Investigating the evolution of major Northern Hemisphere ice sheets during the last glacial-interglacial cycle

A 2.5-dimensional climate model of intermediate complexity, CLIMBER-2, fully coupled with the GREMLINS 3-D thermo-mechanical ice sheet model is used to simulate the evolution of major Northern Hemisphere ice sheets during the last glacial-interglacial cycle and to investigate the ice sheets responses to both insolation and atmospheric CO<sub>2</sub> concentration. This model reproduces the main phases of advance and retreat of Northern Hemisphere ice sheets during the last glacial cycle, although the amplitude of these variations is less pronounced than those based on sea level reconstructions. At the last glacial maximum, the simulated ice volume is 52.5×10<sup>15</sup> m<sup>3</sup> and the spatial distribution of both the American and Eurasian ice complexes is in reasonable agreement with observations, with the exception of the marine parts of these former ice sheets. <br> A set of sensitivity studies has also been performed to assess the sensitivity of the Northern Hemisphere ice sheets to both insolation and atmospheric CO<sub>2</sub>. Our results suggest that the decrease of summer insolation is the main factor responsible for the early build up of the North American ice sheet around 120 kyr BP, in agreement with benthic foraminifera δ<sup>18</sup>O signals. In contrast, low insolation and low atmospheric CO<sub>2</sub> concentration are both necessary to trigger a long-lasting glaciation over Eurasia

Mixed quantum state detection with inconclusive results

We consider the problem of designing an optimal quantum detector with a fixed rate of inconclusive results that maximizes the probability of correct detection, when distinguishing between a collection of mixed quantum states. We develop a sufficient condition for the scaled inverse measurement to maximize the probability of correct detection for the case in which the rate of inconclusive results exceeds a certain threshold. Using this condition we derive the optimal measurement for linearly independent pure-state sets, and for mixed-state sets with a broad class of symmetries. Specifically, we consider geometrically uniform (GU) state sets and compound geometrically uniform (CGU) state sets with generators that satisfy a certain constraint. We then show that the optimal measurements corresponding to GU and CGU state sets with arbitrary generators are also GU and CGU respectively, with generators that can be computed very efficiently in polynomial time within any desired accuracy by solving a semidefinite programming problem.Comment: Submitted to Phys. Rev.

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

A comparative analysis of contraceptive use in Africa: evidence from DHS

The aim of this article is to show a comparative analysis of contraceptive use in areas of traditionally high fertility that have gone through profound changes. Data have been taken from the latest Demographic and Health Surveys (DHS). Logistic regression models were adopted for four selected representative countries, namely Egypt, Mali, Namibia and Niger. There were two selection criteria: data should be recent, and selected countries should have high (Egypt 57.4%; Namibia 46.4%) or low (Mali 7.5%; Niger 10.0%) contraceptive use. The probability of using contraception when a woman has had one to four children is 2.4 times higher than when they have had no children. Contraception data are always gathered at a point of time, but crosssectional data are not sufficient to understand all the mechanisms hidden behind contraceptive use. Different contraceptive behaviours need good estimation tools to develop specific family planning programmes.Web of Scienc

Molecular control of sucrose utilization in Escherichia coli W, an efficient sucrose-utilizing strain

Sucrose is an industrially important carbon source for microbial fermentation. Sucrose utilization in Escherichia coli, however, is poorly understood, and most industrial strains cannot utilize sucrose. The roles of the chromosomally encoded sucrose catabolism (csc) genes in E. coli W were examined by knockout and overexpression experiments. At low sucrose concentrations, the csc genes are repressed and cells cannot grow. Removal of either the repressor protein (cscR) or the fructokinase (cscK) gene facilitated derepression. Furthermore, combinatorial knockout of cscR and cscK conferred an improved growth rate on low sucrose. The invertase (cscA) and sucrose transporter (cscB) genes are essential for sucrose catabolism in E. coli W, demonstrating that no other genes can provide sucrose transport or inversion activities. However, cscK is not essential for sucrose utilization. Fructose is excreted into the medium by the cscK-knockout strain in the presence of high sucrose, whereas at low sucrose (when carbon availability is limiting), fructose is utilized by the cell. Overexpression of cscA, cscAK, or cscAB could complement the W Delta cscRKAB knockout mutant or confer growth on a K-12 strain which could not naturally utilize sucrose. However, phenotypic stability and relatively good growth rates were observed in the K-12 strain only when overexpressing cscAB, and full growth rate complementation in W Delta cscRKA Balso required cscAB. Our understanding of sucrose utilization can be used to improve E. coli Wand engineer sucrose utilization in strains which do not naturally utilize sucrose, allowing substitution of sucrose for other, less desirable carbon sources in industrial fermentations

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Methylation levels of a novel genetic element, EgNB3 as a candidate biomarker associated with the embryogenic competency of oil palm

The association between DNA methylation status and embryogenic competency in oil palm tissue culture was examined through Representational Difference Analysis (RDA) approach, using methylation-sensitive restriction endonucleases. "Difference Products" (DPs) of RDA derived from palms of similar genetic backgrounds but exhibiting different embryogenesis rates during the regeneration process were isolated. The DPs were sequenced using a pyrosequencing platform. To our knowledge, this is the first study profiling partial HpaII methylation sites in oil palm young leaf tissues which are potentially associated with embryogenic amenability through a genomic subtractive approach. Quantitative real-time PCR analysis demonstrated that the methylation status of a novel fragment, EgNB3, was higher in highly embryogenic leaf explants compared to low embryogenesis rate materials. These differences are likely to be contributed by the 5′-mCCGG-3′ and/or 5′-mCmCGG-3′ methylation patterns. Our data suggest that the differentially methylated site in EgNB3 has potential as a molecular biomarker for the screening of oil palm leaf explants for their embryogenic potentials

Nanopores: maltoporin channel as a sensor for maltodextrin and lambda-phage

BACKGROUND: To harvest nutrition from the outside bacteria e.g. E. coli developed in the outer cell wall a number of sophisticated channels called porins. One of them, maltoporin, is a passive specific channel for the maltodextrin uptake. This channel was also named LamB as the bacterial virus phage Lambda mis-uses this channel to recognise the bacteria. The first step is a reversible binding followed after a lag phase by DNA injection. To date little is known about the binding capacity and less on the DNA injection mechanism. To elucidate the mechanism and to show the sensitivity of our method we reconstituted maltoporin in planar lipid membranes. Application of an external transmembrane electric field causes an ion current across the channel. Maltoporin channel diameter is around a few Angstroem. At this size the ion current is extremely sensitive to any modification of the channels surface. Protein conformational changes, substrate binding etc will cause fluctuations reflecting the molecular interactions with the channel wall. The recent improvement in ion current fluctuation analysis allows now studying the interaction of solutes with the channel on a single molecular level. RESULTS: We could demonstrate the asymmetry of the bacterial phage Lambda binding to its natural receptor maltoporin. CONCLUSION: We suggest that this type of measurement can be used as a new type of biosensors

Relative importance of the mechanisms triggering the Eurasian ice sheet deglaciation in the GRISLI2.0 ice sheet model

The last deglaciation (21 to 8 ka) of the Eurasian ice sheet (EIS) is thought to have been responsible for a sea level rise of about 20 m. While many studies have examined the timing and rate of the EIS retreat during this period, many questions remain about the key processes that triggered the EIS deglaciation 21 kyr ago. Due to its large marine-based parts in the Barents–Kara (BKIS) and British Isles sectors, the BKIS is often considered to be a potential analogue of the current West Antarctic ice sheet (WAIS). Identifying the mechanisms that drove the EIS evolution might provide a better understanding of the processes at play in the West Antarctic destabilization. To investigate the relative impact of key drivers on the EIS destabilization, we used the three-dimensional ice sheet model GRISLI (GRenoble Ice Shelf and Land Ice) (version 2.0) forced by climatic fields from five Paleoclimate Modelling Intercomparison Project phases 3 and 4 (PMIP3, PMIP4) Last Glacial Maximum (LGM) simulations. In this study, we performed sensitivity experiments to test the response of the simulated Eurasian ice sheets to surface climate, oceanic temperatures (and thus basal melting under floating ice tongues), and sea level perturbations. Our results highlight that the EIS retreat simulated with the GRISLI model is primarily triggered by atmospheric warming. Increased atmospheric temperatures further amplify the sensitivity of the ice sheets to sub-shelf melting. These results contradict those of previous modelling studies mentioning the central role of basal melting on the deglaciation of the marine-based Barents–Kara ice sheet. However, we argue that the differences with previous works are mainly related to differences in the methodology followed to generate the initial LGM ice sheet. Due to the strong sensitivity of EIS to the atmospheric forcing highlighted with the GRISLI model and the limited extent of the confined ice shelves during the LGM, we conclude by questioning the analogy between EIS and the current WAIS. However, because of the expected rise in atmospheric temperatures, the risk of hydrofracturing is increasing and could ultimately put the WAIS in a configuration similar to the past Eurasian ice sheet.</p

Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence

BACKGROUNDMucus plugs form in acute asthma and persist in chronic disease. Although eosinophils are implicated in mechanisms of mucus pathology, many mechanistic details about mucus plug formation and persistence in asthma are unknown.METHODSUsing histology and spatial, single-cell proteomics, we characterized mucus-plugged airways from nontransplantable donor lungs of 14 patients with asthma (9 with fatal asthma and 5 with nonfatal asthma) and individuals acting as controls (10 with chronic obstructive pulmonary disease and 14 free of lung disease). Additionally, we used an airway epithelial cell-eosinophil (AEC-eosinophil) coculture model to explore how AEC mucus affects eosinophil degranulation.RESULTSAsthma mucus plugs were tethered to airways showing infiltration with innate lymphoid type 2 cells and hyperplasia of smooth muscle cells and MUC5AC-expressing goblet cells. Asthma mucus plugs were infiltrated with immune cells that were mostly dual positive for eosinophil peroxidase (EPX) and neutrophil elastase, suggesting that neutrophils internalize EPX from degranulating eosinophils. Indeed, eosinophils exposed to mucus from IL-13-activated AECs underwent CD11b- and glycan-dependent cytolytic degranulation. Dual-positive granulocytes varied in frequency in mucus plugs. Whereas paucigranulocytic plugs were MUC5AC rich, granulocytic plugs had a mix of MUC5AC, MUC5B, and extracellular DNA traps. Paucigranulocytic plugs occurred more frequently in (acute) fatal asthma and granulocytic plugs predominated in (chronic) nonfatal asthma.CONCLUSIONTogether, our data suggest that mucin-rich mucus plugs in fatal asthma form because of acute goblet cell degranulation in remodeled airways and that granulocytic mucus plugs in chronic asthma persist because of a sustaining niche characterized by epithelial cell-mucin-granulocyte cross-talk.FUNDINGNIH grants HL080414, HL107202, and AI077439