Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1)

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.     

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.     

A polymer/semiconductor write-once read-many-times memory

Organic devices promise to revolutionize the extent of, and access to, electronics by providing extremely inexpensive, lightweight and capable ubiquitous components that are printed onto plastic, glass or metal foils. One key component of an electronic circuit that has thus far received surprisingly little attention is an organic electronic memory. Here we report an architecture for a write-once read-many-times (WORM) memory, based on the hybrid integration of an electrochromic polymer with a thin-film silicon diode deposited onto a flexible metal foil substrate. WORM memories are desirable for ultralow-cost permanent storage of digital images, eliminating the need for slow, bulky and expensive mechanical drives used in conventional magnetic and optical memories. Our results indicate that the hybrid organic/inorganic memory device is a reliable means for achieving rapid, large-scale archival data storage. The WORM memory pixel exploits a mechanism of current-controlled, thermally activated un-doping of a two-component electrochromic conducting polymer.     

Cell-mediated cytotoxicity by natural killer and killer cells, lipid peroxidation and glutathione

In the course of spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) with human peripheral lymphocytes as effector cells, no lipid peroxidation occurred as measured by the production of ethane and thiobarbituric acid-reactive material. Furthermore, impairment of major cellular defense systems of target cells (K562 cells for SCMC, Chang liver cells for ADCC), by decreasing their glutathione content, had no effect on either lipid peroxidation or the cytotoxic response. These findings indicate that peroxidative damage is not a mechanism of NK and K cell-mediated cytotoxicity.     

A sporulating strain ofBacillus popilliae

Zusammenfassung Durch Behandlung mit Chloroform ist es möglich,Bacillus popilliae in flüssigem Medium zur Sporenbildung zu veranlassen. Diese Bakterien können zur Bekämpfung von Insekten, derPopilliae japonica, benützt werden.