Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Sex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women

Lab and Field Tests of a Low-Cost 3-Component Seismometer for Shallow Passive Seismic Applications

We performed laboratory tests and field surveys to evaluate the performance of a low-cost 3-component seismometer, consisting of three passive electromagnetic spring-mass sensors, whose 4.5 Hz natural frequency is extended down to 0.5 Hz thanks to hyper damping. Both lab and field datasets show that the −3 dB band of the seismometer ranges approximately from 0.7 to 39 Hz, in agreement with the nominal specifications. Median magnitude frequency response curves obtained from processing field data indicate that lower corner of the −3 dB band could be extended down to 0.55 Hz and the nominal sensitivity may be overestimated. Lab results confirm the non-linear behavior of the passive spring-mass sensor expected for high-level input signals (a few to tens of mm/s) and field data confirm relative timing accuracy is ±10 ms (1 sample). We found that absolute timing of data collected with USB GPS antennas can be affected by lag as large as +0.5 s. By testing two identical units, we noticed that there could be differences around 0.5 dB (i.e., about 6%) between the components of the same unit as well as between the same component of the two units. Considering shallow passive seismic applications and mainly focusing on unstable slope monitoring, our findings show that the tested seismometer is able to identify resonance frequencies of unstable rock pillars and to generate interferograms that can be processed to estimate subsurface velocity variations

Deglacial landform assemblage records fast ice-flow and retreat, Inner Hebrides, Scotland

High-resolution bathymetric data have been central to recent advances in the understanding of past dynamics of the former British–Irish Ice Sheet (BIIS). As approximately two-thirds of the former BIIS was probably marine-based during the Last Glacial Maximum (LGM) (c. 29–23 ka), geomorphic observations of the seabed are required increasingly to understand the extent, pattern and timing of past glaciation. Until recently, glacial reconstructions for the Inner Hebrides, offshore of western Scotland, have been based primarily on terrestrial observations. Previous workers have proposed generalized reconstructions in which the Inner Hebrides are located within a significant former ice-sheet flow pathway that drained the western Scottish sector of the BIIS, feeding the Barra Fan during the LGM and earlier glaciations (Fig. 1). Results from numerical ice-sheet modelling suggest that former ice-flow velocities within the region were on the order of hundreds to thousands of metres per year, but yield further insight by demonstrating how dynamic binge/purge cycles may have affected ice-sheet mass balance over time (Hubbard et al. 2009). Following the LGM, ice-sheet retreat through the area is estimated to have been in the order of 20 m per year (Clark et al. 2012). Here we present swath-bathymetric data from the Inner Hebrides that provide in situ constraints on ice-sheet flow and subsequent retreat dynamics from within this important sector of the BIIS

Stereodivergent Synthesis of 5-Aminopipecolic Acids and Application in the Preparation of a Cyclic RGD Peptidomimetic as a nanomolar αVβ3 Integrin Ligand

A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained \u3b1- and \u3b4-amino acids. The cis isomer was used as a \u3b4-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for the binding to the isolated \u3b1V\u3b23 integrin was measured (IC50 = 4.2 \ub1 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with Cilengitide

Long-term hydrogeophysical monitoring of the internal conditions of river levees

To evaluate the vulnerability of the earthen levee of an irrigation canal in San Giacomo delle Segnate, Italy, a customized electrical resistivity tomography (ERT) monitoring system was installed in September 2015 and has been continuously operating since then. Thanks to a meteorological station deployed at the study site, we could investigate the relationship between the inverted resistivity values and different parameters, namely air temperature, rainfall and water level in the canal. Air temperature seems to have a minor but not negligible influence on resistivity variations, especially at shallow depth. A model of soil temperature versus depth was used to correct resistivity sections for air temperature variations through the different seasons. Changes of the water level in the canal and rainfall significantly affect measured resistivity values. At the study site, the most important variations of resistivity are related to saturation and dewatering processes in the irrigation periods. Although we explored the effect of drawdown procedures on resistivity data, this process, causing rapid variations of resistivity values, is still not completely understood because the canal is rapidly emptied during rainfall events. Therefore, the effect of variations of the water level in the canal on levee resistivity cannot be distinguished from the effect of rainfalls. To study the effect of water level variations alone, we considered the beginning of the irrigation period when the dry canal is gradually filled and we observed a smooth trend of resistivity changes. The effect of rainfall on the data was studied during different periods of the year and at different depths of the levee so that the resistivity variations could be evaluated under different conditions. To convert the inverted resistivity sections into water content maps, an empirical and site-dependent relationship between resistivity and water content was obtained using core samples. Water content data can then be used for the implementation of stability analysis using custom modeling. This study introduces an efficient technique to monitor earthen levees and to control the evolution of seepage and water saturation in pseudo-real time. Such a technique can be exploited by Public Administrations to reduce hydrogeological risks significantly

ENVIRONMENTAL IMPACTS OF USING DESALINATED WATER IN CONCRETE PRODUCTION IN AREAS AFFECTED BY FRESHWATER SCARCITY

Up to 500 litres of water may be consumed at the batching plant per cubic meter of ready mix concrete, if water for washing mixing trucks and equipment is included. Demand for concrete is growing almost everywhere, regardless of local availability of freshwater. The use of freshwater for concrete production exacerbates stress on natural water resources. In water-stressed coastal countries such as Israel, desalinated seawater (DSW) is often used in the production of concrete. However, the environmental impacts of this practice have not yet been assessed. In this study the effect of using DSW on the water and carbon footprints of concrete was investigated using life cycle assessment. Water footprint results highlight the benefits of using DSW rather than freshwater to produce concrete in Israel. In contrast, because desalination is an energy intensive process, using DSW increases the greenhouse gas intensity of concrete. Nevertheless, this increase (0.27 kg CO2e/m3 concrete) is small, if compared to the life cycle greenhouse gas emissions of concrete. Our results show that using untreated seawater in the mix (transported by truck from the coast) in place of DSW, would be beneficial in terms of water and carbon footprints if the batching plant were located less than 13 km from the withdrawal point. However, use of untreated seawater increases steel reinforcement corrosion, resulting in loss of structural integrity of the reinforced concrete composite. Sustainability of replacing steel with non-corrosive materials should be explored as a way to reduce both water and carbon footprints of concrete

Geoelectrical characterization and monitoring of slopes on a rainfall-triggered landslide simulator

In this paper, we present the results of time-lapse electrical resistivity tomography (ERT) monitoring of rainfall-triggered shallow landslides reproduced on a laboratory-scale physical model. The main objective of our experiments was to monitor rainwater infiltration through landslide body in order to improve our understanding of the precursors of failure. Time-domain reflectometry (TDR) data were also acquired to obtain the volumetric water content. Knowing the porosity, water saturation was calculated from the volumetric water content and we could calibrate Archie's equation to calculate water saturation maps from inverted resistivity values. Time-lapse ERT images proved to be effective in monitoring the hydrogeological conditions of the slope as well as in detecting the development of fracture zones before collapse. We performed eight laboratory tests and the results show that the landslide body becomes unstable at zones where the water saturation exceeds 45%. It was also observed that instability could occur at the boundaries between areas with different water saturations. Our study shows that time-lapse ERT technique can be employed to monitor the hydrogeological conditions of landslide bodies and the monitoring strategy could be extended to field-scale applications in areas prone to the development of shallow landslides

Effective targeting of DC-sign by α-fucosylamide functionalized gold nanoparticles

Dendritic Cells (DCs), the most potent antigenpresenting cells, play a critical role in the detection of invading pathogens, which are recognized also by multiple carbohydrate-specific receptors. Among them, DC-SIGN is one of the best characterized, with high-mannose and Lewis-type glycan specificity. In this study, we present a potent DC-SIGN targeting device developed using gold nanoparticles functionalized with \u3b1-fucosyl-\u3b2-alanyl amide. The nanoparticles bound to cellular DC-SIGN and induced internalization as effectively as similar particles coated with comparable amounts of LewisX oligosaccharide. They were found to be neutral toward dendritic cell maturation and IL-10 production, thus envisaging a possible use as targeted imaging tools and antigen delivery devices

β-Glucuronidase triggers extracellular MMAE release from an integrin-targeted conjugate

A non-internalizing \u3b1v\u3b23 integrin ligand was conjugated to the anticancer drug MMAE through a \u3b2-glucuronidase-responsive linker. In the presence of \u3b2-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics