Amniotic-Fluid Stem Cells: Growth Dynamics and Differentiation Potential after a CD-117-Based Selection Procedure

Amniotic fluid (AF) has become an interesting source of fetal stem cells. However, AF contains heterogeneous and multiple, partially differentiated cell types. After isolation from the amniotic fluid, cells were characterized regarding their morphology and growth dynamics. They were sorted by magnetic associated cell sorting using the surface marker CD 117. In order to show stem cell characteristics such as pluripotency and to evaluate a possible therapeutic application of these cells, AF fluid-derived stem cells were differentiated along the adipogenic, osteogenic, and chondrogenic as well as the neuronal lineage under hypoxic conditions. Our findings reveal that magnetic associated cell sorting (MACS) does not markedly influence growth characteristics as demonstrated by the generation doubling time. There was, however, an effect regarding an altered adipogenic, osteogenic, and chondrogenic differentiation capacity in the selected cell fraction. In contrast, in the unselected cell population neuronal differentiation is enhanced

Blind Rule-Following and the Regress of Motivations

Normativists about belief hold that belief formation is essentially rule- or norm-guided. On this view, certain norms are constitutive of or essential to belief in such a way that no mental state not guided by those norms counts as a belief, properly construed. In recent influential work, Kathrin Glüer and Åsa Wikforss develop novel arguments against normativism. According to their regress of motivations argument, not all belief formation can be rule- or norm-guided, on pain of a vicious infinite regress. I argue that the regress of motivations argument is unsuccessful: an appeal to the notion of blind rule-following, drawn from a plausible interpretation of Ludwig Wittgenstein’s remarks on rule-following, stops the regress of motivations in its tracks

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene-targeted replacement mice

Scope Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. Methods and results Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele

Russell-names: an introduction to Millian descriptivism

This essay studies the semantic properties of what I call Russell-names. Russell-names bear intimate semantic relations with descriptive conditions, in consonance with the main tenets of descriptivism. Yet, they are endowed with the semantic properties attributed to ordinary proper names by Millianism: they are rigid and non-indexical devices of direct reference. This is not an essay in natural language semantics, and remains deliberately neutral with respect to the question whether any among the expressions we ordinarily classify as proper names behave as Russell-names. Its aim is rather that of casting a new light on the traditional debate about descriptivism on the one hand, and, on the other, what is commonly understood as a radically anti-descriptivist approach. From the viewpoint of descriptivism, the conceivability of Russell-names provides welcome relief from the pressure exerted by considerations at odds with a flaccid and/or indexical treatment of proper names. Conversely, from a Millian standpoint, the conceivability of Russell-names indicates that the Millian stance, far from providing a meagre picture of names as ‘mere tags’, is at least in principle consistent with the recognition of their semantic bonds with richer descriptive material. The Appendix provides a formal treatment of Russell-names within a model theoretic semantics for indexical intensional languages, developed within an original ‘double-context’ framework

An Analysis by Synthesis Approach for Automatic Vertebral Shape Identification in Clinical QCT

Quantitative computed tomography (QCT) is a widely used tool for osteoporosis diagnosis and monitoring. The assessment of cortical markers like cortical bone mineral density (BMD) and thickness is a demanding task, mainly because of the limited spatial resolution of QCT. We propose a direct model based method to automatically identify the surface through the center of the cortex of human vertebra. We develop a statistical bone model and analyze its probability distribution after the imaging process. Using an as-rigid-as-possible deformation we find the cortical surface that maximizes the likelihood of our model given the input volume. Using the European Spine Phantom (ESP) and a high resolution \mu CT scan of a cadaveric vertebra, we show that the proposed method is able to accurately identify the real center of cortex ex-vivo. To demonstrate the in-vivo applicability of our method we use manually obtained surfaces for comparison.Comment: Presented on German Conference on Pattern Recognition (GCPR) 2018 in Stuttgar

Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: −0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD) n = 14) from those without osteoporosis (δ44/42CaBlood: −0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were − 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients

Who’s afraid of the predicate theory of names?

This essay is devoted to an analysis of the semantic significance of a fashionable view of proper names, the Predicate Theory of names (PT), typically developed in the direction of the Metalinguistic Theory of names (MT). According to MT, ‘syntactic evidence supports the conclusion that a name such as ‘Kennedy’ is analyzable in terms of the predicate (general term) ‘individual named ‘Kennedy’’. This analysis is in turn alleged to support a descriptivist treatment of proper names in designative position, presumably in contrast with theories of names as ‘directly referring rigid designators’. The main aim of this essay is that of questioning the significance of PT and MT as theories of designation: even granting for the argument’s sake that names are analyzable as (metalinguistic) predicates, their designative occurrences may be interpreted in consonance with the dictates of Direct Reference—indeed, in consonance with the radically anti-descriptivist version of Direct Reference I call Millianism

Spatio-temporal atlas of bone mineral density ageing

Osteoporosis is an age-associated bone disease characterised by low bone mass. An improved understanding of the underlying mechanism for age-related bone loss could lead to enhanced preventive and therapeutic strategies for osteoporosis. In this work, we propose a fully automatic pipeline for developing a spatio-temporal atlas of ageing bone. Bone maps are collected using a dual-energy X-ray absorptiometry (DXA) scanner. Each scan is then warped into a reference template to eliminate morphological variation and establish a correspondence between pixel coordinates. Pixel-wise bone density evolution with ageing was modelled using smooth quantile curves. To construct the atlas, we amalgamated a cohort of 1714 Caucasian women (20–87 years) from five different centres in North Western Europe. As a systematic difference exists between different DXA manufacturers, we propose a novel calibration technique to homogenise bone density measurements across the centres. This technique utilises an alternating minimisation technique to map the observed bone density measurements into a latent standardised space. To the best of our knowledge, this is the first spatio-temporal atlas of ageing bone