Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption.
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the “epidemic of diagnosis.” Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017. © 2017 American Cancer Society.
Social insects make elaborate use of simple mechanisms to achieve seemingly complex behavior and may thus provide a unique resource to discover the basic cognitive elements required for culture, i.e., group-specific behaviors that spread from “innovators” to others in the group via social learning. We first explored whether bumblebees can learn a nonnatural object manipulation task by using string pulling to access a reward that was presented out of reach. Only a small minority “innovated” and solved the task spontaneously, but most bees were able to learn to pull a string when trained in a stepwise manner. In addition, naïve bees learnt the task by observing a trained demonstrator from a distance. Learning the behavior relied on a combination of simple associative mechanisms and trial-and-error learning and did not require “insight”: naïve bees failed a “coiled-string experiment,” in which they did not receive instant visual feedback of the target moving closer when tugging on the string. In cultural diffusion experiments, the skill spread rapidly from a single knowledgeable individual to the majority of a colony’s foragers. We observed that there were several sequential sets (“generations”) of learners, so that previously naïve observers could first acquire the technique by interacting with skilled individuals and, subsequently, themselves become demonstrators for the next “generation” of learners, so that the longevity of the skill in the population could outlast the lives of informed foragers. This suggests that, so long as animals have a basic toolkit of associative and motor learning processes, the key ingredients for the cultural spread of unusual skills are already in place and do not require sophisticated cognition.
Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however, direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of magnetic resonance image-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) and included 527 individuals aged 20-87 years. Cortical reconstruction techniques were used to generate measures of whole-brain cerebral white-matter volume, cortical thickness, and surface area. Results indicated that cerebral white-matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle-age corresponding to an estimated increase of brain age of 10 years. There were no similar body mass index-related changes in cortical parameters. This study suggests that at a population level, obesity may increase the risk of neurodegeneration.
Cat-scratch disease (CSD) is mostly preventable. More information about the epidemiology and extent of CSD would help direct prevention efforts to those at highest risk. To gain such information, we reviewed the 2005-2013 MarketScan national health insurance claims databases and identified patients <65 years of age with an inpatient admission or outpatient visit that included a CSD code from the International Classification of Diseases, Ninth Revision, Clinical Modification. Incidence of CSD was highest among those who lived in the southern United States (6.4 cases/100,000 population) and among children 5-9 years of age (9.4 cases/100,000 population). Inpatients were significantly more likely than outpatients to be male and 50-64 years of age. We estimate that each year, 12,000 outpatients are given a CSD diagnosis and 500 inpatients are hospitalized for CSD. Prevention measures (e.g., flea control for cats) are particularly helpful in southern states and in households with children.
The gecko genus Geckolepis, endemic to Madagascar and the Comoro archipelago, is taxonomically challenging. One reason is its members ability to autotomize a large portion of their scales when grasped or touched, most likely to escape predation. Based on an integrative taxonomic approach including external morphology, morphometrics, genetics, pholidosis, and osteology, we here describe the first new species from this genus in 75 years: Geckolepis megalepissp. nov. from the limestone karst of Ankarana in northern Madagascar. The new species has the largest known body scales of any gecko (both relatively and absolutely), which come off with exceptional ease. We provide a detailed description of the skeleton of the genus Geckolepis based on micro-Computed Tomography (micro-CT) analysis of the new species, the holotype of G. maculata, the recently resurrected G. humbloti, and a specimen belonging to an operational taxonomic unit (OTU) recently suggested to represent G. maculata. Geckolepis is characterized by highly mineralized, imbricated scales, paired frontals, and unfused subolfactory processes of the frontals, among other features. We identify diagnostic characters in the osteology of these geckos that help define our new species and show that the OTU assigned to G. maculata is probably not conspecific with it, leaving the taxonomic identity of this species unclear. We discuss possible reasons for the extremely enlarged scales of G. megalepis in the context of an anti-predator defence mechanism, and the future of Geckolepis taxonomy.
Sea surface temperature (SST) records are subject to potential biases due to changing instrumentation and measurement practices. Significant differences exist between commonly used composite SST reconstructions from the National Oceanic and Atmospheric Administration’s Extended Reconstruction Sea Surface Temperature (ERSST), the Hadley Centre SST data set (HadSST3), and the Japanese Meteorological Agency’s Centennial Observation-Based Estimates of SSTs (COBE-SST) from 2003 to the present. The update from ERSST version 3b to version 4 resulted in an increase in the operational SST trend estimate during the last 19 years from 0.07° to 0.12°C per decade, indicating a higher rate of warming in recent years. We show that ERSST version 4 trends generally agree with largely independent, near-global, and instrumentally homogeneous SST measurements from floating buoys, Argo floats, and radiometer-based satellite measurements that have been developed and deployed during the past two decades. We find a large cooling bias in ERSST version 3b and smaller but significant cooling biases in HadSST3 and COBE-SST from 2003 to the present, with respect to most series examined. These results suggest that reported rates of SST warming in recent years have been underestimated in these three data sets.
Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian-Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America.
Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.
Computer imaging techniques are commonly used to preserve and share readable manuscripts, but capturing writing locked away in ancient, deteriorated documents poses an entirely different challenge. This software pipeline-referred to as “virtual unwrapping”-allows textual artifacts to be read completely and noninvasively. The systematic digital analysis of the extremely fragile En-Gedi scroll (the oldest Pentateuchal scroll in Hebrew outside of the Dead Sea Scrolls) reveals the writing hidden on its untouchable, disintegrating sheets. Our approach for recovering substantial ink-based text from a damaged object results in readable columns at such high quality that serious critical textual analysis can occur. Hence, this work creates a new pathway for subsequent textual discoveries buried within the confines of damaged materials.