Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial Protein Homeostasis and Cardiomyopathy

Human mitochondrial disorders impact tissues with high energetic demands and can be associated with cardiac muscle disease (cardiomyopathy) and early mortality. However, the mechanistic link between mitochondrial disease and the development of cardiomyopathy is frequently unclear. In addition, there is often marked phenotypic heterogeneity between patients, even between those with the same genetic variant, which is also not well understood. Several of the mitochondrial cardiomyopathies are related to defects in the maintenance of mitochondrial protein homeostasis, or proteostasis. This essential process involves the importing, sorting, folding and degradation of preproteins into fully functional mature structures inside mitochondria. Disrupted mitochondrial proteostasis interferes with mitochondrial energetics and ATP production, which can directly impact cardiac function. An inability to maintain proteostasis can result in mitochondrial dysfunction and subsequent mitophagy or even apoptosis. We review the known mitochondrial diseases that have been associated with cardiomyopathy and which arise from mutations in genes that are important for mitochondrial proteostasis. Genes discussed include DnaJ heat shock protein family member C19 (DNAJC19), mitochondrial import inner membrane translocase subunit TIM16 (MAGMAS), translocase of the inner mitochondrial membrane 50 (TIMM50), mitochondrial intermediate peptidase (MIPEP), X-prolyl-aminopeptidase 3 (XPNPEP3), HtraA serine peptidase 2 (HTRA2), caseinolytic mitochondrial peptidase chaperone subunit B (CLPB) and heat shock 60-kD protein 1 (HSPD1). The identification and description of disorders with a shared mechanism of disease may provide further insights into the disease process and assist with the identification of potential therapeutics.
The Efficacy of Completing Form-focused Tasks Collaboratively vs Individually: Utilizing Interventionist Dynamic Assessment to Quantify Learning Gains

Many language teachers employ collaborative learning within their classrooms. However, expectations surrounding the efficacy of working collaboratively need to be empirically verified. This study employed dynamic assessment to investigate whether learners who are situated within an undergraduate Qatari EFL context learn second language grammatical structures more effectively by working either collaboratively with their peers or individually. Interventionist dynamic assessment was used to quantify the extent of the learning gains made by male Arabic undergraduate EFL learners (N = 52) three times (pretest, posttest, and delayed posttest) over a 12-week period. In between the pretest and the posttest, six form-focused treatment tasks were administered. The experimental group (n = 20) completed the tasks collaboratively with their peers; a comparison group (n = 16) completed the tasks individually; and a control group (n = 16) did not complete the tasks. The target structures were the simple past passive and the present continuous passive. A Mood’s median test (Mood, 1954) found no statistically significant differences between the collaborative condition and the individual condition. Although measuring emergent abilities which are still in the process of developing provided a more complete picture of the efficacy of working collaboratively, the lack of a statistically significant difference between the performances of the experimental and comparison groups for both target structures suggests that working collaboratively is not statistically more effective in facilitating learners’ linguistic development than working individually.
Revisiting the governance-growth nexus: Evidence from the world’s largest economies

Abstract This study delves into the symmetric effects of governance on economic growth for the world’s ten largest economies, employing a model augmented with well-known growth, governance, and control predictors to inform model specification. Using panel and time-series techniques, both collectively and individually, the initial results reveal that governance predictors and growth postulate a long-run symmetric nexus. Applying the autoregressive distributed lags (ARDL) model, the results show that although governance predictors positively impact the economic growth of the panel both in the short and long runs, growth is weakly sensitive to governance predictors. The results of the ARDL estimates for cross-country show that Canada’s growth is highly sensitive to governance predictors, followed by France, showing moderate sensitivity. Moreover, the findings support the notion that the US, China, Germany, India, the UK, Brazil, and Italy exhibit weak sensitivity to governance predictors. Besides, the error-correction results demonstrate a high speed of adjustment of the short-run symmetries of the panel to its long-run equilibrium. Since economic growth swiftly responds to the rise and fall of governance predictors, specific policy adjustments are required to maintain sustainable and long-run growth.
Vegetative growth, yield, and water productivity of an early maturing peach cultivar under deficit irrigation strategies in a warm and arid area

Deficit irrigation strategies are considered as promising irrigation management for water saving. In the arid areas of southern Tunisia, agriculture relies heavily on irrigation. With rainfall scarcity, valuable management of water requires efficient approaches. In this context, the effects of deficit irrigation (CDI) and partial root zone drying (PRD) on the vegetative and fruiting behaviour of an early maturing peach (Prunus persica cv. Flordastar) were investigated. Shoot and trunk growth, yield, and fruit size were evaluated during three successive years (2013–2015). In reference to full irrigation (FI) treatment, a 50% water restriction was applied using CDI and PRD. The results obtained showed that both strategies at 50% crop evapotranspiration induced a similar significant reduction of tree vigour mediated by shoot length, trunk cross‐sectional area, and pruning wood weight. Consequently, there was a significant yield loss of 25% following the continuous water restriction of 50% observed throughout the experimental period. However, these yield losses were offset by substantial water savings in the range of 48%–52% and a significant increase of agricultural water productivity. Hence, these techniques lead to significant water savings and vegetative and yield losses offset by a significant increase in water productivity.
Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy

Simple Summary The mammalian target of rapamycin (mTOR) pathway promotes cell growth and metabolism in response to growth factors, nutrients, and cellular energy status. Dysregulation and mutation of the mTOR pathway can contribute to tumor initiation and progression. mTOR pathway abnormalities have been found in approximately 70% of urothelial carcinomas (UCs). This review summarizes recent advances in knowledge of the mTOR pathway, highlights the role of the mTOR pathway in UC, and explores the potential of the mTOR pathway as a therapeutic target in UC. This review also explores current preclinical studies and clinical trials targeting the mTOR pathway, and concludes with future directions of research that could more robustly define and target aberrant mTOR activity in bladder cancer. Abstract The mammalian target of rapamycin (mTOR) pathway regulates important cellular functions. Aberrant activation of this pathway, either through upstream activation by growth factors, loss of inhibitory controls, or molecular alterations, can enhance cancer growth and progression. Bladder cancer shows high levels of mTOR activity in approximately 70% of urothelial carcinomas, suggesting a key role for this pathway in this cancer. mTOR signaling initiates through upstream activation of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) and results in activation of either mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2). While these complexes share several key protein components, unique differences in their complex composition dramatically alter the function and downstream cellular targets of mTOR activity. While significant work has gone into analysis of molecular alterations of the mTOR pathway in bladder cancer, this has not yielded significant benefit in mTOR-targeted therapy approaches in urothelial carcinoma to date. New discoveries regarding signaling convergence onto mTOR complexes in bladder cancer could yield unique insights the biology and targeting of this aggressive disease. In this review, we highlight the functional significance of mTOR signaling in urothelial carcinoma and its potential impact on future therapy implications.
Nimodipine Exerts Time-Dependent Neuroprotective Effect after Excitotoxical Damage in Organotypic Slice Cultures

During injuries in the central nervous system, intrinsic protective processes become activated. However, cellular reactions, especially those of glia cells, are frequently unsatisfactory, and further exogenous protective mechanisms are necessary. Nimodipine, a lipophilic L-type calcium channel blocking agent is clinically used in the treatment of aneurysmal subarachnoid haemorrhage with neuroprotective effects in different models. Direct effects of nimodipine on neurons amongst others were observed in the hippocampus as well as its influence on both microglia and astrocytes. Earlier studies proposed that nimodipine protective actions occur not only via calcium channel-mediated vasodilatation but also via further time-dependent mechanisms. In this study, the effect of nimodipine application was investigated in different time frames on neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures. Nimodipine, but not nifedipine if pre-incubated for 4 h or co-applied with NMDA, was protective, indicating time dependency. Since blood vessels play no significant role in our model, intrinsic brain cell-dependent mechanisms seems to strongly be involved. We also examined the effect of nimodipine and nifedipine on microglia survival. Nimodipine seem to be a promising agent to reduce secondary damage and reduce excitotoxic damage.
Performance Assessment of Low-Temperature Solar Collector with Fullerenes C60 Manufactured at Low Cost in an Emerging Country

In this work, the performance of a low-temperature solar collector (LTSC) is evaluated, using carbon nanoparticles in water as working fluid. The nanoparticles used are crystallized fullerenes, with a red parameter of 1.42 nm ± 0.5 nm, with different volume fractions in water. The thickness of the carbon film was approximately 140 to 520 nm. The study is divided into three parts: modeling and simulation of an LTSC, low-cost production and characterization of nanoparticles, and thermal evaluation of the LTSC. For the study, fullerenes were produced by microwave synthesis from a terpenoid resin (Camphor) and the nanoparticles were characterized by scanning electron microscopy (SEM) and High-Resolution Transmission (HRTEM). Tests were carried out with different volumetric flow rates, 0.0111 LT/s, 0.0166 LT/s and 0.0194 L/s, and two volumetric concentrations, 0.035% and 0.063%. The results obtained from the fullerene nanofluid showed an improvement in the thermophysical properties compared to the properties of water. The performance results showed that the efficiency increases up to 47.2% compared to that of water, with a volume fraction of 0.063%, and a flow rate of 0.0194 LT/s.
First Principles Density Functional Theory Investigation on the Structural, Energetic and Electronic Properties of 6–Bromo–4–Oxo–4H–Chromene–3–Carbaldehyde

In this paper, we report the first principles Density Functional Theory (DFT) calculation to study the structural, energetic, and electronics properties of the 6–Bromo–4–Oxo–4H–Chromene–3–Carbaldehyde, C10H5BrO3 molecular framework. Geometry optimization technique was carried out to find the local energy minimum of the title compound using four hybrid DFT functionals with the basis set of 6–311++G**. The optimized molecular structure of C10H5BrO3 cluster was then used to determine the HOMO–LUMO gaps, Molecular Electrostatic Potential (MEP), Mulliken atomic charges, and others. Using the four hybrid DFT techniques, the optimized geometries of C10H5BrO3 molecular cluster is close to that of measurement data. Our calculation results also show that the total energies obtained are close to each other with the four hybrid DFT procedures. The diagram of electrostatic potential surface show that the regions of negative electrostatic potential around the oxygen atoms, O1 and O2. Using the scheme of Mulliken Population Analysis (MPA), the distributions of atomic charges follow the same arguments for the B3LYP/6–311++G**, B3PW91/6–311++G**, M06/6–311++G**, and PBE1PBE/6–311++G** simulation approaches. For example, the atom of C5 has the highest positively charge, whereas the highest negatively charge was found in the C4 atom. For Br atom, the atomic charge values obtained are –0.158, –0.222, –0.277, and –0.224, respectively for the B3LYP/6–311++G**, B3PW91/6–311++G**, M06/6–311++G**, and PBE1PBE/6–311++G** computational methods.
Milk Thistle (Silybum Marianum L.) as a Novel Multipurpose Crop for Agriculture in Marginal Environments: A Review

Milk thistle (Silybum marianum (L.) Gaertn. ) is a versatile crop that has adapted to the broadly different soil and environmental conditions throughout all continents. To date, the fruits (“seeds”) of the plant are the only reliable source of silymarin, which, given its recognized therapeutic effects and its many present and potential uses, has led to a significant re-discovery and enhancement of the crop in recent years. Overall, although many studies have been carried out globally on the bioactivity, phytochemistry, and genetics of milk thistle, few and discontinuous research activity has been conducted on its basic agronomy as well as on the farm opportunities offered by the cultivation of this species. However, the multiple potential uses of the plant and its reduced need for external inputs suggest that milk thistle can perfectly fit among the most interesting alternative crops, even for marginal environments. The growing interest in natural medicine, the increasing popularity of herbal dietary supplements, and the multiple possibilities for livestock feeding are all arguments supporting the idea that in many rural areas, this crop could represent a significant tool for enhancing and stabilizing farm income. However, several issues still have to be addressed. The species retains some morphological and physiological traits belonging to non-domesticated plants, which make the application of some common agronomic practices challenging. Furthermore, the lack of reliable field data devoted to the definition of suitable cropping protocols represents a major constraint on the spread of this crop among farmers. This review has therefore focused on updating information on the main morphological and phytochemical traits of the crop and its agronomic characteristics and novel uses. Several gaps in technical knowledge have been addressed, and further goals for experimental activity have been outlined in order to guide farmers eager to cope with the cultivation of such a challenging and resource-rich crop.
Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells

Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.
Media Diet and Polarisation: Evidence from Spain

ABSTRACT Does media diet diversity influence affective polarisation of the public? To test this hypothesis we analyse data from Spain, which like other South European countries has a highly politicised media system. The study operationalises media diet diversity based on survey and web-tracking data. It considers diversity both in terms of the quantity of media consumed and exposure to opposing viewpoints using the two politico-ideological dimensions that conventionally define Spanish politics: left–right and centre–periphery. The results are rather complex and show certain ambivalence. As expected, a more diverse media diet generally tends to depolarise individuals; however, when considering the centre-periphery dimension, we find that media diet diversity can further exacerbate polarisation. That highlights the role identities can play as a potential source of polarisation.
Relationships of Cannabis Policy Liberalization With Alcohol Use and Co-Use With Cannabis: A Narrative Review

PURPOSE The liberalization of cannabis policies has the potential to affect the use of other substances and the harms from using them, particularly alcohol. Although a previous review of this literature found conflicting results regarding the relationship between cannabis policy and alcohol-related outcomes, cannabis policies have continued to evolve rapidly in the years since that review. SEARCH METHODS The authors conducted a narrative review of studies published between January 1, 2015, and December 31, 2020, that assessed the effects of cannabis policies on the use of alcohol in the United States or Canada. SEARCH RESULTS The initial search identified 3,446 unique monographs. Of these, 23 met all inclusion criteria and were included in the review, and five captured simultaneous or concurrent use of alcohol and cannabis. DISCUSSION AND CONCLUSIONS Associations between cannabis policy liberalization and alcohol use, alcohol-related outcomes, and the co-use of alcohol and cannabis were inconclusive, with studies finding positive associations, no associations, and negative associations. Although several studies found that cannabis policy liberalization was associated with decreases in alcohol use measures, these same studies showed no impact of the cannabis policy on cannabis use itself. The lack of a consistent association was robust to subject age, outcome measure (e.g., use, medical utilization, driving), and type of cannabis policy; however, this may be due to the small number of studies for each type of outcome. This paper discusses several notable limitations of the evidence base and offers suggestions for improving consistency and comparability of research going forward, including a stronger classification of cannabis policy, inclusion of measures of the alcohol policy environment, verification of the impact of cannabis policy on cannabis use, and consideration of mediation effects.
Electronic States of Tris(bipyridine) Ruthenium(II) Complexes in Neat Solid Films Investigated by Electroabsorption Spectroscopy

We present the electric field-induced absorption (electroabsorption, EA) spectra of the solid neat films of tris(bipyridine) Ru(II) complexes, which were recently functionalized in our group as photosensitizers in dye-sensitized solar cells, and we compare them with the results obtained for an archetypal [Ru(bpy)3]2+ ion (RBY). We argue that it is difficult to establish a unique set of molecular parameter values by discrete parametrization of the EA spectra under the Liptay formalism for non-degenerate excited states. Therefore, the experimental EA spectra are compared with the spectra computed by the TDDFT (time-dependent density-functional theory) method, which for the first time explains the mechanism of electroabsorption in tris(bipyridine) Ru complexes without any additional assumptions about the spectral lineshape of the EA signal. We have shown that the main EA feature, in a form close to the absorption second derivative observed in the spectral range of the first MLCT (metal-to-ligand charge transfer) absorption band in Ru(bpy)3(PF6)2, can be attributed to a delocalized and orbitally degenerate excited state. This result may have key implications for the EA mechanism in RBY-based systems that exhibit similar EA spectra due to the robust nature of MLCT electronic states in such systems.
Ethanolic extract of Turkish bee pollen and propolis: phenolic composition, antiradical, antiproliferative and antibacterial activities

Abstract Bee pollen and propolis are considered as health-promoting foods with many therapeutic (antibacterial, antifungal and antioxidant) activities. This study analyzed the phenolic profile and the antioxidant properties of Turkish bee pollen and propolis ethanolic extracts and assayed their antiproliferative effect on myeloma cells and in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity assays included agar well diffusion and microdilution methods. The phenolic profile and several aromatic compounds of the extracts were determined by high-performance liquid chromatography with diode-array detection (HPLC-DAD). The antiproliferative activity on myeloma cells was determined by MTT test. The propolis extract had higher total phenolic content (TPC), free-radical scavenging activity (DPPH) and half-maximal inhibitory concentration (IC50) than the pollen ethanolic extract. Benzoic and cinnamic acid were the most abundant aromatic substances in the pollen and propolis extracts, respectively. The IC50 values of pollen and propolis extracts on myeloma cells were 1.49% and 2.88%, respectively. The propolis extract was active against S. aureus and E. coli, but not P. aeruginosa. The pollen extract presented no detectable inhibition zone against the three bacterial strains. The minimum inhibitory concentration (MIC) of both extracts for S. aureus and E. coli was 0.63% (w/v). The minimum bactericidal concentration (MBC) of the propolis extract was 1.25% for S. aureus and E. coli. MIC could not be determined for the pollen extract in the tested bacteria. The pollen and propolis extracts did not exert antimicrobial activity against P. aeruginosa up to 2.5% concentration.