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Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction
(2019)
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subangstrom length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
Following the Middle Permian (Capitanian) mass extinction there was a global ‘reef eclipse’, and this event had an important role in the Paleozoic-Mesozoic transition of reef ecosystems. Furthermore, the recovery pattern of reef ecosystems in the Wuchiapingian of South China, before the radiation of Changhsingian reefs, is poorly understood. Here, we present a detailed sedimentological account of the Tieqiao section, South China, which records the only known Wuchiapingian reef setting from South China. Six reef growing phases were identified within six transgressive-regressive cycles. The cycles represent changes of deposition in a shallow basin to a subtidal outer platform setting, and the reefal build-ups are recorded in the shallowest part of the cycles above wave base in the euphotic zone. Our results show that the initial reef recovery started from the shallowing up part of the 1st cycle, within the Clarkina leveni conodont zone, which is two conodont zones earlier than previously recognized. In addition, even though metazoans, such as sponges, do become important in the development of the reef bodies, they are not a major component until later in the Wuchiapingian in the 5th and 6th transgressive-regressive cycles. This suggests a delayed recovery of metazoan reef ecosystems following the Middle Permian extinction. Furthermore, even though sponges do become abundant within the reefs, it is the presence and growth of the encrusters Archaeolithoporella and Tubiphytes and abundance of microbial micrites that play an important role in stabilizing the reef structures that form topographic highs.
Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
A new species, Gastrochilus kadooriei, is described from Hong Kong. Notes are presented on its distribution, ecology and conservation status, and its distinguishing features are compared with those of allied taxa. Gastrochilus jeitouensis is reduced to the synonymy of G. distichus, and a lectotype is assigned for G. pseudodistichus. Gastrochilus fuscopunctatus is reinstated as an accepted species. Dichotomous keys to this taxonomically difficult group of morphologically similar species are presented.
Along the NE Pamir margin, flights of late Quaternary fluvial terraces span actively deforming fault-related folds. We present detailed results on two terraces dated using optically stimulated luminescence (OSL) and cosmogenic radionuclide Be-10 (CRN) techniques. Quartz OSL dating of two different grain sizes (4-11 mu m and 90-180 mu m) revealed the fine-grain quartz fraction may overestimate the terrace ages by up to a factor of ten. Two-mm, small-aliquot, coarse-grain quartz OSL ages, calculated using the minimum age model, yielded stratigraphically consistent ages within error and dated times of terrace deposition to similar to 9 and similar to 16 ka. We speculate that, in this arid environment, fine-grain samples can be transported and deposited in single, turbid, and (sometimes) night-time floods that prevent thorough bleaching and, thereby, can lead to relatively large residual OSL signals. In contrast, sand in the fluvial system is likely to have a much longer residence time during transport, thereby providing greater opportunities for thorough bleaching. CRN Be-10 depth profiles date the timing of terrace abandonment to similar to 8 and similar to 14 ka: ages that generally agree with the coarse-grain quartz OSL ages. Our new terrace age of similar to 13-14 ka is broadly consistent with other terraces in the region that indicate terrace deposition and subsequent abandonment occurred primarily during glacial-interglacial transitions, thereby suggesting a climatic control on the formation of these terraces on the margins of the Tarim Basin. Furthermore, tectonic shortening rates calculated from these deformed terraces range from similar to 1.2 to similar to 4.6 mm/a and, when combined with shortening rates from other structures in the region, illuminate the late Quaternary basinward migration of deformation to faults and folds along the Pamir-Tian Shan collisional interface.