Thyroid neoplasia following low-dose radiation in childhood

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.     

The Arabidopsis MYB5 Transcription Factor Regulates Mucilage Synthesis,Seed Coat Development,and Trichome Morphogenesis

The Arabidopsis thaliana MYB5 gene is expressed in trichomes and seeds, including the seed coat. Constitutive expression of MYB5 resulted in the formation of more small trichomes and ectopic trichomes and a reduction in total leaf trichome numbers and branching. A myb5 mutant displayed minimal changes in trichome morphology, while a myb23 mutant produced increased numbers of small trichomes and two-branched trichomes. A myb5 myb23 double mutant developed more small rosette trichomes and two-branched trichomes than the single mutants. These results indicate that MYB5 and MYB23 regulate trichome extension and branching. The seed coat epidermal cells of myb5 and myb5 myb23 were irregular in shape, developed flattened columellae, and produced less mucilage than those of the wild type. Among the downregulated genes identified in the myb5 seeds using microarray analysis were ABE1 and ABE4 (α/β fold hydrolase/esterase genes), MYBL2, and GLABRA2. The same genes were also downregulated in transparent testa glabra1 (ttg1) seeds, suggesting that MYB5 collaborates with TTG1 in seed coat development. These genes were upregulated in leaves and roots by ectopically expressed MYB5. The MYBL2, ABE1, and ABE4 promoters were active in seeds, including seed coats, and the latter two also in trichomes. Models of the MYB5 regulatory networks involved in seed coat and trichome development are presented.     

MADS-box gene expression and implications for developmental origins of the grass spikelet

Basic questions regarding the origin and evolution of grass (Poaceae) inflorescence morphology remain unresolved, including the developmental genetic basis for evolution of the highly derived outer spikelet organs. To evaluate homologies between the outer sterile organs of grass spikelets and inflorescence structures of nongrass monocot flowers, we describe expression patterns of APETALA1/FRUITFULL-like (AP1/FUL) and LEAFY HULL STERILE-like (LHS1) MADS-box genes in an early-diverging grass (Streptochaeta angustifolia) and a nongrass outgroup (Joinvillea ascendens). AP1/FUL-like genes are expressed only in floral organs of J. ascendens, supporting the hypothesis that they mark the floral boundary in nongrass monocots, and JaLHS1/OsMADS5 is expressed in the inner and outer tepals, stamen filaments and pistil. In S. angustifolia, SaFUL2 is expressed in all 11 (or 12) bracts of the primary inflorescence branch, but not in the suppressed floral bract below the abscission zone. In contrast, SaLHS1 is only expressed in bracts 6-11 (or 12). Together, these data are consistent with the hypotheses that (1) bracts 1-5 of S. angustifolia primary inflorescence branches and glumes of grass spikelets are homologous and that (2) the outer tepals of immediate grass relatives, bracts 6-8 of S. angustifolia, and the lemma/palea are homologous, although other explanations are possible.     

Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection

In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8⁺ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8⁺ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4⁺ and CD4⁻CD8⁻ T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection.     

Genetic Engineering of Enterobacter asburiae Strain JDR-1 for Efficient Production of Ethanol from Hemicellulose Hydrolysates

Dilute acid pretreatment is an established method for hydrolyzing the methylglucuronoxylans of hemicellulose to release fermentable xylose. In addition to xylose, this process releases the aldouronate methylglucuronoxylose, which cannot be metabolized by current ethanologenic biocatalysts. Enterobacter asburiae JDR-1, isolated from colonized wood, was found to efficiently ferment both methylglucuronoxylose and xylose in acid hydrolysates of sweet gum xylan, producing predominantly ethanol and acetate. Transformation of E. asburiae JDR-1 with pLOI555 or pLOI297, each containing the PET operon containing pyruvate decarboxylase (pdc) and alcohol dehydrogenase B (adhB) genes derived from Zymomonas mobilis, replaced mixed-acid fermentation with homoethanol fermentation. Deletion of the pyruvate formate lyase (pflB) gene further increased the ethanol yield, resulting in a stable E. asburiae E1(pLOI555) strain that efficiently utilized both xylose and methylglucuronoxylose in dilute acid hydrolysates of sweet gum xylan. Ethanol was produced from xylan hydrolysate by E. asburiae E1(pLOI555) with a yield that was 99% of the theoretical maximum yield and at a rate of 0.11 g ethanol/g (dry weight) cells/h, which was 1.57 times the yield and 1.48 times the rate obtained with the ethanologenic strain Escherichia coli KO11. This engineered derivative of E. asburiae JDR-1 that is able to ferment the predominant hexoses and pentoses derived from both hemicellulose and cellulose fractions is a promising subject for development as an ethanologenic biocatalyst for production of fuels and chemicals from agricultural residues and energy crops.Lignocellulosic resources, including forest and agricultural residues and evolving energy crops, offer benign alternatives to petroleum-based resources for production of fuels and chemicals. As renewable resources, these lignocellulosic materials are expected to decrease dependence on exhaustible supplies of petroleum and mitigate the net release of carbon dioxide into the atmosphere. The development of economically acceptable bioconversion processes requires pretreatments that release the maximal quantities of hexoses (predominantly glucose released from cellulose) and pentoses (arabinose and xylose) from hemicelluloses and also requires microbial biocatalysts that efficiently convert these compounds to a single targeted product.As one of three main components of lignocellulosics, hemicellulose contains polysaccharides comprised of pentoses, hexoses and sugar acids that account for 20 to 35% of the total biomass from different sources (21). Methylglucuronoxylans (MeGAX_n), consisting of long chains of as many as 70 β-xylopyranose residues linked by β-1,4-glycosidic bonds (25), are the predominant components in the hemicellulose fractions of agricultural residues and energy crops, including corn stover, sugarcane bagasse, poplar, and switchgrass (7, 18, 23, 24). In hardwood and softwood xylans, a 4-O-methylglucuronic acid is attached at the 2′ position of every sixth to eighth xylose residue (12, 15). Dilute acid hydrolysis is commonly used to make the monosaccharides comprising hemicellulose accessible for fermentation (7, 22). However, the α-1,2 glucuronosyl linkage in xylan is resistant to dilute acid hydrolysis, which results in the release of methylglucuronoxylose (MeGAX) along with xylose and other monosaccharides. MeGAX is not fermented by bacterial biocatalysts currently used to convert hemicellulose to ethanol, such as Escherichia coli KO11 (2, 6). In sweet gum xylan, as much as 27% of the carbohydrate may be in this unfermentable fraction after dilute acid pretreatment (2, 20). Complete utilization of all hemicellulosic sugars can improve the efficiency of conversion of lignocellulosic materials to fuel ethanol and other value-added products.Our previous research on the processing of hemicelluloses for fermentation led to isolation of Enterobacter asburiae strain JDR-1. This isolate performed mixed-acid fermentation of the principal hexoses and pentoses that can be derived from cellulose and hemicellulose fractions of lignocellulosic biomass and exhibited a novel metabolic potential based on its ability to ferment MeGAX and xylose to ethanol and acetate as major fermentation products from sweet gum MeGAX_n hydrolysates generated by dilute acid pretreatment (2). This strain has been genetically modified to produce d-(−)-lactate as the predominant product from acid hydrolysates of MeGAX_n (3).In this study, the PET operon containing the pdc, adhA, and adhB genes from Zymomonas mobilis (10, 11) was incorporated into a pflB E. asburiae JDR-1 isolate by plasmid transformation to construct homoethanologenic strains. The resulting recombinant strains were compared with E. asburiae wild-type strain JDR-1 and the ethanologenic strain E. coli KO11 to evaluate their efficiencies of production of ethanol from dilute acid hydrolysates of sweet gum MeGAX_n.     

Does Sleep Play a Role in Memory Consolidation? A Comparative Test

Sleep is a pervasive characteristic of mammalian species, yet its purpose remains obscure. It is often proposed that ‘sleep is for the brain’, a view that is supported by experimental studies showing that sleep improves cognitive processes such as memory consolidation. Some comparative studies have also reported that mammalian sleep durations are higher among more encephalized species. However, no study has assessed the relationship between sleep and the brain structures that are implicated in specific cognitive processes across species. The hippocampus, neocortex and amygdala are important for memory consolidation and learning and are also in a highly actived state during sleep. We therefore investigated the evolutionary relationship between mammalian sleep and the size of these brain structures using phylogenetic comparative methods. We found that evolutionary increases in the size of the amygdala are associated with corresponding increases in NREM sleep durations. These results are consistent with the hypothesis that NREM sleep is functionally linked with specializations of the amygdala, including perhaps memory processing.