InSAR Time Series Analysis of Natural and Anthropogenic Coastal Plain Subsidence: The Case of Sibari (Southern Italy)

We applied the Small Baseline Subset multi-temporal InSAR technique (SBAS) to two SAR datasets acquired from 2003 up to 2013 by Envisat (ESA, European Space Agency) and COSMO-SkyMed (ASI, Italian Space Agency) satellites to investigate spatial and temporal patterns of land subsidence in the Sibari Plain (Southern Italy). Subsidence processes (up to ~20 mm/yr) were investigated comparing geological, hydrogeological, and land use information with interferometric results. We suppose a correlation between subsidence and thickness of the Plio-Quaternary succession suggesting an active role of the isostatic compensation. Furthermore, the active back thrusting in the Corigliano Gulf could trigger a flexural subsidence mechanism even if fault activity and earthquakes do not seem play a role in the present subsidence. In this context, the compaction of Holocene deposits contributes to ground deformation. Despite the rapid urbanization of the area in the last 50 years, we do not consider the intensive groundwater pumping and related water table drop as the main triggering cause of subsidence phenomena, in disagreement with some previous publications. Our interpretation for the deformation fields related to natural and anthropogenic factors would be a comprehensive and exhaustive justification to the complexity of subsidence processes in the Sibari Plain

Physiological Basis of No-go Decay with Sod1Δ Saccharomyces cerevisiae

Chromium VI (Cr (VI)), a common byproduct of industry, induces oxidative stress in cells, resulting in altered gene expression, increased apoptosis, and cell death. Previous work has shown showed that Cr (VI) exposure results in the formation of 8-oxoguanines (8- oxo(G) bases) in mRNA. These 8-oxo(G) bases lead to ribosome stalls during translation and the activation of no-go decay. Upon ribosome stalls, no-go decay is activated. During no-go decay, the Dom34p/Hbsp1p complex acts to remove stalled ribosomes and promote endonucleolytic cleavage of the damaged mRNA at the stall site. Although oxidative agents and other non-physiological substrates have been used to activate no-go decay, very little work exists to elucidate the true physiological role of this pathway. Sod1p (superoxide dismutase 1) scavenges free oxygen species by catalyzing the partitioning of superoxide (O2- ) into O2 and H2O2. Cells that lack functional Sod1p have been observed to have increased oxidative stress resulting in increased P-body assembly, while leading only to an attenuation of global translation. To determine whether no-go decay is being activated in strains lacking Sod1p, double mutant strains were created in which SOD1 was knocked out in conjunction with one of the effectors of no-go decay. Consistent with no-go decay being activated in response to oxidation, the hbs1Δsod1Δ strain resulted in a decrease in Pbody assembly, as compared to wild-type strain, even in the presence of Cr (VI). To assess how effective Sod1p is as a deterrent to 8-oxo(G) base formation in the presence of Cr (VI), the SOD1 gene was overexpressed in yeast cells. The presence of high levels of Sod1p was hypothesized to limit the number of 8-oxo(G) in response to the Cr (VI) and affect P-body assembly. However, overexpression of Sod1p does not seem to compensate for Cr (VI) mediated oxidation. Instead, we will look under milder oxidative conditions. Interestingly, Stm1p is thought to potentially to aid in the dissociation and recycling of the ribosomal subunits. In the stm1Δ and wild-type strain, P-body assembly was mildly decreased when treated with 17 Cr (VI), which is consistent with Stm1p functioning to recycle ribosomes downstream of no-go decay. Additionally, stm1Δ can suppress sod1Δ growth defects on Cr (VI) containing media.https://openriver.winona.edu/urc2019/1068/thumbnail.jp

Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect

Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9 years) naïve to incretin-based therapies were treated with liraglutide (1.2 mg/day) as add-on therapy to metformin (1500–3000 mg/day) for 4 months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. Results: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p < 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p < 0.0001). Conclusion: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. Trial Registration: ClinicalTrials.gov: NCT01715428

An eleven-year history of Vanishing White Matter Disease in an adult patient with no cognitive decline and EIF2B5 mutations. A case report

Vanishing White Matter Disease (VWMD) is a rare autosomal recessive leukoencephalopathy. The classical presentation is characterized by a severe cerebellar ataxia, spasticity, neurological deterioration with a chronic progressive course and episodes of acute neurological deterioration after stress conditions. We report a 52-year-old man with VWMD and atypical features who manifested two major events of transient aphasia eleven years apart with complete recovery in 48 hours. No cognitive decline was present. Brain MRI revealed typical aspects of VWMD including diffuse leukoencephalopathy with relative sparing of U-fibers. We identified the presence of c.592G>A (p.Glu198Lys) and c.1360 C>T (p.Pro454Ser) mutations in EIF2B5

Protective Role for Properdin in Progression of Experimental Murine Atherosclerosis

Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP) of complement is beneficial in LDLR−/− mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD) or high fat (HFD) Western type diets to newly generated LDLR−/− ProperdinKO (LDLR−/−PKO) and LDLR−/−PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR−/−PKO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA) were decreased in male LDLR−/−PKO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR−/− mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR−/−mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions

How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion

Obesity is an important independent cardiovascular (CV) risk factor and a chronic inflammatory disease related to the development of insulin resistance, type 2 diabetes, dyslipidaemia, coronary artery disease, hypertension, heart failure, atrial fibrillation and obstructive sleep apnoea. Body Mass Index (BMI) values >27 kg/m2 are associated with an exponential increase in the risk for Major Adverse Cardiac Events (MACE). On the other hand, weight reduction can significantly reduce metabolic, CV and oncological risk. Orlistat, bupropion/naltrexone, liraglutide and semaglutide, combined with lifestyle changes, have proven to be effective in weight loss; the last two have been tested in randomized clinical trials (RCTs) with CV outcomes only in diabetic patients, and not in obese patients. To fill a fundamental gap of knowledge, the SELECT trial on patients with obesity and CV disease treated with semaglutide is ongoing, aiming at MACE as the primary endpoint. The battle against the social and clinical stigma towards obesity must be counteracted by promoting an awareness that elevates obesity to a complex chronic disease. Several actions should be implemented to improve the management of obesity, and cardiologists have a key role for achieving a global approach to patients with excess weight also through the correct implementation of available treatment strategies