Behavioural addiction and substance addiction should be defined by their similarities not their dissimilarities

Following the recent changes to the diagnostic category for addictive disorders in DSM-5, it is urgent to clarify what constitutes behavioural addiction to have a clear direction for future research and classification. However, in the years following the release of DSM-5, an expanding body of research has increasingly classified engagement in a wide range of common behaviours and leisure activities as possible behavioural addiction. If this expansion does not end, both the relevance and the credibility of the field of addictive disorders might be questioned, which may prompt a dismissive appraisal of the new DSM-5 subcategory for behavioural addiction. We propose an operational definition of behavioural addiction together with a number of exclusion criteria, to avoid pathologizing common behaviours and provide a common ground for further research. The definition and its exclusion criteria are clarified and justified by illustrating how these address a number of theoretical and methodological shortcomings that result from existing conceptualizations. We invite other researchers to extend our definition under an Open Science Foundation framework

An empirical investigation of factors influencing teacher attraction to a career as school counselor.

This study addressed the administrative task of recruiting school counselors in the largest school district of Kentucky, a state undergoing systemic school reform. The participants (N = 553) were elementary (n = 162), middle (n = 113), and high (n = 278) school teachers.The independent variables included personal characteristics of the participants (age, gender, number of dependent children, ethnicity, education, current school enrollment, current school level, current school CATS level, years of teaching experience, years of teaching experience in JCPS, years of teaching experience in Kentucky) serving as control variables. The other independent variables were counselor job facets (predictor variables) and job satisfaction (current, expected). The dependent variable was a two-item composite score for applicant rating of a school counselor position as depicted in a simulated counselor job description. The coefficient alpha for the composite rating was .9531. This research study utilized a correlation design with hierarchical multiple regression analysis as the primary analytical procedure. The results indicated one control variable (years of experience in JCPS) and four predictor variables (ECE paperwork, administration, testing/assessment, counsel/mentor) explained significant variance in the dependent variable (rating of a school counselor). JCPS experience (beta = -.20, p \u3c .01) was a negative coefficient indicating as teaching experience in JCPS increased, participant rating of a counselor job decreased. The full model (adjusted-R2 = .35) explained 35% of the variance in the rating of a counselor job. Additional statistical procedures included the independent-samples t-test and one-way analysis of variance (ANOVA) to analyze group mean scores with the two-item composite (counselor job rating) serving as the dependent variable. The one-way ANOVA with highest degree serving as the independent variable was significant (p \u3c; .05). The participants with a bachelors degree (M = 6.0) as the highest degree earned was significantly higher than the mean for participants with masters degree +30 hours (M = 5.1) as the highest degree earned. The Pearson correlation between age and job rating (R = -.19) was significant (p \u3c .0001) indicating as age increased, the score for job rating decreased. Paired t-tests results indicated that teachers rated their current satisfaction with six job factors as teachers higher than they did their expected job satisfaction as a school counselor. The participants completed three open-ended questions which have implications for counselor recruitment and job restructuring. Implications for future research might involve casting practicing counselors in the role of simulated applicants for position vacancies

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove

Problematic gaming exists and is an example of disordered gaming

Background: The recent paper by Aarseth et al. (2016) questioned whether problematic gaming should be considered a new disorder particularly because “Gaming Disorder” (GD) has been identified as a disorder to be included in the next (11th) revision of the World Health Organization’s International Classification of Diseases (ICD-11). Methods: This study uses contemporary literature to argue why GD should be included in the ICD-11. Results: Aarseth and colleagues acknowledge that there is much literature (including papers by some of the authors themselves) that some individuals experience serious problems with video gaming. How can such an activity be seriously problematic yet not disordered? Similar to other addictions, gaming addiction is relatively rare and is in essence a syndrome (i.e., a condition or disorder characterized by a set of associated symptoms that tend to occur under specific circumstances). Consequently, not everyone will exhibit exactly the same set of symptoms and consequences, and this partly explains why those working in the problematic gaming field often disagree on symptomatology. Conclusions: Research into gaming is not about pathologizing healthy entertainment, but about pathologizing excessive and problematic behaviors that cause significant psychological distress and impairment in an individual’s life. These are two related, but (ultimately) very distinct phenomena. While being aware that gaming is a pastime activity which is enjoyed non-problematically by many millions of individuals worldwide, it is concluded that problematic gaming exists and that it is an example of disordered gaming

On the nonlinear dynamics of topological solitons in DNA

Dynamics of topological solitons describing open states in the DNA double helix are studied in the frameworks of the model which takes into account asymmetry of the helix. It is shown that three types of topological solitons can occur in the DNA double chain. Interaction between the solitons, their interactions with the chain inhomogeneities and stability of the solitons with respect to thermal oscillations are investigated.Comment: 16 pages, 16 figure

Harnessing Genomic and Bioinformatic Tools To Inform Conservation Decisions of Species That Are Vulnerable to Human-driven Impacts of Climate Change

The field of bioinformatics began late in the 20th century to enable the analysis of proteomic, genetic, and genomic datasets. Since the 1990s and the advent of 'big data', there has been a glut of genomic data, and a dearth of people with the skillsets to analyze them. As of 2019, the world&rsquo;s largest genetic sequence archive, NCBI's Short-Read Archive, was home to over 40 petabytes of genetic data, and that number is growing larger every day. Hidden within those sequences of As, Cs, Ts, and Gs, are the answers to many biological questions, including those pertaining to how we may best conserve species in the face of the existential threat of a drastically changing climate. One such species is the Warm Springs pupfish, which is endemic to several low-flow springs in the Ash Meadows National Wildlife Refuge in Southwestern Nevada. One population, at South Scruggs Spring, was facing a demographic collapse due to predation by invasive species, declining spring flow, and what may have been an extinction vortex. An extinction vortex is caused when inbreeding in small populations leads to the accumulation of deleterious genotypes, which causes low fecundity, feeding back into the low population size. Once a species enters into one, there is little we know of outside of human-facilitated introgression of novel genetic material that can save the population from extirpation. In 2009, ten individuals from a neighboring spring were added to South Scruggs and the population demographics were monitored over the following three years using mark-recapture combined with microsatellite genotyping. Based on the probability of recapture, I calculated that hybrid offspring of the ten introgressed individuals had a probability of survival between mark/recapture events that was 20% higher than that of the genetically poor resident individuals. In the process of the study, I sequenced and assembled the nuclear and mitochondrial genomes of the Warm Springs pupfish, which are resources that may be used to monitor the health of these isolated populations of endangered fish. Another class of organisms that is especially sensitive to changing environmental conditions are lichens, which are visually stunning symbiotic assemblages of a fungus, or mycobiont, and at least one photosynthetic partner, called the photobiont. Their genomes are relatively small, enabling a low cost of sequencing the genomes of both partners in the symbiosis. I was able to sequence and assemble the genomes of over 500 lichen specimens. Many of the mitochondrial genomes of these species were assembled, annotated, and published on NCBI as a result of this study. One of the primary resources to come from these sequences is a formidable database of molecular barcoding sequences&ndash;the ribosomal DNA complexes of over 400 of the different lichen species assemblies came together. Using this database, I developed a novel bioinformatic pipeline that was able to detect which lichen propagules are present in environmental metagenomic samples. Such a tool should enable researchers to evaluate factors leading to the ability of a lichen to establish in an area, versus which ones are only able to disperse into it, but not establish. In addition to the fungal rDNA complexes, algal rDNA complexes also assembled. By aligning metagenomic reads to these algal and cyanobacterial complexes, I was able to calculate the diversity of the photobiont communities within each lichen thallus and test the conditions determining photobiont diversity. I concluded that algal photobiont diversity is highest in the surface-adhering crustose lichens, and lowest in the tufty, three-dimensional fruticose lichens. In lichens that use cyanobacteria as their photobiont, diversity decreases with elevation. Surprisingly, and contrary to our expectations, lichen photobiont diversity did not differ between sexual and asexual species. The bioinformatic pipelines and data sets generated in this thesis provide valuable information on understudied and threatened species. These resources will enable adjacent researchers to make better decisions about conservation of these species in the face of habitat loss, pollution, and a changing climate.</p

A CHANGE OF HEART: NOVEL APPROACHES TO DIRECT CARDIAC REPROGRAMMING

Heart disease remains the leading cause of death in the United States, despite enormous progress in prevention, diagnosis, and treatment. Further reductions in heart disease mortality are hindered by the lack of regenerative capacity of the human myocardium. Direct cardiac reprogramming is a promising therapeutic strategy for creating new myocardium by converting cardiac fibroblasts into cardiomyocytes. While a number of technical hurdles to clinical translation remain, the past twelve years of study have borne important lessons that can be leveraged to improve cardiac reprogramming and make it more amenable for use in patients. This dissertation is comprised of work aimed both at developing new reprogramming approaches and deepening knowledge about the reprogramming process. A CRISPR activation-based method of reprogramming human fibroblasts is developed, demonstrating that endogenous Mef2c, Gata4, and Tbx5 expression is sufficient for transdifferentiation. Second, an unbiased, genome-wide comparative study of direct reprogramming of neurons, hepatocytes, and cardiomyocytes is undertaken, revealing shared features between these disparate cell types. Driven by these data, the cardiogenic potential of Ascl1 – a neuron reprogramming factor – is tested; cardiac reprogramming via Mef2c and Ascl1 is demonstrated and, furthermore, found to be more efficient. Unbiased transcriptomic and epigenomic assessment reveals that co-operation between Mef2c and Ascl1 is key to their cardiogenic activities. These results leave open the possibility that other cross-lineage reprogramming factors exist and are awaiting discovery. Exploration of this question and others may lead to insights that have broad implications.Doctor of Philosoph

Marine Cyanobacteria Compounds with Anticancer Properties: Implication of Apoptosis

Marine cyanobacteria have been proved to be an important source of potential anticancer drugs. Although several compounds were found to be cytotoxic to cancer cells in culture, the pathways by which cells are affected are still poorly elucidated. For some compounds, cancer cell death was attributed to an implication of apoptosis through morphological apoptotic features, implication of caspases and proteins of the Bcl-2 family, and other mechanisms such as interference with microtubules dynamics, cell cycle arrest and inhibition of proteases other than caspases