Evaluation of bone marrow glucose uptake and adiposity in male rats after diet and exercise interventions.

Objectives: Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats.

Mechanisms Leading to Increased Insulin-Stimulated Cerebral Glucose Uptake in Obesity and Insulin Resistance: A High-Fat Diet and Exercise Training Intervention PET Study with Rats (CROSRAT).

Recent studies have shown that obesity and insulin resistance are associated with increased insulin-stimulated glucose uptake (GU) in the brain. Thus, insulin sensitivity seems to work differently in the brain compared to the peripheral tissues like skeletal muscles, but the underlying mechanisms remain unknown. Regular exercise training improves skeletal muscle and whole-body insulin sensitivity.

Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab-Auristatin Conjugate with a Wide Therapeutic Window.

CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy of AML. Although previous CD33-targeting antibody-drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window. This study aimed to develop a novelADCwith improved tolerability and a wider therapeutic window.

In-target production of [C]CH from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature.

Background: Production of [C]CH from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [C]CO to [C]CH is a widely used roundabout method in C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [C]CH is superior with respect to molar activity.

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [C]SMW139 and [F]F-DPA.

Background: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [F]F-DPA targeting TSPO at the final imaging time point.

Trastuzumab-MMAU Antibody-Auristatin Conjugates: Valine-Glucoserine Linker with Stabilized Maleimide Conjugation Improves In Vivo Efficacy and Tolerability.

Antibody-drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain with both efficacy and safety of ADCs. This study describes novel trastuzumab-auristatin conjugates with the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, and optimization of a glycopeptide linker leading to a wider therapeutic window.

Segmentation of Dynamic Total-Body [F]-FDG PET Images Using Unsupervised Clustering.

Clustering time activity curves of PET images have been used to separate clinically relevant areas of the brain or tumours. However, PET image segmentation in multiorgan level is much less studied due to the available total-body data being limited to animal studies. Now, the new PET scanners providing the opportunity to acquire total-body PET scans also from humans are becoming more common, which opens plenty of new clinically interesting opportunities.

Does Resectoscope Sheath Size Influence Holmium Laser Enucleation of the Prostate Outcomes? A Prospective Randomized Controlled Trial.

Holmium laser enucleation of the prostate (HoLEP) is routinely performed with a 24F, 26F, or a 28F scope. Proponents of the larger scopes propose that a bigger sheath size allows for superior flow and visibility leading to a more efficient operation and better hemostasis. Those utilizing the smaller scopes suggest that the smaller sheath is less traumatic, resulting in lower stricture rates and temporary incontinence.

Direct Comparison of [F]F-DPA with [F]DPA-714 and [C]PBR28 for Neuroinflammation Imaging in the same Alzheimer's Disease Model Mice and Healthy Controls.

Purpose: In this study we compared the recently developed TSPO tracer [F]F-DPA, with [F]DPA-714 and [C]PBR28 by performing in vivo PET imaging on the same Alzheimer's disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers.

Procedures: To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVR), and voxel-wise analyses were performed.

Results: The peak uptake of [F]F-DPA was higher than 4.

(S)-[F]THK5117 brain uptake is associated with Aβ plaques and MAO-B enzyme in a mouse model of Alzheimer's disease.

The mouse model of beta-amyloid (Aβ) deposition, APP/PS1-21, exhibits high brain uptake of the tau-tracer (S)-[F]THK5117, although no neurofibrillary tangles are present in this mouse model. For this reason we investigated (S)-[F]THK5117 off-target binding to Aβ plaques and MAO-B enzyme in APP/PS1-21 transgenic (TG) mouse model of Aβ deposition. APP/PS1-21 TG and wild-type (WT) control mice in four different age groups (2-26 months) were imaged antemortem by positron emission tomography with (S)-[F]THK5117, and then brain autoradiography.

Development of an Affordable, Sustainable and Efficacious Plant-Based Immunomodulatory Food Ingredient Based on Bell Pepper or Carrot RG-I Pectic Polysaccharides.

The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity-guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study.

Developing improved methods for identifying the cost-efficient abatement set in coastal water quality protection.

Eutrophication of coastal waters is a recognised problem in estuaries around the globe. To analyse cross-boundary water quality management, such as protection of the Baltic Sea, economic nutrient abatement models commonly operate on a large scale, grouping river systems to large catchment areas. Theoretical deliberation suggests that modelling abatement in such a way removes the opportunity of targeting measures to the most vulnerable regions within the catchment, while overestimating the capacity of abatement measures in the upstream areas.

Structure and Function of Bovine Whey Derived Oligosaccharides Showing Synbiotic Epithelial Barrier Protective Properties.

Commensal gut microbiota and probiotics have numerous effects on the host's metabolic and protective systems, which occur primarily through the intestinal epithelial cell interface. Prebiotics, like galacto-oligosaccharides (GOS) are widely used to modulate their function and abundance. However, important structure-function relations may exist, requiring a detailed structural characterization.

Ruthenium-Mediated F-Fluorination and Preclinical Evaluation of a New CB Receptor Imaging Agent [F]FPATPP.

Cannabinoid receptor 1 (CB1R) controls various physiological and pathological conditions, including memory, motivation, and inflammation, and is thus an interesting target for positron emission tomography (PET). Herein, we report a ruthenium-mediated radiolabeling synthesis and preclinical evaluation of a new CB1R specific radiotracer, [F]FPATPP. [F]FPATPP was produced with 16.

The value of manure - Manure as co-product in life cycle assessment.

Livestock production is important for food security, nutrition, and landscape maintenance, but it is associated with several environmental impacts. To assess the risk and benefits arising from livestock production, transparent and robust indicators are required, such as those offered by life cycle assessment. A central question in such approaches is how environmental burden is allocated to livestock products and to manure that is re-used for agricultural production.

Hydrophilic Auristatin Glycoside Payload Enables Improved Antibody-Drug Conjugate Efficacy and Biocompatibility.

Antibody-drug conjugates (ADCs) offer a combination of antibody therapy and specific delivery of potent small-molecule payloads to target cells. The properties of the ADC molecule are determined by the balance of its components. The efficacy of the payload component increases with higher drug-to-antibody ratio (DAR), while homogeneous DAR = 8 ADCs are easily prepared by conjugation to the four accessible antibody hinge cystines.

Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody-Drug Conjugation Chemistry.

Antibody-drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug-delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site-selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC.

Synthesis of the copper chelator TGTA and evaluation of its ability to protect biomolecules from copper induced degradation during copper catalyzed azide-alkyne bioconjugation reactions.

One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

Effect of catchment land use and soil type on the concentration, quality, and bacterial degradation of riverine dissolved organic matter.

We studied the effects of catchment characteristics (soil type and land use) on the concentration and quality of dissolved organic matter (DOM) in river water and on the bacterial degradation of terrestrial DOM. The share of organic soil was the strongest predictor of high concentrations of dissolved organic carbon, nitrogen, and phosphorus (DOC, DON, and DOP, respectively), and was linked to DOM quality. Soil type was more important than land use in determining the concentration and quality of riverine DOM.

Model for quantifying the synergies between farmland biodiversity conservation and water protection at catchment scale.

This paper studies joint provision of two environmental non-market commodities related to agriculture: biodiversity conservation and water protection. We provide an optimising tool for analysing spatial dependencies of multifunctional agriculture at catchment scale. We show that efficiency gains can be achieved by spatial allocation and choice of the type of vegetation.

Diversity in prokaryotic glycosylation: an archaeal-derived N-linked glycan contains legionaminic acid.

VP4, the major structural protein of the haloarchaeal pleomorphic virus, HRPV-1, is glycosylated. To define the glycan structure attached to this protein, oligosaccharides released by β-elimination were analysed by mass spectrometry and nuclear magnetic resonance spectroscopy. Such analyses showed that the major VP4-derived glycan is a pentasaccharide comprising glucose, glucuronic acid, mannose, sulphated glucuronic acid and a terminal 5-N-formyl-legionaminic acid residue.

The N-glycome of human embryonic stem cells.

Background: Complex carbohydrate structures, glycans, are essential components of glycoproteins, glycolipids, and proteoglycans. While individual glycan structures including the SSEA and Tra antigens are already used to define undifferentiated human embryonic stem cells (hESC), the whole spectrum of stem cell glycans has remained unknown. We undertook a global study of the asparagine-linked glycoprotein glycans (N-glycans) of hESC and their differentiated progeny using MALDI-TOF mass spectrometric and NMR spectroscopic profiling.

Glycoforms of human endothelial CD34 that bind L-selectin carry sulfated sialyl Lewis x capped O- and N-glycans.

Endothelial sialomucin CD34 functions as an L-selectin ligand mediating lymphocyte extravasation only when properly glycosylated to express a sulfated carbohydrate epitope, 6-sulfo sialyl Lewis x (6-sulfo SLe(x)). It is thought that multivalent 6-sulfo SLe(x) expression promotes high-affinity binding to L-selectin by enhancing avidity. However, the reported low amount of 6-sulfo SLe(x) in total human CD34 is inconsistent with this model and prompted us to re-evaluate CD34 glycosylation.

Helicobacter pylori binding to new glycans based on N-acetyllactosamine.

Previously we reported binding of Helicobacter pylori to various nonacid and sialylated neolacto carbohydrate structures using a wide range of natural and chemically modified sequences. A novel nonsialylated neolacto-based binding epitope, GlcNAc beta 3Gal beta 4GlcNAc, and analogous structures carrying terminal GalNAc beta 3, GalNAc alpha 3, or Gal alpha 3 showed the binding activity (Miller-Podraza H, Lanne B, Angström J, Teneberg S, Abul-Milh M, Jovall P-A, Karlsson H, Karlsson K-A. 2005.