A Study of the Steric Requirements of the 9-Anthracyl Group and Their Contribution to the Preparation of 9-Anthracylboron Compounds

Author Institution: Department of Chemistry, University of Toledo, Toledo, Ohi

The Paleoecological Record of 6 ka BP Climate in the Canadian Prairie Provinces

Synthesis of available paleoecological studies in the Prairie provinces of Canada indicates that although the peak in postglacial aridity that characterized early Holocene climate of the western foothills and plains had passed, conditions remained warmer and drier than present throughout the region ca. 6000 yr BP Compared to today, treeline elevations were higher and alpine glaciers were reduced in size in the Rocky Mountains, lake levels were lower over much of the Interior Plains, and the grassland and boreal forest ecozones extended north of their present positions. Forest fires were more prevalent ca. 6000 yr BP than they are today, aiding westward migration of jack pine (Pinus banksiana) through the boreal forest and increasing the area occupied by grassland in boreal and montane forest regions. Attempts to quantify the magnitude of 6 ka temperature and precipitation differences have produced variable results, but suggest that mean annual temperature was 0.50°C to 1.50°C higher than today (summer temperature may have been up to 3°C higher) and mean annual precipitation was reduced by 65 mm (or summer precipitation was reduced by 50 mm), compared to present. The nature and scale of these changes suggests that a vigorous zonal atmospheric circulation pattern, similar to that of the 1930s but shifted northward, prevailed at 6 ka.La synthèse des études paléoécologiques montrent qu'à 6 ka le maximum d'aridité, qui caractérisait l'Holocène inférieur, avait été atteint, mais le climat demeurait plus chaud et plus sec que maintenant dans toute la région. Les différentes limites des arbres étaient plus élevées qu'aujourd'hui et la superficie des glaciers alpins étaient plus petite, les niveaux lacustres étaient moins élevés dans la plus grande partie des plaines intérieures et les écozones des Prairies et de la forêt boréale s'étendaient plus au nord qu'aujourd'hui. Les feux de forêt étaient plus fréquents à 6 ka qu'actuellement, ce qui a favorisé la migration du pin gris (Pinus banksiana) vers l'ouest à travers la forêt boréale et accru la superficie de la prairie dans les zones de forêts boréale et alpine. Les essais faits dans le but de mesurer l'ampleur des différences de températures et de précipitations à 6 ka ont donné des résultats variables, mais montrent que la température était de 0,5 à 1,5°C plus élevé que maintenant (avec une température estivale jusqu'à 3°C plus élevée) et les précipitations annuelles moyennes étaient de 65 mm inférieures (avec des précipitations estivales de 50 mm inférieures) à maintenant. La nature et le degré des changements laissent croire qu'une forte circulation atmosphérique zonale, semblable à celle des années 1930, mais plus nordique, existait à 6 ka.Die Synthèse der verfùgbaren palâoôkologischen Studien in den Prârie-Provinzen Kanadas zeigt, daf3 das Klima in der ganzen Region um etwa 6000 Jahre v.u.Z. warmer und trockener als gegenwârtig blieb, wenn auch das Maximum an postglazialer Trockenheit, welches im frùhen Holozàn das Klima der westlichen Gebirgsauslâufer und Ebenen charakterisierte, vorùber war. Verglichen mit heute waren die Baumgrenzen hôher und die alpinen Gletscher in den Rocky Mountains kleiner, die Seehôhen waren niedriger im grôBten Teil der inneren Ebenen, und die Ôkozonen von Grasland und nôrdlichem WaId erstreckten sich weiter nôrdlich als heute. Waldbrânde traten um etwa 6000 v.u.Z. hâufiger als gegenwârtig auf und haben so die Westwàrtswanderung von Graukiefer (Pinus banksiana) durch den nôrdlichen WaId begùnstigt und die Graslandflàchen in den Gebieten des nôrdlichen und alpinen Waldes vergrôBert. Versuche, den Umfang der Unterschiede in Temperatur und Niederschlàgen um 6 ka zu bestimmen, ergaben wechselnde Ergebnissse, doch zeigen sie, daB die durchschnittliche jâhrliche Temperatur 0.5° C bis 1.50C hôher als gegenwârtig war (die Sommertemperatur dûrfte bis zu 3°C hôher gewesen sein) und die durchschnittlichen jâhrlichen Niederschlâge waren um 65 mm geringer (oder die Sommer-Niederschlàge waren um 50 mm geringer) verglichen mit heute. Die Natur und der Grad dieser Wechsel lassen vermuten, daB eine krâftige zonale atmosphàrische Strômung, àhnlich der von den 1930 iger Jahren aber nôrdlicher gelagert, um 6 ka vorherrschte

Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra.

The bacterium Mycobacterium tuberculosis (Mtb) causes tuberculosis and is responsible for more human mortality than any other single pathogen1. Progression to active disease occurs in only a fraction of infected individuals and is predicted by an elevated type I interferon (IFN) response2-7. Whether or how IFNs mediate susceptibility to Mtb has been difficult to study due to a lack of suitable mouse models6-11. Here, we examined B6.Sst1S congenic mice that carry the 'susceptible' allele of the Sst1 locus that results in exacerbated Mtb disease12-14. We found that enhanced production of type I IFNs was responsible for the susceptibility of B6.Sst1S mice to Mtb. Type I IFNs affect the expression of hundreds of genes, several of which have previously been implicated in susceptibility to bacterial infections6,7,15-18. Nevertheless, we found that heterozygous deficiency in just a single IFN target gene, Il1rn, which encodes interleukin-1 receptor antagonist (IL-1Ra), is sufficient to reverse IFN-driven susceptibility to Mtb in B6.Sst1S mice. In addition, antibody-mediated neutralization of IL-1Ra provided therapeutic benefit to Mtb-infected B6.Sst1S mice. Our results illustrate the value of the B6.Sst1S mouse to model IFN-driven susceptibility to Mtb, and demonstrate that IL-1Ra is an important mediator of type I IFN-driven susceptibility to Mtb infections in vivo

Correspondence between geometrical and differential definitions of the sine and cosine functions and connection with kinematics

In classical physics, the familiar sine and cosine functions appear in two forms: (1) geometrical, in the treatment of vectors such as forces and velocities, and (2) differential, as solutions of oscillation and wave equations. These two forms correspond to two different definitions of trigonometric functions, one geometrical using right triangles and unit circles, and the other employing differential equations. Although the two definitions must be equivalent, this equivalence is not demonstrated in textbooks. In this manuscript, the equivalence between the geometrical and the differential definition is presented assuming no a priori knowledge of the properties of sine and cosine functions. We start with the usual length projections on the unit circle and use elementary geometry and elementary calculus to arrive to harmonic differential equations. This more general and abstract treatment not only reveals the equivalence of the two definitions but also provides an instructive perspective on circular and harmonic motion as studied in kinematics. This exercise can help develop an appreciation of abstract thinking in physics.Comment: 6 pages including 1 figur

STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection.

UnlabelledSTING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ligand remains unknown. In this report, we provide evidence that Chlamydia synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite not previously identified in Gram-negative bacteria, and that this metabolite is a prominent ligand for STING-mediated activation of IFN responses during infection. We used primary mouse lung fibroblasts and HEK293T cells to compare IFN-β responses to Chlamydia infection, c-di-AMP, and other type I IFN-inducing stimuli. Chlamydia infection and c-di-AMP treatment induced type I IFN responses in cells expressing STING but not in cells expressing STING variants that cannot sense cyclic dinucleotides but still respond to cytoplasmic DNA. The failure to induce a type I IFN response to Chlamydia and c-di-AMP correlated with the inability of STING to relocalize from the endoplasmic reticulum to cytoplasmic punctate signaling complexes required for IFN activation. We conclude that Chlamydia induces STING-mediated IFN responses through the detection of c-di-AMP in the host cell cytosol and propose that c-di-AMP is the ligand predominantly responsible for inducing such a response in Chlamydia-infected cells.ImportanceThis study shows that the Gram-negative obligate pathogen Chlamydia trachomatis, a major cause of pelvic inflammatory disease and infertility, synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite that thus far has been described only in Gram-positive bacteria. We further provide evidence that the host cell employs an endoplasmic reticulum (ER)-localized cytoplasmic sensor, STING (stimulator of interferon [IFN] genes), to detect c-di-AMP synthesized by Chlamydia and induce a protective IFN response. This detection occurs even though Chlamydia is confined to a membrane-bound vacuole. This raises the possibility that the ER, an organelle that innervates the entire cytoplasm, is equipped with pattern recognition receptors that can directly survey membrane-bound pathogen-containing vacuoles for leaking microbe-specific metabolites to mount type I IFN responses required to control microbial infections

Timing and causes of North African wet phases during the last glacial period and implications for modern human migration

We present the first speleothem-derived central North Africa rainfall record for the last glacial period. The record reveals three main wet periods at 65-61 ka, 52.5-50.5 ka and 37.5-33 ka that lead obliquity maxima and precession minima. We find additional minor wet episodes that are synchronous with Greenland interstadials. Our results demonstrate that sub-tropical hydrology is forced by both orbital cyclicity and North Atlantic moisture sources. The record shows that after the end of a Saharan wet phase around 70 ka ago, North Africa continued to intermittently receive substantially more rainfall than today, resulting in favourable environmental conditions for modern human expansion. The encounter and subsequent mixture of Neanderthals and modern humans – which, on genetic evidence, is considered to have occurred between 60 and 50 ka – occurred synchronously with the wet phase between 52.5 and 50.5 ka. Based on genetic evidence the dispersal of modern humans into Eurasia started less than 55 ka ago. This may have been initiated by dry conditions that prevailed in North Africa after 50.5 ka. The timing of a migration reversal of modern humans from Eurasia into North Africa is suggested to be coincident with the wet period between 37.5 and 33 ka

Spectral-domain optical coherence tomography as a noninvasive method to assess damaged and regenerating adult zebrafish retinas.

These experiments assessed the ability of spectral-domain optical coherence tomography (SD-OCT) to accurately represent the structural organization of the adult zebrafish retina and reveal the dynamic morphologic changes during either light-induced damage and regeneration of photoreceptors or ouabain-induced inner retinal damage. Retinas of control dark-adapted adult albino zebrafish were compared with retinas subjected to 24 hours of constant intense light and recovered for up to 8 weeks or ouabain-damaged retinas that recovered for up to 3 weeks. Images were captured and the measurements of retinal morphology were made by SD-OCT, and then compared with those obtained by histology of the same eyes. Measurements between SD-OCT and histology were very similar for the undamaged, damaged, and regenerating retinas. Axial measurements of SD-OCT also revealed vitreal morphology that was not readily visualized by histology. SD-OCT accurately represented retinal lamination and photoreceptor loss and recovery during light-induced damage and subsequent regeneration. SD-OCT was less accurate at detecting the inner nuclear layer in ouabain-damaged retinas, but accurately detected the undamaged outer nuclear layer. Thus, SD-OCT provides a noninvasive and quantitative method to assess the morphology and the extent of damage and repair in the zebrafish retina