Enhancement of Photosynthetic Productivity by Quantum Dots Application

The challenge of climate change promotes use of carbon neutral fuels. Biofuels are made via fixing carbon dioxide via photosynthesis which is inefficient. Light trapping pigments use restricted light wavelengths. A study using the microalga Botryococcus braunii (which produces bio-oil), the bacterium Rhodobacter sphaeroides (which produces hydrogen), and the cyanobacterium Arthrospira platensis (for bulk biomass) showed that photosynthetic productivity was increased by up to 2.5-fold by upconverting unused wavelengths of sunlight via using quantum dots. For large scale commercial energy processes, a 100-fold cost reduction was calculated as the break-even point for adoption of classical QD technology into large scale photobioreactors (PBRs). As a potential alternative, zinc sulfide nanoparticles (NPs) were made using waste H2S derived from another process that precipitates metals from mine wastewaters. Biogenic ZnS NPs behaved identically to ZnS quantum dots with absorbance and emission maxima of 290 nm (UVB, which is mostly absorbed by the atmosphere) and 410 nm, respectively; the optimal wavelength for chlorophyll a is 430 nm. By using a low concentration of citrate (10 mM) during ZnS synthesis, the excitation wavelength was redshifted to 315 nm (into the UVA, 85% of which reaches the earth’s surface) with an emission peak of 425 nm, i.e., appropriate for photosynthesis. The potential for use in large scale photobioreactors is discussed in the light of current PBR designs, with respect to the need for durable UV-transmitting materials in appropriate QD delivery systems

Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review

BACKGROUND Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION PROSPERO 2020 CRD42020175648

Physical Activity Producing Low, but Not Medium or Higher, Vertical Impacts Is Inversely Related to BMI in Older Adults: Findings from a Multicohort Study

© 2018 Oxford University Press. All rights reserved. Background: High impact physical activity (PA) is thought to improve skeletal health, but its relation to other health outcomes are unclear. We investigated associations between PA impact magnitude and body mass index (BMI) in older adults. Methods: Data were taken from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), Hertfordshire Cohort Study, and MRC National Survey of Health and Development. Vertical acceleration peaks from 7-day hip-worn accelerometer recordings were used to classify PA as low (0.5 < g < 1.0g), medium (1 < g < 1.5g), or higher (=1.5g) impact. Cohort-specific associations of low, medium, and higher impact PA with BMI were examined using linear regressions and estimates combined using random-effects meta-analysis. Results: A total of 1182 participants (mean age = 72.7 years, 68% female) were included. Low, medium, and higher impact PA were inversely related to BMI in initial models. After adjustment for confounders and other impacts, low, but not medium or higher, impacts were inversely related to BMI (-0.31, p < .001: overall combined standard deviation change in BMI per doubling in the number of low impacts). In adjusted analyses of body composition measured by dual-energy X-ray absorptiometry in COSHIBA, low, but not medium or higher, impacts were inversely related to total body fat mass (-0.19, p < .001) and android:gynoid fat mass ratio (-0.16, p = .01), whereas high impact PA was weakly and positively associated with lean mass (0.05, p = .06). Conclusions: Greater exposure to PA producing low magnitude vertical impacts was associated with lower BMI and fat mass at older age. Low impact PA may help reduce obesity risk in older adults

Correlates of high-impact physical activity measured objectively in older British adults

© The Author(s) 2017. Background Exposure to higher magnitude vertical impacts is thought to benefit bone health. The correlates of this high-impact physical activity (PA) in later life are unknown. Methods Participants were from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Associations of demographic, behavioural, physiological and psychological factors with vertical acceleration peaks ≥1.5 g (i.e. high-impact PA) from 7-day hip-worn accelerometer recordings were examined using linear regression. Results A total of 1187 participants (mean age = 72.7 years, 66.6% females) were included. Age, sex, education, active transport, selfreported higher impact PA, walking speed and self-rated health were independently associated with high-impact PA whereas BMI and sleep quality showed borderline independent associations. For example, differences in log-high-impact counts were 0.50 (P < 0.001) for men versus women and -0.56 (P < 0.001) for worst versus best self-rated health. Our final model explained 23% of between-participant variance in high impacts. Other correlates were not associated with high-impact activity after adjustment. Conclusions Besides age and sex, several factors were associated with higher impact PA in later life. Our findings help identify characteristics of older people that might benefit from interventions designed to promote osteogenic PA

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Cell-Permeating α-Ketoglutarate Derivatives Alleviate Pseudohypoxia in Succinate Dehydrogenase-Deficient Cells▿

Succinate dehydrogenase (SDH) and fumarate hydratase (FH) are components of the tricarboxylic acid (TCA) cycle and tumor suppressors. Loss of SDH or FH induces pseudohypoxia, a major tumor-supporting event, which is the activation of hypoxia-inducible factor (HIF) under normoxia. In SDH- or FH-deficient cells, HIF activation is due to HIF1α stabilization by succinate or fumarate, respectively, either of which, when in excess, inhibits HIFα prolyl hydroxylase (PHD). To reactivate PHD, we focused on its substrate, α-ketoglutarate. We designed and synthesized cell-permeating α-ketoglutarate derivatives, which build up rapidly and preferentially in cells with a dysfunctional TCA cycle. This study shows that succinate- or fumarate-mediated inhibition of PHD is competitive and is reversed by pharmacologically elevating intracellular α-ketoglutarate. Introduction of α-ketoglutarate derivatives restores normal PHD activity and HIF1α levels to SDH-suppressed cells, indicating new therapy possibilities for the cancers associated with TCA cycle dysfunction