Dark-field X-ray imaging for the assessment of osteoporosis in human lumbar spine specimens

Background: Dark-field imaging is a novel imaging modality that allows for the assessment of material interfaces by exploiting the wave character of x-ray. While it has been extensively studied in chest imaging, only little is known about the modality for imaging other tissues. Therefore, the purpose of this study was to evaluate whether a clinical X-ray dark-field scanner prototype allows for the assessment of osteoporosis.Materials and methods: In this prospective study we examined human cadaveric lumbar spine specimens (vertebral segments L2 to L4). We used a clinical prototype for dark-field radiography that yields both attenuation and dark-field images. All specimens were scanned in lateral orientation in vertical and horizontal position. All specimens were additionally imaged with CT as reference. Bone mineral density (BMD) values were derived from asynchronously calibrated quantitative CT measurements. Correlations between attenuation signal, dark-field signal and BMD were assessed using Spearman’s rank correlation coefficients. The capability of the dark-field signal for the detection of osteoporosis/osteopenia was evaluated with receiver operating characteristics (ROC) curve analysis.Results: A total of 58 vertebrae from 20 human cadaveric spine specimens (mean age, 73 years ±13 [standard deviation]; 11 women) were studied. The dark-field signal was positively correlated with the BMD, both in vertical (r = 0.56, p < .001) and horizontal position (r = 0.43, p < .001). Also, the dark-field signal ratio was positively correlated with BMD (r = 0.30, p = .02). No correlation was found between the signal ratio of attenuation signal and BMD (r = 0.14, p = .29). For the differentiation between specimens with and without osteoporosis/osteopenia, the area under the ROC curve (AUC) was 0.80 for the dark-field signal in vertical position.Conclusion: Dark-field imaging allows for the differentiation between spine specimens with and without osteoporosis/osteopenia and may therefore be a potential biomarker for bone stability

Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease

Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA[Ser]Sec, required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome

Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers

Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease.info:eu-repo/semantics/publishedVersio

Multi-Parametric Analysis and Modeling of Relationships between Mitochondrial Morphology and Apoptosis

Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis

Accessing ns–μs side chain dynamics in ubiquitin with methyl RDCs

This study presents the first application of the model-free analysis (MFA) (Meiler in J Am Chem Soc 123:6098–6107, 2001; Lakomek in J Biomol NMR 34:101–115, 2006) to methyl group RDCs measured in 13 different alignment media in order to describe their supra-τc dynamics in ubiquitin. Our results indicate that methyl groups vary from rigid to very mobile with good correlation to residue type, distance to backbone and solvent exposure, and that considerable additional dynamics are effective at rates slower than the correlation time τc. In fact, the average amplitude of motion expressed in terms of order parameters S2 associated with the supra-τc window brings evidence to the existence of fluctuations contributing as much additional mobility as those already present in the faster ps-ns time scale measured from relaxation data. Comparison to previous results on ubiquitin demonstrates that the RDC-derived order parameters are dominated both by rotameric interconversions and faster libration-type motions around equilibrium positions. They match best with those derived from a combined J-coupling and residual dipolar coupling approach (Chou in J Am Chem Soc 125:8959–8966, 2003) taking backbone motion into account. In order to appreciate the dynamic scale of side chains over the entire protein, the methyl group order parameters are compared to existing dynamic ensembles of ubiquitin. Of those recently published, the broadest one, namely the EROS ensemble (Lange in Science 320:1471–1475, 2008), fits the collection of methyl group order parameters presented here best. Last, we used the MFA-derived averaged spherical harmonics to perform highly-parameterized rotameric searches of the side chains conformation and find expanded rotamer distributions with excellent fit to our data. These rotamer distributions suggest the presence of concerted motions along the side chains

Guidelines and Recommendations on Yeast Cell Death Nomenclature

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research

Hybrid cosmic ray measurements using the IceAct telescopes in coincidence with the IceCube and IceTop detectors

IceAct is a proposed surface array of compact (50 cm diameter) and cost-effective Imaging Air Cherenkov Telescopes installed at the site of the IceCube Neutrino Observatory at the geographic South Pole. Since January 2019, two IceAct telescope demonstrators, featuring 61 silicon photomultiplier (SiPM) pixels have been taking data in the center of the IceTop surface array during the austral winter. We present the first analysis of hybrid cosmic ray events detected by the IceAct imaging air-Cherenkov telescopes in coincidence with the IceCube Neutrino Observatory, including the IceTop surface array and the IceCube in-ice array. By featuring an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of improving current cosmic ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors, enabling significantly better primary particle type discrimination on a statistical basis. The hybrid measurement also allows for detailed feasibility studies of detector cross-calibration and of cosmic ray veto capabilities for neutrino analyses. We present the performance of the telescopes, the results from the analysis of two years of data, and an outlook of a hybrid simulation for a future telescope array