Validation and Optimization of a Stable Isotope-Labeled Substrate Assay for Measuring AGAT Activity.

L-arginine: glycine amidinotransferase (AGAT) gained academic interest as the rate-limiting enzyme in creatine biosynthesis and its role in the regulation of creatine homeostasis. Of clinical relevance is the diagnosis of patients with AGAT deficiency but also the potential role of AGAT as therapeutic target for the treatment of another creatine deficiency syndrome, guanidinoacetate N-methyltransferase (GAMT) deficiency. Applying a stable isotope-labeled substrate method, we utilized ARG 15N (ARG-δ2) and GLY 13C15N (GLY-δ3) to determine the rate of 1,2-13C,15N guanidinoacetate (GAA-δ5) formation to assess AGAT activity in various mouse tissue samples and human-derived cells.

Ultrafiltration and composite microfiltration biocatalytic membrane activity and steroid hormone micropollutant degradation at environmentally relevant concentrations.

Biocatalytic degradation of micropollutants has been extensively explored in both batch and membrane reactors in µg/L to mg/L concentrations and variable water compositions. The degradation of micropollutants by biocatalytic membranes at environmentally relevant concentrations of ng/L range found in natural surface water matrices has not yet been investigated, presumably because of the challenging concentration analysis. This study investigated the limitations of biocatalytic degradation of estradiol (E2) micropollutant at environmentally relevant concentrations by a biocatalytic membrane.

You say it's not me: the influence of offering external explanations of rejection and acceptance behavior on the perception of benevolence in borderline personality disorder.

Background: Interpersonal impairments in patients diagnosed with borderline personality disorder (BPD) are characterized by the fear of being rejected and high levels of loneliness. Potential underlying factors are alterations in the processing of social interactions and the associated perceptions of social partners. In this regard, BPD patients tend to attribute the cause of negative rather than positive events to their own person and to perceive others as less trustworthy than healthy controls (HCs).

Targeting AGAT gene expression - a drug screening approach for the treatment of GAMT deficiency.

Background: Targeting the enzyme L-Arginine:glycine amidinotransferase (AGAT) to reduce the formation of guanidinoacetate (GAA) in patients with guanidinoacetate methyltransferase (GAMT) deficiency, we attempted to identify drugs for repurposing that reduce the expression of AGAT via transcriptional inhibition.

Research Design And Methods: The authors applied a HeLa cell line stably expressing AGAT promoter and firefly luciferase reporter for high-content screening and secondary screening. For further assessment, the authors integrated Nanoluc luciferase as a reporter into the endogenous AGAT gene in HAP1 cell lines and used the human immortalized cell line RH30 as model of GAMT deficiency.

Aliado - A design concept of AI for decision support in oncological liver surgery.

Background: The interest in artificial intelligence (AI) is increasing. Systematic reviews suggest that there are many machine learning algorithms in surgery, however, only a minority of the studies integrate AI applications in clinical workflows. Our objective was to design and evaluate a concept to use different kinds of AI for decision support in oncological liver surgery along the treatment path.

Adherence to long-term telemonitoring-supported physical activity in patients with chronic heart failure.

Chronic heart failure (CHF) is one of the most common diseases with a prevalence of 1-2% in adults, disproportionately affecting the elderly. Despite consistent drug therapy, physical activity (PA) is an integral part of current guidelines. Yet adherence to regular PA and exercise interventions is poor and potential predictors and barriers to PA remain elusive.

Chemo-Enzymatic Depolymerization of Functionalized Low-Molecular-Weight Polyethylene.

Polyethylene (PE) is the most commonly used plastic type in the world, contributing significantly to the plastic waste crisis. Microbial degradation of PE in natural environments is unlikely due to its inert saturated carbon-carbon backbones, which are difficult to break down by enzymes, challenging the development of a biocatalytic recycling method for PE waste. Here, we demonstrated the depolymerization of low-molecular-weight (LMW) PE using an enzyme cascade that included a catalase-peroxidase, an alcohol dehydrogenase, a Baeyer Villiger monooxygenase, and a lipase after the polymer was chemically pretreated with m-chloroperoxybenzoic acid (mCPBA) and ultrasonication.

Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.

While heterogeneity is a key feature of cancer, understanding metabolic heterogeneity at the single-cell level remains a challenge. Here we present C-SpaceM, a method for spatial single-cell isotope tracing that extends the previously published SpaceM method with detection of C-glucose-derived carbons in esterified fatty acids. We validated C-SpaceM on spatially heterogeneous models using liver cancer cells subjected to either normoxia-hypoxia or ATP citrate lyase depletion.

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series.

Background: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.

Patients And Methods: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified.

Preparation and Preclinical Evaluation of F-Labeled Olutasidenib Derivatives for Non-Invasive Detection of Mutated Isocitrate Dehydrogenase 1 (mIDH1).

Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib.

Attributional style in Borderline personality disorder is associated with self-esteem and loneliness.

Background: Attributions are the processes by which individuals explain the causes of positive and negative events. A maladaptive attributional style has been associated with reduced self-esteem, psychosocial functioning, and mental health. Although many psychosocial interventions target an individual's attributional style in mental disorders, studies of its alterations in Borderline Personality Disorder (BPD) are sparse.

Developing molecular classifiers to detect environmental stressors, smolt stages and morbidity in coho salmon, Oncorhynchus kisutch.

Aquatic species are increasingly confronted with environmental stressors because of climate change. Although molecular technologies have advanced our understanding of how organisms respond to stressors in laboratory settings, the ability to detect physiological responses to specific stressors under complex field conditions remains underdeveloped. This research applied multi-stressor challenge trials on coho salmon, employing the "Salmon Fit-Chips" genomic tool and a random forest-based classification model to develop classifiers predictive for chronic thermal and hypoxic stress, as well as salinity acclimation, smolt stage and morbidity status.

The core microbiome of cultured Pacific oyster spat is affected by age but not mortality.

The Pacific oyster is the most widely cultured shellfish worldwide, but production has been affected by mortality events, including in hatcheries that supply the seed for growers. Several pathogens cause disease in oysters, but in many cases, mortality events cannot be attributed to a single agent and appear to be multifactorial, involving environmental variables and microbial interactions. As an organism's microbiome can provide resilience against pathogens and environmental stressors, we investigated the microbiomes in cohorts of freshly settled oyster spat, some of which experienced notable mortality.

Long-term neurodevelopmental outcomes following liver transplantation for metabolic disease-a single centre experience.

This study describes the neurodevelopmental outcome of children with urea cycle disorders (UCD) and organic acidemias (OA) preliver transplant (LT), 1-year, and 3-years post-LT. We performed a retrospective chart review of children with OA or UCD transplanted between January 2014 and December 2021. Standardized motor and cognitive assessment scores were collected from children who had ≥1 motor/cognitive assessment at any timepoint.

Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises.

Background: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.

Methods: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.

Elucidating regulation of polyhydroxyalkanoate metabolism in Ralstonia eutropha: Identification of transcriptional regulators from phasin and depolymerase genes.

Despite the ever-growing research interest in polyhydroxyalkanoates (PHAs) as green plastic alternatives, our understanding of the regulatory mechanisms governing PHA synthesis, storage, and degradation in the model organism Ralstonia eutropha remains limited. Given its importance for central carbon metabolism, PHA homeostasis is probably controlled by a complex network of transcriptional regulators. Understanding this fine-tuning is the key for developing improved PHA production strains thereby boosting the application of PHAs.

Cardiovascular and Vector-Cardiographic Effects of Articaine Anesthesia with Epinephrine.

The aim was to investigate the vector-cardiographic effects in patients submitted to dental extraction under local anesthesia. Twenty-one patients aged 36.6 ± 12.

Interactions of Fatty Acid and Cholesterol Metabolism with Cellular Stress Response Pathways in Cancer.

Lipids have essential functions as structural components of cellular membranes, as efficient energy storage molecules, and as precursors of signaling mediators. While deregulated glucose and amino acid metabolism in cancer have received substantial attention, the roles of lipids in the metabolic reprogramming of cancer cells are less well understood. However, since the first description of de novo fatty acid biosynthesis in cancer tissues almost 70 years ago, numerous studies have investigated the complex functions of altered lipid metabolism in cancer.

A surgical activity model of laparoscopic cholecystectomy for co-operation with collaborative robots.

Background: Laparoscopic cholecystectomy is a very frequent surgical procedure. However, in an ageing society, less surgical staff will need to perform surgery on patients. Collaborative surgical robots (cobots) could address surgical staff shortages and workload.