1,370 research outputs found
Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia
Myopia, or nearsightedness, is the most common eye disorder, resulting
primarily from excess elongation of the eye. The etiology of myopia, although
known to be complex, is poorly understood. Here we report the largest ever
genome-wide association study (43,360 participants) on myopia in Europeans. We
performed a survival analysis on age of myopia onset and identified 19
significant associations (p < 5e-8), two of which are replications of earlier
associations with refractive error. These 19 associations in total explain 2.7%
of the variance in myopia age of onset, and point towards a number of different
mechanisms behind the development of myopia. One association is in the gene
PRSS56, which has previously been linked to abnormally small eyes; one is in a
gene that forms part of the extracellular matrix (LAMA2); two are in or near
genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are
near genes known to be involved in the growth and guidance of retinal ganglion
cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal
signaling or development. These novel findings point towards multiple genetic
factors involved in the development of myopia and suggest that complex
interactions between extracellular matrix remodeling, neuronal development, and
visual signals from the retina may underlie the development of myopia in
humans
Complexity of diatom response to Lateglacial and Holocene climate and environmental change in ancient, deep and oligotrophic Lake Ohrid (Macedonia and Albania)
© Author(s) 2016. Lake Ohrid (Macedonia and Albania) is a rare example of a deep, ancient Mediterranean lake and is a key site for palaeoclimate research in the northeastern Mediterranean region. This study conducts the analysis of diatoms as a proxy for Lateglacial and Holocene climate and environmental change in Lake Ohrid at a higher resolution than in previous studies. While Lake Ohrid has the potential to be sensitive to water temperature change, the data demonstrate a highly complex diatom response, probably comprising a direct response to temperature-induced lake productivity in some phases and an indirect response to temperaturerelated lake stratification or mixing and epilimnetic nutrient availability in others. The data also demonstrate the possible influence of physical limnological (e.g. the influence of wind stress on stratification or mixing) and chemical processes (e.g. the influence of catchment dynamics on nutrient input) in mediating the complex response of diatoms. During the Lateglacial (ca. 12 300-11 800 cal yr BP), the low-diversity dominance of hypolimnetic Cyclotella fottii indicates low lake productivity, linked to low water temperature. Although the subsequent slight increase in small, epilimnetic C. minuscula during the earliest Holocene (ca. 11 800-10 600 cal yr BP) suggests climate warming and enhanced stratification, diatom concentration remains as low as during the Lateglacial, suggesting that water temperature increase was muted across this major transition. The early Holocene (ca. 10 600-8200 cal yr BP) is characterised by a sustained increase in epilimnetic taxa, with mesotrophic C. ocellata indicating high water-temperature-induced productivity between ca. 10 600-10 200 cal yr BP and between ca. 9500-8200 cal yr BP and with C. minuscula in response to low nutrient availability in the epilimnion between ca. 10 200-9500 cal yr BP. During the middle Holocene (ca. 8200-2600 cal yr BP), when sedimentological and geochemical proxies provide evidence for maximum Holocene water temperature, anomalously low C. ocellata abundance is probably a response to epilimnetic nutrient limitation, almost mimicking the Lateglacial flora apart from the occurrence of mesotrophic Stephanodiscus transylvanicus in the hypolimnion. During the late Holocene (ca. 2600 cal yr BP-present), high abundance and fluctuating composition of epilimnetic taxa are probably a response more to enhanced anthropogenic nutrient input, particularly nitrogen enrichment, than to climate. Overall, the data indicate that previous assumptions concerning the linearity of diatom response in this deep, ancient lake are invalid, and multi-proxy analysis is essential to improve understanding of palaeolimnological dynamics in future research on the long, Quaternary sequence
Efficient Replication of Over 180 Genetic Associations with Self-Reported Medical Data
While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for amassing large amounts of medical information in a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggests that online collection of self-reported data in a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations
The Successful Operation of Hole-type Gaseous Detectors at Cryogenic Temperatures
We have demonstrated that hole-type gaseous detectors, GEMs and capillary
plates, can operate up to 77 K. For example, a single capillary plate can
operate at gains of above 10E3 in the entire temperature interval between 300
until 77 K. The same capillary plate combined with CsI photocathodes could
operate perfectly well at gains (depending on gas mixtures) of 100-1000.
Obtained results may open new fields of applications for capillary plates as
detectors of UV light and charge particles at cryogenic temperatures: noble
liquid TPCs, WIMP detectors or LXe scintillating calorimeters and cryogenic
PETs.Comment: Presented at the IEEE Nuclear Science Symposium, Roma, 200
Complexity of diatom response to Lateglacial and Holocene climate and environmental change in ancient, deep and oligotrophic Lake Ohrid (Macedonia and Albania)
Lake Ohrid (Macedonia and Albania) is a rare example of a deep, ancient Mediterranean lake and is a key site for palaeoclimate research in the northeastern Mediterranean region. This study conducts the analysis of diatoms as a proxy for Lateglacial and Holocene climate and environmental change in Lake Ohrid at a higher resolution than in previous studies. While Lake Ohrid has the potential to be sensitive to water temperature change, the data demonstrate a highly complex diatom response, probably comprising a direct response to temperature-induced lake productivity in some phases and an indirect response to temperature-related lake stratification or mixing and epilimnetic nutrient availability in others. The data also demonstrate the possible influence of physical limnological (e.g. the influence of wind stress on stratification or mixing) and chemical processes (e.g. the influence of catchment dynamics on nutrient input) in mediating the complex response of diatoms. During the Lateglacial (ca. 12 300–11 800 cal yr BP), the low-diversity dominance of hypolimnetic Cyclotella fottii indicates low lake productivity, linked to low water temperature. Although the subsequent slight increase in small, epilimnetic C. minuscula during the earliest Holocene (ca. 11 800–10 600 cal yr BP) suggests climate warming and enhanced stratification, diatom concentration remains as low as during the Lateglacial, suggesting that water temperature increase was muted across this major transition. The early Holocene (ca. 10 600–8200 cal yr BP) is characterised by a sustained increase in epilimnetic taxa, with mesotrophic C. ocellata indicating high water-temperature-induced productivity between ca. 10 600–10 200 cal yr BP and between ca. 9500–8200 cal yr BP and with C. minuscula in response to low nutrient availability in the epilimnion between ca. 10 200–9500 cal yr BP. During the middle Holocene (ca. 8200–2600 cal yr BP), when sedimentological and geochemical proxies provide evidence for maximum Holocene water temperature, anomalously low C. ocellata abundance is probably a response to epilimnetic nutrient limitation, almost mimicking the Lateglacial flora apart from the occurrence of mesotrophic Stephanodiscus transylvanicus in the hypolimnion. During the late Holocene (ca. 2600 cal yr BP–present), high abundance and fluctuating composition of epilimnetic taxa are probably a response more to enhanced anthropogenic nutrient input, particularly nitrogen enrichment, than to climate. Overall, the data indicate that previous assumptions concerning the linearity of diatom response in this deep, ancient lake are invalid, and multi-proxy analysis is essential to improve understanding of palaeolimnological dynamics in future research on the long, Quaternary sequence
Complexity of diatom response to Lateglacial and Holocene climate and environmental change in ancient, deep, and oligotrophic Lake Ohrid (Macedonia/Albania)
Lake Ohrid (Macedonia/Albania) is a rare example of a deep, ancient Mediterranean lake and is a key site for palaeoclimate research in the northeastern Mediterranean region. This study conducts the first high-resolution diatom analysis during the Lateglacial and Holocene in Lake Ohrid. It demonstrates a complex diatom response to temperature change, with a direct response to temperature-induced productivity and an indirect response to temperature-related stratification/mixing regime and epilimnetic nutrient availability. During the Lateglacial (ca. 12 300–11 800 cal yr BP), the low-diversity dominance of hypolimnetic Cyclotella fottii indicates low temperature-dependent lake productivity. During the earliest Holocene (ca. 11 800–10 600 cal yr BP), although the slight increase in small, epilimnetic C. minuscula suggests climate warming and enhanced thermal stratification, diatom concentration remains very low as during the Lateglacial, indicating that temperature increase was muted. The early Holocene (ca. 10 600–8200 cal yr BP) marked a sustained increase in epilimnetic taxa, with mesotrophic C. ocellata indicating high temperature-induced lake productivity between ca. 10 600–10 200 cal yr BP and between ca. 9500–8200 cal yr BP, and with C. minuscula in response to low nutrient availability in the epilimnion between ca. 10 200–9500 cal yr BP. During the mid Holocene (ca. 8200–2600 cal yr BP), when sedimentological and geochemical proxies provide evidence for high temperature, anomalously low C. ocellata abundance is probably a response to epilimnetic nutrient limitation, almost mimicking the Lateglacial flora apart from mesotrophic Stephanodiscus transylvanicus indicative of high temperature-induced productivity in the hypolimnion. During the late Holocene (ca. 2600–0 cal yr BP), high abundance and fluctuating composition of epilimnetic taxa is largely a response to enhanced anthropogenic nutrient input. In this deep, oligotrophic lake, this study demonstrates the strong influence of lake physical and chemical processes in mediating the complex response of diatoms to climate change with particular respect to temperature
Mediterranean climate since the Middle Pleistocene: a 640 ka stable isotope record from Lake Ohrid (Albania/Macedonia)
Lake Ohrid (Macedonia/Albania) is an ancient lake with a unique biodiversity and a site of global significance for investigating the influence of climate, geological and tectonic events on the generation of endemic populations. Here, we present oxygen (δ18O) and carbon (δ13C) isotope data on carbonate from the upper ca. 248 m of sediment cores recovered as part of the Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project, covering the past 640 ka. Previous studies on short cores from the lake (up to 15 m, < 140 ka) have indicated the Total Inorganic Carbon (TIC) content of sediments to be highly sensitive to climate change over the last glacial–interglacial cycle, comprising abundant endogenic calcite through interglacials and being almost absent in glacials, apart from discrete bands of early diagenetic authigenic siderite. Isotope measurements on endogenic calcite (δ18Oc and δ13Cc) reveal variations both between and within interglacials that suggest the lake has been subject to hydroclimate fluctuations on orbital and millennial timescales. We also measured isotopes on authigenic siderite (δ18Os and δ13Cs) and, with the δ18OCc and δ18Os, reconstruct δ18O of lakewater (δ18Olw) through the 640 ka. Overall, glacials have lower δ18Olw when compared to interglacials, most likely due to cooler summer temperatures, a higher proportion of winter precipitation (snowfall), and a reduced inflow from adjacent Lake Prespa. The isotope stratigraphy suggests Lake Ohrid experienced a period of general stability through Marine Isotope Stage (MIS) 15 to MIS 13, highlighting MIS 14 as a particularly warm glacial, and was isotopically freshest during MIS 9. After MIS 9, the variability between glacial and interglacial δ18Olw is enhanced and the lake became increasingly evaporated through to present day with MIS 5 having the highest average δ18Olw. Our results provide new evidence for long-term climate change in the northern Mediterranean region, which will form the basis to better understand the influence of major environmental events on biological evolution within the lake
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