Effect of cholecalciferol on unsaturated model membranes

Vitamin D plays an important role in many physiological processes, particularly calcium and phosphorous homeostasis. The biochemistry of vitamin D is also complex, encompassing a range of active molecules that may be either endogenous or dietary in origin. The role of lipids and fats in the production, processing and use of vitamin D is an interesting one, with a relative paucity of model studies into the interactions of vitamin D with lipidic systems such as micelles and vesicles. Here, we have studied the effect of vitamin D3 in simple unsaturated phospholipid systems. We used NMR and FTIR spectroscopy to investigate the effect of increasing vitamin D concentration on the structure and dynamics of the lipid chains and interfacial region. In order to link these model studies with more complex biomimetic environments, we compare results in the presence of buffer and vitamin D binding protein. We have also used DLS to determine that vitamin D3-DOPC vesicles can retain their size distribution for varying amounts of time in different conditions. We find that the acyl chain region of vitamin D3-DOPC membranes are generally disordered, and that the addition of buffer and/or protein alters the properties of the interfacial region

Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Layered, Tunable Graphene Oxide-Nylon Heterostructures for Wearable Electrocardiogram Sensors

Nanoscale engineered materials combined with wearable wireless technologies can deliver a new level of health monitoring. A reduced graphene oxide-nylon composite material is developed and tested, demonstrating its usefulness as a material for sensors in wearable, long-term electrocardiogram (ECG) monitoring via a comparison to one of the widely used ECG sensors. The structural analysis by scanning electron (SEM) and atomic force microscopy (AFM) shows a limited number of defects on a macroscopic scale. Fourier Transform Infrared (FTIR) and Raman spectroscopy confirm the presence of rGOx, and the ratio of D- and G-features as a function of thickness correlates with the resistivity analysis. The negligible effect of the defects and the tunability of electrical and optical properties, together with live ECG data, demonstrate its signal transduction capability.Comment: 7 main text and 4 supporting figures, under revie

Urinary nitrate might be an early biomarker for pediatric acute kidney injury in the emergency department

NO is involved in normal kidney function and perturbed in acute kidney injury (AKI). We hypothesized that urinary concentration of NO metabolites, nitrite, and nitrate would be lower in children with early AKI presenting to the emergency department (ED), when serum creatinine (SCr) was uninformative. Patients up to 19 y were recruited if they had a urinalysis and SCr obtained for routine care. Primary outcome, AKI, was defined by pediatric Risk, Injury, Failure, Loss of function, End-stage renal disease (pRIFLE) criteria. Urinary nitrite and nitrate were determined by HPLC. A total of 252 patients were enrolled, the majority (93%) of whom were without AKI. Although 18 (7%) had AKI by pRIFLE, 50% may not have had it identified by the SCr value alone at the time of visit. Median urinary nitrate was lower for injury versus risk (p = 0.03); this difference remained significant when the injury group was compared against the combined risk and no AKI groups (p = 0.01). Urinary nitrite was not significantly different between groups. Thus, low urinary nitrate is associated with AKI in the pediatric ED even when SCr is normal. Predictive potential of this putative urinary biomarker for AKI needs further evaluation in sicker patients

Targeting IL-11R/EZH2 Signaling Axis as a Therapeutic Strategy for Osteosarcoma Lung Metastases

Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression of genes repressed by histone methyltransferase EZH2, including members of the WNT pathway, a known target pathway of EZH2. Exogenous IL-11 increased the global levels of histone H3 lysine 27 trimethylation, evidence of EZH2 activation. Treatment with the EZH2 inhibitor GSK126 significantly reduced in vitro proliferation and increased cell-cycle arrest and apoptosis, which were partially mediated through the WNT pathway. In vivo, treatment of an orthotopic nude mouse model of OS with GSK126 inhibited lung metastatic growth and prolonged survival. In addition, significantly shorter recurrence-free survival was seen in OS patients with high levels of EZH2 in their primary tumors (P \u3c .05). This suggests that IL-11Rα promotes OS lung metastasis via activation of EZH2. Thus, blocking EZH2 activity may be an effective strategy for inhibiting OS lung metastasis and improving prognosis

Artificial neural network for performance modelling of shape memory alloy

In recent years, significant strides in technological advancement have revolutionized our lifestyles, driving a surge in demand for multifunctional and intelligent materials. Among these materials, Shape Memory Alloy (SMA) stands out for its unique ability to memorize and revert to its original shape through phase transformation. Despite its remarkable properties, SMAs exhibit a minor limitation in accurately retaining their original shape or length. Furthermore, there is a notable dearth of information regarding the modelling of SMA behaviour with high precision. This study endeavors to address these challenges by integrating experimental data with neural network modelling to comprehensively examine SMA behaviour for mechanical applications. Leveraging an experimental dataset, this research employs feedforward backpropagation neural network (BPNN) modelling to forecast the strain recovery of SMA Nitinol alloy. The model aims to predict the recovery strain of SMA by utilizing three input parameters: temperature conditional, number of coils, and initial length. Remarkably, the achieved error rates of 0.29%, 0.80%, and 9.20% for various strain measurements significantly undercut the commonly accepted error threshold of 10% for nonlinear data predictions in SMA behaviour. The final results underscore the high prediction accuracy of the Artificial Neural Network (ANN), offering promising prospects for SMA applications involving temperature-strain interactions and enhancing engineering design

The Keynesian Multiplier Effect Reconsidered

The Keynesian multiplier effect is reinterpreted and several issues that may have misled assessments of the effect of fiscal spending are discussed. It is shown that even in the textbook Keynesian framework some transfer policy 'reduces' aggregate demand and that public works spending may completely crowd out private consumption. Useless public works are found to be equivalent to transfers although they increase accounting national income more than transfers do. The net effect of fiscal spending on national benefits is explored and shown to equal only the direct benefit created by the spending