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Key messageWe reconstructed the needle tissue Transcriptome of P. pinceana for individuals from distinct biogeographic regions across a temperature and precipitation gradient that represents its natural distribution. Gene expression analysis via RNA-Seq identified differential response to biotic stress.Phenotypic plasticity includes physiological traits affected by subtle changes in mRNA expression levels, causing different molecular phenotypes. We assessed the differential response to climate heterogeneity across the geographic range of Pinus pinceana G. Gordon & Glendinning. This pinyon pine shows a fragmented geographic distribution suggesting adaptation to the arid and extreme conditions of the eastern mountain slopes of the Chihuahuan desert. The geographic distribution of P. pinceana spans regions with significant variation in annual temperature and precipitation. We tested whether phenotypic divergence is supported by differences in expression profiles in P. pinceana mature trees along its natural distribution and corresponds to the changes in drought and other environmental stress. The reconstructed Transcriptome included 45,431 high-quality annotations derived from the needles of seven individuals across contrasting biogeographic and climatic localities. Trees from the driest regions shared active responses related to abiotic factors. The differential expression analysis identified intermediates and regulators of abiotic stress response for 26 genes, highlighting families involved in the environmental response to abiotic stress, and proteins linked to up-regulated responses, such as LRR receptor-like serine/threonine-protein kinase and L-type lectin receptor kinases (LecRK), directly related to pathogens. When Chihuahuan desert samples were compared with arboretum samples, we found differential expression of a regulator of root morphogenesis, cysteine-rich receptor-like protein kinase (CRK28), which could relate to differential absorption in drought conditions.

β-Glucans stimulate the immune system, training it to recognize and respond to antigens, which bolsters immunity, including to vaccines. The present study evaluated the capacity of β-glucans to stimulate immunity subsequent to primary vaccination for SARS-CoV-2 with ChAdOx1. Thirty-four SARS-CoV-2-non-immune men (18–49 years) were split into two groups: one receiving 500 mg of oral insoluble yeast β-glucans daily (the glucan group) and the other a placebo (the control group). The supplementation period lasted fourteen days in total, including seven days before and seven days after the initial vaccine dosage. A series of blood samples were collected at three time points: M1 (prevaccination); M2 (30 days after the first vaccination); and M3 (30 days after booster). A lateral flow immunoassay was used to qualitatively identify IgM and IgG against the virus. The levels of antigen-specific IgG anti-spike (S1), receptor-binding domain (RBD), and nucleocapsid (N) were quantified using a LEGENDplex assay. The NeutraLISA assay was used to evaluate the neutralizing antibodies (NAbs). Statistically significant results were defined as those with p < 0.05. Both groups produced similar amounts of NAbs after the first vaccination (M2). However, the glucan group had higher levels in M3, with a more uniform distribution. Furthermore, the levels of anti-S1 IgG in M2 exhibited elevated concentrations, indicating a significant positive correlation with NAbs levels obtained post-second dose (M3). In contrast, individuals who had immunity to common cold human coronaviruses (HCoVs), evidenced by the presence of IgG anti-N in M1 were associated with IgG anti-S1 only in M3, not correlated with NAbs levels. This finding indicates that cross-immunity from other HCoVs did not accelerate or direct the humoral immune response as was observed in the glucan group. Therefore, it can be inferred that the β-glucan supplementation was more effective than immunity from other HCoVs. The capacity of β-glucan to induce trained immunity (TRIM) has the potential to augment immune responses, thereby modifying antibody production in response to the vaccine stimulus. Future studies should evaluate the potential of β-glucan as an adjuvant to vaccines, especially in children, the elderly, and immunocompromised individuals. They should also assess long-term immunity and cross-protection.

Aim: The aim of this study was to evaluate the correlation between malocclusions and visual defects. This is a case-control study evaluating the prevalence of visual defects in patients with different types of malocclusions. Methods: One-hundred and sixty patients aged from 5 to 14 were evaluated using the ROMA index to detect malocclusion; the ones with the lowest scores were used as the control group. They were also submitted to visual-capacity inspection for motility and refractive disorders. Results: Our work showed an enhanced prevalence of refractive defects or fusional vergence defects and alteration of eye movements (especially the saccades) in almost all dental malocclusions. Statistics: The Kappa test values for ROMA index were between 0.643 and 1.00 for the intraoperator agreement (0.00 < p < 0.002) and between 0.773 and 1.00 for the agreement between operators (p = 0 < 0.001). The statistically significance level for the correlation malocclusion/visual defects was set at p < 0.05. Statistical analyses were performed with the STATA software (version 15.0, Stata Corp LP, College Station, TX, USA). Conclusion: Considering the high level of the statistical analysis and the accuracy of the methodology used, these data allows the establishment of a huge correlation between sagittal, transversal and vertical malocclusions with ocular disorders (myopia, hyperopia, astigmatism and ocular motility defects).

Seed production, quality, germination and seedling establishment are indicators of reproductive success in conifers. Monitoring of these parameters is essential to determine the viability of populations for the purposes of conservation. We analyze cone and seed traits as indicators of reproductive success in the endangered Rzedowski´s pine (Pinus rzedowskii (Madrigal et Caballero) and near-threatened veitchii pine (Pinus ayacahuite var. veitchii (Shaw)) in west-central Michoacán, Mexico. These traits were systematically quantified and their variation assessed using Generalized Linear Mixed Models (GLMMs). We found that the reproductive success of Rzedowski’s pine seems to be critical, presenting low seed efficiency (17.10%), germination (5.0%) and seedling establishment (27.7%), with high levels of inbreeding (0.79). In contrast, veitchii pine presents moderate seed efficiency (54.9%), high germination (71.5%) and seedling establishment (84%–97%) and low inbreeding (0.33). Reproductive indicators differed significantly among zones and populations for each species, where fragment sizes mainly affected seed production and efficiency. This result indicates that fragmentation has played a more important role in the reproductive success of Rzedowski’s pine than in veitchii pine, perhaps by limiting pollen flow among zones and populations and producing higher levels of inbreeding and lower seed efficiency in the former species. We propose a conservation strategy for these important pine species in order to increase their long-term genetic viability.

Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.

This study was conducted to determine the genetic diversity, structure and gene flow of 11 wild populations of Phaseolus lunatus L. in four regions of traditional agriculture in the Yucatan Peninsula, Mexico, part of the putative domestication area of its Mesoamerican gene pool. Analyzing eight microsatellite loci, the populations showed high values of diversity: observed heterozygosity (Ho) 0.46 to 0.9; Nei's index of diversity (H) 0.35 to 0.59 and average number of alleles per locus (A) 2.37 to 3.38. Both Nei's index of populations differentiation (Gst) and analysis of molecular variance (AMOVA) indicated strong differentiation. The Bayesian analysis of grouping and the Mantel test suggested isolation among agricultural regions as a major factor for population differentiation. Even though a low long-term gene flow (Nm = 0.66) and low rates of recent migration among populations were observed, there were some cases where the accidental transport of seeds could be favoring a gene flow at a long distance. Data found in this study suggest a positive correlation between agricultural intensification and increase in diversity, suggesting that wild populations are favored by the intensification of disturbance in situations involving at least 3 yr of fallow. However, the opposite could be true at higher levels of intensification as has been reported in the Central Valley of Costa Rica, where the diversity is diminishing.

p53 is a well-known tumor suppressor that has emerged as an important player in energy balance. However, its metabolic role in the hypothalamus remains unknown. Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity. AgRP-specific ablation of p53 resulted in increased hypothalamic c-Jun N-terminal kinase (JNK) activity before the mice developed obesity, and central inhibition of JNK reversed the obese phenotype of these mice. The overexpression of p53 in the ARC or specifically in AgRP neurons of obese mice decreased body weight and stimulated BAT thermogenesis, resulting in body weight loss. Finally, p53 in AgRP neurons regulates the ghrelin-induced food intake and body weight. Overall, our findings provide evidence that p53 in AgRP neurons is required for normal adaptations against diet-induced obesity. Emerging studies suggest that p53 is an important regulator of energy metabolism, yet there is little known about the metabolic function of this tumor suppressor in the hypothalamus. Here, authors illustrate that p53, specifically in AgRP neurons, is required for adaptation to diet-induced obesity.

Analgesia is paramount to improving critically ill patients recovery and preventing complications, especially during the post-operative time. Nonsteroidal anti-inflammatory drugs (NSAIDs) provide cost-effective analgesia but also carry risks, including gastrointestinal bleeding and acute kidney injury (AKI). Their safety in this setting is poorly understood. All patients admitted to the Hospital Vila Franca de Xira ICU for more than 24 h, from January 1st 2015, to December 31st 2023, were included. Acute kidney injury was tracked throughout the ICU and hospital stay for all included patients, using the serum creatinine and urine output. Patients already with kidney dysfunction on admission to the ICU, either chronic or acute, were excluded. Short- and long-term outcomes (until 2 years of follow-up) were retrieved. The study included 1157 patients. NSAIDs were more commonly used among surgical patients (62. in non-scheduled and 61. in scheduled surgery) than medical patients (23., p < 0.001). Its use was associated with higher AKI rates (67. vs. 51., p = 0.009), including severe AKI (stage 3, 34. vs. 26., p = 0.008). Notably, while non-severe AKI had no significant impact on 2-year survival, severe AKI was associated with significantly worse survival (adjusted hazard ratio 1.42, confidence interval 1.09–1.86, p = 0.011). Recovery of renal function did not significantly decrease the long-term survival (80. vs. 78., log-rank test, p = 0.636). In critically ill patients, the use of NSAIDs is associated with AKI and may lead to a worse prognosis. [Display omitted] •Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for analgesia.•NSAIDs were independently associated with acute kidney injury (odds ratio 1.98).•Patients with severe acute kidney injury had significantly lower 2-year survival.

Nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with obesity and insulin resistance, is characterized by hepatic lipid accumulation and activation of the endoplasmic reticulum (ER) stress response. The sirtuin 2 (SIRT2) protein deacetylase is emerging as a new player in metabolic homeostasis, but its role in the development of hepatic steatosis and its link with ER stress activation remains unknown. SIRT2-knockout (SIRT2-KO) and wild-type mice were fed either a control or a high-fat diet (HFD) for 4 weeks. Genetic manipulation of SIRT2 levels was performed in human hepatic cells. Although apparently normal under a control diet, SIRT2-KO mice showed accelerated body weight gain and adiposity on a HFD, accompanied by severe insulin resistance. Importantly, SIRT2-KO mice exhibited worsened hepatic steatosis independently from diet, consistent with upregulated gene expression of lipogenic enzymes and increased expression of ER stress markers. Exposure of hepatic cells to palmitate induced lipid accumulation, increased ER stress, and decreased SIRT2 expression. Moreover, SIRT2-silenced cells showed enhanced lipid accumulation and ER stress activation under basal conditions, whereas SIRT2 overexpression abrogated palmitate-induced lipid deposition and ER stress activation. Our findings reveal a role for SIRT2 in the regulation of hepatic lipid homeostasis, potentially through the ER stress response, suggesting that SIRT2 activation might constitute a therapeutic strategy against obesity and its metabolic complications.