Capping protein binding to actin in yeast: biochemical mechanism and physiological relevance

The mechanism by which capping protein (CP) binds barbed ends of actin filaments is not understood, and the physiological significance of CP binding to actin is not defined. The CP crystal structure suggests that the COOH-terminal regions of the CP α and β subunits bind to the barbed end. Using purified recombinant mutant yeast CP, we tested this model. CP lacking both COOH-terminal regions did not bind actin. The α COOH-terminal region was more important than that of β. The significance of CP's actin-binding activity in vivo was tested by determining how well CP actin-binding mutants rescued null mutant phenotypes. Rescue correlated well with capping activity, as did localization of CP to actin patches, indicating that capping is a physiological function for CP. Actin filaments of patches appear to be nucleated first, then capped with CP. The binding constants of yeast CP for actin suggest that actin capping in yeast is more dynamic than in vertebrates

Prospectus, February 22, 1984

MILLER SAYS TAX ABATEMENT NOT EQUITABLE FOR OTHER COUNTIES: REQUEST FOR TAX ABATEMENT DENIED BY PARKLAND BOARD; News Digest; Mayor Markland concered about area landfill issue; Meet the Prospectus Staff; PC Happenings: Professor to speak at Parkland, Testing for self knowledge, Computer workshop offered at Parkland, EMT workshop at Parkland; Which is better juvenile and pointless; Letter; Sonja Williams--views on Nicaragua; Yaxley scholarship; In the Library-- PS section; \u27I was only gone a minute\u27; Contraceptives--become aware of your choices; Internships produce anxieties; Did You Know...; Archaeology trip a success; Alabama shines at Assembly Hall; Creative Corner...Especially for you!!: Fleeting Moments, Untitled, Reflections and contemplations, Down, down, down, The Talkers , My Grandfather, Windows From the Soul, Realities, Banging heads on the floor with you...; Moore of the same; \u27Alabama\u27 succeeds at local concert; \u27I Write Your Name\u27 Carroll album released; Hitchcock\u27s classic revisited in the film \u27Vertigo\u27; Classifieds; More than tickets...; I.M.; Movie Magazine in next issue; Men\u27s Basketball season 20-11; Men\u27s track team places third; Parkland to host basket ball tournament; Women\u27s track team 2nd in region; Fitness Center to openhttps://spark.parkland.edu/prospectus_1984/1030/thumbnail.jp

Radioprotectant Activity of 5-Diethylsulfonamoylsalicylatocopper(II) in Gamma Irradiated Mice

Survival and changes in mean body mass of whole-body irradiated mice were determined to examine the radioprotectant activity of 5-diethylsulfonamoylsalicylatocopper(II) [Cu(II) (5-DESS)]. One of four groups of 25 female C57BL/6 mice were treated subcutaneously (sc)with 0, 10, 20, 40, 60, 80, 100, or 120 μmol Cu(II)(5- DESS)/kg of body mass 3 hours before exposure to 8.0 Gy, gamma irradiation. In this paradigm, doses of Cu(II)(5- DESS) increased survival up to 92% above vehicle-treated control mice (P = 0.008). Mean body mass determinations revealed that mice treated with 80 to 120 μmol Cu(II)(5-DESS)/kg of body mass exhibited a smaller decrease in body mass than other complex-treated groups. These results support the hypothesis that Cu(II)(5-DESS) is an effective radioprotectant

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Draft genome sequence of marine alphaproteobacterial strain HIMB11, the first cultivated representative of a unique lineage within the Roseobacter clade possessing an unusually small genome

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Standards in Genomic Sciences 9 (2014): 632-645, doi:10.4056/sigs.4998989.Strain HIMB11 is a planktonic marine bacterium isolated from coastal seawater in Kaneohe Bay, Oahu, Hawaii belonging to the ubiquitous and versatile Roseobacter clade of the alphaproteobacterial family Rhodobacteraceae. Here we describe the preliminary characteristics of strain HIMB11, including annotation of the draft genome sequence and comparative genomic analysis with other members of the Roseobacter lineage. The 3,098,747 bp draft genome is arranged in 34 contigs and contains 3,183 protein-coding genes and 54 RNA genes. Phylogenomic and 16S rRNA gene analyses indicate that HIMB11 represents a unique sublineage within the Roseobacter clade. Comparison with other publicly available genome sequences from members of the Roseobacter lineage reveals that strain HIMB11 has the genomic potential to utilize a wide variety of energy sources (e.g. organic matter, reduced inorganic sulfur, light, carbon monoxide), while possessing a reduced number of substrate transporters.We gratefully acknowledge the support of the Gordon and Betty Moore Foundation, which funded the sequencing of this genome. Annotation was performed as part of the 2011 C-MORE Summer Course in Microbial Oceanography (http://cmore.soest.hawaii.edu/summercourse/2011/index.htm), with support by the Agouron Institute, the Gordon and Betty Moore Foundation, the University of Hawaii and Manoa School of Ocean and Earth Science and Technology (SOEST), and the Center for Microbial Oceanography: Research and Education (C-MORE), a National Science Foundation-funded Science and Technology Center (award No. EF0424599)

The self-reference effect in dementia: Differential involvement of cortical midline structures in Alzheimer’s disease and behavioural-variant frontotemporal dementia

Encoding information in reference to the self enhances subsequent memory for the source of this information. In healthy adults, self-referential processing has been proposed to be mediated by the cortical midline structures (CMS), with functional differentiation between anterior-ventral, anterior-dorsal and posterior regions. While both Alzheimer’s disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) patients show source memory impairment, it remains unclear whether they show a typical memory advantage for self-referenced materials. We also sought to identify the neural correlates of this so-called ‘self-reference effect’ (SRE) in these patient groups. The SRE paradigm was tested in AD (n=16) and bvFTD (n=22) patients and age-matched healthy controls (n=17). In this task, participants studied pictures of common objects paired with one of two background scenes (sources) under self-reference or other-reference encoding instructions, followed by an item and source recognition memory test. Voxel-based morphometry was used to investigate correlations between SRE measures and regions of grey matter atrophy in the CMS. The behavioural results indicated that self-referential encoding did not ameliorate the significant source memory impairments in AD and bvFTD patients. Furthermore, the reduced benefit of self-referential relative to other-referential encoding was not related to general episodic memory deficits. Our imaging findings revealed that reductions in the SRE were associated with atrophy in the anterior-dorsal CMS across both patient groups, with additional involvement of the posterior CMS in AD and anterior-ventral CMS in bvFTD. These findings suggest that although the SRE is comparably reduced in AD and bvFTD, this arises due to impairments in different subcomponents of self-referential processing

Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients

Myasthenia Gravis (MG) is mediated by autoantibodies against acetylcholine receptors that cause loss of the receptors in the neuromuscular junction. Eculizumab, a C5-inhibitor, is the only approved treatment for MG that mechanistically addresses complement-mediated loss of nicotinic acetylcholine receptors. It is an expensive drug and was approved despite missing the primary efficacy endpoint in the Phase 3 REGAIN study. There are two observations to highlight. Firstly, further C5 inhibitors are in clinical development, but other terminal pathway proteins, such as C7, have been relatively understudied as therapeutic targets, despite the potential for lower and less frequent dosing. Secondly, given the known heterogenous mechanisms of action of autoantibodies in MG, effective patient stratification in the REGAIN trial may have provided more favorable efficacy readouts. We investigated C7 as a target and assessed the in vitro function, binding epitopes and mechanism of action of three mAbs against C7. We found the mAbs were human, cynomolgus monkey and/or rat cross-reactive and each had a distinct, novel mechanism of C7 inhibition. TPP1820 was effective in preventing experimental MG in rats in both prophylactic and therapeutic dosing regimens. To enable identification of MG patients that are likely to respond to C7 inhibition, we developed a patient stratification assay and showed in a small cohort of MG patients (n=19) that 63% had significant complement activation and C7-dependent loss of AChRs in this in vitro set up. This study provides validation of C7 as a target for treatment of MG and provides a means of identifying patients likely to respond to anti-C7 therapy based on complement-activating properties of patient autoantibodies

Exploring the development of a cultural care framework for European caring science

The aim of this paper is to discuss the development of a cultural care framework that seeks to inform and embrace the philosophical ideals of caring science. Following a review of the literature that identified a lack of evidence of an explicit relationship between caring science and cultural care, a number of well-established transcultural care frameworks were reviewed. Our purpose was to select one that would resonate with underpinning philosophical values of caring science and that drew on criteria generated by the European Academy of Caring Science members. A modified framework based on the work of Giger and Davidhizar was developed as it embraced many of the values such as humanism that are core to caring science practice. The proposed caring science framework integrates determinants of cultural lifeworld-led care and seeks to provide clear directions for humanizing the care of individuals. The framework is offered to open up debate and act as a platform for further academic enquiry