Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites

H-2 class I antigens appear to direct the recognition of virus-infected and neoplastic transformed cells by cytotoxic T lymphocytes (CTLs). Here, to identify the regions of class I antigens involved in CTL recognition, four hybrid class I genes were constructed in which exons were exchanged between the H-2Kb and H-2Db genes. These class I genes were expressed in mouse L cells and recognition of the hybrid Kb/Db antigens by CTLs and monoclonal antibodies specific for either Kb or Db was investigated. The pattern of CTL and monoclonal antibody recognition obtained indicates three correlations between structure and function of class I antigens. First, most CTL recognition sites and alloantigenic determinants are located on domains 1 and 2 of the antigen molecule. Second, these CTL recognition sites and alloantigenic determinants are not influenced by interaction of domains 1 and 2 with polymorphic regions of domain 3. Third, in contrast, interaction between domains 1 and 2 alters these CTL recognition sites and alloantigenic determinants. The alteration of CTL recognition sites by interaction between domains 1 and 2 suggests that a CTL site may be formed by amino acids from both domains 1 and 2, or that the conformation of amino acids at a CTL site may be altered by interactions between domains 1 and 2. Through these two features, the conformation of CTL recognition sites on H-2 class I antigens may be sensitive to alteration by interaction of either domain 1 or 2 with viral antigens.     

Calcium channels activated by hydrogen peroxide mediate abscisic acid signalling in guard cells

Drought is a major threat to agricultural production. Plants synthesize the hormone abscisic acid (ABA) in response to drought, triggering a signalling cascade in guard cells that results in stomatal closure, thus reducing water loss. ABA triggers an increase in cytosolic calcium in guard cells ([Ca2+]cyt) that has been proposed to include Ca2+ influx across the plasma membrane. However, direct recordings of Ca2+ currents have been limited and the upstream activation mechanisms of plasma membrane Ca2+ channels remain unknown. Here we report activation of Ca2+-permeable channels in the plasma membrane of Arabidopsis guard cells by hydrogen peroxide. The H2O2-activated Ca2+ channels mediate both influx of Ca2+ in protoplasts and increases in [Ca2+]cyt in intact guard cells. ABA induces the production of H2O2 in guard cells. If H2O2 production is blocked, ABA-induced closure of stomata is inhibited. Moreover, activation of Ca2+ channels by H2O2 and ABA- and H2O2-induced stomatal closing are disrupted in the recessive ABA-insensitive mutant gca2. These data indicate that ABA-induced H2O2 production and the H2O2-activated Ca2+ channels are important mechanisms for ABA-induced stomatal closing.     

A map of the day-night contrast of the extrasolar planet HD 189733b

'Hot Jupiter' extrasolar planets are expected to be tidally locked because they are close (<0.05 astronomical units, where 1 au is the average Sun-Earth distance) to their parent stars, resulting in permanent daysides and nightsides. By observing systems where the planet and star periodically eclipse each other, several groups have been able to estimate the temperatures of the daysides of these planets. A key question is whether the atmosphere is able to transport the energy incident upon the dayside to the nightside, which will determine the temperature at different points on the planet's surface. Here we report observations of HD 189733, the closest of these eclipsing planetary systems, over half an orbital period, from which we can construct a 'map' of the distribution of temperatures. We detected the increase in brightness as the dayside of the planet rotated into view. We estimate a minimum brightness temperature of 973 +/- 33 K and a maximum brightness temperature of 1,212 +/- 11 K at a wavelength of 8 mum, indicating that energy from the irradiated dayside is efficiently redistributed throughout the atmosphere, in contrast to a recent claim for another hot Jupiter. Our data indicate that the peak hemisphere-integrated brightness occurs 16 +/- 6 degrees before opposition, corresponding to a hotspot shifted east of the substellar point. The secondary eclipse (when the planet moves behind the star) occurs 120 +/- 24 s later than predicted, which may indicate a slightly eccentric orbit.     

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.     

Giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder affecting both the central and peripheral nervous systems. Cytopathologically, the disorder is characterized by giant axons with derangements of cytoskeletal components. Geneticists refined the chromosomal interval containing the locus, culminating in the cloning of the defective gene, GAN. To date, many distinct mutations scattered throughout the coding region of the locus have been reported by researchers from different groups around the world. GAN encodes the protein, gigaxonin. Recently, a genetic mouse model of the disease was generated by targeted disruption of the locus. Over the years, the molecular mechanisms underlying GAN have attracted much interest. Studies have revealed that gigaxonin appears to play an important role in cytoskeletal functions and dynamics by directing ubiquitin-mediated degradations of cytoskeletal proteins. Aberrant accumulations of cytoskeletal-associated proteins caused by a defect in the ubiquitinproteasome system (UPS) have been shown to be responsible for neurodegeneration occurring in GAN-null neurons, providing strong support for the notion that UPS plays crucial roles in cytoskeletal functions and dynamics. However, many key questions about the disease remain unanswered. Received 6 September 2006; received after revision 11 October 2006; accepted 5 December 2006 Y. Yang, E. Allen The authors contributed equally to this work.