Правові засади здійснення діяльності зі спільного інвестування

We describe the expression of the bispecific antibody biscFv2429 in transgenic suspension culture cells and tobacco plants. biscFv2429 consists of two single chain antibodies, scFv24 and scFv29, connected by the Trichoderma reesi cellobiohydrolase I linker. biscFv2429 binds two epitopes of tobacco mosaic virus (TMV): the scFv24 domain recognizes neotopes of intact virions, and the scFv29 domain recognizes a cryptotope of the TMV coat protein monomer. biscFv2429 was functionally expressed either in the cytosol (biscFv2429-cyt) or targeted to the apoplast using a murine leader peptide sequence (biscFv2429-apoplast). A third construct contained the C-terminal KDEL sequence for retention in the ER (biscFv2429-KDEL). Levels of cytoplasmic biscFv2429 expression levels were low. The highest levels of antibody expression were for apoplast targeted biscFv2429-apoplast and ER retained biscFv2429-KDEL, which reached a maximum expression level of 1.65% total soluble protein in transgenic plants. P lant expressed biscFv2429 retained both epitope specificities, and bispecificity and bivalency were confirmed by ELISA and surface plasmon resonance analysis. This study establishes plant cells as an expression system for bispecific single chain antibodies for use in medical and biological applications

Застосування інформаційних технологій в міжнародній торгівлі і на транспорті

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 mg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries

Dietary flavonoid intake and risk of incident depression in midlife and older women

Background: The impact of dietary flavonoid intakes on risk of depression is unclear. Objective: We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk. Design: We followed 82,643 women without a previous history of depression at baseline from the Nurses’ Health Study [(NHS) aged 53–80 y] and the Nurses’ Health Study II [(NHSII) aged 36–55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2–4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations. Results: A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable-adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004–0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed ≥2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significant (9–12%) lower depression risks. In analyses among late-life NHS participants (aged ≥65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90). Conclusions: Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations

Wie könnte eine curriculare Verankerung des Themas Patientensicherheit aussehen? Eine Handreichung des Ausschusses für Patientensicherheit und Fehlermanagement der GMA

The topic of patient safety is of fundamental interest for the health care sector. In view of the realisation of the National Competence-Based Learning Objectives Catalogue for Undergraduate Medical Education (NKLM) this topic now has to be prepared for medical education. For a disciplinary and content-related orientation the GMA Committee developed the Learning Objectives Catalogue Patient Safety for Undergraduate Medical Education (GMA-LZK). To ensure an optimal implementation of the GMA-LZK we recommend a longitudinal embedding into the existing curriculum. This position paper supports the implementation of the GMA-LZK and is aimed at everyone who wants to establish teaching courses on the topic patient safety and embed them in the curriculum. In light of this, we will initially describe the key features for a structured analysis of the current situation. Based on three best-practice-examples, as seen in the faculties of Freiburg, Bonn and Munich, different approaches to the implementation of the GMA-LZK will be illustrated. Lastly, we will outline the methodical requirements regarding the curriculum development as well as the disciplinary and methodical competences that the lecturers will have to hold or develop to fulfil the requirements.Das Thema Patientensicherheit steht im Zentrum des Interesses des Gesundheitswesens. Im Hinblick auf die Umsetzung des Nationalen Kompetenzbasierten Lernzielkataloges für das Medizinstudium (NKLM) muss das Thema nun für die medizinische Lehre vorbereitet werden. Zur fachlich-inhaltlichen Orientierung wurde vom GMA-Ausschuss der Lernzielkatalog Patientensicherheit für das Medizinstudium (GMA-LZK) entwickelt. Für eine optimale Umsetzung des GMA-LZK wird eine longitudinale Einbettung in das bestehende Curriculum empfohlen. Das vorliegende Positionspapier soll als Hilfestellung zur Implementierung des GMA-LZK dienen und richtet sich an alle Personen, die Lehre zum Thema Patientensicherheit etablieren und im Curriculum verankern möchten. In diesem Zusammenhang werden zunächst Eckpunkte für eine strukturierte Standortanalyse beschrieben. Anhand dreier Best-Practice-Beispiele der Fakultäten Freiburg, Bonn und München wird aufgezeigt, welche unterschiedlichen Herangehensweisen zur Implementierung des GMA-LZK bereits genutzt werden. Abschließend wird dargestellt, welche methodischen Anforderungen sich für die Curriculumsentwicklung ergeben und welche fachlichen und methodischen Kompetenzen Lehrende mitbringen bzw. entwickeln müssen, um den Anforderungen gerecht zu werden