Protocol to infer off-target effects of drugs on cellular signaling using interactome-based deep learning.

Drugs that target specific proteins often have off-target effects. We present a protocol using artificial neural networks to model cellular transcriptional responses to drugs, aiming to understand their mechanisms of action. We detail steps for predicting transcriptional activities, inferring drug-target interactions, and explaining the off-target mechanism of action.

Protocol for cell image-based spatiotemporal proteomics in budding yeast.

The eukaryotic cell division cycle is a highly conserved process, featuring fluctuations in protein localization and abundance required for key cell cycle transitions. Here, we present a protocol for the spatiotemporal analysis of the proteome during the budding yeast cell division cycle using live-cell imaging. We describe steps for strain construction, cell cultivation, microscopy, and image analysis.

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages.

Plasticity of cell death pathways ensures GSDMD activation during Yersinia pseudotuberculosis infection.

Macrophages express pattern recognition and cytokine receptors that mediate proinflammatory signal transduction pathways to combat microbial infection. To retaliate against such responses, pathogenic microorganisms have evolved multiple strategies to impede innate immune signaling. Recent studies demonstrated that YopJ suppression of TAK1 signaling during Yersinia pseudotuberculosis infection promotes the assembly of a RIPK1-dependent death-inducing complex that enables caspase-8 to directly cleave and activate gasdermin D (GSDMD).

Unraveling the Stoichiometric Interactions and Synergism between Ligand-Protected Gold Nanoparticles and Proteins.

Nanomaterials that engage in well-defined and tunable interactions with proteins are pivotal for the development of advanced applications. Achieving a precise molecular-level understanding of nano-bio interactions is essential for establishing these interactions. However, such an understanding remains challenging and elusive.

Without visual feedback voluntary torque is overestimated during muscle potentiation despite similar motor unit firing rate and perception of exertion.

The purpose was to assess whether visual feedback of torque contributes to motor unit (MU) firing rate reduction observed during post-activation potentiation (PAP) of skeletal muscle. From 15 participants 23 MUs were recorded with intramuscular fine-wire electrodes from the tibialis anterior during isometric dorsiflexion contractions at 20% of maximum, with and without both PAP and visual feedback of torque. A 5s maximal voluntary contraction (MVC) was used to induce PAP, and evoked twitch responses were assessed before and after.

Advancements in molecular imaging probes for precision diagnosis and treatment of prostate cancer.

Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis.

Barcoded Hybrids of Extracellular Vesicles and Lipid Nanoparticles for Multiplexed Analysis of Tissue Distribution.

Targeted delivery of therapeutic agents is a persistent challenge in modern medicine. Recent efforts in this area have highlighted the utility of extracellular vesicles (EVs) as drug carriers, given that they naturally occur in bloodstream and tissues, and can be loaded with a wide range of therapeutic molecules. However, biodistribution and tissue tropism of EVs remain difficult to study systematically.

Bacteria in hypertrophic scars promote scar formation through HSBP1-mediated autophagy.

Bacterial colonisation in hypertrophic scars (HSs) has been reported, yet the precise mechanism of their contribution to scar formation remains elusive. To address this, we examined HS and normal skin (NS) tissues through Gram staining and immunofluorescence. We co-cultured fibroblasts with heat-inactivated Staphylococcus aureus (S.

Immunoinfiltration Analysis of Mitochondrial Damage-Related Genes in Lung Adenocarcinoma and Construction of a Classification and Prognostic Model Integrated With WGCNA and Machine Learning Algorithms.

Background: Lung adenocarcinoma (LUAD) exhibits molecular heterogeneity, with mitochondrial damage affecting progression. The relationship between mitochondrial damage and immune infiltration, and Weighted Gene Co-expression Network Analysis (WGCNA)-derived biomarkers for LUAD classification and prognosis, remains unexplored.

Aims: The objective of our research is to identify gene modules closely related to the clinical stages of LUAD using the WGCNA method.

Salpingectomy With Delayed Oophorectomy Versus Salpingo-Oophorectomy in BRCA1/2 Carriers: Three-Year Outcomes of a Prospective Preference Trial.

Objective: To compare menopause-related quality of life (QoL) after risk-reducing salpingectomy (RRS) versus risk-reducing salpingo-oophorectomy (RRSO) until 3 years of post-surgery.

Design: A prospective study (TUBA study) with treatment allocation based on patients' preference. Data were collected pre-surgery and at 3 months, 1 and 3 years of post-surgery.

Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.

Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.

Comparison of Demographic Life-History Traits of the Snake-Eyed Skink: Observations From an Island and a Mainland Population.

The life-history traits of animals are influenced by several factors. It has been proposed that key factors such as competition, predation pressure, and resource availability may differ between mainland and island populations of the same species. In this context, our study focused on an island (Yayla, Cyprus) and mainland (Hassa, Türkiye) populations of the snake-eyed skink, .

The Importance of Olfaction for Mixed Paternity in Birds.

Olfaction can aid individuals in finding genetically compatible mates in many animals, while high levels of mixed paternity may result from a limited ability to evaluate their mate's genetic profile against their own before mating. To test this suggestion and explore if olfaction may indeed influence mating patterns in birds, we combined published measures of olfactory ability with data on genetic mating pattern in the same species, across a phylogenetically broad range of species. We used three measures of olfaction: (1) olfactory bulb diameter, (2) olfactory bulb volume and (3) number of olfactory receptor genes (148, 134 and 48 species, respectively).

Similar Conditions With Opposite Effects: Predation-Risk Effects on Prey Abundance Are Highly Contingent.

Experiments have shown that predation-risk effects on prey fitness can be highly contingent on environmental conditions, suggesting a potential difficulty in generalizing risk effects on prey abundance in natural settings. Rather than study the influence of a particular controlled factor, we examine the problem with a novel approach. We examined the influence of risk effects in multiple experiments performed under similar study conditions.

Breaking boundaries: A rare case of glioblastoma with uncommon extraneural metastases: A case report and literature review.

Introduction: Extraneural metastases (ENM) from glioblastoma (GBM) remain extremely rare with only a scarce number of cases described in the literature. The lack of cases leads to no consensus on the optimal treatment and follow-up of these patients.

Research Question: Do patient or tumor characteristics describe risk factors for ENM in GBM patients, and is it possible to identify mechanisms of action?

Material And Methods: This study presents a 55-year-old man with diagnosed GBM who was referred to a CT due to reduced general condition and mild back pain which revealed extensive systemic metastases.

Recurrent glioblastoma in national guidelines on the diagnosis and treatment of gliomas: A matter of European practice variation.

Introduction: The optimal treatment for recurrent glioblastoma patients remains not well-defined in international guidelines. On top of that, the availability of national guidelines is uncharted.

Research Question: This study aimed to investigate the availability of national guidelines on the diagnosis and treatment of adult glioma throughout Europe, specifically focusing on recurrent glioblastoma.

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Extracellular vesicles: from intracellular trafficking molecules to fully fortified delivery vehicles for cancer therapeutics.

Extracellular vesicles (EVs) are emerging as viable tools in cancer treatment due to their ability to carry a wide range of theranostic activities. This review summarizes different forms of EVs such as exosomes, microvesicles, apoptotic bodies, and oncosomes. It also sheds the light onto isolation methodologies, characterization techniques and therapeutic applications of all discussed EVs.

Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance.

Despite the success of endocrine therapies in treating ER-positive breast cancer, the development of resistance remains a significant challenge. Estrogen receptor targeting proteolysis-targeting chimeras (ER PROTACs) offer a unique approach by harnessing the ubiquitin-proteasome system to degrade ER, potentially bypassing resistance mechanisms. In this review, we present the drug design, efficacy and early clinical trials of these ER PROTACs.

Dimples as Desired Outcomes: Rethinking Their Role in Thread Lifting Procedures.

Facial thread lifts, known for being minimally invasive with quick results, can sometimes lead to dimpling. A case report of a 35-year-old Asian man who developed a pleasing unilateral dimple after a thread lift highlights the potential for intentional dimple creation through this method. With surgical dimple creation in demand, as dimples symbolize good luck in Chinese culture and beauty in Arabic traditions, thread lifts may offer a less invasive alternative for those seeking dimples without surgery.

To stay or to go: resource diversity alters the dispersal behavior of sympatric cryptic marine nematodes.

Animals can use specific environmental cues to make informed decisions about whether and where to disperse. Patch conditions are known to affect the dispersal behavior of animals, but empirical studies investigating the impact of resource diversity on the dispersal of closely related species are largely lacking. In this study, we investigated how food diversity affects the dispersal behavior of three co-occurring cryptic species of the marine bacterivorous nematode complex (Pm I, Pm III and Pm IV).

Exploring the anti-aging potential of natural products and plant extracts in budding yeast : A review.

Historically, plant derived natural products and their crude extracts have been used to treat a wide range of ailments across the world. Biogerontology research aims to explore the molecular basis of aging and discover new anti-aging therapeutic compounds or formulations to combat the detrimental effects of aging and promote a healthy life span. The budding yeast has been, and continues to be, an indispensable model organism in the field of biomedical research for discovering the molecular basis of aging has preserved nutritional signaling pathways (such as the target of rapamycin (TOR)-Sch9 and the Ras-AC-PKA (cAMP-dependent protein kinase) pathways, and shows two distinct aging paradigms chronological life span (CLS) and replicative life span (RLS).

Synthesis of Glycosylphosphatidylinositol Analogues with an Unnatural -D-Glucosamine-(1→6)--Inositol Motif.

Glycosylphosphatidylinositol (GPI) anchors contain a unique α-D-glucosamine-(1→6)--inositol [αGlcN(1,6)Ins] motif in their conserved core structure. To facilitate investigations of the functional roles of this structural motif, two GPI analogues containing unnatural βGlcN(1,6)Ins, instead of αGlcN(1,6)Ins, and an alkyne group at different positions of the GPI core were designed and synthesized. To this end, an orthogonally protected pseudopentasaccharide derivative of GPIs with the βGlcN(1,6)Ins motif was convergently constructed via [3+2] glycosylation and used as the common intermediate to prepare both GPI analogues by streamlined synthetic protocols.

Metabolic skinflint or spendthrift? Insights into ground sloth integument and thermophysiology revealed by biophysical modeling and clumped isotope paleothermometry.

Unlabelled: Remains of megatheres have been known since the 18th -century and were among the first megafaunal vertebrates to be studied. While several examples of preserved integument show a thick coverage of fur for smaller ground sloths living in cold climates such as and , comparatively very little is known about megathere skin. Assuming a typical placental mammal metabolism, it was previously hypothesized that megatheres would have had little-to-no fur as they achieved giant body sizes.