Leishmania mexicana N-Acetyltransferease 10 Is Important for Polysome Formation and Cell Cycle Progression.

Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs.

Imlunestrant is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wildtype and Mutant Breast Cancer.

Targeting of the estrogen receptor (ER) by anti-estrogens is the standard-of-care for patients with ER+ HER2- advanced/metastatic breast cancer. While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

Background: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis.

Portion size affects food selection in an immersive virtual reality buffet and is related to measured intake in laboratory meals varying in portion size.

A crucial step for validating the utility of an immersive virtual reality (iVR) buffet to study eating behavior is to determine whether variations in food characteristics such as portion size (PS) are relevant predictors of food selection in an iVR buffet. We tested whether manipulating PS in an iVR buffet affects the weight of food selected, and whether this response to PS is similar to participants' measured intake when PS varies at laboratory meals. In a randomized crossover design, 91 adults (18-71 y; 64 females; BMI = 25.

Efficacy of Acceptance and Commitment Therapy in Daily Life in Early Psychosis: Results from the Multi-Center INTERACT Randomized Controlled Trial.

Introduction/objective: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU.

Methods: Individuals aged 15-65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app.

Yeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughput.

The routes of uptake and efflux should be considered when developing new drugs so that they can effectively address their intracellular targets. As a general rule, drugs appear to enter cells via protein carriers that normally carry nutrients or metabolites. A previously developed pipeline that searched for drug transporters using Saccharomyces cerevisiae mutants carrying single-gene deletions identified import routes for most compounds tested.

Modelling the temporal interplay between stress and affective disturbances in pathways to psychosis: an experience sampling study.

Background: One putative psychological mechanism through which momentary stress impacts on psychosis in individuals with increased liability to the disorder is via affective disturbance. However, to date, this has not been systematically tested. We aimed to investigate whether (i) cross-sectional and temporal effects of momentary stress on psychotic experiences via affective disturbance, and (ii) the reverse pathway of psychotic experiences on stress via affective disturbance were modified by familial liability to psychosis.

Structural features and development of an assay platform of the parasite target deoxyhypusine synthase of Brugia malayi and Leishmania major.

Deoxyhypusine synthase (DHS) catalyzes the first step of the post-translational modification of eukaryotic translation factor 5A (eIF5A), which is the only known protein containing the amino acid hypusine. Both proteins are essential for eukaryotic cell viability, and DHS has been suggested as a good candidate target for small molecule-based therapies against eukaryotic pathogens. In this work, we focused on the DHS enzymes from Brugia malayi and Leishmania major, the causative agents of lymphatic filariasis and cutaneous leishmaniasis, respectively.

NMR-Based Assay for the Determination of Soluble CD73 Activity in Serum.

Extracellular adenosine, produced through the activity of ecto-5'-nucleotidase CD73, elicits potent immunosuppressive effects, and its upregulation in tumor cells as well as in stromal and immune cell subsets within the tumor microenvironment is hypothesized to represent an important resistance mechanism to current cancer immunotherapies. Soluble CD73 (sCD73) enzymatic activity measured in patient serum or plasma at a baseline is reported to have prognostic as well as predictive relevance, with higher sCD73 activity associating with poor overall and progression-free survival in melanoma patients undergoing anti-PD1 monoclonal antibody treatment. Here, we report a novel NMR-based method that measures the ex-vivo kinetics of sCD73 activity with high specificity and reproducibility and is suitable for future high-throughput implementation.

Exploring the Effects of Geographic Scale on Spatial Learning.

Background: Investigating the relationship between the human body and its spatial environment is a critical component in understanding the process of acquiring spatial knowledge. However, few empirical evaluations have looked at how the visual accessibility of an environment affects spatial learning. To address this gap, this paper focuses on geographic scale, defined as the spatial extent visually accessible from a single viewpoint.

Efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL) in early psychosis: study protocol for a multi-centre randomized controlled trial.

Background: Psychotic experiences, social functioning and general psychopathology are important targets for early intervention in individuals with Ultra-High-Risk state (UHR) and a first-episode psychosis (FEP). Acceptance and Commitment Therapy (ACT) is a promising, next-generation Cognitive Behavioural Therapy (CBT) that aims to modify these targets, but evidence on sustainable change and its underlying mechanisms in individuals' daily lives remains limited. The aim of the INTERACT study is to investigate the efficacy of a novel ecological momentary intervention, Acceptance and Commitment Therapy in Daily Life (ACT-DL) in a multi-centre randomised controlled trial of individuals with UHR or FEP.

Stabilizing Techniques and Guided Imagery for Traumatized Male Refugees in a German State Registration and Reception Center: A Qualitative Study on a Psychotherapeutic Group Intervention.

Refugees have an increased risk of developing mental health problems. Due to the unstable setting in refugee state registration and reception centers, recommended trauma-focused treatment approaches are often not applicable. For this purpose, we devised a suitable therapeutic approach to treat traumatized refugees in a German state registration and reception center: Group therapy, focusing on stabilizing techniques and guided imagery according to Reddemann (2017).

Acquisition and transfer of spatial knowledge during wayfinding.

In the current study, we investigated the ways in which the acquisition and transfer of spatial knowledge were affected by (a) the type of spatial relations predominately experienced during learning (routes determined by walkways vs. straight-line paths between locations); (b) environmental complexity; and (c) the availability of rotational body-based information. Participants learned the layout of a virtual shopping mall by repeatedly searching for target storefronts located in 1 of the buildings.

Sensitivity to Peer Evaluation and Its Genetic and Environmental Determinants: Findings from a Population-Based Twin Study.

Adolescents and young adults are highly focused on peer evaluation, but little is known about sources of their differential sensitivity. We examined to what extent sensitivity to peer evaluation is influenced by interacting environmental and genetic factors. A sample of 354 healthy adolescent twin pairs (n = 708) took part in a structured, laboratory task in which they were exposed to peer evaluation.

The Impact of Treatments for Depression on the Dynamic Network Structure of Mental States: Two Randomized Controlled Trials.

Evidence is growing that vulnerability to depression may be characterized by strong negative feedback loops between mental states. It is unknown whether such dynamics between mental states can be altered by treatment. This study examined whether treatment with imipramine or treatment with Mindfulness-Based Cognitive Therapy (MBCT) reduces the connectivity within dynamic networks of mental states in individuals with depressive symptoms.

The Cascade of Stress: A Network Approach to Explore Differential Dynamics in Populations Varying in Risk for Psychosis.

Stress plays a central role in the development and persistence of psychosis. Network analysis may help to reveal mechanisms at the level of the micro-dynamic effects between stress, other daily experiences and symptomatology. This is the first study to examine time-lagged networks of the relations between minor daily stress, momentary affect/thoughts, psychotic experiences, and other potentially relevant daily life contexts in individuals varying in risk for psychosis.

Modeling the Interplay Between Psychological Processes and Adverse, Stressful Contexts and Experiences in Pathways to Psychosis: An Experience Sampling Study.

Several integrated models of psychosis have implicated adverse, stressful contexts and experiences, and affective and cognitive processes in the onset of psychosis. In these models, the effects of stress are posited to contribute to the development of psychotic experiences via pathways through affective disturbance, cognitive biases, and anomalous experiences. However, attempts to systematically test comprehensive models of these pathways remain sparse.

Ecological momentary interventions in psychiatry.

Purpose Of Review: In this review, we discuss feasibility, content, and where possible efficacy of ecological momentary interventions (EMIs) in psychiatry. EMIs adopt mobile devices, such as personal digital assistants or smartphones, for the delivery of treatments in the daily life of patients. We will discuss EMIs in the field of schizophrenia, bipolar disorder and major depression disorder, as well as one generic, transdiagnostic EMI.

Rate of CRL4(CRBN) substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4.

Recent discoveries suggest that the critical events leading to the anti-proliferative activity of the IMiD immunomodulatory agents lenalidomide and pomalidomide in multiple myeloma (MM) cells are initiated by Cereblon-dependent ubiquitination and proteasomal degradation of substrate proteins Ikaros (IKZF1) and Aiolos (IKZF3). By performing kinetic analyses, we found that the downregulation or proteasomal degradation of Ikaros and Aiolos led to specific and sequential downregulation of c-Myc followed by IRF4 and subsequent growth inhibition and apoptosis. Notably, to ensure growth inhibition and cell death, sustained downregulation of Ikaros and Aiolos, c-Myc or IRF4 expression was required.

Using DNA Barcodes to Identify Road-Killed Animals in Two Atlantic Forest Nature Reserves, Brazil.

Road mortality is the leading source of biodiversity loss in the world, especially due to fragmentation of natural habitats and loss of wildlife. The survey of the main species victims of roadkill is of fundamental importance for the better understanding of the problem, being necessary, for this, the correct species identification. The aim of this study was to verify if DNA barcodes can be applied to identify road-killed samples that often cannot be determined morphologically.