A scientist's guide for submitting data to ZFIN.

The Zebrafish Model Organism Database (ZFIN; zfin.org) serves as the central repository for genetic and genomic data produced using zebrafish (Danio rerio). Data in ZFIN are either manually curated from peer-reviewed publications or submitted directly to ZFIN from various data repositories. Data types currently supported include mutants, transgenic lines, DNA constructs, gene expression, phenotypes, antibodies, morpholinos, TALENs, CRISPRs, disease models, movies, and images. The rapidly changing methods of genomic science have increased the production of data that cannot readily be represented in standard journal publications. These large data sets require web-based presentation. As the central repository for zebrafish research data, it has become increasingly important for ZFIN to provide the zebrafish research community with support for their data sets and guidance on what is required to submit these data to ZFIN. Regardless of their volume, all data that are submitted for inclusion in ZFIN must include a minimum set of information that describes the data. The aim of this chapter is to identify data types that fit into the current ZFIN database and explain how to provide those data in the optimal format for integration. We identify the required and optional data elements, define jargon, and present tools and templates that can help with the acquisition and organization of data as they are being prepared for submission to ZFIN. This information will also appear in the ZFIN wiki, where it will be updated as our services evolve over time.

Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians.

AIMS: The aldose reductase gene (AKR1B1) is a strong candidate for diabetic nephropathy, and the T allele at rs759853 and the Z-2 allele at an [AC]n microsatellite are associated with diabetic kidney disease in some populations. As AKR1B1 is located on 7q35, where we have previously reported linkage to diabetic nephropathy in Pima Indians, this study examined the association of AKR1B1 variants with diabetic nephropathy in this population. METHODS: AKR1B1 variants were identified by sequencing and genotyped using allelic discrimination and pyrosequencing. Genotype distributions were compared between 107 cases with diabetic end-stage renal disease and 108 control subjects with diabetes for > or = 10 years and no evidence of nephropathy, and between 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships. RESULTS: We identified 11 AKR1B1 single nucleotide polymorphisms (SNPs) and the [AC]n microsatellite polymorphism. Three SNPs were rare and two were in 100% genotypic concordance; thus, eight polymorphisms were genotyped. No variant was associated with diabetic kidney disease in the case-control or family-based study. For example, the T allele at rs759853 had an allele frequency of 0.165 in cases and 0.171 in control subjects (OR = 0.96, 95% CI, 0.57-1.59, P = 0.86); in the family study its frequency was 0.140 and 0.169 in affected and unaffected individuals, respectively (OR = 0.90, 95% CI, 0.53-1.54 P = 0.71). Corresponding values for the Z-2 allele at the [AC]n microsatellite were OR = 1.09 (95% CI 0.72-1.66, P = 0.67) and OR = 1.25 (95% CI 0.81-1.95, P = 0.31) in the case-control and family studies, respectively. CONCLUSIONS: Common AKR1B1 polymorphisms are unlikely to be major determinants of diabetic nephropathy in this population.

Synthesis, characterization, and electrochemistry of cis-oxothio- and cis-bis(thio)tungsten(VI) complexes of hydrotris(3,5-dimethylpyrazol-1-yl)borate.

The complexes TpWO2X react with sulfiding agents such as B2S3 or P4S10 to give the oxothio- and bis(thio)tungsten(VI) complexes TpWOSX (X = Cl(-)) and TpWS2X [X = Cl(-), S2PPh2(-); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. The reaction of TpWS2Cl with (i) PPh3 in pyridine and (ii) dimethyl sulfoxide affords TpWOSCl in good overall yield. The chloro complexes undergo metathesis with alkali metal salts to yield species of the type TpWOSX and TpWS2X [X = OPh(-), SPh(-), SePh(-), (-)-mentholate]. The diamagnetic complexes exhibit NMR spectra indicative of C(1) (TpWOSX) or C(s) (TpWS2X) symmetry and IR spectra consistent with terminal oxo and thio ligation (nu(W=O), 940-925 cm(-1); nu(W=S) or nu(WS2), 495-475 cm(-1)). Crystals of (R,S)-TpWOS[(-)-mentholate] are monoclinic, space group P2(1), with a = 11.983(2) A, b = 18.100(3) A, c = 13.859(3) A, beta = 91.60(2) degrees, V = 3004.6(8) A(3), and Z = 4. Crystals of TpWS2(OPh)-CH2Cl2 are orthorhombic, space group Pbca, with a = 16.961(4) A, b = 33.098(7) A, c = 9.555(2) A, V = 5364(2) A(3), and Z = 8. The mononuclear, distorted-octahedral tungsten centers are coordinated by a tridentate Tp ligand, an alkoxy or aryloxy ligand, and two terminal chalcogenide ligands. The average W=O and W=S distances are 1.726(7) and 2.125(2) A, respectively, and the O=W=S and S=W=S angles 102.9(3) and 102.9(1) degrees, respectively. The tungsten and sulfur X-ray absorption spectra of TpWOSCl and TpWS2Cl are consistent with the presence of terminal pi-bonded thio ligands in both complexes. The thio complexes generally undergo a reversible one-electron reduction at potentials significantly more positive than their oxo analogues. The chemical, spectroscopic, and electrochemical properties of the complexes are heavily influenced by the presence of W=S pi frontier orbitals.

2-CAT: 2-concentric arc technique.

We used conventional three-dimensional (3D) planning software and blocking to design a radiation dose distribution in the shape of a hollow sphere. The technique, known as 2-CAT, employs arcing beams with blocking of the center of the field, along with partial transmission blocking of the poles of the portal. The central core can subsequently be irradiated to deliver a relatively even dose to the entire volume. The technique differs from conventional planning in that the central portion of the tumor, while surrounded, is not included in the initial treatment volume. The clinical usefulness of the method will require future testing, as the technique has not yet been clinically proven.

Generation and biomimetic chemistry of tungsten-dithiolene complexes containing the hydrotris(3,5-dimethylpyrazol-1-yl)borate ligand.

Reactions of bis(thio)-W(VI) complexes, LWS2X (L = hydrotris (3,5-dimethylpyrazol-1-yl)borate, X = monoanion), with alkynes produce dithiolene complexes, LWX(dithiolene). The synthesis and characterization of orange LW(OPh){S2C2(CO2Me)2} (1) and burgundyred LW(SePh) {S2C2(Ph)(2-quinoxalinyl)} (2) and the X-ray crystal structure of 1.0.5CH2Cl2, are described in detail. Crystals of 1.0.5CH2Cl2 are orthorhombic, space group Pbcn, with a = 29.826(6), b = 13.291(4), c = 16.078(4) A, V = 6373(5) A3, and Z = 8. The six-coordinate, distorted-octahedral complex features a tridentate L ligand, a monodentate phenoxide ligand, and a bidentate dithiolene ligand. The short W-S bonds (2.267(4) and 2.279(4) A) and the parameters associated with the phenoxide ligand (W-O = 1.850(8) A, W-O-C = 146(1) degree), point to a considerable degree of W-ligand multiple bonding in the [W(OPh)(dithiolene)]+ unit. For 2, W-Se and average W-S distances of 2.49(2) A and 2.30(2) A, respectively, have been obtained from EXAFS studies. The formation of yellow 3,3'-dithiobis[2-(phenyl)thieno[2,3-b]quinoxaline] (3) upon oxidation of 2 supports the likely generation of urothione upon oxidative degradation of molybdopterin-containing tungsten enzymes from hyperthermophilic organisms.

Does providing more accessible primary care psychology services lower the clinical threshold for referrals?

BACKGROUND: The growing number of specialist services being provided within primary care has lead to the argument that this will reduce the clinical threshold for referrals to these clinics. AIM: The possibility that increasing the accessibility of primary care psychology services will reduce the threshold for referral was examined by comparing levels of psychological disturbance among patients seen by practice-based clinical psychologists with those attending outpatient clinics. METHOD: Psychological symptoms, distress, disruption in daily life and satisfaction with life were assessed using a questionnaire-based methodology. A consecutive series of 177 patients, assessed in a local general practice or an outpatient department across a wide range of urban locations, was studied over a fixed period. RESULTS: The study revealed equivalent levels of psychopathology within both specialist and primary care clinics. Of the overall sample, 79% were likely to merit a formal psychiatric diagnosis, relating primarily to mood disorder. Levels of subjective distress and life satisfaction were also equivalent at both service locations. CONCLUSION: The lack of evidence for a reduction in clinical threshold for referral within the primary care sample suggests that general practitioners' referral rates are similar regardless of whether practice-based clinical psychology services are available. This has implications for primary-care-led commissioning of mental health services.

Ferritin measurement in synovial tissue and fluid in patients with inflammatorys joint disease

Se dosificó mediante ensayo inmunorradiométrico la concentración de ferritina (FET), una proteína que almacena hierro, en el líquido sinovial (LS) de 41 pacientes con sinovitis clínicamente activa de distinta etiología. De acuerdo al diagnóstico los enfermos se distribuyeron en cuatro grupos: el grupo de artropatía degenerativa (DA) formado por cuatro enfermos con osteoartosis; siete pacientes con gota y uno con pseudogota integraron el grupo de artropatía por depósito de cristales (AC); el grupo de artropatía inmune (AI) constituido por trece enfermos con artritis reumatoide y siete con lupus eritematoso sistémico; y un grupo de artropatías misceláneas (AM) formado por nueve pacientes. El grupo AD mostró nivele sde FET significativamente menores a los encontrados en los grupos AC, AI y AM. En cambio, no se observaron diferencias significativas en los valores de FET en LS entre los grupos AC, AI y AM. Además, se cuantificó FET en nueve muestras de suero y en cinco de tejido sinovial (TS). Los niveles de FET en LS correlacionaron en forma significativa con la cantidad de FET en TS y con el número de leucocitos en el LS, pero no existió correlación entre la FET en LS y en suero. Estos resultados indican que la dosificación de FET en LS tiene poca utilidad en el diagnóstico diferencial de las artropatías inflamatorias, y sugiere que probablemente los leucocitos y/o las células sinoviales sean la fuente de FET en el LS