Microbial response to limited nutrients in shallow water immediately after the end-Permian mass extinction

Previous work indicates that a variety of microbes bloomed in the oceans after the end-Permian faunal mass extinction, but evidence is sporadically documented. Thus, the nature and geographic distribution of such microbes and their associations are unclear, addressed in this study using a series of biomarker groups. On the basis of microbial biomarker records of the 2-methylhopane index, evidence is presented for cyanobacterial blooms in both the western and eastern Tethys Sea and in both shallow and deep waters, after the mass extinction. The enhanced relative abundance of C(28) (expressed by the C(28) /C(29) ratio of) regular steranes suggests a bloom of prasinophyte algae occurred immediately after the end-Permian faunal extinction, comparable with those observed in some other mass extinctions in Phanerozoic. Significantly, cyanobacteria and prasinophyte algae show a synchronized onset of bloom in the shallow water Bulla section, north Italy, inferring for the first time their coupled response to the biotic crisis and the associated environmental conditions. However, in Meishan of Zhejiang Province in south China, the bloom declined earlier than in Bulla. The association of increased 2-methylhopane index with a negative shift in the nitrogen isotope composition infers a scenario of enhanced nitrogen fixation by cyanobacteria immediately after the faunal mass extinction. N(2) fixation by cyanobacteria is here interpreted to have provided prasinophyte algae with ammonium in nutrient-limited shallow waters, and thus caused their associated blooms.     

Microbialites and global environmental change across the Permian-Triassic boundary: a synthesis

Permian-Triassic boundary microbialites (PTBMs) are thin (0.05-15 m) carbonates formed after the end-Permian mass extinction. They comprise Renalcis-group calcimicrobes, microbially mediated micrite, presumed inorganic micrite, calcite cement (some may be microbially influenced) and shelly faunas. PTBMs are abundant in low-latitude shallow-marine carbonate shelves in central Tethyan continents but are rare in higher latitudes, likely inhibited by clastic supply on Pangaea margins. PTBMs occupied broadly similar environments to Late Permian reefs in Tethys, but extended into deeper waters. Late Permian reefs are also rich in microbes (and cements), so post-extinction seawater carbonate saturation was likely similar to the Late Permian. However, PTBMs lack widespread abundant inorganic carbonate cement fans, so a previous interpretation that anoxic bicarbonate-rich water upwelled to rapidly increase carbonate saturation of shallow seawater, post-extinction, is problematic. Preliminary pyrite framboid evidence shows anoxia in PTBM facies, but interbedded shelly faunas indicate oxygenated water, perhaps there was short-term pulsing of normally saturated anoxic water from the oxygen-minimum zone to surface waters. In Tethys, PTBMs show geographic variations: (i) in south China, PTBMs are mostly thrombolites in open shelf settings, largely recrystallised, with remnant structure of Renalcis-group calcimicrobes; (ii) in south Turkey, in shallow waters, stromatolites and thrombolites, lacking calcimicrobes, are interbedded, likely depth-controlled; and (iii) in the Middle East, especially Iran, stromatolites and thrombolites (calcimicrobes uncommon) occur in different sites on open shelves, where controls are unclear. Thus, PTBMs were under more complex control than previously portrayed, with local facies control playing a significant role in their structure and composition.     

The origin of glucocorticoid hormone oscillations

Oscillating levels of adrenal glucocorticoid hormones are essential for optimal gene expression, and for maintaining physiological and behavioural responsiveness to stress. The biological basis for these oscillations is not known, but a neuronal "pulse generator" within the hypothalamus has remained a popular hypothesis. We demonstrate that pulsatile hypothalamic activity is not required for generating ultradian glucocorticoid oscillations. We show that a constant level of corticotrophin-releasing hormone (CRH) can activate a dynamic pituitary-adrenal peripheral network to produce ultradian adrenocorticotrophic hormone and glucocorticoid oscillations with a physiological frequency. This oscillatory response to CRH is dose dependent and becomes disrupted for higher levels of CRH. These data suggest that glucocorticoid oscillations result from a sub-hypothalamic pituitary-adrenal system, which functions as a deterministic peripheral hormone oscillator with a characteristic ultradian frequency. This constitutes a novel mechanism by which the level, rather than the pattern, of CRH determines the dynamics of glucocorticoid hormone secretion.     

Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase

Numerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis. Despite its high clinical relevance, the molecular function of ADPN and the mechanism by which I148M variant affects hepatic metabolism are unclear. Here we show that ADPN promotes cellular lipid synthesis by converting lysophosphatidic acid (LPA) into phosphatidic acid. The ADPN-catalyzed LPA acyltransferase (LPAAT) reaction is specific for LPA and long-chain acyl-CoAs. Wild-type mice receiving a high-sucrose diet exhibit substantial upregulation of Adpn in the liver and a concomitant increase in LPAAT activity. In Adpn-deficient mice, this diet-induced increase in hepatic LPAAT activity is reduced. Notably, the I148M variant of human ADPN exhibits increased LPAAT activity leading to increased cellular lipid accumulation. This gain of function provides a plausible biochemical mechanism for the development of liver steatosis in subjects carrying the I148M variant.     

Mutations in the U5 snRNA result in altered splicing of subsets of pre-mRNAs and reduced stability of Prp8

The U5 snRNA loop 1 aligns the 5′ and 3′ exons for ligation during the second step of pre-mRNA splicing. U5 is intimately associated with Prp8, which mediates pre-mRNA repositioning within the catalytic core of the spliceosome and interacts directly with U5 loop 1. The genome-wide effect of three U5 loop 1 mutants has been assessed by microarray analysis. These mutants exhibited impaired and improved splicing of subsets of pre-mRNAs compared to wild-type U5. Analysis of pre-mRNAs that accumulate revealed a change in base prevalence at specific positions near the splice sites. Analysis of processed pre-mRNAs exhibiting mRNA accumulation revealed a bias in base prevalence at one position within the 5′ exon. While U5 loop 1 can interact with some of these positions the base bias is not directly related to sequence changes in loop 1. All positions that display a bias in base prevalence are at or next to positions known to interact with Prp8. Analysis of Prp8 in the presence of the three U5 loop 1 mutants revealed that the most severe mutant displayed reduced Prp8 stability. Depletion of U5 snRNA in vivo also resulted in reduced Prp8 stability. Our data suggest that certain mutations in U5 loop 1 perturb the stability of Prp8 and may affect interactions of Prp8 with a subset of pre-mRNAs influencing their splicing. Therefore, the integrity of U5 is important for the stability of Prp8 during splicing and provides one possible explanation for why U5 loop 1 and Prp8 are so highly conserved.     

Bronchiectasis in acute leukaemia.

Five children in remission from acute lymphoblastic leukaemia developed bronchiectasis when on chemotherapy. Persistent collapse or consolidation on chest radiographs was helpful in suggesting the diagnosis. Necropsy established the diagnosis in one child who died of massive haemoptysis when in complete remission, and bronchography confirmed the diagnosis in three. In a further child the diagnosis was based on clinical and chest X-ray findings alone. The surviving children were treated with prophylactic rotating antibiotics. Routine chest radiographs are recommended in children with acute lymphoblastic leukaemia, as bronchiectasis may otherwise be underdiagnosed.     

Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo

NK cells hold great potential for improving the immunotherapy of cancer. Nevertheless, tumor cells can effectively escape NK cell-mediated apoptosis through interaction of MHC molecules with NK cell inhibitory receptors. Thus, to harness NK cell effector function against tumors, we used Amaxa gene transfer technology to gene-modify primary mouse NK cells with a chimeric single-chain variable fragment (scFv) receptor specific for the human erbB2 tumor-associated Ag. The chimeric receptor was composed of the extracellular scFv anti-erbB2 Ab linked to the transmembrane and cytoplasmic CD28 and TCR-zeta signaling domains (scFv-CD28-zeta). In this study we demonstrated that mouse NK cells gene-modified with this chimera could specifically mediate enhanced killing of an erbB2(+) MHC class I(+) lymphoma in a perforin-dependent manner. Expression of the chimera did not interfere with NK cell-mediated cytotoxicity mediated by endogenous NK receptors. Furthermore, adoptive transfer of gene-modified NK cells significantly enhanced the survival of RAG mice bearing established i.p. RMA-erbB2(+) lymphoma. In summary, these data suggest that use of genetically modified NK cells could broaden the scope of cancer immunotherapy for patients.     

?Microbialites in the Permian-Triassic boundary interval in central China: Structure, age and distribution

Summary A carbonate crust, with a principally digitate structure, caps latest Permian reef complexes in east Sichuan, China. The crust contains the conodontHindeodus parvus, confirming its age as earliest Triassic; it therefore closely postdates the end-Permian mass extinction, and is related to associated palaeoenvironmental change. Although its branches have lobate margins, and internal structures of radial fabrics and lobate fabrics in different specimens, an organic origin cannot be confirmed, because crust fabric is largely recrystallised. Therefore we apply the term ?microbialite to reflect uncertainty of its nature. The crust is co-eval (within theparvus Zone) with confirmed microbial biostromes and mounds in Guizhou Province, south of Sichuan. The sum of evidence, assembled by workers in several sites worldwide, indicates a sea-level rise occurred in the boundary interval, and this is corroborated by facies of the Sichuan crust. Abrupt appearance and disappearance of the crust, formed by precipitated carbonates, in east Sichuan, represents short-lived unusual post-extinction marine conditions which were switched abruptly on, then off. Microbial deposits overlying the P/T boundary in other locations in the Tethys Ocean (Iran and Japan) support the view that the unusual oceanic conditions had at least a regional distribution. Because the crust abruptly terminates, and is not succeeded by fossil-rich deposits, application of the disaster biota concept is inappropriate; an environmentally-driven control on carbonate precipitation is better supported by the evidence, whether or not it was biotically-mediated.     

Study of the mitotic and meiotic chromosomes of sotol (<i>Dasylirion cedrosanum</i> Trel.)

The genus Dasylirion is a group of plants typically present in the Chihuahuan Desert, perennial, with a dioecious sexual behavior and commonly called sotoles. This genus has been little studied from the biological point of view, and the bases of its reproductive response remain unknown. In this work we studied the chromosome number and meiotic response of Dasylirion cedrosanum in the county of Saltillo, Coahuila, located at the North East of Mexico. For the preparation of mitotic chromosomes, we used a technique based on enzymatic treatment with pectolyase and cellulase, as well as staining with acetocarmin dye. For the study of meiosis, male flower buds were collected, fixed and stained for analysis with the same dye. As a result, the gametic (n = x = 19) and somatic chromosome (2n = 38) numbers of D. cedrosanum are reported for the first time, being consistent with previous findings in other Dasylirion species, which points to a constant ploidy level across the genus. Variation was observed in the morphology and size of the somatic chromosomes, with types ranging from submetacentric to subtelocentric, and sizes oscillating in a range of 4.43 µm, with an average total length of 112.38 µm for the diploid chromosome complement. This shows that the chromosome complement of D. cedrosanom would belong to a 3B classification of Stebins, with a medium variation between chromosome lengths and low chromosome asymmetry. This variation indicates the feasibility of constructing a chromosome ideotype for this species. The meiotic chromosome pairing showed a chromosome behavior consistent with a disomic inheritance characteristic of a diploid species, with prevalence of ring and chain bivalents, typically without pairing abnormalities. Bivalent configurations in all cases were symmetrical.The normal and symmetrical meiotic pairing indicates a balanced production of gametes, and suggests the absence of heteromorphic sex determination.