X-ray phase-contrast tomography of cells manipulated with an optical stretcher.

X-rays can penetrate deeply into biological cells and thus allow for examination of their internal structures with high spatial resolution. In this study, X-ray phase-contrast imaging and tomography is combined with an X-ray-compatible optical stretcher and microfluidic sample delivery. Using this setup, individual cells can be kept in suspension while they are examined with the X-ray beam at a synchrotron.

Jetting bubbles observed by x-ray holography at a free-electron laser: internal structure and the effect of non-axisymmetric boundary conditions.

Unlabelled: In this work, we study the jetting dynamics of individual cavitation bubbles using x-ray holographic imaging and high-speed optical shadowgraphy. The bubbles are induced by a focused infrared laser pulse in water near the surface of a flat, circular glass plate, and later probed with ultrashort x-ray pulses produced by an x-ray free-electron laser (XFEL). The holographic imaging can reveal essential information of the bubble interior that would otherwise not be accessible in the optical regime due to obscuration or diffraction.

An Isocaloric High-Fat Diet Regulates Partially Genetically Determined Fatty Acid and Carbohydrate Uptake and Metabolism in Subcutaneous Adipose Tissue of Lean Adult Twins.

Background: The dysfunction of energy metabolism in white adipose tissue (WAT) induces adiposity. Obesogenic diets that are high in saturated fat disturb nutrient metabolism in adipocytes. This study investigated the effect of an isocaloric high-fat diet without the confounding effects of weight gain on the gene expression of fatty acid and carbohydrate transport and metabolism and its genetic inheritance in subcutaneous (s.

Micropipette aspiration as a tool for single-particle X-ray imaging and diffraction.

A sample environment and manipulation tool is presented for single-particle X-ray experiments in an aqueous environment. The system is based on a single water droplet, positioned on a substrate that is structured by a hydrophobic and hydrophilic pattern to stabilize the droplet position. The substrate can support several droplets at a time.

Predicting Factors for Metabolic Non-Response to a Complex Lifestyle Intervention-A Replication Analysis to a Randomized-Controlled Trial.

Background: T2DM heterogeneity affects responsiveness to lifestyle treatment. Beta-cell failure and nonalcoholic fatty liver disease (NAFLD) independently predict T2DM, but NAFLD inconsistently predicts metabolic response to lifestyle intervention.

Aim: We attempt to replicate a prediction model deducted from the Tübinger Lifestyle Intervention Program by assessing similar metabolic factors to predict conversion to normal glucose regulation (NGR) in a comparable lifestyle intervention trial.

Combined optical fluorescence microscopy and X-ray tomography reveals substructures in cell nuclei in 3D.

The function of a biological cell is fundamentally defined by the structural architecture of packaged DNA in the nucleus. Elucidating information about the packaged DNA is facilitated by high-resolution imaging. Here, we combine and correlate hard X-ray propagation-based phase contrast tomography and visible light confocal microscopy in three dimensions to probe DNA in whole cell nuclei of NIH-3T3 fibroblasts.

Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients.

Objectives: Some individuals develop type 2 diabetes mellitus (T2DM) despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that insulin growth factor 1 (IGF1) and its binding proteins 1 and 2 predict the onset of T2DM in prediabetes patients and determine the capacity for metabolic regeneration.

Design: We measured fasting serum IGF1, insulin growth factor-binding protein 1 (IGFBP1) and IGFBP2 in three randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up.

Coherent Diffractive Imaging with Diffractive Optics.

We present a novel approach to x-ray microscopy based on a multilayer zone plate which is positioned behind a sample similar to an objective lens. However, unlike transmission x-ray microscopy, we do not content ourselves with a sharp intensity image; instead, we incorporate the multilayer zone plate transfer function directly in an iterative phase retrieval scheme to exploit the large diffraction angles of the small layers. The presence of multiple diffraction orders, which is conventionally a nuisance, now comes as an advantage for the reconstruction and photon efficiency.

Off-axis multilayer zone plate with 16 nm × 28 nm focus for high-resolution X-ray beam induced current imaging.

Using multilayer zone plates (MZPs) as two-dimensional optics, focal spot sizes of less than 10 nm can be achieved, as we show here with a focus of 8.4 nm × 9.6 nm, but the need for order-sorting apertures prohibits practical working distances.

Dose-dependent effects of insoluble fibre on glucose metabolism: a stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT).

Aims: As the first long-term RCT on insoluble cereal fibre, the optimal fibre trial demonstrated glycometabolic benefits, confirming cohort studies. The combined study intervention of lifestyle recommendations and supplementation with insoluble oat hulls fibre allows to clarify, which amount of fibre is required for a beneficial effect.

Methods: One hundred and eighty participants with impaired glucose tolerance underwent the one-year PREDIAS lifestyle programme and received a blinded, randomized fibre or placebo supplement for two years.

Insulin Directly Regulates the Circadian Clock in Adipose Tissue.

Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a "zeitgeber" aligning the clock in AT with the external time, but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated a transcriptional-dependent mechanism of this regulation.

Pump-probe X-ray holographic imaging of laser-induced cavitation bubbles with femtosecond FEL pulses.

Cavitation bubbles can be seeded from a plasma following optical breakdown, by focusing an intense laser in water. The fast dynamics are associated with extreme states of gas and liquid, especially in the nascent state. This offers a unique setting to probe water and water vapor far-from equilibrium.

Nanosecond timing and synchronization scheme for holographic pump-probe studies at the MID instrument at European XFEL.

Single-pulse holographic imaging at XFEL sources with 10 photons delivered in pulses shorter than 100 fs reveal new quantitative insights into fast phenomena. Here, a timing and synchronization scheme for stroboscopic imaging and quantitative analysis of fast phenomena on time scales (sub-ns) and length-scales (≲100 nm) inaccessible by visible light is reported. A fully electronic delay-and-trigger system has been implemented at the MID station at the European XFEL, and applied to the study of emerging laser-driven cavitation bubbles in water.

Effects of Insoluble Cereal Fibre on Body Fat Distribution in the Optimal Fibre Trial.

Scope: The Optimal Fibre Trial (OptiFiT) investigates metabolic effects of insoluble cereal fibre in subjects with impaired glucose tolerance (IGT), showing moderate glycemic and anti-inflammatory benefits, especially in subjects with an obesity-related phenotype. An OptiFiT sub-group is analysed for effects on body fat distribution.

Methods And Results: 180 participants with IGT receive a blinded, randomized supplementation with insoluble cereal fibre or placebo for 2 years.

Similar dietary regulation of IGF-1- and IGF-binding proteins by animal and plant protein in subjects with type 2 diabetes.

Increased animal but not plant protein intake has been associated with increased mortality in epidemiological studies in humans and with reduced lifespan in animal species. Protein intake increases the activity of the IGF-1 system which may provide a link to reduced lifespan. We, therefore, compared the effects of animal versus plant protein intake on circulating levels of IGF-1 and the IGF-binding proteins (IGFBP)-1 and IGFBP-2 over a 6-week period.

Combined scanning small-angle X-ray scattering and holography probes multiple length scales in cell nuclei.

X-rays are emerging as a complementary probe to visible-light photons and electrons for imaging biological cells. By exploiting their small wavelength and high penetration depth, it is possible to image whole, intact cells and resolve subcellular structures at nanometer resolution. A variety of X-ray methods for cell imaging have been devised for probing different properties of biological matter, opening up various opportunities for fully exploiting different views of the same sample.

Single-pulse phase-contrast imaging at free-electron lasers in the hard X-ray regime.

X-ray free-electron lasers (XFELs) have opened up unprecedented opportunities for time-resolved nano-scale imaging with X-rays. Near-field propagation-based imaging, and in particular near-field holography (NFH) in its high-resolution implementation in cone-beam geometry, can offer full-field views of a specimen's dynamics captured by single XFEL pulses. To exploit this capability, for example in optical-pump/X-ray-probe imaging schemes, the stochastic nature of the self-amplified spontaneous emission pulses, i.

3D virtual histology of human pancreatic tissue by multiscale phase-contrast X-ray tomography.

A multiscale three-dimensional (3D) virtual histology approach is presented, based on two configurations of propagation phase-contrast X-ray tomography, which have been implemented in close proximity at the GINIX endstation at the beamline P10/PETRA III (DESY, Hamburg, Germany). This enables the 3D reconstruction of characteristic morphological features of human pancreatic normal and tumor tissue, as obtained from cancer surgery, first in the form of a large-scale overview by parallel-beam illumination, followed by a zoom into a region-of-interest based on zoom tomography using a Kirkpatrick-Baez mirror with additional waveguide optics. To this end 1 mm punch biopsies of the tissue were taken.

Dietary Rapeseed Oil Supplementation Reduces Hepatic Steatosis in Obese Men-A Randomized Controlled Trial.

Scope: Effective treatment for obesity associated non-alcoholic fatty liver disease (NAFLD) is limited. Dietary supplementation of n-3 polyunsaturated fatty acids, specifically alpha linolenic acid (ALA), can resolve intrahepatic lipid content (IHL). This study investigates the effect of daily supplementation of either refined rapeseed (RA), containing high amounts of ALA, or refined olive (OL) oil on IHL and glucose metabolism in NAFLD patients.

3D virtual pathohistology of lung tissue from Covid-19 patients based on phase contrast X-ray tomography.

We present a three-dimensional (3D) approach for virtual histology and histopathology based on multi-scale phase contrast x-ray tomography, and use this to investigate the parenchymal architecture of unstained lung tissue from patients who succumbed to Covid-19. Based on this first proof-of-concept study, we propose multi-scale phase contrast x-ray tomography as a tool to unravel the pathophysiology of Covid-19, extending conventional histology by a third dimension and allowing for full quantification of tissue remodeling. By combining parallel and cone beam geometry, autopsy samples with a maximum cross section of 8 mm are scanned and reconstructed at a resolution and image quality, which allows for the segmentation of individual cells.

Sexually dimorphic metabolic responses to exposure of a high fat diet during pregnancy, lactation and early adulthood in Gipr mice.

Obesity has a multifactorial origin. It is known that alterations of the intra uterine milieu induce developmental programming effects leading to metabolic diseases in offspring. Obesity is diminished in mice lacking the glucose-dependent insulinotropic polypeptide receptor (Gipr) when exposed to a high fat diet (HFD).

Obesity Does Not Modulate the Glycometabolic Benefit of Insoluble Cereal Fibre in Subjects with Prediabetes-A Stratified Post Hoc Analysis of the Optimal Fibre Trial (OptiFiT).

Unlabelled: Obesity does not modulate the glycometabolic benefit of insoluble cereal fibre in subjects with prediabetes-a stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT).

Background: OptiFiT demonstrated the beneficial effect of insoluble oat fibres on dysglycemia in prediabetes. Recent analyses of OptiFiT and other randomised controlled trials (RCTs) indicated that this effect might be specific for the subgroup of patients with impaired fasting glucose (IFG).

Fasting Glucose State Determines Metabolic Response to Supplementation with Insoluble Cereal Fibre: A Secondary Analysis of the Optimal Fibre Trial (OptiFiT).

Background: High intake of cereal fibre is associated with reduced risk for type 2 diabetes and long-term complications. Within the first long-term randomized controlled trial specifically targeting cereal fibre, the Optimal Fibre Trial (OptiFiT), intake of insoluble oat fibre was shown to significantly reduce glycaemia. Previous studies suggested that this effect might be limited to subjects with impaired fasting glucose (IFG).

Focus characterization of the NanoMAX Kirkpatrick-Baez mirror system.

The focusing and coherence properties of the NanoMAX Kirkpatrick-Baez mirror system at the fourth-generation MAX IV synchrotron in Lund have been characterized. The direct measurement of nano-focused X-ray beams is possible by scanning of an X-ray waveguide, serving basically as an ultra-thin slit. In quasi-coherent operation, beam sizes of down to 56 nm (FWHM, horizontal direction) can be achieved.