Neuregulins are important growth factors involved in cardiac development and response to stress. Certain isoforms and fragments of neuregulin have been found to be cardioprotective. The effects of a ...full-length neuregulin-1β isoform, glial growth factor 2 (GGF2; USAN/INN; also called cimaglermin) were investigated in vitro. Various dosing regimens were then evaluated for their effects on left ventricular (LV) function in rats with surgically-induced myocardial infarction. In vitro, GGF2 bound with high affinity to erythroblastic leukemia viral oncogene (ErbB) 4 receptors, potently promoted Akt phosphorylation, as well as reduced cell death following doxorubicin exposure in HL1 cells. Daily GGF2 treatment beginning 7–14 days after left anterior descending coronary artery ligation produced improvements in LV ejection fraction and other measures of LV function and morphology. The improvements in LV function (e.g. 10% point increase in absolute LV ejection fraction) with GGF2 were dose-dependent. LV performance was substantially improved when GGF2 treatment was delivered infrequently, despite a serum half-life of less than 2h and could be maintained for more than 10 months with treatment once weekly or once every 2 weeks. These studies confirm previous findings that GGF2 may improve contractile performance in the failing rat heart and that infrequent exposure to GGF2 may improve LV function and impact remodeling in the failing myocardium. GGF2 is now being developed for the treatment of heart failure in humans.
The current study examines the reciprocal relations between children's values and value‐expressive behavior over a sixth‐month period. Three hundred and ten sixth‐grade students in Italy completed ...value and value‐expressive behavior questionnaires three times in three‐month intervals during the scholastic year. We assessed Schwartz's (1992) higher‐order values of conservation, openness to change, self‐enhancement, and self‐transcendence, as well as their respective expressive behaviors. Reciprocal relations over time between values and behaviors were examined using a cross‐lagged longitudinal design. Results showed that values and behaviors had reciprocal longitudinal effects on one another, after the stability of the variables was taken into account (i.e., values predicted change in behaviors, but also behaviors predicted change in values). Our findings also revealed that: (1) values were more stable over time than behaviors and (2) the longitudinal effect of values on behaviors tended to be stronger than the longitudinal effect of behaviors on values. Findings are discussed in light of the recent developmental literature on value change.
COVID-19 infection evokes various systemic alterations that push patients not only towards severe acute respiratory syndrome but causes an important metabolic dysregulation with following multi-organ ...alteration and potentially poor outcome. To discover novel potential biomarkers able to predict disease’s severity and patient’s outcome, in this study we applied untargeted lipidomics, by a reversed phase ultra-high performance liquid chromatography-trapped ion mobility mass spectrometry platform (RP-UHPLC-TIMS-MS), on blood samples collected at hospital admission in an Italian cohort of COVID-19 patients (45 mild, 54 severe, 21 controls). In a subset of patients, we also collected a second blood sample in correspondence of clinical phenotype modification (longitudinal population). Plasma lipid profiles revealed several lipids significantly modified in COVID-19 patients with respect to controls and able to discern between mild and severe clinical phenotype. Severe patients were characterized by a progressive decrease in the levels of LPCs, LPC-Os, PC-Os, and, on the contrary, an increase in overall TGs, PEs, and Ceramides. A machine learning model was built by using both the entire dataset and with a restricted lipid panel dataset, delivering comparable results in predicting severity (AUC= 0.777, CI: 0.639–0.904) and outcome (AUC= 0.789, CI: 0.658–0.910). Finally, re-building the model with 25 longitudinal (t1) samples, this resulted in 21 patients correctly classified. In conclusion, this study highlights specific lipid profiles that could be used monitor the possible trajectory of COVID-19 patients at hospital admission, which could be used in targeted approaches.
•An untargeted lipidomics study was performed on 99 Covid-19 patients.•A RP-UHPLC-TIMS-MS approach was used to profile plasma lipid signatures.•Significant differences were found in lipid levels of severe patients.•LPCs, LPC-Os. PC-Os were found highly decreased in severe and deceased patients.•A machine learning model was built to predict severity and outcome.
Overcoming the systemic administration of chemotherapy to reduce drug toxicity and the application of personalised medicine are two of the major challenges in the treatment of cancer. To this aim, ...efforts are focused on finding novel nanomaterials for the targeted administration of drugs and bioactive molecules in the tumor sites. DNA-based hydrogels are promising candidates for these applications. However, while such materials are fairly known from a structural and physical standpoint, their effects on cell cultures are far less investigated. Here, we studied the biological response of three different cell lines (clear cell renal cell carcinoma 786-O, lung adenocarcinoma H1975 and glioblastoma U87MG) to the treatment with DNA-GEL - a DNA-based hydrogel composed of interacting DNA nanostars. Additionally, we investigated the structural modification of DNA-GELs under cell culture conditions. The results we collected show a cell type specificity of the response, with interesting implications for future applications.
Can DNA-GELs made of DNA nanostars help with the treatment of tumor cell lines?
Biomarkers are biological measures of a biological state. An ideal marker should be safe and easy to measure, cost efficient, modifiable with treatment, and consistent across gender and ethnic ...groups. To date, none of the available biomarkers satisfy all of these criteria. In addition, the major limitations of these markers are low specificity, sensitivity, and false positive results. Recently identified, microRNAs (miRNAs) are endogenous, evolutionarily conserved small non-coding RNA (about 22-25 nt long), also known as micro-coordinators of gene expression, which have been shown to be an effective tools to study the biology of diseases and to have great potential as novel diagnostic and prognostic biomarkers with high specificity and sensitivity. In fact, it has been demonstrated that miRNAs play a pivotal role in the regulation of a wide range of developmental and physiological processes and their deficiencies have been related to a number of disease. In addition, miRNAs are stable and can be easily isolated and measured from tissues and body fluids. In this review, we provide a perspective on emerging concepts and potential usefulness of miRNAs as diagnostic markers, emphasizing the involvement of specific miRNAs in particular tumor types, subtypes, cardiovascular diseases, diabetes, infectious diseases, and forensic test.
Nitric oxide (NO) is a biologically active inorganic molecule involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, ...neurotransmission and neuromodulation. In the present study, for the first time, we investigated the modulation of NO signaling in platelets of HD patients. We recruited 55 patients with manifest HD and 28 gender- and age-matched healthy controls. Our data demonstrated that NO-mediated vasorelaxation, when evoked by supernatant from insulin-stimulated HD platelets, gradually worsens along disease course. The defective vasorelaxation seems to stem from a faulty release of NO from platelets of HD patients and, it is associated with impairment of eNOS phosphorylation (Ser(1177)) and activity. This study provides important insights about NO metabolism in HD and raises the hypothesis that the decrease of NO in platelets of HD individuals could be a good tool for monitoring advanced stages of the disease.
In Bacillus subtilis the protective layers that surround the mature spore are formed by over seventy different proteins. Some of those proteins have a regulatory role on the assembly of other coat ...proteins and are referred to as morphogenetic factors. CotE is a major morphogenetic factor, known to form a ring around the forming spore and organize the deposition of the outer surface layers. CotH is a CotE-dependent protein known to control the assembly of at least nine other coat proteins. We report that CotH also controls the assembly of CotE and that this mutual dependency is due to a direct interaction between the two proteins. The C-terminal end of CotE is essential for this direct interaction and CotH cannot bind to mutant CotE deleted of six or nine C-terminal amino acids. However, addition of a negatively charged amino acid to those deleted versions of CotE rescues the interaction.
With a recent surge of research on narcissism, narcissism questionnaires are increasingly being translated and applied in various countries. The measurement invariance of an instrument across ...countries is a precondition for being able to compare scores across countries. We investigated the cross-cultural measurement invariance of three narcissism questionnaires (Brief Pathological Narcissism Inventory B-PNI, Narcissistic Personality Inventory NPI, and Narcissistic Admiration and Rivalry Questionnaire NARQ) and mean-level differences across samples from the United States (N = 2,464), the United Kingdom (N = 307), and Germany (N = 925). Overall, the B-PNI and NARQ functioned equivalently for the U.S. and U.K. participants. More violations of measurement invariance were found between Germany and the combined U.S. and U.K. samples, and for the NPI. In the B-PNI and NARQ, Americans scored higher than individuals from the United Kingdom regarding agentic aspects (self-sacrificing self-enhancement, admiration), while Germans scored lower than both Americans and U.K. individuals regarding antagonistic (entitlement rage, rivalry) and neurotic (hiding the self, contingent self-esteem) aspects. More inconsistent results were found for NPI facets. When noninvariance was present, observed means yielded biased results. Thus, the degree of measurement invariance across translated instrument versions should be considered in cross-cultural comparisons, even with culturally similar countries.
Photocathode Materials
The discovery of high‐brightness photocathode materials can considerably expand the capabilities of X‐ray free‐electron laser facilities. In article number 2104081, Evan R. ...Antoniuk, Evan J. Reed, and co‐workers perform a comprehensive screening of over 74 000 materials to identify novel photocathode candidates. The newly discovered materials are demonstrated to achieve higher brightness and superior air stability than the current state‐of‐the‐art.
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