Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Cantú syndrome with coexisting familial pituitary adenoma

Context: Pseudoacromegaly describes conditions with an acromegaly related physical appearance without abnormalities in the growth hormone (GH) axis. Acromegaloid facies, together with hypertrichosis, are typical manifestations of Cantú syndrome. Case description: We present a three-generation family with 5 affected members, with marked acromegaloid facies and prominent hypertrichosis, due to a novel missense variant in the ABCC9 gene. The proband, a 2-year-old girl, was referred due to marked hypertrichosis, noticed soon after birth, associated with coarsening of her facial appearance. Her endocrine assessment, including of the GH axis, was normal. The proband's father, paternal aunt, and half-sibling were referred to the Endocrine department for exclusion of acromegaly. Although the GH axis was normal in all, two subjects had clinically non-functioning pituitary macroadenomas, a feature which has not previously been associated with Cantú syndrome. Conclusions: Activating mutations in the ABCC9 and, less commonly, KCNJ8 genes—representing the two subunits of the ATP-sensitive potassium channel—have been linked with Cantú syndrome. Interestingly, minoxidil, a well-known ATP-sensitive potassium channel agonist, can cause a similar phenotype. There is no clear explanation why activating this channel would lead to acromegaloid features or hypertrichosis. This report raises awareness for this complex condition, especially for adult or pediatric endocrinologists who might see these patients referred for evaluation of acromegaloid features or hirsutism. The link between Cantú syndrome and pituitary adenomas is currently unclear

Learning Biomarker Models for Progression Estimation of Alzheimer’s Disease

Being able to estimate a patient’s progress in the course of Alzheimer’s disease and predicting future progression based on a number of observed biomarker values is of great interest for patients, clinicians and researchers alike. In this work, an approach for disease progress estimation is presented. Based on a set of subjects that convert to a more severe disease stage during the study, models that describe typical trajectories of biomarker values in the course of disease are learned using quantile regression. A novel probabilistic method is then derived to estimate the current disease progress as well as the rate of progression of an individual by fitting acquired biomarkers to the models. A particular strength of the method is its ability to naturally handle missing data. This means, it is applicable even if individual biomarker measurements are missing for a subject without requiring a retraining of the model. The functionality of the presented method is demonstrated using synthetic and—employing cognitive scores and image-based biomarkers—real data from the ADNI study. Further, three possible applications for progress estimation are demonstrated to underline the versatility of the approach: classification, construction of a spatio-temporal disease progression atlas and prediction of future disease progression

Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in cardiac surgery? A meta-analysis of randomized head-to-head trials

BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative blood loss and the need for re-operation due to continued bleeding in cardiac surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are cheaper, but it is not known if they are as effective as aprotinin. METHODS: Studies were identified by searching electronic databases and bibliographies of published articles. Data from head-to-head trials were pooled using a conventional (Cochrane) meta-analytic approach and a Bayesian approach which estimated the posterior probability of TXA and EACA being equivalent to aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of transfusion or re-operation because of bleeding. RESULTS: Peri-operative blood loss was significantly greater with TXA and EACA than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority boundary, the posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion of one small trial. CONCLUSION: The available data are conflicting regarding the equivalence of lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion and the need for re-operation. Decisions are sensitive to the choice of clinical outcome and non-inferiority boundary. The data are an uncertain basis for replacing aprotinin with the cheaper lysine analogues in clinical practice. Progress has been hampered by small trials and failure to study clinically relevant outcomes

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Comparison of Promoter Hypermethylation Pattern in Salivary Rinses Collected with and without an Exfoliating Brush from Patients with HNSCC

Background: Salivary rinses have been recently proposed as a valuable resource for the development of epigenetic biomarkers for detection and monitoring of head and neck squamous cell carcinoma (HNSCC). Both salivary rinses collected with and without an exfoliating brush from patients with HNSCC are used in detection of promoter hypermethylation, yet their correlation of promoter hypermethylation has not been evaluated. This study was to evaluate the concordance of promoter hypermethylation between salivary rinses collected with and without an exfoliating brush from patients with HNSCC. Methodolgy: 57 paired salivary rinses collected with or without an exfoliating brush from identical HNSCC patients were evaluated for promoter hypermethylation status using Quantitative Methylation-Specific PCR. Target tumor suppressor gene promoter regions were selected based on our previous studies describing a panel for HNSCC screening an

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Induction of androgenesis and production of haploid embryos in anther cultures of borage (Borago officinalis L.)

[EN] Borage (Borago officinalis L.) is an important medicinal plant with different culinary, pharmaceutical and industrial properties. Unfortunately, there are no published reports on the establishment of protocols to produce DHs in this species up to now. In this work, we show for the first time the induction of borage microspores to become embryogenic calli, from which haploid embryos are produced. In addition, we evaluated the effect of using different flower bud sizes, carbon sources, concentrations of 2,4-D and BAP, cold (4 A degrees C) pretreatments and heat shock treatments. Production of total calli, embryogenic calli and callus-derived embryos was differently affected by the different parameters studied. Our results showed that the use of 5-7 mm-long flower buds, a cold (4 A degrees C) pretreatment during 4 days, a 32 A degrees C heat shock for 3 days, and the addition of 3 % maltose and 2 mgl(-1) 2,4-D and 1 mgl(-1) BAP to the culture medium, was beneficial for embryo production. Overall, this work demonstrates that DH technology is possible in borage, and opens the door for future improvements needed to finally obtain borage DH plants.Eshaghi, ZC.; Abdollahi, MR.; Moosavi, SS.; Deljou, A.; Seguí-Simarro, JM. (2015). Induction of androgenesis and production of haploid embryos in anther cultures of borage (Borago officinalis L.). Plant Cell, Tissue and Organ Culture. 122:321-329. doi:10.1007/s11240-015-0768-5S321329122Abdollahi MR, Moieni A, Javaran MJ (2004) Interactive effects of shock and culture density on embryo induction in isolated microspore culture of Brassica napus L. cv. Global Iranian J Biotech 2:97–100Bohanec B, Neskovic M, Vujicic R (1993) Anther culture and androgenetic plant regeneration in buckwheat (Fagopyrum esculentum Moench). Plant Cell Tissue Organ Cult 35:259–266Calleberg E, Johansson L (1996) Effect of gelling agents on anther cultures. In: Jain SM, Sopory SK, Veilleux RE (eds) In vitro haploid production in higher plants, vol 23. Springer, Netherlands, pp 189–203Custers JBM, Cordewener JHG, Nöllen Y, Dons JJ, van Lookeren-Campagne MM (1994) Temperature controls both gametophytic and sporophytic development in microspore cultures of Brassica napus. Plant Cell Rep 13:267–271Ferrie AMR (2013) Advances in microspore culture technology: a biotechnological tool for the improvement of medicinal plants. In: Chandra S et al (eds) Biotechnology for medicinal plants. Springer, Berlin, pp 191–206Ferrie AMR, Caswell KL (2011) Isolated microspore culture techniques and recent progress for haploid and doubled haploid plant production. Plant Cell Tissue Organ Cult 104:301–309Ferrie AMR, Bethune T, Mykytyshyn M (2011) Microspore embryogenesis in the Apiaceae. Plant Cell Tissue Organ Cult 104:399–406Forster BP, Heberle-Bors E, Kasha KJ, Touraev A (2007) The resurgence of haploids in higher plants. Trends Plant Sci 12:368–375Gamborg OL, Miller RA, Ojiwa K (1968) Nutrient requirements of suspension culture of soybean root callus. Exp Cell Res 50:151–158Guil-Guerrero JL, García-Maroto F, Vilches-Ferrón MA, López-Alonso D (2003) Gamma-linolenic acid from fourteen Boraginaceae species. Ind Crop Prod 18:85–89Horrobin DF (1983) The regulation of prostaglandin biosynthesis by the manipulation of essential fatty acid metabolism. Rev Pure Appl Pharmacol Sci 4:339–383Irikova T, Grozeva S, Rodeva V (2011) Anther culture in pepper (Capsicum annuum L.) in vitro. Acta Physiol Plant 33:1559–1570Lauxen MS, Kaltchuk-Santos E, Hu CY, Callegari-Jacques SM, Bodanese-Zanettini MH (2003) Association between floral bud size and developmental stage in soybean microspores. Braz Arch Biol Technol 46:515–520Leach CR, Mayo O, Bürger R (1990) Quantitatively determined self-incompatibility. Outcrossing in Borago officinalis. Theoret Appl Genetics 79:427–430Lichter R (1982) Induction of haploid plants from isolated pollen of Brassica napus. Z Pflanzenphysiol 105:427–434Maluszynski M, Kasha KJ, Szarejko I (2003) Published doubled haploid protocols in plant species. In: Maluszynski M, Kasha KJ, Forster BP, Szarejko I (eds) Doubled haploid production in crop plants. A manual. Kluwer, Dordrecht, pp 309–335Maraschin SF, de Priester W, Spaink HP, Wang M (2005) Androgenic switch: an example of plant embryogenesis from the male gametophyte perspective. J Exp Bot 56:1711–1726McDonald BE, Fitzpatrick K (1998) Designer Vegetable Oils. In: Mazza G (ed) Functional foods, biochemical and processing aspects. Technomic Publ Co. Inc, Lancaster, pp 265–291Ozkum D, Tipirdamaz R (2002) The effects of cold treatment and charcoal on the in vitro androgenesis of pepper (Capsicum annuum L.). Turk J Bot 26:131–139Parra-Vega V, González-García B, Seguí-Simarro JM (2013a) Morphological markers to correlate bud and anther development with microsporogenesis and microgametogenesis in pepper (Capsicum annuum L.). Acta Physiol Plant 35:627–633Parra-Vega V, Renau-Morata B, Sifres A, Seguí-Simarro JM (2013b) Stress treatments and in vitro culture conditions influence microspore embryogenesis and growth of callus from anther walls of sweet pepper (Capsicum annuum L.). Plant Cell Tissue Organ Cult 112:353–360Raquin C (1983) Utilization of different sugars as carbon sources for in vitro cultures of Petuina. Z Pflanzenphysol 111:453–457Salas P, Rivas-Sendra A, Prohens J, Seguí-Simarro JM (2012) Influence of the stage for anther excision and heterostyly in embryogenesis induction from eggplant anther cultures. Euphytica 184:235–250Seguí-Simarro JM (2010) Androgenesis revisited. Bot Rev 76:377–404Seguí-Simarro JM, Nuez F (2006) Androgenesis induction from tomato anther cultures: callus characterization. Acta Hort 725:855–861Seguí-Simarro JM, Corral-Martínez P, Parra-Vega V, González-García B (2011) Androgenesis in recalcitrant solanaceous crops. Plant Cell Rep 30:765–778Shariatpanahi ME, Bal U, Heberle-Bors E, Touraev A (2006) Stresses applied for the reprogramming of plant microspores towards in vitro embryogenesis. Physiol Plant 127:519–534Simon JE, Chadwick AF, Craker LE (1984) Herbs: an indexed bibliography. 1971–1980. The scientific literature on selected herbs, and aromatic and medicinal plants of the temperate zone. Archon Books, Hamden, CTSkrzypek E, Czyczyło-Mysza I, Marcińska I, Wędzony M (2008) Prospects of androgenetic induction in Lupinus spp. Plant Cell Tissue Organ Cult 94(2):131–137Snape JW (1989) Doubled haploid breeding: theoretical basis and practical applications. In: Mujeeb-Kazi A, Sitch LA (eds) Review of advances in plant biotechnology, 1985–1988: 2nd international symposium genetic manipulation in crops. Mexico and Manila, CIMMYT and IRRI, pp 19–30Tipirdamaz R, Ellialtioğlu Ş (1998) The effects of cold treatments and activated charcoal on ABA contents of anthers and in vitro androgenesis in eggplant (Solanum melongena L.). In: Tsekos I, Moustakas M (eds) Progress in botanical research, Proceedings of the 1st Balkan botanical congress. Kluwer Academic Publishers, The NetherlandsVagera J, Havranek P (1985) In vitro induction of androgenesis in Capsicum annuum L. and its genetic aspests. Biol Plant 27(1):10–21Zur I, Dubas E, Golemiec E, Szechynska-Hebda M, Golebiowska G, Wedzony M (2009) Stress-related variation in antioxidative enzymes activity and cell metabolism efficiency associated with embryogenesis induction in isolated microspore culture of triticale (×Triticosecale Wittm.). Plant Cell Rep 28:1279–128

Modular hybrid total hip arthroplasty. Experimental study in dogs

Background: This prospective experimental study evaluated the surgical procedure and results of modular hybrid total hip arthroplasty in dogs.Methods: Ten skeletally mature healthy mongrel dogs with weights varying between 19 and 27 kg were used. Cemented modular femoral stems and uncemented porous-coated acetabular cups were employed. Clinical and radiographic evaluations were performed before surgery and at 30, 60, 90, 120, 180 and 360 days post-operation.Results: Excellent weight bearing was noticed in the operated limb in seven dogs. Dislocation followed by loosening of the prosthesis was noticed in two dogs, which were therefore properly treated with a femoral head osteotomy. Femoral fracture occurred in one dog, which was promptly treated with full implant removal and femoral osteosynthesis.Conclusions: The canine modular hybrid total hip arthroplasty provided excellent functionality of the operated limb

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente