Beating heart coronary surgery and renal function: a prospective randomised study (Presented at 18th Spring Meeting of the Association of Cardiothoracic Anaesthetists: Selected abstracts, Cambridge, UK. 22 June 2001)

Introduction Cardiopulmonary bypass (CPB) is widely regarded as an important contributor to renal failure, a well recognised complication, following coronary artery surgery (CABG). Off-pump coronary surgery (OPCAB) is intuitively considered renoprotective. We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass (ONCAB).Methods Forty patients awaiting elective CABG were prospectively randomized into those undergoing OPCAB (n = 20) and ONCAB (n = 20). Table 1 illustrates the exclusion criteria. Glomerular and tubular injury were assessed, respectively, by urinary excretion of microalbumin and retinol binding protein (RBP) indexed to urinary creatinine [1]. Daily measurements were made from admission to postoperative day 5. Fluid balance, serum creati-nine and blood urea were also monitored. Results No mortality or renal complication was observed. Both groups had similar demographic make-up. The OPCAB group received fewer coronary grafts than their counterparts (1.8 versus 2.8; P = 0.002). Serum creatinine and blood urea remained normal in both groups throughout the study. A dramatic and similar rise in mean ± 2SD urinary RBP:creatinine ratio occurred in both groups peaking on day 1 (3183 ± 2534 versus 4035 ± 4078; P = 0.43) before returning to baseline levels. These trends were also observed with the urinary microalbumin:creatinine ratio (5.05 ± 2.66 versus 6.77 ± 5.76; P = 0.22). ONCAB patients had a significantly more negative fluid balance on postoperative day 2 (-183 ± 1118 versus 637 ± 847 ml; P < 0.05). Conclusions Although renal dysfunction did not clinically occur in any patient, sensitive indicators revealed significant and similar injury to both renal tubules and glomeruli following either OPCAB or ONCAB. These suggest that avoidance of CPB per se does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG

{beta}3GnT2 Maintains Adenylyl Cyclase-3 Signaling and Axon Guidance Molecule Expression in the Olfactory Epithelium

In the olfactory epithelium (OE), odorant receptor stimulation generates cAMP signals that function in both odor detection and the regulation of axon guidance molecule expression. The enzyme that synthesizes cAMP, adenylyl cyclase 3 (AC3), is coexpressed in olfactory sensory neurons (OSNs) with poly-N-acetyllactosamine (PLN) oligosaccharides determined by the glycosyltransferase beta3GnT2. The loss of either enzyme results in similar defects in olfactory bulb (OB) innervation and OSN survival, suggesting that glycosylation may be important for AC3 function. We show here that AC3 is extensively modified with N-linked PLN, which is essential for AC3 activity and localization. On Western blots, AC3 from the wild-type OE migrates diffusely as a heavily glycosylated 200 kDa band that interacts with the PLN-binding lectin LEA. AC3 from the beta3GnT2(-/-) OE loses these PLN modifications, migrating instead as a 140 kDa glycoprotein. Furthermore, basal and forskolin-stimulated cAMP production is reduced 80-90% in the beta3GnT2(-/-) OE. Although AC3 traffics normally to null OSN cilia, it is absent from axon projections that aberrantly target the OB. The cAMP-dependent guidance receptor neuropilin-1 is also lost from beta3GnT2(-/-) OSNs and axons, while semaphorin-3A ligand expression is upregulated. In addition, kirrel2, a mosaically expressed adhesion molecule that functions in axon sorting, is absent from beta3GnT2(-/-) OB projections. These results demonstrate that PLN glycans are essential in OSNs for proper AC3 localization and function. We propose that the loss of cAMP-dependent guidance cues is also a critical factor in the severe axon guidance defects observed in beta3GnT2(-/-) mice

Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance

<p>Abstract</p> <p>Background</p> <p>The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2^−/− mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2^−/− neurons.</p> <p>Results</p> <p>Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2^−/− mice compared to controls. Analysis of OR expression by quantitative PCR and <it>in situ</it> hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2^−/− olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2^−/− mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, <it>in situ</it> hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2^−/− olfactory neurons.</p> <p>Conclusions</p> <p>Results presented here show that many odorant receptors are under-expressed in β3GnT2^−/− mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2^−/− mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2^−/− mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.</p

Discovery of two new super-eruptions from the Yellowstone hotspot track (USA): is the Yellowstone hotspot waning?

Super-eruptions are amongst the most extreme events to affect Earth’s surface, but too few examples are known to assess their global role in crustal processes and environmental impact. We demonstrate a robust approach to recognize them at one of the best-preserved intraplate large igneous provinces, leading to the discovery of two new super-eruptions. Each generated huge and unusually hot pyroclastic density currents that sterilized extensive tracts of Idaho and Nevada in the United States. The ca. 8.99 Ma McMullen Creek eruption was magnitude 8.6, larger than the last two major eruptions at Yellowstone (Wyoming). Its volume exceeds 1700 km3, covering ≥12,000 km2. The ca. 8.72 Ma Grey’s Landing eruption was even larger, at magnitude of 8.8 and volume of ≥2800 km3. It covers ≥23,000 km2 and is the largest and hottest documented eruption from the Yellowstone hotspot. The discoveries show the effectiveness of distinguishing and tracing vast deposit sheets by combining trace-element chemistry and mineral compositions with field and paleomagnetic characterization. This approach should lead to more discoveries and size estimates, here and at other provinces. It has increased the number of known super-eruptions from the Yellowstone hotspot, shows that the temporal framework of the magmatic province needs revision, and suggests that the hotspot may be waning

Tectonic and Crustal Processes Drive Multi-Million Year Arc Magma Evolution Leading up to Porphyry Copper Deposit Formation in Central Chile

Subduction zone magmatism is a major control of volcanism, the generation of modern continental crust and the formation of economically important porphyry Cu–(Mo–Au) deposits. Reading the magmatic record of individual arc segments and constraining the rates of magmatic changes are critical in order to fully understand and quantify the processes that drive magma evolution in subduction settings during arc growth. This study focuses on the San Francisco Batholith and the Rio Blanco-Los Bronces porphyry deposit cluster in central Chile, which provides an igneous rock record over ~13.5 Myr of arc evolution. We use whole-rock geochemistry, zircon geochronology and Hf isotope geochemistry to track changes in the crustal magmatic system of this arc segment during crustal thickening and porphyry Cu deposit formation. By combining the analytical dataset with Monte Carlo fractional crystallisation and assimilation fractional crystallisation modelling, we test a model for significant crustal involvement during magma evolution. Systematic and continuous increases in Dy/Yb, La/Yb, V/Sc and Sr/Y in the magmas over time indicate a transition in the main fractionation assemblage from plagioclase-dominated to amphibole-dominated that reflects deeper crystallisation and/or a higher meltwater content. Concomitant decreases in εHf and Th/La as well as increasing Ba/Th are best explained by assimilation of progressively deeper crustal lithologies from low (Chilenia) to high Ba/Th (Cuyania) basement terranes. Our study highlights that an increasingly hydrous magma and a deepening locus of crustal magma differentiation and assimilation, driven by crustal thickening contemporaneous with increased tectonic convergence and ingression of the aseismic Juan Fernandez ridge, can account for all investigated aspects of the multi-Myr magmatic evolution leading up to the formation of the Rio Blanco-Los Bronces porphyry Cu deposits. Our findings corroborate the importance of high-pressure differentiation of hydrous magma for the formation of Andean-style porphyry deposits. Once magmas favourable for porphyry Cu mineralisation were generated in the lower crust, multiple episodes of efficient magma migration into the upper crust fed several, discrete, shallow magmatic-hydrothermal systems over ~3.5 Myr to form the world’s largest known Cu resource at Rio Blanco-Los Bronces

The Dialectics of Identity of the Modern and Postmodern Art

Ako pojam identiteta shvatimo u hegelijanskom smislu kao iskustvo što ga svijest stječe o sebi, onda se taj pojam nameće kao ključan u razmatranju (vizualne) umjetnosti XX. stoljeća. Prema Hegelu, moderna umjetnost transcendira mogućnost adekvatnog izražavanja svoga duhovnog sadržaja pukom osjetilnom reprezentacijom (koja je kao takvu određuje) te stoga zahtijeva pojmovnu refleksiju. Budući da je umjetnost uvijek i dio stvarnosti i o stvarnosti, propitivanje njezina vlastita pojma ide ruku pod ruku s ontološkom problematikom. Epistemološke promjene koje konstituiraju i modernu i postmodernu odražavaju se tako u dijalektici pojma moderne i postmoderne umjetnosti. Prema nekim autorima ta je dijalektika određena značajnim promjenama u teoriji subjekta, kulturalnim razlikama i tehnologiji.If the notion of identity is considered in the Hegelian sense as the experience of the consciousness about itself, then this notion becomes of key importance in reflecting upon the 20th-century (visual) art. Modern art, in Hegel’s view, transcends the possibility of an adequate expression of its spiritual content by its merely sensuous representation (that defines it as such) and hence calls for a reflection on its notion. Since art has always been both part of and about reality, the questioning of its own notion goes hand in hand with the ontological problematics. The epistemological changes that constitute both Modernism and Postmodernism thus reflect themselves in the dialectics of the notion of modern and postmodern art. According to some authors, such dialectics is determined by important changes which took place in the theory of the subject, in cultural differences as well as in technology

Mobilisation of deep crustal sulfide melts as a first order control on upper lithospheric metallogeny

Magmatic arcs are terrestrial environments where lithospheric cycling and recycling of metals and volatiles is enhanced. However, the first-order mechanism permitting the episodic fluxing of these elements from the mantle through to the outer Earth’s spheres has been elusive. To address this knowledge gap, we focus on the textural and minero-chemical characteristics of metal-rich magmatic sulfides hosted in amphibole-olivine-pyroxene cumulates in the lowermost crust. We show that in cumulates that were subject to increasing temperature due to prolonged mafic magmatism, which only occurs episodically during the complex evolution of any magmatic arc, Cu-Au-rich sulfide can exist as liquid while Ni-Fe rich sulfide occurs as a solid phase. This scenario occurs within a ‘Goldilocks’ temperature zone at ~1100–1200 °C, typical of the base of the crust in arcs, which permits episodic fractionation and mobilisation of Cu-Au-rich sulfide liquid into permeable melt networks that may ascend through the lithosphere providing metals for porphyry and epithermal ore deposits

SAS-1 Is a C2 Domain Protein Critical for Centriole Integrity in C. elegans

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C. elegans sas-1 in a genetic screen as a locus required for bipolar spindle assembly in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is lacking. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles in C. elegans, and which can bind and stabilize microtubules when expressed in human cells. Moreover, we uncover that SAS-1 is related to C2CD3, a protein required for complete centriole formation in human cells and affected in a type of oral-facial-digital (OFD) syndrome

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Single nucleotide polymorphisms in several porcine cathepsin genes are associated with growth, carcass, and production traits in Italian Large White pigs

To identify DNA markers associated with performance, carcass, and meat production traits including muscle postmortem cathepsin activity, sev- eral porcine genes encoding for lysosomal proteinases (cathepsin B, CTSB; cathepsin D, CTSD; cathepsin F, CTSF; cathepsin H, CTSH; cathepsin L, CTSL; and cathepsin Z, CTSZ) and for a cathepsin inhibitor (cys- tatin B) were investigated. Single nucleotide polymor- phisms were identified in CTSD, CTSH, CTSL, and CTSZ genes with a combination of in silico expressed sequence tag database mining and single-strand confor- mation polymorphism analysis. Sequencing and PCR- RFLP protocols were used to validate the identified polymorphisms. Allele frequencies at these loci were investigated in Italian Large White, Landrace, Duroc, Pietrain, Belgian Landrace, Hampshire, and Meishan breeds. Genotyping CTSD and CTSH markers made it possible to genetically map these genes to SSC 2 and 7, respectively. Markers in CTSD, CTSH, CTSL, and CTSZ genes, together with mutations we previously re- ported in cystatin B, CTSB, and CTSF genes, were genotyped in an Italian Large White sib-tested popu- lation (272 or 482 animals). For these animals, meat quality traits (cathepsin B activity, pH measured at 2 h postmortem, pH measured at 24 h postmortem, glyco- gen, lactate, and glycolytic potential of semimembrano- sus muscle) and EBV for ADG, lean cuts (LC), backfat thickness (BFT), ham weight (HW), and feed:gain ra- tio (FGR) were determined. Analyzed markers did not show any association with muscle cathepsin B activity. Thus, it could be possible that different genes, other than these investigated candidates, affect this trait, which is correlated with the excessive softness defect of dry-cured hams. The results of association analysis confirmed the effects we already reported in another study for CTSF on ADG (P = 0.008), LC (P = 0.001), and BFT (P = 0.02). Moreover, CTSD was associated with ADG, LC (P < 0.0001), BFT, HW, and FGR (P < 0.001); CTSH was associated with FGR (P = 0.026); and CTSZ was associated with ADG (P = 0.006), LC (P = 0.01), HW (P = 0.024), and FGR (P = 0.029). The biochemical and physiological functions of the lys- osomal proteinases, together with the results obtained in our investigation, suggest that the cathepsin gene family might play important roles affecting economic traits in pigs