A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection.

Immune systems must rapidly sense viral infections to initiate antiviral signaling and protect the host. Bacteria encode >100 distinct viral (phage) defense systems and each has evolved to sense crucial components or activities associated with the viral lifecycle. Here we used a high-throughput AlphaFold-multimer screen to discover that a bacterial NLR-related protein directly senses multiple phage proteins, thereby limiting immune evasion.

Investigating the Role of TNF-Alpha through Blood-Brain Barrier Integrity in Stress-Induced Depression.

Background: Major depressive disorder (MDD) is a complex psychiatric condition significantly impacted by environmental stress and inflammation. Previous research suggests that stress-induced alterations in the blood-brain barrier (BBB) may allow pro-inflammatory cytokines like interleukin-6 (IL-6) to enter the brain, contributing to depression. Tumor necrosis factor-alpha (TNF-α) is another prominent cytokine implicated in depression, but its role in the context of BBB integrity and stress-mediated depression remains unclear.

The Relationship of Metabolic Activity and αvβ3 Receptor Expression in Aggressive Breast Cancer Subtypes Tumors: A Preliminary Report.

Background/aim: Angiogenesis imaging has been a valuable complement to metabolic imaging with 2-deoxy-2-[F]fluoroglucose (FDG). In our longitudinal study, we investigated the tumour heterogeneity and the relationship between FDG and [Ga]Ga-NODAGA-c(RGDfK) (RGD) accumulation in breast cancer xenografts.

Materials And Methods: Two groups of cell lines, a fast-growing (4T1) and a slow-growing cell line (MDA-MB-HER2+), were inoculated into SCID mice.

Could the transcription factor AtnN coordinating the aspercryptin secondary metabolite gene cluster in Aspergillus nidulans be a global regulator?

Products of dormant secondary metabolite gene clusters of fungal genomes can be exploited for medical purposes as bioactive agents. These clusters can be switched on under oxidative stress and may endow fungi with a versatile chemical armory in a competitive niche. In Aspergillus nidulans, the aspercryptin gene cluster, including the synthase [atnA (AN7884)] and its transcription factor (atnN), was activated under menadione sodium bisulfite (MSB) treatment.

Aggressive behaviour in mentally altered patients in prehospital setting as a threat to emergency medical service personnel: potential predictors identification.

Objectives: Patients are the most common source of violence against EMS personnel. This study aims at elucidating specific clinical features in patients with mental alteration and aggressive behaviour increasing risk of violence.

Material And Methods: This consecutive cross-sectional retrospective study analysed consecutive patients treated for prespecified list of primary diagnoses by one EMS provider in the Czech Republic between 1 January 2021 and 31 December 2023.

Hybrid Mass Spectrometry Applied across the Production of Antibody Biotherapeutics.

Post expression from the host cells, biotherapeutics undergo downstream processing steps before final formulation. Mass spectrometry and biophysical characterization methods are valuable for examining conformational and stoichiometric changes at these stages, although typically not used in biomanufacturing, where stability is assessed via bulk property studies. Here we apply hybrid MS methods to understand how solution condition changes impact the structural integrity of a biopharmaceutical across the processing pipeline.

Dose-related effect of acetylcholine on human gingival blood flow.

Background: This study investigates the dose-response relationship of acetylcholine (ACh) on healthy human gingival blood flow (GBF). Understanding this dose-response relationship contributes to studying vasodilatory mechanisms in various pathological conditions.

Methods: The study involved 22 young healthy men (21 - 32 years) to investigate the dose-response relationship of ACh on GBF.

Ho:YLF regenerative amplifier delivering 22 mJ, 2.0 ps pulses at a 1 kHz repetition rate.

We report on a high-energy, few-ps, continuous-wave pumped Ho:YLF regenerative amplifier (RA) operating in a chirped-pulse amplification arrangement. A three-stage optical parametric amplifier serves as versatile seed source emitting broadband pulses centered at 2050 nm. It provides seed pulses with 4 µJ energy within the Ho:YLF amplification bandwidth centered at 2051 nm.

The effect of unilateral hand muscle contraction on frontal alpha asymmetry and inhibitory control in intrinsic reward contexts, a randomized controlled trial.

Challenged inhibitory control has been implicated in various disorders, including addiction. Previous research suggests that asymmetry of frontal brain activity, indexed by frontal alpha asymmetry (FAA), is associated with inhibitory control and could be a target for neuromodulatory intervention. Some evidence suggests that unilateral muscle contraction (UMC) can modulate FAA; however, experimental evidence is scarce.

Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix.

High tissue density of the mammary gland is considered a pro-tumorigenic factor, hence suppressing the stimuli that induce matrix buildup carries the potential for cancer interception. We found that in non-malignant mammary epithelial cells the combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through an interaction of ARID1A with a proximal enhancer. Bex + Carv also reduced ZG16B levels in vivo in normal breast tissue and MDA-MB231 tumor xenografts.

Basal State Calibration of a Chemical Reaction Network Model for Autophagy.

The modulation of autophagy plays a dual role in tumor cells, with the potential to both promote and suppress tumor proliferation. In order to gain a deeper understanding of the nature of autophagy, we have developed a chemical reaction kinetic model of autophagy and apoptosis based on the mass action kinetic models that have been previously described in the literature. It is regrettable that the authors did not provide all of the information necessary to reconstruct their model, which made their simulation results irreproducible.

Cooperative folding as a molecular switch in an evolved antibody binder.

Designing proteins with tunable activities from easily accessible external cues remains a biotechnological challenge. Here, we set out to create a small antibody-binding domain equipped with a molecular switch inspired by the allosteric response to calcium seen in naturally derived proteins like calmodulin. We have focused on one of the three domains of Protein G that show inherent affinity to antibodies.

Magnesium induced structural reorganization in the active site of adenylate kinase.

Phosphoryl transfer is a fundamental reaction in cellular signaling and metabolism that requires Mg as an essential cofactor. While the primary function of Mg is electrostatic activation of substrates, such as ATP, the full spectrum of catalytic mechanisms exerted by Mg is not known. In this study, we integrate structural biology methods, molecular dynamic (MD) simulations, phylogeny, and enzymology assays to provide molecular insights into Mg-dependent structural reorganization in the active site of the metabolic enzyme adenylate kinase.

Probenecid Inhibits Human Metapneumovirus (HMPV) Replication In Vitro and in BALB/c Mice.

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice.

Neutrophils actively swell to potentiate rapid migration.

While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury, and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes are not known.

Multicentric Assessment of a Multimorbidity-Adjusted Disability Score to Stratify Depression-Related Risks Using Temporal Disease Maps: Instrument Validation Study.

Background: Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions.

Phage detection by a bacterial NLR-related protein is mediated by DnaJ.

Bacteria encode a wide range of antiphage systems and a subset of these proteins are homologous to components of the human innate immune system. Mammalian nucleotide-binding and leucine-rich repeat containing proteins (NLRs) and bacterial NLR-related proteins use a central NACHT domain to link detection of infection with initiation of an antimicrobial response. Bacterial NACHT proteins provide defense against both DNA and RNA phages.

Synthesis and Application of Robust Spiro [Fluorene-9] CAAC Ruthenium Alkylidene Complexes for the "One-Pot" Conversion of Allyl Acetate to Butane-1,4-diol.

A series of a novel CAAC ligands featuring a spiro-fluorene group have been synthesized and complexed with ruthenium alkylidenes, yielding the corresponding Hoveyda-type derivatives as a new family of olefin metathesis catalysts. The novel complexes have been characterized by XRD, HRMS and NMR measurements. The synthetised complexes were tested in catalysis and showed good activity in olefin metathesis, as demonstrated on diethyl diallylmalonate and allyl acetate substrates.

The relationship between frontal alpha asymmetry and behavioral and brain activity indices of reactive inhibitory control.

Reactive inhibitory control plays an important role in phenotype of different diseases/different phases of a disease. One candidate electrophysiological marker of inhibitory control is frontal alpha asymmetry (FAA). FAA reflects the relative difference in contralateral frontal brain activity.

Temporal contrast enhancement of a Ti:Sapphire laser by nonlinear Fourier filtering.

Temporal cleaning of high-power infrared (IR) pulses generated by a Ti:Sapphire system is demonstrated by the use of the Nonlinear Fourier Filtering (NFF) method. In a proof-of-principle experiment suppression of up to 1000 is achieved for the temporal pedestal prior to the main pulse, with a moderate (20-25%) overall throughput. This includes the same suppression ratio for the picosecond coherent pedestal in the direct vicinity of the main pulse.

Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism.

[Mn]Mn-BPPA-Trastuzumab: A Promising HER2-Specific PET Radiotracer.

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [Mn]Mn isotope.

Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice.

Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity.

Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles).

Olfactory genes affect major depression in highly educated, emotionally stable, lean women: a bridge between animal models and precision medicine.

Most current approaches to establish subgroups of depressed patients for precision medicine aim to rely on biomarkers that require highly specialized assessment. Our present aim was to stratify participants of the UK Biobank cohort based on three readily measurable common independent risk factors, and to investigate depression genomics in each group to discover common and separate biological etiology. Two-step cluster analysis was run separately in males (n = 149,879) and females (n = 174,572), with neuroticism (a tendency to experience negative emotions), body fat percentage, and years spent in education as input variables.