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Background The use of thermotolerant yeast strains can improve the efficiency of ethanol fermentation, allowing fermentation to occur at temperatures higher than 40 °C. This characteristic could benefit traditional bio-ethanol production and allow simultaneous saccharification and fermentation (SSF) of starch or lignocellulosic biomass. Results We identified and characterized the physiology of a new thermotolerant strain (LBGA-01) able to ferment at 40 °C, which is more resistant to stressors as sucrose, furfural and ethanol than CAT-1 industrial strain. Furthermore, this strain showed similar CAT-1 resistance to acetic acid and lactic acid, and it was also able to change the pattern of genes involved in sucrose assimilation (SUC2 and AGT1). Genes related to the production of proteins involved in secondary products of fermentation were also differentially regulated at 40 °C, with reduced expression of genes involved in the formation of glycerol (GPD2), acetate (ALD6 and ALD4), and acetyl-coenzyme A synthetase 2 (ACS2). Fermentation tests using chemostats showed that LBGA-01 had an excellent performance in ethanol production in high temperature. Conclusion The thermotolerant LBGA-01 strain modulates the production of key genes, changing metabolic pathways during high-temperature fermentation, and increasing its resistance to high concentration of ethanol, sugar, lactic acid, acetic acid, and furfural. Results indicate that this strain can be used to improve first- and second-generation ethanol production in Brazil.

Background At this moment, there is no information in the literature showing the impact of comprehensive medication management (CMM) service delivered to patients with chronic obstructive pulmonary disease. Objective This study aims to present the clinical outcomes of this service provided to patients with chronic obstructive pulmonary disease. Settings Public specialty pharmacy where high cost drug treatments are provided for medical conditions not covered by the primary care such as COPD, located in Minas Gerais State, Brazil. Methods A retrospective analysis was conducted for 83 patients. The dependent variable in this study was the sum of the drug therapy problems detected during the first and second consultation. The independent variables were age, number of diseases and medications, diagnosis of hypertension, dyslipidemia and diabetes, and tabagism. Univariate and multivariate analyses were performed using Pearson’s Chisquare test. A level of significance of 5% was adopted for all analyses. Main outcomes Number, types and proportion of resolved drug therapy problems. Results Two hundred seventy seven drug therapy problems were identified, of which 53.1% were resolved. The most frequent drug therapy problem was the “use of unnecessary drug therapy” (n = 55; 19.8%). The identification of three or more drug therapy problem was higher among patients using five medications or more and among those using ten or more ( p  < 0.05). After the delivery of medication therapy management, the proportion of patients presenting “stable” clinical status was raised from 27 to 54% ( p  = 0.001). Conclusion CMM service demonstrates a positive impact on clinical outcomes of patients with chronic obstructive pulmonary disease and should prioritize patients with polypharmacy because they might have a higher number of drug therapy problems.

The present study aims to: (i) Identify the aroma/flavour descriptors of C. canephora samples from 13 different countries of origin and submitted to various postharvest processes, with different quality levels, and organize them in an aroma/flavour wheel for use as a descriptive tool in quality assessment; (ii) Investigate differences in description as well as quality scores attributed to the C. canephora samples by professional exporting and importing coffee graders.

Ethionamide (ETH) is a second-line drug widely used to treat multidrug-resistant tuberculosis (MDR-TB), but its low aqueous solubility compromises bioavailability and limits its therapeutic efficacy. To understand the ways to improve these properties, we combined experimental and computational approaches to elucidate the structural, electronic, thermal, and vibrational properties of ETH crystals. Powder X-ray diffraction analysis revealed a monoclinic crystal system (C1 c 1-space group), stabilized by intermolecular interactions, primarily H⋯H (49.3%) and H⋯S/S⋯H (22.1%) contacts. Energy framework analysis revealed the anisotropic nature of intermolecular interactions, with dispersion forces accounting for approximately 60% of the total stabilization energy, while Coulombic interactions showed significant directionality along the crystallographic a -axis and within the bc -plane. The total energy framework indicated that the strongest stabilization propagates along the b -axis, suggesting the formation of highly stable molecular chains, which directly influence crystal morphology and dissolution behavior. Thermal analysis confirmed ETH stability up to 162.2 °C, with melting and decomposition events characterized by endothermic peaks. Density functional theory (DFT) calculations confirmed ETH high electronic gap (7.84–8.09 eV), indicating low reactivity, while solvation studies highlighted its greater stability in polar solvents like water and methanol. Theoretical nuclear magnetic resonance studies ( 1 H and 13 C) showed minimal solvent influence on chemical shifts, reinforcing the structural stability of ETH across environments. Vibrational spectroscopy, supported by DFT, identified key modes associated with the pyridine ring, NH 2 , and C=S groups. Hirshfeld surface analysis further revealed the dominance of hydrogen bonds and van der Waals interactions, with minimal void space (5.3%) in the crystal lattice. Electrostatic potential maps identified electron-rich regions around nitrogen atoms as potential sites for hydrogen bonding and protonation, which are relevant for pharmacological interactions. These findings offer critical insights for optimizing ETH’s solid-state properties to enhance its solubility and bioavailability, paving the way for improved formulations against MDR-TB.

Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.

Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression. Through re-exposure to an unpredictable chronic mild stress protocol in rats, we observed the re-appearance of emotional and cognitive deficits. Furthermore, treatment with the antidepressants fluoxetine and imipramine was effective to promote sustained reversion of a depressive-like phenotype; however, their differential impact on adult hippocampal neuroplasticity triggered a distinct response to stress re-exposure: while imipramine re-established hippocampal neurogenesis and neuronal dendritic arborization contributing to resilience to recurrent depressive-like behavior, stress re-exposure in fluoxetine-treated animals resulted in an overproduction of adult-born neurons along with neuronal atrophy of granule neurons, accounting for an increased susceptibility to recurrent behavioral changes typical of depression. Strikingly, cell proliferation arrest compromised the behavior resilience induced by imipramine and buffered the susceptibility to recurrent behavioral changes promoted by fluoxetine. This study shows that previous exposure to a depressive-like episode impacts on the behavioral and neuroanatomical changes triggered by subsequent re-exposure to similar experimental conditions and reveals that the proper control of adult hippocampal neuroplasticity triggered by antidepressants is essential to counteract recurrent depressive-like episodes.

Sequential testing with brief cognitive tools has been recommended to improve cognitive screening and monitoring, however the few available tools still depend on an external evaluator and periodic visits. We developed a self-administered computerized test intended for longitudinal cognitive testing (Brain on Track). The test can be performed from a home computer and is composed of several subtests, expected to evaluate different cognitive domains, all including random elements to minimize learning effects. An initial (A) and a refined version of the test (B) were applied to patients with mild cognitive impairment or early dementia (n = 88) and age and education-matched controls. A subsample of a population-based cohort (n = 113) performed the test at home every three months to evaluate test-retest reliability. The test’s final version Cronbach’s alpha was 0.90, test scores were significantly different between patients and controls ( p  = 0.001), the area under the receiver operating characteristic curve was 0.75 and the smallest real difference (43.04) was lower than the clinical relevant difference (56.82). In the test-retest reliability analysis 9/10 subtests showed two-way mixed single intraclass consistency correlation coefficient >0.70. These results imply good internal consistency, discriminative ability and reliability when performed at home, encouraging further longitudinal clinical and population-based studies.

Depression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization.

Accelerators are behind many major scientific and technological breakthroughs giving a gigantic contribution to unveil the mysteries of matter. This quest continues nowadays using the high-energy machines operating at large research centres like CERN, GANIL and FAIR, among others. Meanwhile most of the small and medium size accelerators running in laboratories located in universities and research institutions around the world begin a new life making available the powerful nuclear-based techniques for multidisciplinary research in several domains. Furthermore, the small and medium size accelerator facilities still play a major role in keeping and providing knowledge in Nuclear Science and training the new generations. The two electrostatic accelerators at Instituto Superior Técnico of the University of Lisbon are devoted to multidisciplinary research as well as education and training students in nuclear-based experimental techniques. The history and work carried out in the laboratory and its role in areas with great societal impact such as materials science, energy, biomedical sciences as well as nuclear experimental physics in support of the large-scale facilities, will be highlighted in the manuscript.

Droughts are predicted to increase in both frequency and intensity by the end of the 21st century, but ecosystem response is not expected to be uniform across landscapes. Here we assess the importance of the hill-to-valley hydrologic gradient in shaping vegetation embolism resistance under different rainfall regimes using hydraulic functional traits. We demonstrate that rainfall and hydrology modulate together the embolism resistance of tree species in different sites and topographic positions. Although buffered by stable access to groundwater, valley plants are intrinsically more vulnerable to drought-induced embolism than those on hills. In all study sites, the variability in resistance to embolism is higher on hills than on valleys, suggesting that the diversity of strategies to cope with drought is more important for tree communities on hills. When comparing our results with previously published data across the tropics, we show greater variability at the local scale than previously reported. Our results reinforce the urgent need to extend sampling efforts across rainfall regimes and topographic positions to improve the characterization of ecosystem resistance to drought at finer spatial scales.