О неустойчивости решений динамических уравнений на временной шкале

В роботi наведено результати аналiзу нестiйкостi динамiчних рiвнянь на часовiй шкалi. Застосовнiсть отриманого результату iлюструється на прикладi системи другого порядку.We present new results on the instability for dynamic equations on time scales. To demonstrate the applicability, we use some examples of dynamic equations of the second order

Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health

Invoegen, uitvoegen en ritsen : over de dynamiek van biologische membranen

De titel 'INVOEGEN, UITVOEGEN EN RITSEN' duidt op dynamische processen, die zich alleen kunnen afspelen door middel van samenwerkingsverbanden. Er valt niets in te voegen, uit te voegen of te ritsen als er geen medespelers zijn. Als deze titel ergens op van toepassing is, dan is het wel de biochemie. Wat is biochemie? Biochemie is ' de chemie van levensverschijnselen', ofwel 'het beschrijven van het leven op moleculair niveau'. Ontstaan uit de chemie, heeft de biochemie heeft zich in een razend tempo ontwikkeld tot een niet meer weg te denken basiswetenschap met toepassingen op vele gebieden van de wetenschap. Met andere woorden, de kracht van de biochemie ligt in het samenwerken met andere disciplines. Ieder van deze disciplines heeft zijn eigen behoefte aan toepassingen van de biochemie. Bij de faculteit der Diergeneeskunde mag ik de leerstoel Veterinaire Biochemie bezetten. Met de toevoeging 'veterinair' geeft de faculteit een duidelijk signaal wat zij van mij verwacht op het gebied van zowel onderwijs als onderzoek. Ik kom hier in het verloop van mijn oratie nog een aantal malen op terug. Ik heb mijn best gedaan deze oratie voor het sterk gedifferentieerde publiek zoals dat hier aanwezig is, begrijpelijk te houden. Mocht het toch zo zijn dat u één en ander nog eens rustig zou willen nalezen, dan kan dat binnenkort via de homepage van onze hoofdafdeling

Novel insights into the function of the conserved domain of the CAP superfamily of proteins

Members of the Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP) superfamily are found in a remarkable variety of biological species. The presence of a highly conserved CAP domain defines the CAP family members, which in many cases is linked to other functional protein domains. As a result, this superfamily of proteins is involved in a large variety of biological processes such as reproduction, tumor suppression, and immune regulation. The role of the CAP domain and its conserved structure throughout evolution in relation to the diverse functions of CAP proteins is, however, poorly understood. Recent studies on the mammalian Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1), which consists almost exclusively of a CAP domain, may shed new light on the function of the CAP domain. GAPR-1 was shown to form amyloid fibrils but also to possess anti-amyloidogenic properties against other amyloid forming peptides. Amyloid prediction analysis reveals the presence of potentially amyloidogenic sequences within the highly conserved sequence motifs of the CAP domain. This review will address the structural properties of GAPR-1 in combination with existing knowledge on CAP protein structure-function relationships. We propose that the CAP domain is a structural domain, which can regulate protein-protein interactions of CAP family members using its amyloidogenic properties