Abrupt ice-age shifts in southern westerly winds and Antarctic climate forced from the north.

The mid-latitude westerly winds of the Southern Hemisphere play a central role in the global climate system via Southern Ocean upwelling1, carbon exchange with the deep ocean2, Agulhas leakage (transport of Indian Ocean waters into the Atlantic)3 and possibly Antarctic ice-sheet stability4. Meridional shifts of the Southern Hemisphere westerly winds have been hypothesized to occur5,6 in parallel with the well-documented shifts of the intertropical convergence zone7 in response to Dansgaard-Oeschger (DO) events- abrupt North Atlantic climate change events of the last ice age. Shifting moisture pathways to West Antarctica8 are consistent with this view but may represent a Pacific teleconnection pattern forced from the tropics9. The full response of the Southern Hemisphere atmospheric circulation to the DO cycle and its impact on Antarctic temperature remain unclear10. Here we use five ice cores synchronized via volcanic markers to show that the Antarctic temperature response to the DO cycle can be understood as the superposition of two modes: a spatially homogeneous oceanic 'bipolar seesaw' mode that lags behind Northern Hemisphere climate by about 200 years, and a spatially heterogeneous atmospheric mode that is synchronous with abrupt events in the Northern Hemisphere. Temperature anomalies of the atmospheric mode are similar to those associated with present-day Southern Annular Mode variability, rather than the Pacific-South American pattern. Moreover, deuterium-excess records suggest a zonally coherent migration of the Southern Hemisphere westerly winds over all ocean basins in phase with Northern Hemisphere climate. Our work provides a simple conceptual framework for understanding circum-Antarctic temperature variations forced by abrupt Northern Hemisphere climate change. We provide observational evidence of abrupt shifts in the Southern Hemisphere westerly winds, which have previously documented1-3 ramifications for global ocean circulation and atmospheric carbon dioxide. These coupled changes highlight the necessity of a global, rather than a purely North Atlantic, perspective on the DO cycle.

Olfactory training with Aromastics: olfactory and cognitive effects.

PURPOSE: The olfactory system can be successfully rehabilitated with regular, intermittent stimulation during multiple daily exposures to selected sets of odors, i.e., olfactory training (OT). OT has been repeatedly shown to be an effective tool of olfactory performance enhancement. Recent advancements in studies on OT suggest that its beneficial effects exceed olfaction and extend to specific cognitive tasks. So far, studies on OT provided compelling evidence for its effectiveness, but there is still a need to search for an optimal OT protocol. The present study examined whether increased frequency of OT leads to better outcomes in both olfactory and cognitive domains. METHOD: Fifty-five subjects (28 females; Mage = 58.2 ± 11.3 years; 26 patients with impaired olfaction) were randomly assigned to a standard (twice a day) or intense (four times a day) OT. Olfactory and cognitive measurements were taken before and after OT. RESULTS: OT performed twice a day was more effective in supporting olfactory rehabilitation and interventions targeted to verbal semantic fluency than OT performed four times a day, even more so in subjects with lower baseline scores. CONCLUSIONS: OT is effective in supporting olfactory rehabilitation and interventions targeted to verbal semantic fluency. However, it may be prone to a ceiling effect, being efficient in subjects presenting with lower baseline olfactory performance and lower verbal semantic fluency.

The Gamburtsev mountains and the origin and early evolution of the Antarctic Ice Sheet.

Ice-sheet development in Antarctica was a result of significant and rapid global climate change about 34 million years ago. Ice-sheet and climate modelling suggest reductions in atmospheric carbon dioxide (less than three times the pre-industrial level of 280 parts per million by volume) that, in conjunction with the development of the Antarctic Circumpolar Current, led to cooling and glaciation paced by changes in Earth's orbit. Based on the present subglacial topography, numerical models point to ice-sheet genesis on mountain massifs of Antarctica, including the Gamburtsev mountains at Dome A, the centre of the present ice sheet. Our lack of knowledge of the present-day topography of the Gamburtsev mountains means, however, that the nature of early glaciation and subsequent development of a continental-sized ice sheet are uncertain. Here we present radar information about the base of the ice at Dome A, revealing classic Alpine topography with pre-existing river valleys overdeepened by valley glaciers formed when the mean summer surface temperature was around 3 degrees C. This landscape is likely to have developed during the initial phases of Antarctic glaciation. According to Antarctic climate history (estimated from offshore sediment records) the Gamburtsev mountains are probably older than 34 million years and were the main centre for ice-sheet growth. Moreover, the landscape has most probably been preserved beneath the present ice sheet for around 14 million years.

Water networks contribute to enthalpy/entropy compensation in protein-ligand binding.

The mechanism (or mechanisms) of enthalpy-entropy (H/S) compensation in protein-ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands--human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination--that we use to define enthalpy/entropy (H/S) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.

Tag-assisted liquid-phase peptide synthesis using hydrophobic benzyl alcohols as supports.

A soluble tag-assisted liquid-phase peptide synthesis was successfully established based on simple hydrophobic benzyl alcohols, which can be easily prepared from naturally abundant materials. Excellent precipitation yields can be obtained at each step, combining the best properties of solid-phase and liquid-phase techniques. This approach can also be applied efficiently to fragment couplings, allowing chemical synthesis of several bioactive peptides.

Bioelectrocatalytic oxidation of glucose with antibiotic channel-containing liposomes.

We developed an efficient bioelectrocatalytic system for glucose oxidation by introducing hydrophilic glucose-permeable antibiotic channels into liposomes.

Northern Hemisphere forcing of climatic cycles in Antarctica over the past 360,000 years.

The Milankovitch theory of climate change proposes that glacial-interglacial cycles are driven by changes in summer insolation at high northern latitudes. The timing of climate change in the Southern Hemisphere at glacial-interglacial transitions (which are known as terminations) relative to variations in summer insolation in the Northern Hemisphere is an important test of this hypothesis. So far, it has only been possible to apply this test to the most recent termination, because the dating uncertainty associated with older terminations is too large to allow phase relationships to be determined. Here we present a new chronology of Antarctic climate change over the past 360,000 years that is based on the ratio of oxygen to nitrogen molecules in air trapped in the Dome Fuji and Vostok ice cores. This ratio is a proxy for local summer insolation, and thus allows the chronology to be constructed by orbital tuning without the need to assume a lag between a climate record and an orbital parameter. The accuracy of the chronology allows us to examine the phase relationships between climate records from the ice cores and changes in insolation. Our results indicate that orbital-scale Antarctic climate change lags Northern Hemisphere insolation by a few millennia, and that the increases in Antarctic temperature and atmospheric carbon dioxide concentration during the last four terminations occurred within the rising phase of Northern Hemisphere summer insolation. These results support the Milankovitch theory that Northern Hemisphere summer insolation triggered the last four deglaciations.

Hydrophobic tag-assisted liquid-phase synthesis of a growth hormone-inhibiting peptide somatostatin.

Hydrophobic tag-assisted liquid-phase peptide synthesis technique and disulfide bond formation have been well-combined, leading to the efficient and practical preparation of a growth hormone-inhibiting peptide somatostatin. Intramolecular disulfide bond formation has successfully been carried out even under relatively high concentrations, enabling the effective peptide modifications in preparative scale.

Atmospheric sea-salt and halogen cycles in the Antarctic.

Atmospheric sea-salt and halogen cycles play important roles in atmospheric science and chemistry including cloud processes and oxidation capacity in the Antarctic troposphere. This paper presents a review and summarizes current knowledge related to sea-salt and halogen chemistry in the Antarctic. First, presented are the seasonal variations and size distribution of sea-salt aerosols (SSAs). Second, SSA origins and sea-salt fractionation on sea-ice and ice sheets on the Antarctic continent are presented and discussed. Third, we discuss SSA release from the cryosphere. Fourth, we present SSA dispersion in the Antarctic troposphere and transport into inland areas. Fifth, heterogeneous reactions on SSAs as a source of reactive halogen species and their relationship with atmospheric chemistry are shown and discussed. Finally, we attempt to propose an outlook for obtaining better knowledge related to sea-salt and halogen chemistry and their effects on the Antarctic and the Arctic.

Putative promoter regions of miRNA genes involved in evolutionarily conserved regulatory systems among vertebrates.

MOTIVATION: Just as transcription factors, miRNA genes modulate global patterns of gene expression during differentiation, metabolic activation, stimulus response and also carcinogenesis. However, little is currently known how the miRNA gene expression itself is regulated owing to lack of basic information of their gene structure. Global prediction of promoter regions of miRNA genes would allow us to explore the mechanisms underlying gene-regulatory mechanisms involving these miRNAs. RESULTS: We speculate that if specific miRNA molecules are involved in evolutionarily conserved regulatory systems in vertebrates, this would entail a high level of conservation of the promoter of miRNA gene as well as the miRNA molecule. By our current screening of putative promoter regions of miRNA genes (miPPRs) on this base, we identified 59 miPPRs that would direct production of 79 miRNAs. We present both biochemical and bioinformatical verifications of these putative promoters.

Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates the splicing patterns of its transcripts in concert with p54(nrb).

We report that a DBHS (Drosophila behaviour, human splicing) family protein, p54(nrb), binds both BRG1 (Brahma-related gene 1) and Brm (Brahma), catalytic subunits of the SWI/SNF (switch/sucrose non-fermentable) chromatin remodelling complex, and also another core subunit of this complex, BAF60a. The N-terminal region of p54(nrb) is sufficient to pull-down other core subunits of the SWI/SNF complex, suggesting that p54(nrb) binds SWI/SNF-like complexes. PSF (polypyrimidine tract-binding protein-associated splicing factor), another DBHS family protein known to directly bind p54(nrb), was also found to associate with the SWI/SNF-like complex. When sh (short hairpin) RNAs targeting Brm were retrovirally expressed in a BRG1-deficient human cell line (NCI-H1299), the resulting clones showed down-regulation of the TERT (telomerase reverse transcriptase) gene and an enhancement of ratios of exon-7-and-8-excluded TERT mRNA that encodes a beta-site-deleted inactive protein. All of these clones display growth arrest within 2 months of the Brm-knockdown. In NCI-H1299 cells, Brm, p54(nrb), PSF and RNA polymerase II phosphorylated on CTD (C-terminal domain) Ser(2) specifically co-localize at a region incorporating an alternative splicing acceptor site of TERT exon 7. These findings suggest that, at the TERT gene locus in human tumour cells containing a functional SWI/SNF complex, Brm, and possibly BRG1, in concert with p54(nrb), would initiate efficient transcription and could be involved in the subsequent splicing of TERT transcripts by accelerating exon-inclusion, which partly contributes to the maintenance of active telomerase.

Asynchrony between Antarctic temperature and CO2 associated with obliquity over the past 720,000 years.

The δD temperature proxy in Antarctic ice cores varies in parallel with CO2 through glacial cycles. However, these variables display a puzzling asynchrony. Well-dated records of Southern Ocean temperature will provide crucial information because the Southern Ocean is likely key in regulating CO2 variations. Here, we perform multiple isotopic analyses on an Antarctic ice core and estimate temperature variations at this site and in the oceanic moisture source over the past 720,000 years, which extend the longest records by 300,000 years. Antarctic temperature is affected by large variations in local insolation that are induced by obliquity. At the obliquity periodicity, the Antarctic and ocean temperatures lag annual mean insolation. Further, the magnitude of the phase lag is minimal during low eccentricity periods, suggesting that secular changes in the global carbon cycle and the ocean circulation modulate the phase relationship among temperatures, CO2 and insolation in the obliquity frequency band.

State dependence of climatic instability over the past 720,000 years from Antarctic ice cores and climate modeling.

Climatic variabilities on millennial and longer time scales with a bipolar seesaw pattern have been documented in paleoclimatic records, but their frequencies, relationships with mean climatic state, and mechanisms remain unclear. Understanding the processes and sensitivities that underlie these changes will underpin better understanding of the climate system and projections of its future change. We investigate the long-term characteristics of climatic variability using a new ice-core record from Dome Fuji, East Antarctica, combined with an existing long record from the Dome C ice core. Antarctic warming events over the past 720,000 years are most frequent when the Antarctic temperature is slightly below average on orbital time scales, equivalent to an intermediate climate during glacial periods, whereas interglacial and fully glaciated climates are unfavourable for a millennial-scale bipolar seesaw. Numerical experiments using a fully coupled atmosphere-ocean general circulation model with freshwater hosing in the northern North Atlantic showed that climate becomes most unstable in intermediate glacial conditions associated with large changes in sea ice and the Atlantic Meridional Overturning Circulation. Model sensitivity experiments suggest that the prerequisite for the most frequent climate instability with bipolar seesaw pattern during the late Pleistocene era is associated with reduced atmospheric CO2 concentration via global cooling and sea ice formation in the North Atlantic, in addition to extended Northern Hemisphere ice sheets.

Enantioselective photooxidation of a sulfide by a chiral ruthenium(II) complex immobilized on a montmorillonite clay surface: the role of weak interactions in asymmetric induction.

The present work pursued a possibility that enantioselectivity was achieved through weak intermolecular interactions between a catalyst and a substrate. For that purpose, we studied the photooxidation of alpha-ethylbenzyl phenyl sulfide catalyzed by a polypyridyl ruthenium(II) complex as a chiral photosensitizer. No covalent bonding was formed between a catalyst and a substrate, because the complexes used ([Ru(phen)(3)](2+) or [Ru(bpy(3))(2+)]) were coordinatively saturated. Enantiomer excess (ee) was attained to be 30% when a chiral photosensitizer was immobilized on montmorillonite clay. It was even improved to 43% in the presence of an additional chiral auxiliary, dibenzoyl-D(+)-tartaric acid. Notably, no enantioselectivity was achieved when the reaction took place in homogeneous solutions. The ab initio calculations were performed on the stability of an associate composed of a catalyst (metal complex) and a product (sulfoxide) to obtain a clue to reaction mechanisms. The calculations suggest that chiral discrimination is achieved even through noncovalent interactions between a substrate and a chiral sensitizer when the attacking direction by a substrate toward a catalyst is limited sterically on a solid surface.

Polysulfated sialic acid derivatives as anti-human immunodeficiency virus.

We report the synthesis of a novel alkyl polysulfated sialic acid derivative denoted as NMSO3. NMSO3 exhibited potent inhibition against both laboratory and clinical human immunodeficiency virus type 1 (HIV-1). The anti-viral activity of this compound (1 uM) was compared to dextran sulfate (3 uM), and was found to be more potent against HIV-1IIIb than AZT (10 uM). The anti-coagulation time was more than 15-fold shorter than that of dextran sulfate. An in vivo anti-viral study of NMSO3 in NOD-SCID-PBL mice HIV model showed complete protection of the animals from virus challenge at the concentration of 10 mg/kg. This suggests that NMSO3 can be effective in the treatment of HIV-infected individuals.

Purification and characterization of polyphenol oxidase from garland chrysanthemum (Chrysanthemum coronarium L.).

Polyphenol oxidase (PPO) of garland chrysanthemum (Chrysanthemum coronarium L.) was purified approximately 32-fold with a recovery rate of 16% by ammonium sulfate fractionation, ion exchange chromatography, hydrophobic chromatography, and gel filtration. The purified enzyme appeared as a single band on PAGE and SDS-PAGE. The molecular weight of the enzyme was estimated to be about 47000 and 45000 by gel filtration and SDS-PAGE, respectively. The purified enzyme quickly oxidized chlorogenic acid and (-)-epicatechin. The K(m) value (Michaelis constant) of the enzyme was 2.0 mM for chlorogenic acid (pH 4.0, 30 degrees C) and 10.0 mM for (-)-epicatechin (pH 8.0, 40 degrees C). The optimum pH was 4.0 for chlorogenic acid oxidase (ChO) and 8.0 for (-)-epicatechin oxidase (EpO). In the pH range from 5 to 11, their activities were quite stable at 5 degrees C for 22 h. The optimum temperatures of ChO and EpO activities were 30 and 40 degrees C, respectively. Both activities were stable at up to 50 degrees C after heat treatment for 30 min. The purified enzyme was strongly inhibited by l-ascorbic acid and l-cysteine at 1 mM.

A repeatedly refuelable mediated biofuel cell based on a hierarchical porous carbon electrode.

Biofuel cells that generate electricity from renewable fuels, such as carbohydrates, must be reusable through repeated refuelling, should these devices be used in consumer electronics. We demonstrate the stable generation of electricity from a glucose-powered mediated biofuel cell through multiple refuelling cycles. This refuelability is achieved by immobilizing nicotinamide adenine dinucleotide (NAD), an electron-transfer mediator, and redox enzymes in high concentrations on porous carbon particles constituting an anode while maintaining their electrochemical and enzymatic activities after the immobilization. This bioanode can be refuelled continuously for more than 60 cycles at 1.5 mA cm(-2) without significant potential drop. Cells assembled with these bioanodes and bilirubin-oxidase-based biocathodes can be repeatedly used to power a portable music player at 1 mW cm(-3) through 10 refuelling cycles. This study suggests that the refuelability within consumer electronics should facilitate the development of long and repeated use of the mediated biofuel cells as well as of NAD-based biosensors, bioreactors, and clinical applications.

Soluble tag-assisted peptide head-to-tail cyclization: total synthesis of mahafacyclin B.

A soluble tag-assisted liquid-phase method was successfully applied to peptide head-to-tail cyclization, leading to the total synthesis of antimalarial cyclic heptapeptide, mahafacyclin B (1). The cyclization was carried out in the liquid phase with the tag remaining, which allowed rapid reaction workup and product isolation.