Local brassinosteroid biosynthesis enables optimal root growth

Brassinosteroid hormones are indispensable for root growth and they control both cell division and cell elongation through the establishment of an increasing signaling gradient along the longitudinal root axis. Because of their limited mobility, the importance of brassinosteroid distribution for achieving the signaling maximum is largely overlooked. Expression pattern analysis of all known brassinosteroid biosynthetic enzymes revealed that not all cells in the Arabidopsis thaliana root possess full biosynthetic machinery and completion of biosynthesis relies on cell-to-cell movement of the hormone precursors. We demonstrate that brassinosteroid biosynthesis is largely restricted to the root elongation zone where it overlaps with brassinosteroid signaling maxima. Moreover, optimal root growth requires hormone concentrations, low in the meristem and high in the root elongation zone attributable to an increased biosynthesis. Our finding that spatiotemporal regulation of hormone synthesis results in a local hormone accumulation provides a paradigm for hormone-driven organ growth in the absence of long-distance hormone transport in plants

Interdisciplinary care of people with Marfan syndrome - Pharmacology, pregnancy, eye, skeleton and organizational aspects

Im ersten Teil des vorliegenden Beitrags wurde im Detail auf die Genetik, Diagnose, Differenzialdiagnose, die diagnostische Bildgebung, Follow-up, die kardiovaskulären Probleme sowie die Manifestation an Aorta und den großen Gefäßen bei Patienten mit dem Marfan-Syndrom (MFS) eingegangen. In diesem zweiten Teil werden die medikamentöse Therapie des MFS, seine Bedeutung im Zusammenhang mit einer Schwangerschaft, die Beteiligung von Augen und Wirbelsäule bei MFSPatienten sowie die organisatorischen Aspekte einer Marfan-Sprechstunde erläutert. Das MFS ist mit einer Prävalenz von etwa 1–2:10.000 die häufigste hereditäre Bindegewebserkrankung mit vaskulärer Komponente. Ursache sind Mutationen im Gen, das für das extrazelluläre Matrixprotein Fibrillin-1 kodiert. Die Erkrankung wird autosomal-dominant vererbt. Es handelt sich um eine Multisystemerkrankung mit Beteiligung der Aorta, der Mitralklappe, Augen- und Skelettveränderungen. Die Augen- und/oder die Wirbelsäulenbeteiligung sind nicht zu unterschätzen, da sowohl die Skoliose als auch die Linsendislokation etwa 60% der Patienten mit MFS betreffen. Bis anhin konnte kein Wirkstoff einen klaren Vorteil hinsichtlich klinischer Ereignisse in MFS-Patienten zeigen. Es besteht jedoch der allgemeine Konsens, Patienten mit MFS einen β-Rezeptoren- oder Angiotensinrezeptorblocker isoliert oder als Kombinationstherapie zu verabreichen. Bei bestehendem Kinderwunsch muss ein besonderes Augenmerk auf die Planung der Schwangerschaft gelegt werden. Im Fall eines Aortenwurzeldurchmessers >4–4,5cm empfiehlt sich, entweder einen prophylaktischen Aortenwurzelersatz zu erwägen oder von einer Schwangerschaft abzuraten. Eine strukturierte Langzeitbetreuung ist für Patienten mit MFS essenziell

Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction

Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor- controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy- associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the fetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting, and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tract, in trophoblast cells from normal and pre-eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer (NK) cells as possible target

Anti-HIV-1 antibodies 2F5 and 4E10 interact differently with lipids to bind their epitopes

© 2011 Wolters Kluwer Health | Lippincott Williams & WilkinsObjectives: 2F5 and 4E10 are two broadly neutralizing monoclonal antibodies (mAbs) targeting the membrane proximal external region (MPER) of HIV-1 gp41 envelope protein. This region, which contacts the viral membrane, is highly conserved and has been regarded as a promising target for vaccine development. We aimed to clarify the basis of 2F5 and 4E10 molecular interactions with epitope cores in MPER and lipid bilayers. Design: Microscopy-based approaches were used to infer and quantify the effects of both mAbs on membranes, in the presence and absence of the epitope cores. Supported lipid bilayers (SLBs), with and without phase separation, were used as membrane models. Fluorescent-labeled and nonlabeled MPER-derived peptides containing both 2F5 and 4E10 epitopes were used. Methods: mAbs 2F5 and 4E10 membrane interactions, in the presence or absence of MPER-derived peptides, were evaluated by combined atomic force and confocal microscopies. Results: Both mAbs form lipid-segregated aggregates on SLBs and do not induce other significant membrane perturbations. Furthermore, the affinity of MPER toward membranes is differently affected by both mAbs and correlates with the mAbs–epitope core lipid interactions. 2F5 is able to dock the MPER peptide on the membrane, whereas 4E10 extracts the MPER from the lipid bilayer. Conclusion: The results reveal the molecular details underneath 2F5/4E10 membraneepitope binding and a model is proposed to explain the differential mAbs neutralization efficacies, which relates to the exposure of the epitopes in the lipid bilayers and the role of the lipids in mAb–epitope binding.The authors are grateful for the support from the Max Planck Gesellschaft (Germany). Fundação para a Ciência e Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (Portugal) is acknowledged for funding (SFRH/BD/39039/2007 grant to H.G.F. and projects PTDC/QUI-BIQ/104787/2008, PTDC/QUI/69937/2006 and REEQ/140/BIO/2005