Structural and torsional properties of the Trachycarpus fortunei palm petiole

The Trachycarpus fortunei palm is a good example of a palm with a large leaf blade supported by a correspondingly large petiole. The way in which the material and functional properties of the petiole interact is analysed using engineering and botanical methods with a view to understanding how the petiole functions from a structural standpoint. Initially, the histological aspects of the petiole are analysed at a microscopic level from sections of the petiole taken at regular intervals along its axis, in order to determine the density and location of the vascular bundles. A modified torsion rig was used to measure the torsion and shear stress variation along petiole sample lengths. Knowledge of vascular bundle placement within the petiole sections and their torsional loading characteristics contribute to understanding the petiole function

Section properties of palm petioles, Part 1: The influence of section shape on the flexural and torsional properties of selected palm petioles

Shape factors have been used to calculate the shape efficiency of palm leaf petiole sections in order to understand how palms compensate for the torsional and bending forces put upon them by their environment. That part of the palm leaf that is similar in form to the leaf stalk (petiole) in dicot leaves will be referred to as a petiole in this paper, whilst recognising that it is probably not an exact homologue. Wind and rain on the blade generate combined flexural and torsion loads on the petiole and a question arises as to how the section properties of the petiole deal with this loading. By isolating the shape from the size of the sections through the use of shape factors, the effects of the petiole section shape can be analysed on its own. Thus micro structural and material factors become a separate issue and will be discussed in a later paper. Cross section profiles from seven palm petioles are modelled, independent of their sizes, in order to calculate and plot the flexural and torsional coupling efficiencies for comparison with other plants and typical engineering cross sections

Von Willebrand Factor multimerization and the polarity of secretory pathways in endothelial cells

The Von Willebrand factor (VWF) synthesised and secreted by endothelial cells is central to haemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization and polarity of the three secretory pathways have only been addressed separately and with conflicting results. We set out to clarify these relationships using polarized Human Umbilical Vein Endothelial Cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of Ultra large (UL) molecular weight VWF predominantly occurred apically, consistent with a role in localised platelet capture in the vessel lumen. We found that constitutive secretion of low molecular weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF

BLOC-2 subunit HPS6 deficiency affects the tubulation and secretion of von Willebrand factor from mouse endothelial cells

Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation is regulated by HPS protein associated complexes such as BLOC (biogenesis of lysosome organelles complex) -1, -2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs. In this study, we found the defective, but varying, release of VWF into plasma after desmopressin (DDAVP) stimulation in HPS1 (BLOC-3 subunit), HPS6 (BLOC-2 subunit), and HPS9 (BLOC-1 subunit) deficient mice. In particular, VWF tubulation, a critical step in VWF maturation, was impaired in HPS6 deficient WPBs. This likely reflects a defective endothelium, contributing to the bleeding tendency in HPS mice or patients. The differentially defective regulated release of VWF in these HPS mouse models suggests the need for precise HPS genotyping before DDAVP administration to HPS patients

Corrigendum: Image-based siRNA screen to identify kinases regulating Weibel-Palade body size control using electroporation.

This corrects the article DOI: 10.1038/sdata.2017.22

The Origin of Black Hole Entropy in String Theory

I review some recent work in which the quantum states of string theory which are associated with certain black holes have been identified and counted. For large black holes, the number of states turns out to be precisely the exponential of the Bekenstein-Hawking entropy. This provides a statistical origin for black hole thermodynamics in the context of a potential quantum theory of gravity.Comment: 18 pages (To appear in the proceedings of the Pacific Conference on Gravitation and Cosmology, Seoul, Korea, February 1-6, 1996.

RGS4 controls secretion of von Willebrand factor to the subendothelial matrix

The haemostatic protein von Willebrand Factor (VWF) exists in plasma and subendothelial pools; the former secreted from endothelial storage granules, Weibel-Palade bodies (WPBs), by basal secretion with a contribution from agonist-stimulated secretion, the latter secreted into the subendothelial matrix by a constitutive pathway, not involving WPBs. We set out to determine if the constitutive release of subendothelial VWF is actually regulated and if so, what functional consequences this might have. Constitutive VWF secretion can be increased by a range of factors; changes in VWF expression, levels of TNF-alpha or other environmental cues. An RNAseq analysis revealed that expression of RGS4 (Regulator of G protein signalling 4) was reduced in endothelial cells (HUVECs) grown under these conditions. si-RGS4 treatment of HUVECs increased constitutive basolateral secretion of VWF, probably by affecting the anterograde secretory pathway. In a simple model of endothelial damage we show that RGS4-silenced cells increased platelet recruitment onto the subendothelial matrix under flow. These results show that changes in RGS4 expression alter levels of subendothelial VWF, affecting platelet recruitment. This introduces a novel control over VWF function

Coming or going? Un-BLOC-ing delivery and recycling pathways during melanosome maturation

Melanosome biogenesis requires successive waves of cargo delivery from endosomes to immature melanosomes, coupled with recycling of the trafficking machinery. Dennis et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201605090) report differential roles for BLOC-1 and BLOC-3 complexes in delivery and recycling of melanosomal biogenetic components, supplying directionality to melanosome maturation

Shrinking Weibel‐Palade bodies prevents high platelet recruitment in assays using thrombotic thrombocytopenic purpura plasma

Background: Thrombotic thrombocytopenic purpura (TTP), caused by a genetic or autoimmune-driven lack of ADAMTS-13 activity, leads to high levels of the ultra-large von Willebrand factor (VWF) multimers produced by endothelial cells, causing excess platelet recruitment into forming thrombi, often with mortal consequences. Treatments include plasma infusion or replacement to restore ADAMTS-13 activity, or prevention of platelet recruitment to VWF. // Objectives: We tested a different approach, exploiting the unique cell biology of the endothelium. Upon activation, the VWF released by exocytosis of Weibel-Palade bodies (WPBs), transiently anchored to the cell surface, unfurls as strings into flowing plasma, recruiting platelets. Using plasma from patients with TTP increases platelet recruitment to the surface of cultured endothelial cells under flow. WPBs are uniquely plastic, and shortening WPBs dramatically reduces VWF string lengths and the recruitment of platelets. We wished to test whether the TTP plasma-driven increase in platelet recruitment would be countered by reducing formation of the longest WPBs that release longer strings. // Methods: Endothelial cells grown in flow chambers were treated with fluvastatin, one of 37 drugs shown to shorten WPBs, then activated under flow in the presence of platelets and plasma of either controls or patients with TTP. // Result: We found that the dramatic increase in platelet recruitment caused by TTP plasma is entirely countered by treatment with fluvastatin, shortening the WPBs. // Conclusions: This potential approach of ameliorating the endothelial contribution to thrombotic risk by intervening far upstream of hemostasis might prove a useful adjunct to more conventional and direct therapies

A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

BACKGROUND: The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. METHODS: A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. RESULTS: Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one subject. Nightmares and vivid dreams occurred in 8/18 subjects (44%), and were statistically more frequent during treatment with donepezil. CONCLUSIONS: In this small study, there was no statistically significant treatment effect of donepezil on the primary outcome measure (MMSE score at 12 weeks) in PCA patients, who appear to be particularly susceptible to the development of nightmares and vivid dreams when treated. TRIAL REGISTRATION: Trial registration: Current Controlled Trials ISRCTN22636071 . Retrospectively registered 19 May 2010