Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire.

Magnetic Resonance-based Assessment of Myocardial 2-Dimensional Strain Using Feature Tracking: Association With Cardiovascular Risk Factors in a Population-based Cohort Free of Cardiovascular Disease.

Purpose: Myocardial strain analysis is a promising tool for the detection of subtle but relevant alterations of left ventricular function, also in asymptomatic subjects. Thus, we determined the feasibility of cardiac magnetic resonance-based 2D global strain analysis using feature tracking and its association with cardiovascular risk factors in a sample from the general population.

Materials And Methods: Subjects without a history of cardiocerebrovascular disease were enrolled in a substudy of the population-based KORA (Cooperative Health Research in the Region of Augsburg) cohort.

Dose-compatible grating-based phase-contrast mammography on mastectomy specimens using a compact synchrotron source.

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses.

Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance.

Introduction: Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls.

Materials And Methods: Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement.

Detection of Post-Therapeutic Effects in Breast Carcinoma Using Hard X-Ray Index of Refraction Computed Tomography - A Feasibility Study.

Objectives: Neoadjuvant chemotherapy is the state-of-the-art treatment in advanced breast cancer. A correct visualization of the post-therapeutic tumor size is of high prognostic relevance. X-ray phase-contrast computed tomography (PC-CT) has been shown to provide improved soft-tissue contrast at a resolution formerly restricted to histopathology, at low doses.

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

Objectives: To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria.

Methods: Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined.

A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.

Unlabelled: Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models.

Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging.

The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery.

Improved visualization of breast cancer features in multifocal carcinoma using phase-contrast and dark-field mammography: an ex vivo study.

Objectives: Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples.

Methods: We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer.

Cartilage and soft tissue imaging using X-rays: propagation-based phase-contrast computed tomography of the human knee in comparison with clinical imaging techniques and histology.

Objectives: This study evaluates high-resolution tomographic x-ray phase-contrast imaging in whole human knee joints for the depiction of soft tissue with emphasis on hyaline cartilage. The method is compared with conventional computed tomography (CT), synchrotron radiation absorption-based CT, and magnetic resonance imaging (MRI).

Material And Methods: After approval of the institutional review board, 2 cadaveric human knees were examined at an synchrotron institution using a monochromatic x-ray beam of 60 keV, a detector with a 90-mm field of view, and a pixel size of 46 × 46 μm.

Visualizing typical features of breast fibroadenomas using phase-contrast CT: an ex-vivo study.

Background: Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging.

Evaluation of phase-contrast CT of breast tissue at conventional X-ray sources - presentation of selected findings.

Background: Grating-based phase contrast computed tomography (PC-CT) at synchrotron radiation sources has been shown to provide improved visualization of breast tumors. However, broad clinical application of phase-contrast imaging will likely depend on transferring the technology to standard polychromatic X-ray sources. On the basis of selected findings, we demonstrate the potential of grating-based PC-CT using a conventional X-ray source.

Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up.

Objective: Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS).

Oxysterol-binding protein (OSBP) enhances replication of intracellular Salmonella and binds the Salmonella SPI-2 effector SseL via its N-terminus.

Effectors translocated into the host cell by Salmonella enterica serovar Typhimurium are critical for bacterial virulence. For many effectors, the mechanisms of their interactions with host pathways are not yet understood. We have recently found an interaction between the SPI-2 effector SseL and oxysterol-binding protein (OSBP).

The deubiquitinase activity of the Salmonella pathogenicity island 2 effector, SseL, prevents accumulation of cellular lipid droplets.

To cause disease, Salmonella enterica serovar Typhimurium requires two type III secretion systems that are encoded by Salmonella pathogenicity islands 1 and 2 (SPI-1 and -2). These secretion systems serve to deliver specialized proteins (effectors) into the host cell cytosol. While the importance of these effectors to promote colonization and replication within the host has been established, the specific roles of individual secreted effectors in the disease process are not well understood.

Quantitative mass spectrometry catalogues Salmonella pathogenicity island-2 effectors and identifies their cognate host binding partners.

Gram-negative bacterial pathogens have developed specialized secretion systems to transfer bacterial proteins directly into host cells. These bacterial effectors are central to virulence and reprogram host cell processes to favor bacterial survival, colonization, and proliferation. Knowing the complete set of effectors encoded by a particular pathogen is the key to understanding bacterial disease.

Inhibition of Salmonella host cell invasion by dimethyl sulfide.

We show that dimethyl sulfoxide (DMSO) inhibits Salmonella hilA expression and that this inhibition is stronger under anaerobiosis. Because DMSO can be reduced to dimethyl sulfide (DMS) during anaerobic growth, we hypothesized that DMS was responsible for hilA inhibition. Indeed, DMS strongly inhibited the expression of hilA and multiple Salmonella pathogenicity island 1 (SPI-1)-associated genes as well as the invasion of cultured epithelial cells.

RNA looping by PTB: Evidence using FRET and NMR spectroscopy for a role in splicing repression.

Alternative splicing plays an important role in generating proteome diversity. The polypyrimidine tract-binding protein (PTB) is a key alternative splicing factor involved in exon repression. It has been proposed that PTB acts by looping out exons flanked by pyrimidine tracts.

Proteomics as a probe of microbial pathogenesis and its molecular boundaries.

Proteomic technology offers an unprecedented systematic approach to investigate the protein complement of any organism. The field of microbial pathogenesis has greatly benefited from other systems approaches, and the application of proteomics to the study of infectious agents is beginning to emerge. Such applications include unambiguously identifying complete virulence factor inventories, studying the response of both host and pathogen to the infection process and elucidating mechanistic actions of virulence factors as they interface with host cells.

Co-evolution and exploitation of host cell signaling pathways by bacterial pathogens.

Bacterial pathogens have evolved by combinations of gene acquisition, deletion, and modification, which increases their fitness. Additionally, bacteria are able to evolve in "quantum leaps" via the ability to promiscuously acquire new genes. Many bacterial pathogens - especially Gram-negative enteric pathogens - have evolved mechanisms by which to subvert signal transduction pathways of eukaryotic cells by expressing genes that mimic or regulate host protein factors involved in a variety of signaling cascades.

Solving the structure of PTB in complex with pyrimidine tracts: an NMR study of protein-RNA complexes of weak affinities.

NMR spectroscopy has proven to be a powerful tool for the structure determination of protein/RNA complexes. However, the quality of these structures depends critically on the number of unambiguous intermolecular and intra-RNA nuclear Overhauser effect (NOE) constraints that can be derived. This number is often limited due to exchange phenomena that can cause signal line broadening and the fact that unambiguous NOE assignments are challenging in systems that exchange between different conformations in the intermediate to fast exchange limit.

Sequence-specific binding of single-stranded RNA: is there a code for recognition?

A code predicting the RNA sequence that will be bound by a certain protein based on its amino acid sequence or its structure would provide a useful tool for the design of RNA binders with desired sequence-specificity. Such de novo designed RNA binders could be of extraordinary use in both medical and basic research applications. Furthermore, a code could help to predict the cellular functions of RNA-binding proteins that have not yet been extensively studied.

Short, synthetic and selectively 13C-labeled RNA sequences for the NMR structure determination of protein-RNA complexes.

We report an optimized synthesis of all canonical 2'-O-TOM protected ribonucleoside phosphoramidites and solid supports containing [13C5]-labeled ribose moieties, their sequence-specific introduction into very short RNA sequences and their use for the structure determination of two protein-RNA complexes. These specifically labeled sequences facilitate RNA resonance assignments and are essential to assign a high number of sugar-sugar and intermolecular NOEs, which ultimately improve the precision and accuracy of the resulting structures. This labeling strategy is particularly useful for the study of protein-RNA complexes with single-stranded RNA in solution, which is rapidly an increasingly relevant research area in biology.