The Effect of Germanium‐Loaded Hydroxyapatite Biomaterials on Bone Marrow Mesenchymal Stem Cells Growth

Hydroxyapatite (HA) is a hard mineral component of mineralized tissues, mainly composed of calcium and phosphate. Due to its bioavailability, HA is potentially used for the repair and regeneration of mineralized tissues. For this purpose, the properties of HA are significantly improved by adding natural and synthetic materials. In this sense, the germanium (Ge) mineral was loaded in HA biomaterial by cold isostatic pressure for the first time and characterization and biocompatibility using bone marrow mesenchymal stem cells (BM-MSCs) were investigated. The addition of Ge at 5% improved the solubility (3.32%), stiffness (18.34 MPa), water holding (31.27%) and biodegradation (21.87%) properties of HA, compared to control. Compared to all composite biomaterials, the drug-releasing behavior of HA-3% Ge was higher at pH 1 and 3 and the maximum drug release was obtained at pH 7 and 9 with HA-5% Ge biomaterials. Among the different mediums tested, the DMEM-medium showed a higher drug release rate, especially at 60 min. HA-Ge biomaterials showed better protein adhesion and apatite layer formation, which ultimately proves the compatibility in BM-MSCs culture. Except for higher concentrations of HA (5 and 10 mg/mL), the different concentrations of Ge and HA and wells coated with 1% of HA-1% Ge had higher BM-MSCs growth than control. All these findings concluded that the fabricated HA biomaterials loaded with Ge could be the potential biomaterial for culturing mammalian cells towards mineralized tissue repair and regeneration.This research was funded by MCIN/AEI/10.13039/501100011033 Grant numbers PID2020-116693RB-C21 and PID2020-116693RB-C22Generalitat Valenciana Grant number CIAICO/2021/157and Internal Research Fund from Universidad Católica San Antonio de Murcia (UCAM), Grant number PMAFI-27/21, Murcia, Spain

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

How do psychosocial determinants in migrant women in the Netherlands differ from these among their counterparts in their country of origin? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Migration of non-Western women into Western countries often results in an increase in smoking prevalence among migrant women. To gain more insight into how to prevent this increase, we compared psychosocial determinants of smoking between Surinamese women in Suriname and those in the Netherlands.</p> <p>Methods</p> <p>Data were obtained between 2000 and 2004 from two cross-sectional studies, the CVRFO study in Suriname (n = 702) and the SUNSET study in the Netherlands (n = 674). For analyses of determinants, we collected additional data in CVRFO study population (n = 85). Differences between the two groups were analysed by chi-square analyses and logistic regression analyses.</p> <p>Results</p> <p>As was found in other studies among migrant women, more Surinamese migrant women in the Netherlands smoked (31%) than women in Suriname (16%). More Surinamese women in the Netherlands than in Suriname had a positive affective and cognitive attitude towards smoking (OR = 2.6 (95%CI 1.05;6.39) and OR = 3.3 (95%CI 1.31;8.41)). They perceived a positive norm within their partners and friends regarding smoking more frequently (OR = 6.5 (95%CI 2.7;15.6) and OR = 3.3 (95%CI 1.50;7.25)).</p> <p>Conclusion</p> <p>Migrant women are more positive towards smoking and perceived a more positive norm towards smoking when compared with women in the country of origin. Interventions targeted at the psychosocial determinants regarding smoking for newly migrated women, in particular the consequences of smoking and the norm towards smoking might help to prevent an increase in smoking in those populations.</p

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Linkage mapping of the Phg-1 and Co-14 genes for resistance to angular leaf spot and anthracnose in the common bean cultivar AND 277

The Andean common bean AND 277 has the Co-14 and the Phg-1 alleles that confer resistance to 21 and eight races, respectively, of the anthracnose (ANT) and angular leaf spot (ALS) pathogens. Because of its broad resistance spectrum, Co-14 is one of the main genes used in ANT resistance breeding. Additionally, Phg-1 is used for resistance to ALS. In this study, we elucidate the inheritance of the resistance of AND 277 to both pathogens using F2 populations from the AND 277 × Rudá and AND 277 × Ouro Negro crosses and F2:3 families from the AND 277 × Ouro Negro cross. Rudá and Ouro Negro are susceptible to all of the above races of both pathogens. Co-segregation analysis revealed that a single dominant gene in AND 277 confers resistance to races 65, 73, and 2047 of the ANT and to race 63-23 of the ALS pathogens. Co-14 and Phg-1 are tightly linked (0.0 cM) on linkage group Pv01. Through synteny mapping between common bean and soybean we also identified two new molecular markers, CV542014450 and TGA1.1570, tagging the Co-14 and Phg-1 loci. These markers are linked at 0.7 and 1.3 cM, respectively, from the Co-14/Phg-1 locus in coupling phase. The analysis of allele segregation in the BAT 93/Jalo EEP558 and California Dark Red Kidney/Yolano recombinant populations revealed that CV542014450 and TGA1.1570 segregated in the expected 1:1 ratio. Due to the physical linkage in cis configuration, Co-14 and Phg-1 are inherited together and can be monitored indirectly with the CV542014450 and TGA1.1570 markers. These results illustrate the rapid discovery of new markers through synteny mapping. These markers will reduce the time and costs associated with the pyramiding of these two disease resistance genes