Vertical and interhemispheric links in the stratosphere-mesosphere as revealed by the day-to-day variability of Aura-MLS temperature data

The coupling processes in the middle atmosphere have been a subject of intense research activity because of their effects on atmospheric circulation, structure, variability, and the distribution of chemical constituents. In this study, the day-to-day variability of Aura-MLS (Microwave Limb Sounder) temperature data are used to reveal the vertical and interhemispheric coupling processes in the stratosphere-mesosphere during four Northern Hemisphere winters (2004/2005–2007/2008). The UKMO (United Kingdom Meteorological Office) assimilated data and mesospheric winds from MF (medium frequency) radars are also applied to help highlight the coupling processes. In this study, a clear vertical link can be seen between the stratosphere and mesosphere during winter months. The coolings and reversals of northward meridional winds in the polar winter mesosphere are often observed in relation to warming events (Sudden Stratospheric Warming, SSW for short) and the associated changes in zonal winds in the polar winter stratosphere. An upper-mesospheric cooling usually precedes the beginning of the warming in the stratosphere by 1–2 days. Inter-hemispheric coupling has been identified initially by a correlation analysis using the year-to-year monthly zonal mean temperature. Then the correlation analyses are performed based upon the daily zonal mean temperature. From the original time sequences, significant positive (negative) correlations are generally found between zonal mean temperatures at the Antarctic summer mesopause and in the Arctic winter stratosphere (mesosphere) during northern mid-winters, although these correlations are dominated by the low frequency variability (i.e. the seasonal trend). Using the short-term oscillations (less than 15 days), the statistical result, by looking for the largest magnitude of correlation within a range of time-lags (0 to 10 days; positive lags mean that the Antarctic summer mesopause is lagging), indicates that the temporal variability of zonal mean temperature at the Antarctic summer mesopause is also positively (negatively) correlated with the polar winter stratosphere (mesosphere) during three (2004/2005, 2005/2006, and 2007/2008) out of the four winters. The highest value of the correlation coefficient is over 0.7 in the winter-stratosphere for the three winters. The remaining winter (2006/2007) has more complex correlations structures; correspondingly the polar vortex was distinguished this winter. The time-lags obtained for 2004/2005 and 2006/2007 are distinct from 2005/2006 and 2007/2008 where a 6-day lag dominates for the coupling between the winter stratosphere and the summer mesopause. The correlations are also provided using temperatures in northern longitudinal sectors in a comparison with the Antarctic-mesopause zonal mean temperature. For northern mid-high latitudes (~50–70° N), temperatures in Scandinavia-Eastern Europe and in the Pacific-Western Canada longitudinal sectors often have opposite signs of correlations with zonal mean temperatures near the Antarctic summer mesopause during northern mid-winters. The statistical results are shown to be associated with the Northern Hemisphere's polar vortex characteristics

Immigration and Internal Migration 'Flight' from US Metropolitan Areas: Toward a New Demographic Balkanisation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68704/2/10.1080_00420989550012861.pd

Prospective associations of coronary heart disease loci in African Americans using the MetaboChip

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of publishe

Phenotypic and functional characterization of macrophages with therapeutic potential generated from human cirrhotic monocytes in a cohort study

AbstractBackground aimsMacrophages have complex roles in the liver. The aim of this study was to compare profiles of human monocyte-derived macrophages between controls and cirrhotic patients, to determine whether chronic inflammation affects precursor number or the phenotype, with the eventual aim to develop a cell therapy for cirrhosis.MethodsInfusion of human macrophages in a murine liver fibrosis model demonstrated a decrease in markers of liver injury (alanine transaminase, bilirubin, aspartate transaminase) and fibrosis (transforming growth factor-β, α-smooth muscle actin, phosphatidylserine receptor) and an increase in markers of liver regeneration (matrix metalloproteinases [MMP]-9, MMP-12 and TNF-related weak inducer of apoptosis). CD14+ monocytes were then isolated from controls. Monocytes were matured into macrophages for 7 days using a Good Manufacturing Practice–compatible technique.ResultsThere was no significant difference between the mean number of CD14+ monocytes isolated from cirrhotic patients (n = 9) and controls (n = 10); 2.8 ± SEM 0.54 × 108 and 2.5 ± 0.56 × 108, respectively. The mean yield of mature macrophages cultured was also not significantly different between cirrhotic patients and controls (0.9 × 108 ± 0.38 × 108, with more than 90% viability and 0.65 × 108 ± 0.16 × 108, respectively. Maturation to macrophages resulted in up-regulation of a number of genes (MMP-9, CCL2, interleukin [IL]-10 and TNF-related weak inducer of apoptosis). A cytokine and chemokine polymerase chain reaction array, comparing the control and cirrhotic macrophages, revealed no statistically significant differences.ConclusionsMacrophages can be differentiated from cirrhotic patients' apheresis-derived CD14 monocytes and develop the same pro-resolution phenotype as control macrophages, indicating their suitability for clinical therapy

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Asymmetry in the interhemispheric planetary wave-tide link between the two hemispheres

This study assesses the relation between the year-to-year variability of the semidiurnal tides (SDT) observed at high latitudes of both hemispheres and the global stratospheric stationary planetary wave (SPW) with zonal wavenumber S=1 (SPW1) derived from the UKMO temperature data. No significant positive correlation can be identified between the interannual variability of the Northern Hemisphere (NH) SDT and the Southern Hemisphere (SH) SPW1 for austral late-winter months. In contrast, a good consistency is evident for the interannual variations between the SDT observed at Rothera (68°S, 68°W) and the Arctic SPW1 for NH mid-winter months. Since it has been observed that during austral summer the non-migrating SDT often plays a significant role at the latitude of Rothera, a physical link between the SH SDT and the NH SPW is suggested. This asymmetry in the interhemispheric link is also noted in a recent study