Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol.

Prenatal Coffin-Siris Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Disease.

Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including and .

Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation.

Background: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored.

Methods: The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice.

Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery.

Objective: Changes in liver fatty acid metabolism are important in understanding the mechanisms of diabetes remission and metabolic changes after bariatric surgery.

Research Design And Methods: Liver fatty acid uptake (LFU), blood flow, and fat content (LFC) were measured in 25 obese subjects before bariatric surgery and 6 months after using positron emission tomography/computed tomography and MRS; 14 lean individuals served as the control subjects.

Results: The increased LFU in obese subjects was associated with body adiposity.

Novel COL1A1 Mutation c.3290G>T Associated With Severe Form of Osteogenesis Imperfecta in a Fetus.

Osteogenesis imperfecta is a genetically and clinically heterogenous group of skeletal dysplasias characterized by bone fragility. Its severity ranges from nearly asymptomatic individuals to perinatal lethality. The majority of cases are caused by mutations in either the COL1A1 or the COL1A2 gene coding for alpha 1 and alpha 2 chains of collagen type 1, respectively, and a large number of pathogenic variants of these genes has been identified.

Gestational hyperglycemia reprograms cardiac gene expression in rat offspring.

BackgroundRat fetuses with maternal pregestational hyperglycemia develop cardiac dysfunction, and their cardiac gene expression differs from that of healthy control fetuses near term. We hypothesized that cardiac gene expression and morphologic abnormalities of rat fetuses with maternal pregestational hyperglycemia become normal after birth.MethodsNine rats were preconceptually injected with streptozotocin to induce maternal hyperglycemia and nine rats served as controls.

Causes of Stillbirth in Turku, Finland, 2001-2011.

The objective of the study was to examine the causes of stillbirth in the district of Southwest Finland and to assess the importance of postmortem examination and the selection of a suitable classification system for classifying stillbirths. This study is a cohort study where the fetal autopsies were performed in the Department of Pathology at Turku University Hospital, Finland, 2001-2011. Stillbirths from singleton pregnancies at the gestational age of ≥ 24 + 0 weeks (if unknown, gestational weight ≥ 500 g) (n = 98) were selected.

Placental structural abnormalities have detrimental hemodynamic consequences in a rat model of maternal hyperglycemia.

Introduction: Human type 1 diabetic pregnancy is associated with placental structural and hemodynamic abnormalities. We hypothesized that in rat fetuses of hyperglycemic dams, placental and fetal blood flow velocity waveforms demonstrate compromised hemodynamics when compared to control fetuses, and these hemodynamic parameters correlate with placental structural abnormalities at near term gestation.

Methods: Streptozotocin-induced maternal hyperglycemia group comprised 10 dams with 107 fetuses and the control group 20 dams with 219 fetuses.

18-kDa translocator protein ligand F-FEMPA: Biodistribution and uptake into atherosclerotic plaques in mice.

Background: Radioligands of 18-kDa translocator protein (TSPO) expressed on activated macrophages are a potential approach for imaging of inflammation in atherosclerosis. We evaluated a novel TSPO-targeted tracer F-FEMPA for the detection of atherosclerotic plaque inflammation in mice.

Methods And Results: The distribution kinetics of F-FEMPA was evaluated by in vivo PET/CT imaging.

Hypoxia, blood flow and metabolism in squamous-cell carcinoma of the head and neck: correlations between multiple immunohistochemical parameters and PET.

Background: The relationship between the uptake of [18F]fluoroerythronitroimidazole ([18F]FETNIM), blood flow ([15O]H2O) and 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and immunohistochemically determined biomarkers was evaluated in squamous-cell carcinomas of the head and neck (HNSCC).

Methods: [18F]FETNIM and [18F]FDG PET were performed on separate days on 15 untreated patients with HNSCC. Hypoxia imaging with [18F]FETNIM was coupled with measurement of tumor blood flow using [15O]H2O.

Cathepsin K overexpression modifies lung development in newborn mice.

Cathepsin K (CatK), contributes to the development of chronic lung disease in newborn infants, but the impact of CatK for the lungs may be multifaceted. We have previously demonstrated that low level of CatK is associated with newborn lung injury and CatK deficiency aggravates lung injury in hyperoxia-exposed newborn mice. Thus, we hypothesized that sustained/higher expression of CatK could ameliorate hyperoxia-induced injury and restrain the development of pulmonary fibrosis.

Effect of bariatric surgery on liver glucose metabolism in morbidly obese diabetic and non-diabetic patients.

Background & Aims: Bariatric surgery reduces weight and improves glucose metabolism in obese patients. We investigated the effects of bariatric surgery on hepatic insulin sensitivity.

Methods: Twenty-three morbidly obese (nine diabetic and fourteen non-diabetic) patients and ten healthy, lean control subjects were studied using positron emission tomography to assess hepatic glucose uptake in the fasting state and during euglycemic hyperinsulinemia.

Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model.

Accelerated fetal myocardial growth with altered cardiac function is a well-documented complication of human diabetic pregnancy, but its pathophysiology is still largely unknown. Our aim was to explore the mechanisms of fetal cardiac remodeling and cardiovascular hemodynamics in a rat model of maternal pregestational streptozotocin-induced hyperglycemia. The hyperglycemic group comprised 107 fetuses (10 dams) and the control group 219 fetuses (20 dams).

Delay in rat lung alveolarization after the combined exposure of maternal hyperglycemia and postnatal hyperoxia.

Background: Maternal diabetes interferes with fetal lung development and postnatal treatments may further disturb pulmonary growth. Therefore, we investigated the effect of postnatal oxygen exposure on alveolar development in neonatal rat lungs pre-exposed to intrauterine hyperglycemia.

Methods: Diabetes was induced in Sprague-Dawley rats with streptozotocin injection before pregnancy.

Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation.

Aneuploidy, deviation from the normal chromosome number, and other chromosomal aberrations are commonly observed in cancer. Integrin-mediated adhesion and dynamic turnover of adhesion sites are required for successful cytokinesis of normal adherent cells and impaired cell division can lead to the generation of cells with abnormal chromosome contents. We find that repeated cytokinesis failure, due to impaired integrin traffic alone, is sufficient to induce chromosome aberrations resulting in the generation of aneuploid cells with malignant properties.

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: a validation study.

Objective: The aim of this study was to evaluate and validate magnetic resonance imaging (MRI) for the visualization and quantification of brown adipose tissue (BAT) in vivo in a rat model. We hypothesized that, based on differences in tissue water and lipid content, MRI could reliably differentiate between BAT and white adipose tissue (WAT) and could therefore be a possible alternative for (18)F-Fluorodeoxyglucose Positron Emission Tomography ((18)FDG-PET), the current gold standard for non-invasive BAT quantification.

Materials/methods: Eleven rats were studied using both (18)FDG-PET/CT and MRI (1.

Immunomodulation in a novel model of experimental chronic pancreatitis.

Chronic pancreatitis is a disease that involves the lymphocytic inflammation of the pancreatic gland, the destruction and fibrous transformation of the endocrine and ductal structures. An involvement of the immune system in the disease progression is assumed and possibly allows immune modulation as a novel treatment strategy. We used a new model of experimental chronic pancreatitis to examine the effect of immune modulation with the mTOR-inhibitor rapamycin on clinical, chemical and histological parameters of chronic pancreatitis.

Uptake of 68gallium in atherosclerotic plaques in LDLR-/-ApoB100/100 mice.

Background: Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice.

Effects of age, diet, and type 2 diabetes on the development and FDG uptake of atherosclerotic plaques.

Objectives: This study investigated the effects of age, duration of a high-fat diet, and type 2 diabetes on atherosclerotic plaque development and uptake of (18)F-fluorodeoxyglucose ((18)F-FDG) in 2 mouse models.

Background: The animal's age and start time and duration of a high-fat diet have effects on plaque composition in atherosclerotic mice.

Methods: The aortas of atherosclerotic low-density lipoprotein receptor deficient mice expressing only apolipoprotein B100 (LDLR(-/-)ApoB(100/100)) and atherosclerotic and diabetic mice overexpressing insulin-like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100)) were investigated at 4, 6, and 12 months of age and older after varying durations of high-fat diet.

Metagenes associated with survival in non-small cell lung cancer.

NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%-55% of these patients develop recurrence within 5 years.

Detection of hypoxia by [18F]EF5 in atherosclerotic plaques in mice.

Objective: Atherosclerotic plaques with large lipid cores and inflammation contain regions of hypoxia. We examined the uptake of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide ([18F]EF5), a specific marker of hypoxia labeled for positron emission tomography, in mouse atherosclerotic plaques.

Methods And Results: Atherosclerotic mice of 2 different genetic backgrounds (low-density lipoprotein receptor-/- apolipoprotein B100/100 and insulin-like growth factor II/low-density lipoprotein receptor-/- apolipoprotein B100/100) were first fed a Western diet to induce development of plaques with variable phenotypes and then injected with [18F]EF5.

Environmental services provided from riparian forests in the Nordic countries.

Riparian forests (RF) growing along streams, rivers and lakes comprise more than 2% of the forest area in the Nordic countries (considering a 10 m wide zone from the water body). They have special ecological functions in the landscape. They receive water and nutrients from the upslope areas, are important habitats for biodiversity, have large soil carbon stores, but may emit more greenhouse gases (GHG) than the uplands.