Effects of environmental and electric perturbations on the pKa of thioredoxin cysteine 35: a computational study

Here we present a theoretical-computational study dealing with the evaluation of the pKa of the Cysteine residues in Thioredoxin (TRX) and in its complex with the Thioredoxin-interacting protein (TXNIP). The free energy differences between the anionic and neutral form of the Cysteine 32 and 35 have been evaluated by means of the Perturbed Matrix Method with classical perturbations due to both the environment and an exogenous electric field as provided by Molecular Dynamics (MD) simulations. The evaluation of the free energies allowed us to show that the effect of the perturbing terms is to lower the pKa of Cysteine 32 and Cysteine 35 with respect to the free amino-acid. On the other hand, in the complex TRX-TXNIP, our data show an enhanced stabilization of the neutral reduced form of Cys 35. These results suggest that external electric stimuli higher than 0.02 V/nm can modulate the Cysteine pKa, which can be connected to the tight regulation of the TRX acting as an antioxidant agent

Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant

Seismogenic sources of the Adriatic domain

We present an overview of the seismogenic source model of the Adriatic domain included in the latest version of the DISS database (http://diss.rm.ingv.it/diss/) and in the European SHARE database (http://diss.rm.ingv.it/SHARE/). The model consists of Composite and Individual Seismogenic Sources located inside and along the margins of the Adria plate. In order to locate and parameterize the sources, we integrated a wide set of geological, geophysical, seismological and geodynamic data, either available from published literature or resulting from our own field work, seismic profile interpretations and numerical modelling studies. We grouped the sources into five regions based on geometrical and kinematic homogeneity criteria. Seismogenic sources of the Central Western Adriatic, North-Eastern Adriatic, Eastern Adriatic and Central Adriatic regions belong to the Northern Apennines, External Dinarides and offshore domains, respectively. They are characterized by NWeSE strike, reverse to oblique kinematics and shallow crustal seismogenic depth. Seismogenic sources of the Southern Western Adriatic region instead are EeW striking, dextral strike-slip faults, cutting both the upper and lower crust. The fastest moving seismogenic sources are the most southern thrusts of the Eastern Adriatic and the strike-slip sources of the Southern Western Adriatic, while the seismogenic sources of the Central Adriatic exhibit the lowest slip rates. Estimates of maximum magnitude are generally in good agreement with the historical and instrumental earthquake records, except for the North-Eastern Adriatic region, where seismogenic sources exhibit a potential for large earthquakes even though no strong events have been reported or registered. All sources included in the database are fully geometrically and kinematically parameterized and can be incorportaed in seismic hazard calculations and earthquake or tsunami scenario simulations

Extreme flooding increases poaching mortality in the southernmost stronghold of the endangered marsh deer

Extreme stochastic perturbations can affect population dynamics, but quantitative assessments are scarce for threatened species. The 2015-2016 El Niño-Southern Oscillation (ENSO) caused extreme flooding in the Delta of the Paraná River in Argentina where the southernmost population of the regionally endangered marsh deer (Blastocerus dichotomus) occurs. Using field surveys and data from informants, we studied the impact of this flood on the mortality, distribution, and abundance of this marsh deer population in an area of 1 236 km2. The occurrence of this extreme flood significantly increased marsh deer mortality. One hundred forty-two marsh deer deaths were recorded over the seven-month flood duration, with poaching accounting for 86.6% of deaths. Mortality of marsh deer was significantly higher near urban areas, embankments, and dirt roads, while mortality from poaching was higher in plantations and permanently inundated lands. Two areas of high spatial clustering of poaching mortality were detected, encompassing plantations with easy access or in proximity to urban areas, while embankments appeared to act as attractive population sinks. Flood-related mortality significantly decreased the occurrence of the species in the study area after the flood, but changes in relative abundance between periods were heterogeneous across the landscape, probably because of local migrations. Since climate change is expected to increase the global frequency and magnitude of extreme flood events, our study provides valuable information for mitigating the negative synergistic effects of extreme flooding on marsh deer, as well as for global wildlife populations subjected to periodic extreme floods.Las perturbaciones estocásticas extremas pueden afectar la dinámica de las poblaciones, pero las evaluaciones cuantitativas son escasas para las especies amenazadas. El fenómeno de “El Niño” de 2015-2016 causó inundaciones extremas en el Delta del río Paraná en Argentina, donde se encuentra la población más austral del ciervo de los pantanos (Blastocerus dichotomus), categorizada como En Peligro a nivel regional. En base a relevamientos de campo y datos de informantes, estudiamos el impacto de esta inundación sobre la mortalidad, distribución y abundancia de esta población de ciervo de los pantanos dentro de un área de 1 236 km2. La ocurrencia de esta inundación incrementó signicativamente la mortalidad del ciervo de los pantanos. Hemos registrado 142 individuos muertos durante los siete meses de duración de la inundación, y la caza furtiva representó el 86.6% de las muertes. La mortalidad del ciervo de los pantanos fue signicativamente mayor en proximidad a áreas urbanas, terraplenes y caminos vehiculares, mientras que la mortalidad por cacería fue mayor en plantaciones y terrenos permanentemente inundados. Se detectaron dos áreas de alta concentración espacial de mortalidad por cacería, que abarcaron plantaciones de fácil acceso o próximas a áreas urbanas, mientras que los terraplenes parecen haber funcionado como sumideros atractivos para los ciervos. La mortalidad relacionada con las inundaciones disminuyó signicativamente la presencia de la especie dentro del área de estudio luego de la inundación, pero los cambios en la abundancia relativa entre períodos fueron heterogéneos en todo el paisaje, probablemente como resultado de migraciones locales. Dado que se espera que el cambio climático aumente la frecuencia global y la magnitud de las inundaciones extremas, nuestro estudio proporciona información valiosa para mitigar los efectos sinérgicos negativos de las inundaciones extremas tanto en el ciervo de los pantanos como en poblaciones de otras especies sujetas a inundaciones extremas periódicas.EEA Delta del ParanáFil: Pereira, Javier A. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Pereira, Javier Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Varela, Diego. Universidad Nacional de Misiones. Instituto de Biología Subtropical; ArgentinaFil: Varela, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Subtropical; ArgentinaFil: Varela, Diego. Asociación Civil Centro de Investigaciones del Bosque AtlánticoFil: Thompson, Jeffrey J. Consejo Nacional de Ciencia y Tecnología. Guyra Paraguay; ParaguayFil: Thompson, Jeffrey J. Instituto Saite; ParaguayFil: Lartigau, Bernardo V. Asociación para la Conservación y el Estudio de la Naturaleza; ArgentinaFil: Fracassi, Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; ArgentinaFil: Kittlein, Marcelo J. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología. Instituto de Investigaciones Marinas y Costeras (IIMyC); ArgentinaFil: Kittlein, Marcelo J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Marinas y Costeras (IIMyC); Argentin

Volumetric Differences in Mapped Hippocampal Regions Correlate with Increase of High Alpha Rhythm in Alzheimer's Disease

Objective. The increase of high alpha relative to low alpha power has been recently demonstrated as a reliable EEG marker of hippocampal atrophy conversion of patients with mild cognitive impairment (MCI) in Alzheimer's disease (AD). In the present study we test the reliability of this EEG index in subjects with AD. Methods. Correlation between EEG markers and volumetric differences in mapped hippocampal regions was estimated in AD patients. Results. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of mapped hippocampal regions in Alzheimer's disease. Conclusions. The findings confirm the possible diagnostic role of EEG markers

Seismogenic sources in northeastern Italy and western Slovenia: an overview from the Database of Individual Seismogenic Sources (DISS 3.0.4)

We present an overview of the seismogenic sources of northeastern Italy and western Slovenia, included in the latest version of the Database of Individual Seismogenic Sources (DISS, v. 3.0.4; DISS WORKING GROUP, 2007).DISS’ main object is the Seismogenic Source. DISS Seismogenic Sources are active faults capable of generating Mw > 5.5 earthquakes. We distinguish two main categories of Seismogenic Sources (BASILI et alii, 2008): Individual and Composite

The 9p21 Rs 1333040 polymorphism is associated with coronary microvascular obstruction in ST-segment elevation myocardial infarction treated by primary angioplasty

Background: Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) leads to higher incidence of both early and late complications. A number of single nucleotide polymorphisms in 9p21 chromosome have been shown to affect angiogenesis in response to ischaemia. In particular, Rs1333040 with its three genotypic vriants C/C, T/C and T/T might influence the occurrence of MVO after pPCI. Methods: We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing pPCI. The Rs1333040 polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism using restriction endonucleases (Bsml). Two expert operators unaware of the patients' identity performed the angiographic analysis; collaterals were assessed applying Rentrop's classification. Angiographic MVO was defined as a post-pPCI Thrombolysis In Myocardial Infarction (TIMI)<3 or TIMI 3 with myocardial blush grade 0 or 1, whereas electrocardiographic MVO was defined as ST segment resolution Results: Among our 133 STEMI patients (mean age 63 +/- 11 years, men 72%), 35 (26%) and 53 (40%) respectively experienced angiographic or electrocardiographic MVO. Angiographic and electrocardiographic MVO were different among the three variants (p= 0.03 and p=0.02 respectively). In particular, T/T genotype was associated with a higher incidence of both angiographic and electrocardiographic MVO compared with C/C genotype (p=0.04 and p=0.03 respectively). Moreover, Rentrop score <2 detection rate differed among the three genotypes (p=0.03). In particular T/T genotype was associated with a higher incidence of a Rentrop score <2 as compared with C/C genotype (p= 0.02). Conclusion: Rs1333040 polymorphism genetic variants portend different MVO incidence. In particular, T/T genotype is related to angiographic and electrocardiographic MVO and to worse collaterals towards the culprit artery

Seismogenic sources of the Adriatic domain: an overview from the Database of Individual Seismogenic Sources (DISS 3.1.0)

We present an overview of the seismogenic sources belonging to the interior and the border zones of the Adriatic microplate, included in the latest version of the Database of Individual Seismogenic Sources (DISS, v. 3.1.0; DISS WORKING GROUP, 2009)