Influence of several sources and amounts of iron on DNA, lipid and protein oxidative damage during anaemia recovery.

The study was designed to assess the effect of several Fe amounts and sources on haematological parameters, DNA, lipid and protein oxidative damage during the course of Fe-deficiency anaemia recovery. Peripheral DNA damage was assessed using an alkaline comet assay. The brain, liver, erythrocyte and duodenal mucosa lipid peroxidation and protein damage were assessed in control and anaemic rats after Fe repletion with three different sources (FeSO4, haem Fe, and FeSO4 + haem Fe) and amounts (45, 12, and 31 mg Fe/kg diet) of Fe: F diet, H diet or C diet, respectively. After supplying the diets, the haematological parameters studied were recovered; being remarkable is the haemoglobin increase. The DNA damage was lower in rats with the H diet, as revealed by the percentage of DNA in head, tail and Olive tail moment compared in rats with the F (P < 0.001) and C (P < 0.05) diets. Lipid peroxidation was similar in all the tissues, except in the duodenal mucosa which was lower with H and C diets (P < 0.001). The animals fed with C diet showed lower oxidative protein damage in the duodenal mucosa (P < 0.001) and was also lower in the liver and erythrocytes for H and C diets (P < 0.001). No differences were found in the brain under our experimental conditions. In conclusion, Fe supplementation with low doses of haem Fe or combined forms of non-haem and haem Fe (FeSO4 + haem) are efficient in restoring the impaired haematological parameters and prevent the evoked oxidative stress associated with Fe supplements.

The neural basis of non-native speech perception in bilingual children.

The goal of the present study is to reveal how the neural mechanisms underlying non-native speech perception change throughout childhood. In a pre-attentive listening fMRI task, English monolingual and Spanish-English bilingual children - divided into groups of younger (6-8yrs) and older children (9-10yrs) - were asked to watch a silent movie while several English syllable combinations played through a pair of headphones. Two additional groups of monolingual and bilingual adults were included in the analyses. Our results show that the neural mechanisms supporting speech perception throughout development differ in monolinguals and bilinguals. While monolinguals recruit perceptual areas (i.e., superior temporal gyrus) in early and late childhood to process native speech, bilinguals recruit perceptual areas (i.e., superior temporal gyrus) in early childhood and higher-order executive areas in late childhood (i.e., bilateral middle frontal gyrus and bilateral inferior parietal lobule, among others) to process non-native speech. The findings support the Perceptual Assimilation Model and the Speech Learning Model and suggest that the neural system processes phonological information differently depending on the stage of L2 speech learning.

Brief report: eye-movement patterns during an embedded figures test in children with ASD.

The present study examined fixation frequency and duration during an Embedded Figures Test (EFT) in an effort to better understand the attentional and perceptual processes by which individuals with autism spectrum disorder (ASD) achieve accelerated EFT performance. In particular, we aimed to elucidate differences in the patterns of eye-movement in ASD and typically developing (TD) children, thus providing evidence relevant to the competing theories of weak central coherence (WCC) and enhanced perceptual functioning. Consistent with prior EFT studies, we found accelerated response time (RT) in children with ASD. No group differences were seen for fixation frequency, but the ASD group made significantly shorter fixations compared to the TD group. Eye-movement results indicate that RT advantage in ASD is related to both WCC and enhanced perceptual functioning.

New York-Structural GenomiX Research Consortium (NYSGXRC): a large scale center for the protein structure initiative.

Structural GenomiX, Inc. (SGX), four New York area institutions, and two University of California schools have formed the New York Structural GenomiX Research Consortium (NYSGXRC), an industrial/academic Research Consortium that exploits individual core competencies to support all aspects of the NIH-NIGMS funded Protein Structure Initiative (PSI), including protein family classification and target selection, generation of protein for biophysical analyses, sample preparation for structural studies, structure determination and analyses, and dissemination of results. At the end of the PSI Pilot Study Phase (PSI-1), the NYSGXRC will be capable of producing 100-200 experimentally determined protein structures annually. All Consortium activities can be scaled to increase production capacity significantly during the Production Phase of the PSI (PSI-2). The Consortium utilizes both centralized and de-centralized production teams with clearly defined deliverables and hand-off procedures that are supported by a web-based target/sample tracking system (SGX Laboratory Information Data Management System, LIMS, and NYSGXRC Internal Consortium Experimental Database, ICE-DB). Consortium management is provided by an Executive Committee, which is composed of the PI and all Co-PIs. Progress to date is tracked on a publicly available Consortium web site (http://www.nysgxrc.org) and all DNA/protein reagents and experimental protocols are distributed freely from the New York City Area institutions. In addition to meeting the requirements of the Pilot Study Phase and preparing for the Production Phase of the PSI, the NYSGXRC aims to develop modular technologies that are transferable to structural biology laboratories in both academe and industry. The NYSGXRC PI and Co-PIs intend the PSI to have a transforming effect on the disciplines of X-ray crystallography and NMR spectroscopy of biological macromolecules. Working with other PSI-funded Centers, the NYSGXRC seeks to create the structural biology laboratory of the future. Herein, we present an overview of the organization of the NYSGXRC and describe progress toward development of a high-throughput Gene-->Structure platform. An analysis of current and projected consortium metrics reflects progress to date and delineates opportunities for further technology development.

A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine --> phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.

Neuroendoscopía cerebral: experiencia previa en modelos experimentales y aplicación clínica / Brain neuroendoscopy: experience in experimental models and clinical application

OBJETIVOS: Diseñar modelos experimentales (ME) para neuroendoscopía cerebral (NEC) que permitan adquirir la destreza necesaria para su aplicación en pacientes tributarios de esta técnica operatoria. MATERIALES Y MÉTODOS: El estudio constó de 3 fases. En las 2 primeras, de diseño y entrenamiento en los ME para NEC, se empleó cadáveres vacunos y humanos. Se dividió aleatoriamente los especímenes en grupos A y B, a los cuales se les aplicó 2 volúmenes diferentes de suero fisiológico (SF) a fin de determinar aquel que genere una hidrocefalia (HC) que permita una NEC exitosa. En la fase 3 se realizó NEC a 5 pacientes con patología cerebral e indicación de NEC confirmada por TAC o RMN. RESULTADOS: En el ME vacuno el volumen de SF que permitió NEC exitosa en mayor número fue 70 ml (p< 0,01). En el ME humano, la FIC artificial fue obtenida con 150 ml de SF (p< 0,01). La NEC fue usada como herramienta diagnóstica o terapéutica. Las complicaciones post NEC fueron: alucinaciones, alza térmica y alteraciones de la memoria; todas respondieron favorablemente al manejo sintomático. CONCLUSIONES: Los ME diseñados en este estudio son herramientas útiles para el, aprendizaje de la NEC. El entrenamiento en ME para NEC es indispensable antes de su aplicación en humanos.