Intersectin associates with synapsin and regulates its nanoscale localization and function.

Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery

Geologically constrained evolutionary geomechanical modelling of diapir and basin evolution: a case study from the Tarfaya basin, West African coast

We systematically incorporate burial history, sea floor geometry and tectonic loads from a sequential kinematic restoration model into a 2D evolutionary geomechanical model that simulates the formation of the Sandia salt diapir, Tarfaya basin, NW African Coast. We use a poro-elastoplastic description for the sediment behaviour and a viscoplastic description for the salt. Sedimentation is coupled with salt flow and regional shortening to determine the sediment porosity and strength and to capture the interaction between salt and sediments. We find that temporal and spatial variation in sedimentation rate is a key control on the kinematic evolution of the salt system. Incorporation of sedimentation rates from the kinematic restoration at a location east of Sandia leads to a final geomechanical model geometry very similar to that observed in seismic reflection data. We also find that changes in the variation of shortening rates can significantly affect the present-day stress state above salt. Overall, incorporating kinematic restoration data into evolutionary models provides insights into the key parameters that control the evolution of geologic systems. Furthermore, it enables more realistic evolutionary geomechanical models, which, in turn, provide insights into sediment stress and porosity

7th Annual Seminar on Securities Law

Materials from the UK/CLE 7th Annual Seminar on Securities Law held February 12-13, 1988

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure

Ketahanan Sumberdaya Genetik Jagung Sulawesi Tenggara terhadap Cekaman Kekeringan pada Berbagai Fase Vegetatif

Maize crops experiencing water stress can experience cell damage, loss of turgor, closed stomata, plant leaf roll then wilt. Germination and vegetative growth are thought to be a very sensitive phases in relation to the availability of water, because it can influence subsequent growth processes. This study aimed to determine the potential tolerance of Southeast Sulawesi\u27s maize genotypes to drought stress at different vegetative growth phases. This study was based on completely randomized design (CRD) with factorial pattern consisting of two factors: the first factor composed of 9 local maize genotypes of Southeast Sulawesi and 1 national variety (cv. Arjuna), while the second factor was drought stress at different vegetative growth phases, consisting of four levels ie: C0 = plants irrigated with 100 % water availability during the growth phase, C1 = Stress for 5 days , at 21-26 days old (vegetative phase), C2 = Stress for 5 days starting at panicle emergence (early flowering stage), and C3 = Stress for 5 days starting 2 weeks after silking. Research results showed that Genotype (G) treatment significantly influenced all observed growth variables (at age 21 and 42 days after planting, DAP), except for the variable of number of leaf, age 21 DAP. However, water stress treatment (C) only significantly affected plant height variable, at the age of 42 DAP. In general, G6 and G7 genotypes tended to have a higher crop and trunk diameter than the other genotypes. Contrary, G3 genotype tended to have shorter crop and smaller stem diameter than the other genotypes. There are indications that the drought stress treatment (C) significantly inhibited the growth of maize crops

Permeability correction factor for fractures with permeable walls

Enhanced Geothermal Systems (EGS) are based on the premise that heat can be extracted from hot dry rocks located at significant depths by circulating fluid through fracture networks in the system. Heated fluid is recovered through production wells and the energy is extracted in a heat exchange chamber. There is much published research on flow through fractures, and many models have been developed to describe an effective permeability of a fracture or a fracture network. In these cases however, the walls of the fracture were modelled as being impermeable. In this paper, we have extended our previous work on fractures with permeable walls, and we introduce a correction factor to the equation that governs fracture permeability. The solution shows that the effective fracture permeability for fractures with permeable walls depends not only on the height of the channel, but also on the wall permeability and the wall Reynolds number of the fluid. We show that our solution reduces to the established solution when the fracture walls become impermeable. We also extend the discussion to cover the effective permeability of a system of fractures with permeable walls.R. Mohais, C. Xu, P. A. Dowd, and M. Han

Morphological characterization of bushy cells and their inputs in the laboratory mouse (Mus musculus) anteroventral cochlear nucleus.

PMC3753269Spherical and globular bushy cells of the AVCN receive huge auditory nerve endings specialized for high fidelity neural transmission in response to acoustic events. Recent studies in mice and other rodent species suggest that the distinction between bushy cell subtypes is not always straightforward. We conducted a systematic investigation of mouse bushy cells along the rostral-caudal axis in an effort to understand the morphological variation that gives rise to reported response properties in mice. We combined quantitative light and electron microscopy to investigate variations in cell morphology, immunostaining, and the distribution of primary and non-primary synaptic inputs along the rostral-caudal axis. Overall, large regional differences in bushy cell characteristics were not found; however, rostral bushy cells received a different complement of axosomatic input compared to caudal bushy cells. The percentage of primary auditory nerve terminals was larger in caudal AVCN, whereas non-primary excitatory and inhibitory inputs were more common in rostral AVCN. Other ultrastructural characteristics of primary auditory nerve inputs were similar across the rostral and caudal AVCN. Cross sectional area, postsynaptic density length and curvature, and mitochondrial volume fraction were similar for axosomatic auditory nerve terminals, although rostral auditory nerve terminals contained a greater concentration of synaptic vesicles near the postsynaptic densities. These data demonstrate regional differences in synaptic organization of inputs to mouse bushy cells rather than the morphological characteristic of the cells themselves.JH Libraries Open Access Fun