Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study

Objectives: To assess the effect on clinical outcome of managing paediatric and adult patients with cystic fibrosis at specialised cystic fibrosis centres.

Molecular Analysis of (R)-(+)-Mandelonitrile Lyase Microheterogeneity in Black Cherry1

The flavoprotein (R)-(+)-mandelonitrile lyase (MDL; EC 4.1.2.10), which plays a key role in cyanogenesis in rosaceous stone fruits, occurs in black cherry (Prunus serotina Ehrh.) homogenates as several closely related isoforms. Biochemical and molecular biological methods were used to investigate MDL microheterogeneity and function in this species. Three novel MDL cDNAs of high sequence identity (designated MDL2, MDL4, and MDL5) were isolated. Like MDL1 and MDL3 cDNAs (Z. Hu, J.E. Poulton [1997] Plant Physiol 115: 1359–1369), they had open reading frames that predicted a flavin adenine dinucleotide-binding site, multiple N-glycosylation sites, and an N-terminal signal sequence. The N terminus of an MDL isoform purified from seedlings matched the derived amino acid sequence of the MDL4 cDNA. Genomic sequences corresponding to the MDL1, MDL2, and MDL4 cDNAs were obtained by polymerase chain reaction amplification of genomic DNA. Like the previously reported mdl3 gene, these genes are interrupted at identical positions by three short, conserved introns. Given their overall similarity, we conclude that the genes mdl1, mdl2, mdl3, mdl4, and mdl5 are derived from a common ancestral gene and constitute members of a gene family. Genomic Southern-blot analysis showed that this family has approximately eight members. Northern-blot analysis using gene-specific probes revealed differential expression of the genes mdl1, mdl2, mdl3, mdl4, and mdl5.

Heat-Shock-Induced Changes in Intracellular Ca2+ Level in Tobacco Seedlings in Relation to Thermotolerance1

Exposure of plants to elevated temperatures results in a complex set of changes in gene expression that induce thermotolerance and improve cellular survival to subsequent stress. Pretreatment of young tobacco (Nicotiana plumbaginifolia) seedlings with Ca2+ or ethylene glycol-bis(β-aminoethylether)-N,N,N′,N′-tetraacetic acid enhanced or diminished subsequent thermotolerance, respectively, compared with untreated seedlings, suggesting a possible involvement of cytosolic Ca2+ in heat-shock (HS) signal transduction. Using tobacco seedlings transformed with the Ca2+-sensitive, luminescent protein aequorin, we observed that HS temperatures induced prolonged but transient increases in cytoplasmic but not chloroplastic Ca2+. A single HS initiated a refractory period in which additional HS signals failed to increase cytosolic Ca2+. However, throughout this refractory period, seedlings responded to mechanical stimulation or cold shock with cytosolic Ca2+ increases similar to untreated controls. These observations suggest that there may be specific pools of cytosolic Ca2+ mobilized by heat treatments or that the refractory period results from a temporary block in HS perception or transduction. Use of inhibitors suggests that HS mobilizes cytosolic Ca2+ from both intracellular and extracellular sources.

Functional analysis of retinoid Z receptor beta, a brain-specific nuclear orphan receptor.

The retinoid Z receptor beta (RZR beta), an orphan receptor, is a member of the retinoic acid receptor (RAR)/thyroid hormone receptor (TR) subfamily of nuclear receptors. RZR beta exhibits a highly restricted brain-specific expression pattern. So far, no natural RZR beta target gene has been identified and the physiological role of the receptor in transcriptional regulation remains to be elucidated. Electrophoretic mobility shift assays reveal binding of RZR beta to monomeric response elements containing the sequence AnnTAGGTCA, but RZR beta-mediated transactivation of reporter genes is only achieved with two property spaced binding sites. We present evidence that RZR beta can function as a cell-type-specific transactivator. In neuronal cells, GaI-RZR beta fusion proteins function as potent transcriptional activators, whereas no transactivation can be observed in nonneuronal cells. Mutational analyses demonstrate that the activation domain (AF-2) of RZR beta and RAR alpha are functionally interchangeable. However, in contrast to RAR and TR, the RZR beta AF-2 cannot function autonomously as a transactivation domain. Furthermore, our data define a novel repressor function for the C-terminal part of the putative ligand binding domain. We propose that the transcriptional activity of RZR beta is regulated by an interplay of different receptor domains with coactivators and corepressors.

In vitro binding of type 1-fimbriated Escherichia coli to uroplakins Ia and Ib: relation to urinary tract infections.

Urinary tract infections, caused mainly by Escherichia coli, are among the most common infectious diseases. Most isolates of the uropathogenic E.coli can express type 1 and P fimbriae containing adhesins that recognize cell receptors. While P fimbriae recognize kidney glycolipid receptors and are involved in peyelonephritis, the urothelial for type 1 fimbriae were not identified. We show that type 1-fimbriated E. coli recognize uroplakins Ia and Ib, two major glycoproteins of urothelial apical plaques. Anchorage of E. coli to urothelial surface via type 1 fimbriae-uroplakin I interactions may play a role in its bladder colonization and eventual ascent through the ureters, against urine flow, to invade the kidneys.

Postembryonic segregation of the germ line in sea urchins in relation to indirect development.

The four small micromeres of the sea urchin embryo contribute only to the coelomic sacs, which produce major components of the adult body plan during postembryonic development. To test the proposition that the small micromeres are the definitive primordial germ cell lineage of the sea urchin, we deleted their 4th cleavage parents, and raised the deleted embryos through larval life and metamorphosis to sexual maturity. Almost all of the experimental animals produced functional gametes, excluding the possibility that the germ cell lineage arises exclusively and obligatorily from descendants of the small micromeres; rather, the germ cell lineage arises during the postembryonic development of the rudiment. A survey of the literature indicates that there is no known case of an embryonic primordial germ cell lineage in a bilaterian species that displays maximal indirect development.

Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA.

A M(r) 140,000 protein has been purified from chicken lungs to apparent homogeneity. The protein binds with high affinity to a non-BNA conformation, which is most likely to the Z-DNA. The protein also has a binding site for double-stranded RNA (dsRNA). Peptide sequences from this protein show similarity to dsRNA adenosine deaminase, an enzyme that deaminates adenosine in dsRNA to form inosine. Assays for this enzyme confirm that dsRNA adenosine deaminase activity and Z-DNA binding are properties of the same molecule. The coupling of these two activities in a single molecule may indicate a distinctive mechanism of gene regulation that is, in part, dependent on DNA topology. As such, DNA topology, through its effects on the efficiency and extent of RNA editing may be important in the generation of new phenotypes during evolution.

Mass-metallicity relation explored with CALIFA I. Is there a dependence on the star-formation rate?

We studied the global and local ℳ-Z relation based on the first data available from the CALIFA survey (150 galaxies). This survey provides integral field spectroscopy of the complete optical extent of each galaxy (up to 2−3 effective radii), with a resolution high enough to separate individual H II regions and/or aggregations. About 3000 individual H II regions have been detected. The spectra cover the wavelength range between [OII]3727 and [SII]6731, with a sufficient signal-to-noise ratio to derive the oxygen abundance and star-formation rate associated with each region. In addition, we computed the integrated and spatially resolved stellar masses (and surface densities) based on SDSS photometric data. We explore the relations between the stellar mass, oxygen abundance and star-formation rate using this dataset. We derive a tight relation between the integrated stellar mass and the gas-phase abundance, with a dispersion lower than the one already reported in the literature (σ_Δlog (O/H) = 0.07 dex). Indeed, this dispersion is only slightly higher than the typical error derived for our oxygen abundances. However, we found no secondary relation with the star-formation rate other than the one induced by the primary relation of this quantity with the stellar mass. The analysis for our sample of ~3000 individual H II   regions confirms (i) a local mass-metallicity relation and (ii) the lack of a secondary relation with the star-formation rate. The same analysis was performed with similar results for the specific star-formation rate. Our results agree with the scenario in which gas recycling in galaxies, both locally and globally, is much faster than other typical timescales, such like that of gas accretion by inflow and/or metal loss due to outflows. In essence, late-type/disk-dominated galaxies seem to be in a quasi-steady situation, with a behavior similar to the one expected from an instantaneous recycling/closed-box model.

Using the R-PAS' Aggressive Content Score For the Evaluation of Aggressive Behaviors in Children

The Rorschach Performance Assessment System (R-PAS) was developed in 2011 as analternative to the previous Comprehensive System. The goal was to improve the psychometrics,and particularly the validity, of this assessment method. The norms for children werequestionable in the Comprehensive system (e.g., outdated, low numbers of subjects) and validitystudies for children were sparse. One of the indicators included in the R-PAS system, theaggressive content indicator (AgC), is intended to reflect aggressive behavior, but few studieshave examined the validity of this indicator. This study examined the validity of AgC in asample of 32 children and adolescents receiving services at a residential treatment center.Subjects' AgC scores were analyzed in relation to demographics and diagnosis, as well as ratingsof aggression and conduct problems from the Behavioral Assessment System for Children-2(BASC-2) Parent and Teacher Reports. Correlations between the AgC score and BASC-2aggression and conduct problems scores were not statistically significant. None of thecorrelations between AgC score and a diagnosis of Conduct Disorder, Oppositional DefiantDisorder, Posttraumatic Stress Disorder, or Mood Disorders were significant either. Given thesmall sample size, null results may be a result of power concerns. The lack of significantcorrelations may however, indicate that operational definitions of aggression used in variousforms of measurement reflect different constructs.

Testing diagnostics of nuclear activity and star formation in galaxies at z > 1

We present some of the first science data with the new Keck/MOSFIRE instrument to test the effectiveness of different AGN/SF diagnostics at z ~ 1.5. MOSFIRE spectra were obtained in three H-band multi-slit masks in the GOODS-S field, resulting in 2 hr exposures of 36 emission-line galaxies. We compare X-ray data with the traditional emission-line ratio diagnostics and the alternative mass-excitation and color-excitation diagrams, combining new MOSFIRE infrared data with previous HST/WFC3 infrared spectra (from the 3D-HST survey) and multiwavelength photometry. We demonstrate that a high [O III]/Hβ ratio is insufficient as an active galactic nucleus (AGN) indicator at z > 1. For the four X-ray-detected galaxies, the classic diagnostics ([O III]/Hβ versus [N II]/Hα and [S II]/Hα) remain consistent with X-ray AGN/SF classification. The X-ray data also suggest that "composite" galaxies (with intermediate AGN/SF classification) host bona fide AGNs. Nearly ~2/3 of the z ~ 1.5 emission-line galaxies have nuclear activity detected by either X-rays or the classic diagnostics. Compared to the X-ray and line ratio classifications, the mass-excitation method remains effective at z > 1, but we show that the color-excitation method requires a new calibration to successfully identify AGNs at these redshifts.

The evolutionary paths among galaxy types on the red sequence at 0.3 < Z < 1.5

We have studied the main evolutionary paths among the galaxy types residing on the massive end of the Red Sequence and nearby locations on the Green Valley during the last ∼9 Gyr. The morphological and star formation properties of a sample of these galaxies at 0 . 3 < z < 1 .5 with stellar masses M_∗ > 5 × 10^10 M_⊙ have been analysed. We present direct observational evidence for the first time of the existence of two main evolutionary paths among the different red galaxy types since z ∼ 1 .5, which provide some clues on the nature of the processes that have governed the assembly of present-day massive quiescent galaxies. The results are in excellent agreement with the hierarchical evolutionary framework proposed in the Eliche-Moral et al. (2010) model. Data from SHARDS (one of the ESO/GTC Large Programmes approved in 2009A) will complement and improve the present findings, shedding some light into many of the still unsettled questions concerning the migration of galaxies from the Blue Cloud to the Red Sequence at z < 1 .5.

Tanwīr al-Burhān

li-Ḥasan Ḥusnī al-Mawṣilī.

al- Khulāṣah al-naqīyah fī umarāʼ Ifrīqīyah: wa-maʻahu ʻUqūd al-farāʼid fī tadhyīl al-Khulāṣah wa-fawāʼid al-rāʼid lil-muʼallif ayḍan

taʼlīf Abī ʻAbd Allāh Muḥammad al-Bājī al-Masʻūdī.