VGF changes during the estrous cycle: a novel endocrine role for TLQP peptides?

Although the VGF derived peptide TLQP-21 stimulates gonadotropin-releasing hormone (GnRH) and gonadotropin secretion, available data on VGF peptides and reproduction are limited. We used antibodies specific for the two ends of the VGF precursor, and for two VGF derived peptides namely TLQP and PGH, to be used in immunohistochemistry and enzyme-linked immunosorbent assay complemented with gel chromatography. In cycling female rats, VGF C-/N-terminus and PGH peptide antibodies selectively labelled neurones containing either GnRH, or kisspeptin (VGF N-terminus only), pituitary gonadotrophs and lactotrophs, or oocytes (PGH peptides only). Conversely, TLQP peptides were restricted to somatostatin neurones, gonadotrophs, and ovarian granulosa, interstitial and theca cells. TLQP levels were highest, especially in plasma and ovary, with several molecular forms shown in chromatography including one compatible with TLQP-21. Among the cycle phases, TLQP levels were higher during metestrus-diestrus in median eminence and pituitary, while increased in the ovary and decreased in plasma during proestrus. VGF N- and C-terminus peptides also showed modulations over the estrous cycle, in median eminence, pituitary and plasma, while PGH peptides did not. In ovariectomised rats, plasmatic TLQP peptide levels showed distinct reduction suggestive of a major origin from the ovary, while the estrogen-progesterone treatment modulated VGF C-terminus and TLQP peptides in the hypothalamus-pituitary complex. In in vitro hypothalamus, TLQP-21 stimulated release of growth hormone releasing hormone but not of somatostatin. In conclusion, various VGF peptides may regulate the hypothalamus-pituitary complex via specific neuroendocrine mechanisms while TLQP peptides may act at further, multiple levels via endocrine mechanisms involving the ovary

Injecting Background Knowledge into Embedding Models for Predictive Tasks on Knowledge Graphs

Embedding models have been successfully exploited for Knowledge Graph refinement. In these models, the data graph is projected into a low-dimensional space, in which graph structural information are preserved as much as possible, enabling an efficient computation of solutions. We propose a solution for injecting available background knowledge (schema axioms) to further improve the quality of the embeddings. The method has been applied to enhance existing models to produce embeddings that can encode knowledge that is not merely observed but rather derived by reasoning on the available axioms. An experimental evaluation on link prediction and triple classification tasks proves the improvement yielded implementing the proposed method over the original ones

Diagnostics of the Tropical Tropopause Layer from in-situ observations and CCM data

A suite of diagnostics is applied to in-situ aircraft measurements and one Chemistry-Climate Model (CCM) data to characterize the vertical structure of the Tropical Tropopause Layer (TTL). The diagnostics are based on vertical tracer profiles and relative vertical tracer gradients, using tropopause-referenced coordinates, and tracer-tracer relationships in the tropical Upper Troposphere/Lower Stratosphere (UT/LS).Observations were obtained during four tropical campaigns performed from 1999 to 2006 with the research aircraft Geophysica and have been compared to the output of the ECHAM5/MESSy CCM. The model vertical resolution in the TTL (similar to 500 m) allows for appropriate comparison with high-resolution aircraft observations and the diagnostics used highlight common TTL features between the model and the observational data.The analysis of the vertical profiles of water vapour, ozone, and nitrous oxide, in both the observations and the model, shows that concentration mixing ratios exhibit a strong gradient change across the tropical tropopause, due to the role of this latter as a transport barrier and that transition between the tropospheric and stratospheric regimes occurs within a finite layer. The use of relative vertical ozone and carbon monoxide gradients, in addition to the vertical profiles, helps to highlight the region where this transition occurs and allows to give an estimate of its thickness. The analysis of the CO-O-3 and H2O-O-3 scatter plots and of the Probability Distribution Function (PDF) of the H2O-O-3 pair completes this picture as it allows to better distinguish tropospheric and stratospheric regimes that can be identified by their different chemical composition.The joint analysis and comparison of observed and modelled data allows to state that the model can represent the background TTL structure and its seasonal variability rather accurately. The model estimate of the thickness of the interface region between tropospheric and stratospheric regimes agrees well with average values inferred from observations. On the other hand, the measurements can be influenced by regional scale variability, local transport processes as well as deep convection, that can not be captured by the model

Diagnostics of the Tropical Tropopause Layer from in-situ observations and CCM data

A suite of diagnostics is applied to in-situ aircraft measurements and one Chemistry-Climate Model (CCM) data to characterize the vertical structure of the Tropical Tropopause Layer (TTL). The diagnostics are based on vertical tracer profiles and relative vertical tracer gradients, using tropopause-referenced coordinates, and tracer-tracer relationships in the tropical Upper Troposphere/Lower Stratosphere (UT/LS). <br><br> Observations were obtained during four tropical campaigns performed from 1999 to 2006 with the research aircraft Geophysica and have been compared to the output of the ECHAM5/MESSy CCM. The model vertical resolution in the TTL (~500 m) allows for appropriate comparison with high-resolution aircraft observations and the diagnostics used highlight common TTL features between the model and the observational data. <br><br> The analysis of the vertical profiles of water vapour, ozone, and nitrous oxide, in both the observations and the model, shows that concentration mixing ratios exhibit a strong gradient change across the tropical tropopause, due to the role of this latter as a transport barrier and that transition between the tropospheric and stratospheric regimes occurs within a finite layer. The use of relative vertical ozone and carbon monoxide gradients, in addition to the vertical profiles, helps to highlight the region where this transition occurs and allows to give an estimate of its thickness. The analysis of the CO-O<sub>3</sub> and H<sub>2</sub>O-O<sub>3</sub> scatter plots and of the Probability Distribution Function (PDF) of the H<sub>2</sub>O-O<sub>3</sub> pair completes this picture as it allows to better distinguish tropospheric and stratospheric regimes that can be identified by their different chemical composition. <br><br> The joint analysis and comparison of observed and modelled data allows to state that the model can represent the background TTL structure and its seasonal variability rather accurately. The model estimate of the thickness of the interface region between tropospheric and stratospheric regimes agrees well with average values inferred from observations. On the other hand, the measurements can be influenced by regional scale variability, local transport processes as well as deep convection, that can not be captured by the model

Growth of a sinkhole in a seismic zone of the northern Apennines (Italy)

Sinkhole collapse is a major hazard causing substantial social and economic losses. However, the surface deformations and sinkhole evolution are rarely recorded, as these sites are known mainly after a collapse, making the assessment of sinkhole-related hazard challenging. Furthermore, more than 40% of the sinkholes of Italy are in seismically hazardous zones; it remains unclear whether seismicity may trigger sinkhole collapse. Here we use a multidisciplinary data set of InSAR, surface mapping and historical records of sinkhole activity to show that the Prà di Lama lake is a long-lived sinkhole that was formed in an active fault zone and grew through several events of unrest characterized by episodic subsidence and lake-level changes. Moreover, InSAR shows that continuous aseismic subsidence at rates of up to 7.1mmyr-1occurred during 2003-2008, between events of unrest. Earthquakes on the major faults near the sinkhole do not trigger sinkhole activity but low-magnitude earthquakes at 4-12 km depth occurred during sinkhole unrest in 1996 and 2016. We interpret our observations as evidence of seismic creep at depth causing fracturing and ultimately leading to the formation and growth of the Prà di Lama sinkhole

Ischemic heart disease and heart failure. role of coronary ion channels

Heart failure is a complex syndrome responsible for high rates of death and hospitalization. Ischemic heart disease is one of the most frequent causes of heart failure and it is normally attributed to coronary artery disease, defined by the presence of one or more obstructive plaques, which determine a reduced coronary blood flow, causing myocardial ischemia and consequent heart failure. However, coronary obstruction is only an element of a complex pathophysiological process that leads to myocardial ischemia. In the literature, attention paid to the role of microcirculation, in the pathophysiology of ischemic heart disease and heart failure, is growing. Coronary microvascular dysfunction determines an inability of coronary circulation to satisfy myocardial metabolic demands, due to the imbalance of coronary blood flow regulatory mechanisms, including ion channels, leading to the development of hypoxia, fibrosis and tissue death, which may determine a loss of myocardial function, even beyond the presence of atherosclerotic epicardial plaques. For this reason, ion channels may represent the link among coronary microvascular dysfunction, ischemic heart disease and consequent heart failure

Clinical Support through Telemedicine in Heart Failure Outpatients during the COVID-19 Pandemic Period: Results of a 12-Months Follow Up

Background: Heart failure (HF) patients are predisposed to recurrences and disease destabilizations, especially during the COVID-19 outbreak period. In this scenario, telemedicine could be a proper way to ensure continuous care. The purpose of the study was to compare two modalities of HF outpatients’ follow up, the traditional in-person visits and telephone consultations, during the COVID-19 pandemic period in Italy. Methods: We conducted an observational study on consecutive HF outpatients. The follow up period was 12 months, starting from the beginning of the COVID-19 Italy lockdown. According to the follow up modality, and after the propensity matching score, patients were divided into two groups: those in G1 (n = 92) were managed with traditional in-person visits and those in G2 (n = 92) were managed with telephone consultation. Major adverse cardiovascular events (MACE) were the primary endpoints. Secondary endpoints were overall mortality, cardiovascular death, cardiovascular hospitalization, and hospitalization due to HF. Results: No significant differences between G1 and G2 have been observed regarding MACE (p = 0.65), cardiovascular death (p = 0.39), overall mortality (p = 0.85), hospitalization due to acute HF (p = 0.07), and cardiovascular hospitalization (p = 0.4). Survival analysis performed by the Kaplan–Meier method also did not show significant differences between G1 and G2. Conclusions: Telephone consultations represented a valid option to manage HF outpatients during COVID-19 pandemic, comparable to traditional in-person visits

Supermassive Black Holes at High Redshift are Expected to be Obscured by their Massive Host Galaxies' Inter Stellar Medium

We combine results from deep ALMA observations of massive ($M_*>10^{10}\;M_{\odot}$) galaxies at different redshifts to show that the column density of their inter stellar medium (ISM) rapidly increases towards early cosmic epochs. Our analysis includes objects from the ASPECS and ALPINE large programs, as well as individual observations of $z\sim 6$ QSO hosts. When accounting for non-detections and correcting for selection effects, we find that the median surface density of the ISM of the massive galaxy population evolves as $\sim(1+z)^{3.3}$. This means that the ISM column density towards the nucleus of a $z>3$ galaxy is typically $>100$ times larger than locally, and it may reach values as high as Compton-thick at $z\gtrsim6$. Remarkably, the median ISM column density is of the same order of what is measured from X-ray observations of large AGN samples already at $z\gtrsim2$. We develop a simple analytic model for the spatial distribution of ISM clouds within galaxies, and estimate the total covering factor towards active nuclei when obscuration by ISM clouds on the host scale is added to that of pc-scale circumnuclear material (the so-called 'torus'). The model includes clouds with a distribution of sizes, masses, and surface densities, and also allows for an evolution of the characteristic cloud surface density with redshift, $\Sigma_{c,*}\propto(1+z)^\gamma$. We show that, for $\gamma=2$, such a model successfully reproduces the increase of the obscured AGN fraction with redshift that is commonly observed in deep X-ray surveys, both when different absorption thresholds and AGN luminosities are considered. Our results suggest that 80-90\% of supermassive black holes in the early Universe ($z>6-8$) are hidden to our view, primarily by the ISM in their hosts. [abridged]Comment: 22 pages, 15 figures, accepted for publication in A&