Callous-Unemotional (CU) traits identify children at high risk of antisocial behavior. A recent theoretical model proposed that CU traits arise from low sensitivity to threat and affiliation. To ...assess these dimensions, we developed the parent- and self-reported Sensitivity to Threat and Affiliative Reward Scale (STARS) and tested its psychometric properties, factor structure, and construct validity. Samples 1 (N =3 03; age 3–10; United States) and 2 (N = 854 age 5–9; Spain) were children and Sample 3 was 514 young adults (Mage = 19.89; United States). In Sample 1, differential item functioning and item response theory techniques were used to identify the best-performing items from a 64-item pool, resulting in 28 items that functioned equivalently across age and gender. Factor analysis indicated acceptable fit for the theorized two-factor structure with separate threat and affiliation factors in all three samples, which showed predictive validity in relation to CU traits in children and psychopathic traits in young adults.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Halitosis in children implies psychosocial repercussions. Risk factors associated with this condition are unclear, and detection methods are inaccurate.
To quantify the levels of sulfur-like ...compounds in children with asthma and healthy children from a novel validated assay, and to establish the risk factors related to halitosis.
One hundred and twenty-eight individuals (63 healthy and 65 asthmatic) from 3 to 17 years of age were tested using a passive colorimetric sensor to measure the levels of sulfur-like compounds in breath and saliva. Information was collected on oral hygiene habits, gingival and dental health, breathing type, and dental malocclusion.
The mean values of hydrogen sulfide were 4.0 ± 6.8 and 19.7 ± 12.2 ppbv (parts per billion in volume) in the control and asthmatic groups, respectively (p < .001). The presence of higher concentrations of sulfur compounds was significantly associated (p < .05) with the presence of gingival inflammation, tongue coating, dental plaque, mouth breathing, hypomineralization, age, tongue brushing, and the use of dental floss.
The level of sulfur in breath and saliva was significantly higher in patients with asthma. These results can serve as a precedent to raise awareness among paediatricians and parents about oral hygiene care in children and adolescents.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Elucidation of the conditions in which associative learning occurs is a critical issue in neuroscience and comparative psychology. In Pavlovian conditioning in mammals, it is thought that the ...discrepancy, or error, between the actual reward and the predicted reward determines whether learning occurs. This theory stems from the finding of Kamin's blocking effect, in which after pairing of a stimulus with an unconditioned stimulus (US), conditioning of a second stimulus is blocked when the two stimuli are presented in compound and paired with the same US. Whether this theory is applicable to any species of invertebrates, however, has remained unknown. We first showed blocking and one-trial blocking of Pavlovian conditioning in the cricket
, which supported the Rescorla-Wagner model but not attentional theories, the major competitive error-correction learning theories to account for blocking. To match the prediction error theory, a neural circuit model was proposed, and prediction from the model was tested: the results were consistent with the Rescorla-Wagner model but not with the retrieval theory, another competitive theory to account for blocking. The findings suggest that the Rescorla-Wagner model best accounts for Pavlovian conditioning in crickets and that the basic computation rule underlying Pavlovian conditioning in crickets is the same to those suggested in mammals. Moreover, results of pharmacological studies in crickets suggested that octopamine and dopamine mediate prediction error signals in appetitive and aversive conditioning, respectively. This was in contrast to the notion that dopamine mediates appetitive prediction error signals in mammals. The functional significance and evolutionary implications of these findings are discussed.
Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood. Here, we show that promoter DNA demethylation is associated with the activation of ...hematopoietic-specific genes. Using genome-wide promoter methylation arrays, we identified 694 hematopoietic-specific genes repressed by promoter DNA methylation in human embryonic stem cells and whose loss of methylation in hematopoietic can be associated with gene expression. The association between promoter methylation and gene expression was studied for many hematopoietic-specific genes including CD45, CD34, CD28, CD19, the T cell receptor (TCR), the MHC class II gene HLA-DR, perforin 1 and the phosphoinositide 3-kinase (PI3K) and results indicated that DNA demethylation was not always sufficient for gene activation. Promoter demethylation occurred either early during embryonic development or later on during hematopoietic differentiation. Analysis of the genome-wide promoter methylation status of induced pluripotent stem cells (iPSCs) generated from somatic CD34+ HSPCs and differentiated derivatives from CD34+ HSPCs confirmed the role of DNA methylation in regulating the expression of genes of the hemato-immune system, and indicated that promoter methylation of these genes may be associated to stemness. Together, these data suggest that promoter DNA demethylation might play a role in the tissue/cell-specific genome-wide gene regulation within the hematopoietic compartment.
Human serum albumin (HSA) has a single reduced cysteine residue, Cys34, whose acidity has been controversial. Three experimental approaches (pH-dependence of reactivity towards hydrogen peroxide, ...ultraviolet titration and infrared spectroscopy) are used to determine that the pKa value in delipidated HSA is 8.1±0.2 at 37°C and 0.1M ionic strength. Molecular dynamics simulations of HSA in the sub-microsecond timescale show that while sulfur exposure to solvent is limited and fluctuating in the thiol form, it increases in the thiolate, stabilized by a persistent hydrogen-bond (HB) network involving Tyr84 and bridging waters to Asp38 and Gln33 backbone. Insight into the mechanism of Cys34 oxidation by H2O2 is provided by ONIOM(QM:MM) modeling including quantum water molecules. The reaction proceeds through a slightly asynchronous SN2 transition state (TS) with calculated Δ‡G and Δ‡H barriers at 298K of respectively 59 and 54kJmol−1 (the latter within chemical accuracy from the experimental value). A post-TS proton transfer leads to HSA–SO− and water as products. The structured reaction site cages H2O2, which donates a strong HB to the thiolate. Loss of this HB before reaching the TS modulates Cys34 nucleophilicity and contributes to destabilize H2O2. The lack of reaction-site features required for differential stabilization of the TS (positive charges, H2O2 HB strengthening) explains the striking difference in kinetic efficiency for the same reaction in other proteins (e.g. peroxiredoxins). The structured HB network surrounding HSA–SH with sequestered waters carries an entropic penalty on the barrier height. These studies contribute to deepen the understanding of the reactivity of HSA–SH, the most abundant thiol in human plasma, and in a wider perspective, provide clues on the key aspects that modulate thiol reactivity against H2O2.
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•The pKa for delipidated HSA thiol is 8.1 at 37°C and 0.1M ionic strength.•HSA thiolate is stabilized by H-bonding with Tyr84 and waters bridging to Asp38.•Calculated ΔH‡ and ΔG‡ to oxidize Cys34 by H2O2 respectively are 54 and 59kJmol−1.•A post-transition state proton transfer leads to HSA sulfenate and water.•Theoretical data is in excellent agreement with temperature dependency of kinetics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is ...thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45+F4/80+CD11b+CX3CR1+CD206-) and pro-fibrotic (CD45+F4/80+CD11b+CX3CR1+CD206+TGFβ+) to an anti-inflammatory (CD45+F4/80+CD11b+CD206+TGFβ-) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and ...non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.
Background
Implant dentistry is subject to major economic pressures as a result of the growth in the manufacturing and commercialization of dental implants.
Purpose
To examine research funding in ...implant dentistry by means of a bibliometric analysis of articles indexed in Web of Science (WoS) published during the period 2008‐2017.
Materials and Methods
The search was conducted applying the truncated term “implant*” in the WoS dentistry area. Only items labeled as “article” or “review” were selected. Records were manually refined and normalized to unify terms and to remove typographical, transcription, and/or indexing errors.
Results
A total of 14 255 records were identified for analysis. About 5002 of the 14 255 published works received funding. Of these, 85.9% of funded research articles received at least one citation. Of the 7733 funding entities mentioned, 29.8% were government entities, 25% NGOs and Foundations, 23.7% private companies, 19.6% academic entities, and 1.9% hospitals and research centers. Clinical Oral Implants Research and the International Journal of Oral & Maxillofacial Implants published the highest numbers of funded articles.
Conclusions
This study revealed an overall increase in the funding of research in implant dentistry in recent years. Funded articles were cited more frequently and published in journals with higher impact factors.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
MicroRNAs (miRNAs) regulate gene expression by binding to target messenger RNAs (mRNAs) and preventing their translation. In general, the number of potential mRNA targets in a cell is much greater ...than the miRNA copy number, complicating high-fidelity miRNA-target interactions. We developed an inducible fluorescent probe to explore whether the maturation of a miRNA could be regulated in space and time in neurons. A precursor miRNA (pre-miRNA) probe exhibited an activity-dependent increase in fluorescence, suggesting the stimulation of miRNA maturation. Single-synapse stimulation resulted in a local maturation of miRNA that was associated with a spatially restricted reduction in the protein synthesis of a target mRNA. Thus, the spatially and temporally regulated maturation of pre-miRNAs can be used to increase the precision and robustness of miRNA-mediated translational repression.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
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