Bundling of actin filaments by aorta caldesmon is not related to its regulatory function

AbstractCa2+-sensitive thin filaments from vascular smooth muscle were disassembled into their constituent proteins, actin, tropomyosin and caldesmon. Caldesmon bound to both actin and to actin-tropomyosin and inhibited actin-tropomyosin activation of skeletal muscle myosin MgATPase. It also promoted the aggregation of actin or actin-tropomyosin into parallel aligned bundles. Quantitative electron microscopy measurements showed that with 1.1 μM actin-tropomyosin, 1.6 ± 0.5% (n = 3) of the filaments were in bundles. At 0.073 μM, caldesmon inhibited MgATPase activity by 50%, whereas bundling was 3.0 ± 1.3% (n = 4). At 0.37 μM caldesmon, MgATPase inhibition was 83% while 28.1 ± 6.9% (n = 4) of filaments were in bundles. Experiments at 4.4 μM in which MgATPase and bundling were measured in the same samples gave similar results. Small bundles of 2–3 filaments showed the most frequent occurrence at 1.1 μM actin. At 4.4 μM actin the most common bundle size was 3-5 filaments, with the occasional occurrence of large bundles consisting of up to 120 filaments. The incidence of bundling was the same in the presence and absence of tropomyosin. Thus caldesmon can induce the formation of actin bundles but this property bears no relationship to its inhibition of MgATPase activity

Revisiting Global Information Systems Management Education

Business enterprises continue to globalize, motivated by their search for new markets, greater efficiency in the use of resources, and greater competitiveness. Information systems and technologies serve as one of the critical success factors for making this possible. Some IS curricula supported this development by either integrating more globalization into current courses or by delivering stand-alone courses in Global IS Management as electives or requirements. The purpose of this paper is to review and propose best practices for the Global IS Management course, and consider contingencies that can be expected to influence the choice and success of various approaches. The paper provides a categorization of such courses based on differences in education level (graduate/undergraduate) and student population (MIS/InternationalBusiness/ mixed). We discuss experiences with approaches and practices that work across these segments, and activities targeted to each segment. The paper revisits and argues for the need to expand this curriculum, and provides practical details for MIS faculty who seek to integrate it into their own programs

Gettysburg College Sustainability Proposal

In the fall of 2011, the Environmental Studies capstone class led by Professor Rutherford Platt was asked to write Gettysburg College’s first Sustainability Plan. The goal of the plan was to develop specific sustainable practices for the campus that were related to the three pillars of sustainability: economic, social, and environmental, and how integrating diligent sustainable practices into each of these respected pillars will result in a more conscious campus, community, and future. In 2010, Gettysburg College turned to the Sustainability Tracking Assessment and Rating System (STARS) to quantify the institution’s sustainability efforts, providing a self-check mechanism to encourage sustainability applications to all aspects of the College. The American College and University Presidents’ Climate Commitment was signed in 2007 by former Gettysburg College President Katherine Haley Will, declaring that Gettysburg College would become carbon neutral by 2032. Gettysburg College has made large strides in the search for sustainability, and aims to continue its dedication to furthering sustainable practice. The following plan outlines the six priority areas identified by the Capstone class: progress of the American College and University Presidents’ Climate Commitment, Dining Services, campus green space, community outreach, integration of sustainability into the Gettysburg College Curriculum, and the Sustainability Advisory Committee. The first priority area identified was monitoring and upholding the American College and University Presidents’ Climate Commitment (ACUPCC). Though creating new sustainability initiatives on campus is the driving force towards an increasingly sustainable college and community, it is imperative that these goals be carried out in full to maximize beneficial returns. In order to reach carbon neutrality, Gettysburg College hopes to increase energy efficiency in buildings, incorporate renewable energy sources on campus, and mitigate remaining emissions through the purchase of carbon offsets. To further the College’s progress, it is proposed that Gettysburg College continue its energy-efficient appliance purchasing policy, as well as create a policy to offset all greenhouse gas emissions generated by air travel for students study abroad. As stated by the ACUPCC, a Sustainability Committee should take responsibility for the updates and progress reports required to meet the goal of carbon neutrality. The second priority area identified was sustainability in Dining Services. Gettysburg College is home to 2,600 students, all of whom require three full meals a day. Dining Services accounts for a large fraction of Gettysburg College’s sustainability efforts, already implementing sustainability through composting, buying local produce, and using biodegradable products. The proposed on-campus sales cuts of non-reusable to-go items, a change in campus mentality on food waste, and improved composting practices will translate to an increasingly sustainable campus, as well as a well-fed campus body. The third priority was maintaining green space on campus. Ranked as the 23rd most beautiful campus in the United States by The Best Colleges, Gettysburg College utilizes campus green space to create an atmosphere that is conducive to activity as well as tranquility. The plan proposes that Gettysburg College and its grounds facilities continue their exceptional efforts, focusing on increasing the use of the student garden, creating a new rain garden or social area on campus, and converting unnecessary parking lots into green space. As these additions are completed, they must be introduced to the student body and faculty alike to assure these areas are known and utilized. The fourth priority was utilizing community outreach to spread awareness of sustainability initiatives on and off campus. To connect the sustainability-geared changes proposed in this plan, community outreach at Gettysburg College is assessed to estimate how well these initiatives are communicated and promoted to both potential and enrolled students, faculty, and other concerned parties. To evaluate the efficiency of communication at Gettysburg College, a quantitative assessment is presented to measure the ease of finding the sustainability webpage, the quality of sustainability-related topics available on the webpage, and quality of webpage design. The webpage is in need of improved text to image ratios, locations of sustainability topics, and data displays. Despite not having a link to the sustainability webpage on the Gettysburg College homepage, sustainability events should be covered and presented on the rotational news feed found on the homepage to maximize outreach to interested parties or simply to add to the definition of Gettysburg College. The fifth priority was integrating sustainability into the Curriculum to build a culture on campus that values academic rigor, supports students as they cultivate intellectual and civic passions, and promotes the development of healthy social relationships and behaviors. The proposed Sustainability Committee on Sustainability in the Curriculum (SCC) will hold sustainability workshops for faculty with the aim to instill sustainability into all academic disciplines, providing all Gettysburg graduates with a means to approach their professional careers in a fashion that is conscious of sustainability. The sixth and last priority was the Sustainability Advisory Committee. Established in 2007, the Sustainability Advisory Committee is currently under review, but it is recommended that the committee restructure itself in accordance with the new Sustainability Committee Bylaws. These bylaws aim to define the purposes, membership, governance, and involvement with the college. With a clearly defined set of goals and methodology, the Sustainability Advisory Committee will be able to improve the solidarity of the sustainability movement on campus as a whole. By following the propositions laid out in the Gettysburg College Sustainability Plan, the student body, faculty, and community alike will become a part of a multi-faceted progression toward a more sustainable future

Is stroke early supported discharge still effective in practice? A prospective comparative study

Objective: Randomised controlled trials have shown the benefits of Early Supported Discharge (ESD) of stroke survivors. Our aim was to evaluate whether ESD is still beneficial when operating in the complex context of frontline healthcare provision. Design: We conducted a cohort study with quasi experimental design. A total of 293 stroke survivors (transfer independently or with assistance of one, identified rehabilitation goals) within two naturally formed groups were recruited from two acute stroke units: ‘ESD’ n=135 and ‘Non ESD’ n=158 and 84 caregivers. The ‘ESD’ group accessed either of two ESD services operating in Nottinghamshire, UK. The ‘Non ESD’ group experienced standard practices for discharge and onward referral. Outcome measures (primary: Barthel Index) were administered at baseline, 6 weeks, 6 months and 12 months. Results: The ESD group had a significantly shorter length of hospital stay (P=0.029) and reported significantly higher levels of satisfaction with services received (P<0.001). Following adjustment for age differences at baseline, participants in the ESD group (n=71) had significantly higher odds (compared to the Non ESD group, n=85) of being in the ⩾90 Barthel Index category at 6 weeks (OR = 1.557, 95% CI 2.579 to 8.733), 6 months (OR = 1.541, 95% CI 2.617 to 8.340) and 12 months (OR 0.837, 95% CI 1.306 to 4.087) respectively in relation to baseline. Carers of patients accessing ESD services showed significant improvement in mental health scores (P<0.01). Conclusion: The health benefits of ESD are still evident when evidence based models of these services are implemented in practice

Mycobacterium tuberculosis pks12 Produces a Novel Polyketide Presented by CD1c to T Cells

CD1c-mediated T cells are activated by a mycobacterial phospholipid antigen whose carbohydrate structure precisely corresponds to mammalian mannosyl β-1-phosphodolichol (MPD), but contains an unusual lipid moiety. Here, we show that this T cell antigen is a member of a family of branched, alkane lipids that vary in length (C30-34) and are produced by medically important mycobacteria such as M. tuberculosis and M. bovis Bacille-Calmette-Guerin. The alkane moiety distinguished these mycobacterial lipid antigens from mammalian MPDs and was necessary for activation of CD1c-restricted T cells, but could not be accounted for by any known lipid biosynthetic pathway. Metabolic labeling and mass spectrometric analyses suggested a mechanism for elongating lipids using alternating C2 and C3 units, rather than C5 isopentenyl pyrophosphate. Inspection of the M. tuberculosis genome identified one candidate gene, pks12, which was predicted to encode the largest protein in M. tuberculosis, consisting of 12 catalytic domains that correspond to key steps in the proposed pathway. Genetic deletion and complementation showed that Pks12 was necessary for antigen production, but did not affect synthesis of true isoprenols. These studies establish the genetic and enzymatic basis for a previously unknown type of polyketide, designated mycoketide, which contains a lipidic pathogen-associated molecular pattern

Carbon concentrations in natural and restoration pools in blanket peatlands

Open-water perennial pools are common natural features of peatlands globally, and peatland restoration often results in new pool creation, yet the concentrations of different forms of aquatic carbon (C) in natural and artificial restoration pools are not well studied. We compared carbon concentrations in both natural pools and restoration pools (4–15 years old) on three blanket peatlands in northern Scotland. At all sites, restoration pools were more acidic and had mean dissolved organic carbon (DOC) concentrations in restoration pools of 23, 22, and 31 mg L−1 compared with natural pool means of 11, 11 and 15 mg L−1 respectively across the three sites. Restoration pools had a greater fulvic acid prevalence than the natural pools and their DOC was more aromatic. Restoration pools were supersaturated with dissolved CO2 at around 10 times atmospheric levels, whereas for natural pools, CO2 concentrations were just above atmospheric levels. Dissolved CH4 concentrations were not different between pool types, but were ~200 times higher than atmospheric levels. Regular sampling at one of the peatland sites over 2.5 years showed that particulate organic carbon (POC) concentrations were generally below 7 mg L−1 except during the warm, dry summer of 2013. At this regularly-sampled site, natural pools were found to process DOC so that mean pool outflow concentrations in overland flow were significantly lower than mean inflow DOC concentrations. Such an effect was not found for the restoration pools. Soil solution and pool water chemistry, and relationships between DOC and CO2 concentrations suggest that different processes are controlling the transformation of C, and therefore the form and amount of C, in natural pools compared to restoration pools

Maximising the Potential of Longitudinal Cohorts for Research in Neurodegenerative Diseases: A Community Perspective

Despite a wealth of activity across the globe in the area of longitudinal population cohorts, surprisingly little information is available on the natural biomedical history of a number of age-related neurodegenerative diseases (ND), and the scope for intervention studies based on these cohorts is only just beginning to be explored. The Joint Programming Initiative on Neurodegenerative Disease Research (JPND) recently developed a novel funding mechanism to rapidly mobilise scientists to address these issues from a broad, international community perspective. Ten expert Working Groups, bringing together a diverse range of community members and covering a wide ND landscape (Alzheimer’s, Parkinson’s, frontotemporal degeneration, amyotrophic lateral sclerosis, Lewy-body and vascular dementia) were formed to discuss and propose potential approaches to better exploiting and coordinating cohort studies. The purpose of this work is to highlight the novel funding process along with a broad overview of the guidelines and recommendations generated by the ten groups, which include investigations into multiple methodologies such as cognition/functional assessment, biomarkers and biobanking, imaging, health and social outcomes, and pre-symptomatic ND. All of these were published in reports that are now publicly available online.The EU Joint Programming Initiative on Neurodegenerative Disease Research (JPND) supported the ten Working Groups described in this manuscript with funding from the following: The Canadian Institutes of Health Research (CIHR), French National Research Agency (ANR), German Federal Ministry of Education and Research (BMBF), Innovation Fund Denmark, Italian Ministry of Health (IT-MOH), Luxembourg National Research Fund (FNR), Netherlands Organisation for Health Research and Development (ZonMw), Research Council of Norway, Swedish Research Council for Health, Working Life and Welfare, and UK Medical Research Council (MRC)

Water-level dynamics in natural and artificial pools in blanket peatlands

Perennial pools are common natural features of peatlands and their hydrological functioning and turnover may be important for carbon fluxes, aquatic ecology and downstream water quality. Peatland restoration methods such as ditch blocking result in many new pools. However, little is known about the hydrological function of either pool type. We monitored six natural and six artificial pools on a Scottish blanket peatland. Pool water levels were more variable in all seasons in artificial pools having greater water level increases and faster recession responses to storms than natural pools. Pools overflowed by a median of 9 and 54 times pool volume per year for natural and artificial pools respectively but this varied widely because some large pools had small upslope catchments and vice versa. Mean peat water-table depths were similar between natural and artificial pool sites but much more variable over time at the artificial pool site, possibly due to a lower bulk specific yield across this site. Pool levels and pool-level fluctuations were not the same as those of local water tables in the adjacent peat. Pool level time-series were much smoother, with more damped rainfall or recession responses than those for peat water tables. There were strong hydraulic gradients between the peat and pools, with absolute water tables often being 20-30 cm higher or lower than water levels in pools only 1-4 m away. However, as peat hydraulic conductivity was very low (median of 1.5×10-5 and 1.4×10-6 cm s-1 at 30 and 50 cm depths at the natural pool site) there was little deep subsurface flow interaction. We conclude that: 1) for peat restoration projects, a larger total pool surface area is likely to result in smaller flood peaks downstream, at least during summer months, because peatland bulk specific yield will be greater; and 2) surface and near-surface connectivity during storm events and topographic context, rather than pool size alone, must be taken into account in future peatland pool and stream chemistry studies

Prevalence of plasmodium falciparum in active conflict areas of eastern Burma: a summary of cross-sectional data

BACKGROUND: Burma records the highest number of malaria deaths in southeast Asia and may represent a reservoir of infection for its neighbors, but the burden of disease and magnitude of transmission among border populations of Burma remains unknown. METHODS: Plasmodium falciparum (Pf) parasitemia was detected using a HRP-II antigen based rapid test (Paracheck-Pf(R)). Pf prevalence was estimated from screenings conducted in 49 villages participating in a malaria control program, and four retrospective mortality cluster surveys encompassing a sampling frame of more than 220,000. Crude odds ratios were calculated to evaluate Pf prevalence by age, sex, and dry vs. rainy season. RESULTS: 9,796 rapid tests were performed among 28,410 villagers in malaria program areas through four years (2003: 8.4%, 95% CI: 8.3 - 8.6; 2004: 7.1%, 95% CI: 6.9 - 7.3; 2005:10.5%, 95% CI: 9.3 - 11.8 and 2006: 9.3%, 95% CI: 8.2 - 10.6). Children under 5 (OR = 1.99; 95% CI: 1.93 - 2.06) and those 5 to 14 years (OR = 2.24, 95% CI: 2.18 - 2.29) were more likely to be positive than adults. Prevalence was slightly higher among females (OR = 1.04, 95% CI: 1.02 - 1.06) and in the rainy season (OR = 1.48, 95% CI: 1.16 - 1.88). Among 5,538 rapid tests conducted in four cluster surveys, 10.2% were positive (range 6.3%, 95% CI: 3.9 - 8.8; to 12.4%, 95% CI: 9.4 - 15.4). CONCLUSION: Prevalence of plasmodium falciparum in conflict areas of eastern Burma is higher than rates reported among populations in neighboring Thailand, particularly among children. This population serves as a large reservoir of infection that contributes to a high disease burden within Burma and likely constitutes a source of infection for neighboring regions