Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research

The inheritance of variants that lead to coding changes in, or the mis-expression of, genes critical to pancreatic beta cell function can lead to alterations in insulin secretion and increase the risk of both type 1 and type 2 diabetes. Recently developed clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) gene editing tools provide a powerful means of understanding the impact of identified variants on cell function, growth, and survival and might ultimately provide a means, most likely after the transplantation of genetically “corrected” cells, of treating the disease. Here, we review some of the disease-associated genes and variants whose roles have been probed up to now. Next, we survey recent exciting developments in CRISPR/Cas9 technology and their possible exploitation for β cell functional genomics. Finally, we will provide a perspective as to how CRISPR/Cas9 technology may find clinical application in patients with diabetes.
Exploring Traumatic Brain Injuries and Aggressive Antisocial Behaviors in Young Male Violent Offenders

Background: Traumatic brain injury (TBI) is a major cause of disabilities and mortality worldwide, with higher prevalence in offender populations than in the general population. Previous research has strongly advocated increased awareness of TBI in offender populations. The aim of this study was to explore the prevalence and characteristics of TBI, and to investigate associations and interactions between TBI, aggressive antisocial behaviors, general intellectual functioning, and substance use disorders (SUD) in a well-characterized group of young violent offenders. Methods: The study investigated a cohort (n = 269) of 18 to 25-year-old male violent offenders in Sweden. Data on TBI (files + self-report), aggressive antisocial behaviors (Life History of Aggression), SUD (clinical interviews), and general intellectual functioning (General Ability Index, Wechsler Adult Intelligence Scales Third Edition) were collected between 2010 and 2012. Parametric (Student's t-test) and non-parametric (Mann-Whitney U-test, Spearman's rho, χ2, Kruskal Wallis test) inferential statistics were applied and effect sizes reported. Results: TBI, both with and without loss of consciousness, was common, with 77.5% of the offenders reporting having suffered at least one TBI during their lifetime. TBI was associated with an increased occurrence of aggressive antisocial behaviors and SUD, and offenders with both TBI and SUD evidenced the largest amount of aggressive antisocial behaviors. No clinically meaningful associations were found between TBI and general intelligence. Effect sizes were in the small to medium range. Conclusions: Our study confirms an increased prevalence of TBI among young violent offenders compared to the general population, as well as associations between TBI, aggressive antisocial behaviors, and SUD. However, it provides no information on the severity of the TBI, nor on the causality of the demonstrated associations. Nevertheless, TBI, and possible related deficits, need to be considered in the assessment and treatment of young violent offenders.
The Genera of American Myrtaceae: An Interim Report

Generic concepts developed slowly in the Myrtaceae. At the beginning of the 19th century few species were known, and these were traditionally distributed among ten or twelve genera. Willdenow, for example (Sp. P1. 2: 935. 1800), knew among the capsular-fruited Myrtaceae 12 species of Leptospermum, 14 of Metrosideros, and 12 of Eucalyptus. The Myrtaceae with baccate fruits he referred to Eugenia (30 species), Psidium (8 species), Myrtus (28 species), Calyptranthes (6 species) and Plinia (1 species). The American Myrtaceae, except for the monotypic Chilean genus Tepualia, belong to the fleshy-fruited group that since the time of De Candolle has been recognized as a tribe, Myrteae. Outstanding contributions to the knowledge of the species and genera of the American Myrteae were made by De Candolle in 1828 and by Berg in 1855-62, but since Berg's time no one person has had an opportunity to become familiar with the group as a whole. The number of described species is very large, especially in tropical South America, and available herbarium material until recent years consisted chiefly of the classical specimens scattered through European herbaria. Within the last quarter century, however, a considerable amount of new herbarium material has been collected, and a number of regional studies of the American Myrtaceae have been published. The species of the North American continent, of the West Indies, of the Guianas, of the central Andes, of Chile and of the Uruguayan-south Brazilian region have become reasonably well known, and it now seems profitable to assess the work of Berg in the light of modern work on the family, and particularly to evaluate his generic concepts and the concepts of later workers. Until the time of A. P. De Candolle, most workers accepted without much question the generic limits that had been set forth by Linnaeus, who assigned most of the Myrtaceae known to him to one of three genera (cf. Syst. Nat. ed. 13. 2: 336. 1770): Eugenia: Calyx and corolla 4-merous; drupe 1-locular, 1-seeded. Psidium: Calyx and corolla 5-merous; berry 1-locular, many-seeded. Myrtus: Calyx 5-fid; corolla "sub 5-petala"; berry 3-locular, 1-seeded.
Why Is Student Deviance Lower in Japan Than in the United States?: Influences of Individual, Parental, Peer, Social, and Environmental Factors

Drawing on the cultural collectivism–individualism literature, we predict that Japanese students, compared to Americans, tend to commit fewer deviant acts because they are less inclined toward individualistic value orientations, risk seeking, negative emotionality, and subjective stress; because they are exposed to greater parental discipline and have stronger parental attachment; because they have weaker peer attachment and associate with peers who react less favorably to deviance; because they have stronger bonds to conventional society and greater social support from significant others; and because they are exposed to fewer deviance opportunities. Analyses of comparable data from college students in Japan (N = 469) and the United States (N = 594) provided mixed support for our predictions. As expected, Japanese students committed fewer deviant acts during their high school days. Furthermore, consistent with expectations, Japanese students had lower scores on all four individual factors, the two peer factors, and the environmental factor of deviance opportunities. After controlling for these seven factors, the effect of Japan versus the United States decreased by one third. The decrease was not greater at least partly because, in Japan, compared to the United States, risk seeking had significantly less influence on student deviance, and subjective stress had significantly more influence on student deviance.
Photonic orbital angular momentum in turbulence: vortex splitting and adaptive optics

Recent works revealed that transmission of light beams carrying orbital-angular-momentum (OAM) through turbulence causes the optical vortex defining these beams to split into multiple vortices with unit topological charge. Here, we consider the numerical propagation of orbital-angular-momentum (OAM) modes through a horizontal atmospheric channel. By analysing the beam's phase front after transmission through turbulence, we confirm the occurence of vortex splitting, but we also witness the emergence of vortex-antivortex pairs. Moreover, by performing performing a decomposition of the transmitted wave into OAM modes, we show that while adaptive optics cannot cancel vortex splitting, it still is pretty efficient in diminishing the turbulence-induced crosstalk between different OAM modes.
Assessment of freely available DSMs for landslide-rockfall studies

Landslides or rockfalls in mountainous areas in Western Greece are a continuous hazard and thus, observation either in situ or through satellite data is of great necessity. In order to study landslides or rockfalls a very accurate representation of the relief is a prerequisite. In now days diverse remote sensing satellites provides digital surface elevation models (DSMs) with global coverage. The specific data sets present the advantages of covering large areas in a very low cost in comparison with the surveys in the field. In addition, high resolution DSMs enable the analysis of topography with high levels of detail and consequently geomorphometric approach becomes more accurate for studying landlsides or rockfall events. Information which can be extracted from geological and topographic maps in GIS format such as the slope angle distribution, deduced from high resolution DSMs, are substantial in rockfalls survey. In the present work, the accuracy of freely available DSMs are under control for landslides areas in Achaia prefecture in NW Peloponnese. The accuracy of the DSMs in the broader area is investigated using reference points of certified elevation while for the landslide area ground control collected with differential GNSS receiver are used. More specifically, free available DSMs as TanDEMX, ASTER GDEM, SRTM DEM with 30m and 90m spatial resolution, ALOS AW3D30 DEM, DSM from photogrammetric airphoto processing and DSM produced by Interferometric processing of radar images, are under examination in the current study. Furthermore, diverse statistical parameters such as the 2D Root Mean Square Error or the percentile value are computed and presented. The purpose of the aforementioned procedure is to detect the most accurate DSMs which are appropriate for landslide of rockfall monitoring.
Advances in C-glycosylflavonoid Research

C-glycosylflavonoids represent a group of oxygen heterocyclic compounds found widespread in a variety of plants. Synthetic organic chemists are now progressively utilizing C-glycosylflavonoid scaffolds due to their high biological potential. The present review deals with advances in C-glycosylflavonoids research, namely establishing a new updated database of the natural occurrence of C- glycosylflavonoids - one hundred and nine new structures have been reported up to 2011. The structural characterization of some novel C-glycosylflavonoids from various plant species is also discussed. The reported organic synthetic routes along with the biosynthetic as- pects of C-glycosylflavonoids are also reviewed. Finally the paper underlines the wide range of C-glycosylflavonoid biological activity. The mentioned topics are detailed in particular chapters and are supported in 187 references.
Effect of Drought on the Methylerythritol 4-Phosphate (MEP) Pathway in the Isoprene Emitting Conifer Picea glauca

The methylerythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis produces chlorophyll side chains and compounds that function in resistance to abiotic stresses, including carotenoids, and isoprene. Thus we investigated the effects of moderate and severe drought on MEP pathway function in the conifer Picea glauca, a boreal species at risk under global warming trends. Although moderate drought treatment reduced the photosynthetic rate by over 70%, metabolic flux through the MEP pathway was reduced by only 37%. The activity of the putative rate-limiting step, 1-deoxy-D-xylulose-5-phosphate synthase (DXS), was also reduced by about 50%, supporting the key role of this enzyme in regulating pathway metabolic flux. However, under severe drought, as flux declined below detectable levels, DXS activity showed no significant decrease, indicating a much-reduced role in controlling flux under these conditions. Both MEP pathway intermediates and the MEP pathway product isoprene incorporate administered 13CO2 to high levels (75–85%) under well-watered control conditions indicating a close connection to photosynthesis. However, this incorporation declined precipitously under drought, demonstrating exploitation of alternative carbon sources. Despite the reductions in MEP pathway flux and intermediate pools, there was no detectable decline in most major MEP pathway products under drought (except for violaxanthin under moderate and severe stress and isoprene under severe stress) suggesting that the pathway is somehow buffered against this stress. The resilience of the MEP pathway under drought may be a consequence of the importance of the metabolites formed under these conditions.
Tolerogenic Immunomodulation by PEGylated Antigenic Peptides

Current treatments for autoimmune disorders rely on non-specific immunomodulatory and global immunosuppressive drugs, which show a variable degree of efficiency and are often accompanied by side effects. In contrast, strategies aiming at inducing antigen-specific tolerance promise an exclusive specificity of the immunomodulation. However, although successful in experimental models, peptide-based tolerogenic “inverse” vaccines have largely failed to show efficacy in clinical trials. Recent studies showed that repetitive T cell epitopes, coupling of peptides to autologous cells, or peptides coupled to nanoparticles can improve the tolerogenic efficacy of peptides, suggesting that size and biophysical properties of antigen constructs affect the induction of tolerance. As these materials bear hurdles with respect to preparation or regulatory aspects, we wondered whether conjugation of peptides to the well-established and clinically proven synthetic material polyethylene glycol (PEG) might also work. We here coupled the T cell epitope OVA323–339 to polyethylene glycols of different size and structure and tested the impact of these nano-sized constructs on regulatory (Treg) and effector T cells in the DO11.10 adoptive transfer mouse model. Systemic vaccination with PEGylated peptides resulted in highly increased frequencies of Foxp3+ Tregs and reduced frequencies of antigen-specific T cells producing pro-inflammatory TNF compared to vaccination with the native peptide. PEGylation was found to extend the bioavailability of the model peptide. Both tolerogenicity and bioavailability were dependent on PEG size and structure. In conclusion, PEGylation of antigenic peptides is an effective and feasible strategy to improve Treg-inducing, peptide-based vaccines with potential use for the treatment of autoimmune diseases, allergies, and transplant rejection.
Enhanced mutation through exposure to EMS affects the evolution of ethanol tolerance in Saccharomyces cerevisiae

Abstract. Ethanol is a multifunctional compound that has many uses and can be made naturally by sugar-fermenting yeast such as Saccharomyces cerevisiae. However, ethanol is toxic to yeast, so in this study we aimed to improve yeast ethanol tolerance, which could result in greater efficiencies in the process of alcohol production. This research explores the effectiveness of artificially inducing population-level variation through the application of ethyl methanesulfonate (EMS) on increasing the ethanol tolerance in S. cerevisiae. After several rounds of selection and increasing ethanol concentrations, ranging from 9-27%, the two treatment populations (AS - Artificial Selection only; and EMS – Exposure to EMS and Artificial Selection) were compared to the initial parental population. The parental strain was tolerant to ethanol concentrations of 13%, while the AS treatment was tolerant to slightly higher levels, 16%. Both of these treatments were well below the EMS treatment which expressed a tolerance of 27%. To test differences between strains, the parental strain, selection strain, and the EMS-exposed strain were separately plated on ten 27% ethanol plates and ten 0% ethanol plates, and growth was checked after 24 hours. The EMS-exposed strain was the only strain that grew at 27% ethanol; all strains grew at 0% ethanol. These results show that EMS, artificial selection, and ethanol as a stressor might be effective in producing strains of S. cerevisiae that are able to produce greater amounts of ethanol before toxicity sets in.
Synthetic auxin 3,5,6-TPA promotes fruit development and climacteric in Prunus persica L. Batsch

SummaryThe application of 3,5,6-TPA advances fruit maturation of peaches and nectarines through different mechanisms, depending on the fruit development stage at treatment. Treatments applied at pit hardening encourage the development of fruit, which grow faster, reach the climateric stage earlier, and can be harvested earlier. The effect is direct, since the number of fruits per tree is not reduced by the treatment and also can be obtained by applying the auxin locally to a small number of fruits per tree. Treatments applied a few days before climateric increase ethylene production without affecting fruit growth.
Enhancing the pedagogical practice of South African Physical Sciences teachers in inquiry-based teaching through empowerment evaluation

ABSTRACT Scientific inquiry has been advocated as a common curriculum goal in school science education in South Africa, and also throughout the world. In South Africa, the introduction of inquiry-based instruction in a reformed science curriculum has met with serious challenges, such as the under-preparedness of in-service teachers. The purpose of this study was to capture, portray and develop the pedagogical practice of Physical Sciences teachers in inquiry-based teaching using an empowerment evaluation approach. The study is a multiple case study in inquiry-based teaching of three Physical Sciences teachers in South Africa using a mixed methods design. Empowerment evaluation is the use of evaluation concepts, techniques, and findings to foster improvement and self-determination. Underlying an inquiry-based pedagogy is the assumption that science education is not merely about knowing-acquisition, but understanding how scientific knowledge is generated, evaluation of knowledge claims and conducting scientific research. Data were collected by means of semi-structured interviews, a pedagogical orientation instrument, and classroom observations. The findings reveal that through empowerment evaluation, teacher practices in the classroom shifted towards an inquiry-based approach. The empowerment evaluation approach thus offers a viable and sustained form of professional development that is likely to empower teachers in assessing, planning, implementing and evaluating what they do.
New Insights Into the Kibenikhoria and Ernestokokenia Faunas and The Implications for the Early Eocene of Patagonia, Argentina

ABSTRACT The Kibenikhoria and Ernestokokenia local faunas were described in the 1930s by George G. Simpson, who defined them as two chronologically consecutive faunas based on a comparison with the Casamayoran South American Land Mammal Age (SALMA). Later, in the 1980s, the two faunas were respectively the basis of the Itaboraian and Riochican SALMAs, a scheme broadly accepted for more than eight decades. However, a systematic revision of their native ungulates is still lacking. In this contribution, we studied several collections performed in the classical localities of Cañadón Hondo and Bajo Palangana (southeastern South America) and discuss the systematic status of the mammals listed in their faunas. Our results allow us to (1) assert that the beds containing the mammal associations in Cañadón Hondo and Bajo Palangana are located in the upper Las Flores Formation and are essentially contemporaneous; (2) improve the knowledge for Kibenikhoria get and Henricosbornia lophodonta; (3) propose H. waitehor and ? Peripantostylops orehor to be synonymous with H. lophodonta; and (4) recognize Shecenia ctirneru, Seudenius cteronc, and ? Postpithecus as Trigonostylopidae aff. Trigonostylops. The Kibenikhoria and Ernestokokenia faunas have six genera in common; five of them are shared with the lower levels of the Sarmiento Formation. Kibenikhoria get, Isotemnus ctalego, Pliodolops winecage, and Gasternia ctalehor are exclusive taxa of the Kibenikhoria fauna. Here, the Riochican sensu stricto from Marshall is used to include both local faunas, which represents a distinct and more derived fauna than that from the Itaboraí Formation, but with a less advanced evolutionary stage than the lower Sarmiento Formation.
Clinical Features and Temporal Changes of RT-PCR and Chest CT in COVID-19 Pediatric Patients

Objective: This work aims to investigate the clinical features and the temporal changes of RT-PCR and CT in COVID-19 pediatric patients. Methods: The clinical, RT-PCR, and CT features of 114 COVID-19 pediatric in-patients were retrospectively reviewed from January 21 to March 14, 2020. All patients had chest CT on admission and were identified as positive by pharyngeal swab nucleic acid test. The clinical features were analyzed, as well as the features and the temporal changes of RT-PCR and CT. Results: Fever (62, 54%) and cough (61, 54%) were the most common symptoms. There were 34 (30%) cases of concurrent infections. The most common imaging features on CT were ground-glass opacities (46, 40%) and consolidation (46, 40%). The bilateral lower lobes were the most common pattern of involvement, with 63 cases (55%) involving one to two lobes, and in 32 (28%) cases CT was normal. Throughout the whole duration of COVID-19 in children, the diagnostic positive rate of RT-PCR has been far higher than that of CT (all P < 0.05). For RT-PCR follow-up, reliable negative results were obtained only 7 days after the onset of symptoms. Though lung involvement on chest CT progressed rapidly in several cases, lung involvement in children with COVID-19 is mild, with a median value of 2 on CT score. Conclusions: RT-PCR is more reliable than CT in the initial diagnosis of pediatric patients with COVID-19. On follow-up, reliable negative RT-PCR results are available 7 days after the initial symptoms. The use of CT should be considered for follow-up purposes only if necessary.
STXBP2-R190C Variant in a Patient With Neonatal Hemophagocytic Lymphohistiocytosis (HLH) and G6PD Deficiency Reveals a Critical Role of STXBP2 Domain 2 on Granule Exocytosis

Neonatal hemophagocytic lymphohistiocytosis (HLH) is a medical emergency that can be associated with significant morbidity and mortality. Often these patients present with familial HLH (f-HLH), which is caused by gene mutations interfering with the cytolytic pathway of cytotoxic T-lymphocytes (CTLs) and natural killer cells. Here we describe a male newborn who met the HLH diagnostic criteria, presented with profound cholestasis, and carried a maternally inherited heterozygous mutation in syntaxin-binding protein-2 [STXBP2, c.568C>T (p.Arg190Cys)] in addition to a severe pathogenic variant in glucose 6-phosphate dehydrogenase [G6PD, hemizygous c.1153T>C (Cys385Arg)]. Although mutations in STXBP2 gene are associated with f-HLH type 5, the clinical and biological relevance of the p.Arg190Cys mutation identified in this patient was uncertain. To assess its role in disease pathogenesis, we performed functional assays and biochemical and microscopic studies. We found that p.Arg190Cys mutation did not alter the expression or subcellular localization of STXBP2 or STX11, neither impaired the STXBP2/STX11 interaction. In contrast, forced expression of the mutated protein into normal CTLs strongly inhibited degranulation and reduced the cytolytic activity outcompeting the effect of endogenous wild-type STXBP2. Interestingly, arginine 190 is located in a structurally conserved region of STXBP2 where other f-HLH-5 mutations have been identified. Collectively, data strongly suggest that STXBP2-R190C is a deleterious variant that may act in a dominant-negative manner by probably stabilizing non-productive interactions between STXBP2/STX11 complex and other still unknown factors such as the membrane surface or Munc13-4 protein and thus impairing the release of cytolytic granules. In addition to the contribution of STXBP2-R190C to f-HLH, the accompanied G6PD mutation may have compounded the clinical symptoms; however, the extent by which G6PD deficiency has contributed to HLH in our patient remains unclear.