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Mitochondrial dysfunction is a hallmark in idiopathic Parkinson’s disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from patients with IPD. Upper arm punch skin biopsy was performed in 41 patients with mid-stage IPD and 21 age-matched healthy controls. At the single-cell level, the basal mitochondrial membrane potential (Ψm) was higher in patients with IPD than in controls. Similarly, under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) stress, the remaining Ψm was increased in patients with IPD. Analysis of mitochondrial morphometric parameters revealed significantly decreased mitochondrial connectivity in patients with IPD, with 9 of 14 morphometric mitochondrial parameters differing from those in controls. Significant morphometric mitochondrial changes included the node degree, mean volume, skeleton size, perimeter, form factor, node count, erosion body count, endpoints, and mitochondria count (all P-values < 0.05). These functional data reveal that resistance to depolarization was increased by treatment with the protonophore FCCP in patients with IPD, whereas morphometric data revealed decreased mitochondrial connectivity and increased mitochondrial fragmentation.

Recent evidence suggests that regulatory pathways might control sustained high levels of FOXP3 in regulatory CD4+CD25hi T (Treg) cells. Based on transcriptional profiling of ex vivo activated Treg and helper CD4+CD25− T (Th) cells we have identified GARP (glycoprotein‐A repetitions predominant), LGALS3 (lectin, galactoside‐binding, soluble, 3) and LGMN (legumain) as novel genes implicated in human Treg cell function, which are induced upon T‐cell receptor stimulation. Retroviral overexpression of GARP in antigen‐specific Th cells leads to an efficient and stable re‐programming of an effector T cell towards a regulatory T cell, which involves up‐regulation of FOXP3, LGALS3, LGMN and other Treg‐associated markers. In contrast, overexpression of LGALS3 and LGMN enhance FOXP3 and GARP expression, but only partially induced a regulatory phenotype. Lentiviral down‐regulation of GARP in Treg cells significantly impaired the suppressor function and was associated with down‐regulation of FOXP3. Moreover, down‐regulation of FOXP3 resulted in similar phenotypic changes and down‐regulation of GARP. This provides compelling evidence for a GARP‐FOXP3 positive feedback loop and provides a rational molecular basis for the known difference between natural and transforming growth factor‐β induced Treg cells as we show here that the latter do not up‐regulate GARP. In summary, we have identified GARP as a key receptor controlling FOXP3 in Treg cells following T‐cell activation in a positive feedback loop assisted by LGALS3 and LGMN, which represents a promising new system for the therapeutic manipulation of T cells in human disease.

Direct human influences on climate have been detected at local scales, such as urban temperature increases and precipitation enhancement 1 , 2 , 3 , and at global scales 4 , 5 . A possible indication of an anthropogenic effect on regional climate is by identification of equivalent weekly cycles in climate and pollution variables. Weekly cycles have been observed in both global surface temperature 6 and local pollution 7 data sets. Here we describe statistical analyses that reveal weekly cycles in three independent regional-scale coastal Atlantic data sets: lower-troposphere pollution, precipitation and tropical cyclones. Three atmospheric monitoring stations record minimum concentrations of ozone and carbon monoxide early in the week, while highest concentrations are observed later in the week. This air-pollution cycle corresponds to observed weekly variability in regional rainfall and tropical cyclones. Specifically, satellite-based precipitation estimates indicate that near-coastal ocean areas receive significantly more precipitation at weekends than on weekdays. Near-coastal tropical cyclones have, on average, significantly weaker surface winds, higher surface pressure and higher frequency at weekends. Although our statistical findings limit the identification of cause–effect relationships, we advance the hypothesis that the thermal influence of pollution-derived aerosols on storms may drive these weekly climate cycles.

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.

In the case of B.1.1.7, estimates suggest R could increase from 1 to about 1.4 with no change in population behavior.3,4 If true, many countries that have succeeded in reducing R to 1 or less will be confronted with a novel wave of viral spread despite the current measures.8,9 Once a more contagious variant has established itself, stabilising the number of new infections will become increasingly difficult. The joint action of all European countries will make each national and local effort more effective and impactful and safeguard public health across Europe.8 The longer restrictions last, and the less effective they become, the more depleted people's psychological, social, and economic resources become. Where novel variants require even stricter and longer measures than existing measures, it is of utmost importance to ensure that people with particularly heavy burdens receive financial and social support, that social burdens are justly distributed, and that mental health services meet the increasing demand to cope with bereavement, isolation, loss of income, fear, alcohol and drug misuse, insomnia, and anxiety as a result of the pandemic and lockdown strategies.

We analyzed hourly precipitation data over the period 1965-1998 for 133 stations located throughout the Hawaiian Islands and found distinctive diurnal cycles in the amount and frequency of the rainfall. The diurnal signals were generally strongest on the island of Hawaii and more pronounced in the summer than in the winter. Windward sides of the islands generally showed the time of maximum for frequency or amount to be before sunrise while the leeward sides generally revealed the primary maximum in the afternoon. We conducted the analyses for El Nino years and La Nina years and found the diurnal patterns in rainfall to be unaffected by this Pacific-area oscillation. The results are consistent with others who have argued, based on work on the island of Hawaii, that anabatic and katabatic wind flows are responsible for the observed diurnal rainfall patterns. A semi-diurnal cycle with two maxima and two minima appears to be important in the summer season in the leeward locations. Our results show that processes and patterns described for the island of Hawaii are found throughout the larger islands of the Hawaii chain. [PUBLICATION ABSTRACT]

Over the past three decades, the sea-surface temperatures of the lower latitudes of the North Atlantic basin have increased while the lower-tropospheric temperatures show no upward trend. This differential warming of the atmosphere may have a destabilizing effect that could influence the development and intensification of tropical cyclones (TCs). In this investigation, we find that in general, TC intensification (a) is higher during the daytime period and during the later months of the storm season, (b) tends to be higher in the western portion of the North Atlantic basin, and (c) is not explained by current month or antecedent SSTs. Any changes associated with warming of the surface compared to a smaller temperature rise in the lower-troposphere (and resultant changes in atmospheric stability) have not produced detectable impacts on intensification rates of tropical cyclones in the North Atlantic basin. [PUBLICATION ABSTRACT]

Many modeling and empirical studies have revealed that summer monsoon precipitation in India is significantly affected by El Niño/Southern Oscillation (ENSO) as well as by seasurface temperatures (SSTs) in the Arabian Sea, Bay of Bengal, and Indian Ocean. Recently, the impact of the Pacific decadal oscillation (PDO) on Indian rainfall has been the focus of research. In this investigation, we collect monthly rainfall data for 18 grid cells covering India and develop statistical indices of ENSO, PDO, and local SSTs over the period 1925–1998. We find that ENSO reduces precipitation in southern India while having a small impact over most of the country. The PDO appears to amplify the ENSO signal in southern India, while local SSTs were directly related to monsoon precipitation totals in the southern peninsula region. While the associations are often statistically significant, the combination of ENSO, PDO, and SSTs explains less than 20% of the variance in monsoon rainfall throughout India.

The purpose of this article is to describe determinants and spatial patterns of atmospheric carbon dioxide (CO 2 ) in Phoenix, Arizona. Specifically, we use geographic information systems (GIS) and regression-based analyses to identify the human and biological factors that contribute to spatial and temporal variations in near-surface (2-meter height) atmospheric CO 2 levels. We use these factors to create estimated surfaces of CO 2 concentrations for the area. We evaluate the surfaces using records of CO 2 from independent monitoring stations and transects. To investigate the temporal patterns and variations in CO 2 concentrations, we estimate CO 2 surfaces for the early mornings and the afternoons, on weekdays when traffic is heavy and spatially focused and on weekends when it is lighter and more spatially dispersed. Findings suggest there is a distinct relationship between the structure of Phoenix CO 2 levels and spatial patterns of human activities and vegetation densities. Morning CO 2 levels are higher than afternoon levels and correspond closely to the density of traffic, population, and employment. The spatial structure of human activity explains the pattern of CO 2 better on weekdays than on weekends. CO 2 surfaces reflect declining densities of human activity with distance from the city center, the pattern of irrigated agriculture in the Phoenix area, and riparian habitats on the urban fringe. Spatial and temporal patterns of CO 2 concentrations are useful in understanding urban climate and ecosystem processes.