Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6–81 kg km−2 a−1) than icebergs (0.0–1.2 kg km−2 a−1). Glacier-fed streams also export more acid-soluble iron (27.0–18,500 kg km−2 a−1) associated with suspended sediment than icebergs (0–241 kg km−2 a−1). Significant fluxes of filterable and sediment-derived iron (1–10 Gg a−1 and 100–1,000 Gg a−1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change

XIAP Protection of Photoreceptors in Animal Models of Retinitis Pigmentosa

BACKGROUND: Retinitis pigmentosa (RP) is a blinding genetic disorder that is caused by the death of photoreceptors in the outer nuclear layer of the retina. To date, 39 different genetic loci have been associated with the disease, and 28 mutated genes have been identified. Despite the complexity of the underlying genetic basis for RP, the final common pathway is photoreceptor cell death via apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, P23H and S334ter rhodopsin transgenic rat models of RP were used to test the neuroprotective effects of anti-apoptotic gene therapy. Adeno-associated viruses (AAV) carrying the X-linked inhibitor of apoptosis (XIAP) or green fluorescent protein (GFP) were delivered subretinally into the eye of transgenic rat pups. Histological and functional measures were used to assess neuroprotection. XIAP is known to block apoptosis by inhibiting the action of caspases-3, -7 and -9. The results show that XIAP gene therapy provides long-term neuroprotection of photoreceptors at both structural and functional levels. CONCLUSIONS/SIGNIFICANCE: Our gene therapy strategy targets the apoptotic cascade, which is the final common pathway in all forms of retinitis pigmentosa. This strategy holds great promise for the treatment of RP, as it allows for the broad protection of photoreceptors, regardless of the initial disease causing mutation

Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis ( XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages ( P = 0.0002) and also with tumour dedifferentiation ( P = 0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early ( pT1) to advanced ( pT3) tumour stages. Moreover, RCCs confined within the organ capsule ( pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney ( pT3; P = 0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.OncologySCI(E)46ARTICLE71349-13579

Home based exercise to improve turning and mobility performance among community dwelling older adults: protocol for a randomized controlled trial

Background: Turning is a common activity for older people, and is one of the activities commonly associated with falls during walking. Falls that occur while walking and turning have also been associated with an increased risk of hip fracture in older people. Despite the importance of stability during turning, there has been little focus on identifying this impairment in at risk older people, or in evaluating interventions aiming to improve this outcome. This study will evaluate the effectiveness of a 16 week tailored home based exercise program in older adults aged (50 years and above) who were identified as having unsteadiness during turning.Methods/Design: A single blind randomized controlled trial will be conducted, with assessors blind to group allocation. Study participants will be aged 50 years and above, living in the community and have been identified as having impaired turning ability [outside of age and gender normal limits on the Step Quick Turn (180 degree turn) task on the Neurocom® Balance Master with long plate]. After a comprehensive baseline assessment, those classified as having balance impairment while turning will be randomized to intervention or control group. The intervention group will receive a 16 week individualized balance and strength home exercise program, based on the Otago Exercise Program with additional exercises focused on improving turning ability. Intervention group will attend four visit to the assessment centre over 16 weeks period, for provision, monitoring, modification of the exercise and encourage ongoing participation. Participants in the control group will continue with their usual activities. All participants will be re-assessed on completion of the 16 week program. Primary outcome measures will be the Step Quick Turn Test and Timed-Up and Go test. Secondary outcomes will include other clinical measures of balance, psychological aspects of falls, incidence of falls and falls risk factors. Discussion: Results of this study will provide useful information for clinicians on the types of exercises to improve turning ability in older people with increased falls risk and the effectiveness of these exercises in improving outcomes