Structural and biochemical insights of CypA and AIF interaction

The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed. We show that AIF(370-394) interacts with CypA on the same surface recognized by AIF(Δ1-121) protein and that the region is very close to the CypA catalytic pocket. Such region partially overlaps with the binding site of cyclosporin A (CsA), the strongest catalytic inhibitor of CypA. Our data point toward distinct CypA structural determinants governing the inhibitor selectivity and the differential biological effects of AIF and CsA, and provide new structural insights for designing CypA/AIF selective inhibitors with therapeutic relevance in neurodegenerative diseases

Early Prediction of Corpus Luteum Functionality Using an Imaging Software

The present study aimed to assess the applicability of luteal blood flow data acquired through the use of color Doppler ultrasonography and a post-processing analysis tool (ImageJ) for predicting pregnancy in buffaloes (Bubalus bubalis). The experiment was carried out on 59 multiparous Italian Mediterranean buffaloes that underwent synchronization of estrus and fixed-time artificial insemination (TAI). Corpus luteum features (size: CLS and blood flow: BFA) were taken from Day 5 to 10 after TAI and retrospectively measured with ImageJ. In the same period, blood samples were taken to assess progesterone (P4) concentrations. Pregnancy diagnosis was carried out on Day 45 by ultrasound and confirmed on Day 70 post-TAI. Differences in CLS, BFA, and P4 concentrations from Day 5 to 10 after TAI measured between groups were analyzed by ANOVA repeated measures as were differences within each day of measuring. Buffaloes that established a pregnancy (n = 29; 55%) had larger CLS (2.2 ± 0.1 vs. 1.9 ± 0.1 cm2; P < 0.01), higher BFA (0.6 ± 0.0 vs. 0.4 ± 0.0 cm2; P < 0.01), and higher P4 blood level (1.8 ± 0.1 vs. 1.4 ± 0.1; P < 0.01) during Day 5–10 as compared to not-pregnant buffaloes (n = 22). Throughout the entire period, the first feature that changed between groups was P4 blood concentration at Day 7 (1.7 ± 0.1 vs. 1.2 ± 0.1; P < 0.05) followed by BFA at Day 8 (0.6 ± 0.0 vs. 0.5 ± 0.0; P < 0.05), respectively, in pregnant and not-pregnant animals. The ROC analyses indicated that P4 was able to predict pregnancy since Day 5 (P < 0.05) although a more reliable result could be obtained from Day 8 (P < 0.01). At Day 10, it was possible to set a cutoff value for every parameter taken into account. The logistic regression analysis showed that pregnancy was positively influenced by P4 concentration (odds ratio 534.127; P < 0.01) and BFA (odds ratio 744.893; P < 0.01). In conclusion, the use of color Doppler ultrasonography, together with ImageJ, identified different patterns of BFA between pregnant and not-pregnant buffaloes starting from Day 8 post-TAI

Charlson Comorbidity Index does not predict long-term mortality in elderly subjects with chronic heart failure

Methods: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI.Findings: in elderly subjects stratified for CCI (1-3 and &gt;= 4), mortality was higher in non-CHF subjects with CCI &gt;= 4 (52.4% versus 70%, P &lt; 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01-1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04-8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF.Conclusion: CCI does not predict long-term mortality in elderly subjects with CHF

Geomorphology of Naples and the Campi Flegrei: human and natural landscapes in a restless land

Naples and its surroundings are a very young landscape, originated from 40 ka in response to strong and explosive volcanic processes, which created the Campi Flegrei, one of the largest volcanic fields of the world. Despite the repeated and continuous volcanic activity, this territory was selected for human settlements since Neolithic times and hosted some of the most important Greek and Roman towns in the Mediterranean area (e.g., Cuma, Parthenope, Neapolis, Baia and Puteoli). Geoarcheological data and historical chronicles testify to human coexistence with eruptions, bradyseismic ground motions, coastline changes, floods and landslides. With the aim of describing the geomorphological evolution of this area to a wide audience, including also non-experts, we constructed a synthetic geomorphological map of the area and sketches that synthesise the main stages of the geomorphological evolution of the historical centre of Naples and the coastal belt of the Gulf of Pozzuoli during the last millennia

Mortality and heart rate in the elderly: role of cognitive impairment

Mortality related to heart rate ( HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment ( CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 ( n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (&lt; 69,70-75,76-80, and &gt; 80 bpm), mortality was linearly associated with increased HR in all ( from 47.7 to 57.0; r(2) = .43, p = .019) and in subjects without ( from 41.7 to 51.1%; r(2) = .50, p = .043) but not in those with CI ( from 57.5 to 66.1; r(2) = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects ( RR 0.69; 95% CI = 0.27-1.73) or in those with CI ( RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI ( RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly

PediaVirus chatline: all together against COVID-19

n/

Waist circumference but not body mass index predicts long-term mortality in elderly subjects with chronic heart failure

OBJECTIVESTo examine whether waist circumference (WC) and body-mass index (BMI) can predict long-term mortality in elderly subjects with and without chronic heart failure (CHF).DESIGNLongitudinal evaluation with a 12-year follow-up.SETTINGCampania, a region of southern Italy.PARTICIPANTSOne thousand three hundred thirty-two subjects aged 65 and older selected from the electoral rolls of Campania.MEASUREMENTSThe relationship between WC or BMI and mortality during a 12-year follow-up in 125 subjects with and 1,143 subjects without CHF.RESULTSMortality increased as WC increased in elderly subjects without CHF (from 47.8% to 56.7%, P=.01), and the increase was even greater in patients with CHF (from 58.1% to 82.0%, P=.01). In contrast, mortality decreased as BMI increased in elderly subjects without CHF (from 53.8% to 46.1%, P0 =.046) but not in those with CHF. According to Cox regression analysis, BMI protected against long-term mortality in the absence but not in the presence of CHF. In the absence of CHF, WC was associated with a 2% increased risk of long-term mortality for each 1-cm greater WC (Hazard Ratio (HR)=1.02, 95% confidence interval (CI)=1.01-1.03; P &lt;.001), versus 5% increased in the presence of CHF (HR=1.06, 95% CI=1.02-1.10; P &lt;.001).CONCLUSIONWC, but not BMI, is predictive of long-term mortality in elderly individuals with CHF and to a lesser extent in those without CHF

Development of In–Cu binary oxide catalysts for hydrogenating CO2 via thermocatalytic and electrocatalytic routes

Carbon dioxide (CO2) hydrogenation to obtain valuable chemicals and fuels via thermocatalysis or electrocatalysis is a promising and sustainable method for CO2 utilization. Here, binary In-Cu oxide co-precipitated materials were investigated to evaluate the catalytic performance in the mentioned conversion processes. The In-rich binary material exhibits remarkable selectivity (>60%) to methanol along with high activity for CO2 conversion (>2%) at 21 bar and 300 °C, achieving a productivity of about 265 mgMeOH h−1 gIn2O3−1, which is almost 3 times higher than that of the bare In2O3 catalyst. CO2-temperature programmed desorption revealed that the basicity of the In-rich catalyst remains constant between the calcined and spent samples, so the capacity to adsorb CO2 does not vary when the catalyst is exposed to the reaction atmosphere. Such a catalyst was demonstrated to be active for formate production in the electrochemical process as the main product. Ex situ characterization after testing proved that the In2O3 phase was the active site of methanol synthesis during CO2 hydrogenation at high temperatures and pressures. In contrast, depending on the cell configuration, different indium interfaces were stabilized at the electrocatalyst surface under ambient conditions. It is envisioned that the co-presence of In0, In2O3, and In(OH)3 phases increases the local amount of *CO intermediates, promoting the formation of more reduced products, such as ethanol and 2-propanol, through the *CO dimerization reaction in the electrochemical process. These findings highlight the potential of nonreducible hydroxides as promoters in the electrochemical CO2 reduction process

Managing Symptom Profile of IBS-D Patients With Tritordeum-Based Foods: Results From a Pilot Study

In the past few years, increasing attention has been given to the pathologic role of specific foods in IBS, like wheat and other cereals. Recent literature describes IBS patients who may experience gastrointestinal (GI) and extra-GI symptoms precipitated by the ingestion of cereals. Tritordeum is a cereal of Spanish origin derived from the hybridization of durum wheat and wild barley. It is different from classic wheat for its gluten protein composition, with fewer carbohydrates and fructans and a higher content of proteins, dietary fibers, and antioxidants. This pilot study aimed to investigate the effects of a 12-week diet with Tritordeum-based foods in substitution of other cereals on the profile of GI symptoms (evaluated by appropriate questionnaire) and the health of the GI barrier (assessed by sugar absorption test and different markers of integrity and functions) in 16 diarrhea-predominant IBS (IBS-D) patients. The diet with Tritordeum-based foods (bread, bakery products, and pasta) significantly reduced IBS-D patients' symptoms. This amelioration appears to occur through an overall improvement of the GI barrier, as demonstrated by the reduced intestinal permeability and the decreased levels of markers of intestinal mucosal integrity, mucosal inflammation, and fermentative dysbiosis