VARIATIONS OF CLIMATE PARAMETERS AND THEIR IMPACT ON CABERNET SAUVIGNON AND SAUVIGNON BLANC PHENOLOGY IN CONDITIONS OF CENTRAL SERBIA

Research carried out in vineyard of King Peter I Karadjordjevic-Royal Winery at Oplenac-Topola municipality, on Sauvignon blanc and Cabernet sauvignon. Vineyard planted with Sauvignon blanc is geographically positioned at GPS coordinates N 44° 14' 4" and E 20° 41' 15" and Cabernet sauvignon is geographically positioned at GPS coordinates N 44° 14' 35" and E 20° 41' 22". Climat parameters (series from 1982-2011 year) included following parameters: mean monthly, vegetation (april-october) and annual temperature, active and effective temperature, precipitation distribution (annual and vegetation) and wind direction. Phenological observation included beginning and end of following phenophases: bleeding, budbreakt, shoot growing, flowering, berry development and ripening. The greatest variation Sauvignon blanc manifested in duration of grape ripening which is in 2010. lasted 46 days while in 2011. lasted 34 days. Cabernet sauvignon in 2011. had a lower number of days that have passed from bleeding to full maturity (209 days) compared to 2010., when it passed 217 days

A Novel Approach of Determining the Risks for the Development of Hyperinsulinemia in the Children and Adolescent Population Using Radial Basis Function and Support Vector Machine Learning Algorithm

Hyperinsulinemia is a condition with extremely high levels of insulin in the blood. Various factors can lead to hyperinsulinemia in children and adolescents. Puberty is a period of significant change in children and adolescents. They do not have to have explicit symptoms for prediabetes, and certain health indicators may indicate a risk of developing this problem. The scientific study is designed as a cross-sectional study. In total, 674 children and adolescents of school age from 12 to 17 years old participated in the research. They received a recommendation from a pediatrician to do an OGTT (Oral Glucose Tolerance test) with insulinemia at a regular systematic examination. In addition to factor analysis, the study of the influence of individual factors was tested using RBF (Radial Basis Function) and SVM (Support Vector Machine) algorithm. The obtained results indicated statistically significant differences in the values of the monitored variables between the experimental and control groups. The obtained results showed that the number of adolescents at risk is increasing, and, in the presented research, it was 17.4%. Factor analysis and verification of the SVM algorithm changed the percentage of each risk factor. In addition, unlike previous research, three groups of children and adolescents at low, medium, and high risk were identified. The degree of risk can be of great diagnostic value for adopting corrective measures to prevent this problem and developing potential complications, primarily type 2 diabetes mellitus, cardiovascular disease, and other mass non-communicable diseases. The SVM algorithm is expected to determine the most accurate and reliable influence of risk factors. Using factor analysis and verification using the SVM algorithm, they significantly indicate an accurate, precise, and timely identification of children and adolescents at risk of hyperinsulinemia, which is of great importance for improving their health potential, and the health of society as a whole

Overloaded adeno-associated virus as a novel gene therapeutic tool for otoferlin-related deafness

Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (<5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches

5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail

The 5-HT2AR (5-hydroxytryptamine-2A receptor) is a GPCR (G-protein-coupled receptor) that is implicated in the actions of hallucinogens and represents a major target of atypical antipsychotic agents. In addition to its classical signalling though PLC (phospholipase C), the receptor can activate several other pathways, including ARF (ADP-ribosylation factor)-dependent activation of PLD (phospholipase D), which appears to be achieved through a mechanism independent of heterotrimeric G-proteins. In the present study we show that wild-type and inactive constructs of PLD1 (but not PLD2) respectively facilitate and inhibit ARF-dependent PLD signalling by the 5-HT2AR. Furthermore we demonstrate that PLD1 specifically co-immunoprecipitates with the receptor and binds to a distal site in GST (glutathione transferase) fusion protein constructs of its C-terminal tail which is distinct from the ARF-interaction site, thereby suggesting the existence of a functional ARF-PLD signalling complex directly associated with this receptor. This reveals the spatial co-ordination of an important GPCR, transducer and effector into a physical complex that is likely to reinforce the impact of receptor activation on a heterotrimeric G-protein-independent signalling pathway. Signalling of this receptor through such non-canonical pathways may be important to its role in particular disorders

Sensory Communication

Contains table of contents for Section 2 and reports on five research projects.National Institutes of Health Contract 2 R01 DC00117National Institutes of Health Contract 1 R01 DC02032National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Contract N01 DC22402National Institutes of Health Grant R01-DC001001National Institutes of Health Grant R01-DC00270National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Air Warfare Center Training Systems Division Contract N61339-94-C-0087U.S. Navy - Naval Air Warfare Center Training System Division Contract N61339-93-C-0055U.S. Navy - Office of Naval Research Grant N00014-93-1-1198National Aeronautics and Space Administration/Ames Research Center Grant NCC 2-77

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

ONE-YEAR CARDIOVASCULAR OUTCOME IN PATIENTS ON CLOPIDOGREL ANTI-PLATELET THERAPY AFTER ACUTE MYOCARDIAL INFARCTION

The aim of this study was to determine the risk factors in patients on clopidogrel anti-platelet therapy after acute myocardial infarction, for cardiovascular mortality, re-hospitalization and admission to emergency care unit. We followed 175 patients on dual antiplatelet therapy, with clopidogrel and acetylsalicylic acid, for 1 year after acute myocardial infarction, both STEMI and NSTEMI. Beside demographic and clinical characteristics, genetic ABCB1, CYP2C19 and CYP2C9 profile was analyzed using Cox-regression analysis. End-points used were: mortality, re-hospitalization and emergency care visits, all related to cardiovascular system. During the accrual and follow-up period, 8 patients (4.6%) died, mostly as a direct consequence of an acute myocardial infarction. Re-hospitalization was needed in 27 patients (15.4%), in nine patients (33.3%) with the diagnosis of re-infarction. Thirty-two patients (18.3%) were admitted to emergency care unit due to cardiovascular causes, up to 15 times during the follow-up. NSTEMI was an independent predictor of all three events registered (mortality OR=7.4, p<0.05; re-hospitalization OR=2.8, p<0.05); emergency care visit OR=2.4, p<0.05). Other significant predictors were related to kidney function (urea and creatinine level, creatinine clearance), co-morbidities such as arterial hypertension and decreased left ventricular ejection fraction, as well as clopidogrel dosing regimen. As a conclusion, it may be suggested that one of the most significant predictors of cardiovascular events (mortality, re-hospitalization and emergency care visits) is NSTEMI. Besides, clopidogrel administration according to up-to-date guidelines, with high loading doses and initial doubled maintenance doses, improves 1-year prognosis in patients with AMI

Differential Spatial Expression and Subcellular Localization of CtBP Family Members in Rodent Brain

C-terminal binding proteins (CtBPs) are well-characterized nuclear transcriptional co-regulators. In addition, cytoplasmic functions were discovered for these ubiquitously expressed proteins. These include the involvement of the isoform CtBP1-S/BARS50 in cellular membrane-trafficking processes and a role of the isoform RIBEYE as molecular scaffolds in ribbons, the presynaptic specializations of sensory synapses. CtBPs were suggested to regulate neuronal differentiation and they were implied in the control of gene expression during epileptogenesis. However, the expression patterns of CtBP family members in specific brain areas and their subcellular localizations in neurons in situ are largely unknown. Here, we performed comprehensive assessment of the expression of CtBP1 and CtBP2 in mouse brain at the microscopic and the ultra-structural levels using specific antibodies. We quantified and compared expression levels of both CtBPs in biochemically isolated brain fractions containing cellular nuclei or synaptic compartment. Our study demonstrates differential regional and subcellular expression patterns for the two CtBP family members in brain and reveals a previously unknown synaptic localization for CtBP2 in particular brain regions. Finally, we propose a mechanism of differential synapto-nuclear targeting of its splice variants CtBP2-S and CtBP2-L in neurons

Achieving global biodiversity goals by 2050 requires urgent and integrated actions

Governments are negotiating actions intended to halt biodiversity loss and put it on a path to recovery by 2050. Here, we show that bending the curve for biodiversity is possible, but only if actions are implemented urgently and in an integrated manner. Connecting these actions to biodiversity outcomes and tracking progress remain a challenge

A metric for spatially explicit contributions to science-based species targets

The Convention on Biological Diversity’s post-2020 Global Biodiversity Framework will probably include a goal to stabilize and restore the status of species. Its delivery would be facilitated by making the actions required to halt and reverse species loss spatially explicit. Here, we develop a species threat abatement and restoration (STAR) metric that is scalable across species, threats and geographies. STAR quantifies the contributions that abating threats and restoring habitats in specific places offer towards reducing extinction risk. While every nation can contribute towards halting biodiversity loss, Indonesia, Colombia, Mexico, Madagascar and Brazil combined have stewardship over 31% of total STAR values for terrestrial amphibians, birds and mammals. Among actions, sustainable crop production and forestry dominate, contributing 41% of total STAR values for these taxonomic groups. Key Biodiversity Areas cover 9% of the terrestrial surface but capture 47% of STAR values. STAR could support governmental and non-state actors in quantifying their contributions to meeting science-based species targets within the framework.acceptedVersionLocked until 8.10.2021 due to copyright restrictions. This is an Accepted Manuscript of an article, available online: https://doi.org/10.1038/s41559-021-01432-