Proteomics for Clinical Assessment of Kidney Disease

Kidney disease is one of the fastest growing causes of death worldwide, disclosing an unmet clinical need for early diagnosis and optimized risk stratification that allows high risk patient selection for clinical trials and for more intensive nephroprotective interventions in the clinic. The current issue of PROTEOMICS—Clinical Applications contains four manuscripts that explore different aspects of clinical proteomics implementation in the context of acute kidney injury, chronic kidney disease and, more specifically, diabetic kidney disease, and kidney transplantation from a diagnostic and risk stratification point of view. Overall, the evidence discussed suggests that chronic kidney disease is an example where clinical proteomics has become a valuable tool ready for clinical implementation, expected to have a major impact in patient management.The author was supported by FIS PI16/02057, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, and Comunidad de Madrid B2017/BMD- 3686 CIFRA2-CM

Albumin-induced apoptosis of tubular cells is modulated by BASP1

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6–48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuriaGrant support: FIS PS09/00447, PI13/00047, CP14/ 00133, ISCIII-RETIC, REDinREN/RD06/0016/and RD012/0021 FEDER funds, Comunidad de Madrid/CIFRA S2010/BMD-2378. Salary support: FIS to MDSN and ABS (Miguel Servet), Beatriz Fernandez-Fernandez (Rio Hortega). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO. IIS-FJD Biobank RD09/0076/0010

Pollutants make rheumatic diseases worse: Facts on polychlorinated biphenyls (PCBs) exposure and rheumatic diseases

Background Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in adipose tissue, disturbing its metabolism and the balance of adipokines, related to obesity. The altering secretion pattern of adipokines from the adipose tissue and the increasing mechanical load in weight-bearing joints presented in obesity condition, are risk factors for osteoarthritis development. The most prevalent rheumatic diseases, osteoarthritis and rheumatoid arthritis, are chronic conditions that target the whole joints, leading to increasing disability and health care cost. The goal of this focused review is to summarize the current knowledge on the role of PCBs in osteoarthritis and rheumatoid arthritis pathogenesis. Search strategy A PubMed search was managed using keywords as “rheumatic diseases”, “polychlorinated biphenyls”, “obesity” and “endocrine disruption”. Main results of the review The incidence of rheumatoid arthritis has been reported to be increased especially in urban areas in industrialized countries, emphasizing the importance of environment in the pathogenesis of rheumatic diseases. Analysis of two cohorts exposed to PCBs food contamination showed high incidence of arthritis. In addition, PCBs in serum correlated positively with the prevalence of self-reported arthritis. Few studies support the hypothesis that osteoarthritis development could be related to PCBs induction of chondrocytes apoptosis. Conclusion Evidences have emerged for a relationship between PCBs and development of several types of arthritis. Further research is encouraged to determine the correlation between PCBs exposure and the development of rheumatic diseases

Total Absorption Spectroscopy Study of 92^{92}Rb Decay: A Major Contributor to Reactor Antineutrino Spectrum Shape

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. $^{92}$Rb makes the dominant contribution to the reactor spectrum in the 5-8 MeV range but its decay properties are in question. We have studied $^{92}$Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed.Comment: 6 pages, 3 figure

Epi-and Mesopelagic Fishes, Acoustic Data, and SST Images Collected Off Lanzarote, Fuerteventura, and Gran Canaria, Canary Islands, During Cruise La Bocaina 04-97

During cruise La Bocaina 0497 a series of 14 tows with a commercial pelagic trawl at depths between 20 and 700 m and an acoustic survey with a SIMRAD EK-500 echosounder were carried out in neritic and adjacent oceanic waters off Lanzarote, Fuerteventura, and Gran Canaria, Canary islands. In addition, SST images were obtained to get some informations on the prevailing hydrological conditions in the study area. Of the 14 trawl tows ten were successful and resulted in capture of a total of 2166 fishes belonging to 81 species, 53 genera and 28 families. Ten species proved to be new records for the area of the Canary Islands. The acoustic survey covered a total of 2404 nm2 and allowed to obtain estimates of the abundance and biomass of fishes. Both the fishing results and the acoustic study revealed considerable spatial variability in biomass of chub mackerel, Scomber japonicus, an epipelagic species of particular fisheries interest, showing clear variations in the numerical dominance of certain age- or size classes among different collecting localities. Furthermore, some juveniles in the first year of life occurred in the oceanic epipelagic during night together with vertically migrating mesopelagic fishes. Preliminary analyses of the stomach and intestinal content suggest that these juveniles fed close to the bottom during the day before and hence may undertake diurnal horizontal migrations between the shelf and adjacent oceanic waters. It is concluded that the great spatial flexibility of this species requires further monitoring surveys at regular intervals as a basis for establishing a sustainable fisheries management. The acoustic data together with the trawling results demonstrate the existence of a dense deep scattering layer at depths between 400 and 700 m which is composed of mesopelagic fishes and invertebrates. Clear indications of diurnal vertical migrations were found in several species with formation of a shallow scattering layer in less than 150 m depth during night. Together with typical mesopelagic species such as stomiids and myctophids also juveniles of three benthopelagic species, which typically undergo a pelagic stage during early life, were collected. Several individuals of mesopelagic species were collected above the shelf what may reflect the ecological boundary situation at ocean rims typical for oceanic islands and seamounts. Some mesopelagic species collected in this study may be closely associated with distinct hydrological conditions such as the myctophid Ceratoscopelus maderensis which was discovered in the SE of Fuerteventura in an area of possible local upwelling. This finding points to the existence of micro-zoogeographic zones within the Canary islands which derserve further investigation using a small-scaled comparative approach

New constraints on protostellar jet collimation from high-density gas UV tracers

The analysis of high-resolution profiles of the semiforbidden UV lines of C III](1908) and Si III](1892) in the spectra of T Tauri stars (TTSs) shows the following : (1) There is C III](1908) and Si III](1892) emission at velocities that are similar to those observed in the optical forbidden lines formed in the TTSs jets. The luminosity of the UV lines is comparable to that of the optical lines. (2) The comparison between the optical and UV light curves indicates that the C III](1908) and Si III](1892) emission of RY Tau is not associated with accretion shocks, but it is produced farther than 2 R-* from the star. (3) The profiles of the UV semiforbidden lines are significantly broader than those of the optical forbidden lines. These profiles cannot be produced in a narrow collimated beam, and they are most likely produced in a bow-shaped shock wave formed at the base of the optical jet, where the hot gas emits in a broad range of projected radial velocities. (4) The atmosphere of RU Lup contributes significantly to the Si III](1892) emission. (5) A puzzling narrow feature is observed close to the C III](1908) line. The feature is blueshifted by -260 km s(-1), which corresponds to the wind terminal velocity measured in the P Cygni profile of the Mg II (UV1) lines. Moreover, constraints are derived on the characteristics of the C III](1908) and Si III](1892) emitting region in RY Tau. It is shown that 4.7 less than or equal to log T-e less than or equal to 5.0 and 10(9) cm(-3) less than or equal to N-e less than or equal to 10(11) cm(-3) provided that the emission is produced in a collisional plasma and that the 1665 Angstrom feature observed in low-dispersion International Ultraviolet Explorer (IUE) spectra is confirmed to be O III](1665) emission produced in the wind. These very high densities are difficult to generate in the shocks produced by the magnetic pinching of centrifugally driven magnetized disk winds. The data also suggest that the shocked layer has a radius of some few stellar radii and it is closer than similar to 38 R-* to the star

Experimental study of the hydrodynamic behaviour of slug flow in a horizontal pipe

This paper investigates the unsteady hydrodynamic behaviour of slug flow occurring within an air–silicone oil mixture, within a horizontal 67 mm internal diameter pipe. A series of slug flow regime experiments were performed for a range of injected air superficial velocities (0.29–1.4 m s−1) and for liquid flows with superficial velocities of between 0.05–0.47 m s−1. A pair of Electrical Capacitance Tomography (ECT) probes was used to determine: the slug translational velocities of the elongated bubbles and liquid slugs, the slug frequencies, the lengths of elongated bubbles and the liquid slugs, the void fractions within the elongated bubbles and liquid slugs. The pressure drop experienced along the pipe was measured using a differential pressure transducer cell (DP cell). A comparative analysis of the current experimental data and that previously published experimental confirms good agreement