Follicular Delivery of Caffeine from a Shampoo for Hair Retention

A key factor in the prevention of hair loss is the provision of optimal conditions on the scalp. In this regard, reduction of oxidative stress on the scalp is one critical requirement to support the hair follicles to function optimally. Recently, a novel shampoo formulation technology containing anti-oxidants such as piroctone olamine has been demonstrated to improve hair retention based on micellar degradation and coacervation effects. Caffeine has also been shown to exhibit anti-oxidant activity including the ability to inhibit lipid peroxidation. As with piroctone olamine, it is expected that follicular delivery of caffeine will enhance its anti-oxidant activity in a region that will be beneficial for hair retention. In this study, two shampoo formulations as well as a control formulation were applied to the calf area of n = 9 male participants. The technique of differential tape stripping was applied to obtain the caffeine penetrated to the stratum corneum and to the hair follicles. Isotope-dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to demonstrate caffeine follicular delivery from the shampoo formulas. The results showed that the percentage of caffeine recovered in the hair follicles was 8–9% of the caffeine absorbed into the skin and matched an existing caffeine-based shampoo. In conclusion, a novel shampoo formulation technology has been developed that effectively delivers beneficial anti-oxidants to improve hair retention. This new shampoo is expected to be especially useful in the goal of retaining hair during aging

Identifying Elements of \u3cem\u3eKinder- und Jugendliteratur\u3c/em\u3e

Kinder- und Jugendliteratur, children’s literature written for the purpose of teaching or entertaining young people, has been present in German literature since the Middle Ages. This genre has changed as German literature progressed, reflecting the developments of each era, including such periods as the Romantic, the Biedermeier, Realism, Modernism and Postmodernism. As such, we examined individual works of German Kinder- und Jugendliteratur for the purpose of identifying distinctive features which situate them within children’s literature as well as in the respective historical genre. The works examined were Nußknacker und Mausekönig (1816) by E. T. A. Hoffmann, Emil und die Detektive (1929) by Erich Kästner, Försters Pucki (1935) by Madge Trott, Jan und das Wildpferd (1957) by Heinrich Denneborg, Die Wolke (1987) by Gudrun Pausewang, and Tintenherz (2003) by Cornelia Funke. We present our findings in the form of a Wimmelbuch, a typical form of German Kinder- und Jugendliteratur made popular during the Biedermeier period of the mid-1800s

Relationship between red blood cell lifespan and endogenous carbon monoxide in the common bottlenose dolphin and beluga

Certain deep-diving marine mammals (i.e., northern elephant seal (Mirounga angustirosis), Weddell seal (Leptonychotes weddellii)) have blood carbon monoxide (CO) levels that are comparable to those of chronic cigarette smokers. Most CO produced in humans is a by-product of heme degradation, which is released when red blood cells (RBC) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy, marine mammal species with different diving capacities and heme stores, the shallow diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga (Delphinapterus leucas) and relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared to humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared to humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long duration breath-holds

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration

Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic ‘gain of function’, such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases

Quantifying the extent to which index event biases influence large genetic association studies

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.As genetic association studies increase in size to 100,000s of individuals, subtle biases may influence conclusions. One possible bias is "index event bias" (IEB) that appears due to the stratification by, or enrichment for, disease status when testing associations between genetic variants and a disease-associated trait. We aimed to test the extent to which IEB influences some known trait associations in a range of study designs and provide a statistical framework for assessing future associations. Analysing data from 113,203 non-diabetic UK Biobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (BMI-decreasing) and one (near MTNR1B) underestimated (BMI-increasing) associations among 11 type 2 diabetes risk alleles (at P  500,000 if the prevalence of those diseases differs by > 10% from the background population. In conclusion, IEB may result in false positive or negative genetic associations in very large studies stratified or strongly enriched for/against disease cases.H.Y., A.R.W. and T.M.F. are supported by the European Research Council grant: 323195; SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). M.A.T., M.N.W. and A.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). R.M.F. is a Sir Henry Dale Fellow (Wellcome Trust and Royal Society grant: 104150/Z/14/Z). R.B. is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z. J.T. is funded by a Diabetes Research and Wellness Foundation Fellowship. Z.K. received financial support from the Leenaards Foundation, the Swiss Institute of Bioinformatics and the Swiss National Science Foundation (31003A-143914) and SystemsX.ch (39). The work of M.P.B was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award no. T32HL007779. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. E.R.P. holds a WT New investigator award 102820/Z/13/Z

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation

Background-In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results-Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. Conclusions-Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD even

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio