Mechanisms of endothelial cell dysfunction in cystic fibrosis

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF

A Late Pleistocene channelized subglacial meltwater system on the Atlantic continental shelf south of Ireland

The study of palaeo-glacial landforms and sediments can give insights into the nature and dynamics of ice sheets. This is particularly the case with regards to the subglacial record, which is challenging to observe in contemporary glaciated settings and hence remains only partially understood. The subglacial hydrological system is an essential component of ice dynamics, where increased water pressure enhances ice motion and sediment deformation, thus reducing ice-bed contact. Tunnel valleys are large, sinuous, steep-sided incisions that, together with smaller scale meltwater channels, indicate subglacial meltwater discharge beneath large ice sheets. Through the use of high-resolution marine geophysical data, a system of buried and exposed tunnel valleys, possible subglacial or proglacial meltwater channels and palaeo-fluvial valleys have been identified across the shelf of the Celtic Sea between Ireland and Britain. The presence of steep-sided and overdeepened tunnel valleys is indicative of a large channelized meltwater drainage system beneath the former Irish Sea Ice Stream, the most extensive ice stream to drain the last British–Irish Ice Sheet. After the rapid ice expansion across the Celtic Sea shelf around 28–26 ka, the tunnel valleys were carved into both bedrock and glacigenic sediments and are associated with rapid ice stream retreat northwards into the Irish Sea Basin between 25.6 and 24.3 ka. The presence of a major subglacial meltwater system on the relatively shallow shelf suggests that significant erosive meltwater discharge occurred during the last deglaciation and highlights the important contribution of meltwater to the retreat of the British–Irish Ice Sheet on the continental shelf

Climate and landscape composition explain agronomic practices, pesticide use and grape yield in vineyards across Italy

Context Worldwide, organic farming is being promoted as one of the main alternatives to intensive conventional farming. However, the benefits of organic agriculture are still controversial and need to be tested across wide environmental gradients. Objective Here, we carried out an observational study to test how agronomic practices, pest management, environmental impact and yield of conventional and organic vineyards changed along wide climatic and landscape gradients across Italy. Methods We used a block design with 38 pairs of conventional and organic vineyards across Italy. Results and conclusions Most agronomic practices did not differ between conventional and organic vineyards. By contrast, landscape composition and climate were strong predictors of management in both systems. First, increasing semi-natural areas around the vineyards reduced pesticide pressure and related environmental impacts, but was also associated with lower yield. Second, irrespective of the farming system, a warm and dry climate was associated with reduced fungicide pressure. Conventional farming had a yield gain of 40% in cold and wet climate compared to organic but the yield gap disappeared in the warmest regions. Significance In both farming systems, we observed a large variability in management practices that was mainly explained by climate and landscape composition. This large variability should be considered when evaluating the benefits and drawbacks of different farming systems under contrasting environmental contexts

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection