Bone Quality in Chronic Kidney Disease: Definitions and Diagnostics

PURPOSE OF REVIEW: In this paper, we review the epidemiology, diagnosis, and pathogenesis of fractures and renal osteodystrophy. RECENT FINDINGS: The role of bone quality in the pathogenesis of fracture susceptibility in chronic kidney disease (CKD) is beginning to be elucidated. Bone quality refers to bone material properties, such as cortical and trabecular microarchitecture, mineralization, turnover, microdamage, and collagen content and structure. Recent data has added to our understanding of the effects of CKD on alterations to bone quality, emerging data on the role of abnormal collagen structure on bone strength, the potential of non-invasive methods to inform our knowledge of bone quality, and how we can use these methods to inform strategies that protect against bone loss and fractures. However, more prospective data is required. CKD is associated with abnormal bone quality and strength which results in high fracture incidence

Early Miocene gastropod and ectothermic vertebrate remains from the Lesvos Petrified Forest (Greece)

The Lesvos Petrified Forest (western Lesvos, Greece) has long been famous for its plant fossils. Recently, one proboscidean (from the Gavathas locality) and seven micromammalian species (from the Lapsarna locality) were described; these were the first animals to be found in the Early Miocene subtropical forest. For the first time, a fauna of gastropods and ectothermic vertebrates from the Lapsarna locality is now available. This fauna derives from lacustrine sediments under the pyroclastic material that contains the petrified plants. Based on fragmented mollusc remains, isolated fish pharyngeal teeth and utricular otoliths (lapilli), fragmented amphibian vertebrae and a tooth-bearing element, and reptile fragmented dentaries, teeth, osteoderms and vertebrae, the presence of eight freshwater and three terrestrial gastropod species, three freshwater cyprinid species, and two amphibian and five reptile taxa has been confirmed. Stratigraphical and radiometric data suggest an age older than 18.4 ± 0.5 Ma (latest Early Miocene), in good agreement with the faunal composition. This paper is the first report of the concurrent presence of three cyprinid fish species in a Greek Early Miocene locality, as well as the first documentation of an Early Miocene proteid amphibian in southeastern Europe. The present findings represent one of the best- documented Early Miocene gastropod and fish faunas in the Aegean/southern Balkans, thus adding to our knowledge of Early Miocene amphibians and reptiles from that region and providing valuable information on the local subtropical ecosystem

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R–mediated apoptosis

Myeloid-derived suppressor cells (MDSCs) dampen the immune response thorough inhibition of T cell activation and proliferation and often are expanded in pathological conditions. Here, we studied the fate of MDSCs in cancer. Unexpectedly, MDSCs had lower viability and a shorter half-life in tumor-bearing mice compared with neutrophils and monocytes. The reduction of MDSC viability was due to increased apoptosis, which was mediated by increased expression of TNF-related apoptosis–induced ligand receptors (TRAIL-Rs) in these cells. Targeting TRAIL-Rs in naive mice did not affect myeloid cell populations, but it dramatically reduced the presence of MDSCs and improved immune responses in tumor-bearing mice. Treatment of myeloid cells with proinflammatory cytokines did not affect TRAIL-R expression; however, induction of ER stress in myeloid cells recapitulated changes in TRAIL-R expression observed in tumor-bearing hosts. The ER stress response was detected in MDSCs isolated from cancer patients and tumor-bearing mice, but not in control neutrophils or monocytes, and blockade of ER stress abrogated tumor-associated changes in TRAIL-Rs. Together, these data indicate that MDSC pathophysiology is linked to ER stress, which shortens the lifespan of these cells in the periphery and promotes expansion in BM. Furthermore, TRAIL-Rs can be considered as potential targets for selectively inhibiting MDSCs

Systematics of Inclusive Photon Production in 158 AGeV Pb Induced Reactions on Ni, Nb, and Pb Targets

The multiplicity of inclusive photons has been measured on an event-by-event basis for 158 AGeV Pb induced reactions on Ni, Nb, and Pb targets. The systematics of the pseudorapidity densities at midrapidity (rho_max) and the width of the pseudorapidity distributions have been studied for varying centralities for these collisions. A power law fit to the photon yield as a function of the number of participating nucleons gives a value of 1.13+-0.03 for the exponent. The mean transverse momentum, , of photons determined from the ratio of the measured electromagnetic transverse energy and photon multiplicity, remains almost constant with increasing rho_max. Results are compared with model predictions.Comment: 16 pages including 4 figure