Using nexus thinking to identify opportunities for mangrove management in the Klang Islands, Malaysia

Despite wide recognition of the multiple ecosystem services provided by mangroves, they continue to experience decline and degradation especially in the face of urbanization. Given the interplay between multiple resources and stakeholders in the fate of mangroves, mangrove management can be framed as a nexus challenge and nexus thinking used to identify potential solutions. Using the Klang Islands, Malaysia, as a case study site, this paper characterizes the mangrove nexus and stakeholders visions for the future to identify potential options for future management. Through a series of stakeholder workshops and focus group discussions conducted over two years results show that local communities can identify benefits from mangroves beyond the provisioning of goods and significant impacts to their lives from mangrove loss. While better protected and managed mangroves remained a central part of participants' visions for the islands, participants foresaw a limited future for fishing around the islands, preferring instead alternative livelihood opportunities such as eco-tourism. The network of influencers of the Klang Islands’ mangroves extends far beyond the local communities and many of these actors were part of the visions put forward. Stakeholders with a high interest in the mangroves typically have a low influence over their management and many high influence stakeholders (e.g. private sector actors) were missing from the engagement. Future nexus action should focus on integrating stakeholders and include deliberate and concerted engagement with high influence stakeholders while at the same time ensuring a platform for high interest/low influence groups. Fortifying existing plans to include mangroves more explicitly will also be essential. Lessons learnt from this study are highly relevant for coastal mangrove systems elsewhere in the Southeast Asian region

Preliminary Clinical Results of a Biphasic Waveform and an RV Lead System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72921/1/j.1540-8159.1999.tb00500.x.pd

BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised. METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (<or=40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions. CONCLUSIONS: Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4-9%)

p21-Activated Kinases Are Required for Transformation in a Cell-Based Model of Neurofibromatosis Type 2

NF2 is an autosomal dominant disease characterized by development of bilateral vestibular schwannomas and other benign tumors in central nervous system. Loss of the NF2 gene product, Merlin, leads to aberrant Schwann cell proliferation, motility, and survival, but the mechanisms by which this tumor suppressor functions remain unclear. One well-defined target of Merlin is the group I family of p21-activated kinases, which are allosterically inhibited by Merlin and which, when activated, stimulate cell cycle progression, motility, and increased survival. Here, we examine the effect of Pak inhibition on cells with diminished Merlin function.Using a specific peptide inhibitor of group I Paks, we show that loss of Pak activity restores normal cell movement in cells lacking Merlin function. In addition, xenografts of such cells form fewer and smaller tumors than do cells without Pak inhibition. However, in tumors, loss of Pak activity does not reduce Erk or Akt activity, two signaling proteins that are thought to mediate Pak function in growth factor pathways.These results suggest that Pak functions in novel signaling pathways in NF2, and may serve as a useful therapeutic target in this disease

Treatment of isoniazid-resistant pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Although resistance to isoniazid (INH) is the most common form of drug resistance seen among <it>Mycobacterium tuberculosis </it>isolates, there have been few studies on the efficacy and optimal duration of treatment for patients with INH-resistant tuberculosis (TB).</p> <p>Methods</p> <p>We evaluated retrospectively the treatment outcomes of 39 patients who were treated for INH-resistant pulmonary TB. The treatment regimens consisted of a 12-month regimen of rifampin (RIF) and ethambutol (EMB), with pyrazinamide (PZA) given during the first 2 months (2HREZ/10RE) (<it>n </it>= 21), a 9-month regimen of RIF and EMB with PZA during the first 2 months (2HREZ/7RE) (<it>n </it>= 5), and a 6-month regimen of RIF, EMB, and PZA (2HREZ/4REZ) (<it>n </it>= 13). After drug susceptibility testing confirmed the INH-resistance of the isolated <it>M. tuberculosis </it>strains, INH was discontinued for all the patients.</p> <p>Results</p> <p>Among the 39 patients, treatment was successfully completed by 36 patients (92%). However, treatment failure occurred, and acquired resistance to other first-line drugs, such as RIF, developed in three patients (8%). Cavitary and bilateral extensive lesions were commonly found in the chest radiographs of the patients who exhibited treatment failure.</p> <p>Conclusion</p> <p>These findings underline the seriousness of concerns regarding treatment failure and the development of multidrug-resistant TB in patients with INH-resistant TB following treatment with recommended regimens.</p

Small-scale, semi-automated purification of eukaryotic proteins for structure determination

A simple approach that allows cost-effective automated purification of recombinant proteins in levels sufficient for functional characterization or structural studies is described. Studies with four human stem cell proteins, an engineered version of green fluorescent protein, and other proteins are included. The method combines an expression vector (pVP62K) that provides in vivo cleavage of an initial fusion protein, a factorial designed auto-induction medium that improves the performance of small-scale production, and rapid, automated metal affinity purification of His8-tagged proteins. For initial small-scale production screening, single colony transformants were grown overnight in 0.4 ml of auto-induction medium, produced proteins were purified using the Promega Maxwell 16, and purification results were analyzed by Caliper LC90 capillary electrophoresis. The yield of purified [U-15N]-His8-Tcl-1 was 7.5 μg/ml of culture medium, of purified [U-15N]-His8-GFP was 68 μg/ml, and of purified selenomethione-labeled AIA–GFP (His8 removed by treatment with TEV protease) was 172 μg/ml. The yield information obtained from a successful automated purification from 0.4 ml was used to inform the decision to scale-up for a second meso-scale (10–50 ml) cell growth and automated purification. 1H–15N NMR HSQC spectra of His8-Tcl-1 and of His8-GFP prepared from 50 ml cultures showed excellent chemical shift dispersion, consistent with well folded states in solution suitable for structure determination. Moreover, AIA–GFP obtained by proteolytic removal of the His8 tag was subjected to crystallization screening, and yielded crystals under several conditions. Single crystals were subsequently produced and optimized by the hanging drop method. The structure was solved by molecular replacement at a resolution of 1.7 Å. This approach provides an efficient way to carry out several key target screening steps that are essential for successful operation of proteomics pipelines with eukaryotic proteins: examination of total expression, determination of proteolysis of fusion tags, quantification of the yield of purified protein, and suitability for structure determination

Two Prp19-Like U-Box Proteins in the MOS4-Associated Complex Play Redundant Roles in Plant Innate Immunity

Plant Resistance (R) proteins play an integral role in defense against pathogen infection. A unique gain-of-function mutation in the R gene SNC1, snc1, results in constitutive activation of plant immune pathways and enhanced resistance against pathogen infection. We previously found that mutations in MOS4 suppress the autoimmune phenotypes of snc1, and that MOS4 is part of a nuclear complex called the MOS4-Associated Complex (MAC) along with the transcription factor AtCDC5 and the WD-40 protein PRL1. Here we report the immuno-affinity purification of the MAC using HA-tagged MOS4 followed by protein sequence analysis by mass spectrometry. A total of 24 MAC proteins were identified, 19 of which have predicted roles in RNA processing based on their homology to proteins in the Prp19-Complex, an evolutionarily conserved spliceosome-associated complex containing homologs of MOS4, AtCDC5, and PRL1. Among these were two highly similar U-box proteins with homology to the yeast and human E3 ubiquitin ligase Prp19, which we named MAC3A and MAC3B. MAC3B was recently shown to exhibit E3 ligase activity in vitro. Through reverse genetics analysis we show that MAC3A and MAC3B are functionally redundant and are required for basal and R protein–mediated resistance in Arabidopsis. Like mos4-1 and Atcdc5-1, mac3a mac3b suppresses snc1-mediated autoimmunity. MAC3 localizes to the nucleus and interacts with AtCDC5 in planta. Our results suggest that MAC3A and MAC3B are members of the MAC that function redundantly in the regulation of plant innate immunity

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung