Mandibulofacial Syndrome With Growth and Mental Retardation, Microcephaly, Ear Anomalies With Skin Tags, and Cleft Palate in a Mother and Her Son: Autosomal Dominant or X-Linked Syndrome?

We report on a Brazilian mother and her son affected with mandibulofacial dysostosis, growth and mental retardation, microcephaly, first branchial arch anomalies, and cleft palate. To date only three males and one female, all sporadic cases, with a similar condition have been reported. This article describes the first familial case with this rare condition indicating autosomal dominant or X-linked inheritance. (C) 2009 Wiley-Liss, Inc.

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This `experiment of nature` indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria.

Hematologically important mutations: X-linked chronic granulomatous disease (third update)

Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide is used to kill phagocytosed micro-organisms in neutrophils, eosinophils, monocytes and macrophages. The leukocyte NADPH oxidase is composed of five subunits, of which the enzymatic component is gp91-phox, also called Nox2. This protein is encoded by the CYBB gene on the X chromosome. Mutations in this gene are found in about 70% of all CGD patients. This article lists all mutations identified in CYBB in the X-linked form of CGD. Moreover, apparently benign polymorphisms in CYBB are also given, which should facilitate the recognition of future disease-causing mutations. (C) 2010 Elsevier Inc. All rights reserved.

Grain size and heavy minerals of the Late Quaternary eolian sediments from the Imbituba-Jaguaruna coast, Southern Brazil: Depositional controls linked to relative sea-level changes

The stratigraphic subdivision and correlation of dune deposits is difficult, especially when age datings are not available. A better understanding of the controls on texture and composition of eolian sands is necessary to interpret ancient eolian sediments. The Imbituba-Jaguaruna coastal zone (Southern Brazil, 28 degrees-29 degrees S) stands out due to its four well-preserved Late Pleistocene (eolian generation 1) to Holocene eolian units (eolian generations 2, 3, and 4). In this study, we evaluate the grain-size and heavy-mineral characteristics of the Imbituba-Jaguartma eolian units through statistical analysis of hundreds of sediment samples. Grain-size parameters and heavy-mineral content allow us to distinguish the Pleistocene from the Holocene units. The grain size displays a pattern of fining and better sorting from generation 1 (older) to 4 (younger), whereas the content of mechanically stable (dense and hard) heavy minerals decreases from eolian generation 1 to 4. The variation in grain size and heavy-mineral content records shifts in the origin and balance (input versus output) of eolian sediment supply attributable mainly to relative sea-level changes. Dunefields submitted to relative sea-level lowstand conditions (eolian generation 1) are characterized by lower accumulation rates and intense post-depositional dissection by fluvial incision. Low accumulation rates favor deflation in the eolian system, which promotes concentration of denser and stable heavy minerals (increase of ZTR index) as well as coarsening of eolian sands. Dissection involves the selective removal of finer sediments and less dense heavy minerals to the coastal source area. Under a high rate of relative sea-level rise and transgression (eolian generation 2), coastal erosion prevents deflation through high input of sediments to the coastal eolian source. This condition favors dunefield growth. Coastal erosion feeds sand from local sources to the eolian system. including sands from previous dunefields (eolian generation 1) and from drowned incised valleys. Therefore, dunefields corresponding to transgressive phases inherit the grain-size and heavy-mineral characteristics of previous dunefields, leading to selective enrichment of finer sands and lighter minerals. Eolian generations 3 and 4 developed during a regressive-progradational phase (Holocene relative sea level highstand). The high rate of sediment supply during the highstand phase prevents deflation. The lack of coastal erosion favors sediment supply from distal sources (fluvial sediments rich in unstable heavy minerals). Thus, dunefields of transgressive and highstand systems tracts may be distinguished from dunefields of the lowstand systems tract through high rates of accumulation (low deflation) in the former. The sediment source of the transgressive dunefields (high input of previously deposited coastal sands) differs from that of the highstand dunefields (high input of fluvial distal sands). Based on this case study, we propose a general framework for the relation between relative sea level, sediment supply and the texture and mineralogy of eolian sediments deposited in siliciclastic wet coastal zones similar to the Imbituba-Jaguaruna coast (C) 2009 Elsevier B.V. All rights reserved.

Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multifactorial and remain unclear. Here we examined DNA damage;p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93) --> Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2`-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This toxic activity of mutant SOD1 in the nucleus may play an important role in the complex mechanisms associated with motor neuron death observed in ALS pathogenesis. (C) 2010 Elsevier B.V. All rights reserved.

Preparation and characterization of cross-linked starch polyurethanes

This study describes the preparation and characterization of new starch cross-linked polyurethanes produced by the reaction of native cornstarch with a propylene oxide toluene diisocyanate oligomer. Infrared analysis confirmed the occurrence of the reaction and solubility and swelling tests showed that it had led to cross-linked structures. These products were totally amorphous and displayed elastomeric properties associated with two T(g)s at -60 and 35 degrees C. (C) 2009 Elsevier Ltd. All rights reserved.

Development and application of a Saccharomyces cerevisiae-expressed nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibodies against infectious bronchitis virus

A Saccharomyces cerevisiae-expressed nucleocapsid (N) polypeptide of the M41 strain of infectious bronchitis virus (IBV) was used as antigen in a recombinant yeast-expressed N protein-based enzyme-linked immunosorbent assay (Y-N-ELISA). The Y-N-ELISA was rapid, sensitive, and specific for detecting chicken serum antibodies to IBV, and it compared favorably with a commercial ELISA.

An enzyme-linked immunosorbent assay for the detection of IgG antibodies against Babesia equi in horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies against Leishmania chagasi in dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The malate synthase of Paracoccidioides brasiliensis is a linked surface protein that behaves as an anchorless adhesin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Susceptibility to Yersinia pseudotuberculosis Infection is Linked to the Pattern of Macrophage Activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 2: Physical parameters, cross-linking degrees and drug delivery relationships

High amylose cross-linked to different degrees with sodium trimetaphosphate by varying base strength (2% or 4%) and contact time (0.5-4 h) was evaluated as non-compacted systems for sodium diclophenac controlled release. The physical properties and the performance of these products for sodium diclophenac controlled release from non-compacted systems were related to the structures generated at each cross-linking degree. For samples at 2% until 2 h the swelling ability, G' and eta* values increased with the cross-linking degree, because the longer polymer chains became progressively more entangled and linked. This increases water uptake and holding, favoring the swelling and resulting in systems with higher viscosities. Additionally, the increase of cross-linking degree should contribute for a more elastic structure. The shorter chains with more inter-linkages formed at higher cross-linking degrees (2%4h and 4%) make water caption and holding difficult, decreasing the swelling, viscosity and elasticity. For 2% samples, the longer drug release time exhibited for 2%4h sample indicates that the increase of swelling and viscosity contribute for a more sustained drug release, but the mesh size of the polymeric network seems to be determinant for the attachment of drug molecules. For the 4% samples, smaller meshes size should determine less sustained release of drug. (C) 2008 Elsevier B.V. All rights reserved.

Preparation and characterization of free films of high amylose/pectin mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of phosphated cross-linked high amylose on in vitro release of different drugs

The influence of structural characteristics of high amylose cross-linked at different degrees on the release of drugs with important molecular differences, namely sodium diclophenac (SD) and nicotinamide (NI), was assessed in vitro from non-compacted systems. The release profiles were related with classical kinetic mathematical models for better understanding of the release mechanism. An increase in polymer cross-linking degree resulted in longer release time for both drugs, although SD generally was released slower than NI. SD release from samples cross-linked at 2% of basis was driven mainly by Fickian diffusion, while from samples cross-linked at 4% of basis follows anomalous mechanism. Inversely, anomalous mechanism was responsible for NI release from 2% samples and Fickian diffusion from 4% samples. Results suggest that the performance of cross-linked high amylose as excipient for controlled drug release not only depends on cross-linking degree but also is highly influenced by structural characteristics of the drug. (C) 2009 Elsevier Ltd. All rights reserved.

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 1: Synthesis and polymer characterization

High amylose was cross-linked with sodium trimetaphosphate (STMP) using 2% and 4% solutions of NaOH at room temperature with reaction contact times of 0.5, 1, 2 and 4 h. The different polymers obtained were analyzed by FT IR, C-13 and P-31 solid state NMR, SEM and C, H and P elemental analysis. The results were used to propose a two-stage mechanism for phosphate incorporation, the first being kinetically controlled. (C) 2008 Elsevier Ltd. All rights reserved.