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Metabolomic Profiles of Mouse Tissues Reveal an Interplay between Aging and Energy Metabolism

Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of the aging process. However, the metabolic changes in tissues responsible for food intake and

Enterocyte-specific ATGL overexpression affects intestinal and systemic cholesterol homeostasis

Enterocytes of the small intestine (SI) play an important role in maintaining systemic lipid levels by regulating dietary lipid absorption and postprandial lipoprotein secretion. An excessive amount of dietary-derived triglycerides (TGs) taken up by the apical side of enterocytes or basolaterally internalized lipoprotein remnants can be transiently stored in cytosolic lipid droplets (cLDs). As mic

Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo

According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency i

Global analysis of protein arginine methylation

Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, because of the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamic

Off-target effects of the lysosomal acid lipase inhibitors Lalistat-1 and Lalistat-2 on neutral lipid hydrolases

OBJECTIVES: Lysosomal acid lipase (LAL) is the key enzyme, which degrades neutral lipids at an acidic pH in lysosomes. The role of LAL in various cellular processes has mostly been studied in LAL-knockout mice, which share phenotypical characteristics with humans suffering from LAL deficiency. In vitro, the cell-specific functions of LAL have been commonly investigated by using the LAL inhibitors

Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated with longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as the brain and kidneys during aging. However, the role of PEMT for systemic PC supply is not

The effect of metastasis location on outcome after cytoreductive surgery and heated intraperitoneal chemotherapy

Objectives: This study aims to evaluate how metastases in the seven topographical regions of the simplified peritoneal cancer index (sPCI) affect the survival of patients treated with cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal (CRC) or appendiceal cancers.Methods: Data was collected retrospectively from patient rec

The measured distance between tumor cells and the peritoneal surface predicts the risk of peritoneal metastases and offers an objective means to differentiate between pT3 and pT4a colon cancer

Substantial variability exists in what pathologists consider as pT4a in colorectal cancer when tumor cells are within 1 mm of the free peritoneal surface. This study aimed to determine if the measured sub-millimeter distance between tumor cells and the free peritoneal surface would offer an objective means of stratifying patients according to the risk of developing peritoneal metastases. Histologi

Scoring systems in sepsis protocols. Discussion about the trial protocol of supplemental immunoglobulin therapy in sepsis and septic shock

When performing a protocol as in the study of Pilz et al. '...immunoglobulin therapy in sepsis and septic shock...' it is necessary to differentiate between those patients with generalized inflammation and those with bacterial sepsis. The Sepsis Severity Score and the Apache II score are mentioned as being insufficient to identify patients with bacterial sepsis. A proposal is formulated to use cli

Innovation with and without patents

A long-standing discussion is to what extent patents can be used to monitor trends in innovation activity. This study quantifies the amount and quality of information about actual innovation contained in the patent system, based on 4,460 Swedish innovations (1970-2015) that have been matched to international patents. The results show that most innovations were not patented and that among those tha

Symmetry breaking yields chimeras in two small populations of Kuramoto-type oscillators

Despite their simplicity, networks of coupled phase oscillators can give rise to intriguing collective dynamical phenomena. However, the symmetries of globally and identically coupled identical units do not allow solutions where distinct oscillators are frequency-unlocked - a necessary condition for the emergence of chimeras. Thus, forced symmetry breaking is necessary to observe chimera-type solu

The glymphatic system : Current understanding and modeling

We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer's disease. We sort existing mode

A MASS TRANSFERENCE PRINCIPLE AND SETS WITH LARGE INTERSECTIONS

I prove a mass transference principle for general shapes, similar to a recent result by H. Koivusalo and M. Rams. The proof relies on Vitali's covering lemma and manipulations with Riesz energies. The main novelty is that it is proved that the obtained limsup-set belongs to the classes of sets with large intersections, as defined by K. Falconer. This has previously not been proved for as general s

Hosting Overnight Guests : Gendered Unpaid Work as a Solidarity Mechanism of Migrants in the Process of Urbanization in Turkey

This article addresses overnight guest hosting, which is a widespread solidarity practice among rural-to-urban migrants in Turkey. The fieldwork, based on in-depth interviews with 28 first-generation migrant women, reveals that it was mostly the young migrant women who shouldered hosting tasks as gendered unpaid work, which deepen their time poverty and reinforce their dependence on family. The an

High need for intensive care in paediatric acute myeloid leukaemia : A population-based study

Aim: Risk of treatment-related life-threatening toxicity is high in childhood acute myeloid leukaemia (AML), and access to intensive care units (ICU) is crucial. We explored the ICU admission rate and outcome after intensive care in childhood AML in Sweden. Methods: Patients diagnosed between 2008 and 2016 were identified from the Swedish Childhood Cancer Registry (SCCR), a national quality regist