Structural basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkB.

Neurotrophin receptors of the Trk family are involved in the regulation of brain development and neuroplasticity, and therefore can serve as targets for anti-cancer and stroke-recovery drugs, antidepressants, and many others. The structures of Trk protein domains in various states upon activation need to be elucidated to allow rational drug design. However, little is known about the conformations of the transmembrane and juxtamembrane domains of Trk receptors.

Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases.

Temperature rise and its influence on the toxic effects caused by cyanotoxins in a neotropical catfish.

Potentially toxic cyanobacterial blooms (cyanoHABs) have become a problem in public water supply reservoirs. Temperature rise caused by climate change can increase the frequency and intensity of blooms, which may influence the cyanotoxins concentration in the environment. This study aimed to evaluate the effect of the temperature on the responses of a Neotropical catfish exposed to a neurotoxin-rich cyanobacterial crude extract (Raphidiopsis raciborskii T3).

Chronotype, Time of Day, and Children's Cognitive Performance in Remote Neuropsychological Assessment.

Research on the influence of chronotype and time of day (TOD) on cognitive performance, especially in children, is limited. We explored potential interactive effects, hypothesizing that performance differs when comparing preferred vs. non-preferred TOD.

Tackling the Unknown: Medical Semiotics of Inflammation and their Legal-Epistemological Boundaries in Brazil.

Do different medico-scientific understandings of autoimmune inflammation, whose carriers disobediently promote the therapeutic use of immunostimulants, have the potential to destabilize the hegemony of the standard palliative treatment based on immunosuppression? Here I explore whether and how medical paradigms in Brazil develop and expand around immunopathologies through practices of exclusion and inclusion in the context of global circulation of knowledges, therapies, and regulatory frameworks. While focusing on concurrent immunotherapeutic models biomedicine, I discuss aspects of legal-epistemological frictions that animate controversies in which distinct ways of co-producing medical evidence affect and are affected by the biomedical establishment.

Mini-ACE: Validation Study Among Older People in Long-Term Care.

Background: The Mini-Addenbrooke's Cognitive Examination (M-ACE) is a valid and reliable tool that accurately differentiates various types of cognitive impairment from Normal-cognition assessed in multiple settings. However, its validity among older individuals in long-term care (LTC) was not yet established. Therefore, we sought to assess the Portuguese M-ACE's validity, reliability, and accuracy in detecting cognitive impairment no-dementia (CIND) in LTC users.

Homebound elderly people psychotherapeutic intervention (HEPPI): Exploring the mediating role of loneliness.

Objectives: The present study aimed to explore whether the Homebound Elderly People Psychotherapeutic Intervention (HEPPI), a home-delivered ten-week cognitive-emotional intervention, was effective in reducing self-reported loneliness among homebound older adults presenting mild cognitive impairment and psychological symptomatology. Effects of HEPPI in total, social, and emotional loneliness, compared with a treatment-as-usual group, were investigated at post-intervention and 3-month follow-up. In addition, the potential role of social and emotional loneliness as mediators of the HEPPI impact on episodic memory and symptoms of depression and anxiety was examined.

BRIEF-A: Factor structure and measurement invariance across self-report and informant forms.

Objective: This study analyzes the psychometric properties of the two forms (self-report and informant) of the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) in a sample of healthy Portuguese adults.

Method: The participants were 608 adults, 304 of whom answered the self-report form (ages 18-59; 137 male and 167 female) and 304 who answered the informant form (ages 18-70; 110 male and 194 female).

Results: The internal consistency for the indexes and the Global Executive Composite was very good (≥.

Antimicrobial resistance of Escherichia coli in the UK: comparison of single vs. pooled samples from healthy pigs.

This study compared the antimicrobial resistance (AMR) of Escherichia coli detected from single samples vs. pooled samples at herd level. The national monitoring dataset included isolates from one sample per pig holding, whereas the research study included isolates from pooled samples of 10 pigs per holding.

Cholinergic neurodegeneration and cholesterol metabolism dysregulation by constitutive p75 signaling in the p75-KO mice.

Degeneration of basal forebrain cholinergic neurons (BFCNs) is a hallmark of Alzheimer's disease (AD). However, few mouse models of AD recapitulate the neurodegeneration of the cholinergic system. The p75 neurotrophin receptor, p75, has been associated with the degeneration of BFCNs in AD.

HEPPI: a randomized controlled trial of the efficacy of a cognitive-emotional intervention for homebound older adults.

Objectives: This randomized controlled trial aimed to assess the efficacy of the Homebound Elderly People Psychotherapeutic Intervention (HEPPI), a home-delivered cognitive-emotional intervention, among the homebound older population presenting with mild cognitive impairment and depressive or anxiety symptoms.

Methods: Participants were randomly assigned either to the intervention group or the treatment-as-usual group and completed baseline, post-intervention, and three-month follow-up assessments. Changes in episodic memory and symptoms of depression and anxiety were the primary outcomes.

Saxitoxin-Producing (Cyanobacteria) Constrains Fitness and Feeding Rate despite High Nutritious Food Availability.

Changes in food quality can dramatically impair zooplankton fitness, especially in eutrophic water bodies where cyanobacteria are usually predominant. Cyanobacteria are considered a food with low nutritional value, and some species can produce bioactive secondary metabolites reported as toxic to zooplankton. Considering that cyanobacteria can limit the survival, growth and reproduction of zooplankton, we hypothesized that the dietary exposure of neotropical ( and ) to saxitoxin-producing cyanobacteria impairs feeding rates and fitness regardless of a high availability of nutritious algae.

Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases.

Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in .

Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionarily conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome.

Apolipoprotein E ε4 triggers neurotoxicity via cholesterol accumulation, acetylcholine dyshomeostasis, and PKCε mislocalization in cholinergic neuronal cells.

The Apolipoprotein E (ApoE) has been known to regulate cholesterol and β-amyloid (Aβ) production, redistribution, and elimination, in the central nervous system (CNS). The ApoE ε4 polymorphic variant leads to impaired brain cholesterol homeostasis and amyloidogenic pathway, thus representing the major risk factor for Alzheimer's Disease (AD). Currently, less is known about the molecular mechanisms connecting ApoE ε4-related cholesterol metabolism and cholinergic system degeneration, one of the main AD pathological features.

Psychedelics promote plasticity by directly binding to BDNF receptor TrkB.

Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to TrkB with affinities 1,000-fold higher than those for other antidepressants, and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers.

Evaluating population histories in Patagonia and Tierra del Fuego, Chile, using ancient mitochondrial and Y-chromosomal DNA.

Objectives: This study aims to characterize the genetic histories of ancient hunter-gatherer groups in Fuego-Patagonia (Chile) with distinct Marine, Terrestrial, and Mixed Economy subsistence strategies. Mitochondrial (mtDNA) and Y-chromosome data were generated to test three hypotheses. H: All individuals were drawn from the same panmictic population; H: Terrestrial groups first populated the region and gave rise to highly specialized Marine groups by ~7,500 cal BP; or H: Marine and Terrestrial groups represent distinct ancestral lineages who migrated independently into the region.

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

Background: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR).

Kazak mitochondrial genomes provide insights into the human population history of Central Eurasia.

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level.

(Eco)Toxicology of Cyanobacteria and Cyanotoxins: From Environmental Dynamics to Adverse Effects.

The problem of artificial eutrophication, together with the effects of climate changes has led to an increase in the frequency of the occurrence of cyanobacterial blooms [...

Healthcare decision-making capacity in old age: A qualitative study.

Objectives: Research about decision-making capacity has been growing in the last decades. That relates to more concerns regarding patients' autonomy, and an increase in diseases that can negatively impact capacity. This research aims to: explore perceptions, legal aspects, and assessment procedures related to healthcare decision-making capacity in older adults with cognitive impairment; and study the first version of a new assessment instrument of this capacity.