Glucose-Binding Dioclea bicolor Lectin (DBL): Purification, Characterization, Structural Analysis, and Antibacterial Properties.

In this study, we purified a lectin isolated from the seeds of Dioclea bicolor (DBL) via affinity purification. Electrophoresis analysis revealed that DBL had three bands, α, ß, and γ chains, with molecular masses of approximately 29, 14, and 12 kDa, respectively. Gel filtration chromatography revealed that the native form of DBL had a molecular mass of approximately 100 kDa, indicating that it is a tetramer. Interestingly, DBL-induced hemagglutination was inhibited by several glucosides, mannosides, ampicillin, and tetracycline with minimum inhibitory concentration (MIC) values of 1.56-50 mM. Analysis of the complete amino acid sequence of DBL revealed the presence of 237 amino acids with high similarity to other Diocleinae lectins. Circular dichroism showed the prominent ß-sheet secondary structure of DBL. Furthermore, DBL structure prediction revealed a Discrete Optimized Protein Energy (DOPE) score of -26,642.69141/Normalized DOPE score of -1.84041. The DBL monomer was found to consist a ß-sandwich based on its 3D structure. Molecular docking showed the interactions between DBL and α-D-glucose, N-acetyl-D-glucosamine, α-D-mannose, α-methyl-D-mannoside, ampicillin, and tetracycline. In addition, DBL showed antimicrobial activity with an MIC of 125 µg/mL and exerted synergistic effects in combination with ampicillin and tetracycline (fractional inhibitory concentration index ≤ 0.5). Additionally, DBL significantly inhibited biofilm formation and showed no toxicity in murine fibroblasts (p < 0.05). These results suggest that DBL exhibits antimicrobial activity and works synergistically with antibiotics.

Autonomous Sensor System for Low-Capacity Wind Turbine Blade Vibration Measurement.

This paper presents the design, implementation, and validation of an on-blade sensor system for remote vibration measurement for low-capacity wind turbines. The autonomous sensor system was deployed on three wind turbines, with one of them operating in harsh weather conditions in the far south of Chile. The system recorded the acceleration response of the blades in the flapwise and edgewise directions, data that could be used for extracting the dynamic characteristics of the blades, information useful for damage diagnosis and prognosis. The proposed sensor system demonstrated reliable data acquisition and transmission from wind turbines in remote locations, proving the ability to create a fully autonomous system capable of recording data for monitoring and evaluating the state of health of wind turbine blades for extended periods without human intervention. The data collected by the sensor system presented in this study can serve as a foundation for developing vibration-based strategies for real-time structural health monitoring.

A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.

BACKGROUND: Natural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index. METHODS: A semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells. A library of rhIL-2 molecules was constructed with single site-specific, biorthogonal chemistry-compatible non-canonical amino acids installed near the interface where IL-2 engages its cognate receptor ßγ (IL-2Rßγ) signaling complex. Biorthogonal site-specific pegylation and functional screening identified variants that retained engagement of the IL-2Rα chain with attenuated potency at the IL-2Rßγ complex. RESULTS: Phenotypic screening in mouse identifies SAR444336 (SAR'336; formerly known as THOR-809), rhIL-2 pegylated at H16, as a potential development candidate that specifically expands peripheral CD4+ Tregs with upregulation of markers that correlate with their suppressive function including FoxP3, ICOS and Helios, yet minimally expands CD8 + T or NK cells. In non-human primate, administration of SAR'336 also induces dose-dependent expansion of Tregs and upregulated suppressive markers without significant expansion of CD8 + T or NK cells. SAR'336 administration reduces inflammation in a delayed-type hypersensitivity mouse model, potently suppressing CD4+ and CD8 + T cell proliferation. CONCLUSION: SAR'336 is a specific Treg activator, supporting its further development for the treatment of AI diseases.

Interleukin-2 (IL-2) is a protein that functions as a master regulator of immune responses. A key function of IL-2 is the stimulation of immune-regulatory cells that suppress autoimmune disease, which occurs when the body's immune system mistakenly attacks healthy tissues. However, therapeutic use of IL-2 is limited by its short duration of action and incomplete selectivity for immune-suppressive cells over off-target immune-stimulatory cells. We employ a platform that we have previously developed, which is a bacterial organism with an expanded DNA code, to identify a new version of IL-2, SAR444336 (SAR'336), with an extended duration of activity and increased selectivity for immune-suppressive cells. In mice and monkeys, SAR'336 was a specific activator of immune suppression, with minimal effect on immune cells that stimulate autoimmunity. Our results support further development of SAR'336 for treatment of autoimmune disorders.

Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia.

Long non-coding RNA (lncRNA) genes represent a large class of transcripts that are widely expressed across species. As most human lncRNAs are non-conserved, we recently employed a unique humanized liver mouse model to study lncRNAs expressed in human livers. We identified a human hepatocyte-specific lncRNA, hLMR1 (human lncRNA metabolic regulator 1), which is induced by feeding and promotes hepatic cholesterol synthesis. Recent genome-wide association studies (GWAS) found that several single-nucleotide polymorphisms (SNPs) from the hLMR1 gene locus are associated with blood lipids and markers of liver damage. These results suggest that dietary and genetic factors may regulate hLMR1 to affect disease progression. In this study, we first screened for nutritional/hormonal factors and found that hLMR1 was robustly induced by insulin/glucose in cultured human hepatocytes, and this induction is dependent on the transcription factor SREBP1. We then tested if GWAS SNPs genetically linked to hLMR1 could regulate hLMR1 expression. We found that DNA sequences flanking rs9653945, a SNP from the last exon of the hLMR1 gene, functions as an enhancer that can be robustly activated by SREBP1c depending on the presence of rs9653945 major allele (G). We further performed CRISPR base editing in human HepG2 cells and found that rs9653945 major (G) to minor (A) allele modification resulted in blunted insulin/glucose-induced expression of hLMR1. Finally, we performed genotyping and gene expression analyses using a published human NAFLD RNA-seq dataset and found that individuals homozygous for rs9653945-G have a higher expression of hLMR1 and risk of NAFLD. Taken together, our data support a model that rs9653945-G predisposes individuals to insulin/glucose-induced hLMR1, contributing to the development of hyperlipidemia and NAFLD.

Early diverting stoma closure is feasible and safe: results from a before-and-after study on the implementation of an early closure protocol at a tertiary referral center.

BACKGROUND: Evidence on early closure (EC) of defunctioning stoma (DS) after colorectal surgery shows a favorable effect when patients are carefully selected. Therefore, a clinical pathway adapted to the implementation of an EC strategy was developed in our center. The aim of this study was to carry out a comparative analysis of time until DS closure and DS-related morbidity before and after the implementation of an EC protocol (ECP). METHODS: This study is a before-and-after comparative analysis. Patients were divided into two cohorts according to the observational period: patients from the period before the ECP implementation (January 2015-December 2019) [Period 1] and those from the period after that (January 2020-December 2022) [Period 2]. All consecutive patients subjected to elective DS closure within both periods were eligible. Early closure was defined as the reversal within 30 days from DS creation. Patients excluded from EC or those not closed within 30 days since primary surgery were analyzed as late closure (LC). Baseline characteristics and DS-related morbidity were recorded. RESULTS: A total of 145 patients were analyzed. Median time with DS was shorter in patients after ECP implementation [42 (21-193) days versus 233 (137-382) days, p < 0.001]. This reduction in time to closure did not impact the DS closure morbidity and resulted in less DS morbidity (68.8% versus 49.2%, p = 0.017) and fewer stoma nurse visits (p = 0.029). CONCLUSIONS: The ECP was able to significantly reduce intervals to restoration of bowel continuity in patients with DS, which in turn resulted in a direct impact on the reduction of DS morbidity without negatively affecting DS closure morbidity.

Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival.

Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.

Tobacco Use and Depression: A Hidden Epidemic among Smokers 18 Years and Older, Puerto Rico, 2018-2020.

OBJECTIVE: According to the literature, depression and tobacco use are closely linked. This study's main objectives were to provide the first population-based epidemiological profile of smokers with depression (SWD) who were 18 years and older and living in Puerto Rico (PR) from 2018 to 2020 and identify any statistically significant differences between SWD and smokers without depression (SWOD). METHODS: A descriptive cross-sectional study was carried out using PR Behavioral Risk Factor Surveillance System (PRBRFSS) data (2018-2020). Univariate analysis was performed to obtain an epidemiological profile of smokers who had depression. Likewise, using bivariate analysis, SWD and SWOD were compared to identify statistically significant differences in terms of chronic conditions, risk factors, and quit attempts. RESULTS: Depression prevalence among smokers 18 years and over in PR from 2018-2020 was 23.7%. Smokers with depression were more likely to be physically inactive (P < .001), overweight or obese (P < .001), have arthritis (P < .001), chronic obstructive pulmonary disease (P < .001), asthma (P < .001), high cholesterol (P < .001), hypertension (P < .001), coronary heart disease (P < .001), diabetes (P < .001), stroke (P < .001), and heart attack (P < .001) compared with SWOD. Likewise, SWD made more quitting attempts in the past year than did SWOD (P < .001). CONCLUSION: Our results indicate that SWD should be targeted in any health-based tobacco-control efforts to develop evidence-based strategies to reduce or eliminate tobacco use in this same population.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Effect of antibiotics and low-crude protein diets on growth performance, health, immune response, and fecal microbiota of growing pigs.

This study aimed to investigate the effects of diets with and without antibiotics supplementation and diets with 18.5% and 13.0% crude protein (CP) on growth performance, carcass characteristics, disease incidence, fecal microbiota, immune response, and antioxidant capacity of growing pigs. One hundred and eighty pigs (59-day-old; 18.5 ±â€…2.5 kg) were distributed in a randomized complete block design in a 2 × 2 factorial arrangement, nine replicates, and five pigs per pen. The factors were CP (18.5% or 13.0%) and antibiotics (none or 100 mg/kg tiamulin + 506 mg/kg oxytetracycline). Medicated diets were fed from days 59 to 73. After that, all pigs were fed their respective CP diets from 73 to 87 days. Data were analyzed using the Mixed procedure in SAS version 9.4. From days 59 to 73, pigs fed antibiotics diets had higher (P < 0.05) average daily feed intake (ADFI), average daily weight gain (ADG), gain to feed ratio (G:F), compared to the diets without antibiotics. From days 73 to 87 (postmedicated period), any previous supplementation of antibiotics did not affect pig growth performance. Overall (days 59 to 87), pigs-fed antibiotics diets had higher (P < 0.05) G:F compared to pigs-fed diets without antibiotics. In all periods evaluated, pigs fed 18.5% CP diets had higher (P < 0.05) ADG and G:F compared to pigs fed 13.0% CP. Pigs fed the 13.0% CP diets had lower (P < 0.05) fecal score and diarrhea incidence than those fed 18.5% CP. Pigs fed 18.5% CP diets had improved (P < 0.05) loin area compared to pigs-fed diets with 13.0% CP. At 66 days of age, pigs-fed antibiotics diets had lower (P < 0.05) alpha diversity estimated with Shannon and Simpson compared to the pig-fed diets without antibiotics. At family level, pigs fed 18.5% CP diets had higher (P < 0.05) relative abundance of Streptococcaceae, and lower (P < 0.05) relative abundance of Clostridiaceae at days 66 and 87 compared with pigs fed 13.0% CP. Pigs-fed antibiotics diets had lower (P < 0.05) immunoglobulin G and protein carbonyl concentrations at day 66 compared to the pigs-fed diets without antibiotics. The reduction of dietary CP from 18.5% to 13.0% reduced the growth performance and loin muscle area of growing pigs, although it was effective to reduce diarrhea incidence. Antibiotics improved growth performance, lowered diarrhea incidence, improved components of the humoral immune response, and reduced microbiota diversity. However, in the postmedicated period, we found no residual effect on the general health of the animals, and considering the overall period, only G:F was improved by the use of antibiotics.

Dietary antibiotics have been used in pig farming practices to avoid health problems and improve animal growth performance. However, their use in production animals is considered a global health challenge, due to its association with selection of resistance in zoonotic bacteria. Another negative impact of pig farming that has gained attention is related to environmental pollution due to the excretion of nitrogenous compounds. Reducing dietary crude protein content has become a goal in the pig feed industry due to the limited availability and high cost of dietary protein sources, as well as the aim of enhancing gut health in pigs. Thus, the aim of this study was to investigate the effects of diets with and without antibiotics supplementation and diets with 18.5% and 13.0% crude protein for pigs. The reduction of dietary crude protein in this study reduced growth performance, although it was effective to reduce diarrhea incidence. Antibiotics improved growth performance, positively affected the overall health of animals, and reduced microbiota diversity. However, during the postmedicated period, we found no residual effect on the general health of the animals, and considering the overall period, only gain to feed ratio was improved by the use of antibiotics.

Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.

Fungi are a diverse group of eukaryotic organisms that infect humans, animals, and plants. To successfully colonize their hosts, pathogenic fungi must continuously adapt to the host's unique environment, e.g., changes in temperature, pH, and nutrient availability. Appropriate protein folding, assembly, and degradation are essential for maintaining cellular homeostasis and survival under stressful conditions. Therefore, the regulation of proteostasis is crucial for fungal pathogenesis. The heat shock response (HSR) is one of the most important cellular mechanisms for maintaining proteostasis. It is activated by various stresses and regulates the activity of heat shock proteins (HSPs). As molecular chaperones, HSPs participate in the proteostatic network to control cellular protein levels by affecting their conformation, location, and degradation. In recent years, a growing body of evidence has highlighted the crucial yet understudied role of stress response circuits in fungal infections. This review explores the role of protein homeostasis and HSPs in fungal pathogenicity, including their contributions to virulence and host-pathogen interactions, as well as the concerted effects between HSPs and the main proteostasis circuits in the cell. Furthermore, we discuss perspectives in the field and the potential for targeting the components of these circuits to develop novel antifungal therapies.

Effective intracellular release of ibuprofen triggered by thermosensitive magnetic nanocarriers.

Stimuli-responsive nanocarriers are being widely applied in the development of new strategies for the diagnosis and treatment of diseases. An inherent difficulty in general drug therapy is the lack of precision with respect to a specific pathological site, which can lead to toxicity, excessive drug consumption, or premature degradation. In this work, the controlled drug delivery is achieved by using magnetite nanoparticles coated with mesoporous silica with core-shell structure (MMS) and grafted with the thermoresponsive polymer poly [N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate] (MMS-P). The efficiency of MMS-P as a temperature-controlled drug delivery system was evaluated by in vitro release experiments using ibuprofen (IBU) in various mammalian cell models. Further, the effects of IBU as a photoprotectant in cells exposed to photodynamic therapy (PDT) in a carbaryl-induced neurodegenerative model were evaluated. The results showed that MMS-P nanocarriers do not exhibit cytotoxicity in HepG2 cells at high doses such as 7600 µg mL-1. Pre-incubation of MMS-P charged with IBU showed no effect on the PDT in N2A cells; however, it produced a further decrease in the viability of HepG2 cells, leading to a reduction to PDT resistance. On the other hand, a cytoprotective effect against carbaryl toxicity in N2A cells was observed in IBU administrated by MMS-P, which confirms the effective intracellular IBU uptake by means of MMS-P. These results encourage the potential application of MMS-P as a drug delivery system and confirm the effect of IBU as a cytoprotective agent in a neurodegenerative model.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Influence of poverty concerns on demand for healthier processed foods: A field experiment in Mexico City.

Living in poverty can present cognitive biases that exacerbate constraints to achieving healthier diets. Better diets could imply food choice upgrades within certain food categories, such as electing processed foods with an improved nutritional profile. This study evaluated the influence of monetary and health concerns on the willingness to pay (WTP) for healthier processed foods in a low-income section of Mexico City. We employed priming techniques from the scarcity literature, which are applied for the first time to healthier food purchasing behaviours in low-income settings. Our predictions are based on a dual system framework, with choices resulting from the interaction of deliberative and affective aspects. The WTP was elicited through a BDM mechanism with 423 participants. Results showed that induced poverty concerns reduced the valuations of one of the study's healthier food varieties by 0.17 standard deviations. The latter effect did not differ by income level. The WTP for a healthier bread product but one with relatively high sugar and fat content was reduced by induced poverty concerns only among certain consumers without bread purchasing restrictions (78% of the sample). Potential mechanisms were assessed through regression analysis and structural equation modelling. The relationship between poverty concerns and WTP was mediated by increased levels of stress. While we could not rule out impact on cognitive load, it was not deemed a mediator in this study. Our findings signal that improvements in economic and psychological well-being among low-income consumers may aid to increase their demand for healthier processed foods.

Near-instantaneous battery End-of-Discharge prognosis via uncertain event likelihood functions.

The prediction of the time of occurrence of future events has been studied for decades in various scientific disciplines. Such events have historically been defined as moments where variables of interest (or indicators) hit pre-determined thresholds (i.e. the first-hitting time). Recently, semi-closed mathematical expressions were reported in the literature to analytically characterize the probability distribution of the occurrence time of future events, extending the event triggering criteria based on thresholds to a more general and intuitive threshold-less approach, where the occurrence of events is declared through the use of uncertain event likelihood functions. The End-of-Discharge time prognosis problem is formalized in this article via the definition of uncertain event likelihood functions. Moreover, a novel numerical method is proposed to compute the probability distribution of its future time of occurrence based on this conceptualization and exploiting the capability of uncertain event likelihood functions to assimilate uncertainty in analytic expressions. A case study related to energy autonomy in electromobility applications is considered; specifically an electric bicycle. Obtained results show that the proposed method achieves an extraordinary level of convergence in less than a tenth of a second, while the same level of convergence using Monte Carlo simulations under the traditional threshold crossing approach takes hours to be achieved.

Essential Oils of Aromatic Plant Species from the Atlantic Rainforest Exhibit Extensive Chemical Diversity and Antimicrobial Activity.

Microbial resistance, caused by the overuse or inadequate application of antibiotics, is a worldwide crisis, increasing the risk of treatment failure and healthcare costs. Plant essential oils (EOs) consist of hydrophobic metabolites with antimicrobial activity. The antimicrobial potential of the chemical diversity of plants from the Atlantic Rainforest remains scarcely characterized. In the current work, we determined the metabolite profile of the EOs from aromatic plants from nine locations and accessed their antimicrobial and biocidal activity by agar diffusion assays, minimum inhibitory concentration, time-kill and cell-component leakage assays. The pharmacokinetic properties of the EO compounds were investigated by in silico tools. More than a hundred metabolites were identified, mainly consisting of sesqui and monoterpenes. Individual plants and botanical families exhibited extensive chemical variations in their EO composition. Probabilistic models demonstrated that qualitative and quantitative differences contribute to chemical diversity, depending on the botanical family. The EOs exhibited antimicrobial biocidal activity against pathogenic bacteria, fungi and multiple predicted pharmacological targets. Our results demonstrate the antimicrobial potential of EOs from rainforest plants, indicate novel macromolecular targets, and contribute to highlighting the chemical diversity of native species.

Main and moderated effects of multimorbidity and depressive symptoms on cognition

Objective: Multimorbidity, or the occurrence of two or more chronic conditions, is a global challenge, with implications for mortality, morbidity, disability, and life quality. Psychiatric disorders are common among the chronic diseases that affect patients with multimorbidity. It is still not well understood whether psychiatric symptoms, especially depressive symptoms, moderate the effect of multimorbidity on cognition. Methods: We used a large (n=2,681) dataset to assess whether depressive symptomatology moderates the effect of multimorbidity on cognition using structural equation modelling. Results: It was found that the more depressive symptoms and chronic conditions, the worse the cognitive performance, and the higher the educational level, the better the cognitive performance. We found a significant but weak (0.009; p = 0.04) moderating effect. Conclusion: We have provided the first estimate of the moderating effect of depression on the relation between multimorbidity and cognition, which was small. Although this moderation has been implied by many previous studies, it was never previously estimated.

The Metamorphosing Professor: Adapting Teaching to Fulfill the Promise of Biology Education.

Teaching students at all levels of education has undergone extensive changes, particularly in the past decade. Our present student population has transformed dramatically in the 21st century due to the changing demographics of the nation, an increasing use of technology both inside and outside the classroom, along with an expectation to have information instantaneously available to peruse and utilize as a source of material. Today's instructors also need to adapt to these changes by assessing how well students are learning new concepts, as well as how much material students retain for future coursework. Here, we explore the recent history of science education, and the progress that has been made to overcome multiple learning obstacles, particularly relevant to PEERs (persons excluded because of their ethnicity or race) in STEM (science, technology, engineering, and mathematics). We hope to provide insight into how educators are restructuring the way they design their teaching portfolios to provide better outcomes for the students of today's educational system.

An Upper-Division, Remote Microbiology Laboratory That Blends Virtual and Hands-on Components to Promote Student Success during the COVID-19 Pandemic.

The COVID-19 shutdown forced many institutions of higher education to shift in-person teaching to emergency remote teaching. This was particularly challenging for laboratory courses, where students are expected to learn hands-on skills needed for their career goals. Here, we describe the transformation of an upper-division microbiology laboratory to a course that seamlessly integrates online simulations with safe, hands-on experiences that can be done from home. This blended lab course helped students attain learning outcomes similar to those achieved in the in-person class. We illustrate the implementation of Unknown Portfolios to help students gain the data analysis and critical thinking skills needed to identify an unknown microorganism. Our data show that students who took these online courses mastered material as well as students who took the lab in person, demonstrating proficiency in laboratory safety skills, hands-on techniques, and theoretical class content. Last, we explore online adaptations to enhance in-person lab classes, aiming at reducing the accessibility and equity gaps inherited in many courses, as well as discussing challenges that instructors might experience in this process.

The Dorsolateral Prefrontal Cortex Presents Structural Variations Associated with Empathy and Emotion Regulation in Psychotherapists.

Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.

Alternative Splicing in Trichophyton rubrum Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs.

Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation of efflux pumps. Alternative splicing (AS) has also been considered as a mechanism that enhances fungal adaptive responses. We used RNA-seq data from the dermatophyte Trichophyton rubrum exposed to undecanoic acid (UDA) to search for and validate AS in genes encoding efflux pumps. The magnitude of this phenomenon was evaluated using UDA and other antifungals (caspofungin, itraconazole, and terbinafine) in planktonic and biofilm cultures. In addition to the conventional isoforms, the efflux pump encoded by TERG_04309 presented two intron-retained isoforms. Biofilms trigger the simultaneous production of at least two isoforms. The intron-retained isoforms showed short lengths and topologically different organization. Furthermore, we identified the putative interaction of efflux pumps (TERG_04309 and TERG_04224). Co-expression of these genes suggests a synergistic action in antifungal resistance. Our data provide new insights into drug tolerance related to differential isoform usage and the co-expression of stress-responsive genes, which may lead to higher antifungal resistance, mainly in biofilms.