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Summary: Autosomal-dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by the formation of fluid-filled renal cysts, loss of mitochondrial function, decreased fatty acid oxidation, increased glycolysis, and likely renal failure. We previously demonstrated that inducing a state of ketosis ameliorates or reverses PKD progression in multiple animal models. In this study, we compare time-restricted feeding and 48-h periodic fasting regimens in both juvenile and adult Cy/+ rats. Both fasting regimens potently prevent juvenile disease progression and partially reverse PKD in adults. To explore the mechanism of fasting, we administered β-hydroxybutyrate (BHB) to Cy/+ rats and orthologous mouse models of PKD (Pkd1RC/RC, Pkd1-Ksp:Cre). BHB recapitulated the effects of fasting in these models independent of stereoisomer, suggesting the effects of BHB are largely due to its signaling functions. These findings implicate the use of ketogenic metabolic therapy and BHB supplementation as potential disease modifiers of PKD and point toward underlying mechanisms.

This article aims to make an initial probe into parent involvement in children's academic-related activities and how this is affected by the parents' gender, education and employment variables. Most of the articles written on parental academic support focus on corroborating the positive relationship of parental involvement with student school achievement and cover samples from countries other than Kosova. This is the first correlational study which aims to show the significance of relationships of the specific demographic variables of Kosovar parents and the frequency of their homework help. Data are analysed using frequency distribution and chi-square for the correlation significance. The findings corroborate a higher percentage of females in parental involvement, and a negative correlation of parental involvement with employment and level of education. Implications and explanations for future research and practice are discussed.

To design the foundation system of waterway bridges, Load and Resistance Factor Design guidelines suggest use of deterministic scour depth prediction models. Understanding the inherent bias of deterministic scour depth prediction models will advance the development of reliability index-based foundation design regime. Four bridge scour depth prediction models were assessed in terms of two statistical parameters, termed herein mean absolute percentage error (MAPE), and conservatism, percentage of cases the predicted scour depth exceeded the measured scour depth. Live-bed laboratory and field scour depth databases were used in analyses to quantify model scatter by comparatively assessing the computed scour depth versus measured data. For live-bed laboratory data, values of MAPE ranged from 23.5% to 59.8%, whereas conservatism ranged from 28.4% to 97.8%. For live-bed field data, conservatism varied from 93.3% to 95.1%, while MAPE ranged from 205.6% to 319%. Statistical models were applied to ascertain the biasness of the four deterministic models. Accuracy and conservatism of a given model were consequently adjusted through proposed modification factors. The proposed approach allows for the selection of a suitable modification factor to satisfy a target probability of deceedance or a target conservatism. Key words: bridge scour, LRFD, probability of exceedance, live-bed, conservatism, statistical models, 1. Introduction Bridge pier scour is a complex process of interaction among flow, sediments, and structure leading to the mobilization and transport of sediments surrounding the structure. When the flow [...]

Mengeš je s številnimi grobišči in utrjeno naselbino na Gobavici ter poselitvenim arealom neposredno ob vznožju gradišča eno pomembnejših najdišč gorenjsko-ljubljanske halštatske skupine. V članku so predstavljeni rezultati arheoloških izkopavanj iz leta 2003 na grobišču Zavrti, kjer so bili odkriti skeletni in žgani grob ter pokop kobile iz mlajšehalštatskega obdobja. Arheološka datacija je bila potrjena z radiokarbonsko analizo. Gre za izjemno odkritje, saj pokop celega konja v okviru pogrebnega obreda in kulta do zdaj iz gorenjsko-ljubljanske skupine še ni bil znan, prav tako je na Gorenjskem v tem času izjemen skeletni pokop. Analiza vseh skeletnih grobov iz starejše železne dobe iz Mengša je pokazala, da se je inhumacija pojavila že od konca 9./8. st. pr. n. št., tak način pokopa se je ohranil tudi v mlajšehalštatski čas. Nova odkritja potrjujejo, da je bil Mengeš v starejši železni dobi na meji interesnih območij posameznih skupnosti, še posebej svetolucijske in dolenjske halštatske skupine.

Grobišče na Dvorišču SAZU v Ljubljani z več kot 300 žganimi grobovi iz mlajše bronaste in starejše železne dobe je še vedno eno ključnih najdišč za razumevanje gorenjsko-ljubljanske skupine. Nove raziskave na Kongresnem trgu so razkrile grobišče, ki se v mnogo vidikih razlikuje od tistega na Dvorišču SAZU. Prvič so bile v Ljubljani izpričane manjše gomile s prodnatim jedrom, zemljenim plaščem in zunanjim obodnim jarkom iz zgodnje železne dobe. Po večini gre za žarne grobove v središču gomile, izstopa gomila 3 s centralnim grobom in sedmimi pokopi okrog njega. Po načinu pokopa izstopajo trije skeletni grobovi iz 8. st. pr. n. št., ti so v članku tudi podrobneje predstavljeni. Podana sta kratek oris pojava skeletnih grobov v drugih sočasnih železnodobnih skupinah in poskus razlage teh skeletnih pokopov v Ljubljani. Na podlagi analize grobnih najdb in novih radiokarbonskih datacij iz Ljubljane so na kratko predstavljene dopolnitve Gabrovčeve kronološke sheme ljubljanskega grobišča in posledično gorenjsko-ljubljanske skupine, predvsem stopenj Ljubljana II in IIIa. Dopolnitve stopnje Ljubljana II tako v relativnem kot absolutnem kronološkem smislu so ključne za razumevanje začetka pokopavanja na Kongresnem trgu ter razdelitev stopenj Podzemelj 1 in 2.

The article represents a short synthesis about settlements from the Middle and the beginning of the Late Bronze Age in central and eastern regions of Slovenia. Special attention is given to two key-sites, Medvode-Svetje and Trata near Škofja Loka, both from the Gorenjska region. Numerous archaeological excavations and subsequent research publications in the last two decades brought about new insights on dwelling features, forms of housing and on settlement characteristics itself. At the same time, a completely new understanding of the spectre of ceramic repertoire has been obtained, while new radiocarbon dating results enable us to complement the absolute chronology of the given time period.

Microbially induced carbonate precipitation (MICP) is a sustainable biological process that catalyzes carbonate mineral precipitation within geomaterials. This study evaluates the performance and mechanisms of the MICP treatment for flocculating the oil sands fine tailings (FT). Column tests showed that the untreated FT did not decant during the 31 days. However, the MICP technique shortened the dewatering process. To elucidate the mechanisms of the MICP-induced flocculation of the FT, the diffuse double layer (DDL) thickness and microstructure of the specimens were evaluated. Three chemical equilibrium scenarios that gradually considered the MICP-biochemical reactions were explored to analyze the change of the DDL thickness. The results showed that increasing of ionic strength by urea hydrolysis decreased the DDL thickness. The fabric observation indicated that the specimens with the most calcium carbonate precipitation had the densest fabric. In summary, the MICP technique densified the fabric of FT via the ureolysis process and precipitating minerals. Key words: oil sands fine tailings, microbially induced carbonate precipitation, diffuse double layer thickness. La precipitation de carbonates par voie microbienne (<< MICP >>) est un processus biologique durable qui catalyse la precipitation des mineraux carbonates dans les geomateriaux. Cette etude evalue le rendement et les mecanismes du traitement MICP pour la floculation des residus fins des sables bitumineux (RF). Les essais sur colonne ont montre que les RF non traites n'ont pas decante pendant les 31 jours. Cependant, la technique de la MICP a raccourci le processus d'assechement. Afin d'elucider les mecanismes de la floculation induite par la MICP des RF, l'epaisseur de la double couche diffuse (DCD) et la microstructure des echantillons ont ete evaluees. Trois scenarios d'equilibre chimique qui ont progressivement pris en compte les reactions biochimiques de la MICP ont ete explores pour analyser le changement d'epaisseur de la DCD. Les resultats ont montre que l'augmentation de la force ionique par l'hydrolyse de l'uree diminuait l'epaisseur de la DCD. L'observation de la microstructure a indique que les echantillons ayant subi le plus de precipitation de carbonate de calcium avaient la microstructure la plus dense. En resume, la technique MICP a densifie la microstructure des RF par procede d'ureolyse et de precipitation des mineraux. [Traduit par la Redaction] Mots-cles : residus fins des sables bitumineux, precipitation de carbonates par voie microbienne, epaisseur de la double couche diffuse., 1. Introduction Microbially induced carbonate precipitation (MICP) is a sustainable biological ground improvement technique. The bacteria cells use the soil surfaces as nucleation sites (Stocks-Fischer et al. 1999) with the [...]

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.

Abstract Tubular aggregates (TA) are honeycomb-like arrays of sarcoplasmic-reticulum (SR) tubules affecting aged glycolytic fibers of male individuals and inducing severe sarcomere disorganization and muscular pain. TA develop in skeletal muscle from Tubular Aggregate Myopathy (TAM) patients as well as in other disorders including endocrine syndromes, diabetes, and ageing, being their primary cause unknown. Nowadays, there is no cure for TA. Intriguingly, both hypoxia and calcium dyshomeostasis prompt TA formation, pointing to a possible role for mitochondria in their setting. However, a functional link between mitochondrial dysfunctions and TA remains unknown. Herein, we investigate the alteration in muscle-proteome of TAM patients, the molecular mechanism of TA onset and a potential therapy in a preclinical mouse model of the disease. We show that in vivo chronic inhibition of the mitochondrial ATP synthase in muscle causes TA. Upon long-term restrained oxidative phosphorylation (OXPHOS), oxidative soleus experiments a metabolic and structural switch towards glycolytic fibers, increases mitochondrial fission, and activates mitophagy to recycle damaged mitochondria. TA result from the overresponse of the fission controller DRP1, that upregulates the Store-Operate-Calcium-Entry and increases the mitochondria-SR interaction in a futile attempt to buffer calcium overloads upon prolonged OXPHOS inhibition. Accordingly, hypoxic muscles cultured ex vivo show an increase in mitochondria/SR contact sites and autophagic/mitophagic zones, where TA clusters grow around defective mitochondria. Moreover, hypoxia triggered a stronger TA formation upon ATP synthase inhibition, and this effect was reduced by the DRP1 inhibitor mDIVI. Remarkably, the muscle proteome of TAM patients displays similar alterations in mitochondrial dynamics and in ATP synthase contents. In vivo edaravone treatment in mice with restrained OXPHOS restored a healthy phenotype by prompting mitogenesis and mitochondrial fusion. Altogether, our data provide a functional link between the ATP synthase/DRP1 axis and the setting of TA, and repurpose edaravone as a possible treatment for TA-associated disorders.

O presente relato de caso identificou a maculopatia média aguda paracentral como a causa de baixa de acuidade visual severa e irreversível após cirurgia de catarata. Existem fatores de risco bem estabelecidos para o desenvolvimento da maculopatia média aguda paracentral que devem ser conhecidos pelos cirurgiões de catarata. Nesse contexto cirúrgico, precauções extras no tocante a procedimentos anestésicos, pressão intraocular e alguns outros aspectos da cirurgia devem ser consideradas. A maculopatia média aguda paracentral é descrita como um sinal clínico observado no exame de tomografia de coerência óptica por domínio espectral e se trata, provavelmente, da evidência de um evento isquêmico no tecido vascular retiniano. Esse diagnóstico deve ser cogitado nos casos de perda de acuidade visual súbita no pós-operatório imediato associada com exame fundoscópico normal, como evidenciado no caso apresentado. [ABSTRACT FROM AUTHOR]

In an era where digital technologies are integral to daily life and sustainable education is increasingly critical, developing higher-order thinking skills with appropriate information and communication technology (ICT) support is crucial for achieving Sustainable Development Goals (SDGs). The purpose of this study was to examine synergies of systems thinking and technology-enhanced learning from the perspective of flow theory within the context of sustainable education. We surveyed more than 65 pre-service preschool teachers engaged in a design, technology, and engineering (DTE) course at the University of Ljubljana. Mapping of systems thinking revealed that pre-service preschool teachers needed support regarding feedback and understanding the interrelationship dimension of systems thinking—essential components of sustainable education. Predictive and mediation analyses yielded noteworthy results. Participants in the ICT-enhanced DTE course rated their cognitive and social engagement above the mid-point of the scale, with this higher engagement correlating with higher systems thinking crucial for sustainable education. In contrast, their aesthetic engagement was below the mid-point of the scale. Experiencing a flow state during ICT activities positively influenced systems thinking, particularly in terms of clear goals and autotelic experiences. Flow theory thus emerges as a solid and appropriate framework to use for studying synergies in technology-enhanced systems thinking for sustainable education. These findings underscore the importance of integrating systems thinking into curricula to enhance learning outcomes and prepare students for future challenges, thereby contributing to the achievement of SDGs through sustainable education. [ABSTRACT FROM AUTHOR]

We synthesized four new copper(II) complexes with acetato and chlorido ligands and methylammonium (MA), dimethylammonium (DMA), and tetramethylammonium (TMA) counterions: (MA)4[Cu2Ac4Cl2]Cl2·2H2O (1), (DMA)2[Cu2Ac4Cl2] (2), (DMA)4[Cu2Ac4Cl2]Cl2·2H2O (3), and (TMA)5[Cu2Ac4Cl]Cl4·4H2O (4). All compounds were characterized by single-crystal X-ray diffraction, magnetic measurements, FTIR spectroscopy, and thermogravimetric analysis. Complexes 1, 2, and 3 consist of a dinuclear coordination anion [Cu2(Ac)4Cl2]2− with bridging acetato ligands arranged in a paddle-wheel conformation and square-pyramidal coordination around Cu(II) atoms, while the coordination anion in compound 4 is a polymeric chain, parallel to the c axis, with Cu2(Ac)4 units connected through bridging chlorido ligands. Magnetic measurements carried out between 2 K and 300 K indicate strong antiferromagnetic interactions between Cu(II) ions. The effective magnetic moments range from 1.94   μ B to 2.21   μ B , exceeding the spin-only value for Cu(II) ions ( μ e f f = 1.73   μ B ) and suggesting significant orbital contributions to the magnetic moment. Thermogravimetric analysis of all complexes showed a multistep decomposition behavior yielding elemental copper as the final product. [ABSTRACT FROM AUTHOR]

In this study, the application of microbially induced carbonate precipitation for coastline protection was investigated. Untreated, moderately, and heavily cemented near-prototype dunes were fabricated in the largest wave flume in North America at the O.H. Hinsdale Wave Research Laboratory at Oregon State University. Dunes were stabilized with two treatment application systems known as surface spraying and prefabricated vertical drains. Untreated and stabilized dunes were subjected to waves similar to Hurricane Sandy conditions recorded in New Jersey in 2012. Laboratory tests and in situ assessments were performed to quantify the improvement of mechanical properties of soil and investigate the performance of dunes subjected to extreme wave actions. Post-treatment cone penetration test sounding results indicated a significant cone tip resistance that was controlled by carbonate content and cementation distribution pattern. Similarly, monitoring the changes in the morphology of dunes demonstrated that the shear strength, cementation level, and cementation distribution pattern control the equilibrium beach profile, erosion rate, and mass loss. [ABSTRACT FROM AUTHOR]

Achalasia is a rare and complex esophageal disease of unknown etiology characterized by difficulty in swallowing due to the lack of opening of the lower esophageal sphincter and the absence of esophageal peristalsis. Recent advancements in technology for analyzing DNA, RNA and biomolecules in high-throughput techniques are offering new opportunities to better understand the etiology and the pathogenetic mechanisms underlying achalasia. Through this narrative review of the scientific literature, we aim to provide a comprehensive assessment of the state-of-the-art knowledge on omics of achalasia, with particular attention to those considered relevant to the pathogenesis of the disease. The notion and importance of the multi-omics approach, its limitations and future directions are also introduced, and it is highlighted how the integration of single omics data will lead to new insights into the development of achalasia and offer clinical tools which will allow early diagnosis and better patient management. [ABSTRACT FROM AUTHOR]

Brain drain is known as the phenomenon in which people with knowledge or technical skills migrate to another country. Nowadays, brain drain is one of the most common forms of migration. Latin American countries are not exempt from this type of migration. Thus, in this article, we will investigate this phenomenon through the study and collection of data on Venezuelan people who migrate to Argentina, identifying the trends, characteristics, and situations in which the brain drain takes place. Keywords: brain drain, Venezuelan migration, humanitarian aid, political transnationalism, political remittances, skilled migration. Se conoce como brain drain el fenomeno por el que personas con conocimientos o competencias tecnicas emigran a otro pais. Es, ademas, una de las formas mas comunes de migracion en la actualidad. Los paises latinoamericanos no estan exentos de este tipo de migracion. Por ello, en esta ocasion, investigaremos este fenomeno a traves del estudio y recoleccion de datos de personas venezolanas que han migrado a Argentina, identificando las tendencias, caracteristicas y situaciones en las que se produce este fenomeno. Palabras claves: brain drain, migracion venezolana, ayuda humanitaria, transnacionalismo politico, remesas politicas, migracion cualificada, Introduction Previous contributions to the study of intra-Latin American brain drain patterns reveal that both Venezuela and Argentina are the main countries of origin of qualified migrants in the region [...]

Abstract Apathy is a clinical symptom prevalent in many neuropsychiatric pathologies. Subclinical apathy is found in 35% of the general population. Despite high prevalence and negative consequences, underlying mechanisms are poorly understood, perhaps because the concept of apathy is one-dimensional. The current investigation aims to address the incidence of multidimensional apathetic trait in three distinct forms in a student population, to specify its determinants and to evaluate its stability during a global pandemic. Two online surveys, conducted 1 year apart on two separate cohorts of university students, with qualitative measures and validated scales. The final analysis included, respectively, 2789 and 1678 students. The three forms of apathetic trait were present, with the same debilitating consequences as apathetic symptom but independent determinants. Executive apathy was predicted by depressive symptoms, emotional apathy by motivational deficit and initiative apathy comprised a mixed executive-emotional form and a pure deficit of action initiation. The three forms of subclinical apathy remained similar in the context of increased depressive symptoms due to a global pandemic. This study confirmed the presence and independence of three forms of subclinical apathy in healthy students, which remained similar even in the light of increased depressive scores. These results shed light on cognitive and neuronal mechanisms underlying multidimensional apathy, allowing new, targeted treatments.

The significance of adapting to a rapidly changing world is quite evident in the current day; thus, the awareness of how to teach students so that they can be ready to face challenges in the future is very important. Early education has a huge impact on the further development of children, so preschool teachers must be competent and use appropriate teaching and educational methods. In this study, the development of self-directed learning (SDL) of future preschool teachers is investigated by considering two variables, namely the type of study (full-time and part-time students) and the learning modalities caused by the COVID-19 pandemic (pre-, during and post-COVID-19 confinement). We collected data from 418 participants and analysed them using descriptive statistics, 2 × 3 factorial analysis of variance (ANOVA) and a two-step cluster analysis. The results show the status of pre-service preschool teachers' perceptions of their SDL development and how the variables influenced it. There were significant differences in the students' self-reported SDL skills, depending on the learning environment and the type of study. The status indicator helps educators identify and change the curriculum and how they work with students. It allows the faculty to highlight the positive aspects of the different educational modalities encountered, as well as the characteristics of the study types and their impact on the learning process to improve students’ SDL skills. The results of the study may help in the design of tailored metacognitive scaffolds that take into account different modalities. Further studies are needed to investigate the effectiveness of digital open learning environments that address both SDL and preschool educational practices.

Music is an integral part of our everyday lives. Through continuous exposure to a particular music style, an individual implicitly learns the laws of music, including the typical progression of chords that accompany the leading melody. Previous research has shown that the typical chord order in compositions is perceived as expected and satisfying, whereas the violations of the typical chord progressions are perceived as unexpected and unsatisfying. In this paper, we investigated how implicit musical knowledge influences satisfaction during listening to expected and unexpected chord progressions by taking into account the participant's music education and the overall pitch height of the chordal sequences. Ninety-seven participants (43 musicians and 54 non-musicians) took part in the experiment. They were asked to rate the degree of their satisfaction during listening to expected and unexpected chord progressions, either during the high-pitch or low-pitch height conditions. The results showed that the participants were more satisfied with expected than unexpected chord progressions, confirming previous findings on the role of implicit learning of rules of harmony. Although results did not reveal an effect of music education during listening to expected chord progressions, musicians evaluated unexpected progressions as less satisfying than non-musicians, suggesting that musicians' are more susceptible to violations of typical chord order. Finally, the results have shown that the difference in satisfaction between expected and unexpected progressions was larger in high-pitch vs. low-pitch condition, suggesting that under low-pitch condition, chord progressions were more difficult to discriminate, confirming the theory of low-interval limit.