Animal study

Advancements in the management of patients with chronic myeloid leukemia (CML) allowed them to achieve survival comparable with their healthy counterparts. Consequently, their care has widened with growing focus on quality of life, including parenting children. Although tyrosine kinase inhibitors (TKI) are contraindicated in pregnancy given their teratogenic effect, their effect on male fertility is less clear with contradictory results from animal studies and case reports/series. We compared the sperm analysis parameters, as the gold-standard assessment for male fertility, of 11 patients with CP- CML before and after TKI therapy...

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the major components of long-chain per- and polyfluorinated alkyl substances (PFAS), known for their chemical stability and environmental persistence. Even if PFOA and PFOS have been phased out or are limited in use, they still represent a concern for human and environmental health. Several studies have been performed to highlight the toxicological behavior of these chemicals and their mode of action (MoA). Data suggested the causal association between PFOA or PFOS exposure and carcinogenicity in humans, but the outcomes of epidemiological studies showed some inconsistency...

Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck-like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation...

Given the nature of horse-human interactions in equine-assisted services (EAS), death of a horse may have significant impacts. In this study, an online survey was distributed to EAS practitioners. The goal of the study was to explore the experiences of practitioners and identify the socioemotional processes that occur upon the death of an equine within an EAS program. Open-ended responses ( N = 84) were analyzed qualitatively using a grounded theory and constant-comparative approach. Responses are situated into two themes (1) Processing the death of an equine and (2) Practical implications...

Clearance of serotonin (5-hydroxytryptamine, 5-HT) from the synaptic cleft after neuronal signaling is mediated by serotonin transporter (SERT), which couples this process to the movement of a Na+ ion down its chemical gradient. After release of 5-HT and Na+ into the cytoplasm, the transporter faces a rate-limiting challenge of resetting its conformation to be primed again for 5-HT and Na+ binding. Early studies of vesicles containing native SERT revealed that K+ gradients can provide an additional driving force, via K+ antiport...

Full understanding of proteostasis and energy utilization in cells will require knowledge of the fraction of cell proteins being degraded with different half-lives and their rates of synthesis. We therefore developed a method to determine such information that combines mathematical analysis of protein degradation kinetics obtained in pulse-chase experiments with Bayesian data fitting using the maximum entropy principle. This approach will enable rapid analyses of whole-cell protein dynamics in different cell types, physiological states, and neurodegenerative disease...

Lysosomes are degradation centers of cells and intracellular hubs of signal transduction, nutrient sensing, and autophagy regulation. Dysfunction of lysosomes contributes to a variety of diseases, such as lysosomal storage diseases (LSDs) and neurodegeneration, but the mechanisms are not well understood. Altering lysosomal activity and examining its impact on the occurrence and development of disease is an important strategy for studying lysosome-related diseases. However, methods to dynamically regulate lysosomal function in living cells or animals are still lacking...

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied...

Glioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target with roles in proliferation and invasion. Resistance to KIF11 inhibitors, which has mainly been studied in animal models, presents significant challenges. We use lineage-tracing barcodes and single-cell RNA sequencing to analyze resistance in patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor. Similar to GBM progression in patients, untreated cells lose their neural lineage identity and become mesenchymal, which is associated with poor prognosis...

Studying the detailed biomechanics of flying animals requires accurate three-dimensional coordinates for key anatomical landmarks. Traditionally, this relies on manually digitizing animal videos, a labor-intensive task that scales poorly with increasing framerates and numbers of cameras. Here, we present a workflow that combines deep learning-powered automatic digitization with filtering and correction of mislabeled points using quality metrics from deep learning and 3D reconstruction. We tested our workflow using a particularly challenging scenario: bat flight...

BACKGROUND AIMS: HCV infection continues to be a major global health burden, despite effective antiviral treatments. The urgent need for a protective vaccine is hindered by the scarcity of suitable HCV permissive animal models tractable in vaccination and challenge studies. Currently, only antibody neutralization studies in infectious cell culture systems or studies of protection by passive immunization of human-liver chimeric mice offer the possibility to evaluate the effect of vaccine-induced antibodies...

Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays...

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity...

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils...

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrated that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cells balance, resulting in the reduction of arthritis progression...

BACKGROUND: Repeated stigmatization due to group membership constitutes a recurrent stressor with negative impact on physical and mental health (minority stress model). Among European countries, Romania ranks low on LGBT+ (lesbian, gay, bisexual, and transgender people. The "+" represents individuals whose identities do not fit typical binary notions of male and female [nonbinary]) inclusion, with 45% of Romanian LGBT+ respondents reporting discrimination in at least 1 area of life in the year preceding the survey...

Our previous research demonstrated that allergic rhinitis could impact behavior and seizure threshold in male mice. However, due to the complex hormonal cycles and hormonal influences on behavior in female mice, male mice are more commonly used for behavioral tests. In this study, we aimed to determine whether these findings were replicable in female mice and to explore the potential involvement of sexual hormones in regulating neuroinflammation in an allergic model. Our results indicate that pain threshold was decreased in female mice with allergic rhinitis and the levels of IL-23/IL-17A/IL-17R were increased in their Dorsal root ganglia...

Neuronal hyperexcitability within developing cortical circuits is a common characteristic of several heritable neurodevelopmental disorders, including Fragile X Syndrome (FXS), intellectual disability and autism spectrum disorders (ASD). While this aberrant circuitry is typically studied from a neuron-centric perspective, glial cells secrete soluble factors that regulate both neurite extension and synaptogenesis during development. The nucleotide-mediated purinergic signalling system is particularly instrumental in facilitating these effects...

The acetylation of α-tubulin on lysine 40 is a well-studied post-translational modification which has been associated with the presence of long-lived stable microtubules that are more resistant to mechanical breakdown. The discovery of α-tubulin acetyltransferase 1 (ATAT1), the enzyme responsible for lysine 40 acetylation on α-tubulin in a wide range of species, including protists, nematodes, and mammals, dates to about a decade ago. However, the role of ATAT1 in different cellular activities and molecular pathways has been only recently disclosed...

Re-evaluation of photographs of the tropical butterfly Morpho helenor from a previous study (Pignataro et al. 2023) revealed that its conclusion regarding increased wing fluctuating asymmetry in forest edge habitats compared to forest interior habitats could not be replicated. This discrepancy likely arises from (i) original measurements not being conducted blindly, (ii) insufficient photograph quality hindering accurate landmark selection, and (iii) a lack of detailed description of the measurement protocol...