ROS-mediated p53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress

The p53 protein is activated by stress signals and exhibits both protective and death-promoting functions that are considered important for its tumor suppressor function. Emerging evidence points toward an additional role for p53 in metabolism. Here, we identify Lpin1 as a p53-responsive gene that is induced in response to DNA damage and glucose deprivation. Lpin1 is essential for adipocyte development and fat metabolism, and mutation in this gene is responsible for the lypodystrophy phenotype in fld mice. We show that p53 and Lpin1 regulate fatty acid oxidation in mouse C2C12 myoblasts. p53 phosphorylation on Ser18 in response to low glucose is ROS and ATM dependent. Lpin1 expression in response to nutritional stress is controlled through the ROS-ATM-p53 pathway and is conserved in human cells. Lpin1 provides a critical link between p53 and metabolism that may be an important component in mediating the tumor suppressor function of p53.     

Synthesis,structure and density functional theory calculations of a novel photoluminescent trisarylborane–bismuth(III) complex

A novel trisarylborane–Bi(III) complex, tris(4‐(dimesitylboryl)phenyl)bismuthine [Bi(PhBMes₂)₃], in which (Ph = phenyl, and Mes = mesityl), was synthesized via the reaction of bismuth (III) chloride (BiCl₃) with three equivalents of lithiated (4‐bromophenyl)‐ dimesitylborane [BrPhBMes₂]. The new trisarylbismuthine was characterized by elemental analysis, ultraviolet–visible (UV–vis) spectroscopy, and NMR (¹H and ¹³C) spectroscopy. The molecular structure of Bi(PhBMes₂)₃ in the solid state was determined using single‐crystal X‐ray diffraction analysis, which showed short intermolecular C–H···H–C contact. The complex is a fluorescent emitter (λ_max = 395 nm) at room temperature and a phosphorescent emitter (λ_max = 423 nm) at 77 K, which displayed a long lifetime of 495 ms. The UV–vis transitions were investigated using density function theory (DFT) and time‐dependent (TD)‐DFT calculations. Natural bond orbital analysis showed that the bismuth (III) center was mainly Lewis acidic in nature.     

HIV-1 Nef promotes cell proliferation and microRNA dysregulation in lung cells

Non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. Lung cancer is the most frequent non-AIDS-defining malignancies in HIV-infected patients. The mechanism of the increased risk for lung cancer in HIV-1 patients is poorly understood. HIV-1 Nef protein has been suggested to be one of the key players in HIV-related lung disease. In here, we showed the involvement of Nef protein in cell modifications such as fibroblasts (IMR-90) and normal (BEAS-2B) or cancerous (A549) epithelial cells. We demonstrated that Nef protein reprograms initial stages of lung cancer (e.g. changes in the metabolism, improved cell survival and invasion, increase the angiogenesis factor VEGF). Additionally, we showed that Nef is provoking a global decrease of mature miRNA and a decrease of DICER1 and AGO expression in lung cells. MiRNAs play a crucial role in cell signaling and homeostasis, functioning as oncogenes or tumor suppressors, and their dysregulation can contribute to the tumorigenic process. These results showed that HIV-1 Nef protein is directly involved in preventing cell death and contributes to tumor progression.     

The effect of time of day on short-term maximal performance in obese and non-obese young men

The purpose of this study was to examine time-of-day effects on short-term performance in obese young men. In a balanced study design, 30 boys were divided into two groups: obese (OG; n = 15) and non-obese (CG; n = 15) groups. Both groups performed anaerobic tests of strength and power (squat-Jump, SJ; counter-movement jump, CMJ; 10-m sprint; and 30-m sprint) at 08:00 and 17:00 h on separate days. The results showed morning–evening differences in all variables in CG, with significant increases at 17:00 h (around the time of peak temperature) in comparison with 08:00 h (p < 0.01) for OG. However, such morning-evening differences were not found in the OG, except for the 30-m sprint. Obesity affects the diurnal variation on performances of 30-m sprint with a significant decrease in the evening for OG of 1.23% (p < 0.01). A correlation between anaerobic performance and oral temperature was observed only in the 30-m sprint test. In conclusion, the findings of the present study indicated that obesity is a problem that can affect circadian rhythms and performance in obese young men; therefore, preventing childhood obesity should become a top priority in efforts to improve performance and health.     

Unique disulfide bonds in epidermal growth factor (EGF) domains of β3 affect structure and function of αIIbβ3 and αvβ3 integrins in different manner

The β3 subunit of αIIbβ3 and αvβ3 integrins contains four epidermal growth factor (EGF)-like domains. Each domain harbors four disulfide bonds of which one is unique for integrins. We previously discerned a regulatory role of the EGF-4 Cys-560-Cys-583 unique bond for αIIbβ3 activation. In this study we further investigated the role of all four integrin unique bonds in both αIIbβ3 and αvβ3. We created β3 mutants harboring serine substitutions of each or both cysteines that disrupt the four unique bonds (Cys-437-Cys-457 in EGF-1, Cys-473-Cys-503 in EGF-2, Cys-523-Cys-544 in EGF-3, and Cys-560-Cys-583 in EGF-4) and transfected them into baby hamster kidney cells together with normal αv or αIIb. Flow cytometry was used to measure surface expression of αIIbβ3 and αvβ3 and their activity state by soluble fibrinogen binding. Most cysteine substitutions caused similarly reduced surface expression of both receptors. Disrupting all four unique disulfide bonds by single cysteine substitutions resulted in variable constitutive activation of αIIbβ3 and αvβ3. In contrast, whereas double C437S/C457S and C473S/C503S mutations yielded constitutively active αIIbβ3 and αvβ3, the C560S/C583S mutation did not, and the C523S/C544S mutation only yielded constitutively active αIIbβ3. Activation of C523S/C544S αvβ3 mutant by activating antibody and dithiothreitol was also impaired. Molecular dynamics of C523S/C544S β3 in αIIbβ3 but not in αvβ3 displayed an altered stable conformation. Our findings indicate that unique disulfide bonds in β3 differently affect the function of αIIbβ3 and αvβ3 and suggest a free sulfhydryl-dependent regulatory role for Cys-560-Cys-583 in both αIIbβ3 and αvβ3 and for Cys-523-Cys-544 only in αvβ3.     

La neurólisis del nervio mediano en el paciente anciano: evaluación a largo plazo

Purpose

Carpal tunnel release by opening the flexor retinaculum is considered a satisfactory treatment. However, several factors, like ageing, may influence postoperative results. We present the long term outcomes in elderly patients.

Methods

This is an historical prospective long term study of 52 patients who received surgical treatment of carpal tunnel syndrome when they were 65 or older. We have carried out a clinical-functional (with the Levine questionnaire), electromyographic and dynamometric valuation of the patients studied, up to ten years from the surgery.

Results

The results of Levine's questionnaire, revealed favourable data for a mean follow-up of 10.35 years, with a mean improvement in the clinical score of 1.93 points (95% confidence interval [CI]: 1.72-2.17) and in the functional score of 0.83 points (95% CI: 0.68-0.99). Similarly, the electromyographic values showed a significant improvement compared to preoperative ones (mean difference of sensory velocity of 8.43 m/s, 95% CI: 8.17-11.63; mean difference of motor latency of 1.65 ms, 95% CI: 1.24-2.25). The data on grip strength did not reach statistical significance.

Conclusions

In elderly patients, complete section of the carpal transverse ligament, allows maintaining favourable differences in most of the parameters studied, ten years after surgery, making the surgical treatment a recommendable option.     

Amniocentesis, maternal psychopathology and prenatal representations of attachment: a prospective comparative study

Background

The aim of the study was to characterize the maternal dimensions of anxiety, depression and prenatal attachment in women undergoing an amniocentesis.

Methodology/Principal Findings

A prospective observational study was conducted. Women were referred to early amniocentesis for increased nuchal translucency, elevated biochemical markers or advanced maternal age. All participants had 3 prenatal (16–18, 20–24, 30–34 weeks of gestation) and one postnatal (30–45 days) interviews reviewing for demographic, medical, and psychiatric information (STAI State-Trait Anxiety Inventory; EPDS: Edinburgh Postnatal Depression Scale; IRMAG: Interview of Maternal Representations of Attachment during pregnancy). We investigated 232 pregnant women who undergone an amniocentesis compared with 160 pregnant controls. Following the procedure, the amniocentesis group experienced transiently significantly higher levels of state-anxiety on the STAI (44.6 vs. 39.3) and depression as measured by the EPDS (9.4 vs. 6.3) than the controls. Overall in both groups, the maternal representations of attachment were well integrated and balanced, but the amniocentesis group experienced significantly more mother-directed representations.

Conclusions/Significance

Amniocentesis is associated with higher affective adaptive reactions that tend to normalize during the pregnancy, with overall preserved maternal fetal representations of attachment.     

Effect of Different Selenium Supplementation Levels on Selenium Status in Camel

Twelve female camels divided into three groups received, after a 2-week adaptation period, an oral Se supplementation (0, 2, and 4 mg, respectively) under sodium selenite form for 3 months. Feed intake was assessed daily, blood samples and body weight were taken on a weekly basis, and feces and urine samples were collected every 2 weeks up to 1 month after the end of the supplementation period. The Se concentration in serum was increased significantly in supplemented groups. The maximum level was observed in the period of supplementation in the camel receiving 4 mg (492.5 ng/mL), which was fourfold higher than the value at the beginning of the trial (126 to 138.5 ng/mL according to the groups). The selenium concentration increased significantly in urine and feces but to a lesser extent. A similar trend was observed with glutathione-peroxidase (GSH-Px) values varying between 8.4 and 96.5 IU/g Hb. However, no difference occurred between the two groups receiving 2 or 4 mg Se at the supplementation period. Vitamin E (mean 1.13 +/- 0.61 microg/mL with range 0.27-3.09) did not change significantly. Significant correlations were reported between serum Se, GSH-Px, fecal, and urinary excretion or concentration.     

Th17 immune response to adipose tissue-derived mesenchymal stromal cells

Adipose tissue-derived mesenchymal stromal cells (ASCs) hold the promise of achieving successful immunotherapeutic results due to their ability to regulate different T-cell fate. ASCs also show significant adaptability to environmental stresses by modulating their immunologic profile. Cell-based therapy for inflammatory diseases requires a detailed understanding of the molecular relation between ASCs and Th17 lymphocytes taking into account the influence of inflammation and cell ratio on such interaction. Accordingly, a dose-dependent increase in Th17 generation was only observed in high MSC:T-cell ratio with no significant impact of inflammatory priming. IL-23 receptor (IL-23R) expression by T cells was not modulated by ASCs when compared to levels in activated T cells, while ROR-γt expression was significantly increased reaching a maximum in high (1:5) unprimed ASC:T-cell ratio. Finally, multiplex immunoassay showed substantial changes in the secretory profile of 15 cytokines involved in the Th17 immune response (IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40, and TNF-α), which was modulated by both cell ratio and inflammatory priming. These findings suggest that Th17 lymphocyte pathway is significantly modulated by ASCs that may lead to immunological changes. Therefore, future ASC-based immunotherapy should take into account the complex and detailed molecular interactions that depend on several factors including inflammatory priming and cell ratio.     

Revisiting methods for assessing and comparing left ventricular diastolic stiffness: impact of relaxation, external forces, hypertrophy, and comparators

Understanding diastolic function mandates feasible and accurate methods to construct and compare the diastolic pressure (P)-volume (V) relationship (PVR). This study compared the relaxation-corrected single beat (RC-SB) to the multiple-beat (MB) (vena cava occlusion) method for constructing the diastolic PVR in 26 young normal or old hypertensive dogs before and after increases in afterload (phenylephrine) or acute volume expansion in the presence (n = 14) or absence (n = 12) of the pericardium. The PVR data were fit to P = alphae(beta x V). Derived stiffness indexes compared included the stiffness coefficient (beta), curve-fitting constant (alpha), and the end-diastolic volume (EDV) at 10, 20, or 30 mmHg [EDV(x) = ln(P(x)/alpha)/beta] to account for covariance in alpha and beta. In pericardium-intact young normal and old hypertensive dogs studied over varying afterloads, the MB and RC-SB PVR appeared identical. The beta (r = 0.62) and alpha (r = 0.69) derived from the RC-SB vs. MB PVR showed moderate correlation but poor agreement. In contrast, the EDV(10-30) derived from RC-SB vs. MB PVR showed excellent correlation (r = 0.97) and agreement. The uncorrected SB method underestimated stiffness. As expected, after acute volume expansion, the RC-SB PVR was shifted upward from the MB PVR (decreased EDV(10-30); P < 0.05) in the pericardium-intact but not pericardium-absent dogs. The RC-SB method can substitute for the MB technique in construction of PVR in the absence of acute volume expansion. The concordance between these two methods was poorly reflected by comparing the derived alpha and beta but apparent when using EDV(10-30), which provides information regarding the position of the PVR in a single number.