Behavioral Implications of Knockout for the Dyslexia-Risk Gene Dcdc2 in Mice

Several genetic linkage and epidemiological studies have provided strong evidence that DCDC2 is a candidate gene for developmental dyslexia, a disorder that impairs a person’s reading ability despite adequate intelligence, education, and socio-economic status. Studies investigating embryonic intra-ventricular RNA interference (RNAi) of Dcdc2, a rat homolog of the DCDC2 gene in humans, indicate disruptions in neuronal migration in the rat cortex during development. Interestingly, these anatomical anomalies are consistent with post mortem histological analysis of human dyslexic patients. Other rodent models of cortical developmental disruption have shown impairment in rapid auditory processing and learning maze tasks in affected subjects. The current study investigates the rapid auditory processing abilities of mice heterozygous for Dcdc2 (one functioning Dcdc2 allele) and mice with a homozygous knockout of Dcdc2 (no functioning Dcdc2 allele). It is important to note that this genetic model for behavioral assessment is still in the pilot stage. However, preliminary results suggest that mice with a genetic mutation of Dcdc2 have impaired rapid auditory processing, as well as non-spatial maze learning and memory ability, as compared to wildtypes. By genetically knocking out Dcdc2 in mice, behavioral features associated with Dcdc2 can be characterized, along with other neurological abnormalities that may arise due to the loss of the functioning gene.

Knockdown of Kiaa0319 Reduces Dendritic Spine Density

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to exhibit differential spatial-temporal expression patterns in the brain throughout development, which suggests that the polycystic kidney disease (PKD) domain encoded by KIAA0319 facilitates cell-cell adhesion to enable neuronal precursors to crawl up the radial glia during neuronal migration. With the knowledge of KIAA0319 involvement in early neurogenesis, we were interested in determining how different KIAA0319 expression may impact cortical neurons in layer II and III during early adulthood. We show that KIAA0319 knockdown in cortical pyramidal neurons significantly reduces the dendritic spine density. Studies have shown that changes in dendritic spine morphology and density affect properties of neural circuitry. Henceforth, this finding may reveal a link between the Kiaa0319 gene and the deficit of the neural processing task of reading due to reduced spines density. Finding a correlation between Kiaa0319 expression and its influence on dendritic spine development may lead to a greater insight of a direct link between the dyslexia susceptibility gene and the biological mechanism that causes dyslexia.

An integrated molecular biology and computational approach to CYP1A1 expression in human brain

The cytochromes P450 comprise a superfamily of heme-containing mono-oxygenases. These enzymes metabolize numerous xenobiotics, but also play a role in metabolism of endogenous compounds. The P450 1A1 enzyme generally metabolizes polycyclic aromatic hydrocarbons, and its expression can be induced by aryl hydrocarbon receptor (AhR) activation. CYP1A1 is an exception to the generality that the majority of CYPs demonstrate highest expression in liver; CYP1Al is present in numerous extrahepatic tissues, including brain. This P450 has been observed in two forms, wildtype (WT) and brain variant (BV), arising from alternatively spliced mRNA transcripts. The CYP1A1 BV mRNA presented an exon deletion and was detected in human brain but not liver tissue of the same individuals. ^ Quantitative PCR analyses were performed to determine CYP1A1 WT and BV transcript expression levels in normal, bipolar disorder or schizophrenic groups. In our samples, we show that CYP1A1 BV mRNA, when present, is found alongside the full-length form. Furthermore, we demonstrate a significant decrease in expression of CYP1A1 in patients with bipolar disorder or schizophrenia. The expression level was not influenced by post-mortem interval, tissue pH, age, tobacco use, or lifetime antipsychotic medication load. ^ There is no indication of increased brain CYP1A1 expression in normal smokers versus non-smokers in these samples. We observed slightly increased CYP1A1 expression only in bipolar and schizophrenic smokers versus non-smokers. This may be indicative of complex interactions between neuronal chemical environments and AhR-mediated CYP1A1 induction in brain. ^ Structural homology modeling demonstrated that P450 1A1 BV has several alterations to positions/orientations of substrate recognition site residues compared to the WT isoform. Automated substrate docking was employed to investigate the potential binding of neurological signaling molecules and neurotropic drugs, as well as to differentiate specificities of the two P450 1A1 isoforms. We consistently observed that the BV isoform produced energetically favorable substrate dockings in orientations not observed for the same substrate in the WT isoform. These results demonstrated that structural differences, namely an expanded substrate access channel and active site, confer greater capacity for unique compound docking positions suggesting a metabolic profile distinct from the wildtype form for these test compounds. ^

AVIAN ROTAVIRUSES

The prevalence of antirotavirus antibodies in chickens and turkeys in the Gonzales, Texas and Llano, Texas areas was studied. Caged layer chicken flocks were found to have a prevalence of 64% when samples were taken randomly. This compares to 45% in chicken broiler breeder flocks and 92% in turkey breeding flocks. The natural occurrence of turkey rotavirus infection in two separate field studies showed an increase in mortality varying from 9% to 45% above expected death losses. Clinically, pasted vents, lacitude, and general malaise were noted in affected poults. Lesions noted on post mortem examination were; slight ballooning of the small intestine, excessively large ceca, and mild hyperemia of the small and large intestines.^ The use of maternal antibody from simian rotavirus immunized chickens' eggs for preventing murine rotavirus infection in infant mice was investigated. There was a reduction from 91% to 15% incidence when infant mice were treated twice daily with egg yolk immunoglobulin.^ The need for a convenient, easily grown and rapidly reproducing model for avian and mammalian rotaviruses led to the use of coturnix chicks. The turkey rotavirus was adapted to the quail chicks be serial passage. Transmission and scanning electron microscopy as well as micropathological methods were used in the study of the pathogenesis of rotavirus infection in quail and infant mice. ^

Cary's Illustrated and Priced Catalogue: Surgical Instruments, Physicians, Hospital Supplies, and Furnishings, Druggist Sundries, Etc.

Second Edition. Pp.5-61 General Surgical Necessities, Gauze, Antiseptic Sundries, Surgical Sundries, Rubber Bandages, Catheters, Bougies, Splints, Tents, Emergency Bags, Surgeon's Needles, Operating Instruments, Amputating, Forceps, Aspiration, Cases, Catheters and Directors, Pocket Case Instruments, Dissecting and Post-Mortem Pp.62-118 General Operating - Osteotomy, Mastoid, Trephining, Eye Instruments, Aural, Nasal, Mouth and Throat, Tooth Forceps, Laryngoscopic Sets, Hydraulic Air Compressor, Variocele, Genito Urinary Pp. 119-167 Genito Urinary-Lithotrity, Alimentary, Anal and Rectal, Gynaecological, Pessaries, Microscopes, Syringes Pp.168-205 Chemical Apparatus and Glassware, Physician's Cabinets, Office Furniture, Operating Chairs and Tables, Hospital Beds, Cautery, Electrolytic, Batteries Pp.206-246 Cases, Varicose, Braces, Abdominal Supporters, Trusses, Invalid Chairs and Supplies, Sterilizers, Saddle-Bags, Deformity Apparatus Advertisements: Bandages, Abdominal Supporters, Rubber Supplies, Bags, Batteries, Cotton, Microscopes, Hypodermic Tablets, Atomizers, Furniture, Sterilizers, Syringes

Illustrated Catalogue of Standard Surgical Instruments and Allied Lines

Section "A": Dissecting and Post-Mortem Instruments Diagnostic Instruments and Apparatus Microscopes and Microscopic Accessories Laboratory Apparatus and Glass Ware Apparatus for Blood and Urine Analysis Apparatus for Phlebotomy, Cupping and Leeching Apparatus for Infusion and Transfusion Syringes for Aspiration and Injection Osteological Preparations Section "B": Anaesthetic, General Operating, Osteotomy, Trepanning, Bullet, Pocket Case, Cautery, Ligatures, Sutures, Dressings, Etc. Section "B" continued Section "C": Eye, Ear, Nasal, Dermal, Oral, Tonsil, Tracheal, Laryngeal,Esophageal, Stomach, Intestinal, Gall Bladder Section "C": continued Section "D": Rectal, Phimosis, Prostatic, Vesical, Urethral, Ureteral, Instruments Section "E": Gynecic, Hysterectomy, Obstetrical, Instrument Satchels, Medicine Cases Section "F": Electric Cautery Transformers, Electro-Cautery Burners and Accessories, Electric Current Controllers, Electro-Diagnostic Outfits, Electrolysis Instruments Electro-Therapeutic Lamps, Faradic Batteries, Galvanic Batteries Section "G": Office Furniture, Office Sterilizing Apparatus, Hospital Supplies, Surgical Rubber Goods, Sick Room Utensils, Invalid Rolling Chairs, Invalid Supplies Section "H": Artificial Limbs, Deformity Apparatus, Fracture Apparatus, Splints, Splint Material, Elastic Hosiery, Abdominal Supporters, Crutches, Trusses, Suspensories, Etc. Index

Northwards and eastwards velocities extracted from a historical run (for the year 2000) of the UVic Earth System Climate Model of Weaver et al. (2001)

This study provides a theoretical assessment of the potential bias due to differential lateral transport on multi-proxy studies based on a range of marine microfossils. Microfossils preserved in marine sediments are at the centre of numerous proxies for paleoenvironmental reconstructions. The precision of proxies is based on the assumption that they accurately represent the overlying watercolumn properties and faunas. Here we assess the possibility of a syn-depositional bias in sediment assemblages caused by horizontal drift in the water column, due to differential settling velocities of sedimenting particles based on their shape, size and density, and due to differences in current velocities. Specifically we calculate the post-mortem lateral transport undergone by planktic foraminifera and a range of other biological proxy carriers (diatoms, radiolaria and fecal pellets transporting coccolithophores) in several regions with high current velocities. We find that lateral transport of different planktic foraminiferal species is minimal due to high settling velocities. No significant shape- or size-dependent sorting occurs before reaching the sediment, making planktic foraminiferal ideal proxy carriers. In contrast, diatoms, radiolaria and fecal pellets can be transported up to 500km in some areas. For example in the Agulhas current, transport can lead to differences of up to 2°C in temperature reconstructions between different proxies in response to settling velocities. Therefore, sediment samples are likely to contain different proportions of local and imported particles, decreasing the precision of proxies based on these groups and the accuracy of the temperature reconstruction.

Patrimonio y producción en los entornos rurales de Buenos Aires. San José de Flores, 1800-1875

En el presente artículo reconstruimos a partir de la información proporcionada por testamentos e inventarios post mortem las características productivas de los establecimientos frutihortícolas y cerealeros del partido de San José de Flores. Abordamos, además, el estudio de los esquemas de inversión de los propietarios y/o arrendatarios de estas unidades esbozando su perfil socioeconómico y político, deteniéndonos especialmente en aquellos que han accedido a la propiedad legal de los terrenos.

Nuevas iluminaciones en las sombras biográficas de Alejandro Sawa - Max Estrella (1892- 1896)

Las nuevas noticias referidas a la biografía de Alejandro Sawa propor¬cionan datos de gran interés para desentrañar las andanzas de la bohemia Hispanoamérica en el París de finales del siglo XIX, a la sombra de la Casa Editorial Garnier y de las tertulias presididas por P. Verlaine, así como para descifrar las claves históricas diseminadas por Valle-Inclán en Luces de bohemia, homenaje póstumo a la memoria del introductor de las novedades literarias francesas en la cultura española de fin de siglo, Alejandro Sawa - Max Estrella.

La comprensión infantil de la muerte : Una mirada desde lo real, lo posible y lo necesario

El artículo refiere a una investigación doctoral en curso sobre el desarrollo de la comprensión infantil de la muerte, y se centra en los conceptos de lo real, lo posible y lo necesario de las últimas investigaciones piagetianas. Aunque se trata de una discusión teórica, se mencionan algunos estudios precedentes acerca de la comprensión de la muerte, puntuando algunos de sus problemas metodológicos vinculados con la distinción entre creencias infantiles sugeridas y espontáneas. Se presentan algunos datos de nuestras exploraciones piloto con niños de 5 a 10 años. Ellos se utilizan como ilustración en la discusión sobre la posibilidad de analizar el desarrollo del concepto de muerte desde la hipótesis 'tendiente a precisar los mecanismos productores de novedad' de la diferenciación gradual entre lo real, lo posible y lo necesario. Se señala que la aceptación de la universalidad, la inevitabilidad y la irreversibilidad de la muerte es una constante en todos los niños entrevistados. Asimismo, sus ideas acerca de la 'persistencia de la existencia' luego de la muerte, y de la 'relocalización' post mórtem en otro espacio, sugieren la presencia de mecanismos análogos a los hallados en otros estudios. Finalmente, la co-existencia de racionalidades diferentes en un mismo sujeto, parecen manifestar las complejas relaciones entre representaciones sociales y creencias espontáneas

Patrimonio y producción en los entornos rurales de Buenos Aires. San José de Flores, 1800-1875

En el presente artículo reconstruimos a partir de la información proporcionada por testamentos e inventarios post mortem las características productivas de los establecimientos frutihortícolas y cerealeros del partido de San José de Flores. Abordamos, además, el estudio de los esquemas de inversión de los propietarios y/o arrendatarios de estas unidades esbozando su perfil socioeconómico y político, deteniéndonos especialmente en aquellos que han accedido a la propiedad legal de los terrenos.

Nuevas iluminaciones en las sombras biográficas de Alejandro Sawa - Max Estrella (1892- 1896)

Las nuevas noticias referidas a la biografía de Alejandro Sawa propor¬cionan datos de gran interés para desentrañar las andanzas de la bohemia Hispanoamérica en el París de finales del siglo XIX, a la sombra de la Casa Editorial Garnier y de las tertulias presididas por P. Verlaine, así como para descifrar las claves históricas diseminadas por Valle-Inclán en Luces de bohemia, homenaje póstumo a la memoria del introductor de las novedades literarias francesas en la cultura española de fin de siglo, Alejandro Sawa - Max Estrella.

La comprensión infantil de la muerte : Una mirada desde lo real, lo posible y lo necesario

El artículo refiere a una investigación doctoral en curso sobre el desarrollo de la comprensión infantil de la muerte, y se centra en los conceptos de lo real, lo posible y lo necesario de las últimas investigaciones piagetianas. Aunque se trata de una discusión teórica, se mencionan algunos estudios precedentes acerca de la comprensión de la muerte, puntuando algunos de sus problemas metodológicos vinculados con la distinción entre creencias infantiles sugeridas y espontáneas. Se presentan algunos datos de nuestras exploraciones piloto con niños de 5 a 10 años. Ellos se utilizan como ilustración en la discusión sobre la posibilidad de analizar el desarrollo del concepto de muerte desde la hipótesis 'tendiente a precisar los mecanismos productores de novedad' de la diferenciación gradual entre lo real, lo posible y lo necesario. Se señala que la aceptación de la universalidad, la inevitabilidad y la irreversibilidad de la muerte es una constante en todos los niños entrevistados. Asimismo, sus ideas acerca de la 'persistencia de la existencia' luego de la muerte, y de la 'relocalización' post mórtem en otro espacio, sugieren la presencia de mecanismos análogos a los hallados en otros estudios. Finalmente, la co-existencia de racionalidades diferentes en un mismo sujeto, parecen manifestar las complejas relaciones entre representaciones sociales y creencias espontáneas

Strontium and neodymium concentrations and isotope compositions in fossil fish teeth and pore waters at ODP Sites 130-807 and 125-786

We analyzed Nd and Sr isotopic compositions of Neogene fossil fish teeth from two sites in the Pacific in order to determine the effect of cleaning protocols and burial diagenesis on the preservation of seawater isotopic values. Sr is incorporated into the teeth at the time of growth; thus Sr isotopes are potentially valuable for chemostratigraphy. Nd isotopes are potential conservative tracers of paleocirculation; however, Nd is incorporated post-mortem, and may record diagenetic pore waters rather than seawater. We evaluated samples from two sites (Site 807A, Ontong Java Plateau and Site 786A, Izu-Bonin Arc) that were exposed to similar bottom waters, but have distinct lithologies and pore water chemistries. The Sr isotopic values of the fish teeth appear to accurately reflect contemporaneous seawater at both sites. The excellent correlation between the Nd isotopic values of teeth from the two sites suggests that the Nd is incorporated while the teeth are in chemical equilibrium with seawater, and that the signal is preserved over geologic timescales and subsequent burial. These data also corroborate paleoseawater Nd isotopic compositions derived from Pacific ferromanganese crusts that were recovered from similar water depths (Ling et al., 1997; doi:10.1016/S0012-821X(96)00224-5). This corroboration strongly suggests that both materials preserve seawater Nd isotope values. Variations in Pacific deepwater e-Nd values are consistent with predictions for the shoaling of the Isthmus of Panama and the subsequent initiation of nonradiogenic North Atlantic Deep Water that entered the Pacific via the Antarctic Circumpolar Current.

Nuevas iluminaciones en las sombras biográficas de Alejandro Sawa - Max Estrella (1892- 1896)

Las nuevas noticias referidas a la biografía de Alejandro Sawa propor¬cionan datos de gran interés para desentrañar las andanzas de la bohemia Hispanoamérica en el París de finales del siglo XIX, a la sombra de la Casa Editorial Garnier y de las tertulias presididas por P. Verlaine, así como para descifrar las claves históricas diseminadas por Valle-Inclán en Luces de bohemia, homenaje póstumo a la memoria del introductor de las novedades literarias francesas en la cultura española de fin de siglo, Alejandro Sawa - Max Estrella.