження А.Байова [6], О.Апанович [7] та вже згадувана монографія Г.Шпитальова. Протягом війни Миргородський полк брав участь як у далеких виправах, так і в ближніх походах різного роду – фортифікаційних, тривожних, для планової охорони кордонів. Залучення козаків Миргородського полку до далеких походів розпочалося вже у червні 1735 р., коли всі полки (крім Стародубського та Чернігівського) вирушили до фортеці Святого Іоанна на Українській лінії, де мали збиратися для виправи на Крим. До прибуття на лінію генерального осавула Ф.Лисенка обов’язки командира цього з’єднання виконував миргородський полковник Павло Апостол [8]. Кількість козаків Миргородського полку, які вирушили в цей похід, точно невідома. Проте є дані щодо старшини, яка очолила виправу – полковник П.Апостол, суддя Ф.Остроградський, писар В.Тихонович, осавул А.Волевач, хорунжі Т.Калницький та К.Шкурка [9]. Згідно з планами Генеральної військової канцелярії (далі – ГВК) передбачалося для Кримської (1736) виправи мобілізувати 16001 гетьманця, в тому числі 1196 шабель Миргородського полку [10]. Виникли певні проблеми з залученням старшини. Наприклад, миргородський обозний С.Родзянка уперто відмовлявся від походу під приводом хвороби, в яку полковник абсолютно не вірив. Проте С.Родзянка апелював до ГВК, де знайшов підтримку. Врешті, полкова старшина миргородців у цій виправі була представлена тими ж постатями, що й 1735 р., лише осавула А.Волевача замінив його колега С.Ґалаґан [11]. За попередніми планами на 1737 р. Миргородський полк мав виставити 849 шабель у Кримський похід. Після рішення фельдмаршала Мініха залишити слобідських козаків для охорони кордону їм на заміну залучили ще 200 миргородців [12]. На цьому зміни не закінчилися. На вимогу фельдмаршала Мініха Миргородський полк перейшов у його підпорядкування і вирушив замість Кримського в Очаківський похід

Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7

Chronic inflammation is a well-known risk factor in development of intestinal tumorigenesis, although the exact mechanisms underlying development of colitis-associated cancer (CAC) still remain obscure. The activity and function of immunoproteasome has been extensively analyzed in the context of inflammation and infectious diseases. Here, we show that the proteasomal immunosubunit LMP7 plays an essential role in development of CAC. Mice devoid of LMP7 were resistant to chronic inflammation and formation of neoplasia, and developed virtually no tumors after AOM/DSS treatment. Our data reveal that LMP7 deficiency resulted in reduced expression of pro-tumorigenic chemokines CXCL1, CXCL2 and CXCL3 as well as adhesion molecule VCAM-1. As a consequence, an impaired recruitment and activity of tumor-infiltrating leukocytes resulting in decreased secretion of cytokines IL-6 and TNF-α was observed. Further, the deletion or pharmacological inhibition of LMP7 and consequent blockade of NF-κB abrogated the production of IL-17A, which possesses a strong carcinogenic activity in the gut. Moreover, in vivo administration of the selective LMP7 inhibitor ONX-0914 led to a marked reduction of tumor numbers in wild-type (WT) mice. Collectively, we identified the immunoproteasome as a crucial mediator of inflammation-driven neoplasia highlighting a novel potential therapeutic approach to limit colonic tumorigenesis