Combined impact of shifts in Southern Ocean westerlies and Antarctic sea ice during LGM on atmospheric CO2

A significant influence of changes in the westerly winds over the Southern Ocean was proposed as a mechanism to explain a large portion of the glacial atmospheric pCO2 drawdown (Toggweiler et al., 2006). However, additional modelling studies with Earth System Models of Intermediate Complexity do not confirm the size and sometimes even the sign of the impact of southern hemispheric winds on the glacial pCO2 as suggested by Toggweiler (Men- viel et al., 2008; Tschumi et al., 2008, d’Orgeville et al., 2010). We here add to this discussion and explore the potential contribution of changes in the latitudinal position of the winds on Southern Ocean physics and the carbon cycle by using a state-of-the-art ocean general circulation model (MITgcm) in a spatial resolution increasing in the Southern Ocean (2◦ longitude; northern hemisphere: 2◦ latitude; southern hemisphere: 2◦cos(α)). We discuss how the change in carbon cycling is related to the upwelling strength and pattern in the Southern Ocean and how they depend on the changing wind fields and/or the sea ice coverage. While the previous studies explored the impact of the westlies starting from present day or pre-industrial back- ground conditions, we here perform simulations from LGM background climate. Ocean surface conditions are for reasons of consistency taken from output of the COSMOS Earth System model for a pre-industrial control and two LGM runs (Zhang et al., in preparation). Additionally, a northwards shift (by 10◦) of the westerly wind belt as proposed by Toggweiler is investigated

Simulation the impact of shifts in Southern Ocean westerlies at LGM on ocean physics and atmospheric CO2

We explore the impact of a latitudinal shift in the we- sterly wind belt over the Southern Ocean (SO) on the Atlantic meridional overturning circulation (AMOC) and on the carbon cycle for Last Glacial Maximum background conditions using a state-of-the-art ocean general circulation model. For this “westerly wind hypothesis” (Toggweiler et al. 2006) we find that a southward shift in the westerly winds leads to an intensification of the AMOC (northward shift to a weakening). This agrees with other studies (Sijp & England 2009) starting from pre-industrial background, but the responsible processes are different. During deglaciation a gradual shift in westerly winds might thus be responsible for a part of the AMOC enhancement, which is indicated by various studies. The net effects of the changes in ocean circulation lead to a rise in atmospheric pCO2 of less than 10 μatm for both a northward and a southward shift in the winds. For northward shifted winds the zone of upwelling of carbon and nutrient rich waters in the Southern Ocean is expanded, leading to more CO2 out-gassing to the atmosphere but also to an enhanced biological pump in the subpolar region. For southward shifted winds the upwelling region contracts around Antarctica leading to less nutrient export northwards and thus a weakening of the biological pump. A shift in the southern hemisphere westerly wind belt is probably not the domi- nant process which tightly couples atmospheric CO2 rise and Antarctic temperature during deglaciation which is suggested by the ice core data

Molecular characterization and exclusion of porcine GUSB as a candidate gene for congenital hernia inguinalis/scrotalis

BACKGROUND: Inguinal hernias are usually caused by a congenital defect, which occurs as a weakness of the inguinal canal. Porcine β-glucuronidase gene (GUSB) was chosen as functional candidate gene because of its involvement in degradation of hyaluronan within gubernacular tissue during descent of testes. Since a genome-wide linkage analysis approach has shown evidence that two regions on porcine chromosome 3 (SSC 3) are involved in the inheritance of hernia inguinalis/scrotalis in German pig breeds, GUSB also attained status as a positional candidate gene by its localization within a hernia-associated chromosomal region. RESULTS: A contig spanning 17,157 bp, which contains the entire GUSB, was assembled. Comparative sequence analyses were conducted for the GUSB gene locus. Single nucleotide polymorphisms (SNPs) located within the coding region of GUSB were genotyped in 512 animals. Results of transmission disequilibrium test (TDT) for two out of a total of five detected SNPs gave no significant association with the outcome of hernia in pigs. CONCLUSION: On the basis of our studies we are able to exclude the two analyzed SNPs within the porcine GUSB gene as causative for the transmission of inguinal hernia

A Hahn-Ramsey scheme for dynamical decoupling of single solid-state qubits

Spin systems in solid state materials are promising qubit candidates for quantum information in particular as quantum memories or for quantum sensing. A major prerequisite here is the coherence of spin phase oscillations. In this work, we show a control sequence which, by applying RF pulses of variable detuning, allows to increase the visibility of spin phase oscillations. We experimentally demonstrate the scheme on single NV centers in diamond and analytically describe how the NV electron spin phase oscillations behave in the presence of classical noise models. We hereby introduce detuning as the enabling factor that modulates the filter function of the sequence, in order to achieve a visibility of the Ramsey fringes comparable to or longer than the Hahn-echo T 2 time and an improved sensitivity to DC magnetic fields in various experimental settings.Peer Reviewe

In Vivo Models for Cholangiocarcinoma—What Can We Learn for Human Disease?

Cholangiocarcinoma (CCA) comprises a heterogeneous group of primary liver tumors. They emerge from different hepatic (progenitor) cell populations, typically via sporadic mutations. Chronic biliary inflammation, as seen in primary sclerosing cholangitis (PSC), may trigger CCA development. Although several efforts were made in the last decade to better understand the complex processes of biliary carcinogenesis, it was only recently that new therapeutic advances have been achieved. Animal models are a crucial bridge between in vitro findings on molecular or genetic alterations, pathophysiological understanding, and new therapeutic strategies for the clinic. Nevertheless, it is inherently difficult to recapitulate simultaneously the stromal microenvironment (e.g., immune-competent cells, cholestasis, inflammation, PSC-like changes, fibrosis) and the tumor biology (e.g., mutational burden, local growth, and metastatic spread) in an animal model, so that it would reflect the full clinical reality of CCA. In this review, we highlight available data on animal models for CCA. We discuss if and how these models reflect human disease and whether they can serve as a tool for understanding the pathogenesis, or for predicting a treatment response in patients. In addition, open issues for future developments will be discussed

Targeted oligonucleotide-mediated microsatellite identification (TOMMI) from large-insert library clones

Background: In the last few years, microsatellites have become the most popular molecular marker system and have intensively been applied in genome mapping, biodiversity and phylogeny studies of livestock. Compared to single nucleotide polymorphism (SNP) as another popular marker system, microsatellites reveal obvious advantages. They are multi-allelic, possibly more polymorphic and cheaper to genotype. Calculations showed that a multi-allelic marker system always has more power to detect Linkage Disequilibrium (LD) than does a di-allelic marker system [1]. Traditional isolation methods using partial genomic libraries are time-consuming and costintensive. In order to directly generate microsatellites from large-insert libraries a sequencing approach with repeat-containing oligonucleotides is introduced. Results: Seventeen porcine microsatellite markers were isolated from eleven PAC clones by targeted oligonucleotide-mediated microsatellite identification (TOMMI), an improved efficient and rapid flanking sequence-based approach for the isolation of STS-markers. With the application of TOMMI, an average of 1.55 (CA/GT) microsatellites per PAC clone was identified. The number of alleles, allele size distribution, polymorphism information content (PIC), average heterozygosity (HT), and effective allele number (NE) for the STS-markers were calculated using a sampling of 336 unrelated animals representing fifteen pig breeds (nine European and six Chinese breeds). Sixteen of the microsatellite markers proved to be polymorphic (2 to 22 alleles) in this heterogeneous sampling. Most of the publicly available (porcine) microsatellite amplicons range from approximately 80 bp to 200 bp. Here, we attempted to utilize as much sequence information as possible to develop STS-markers with larger amplicons. Indeed, fourteen of the seventeen STS-marker amplicons have minimal allele sizes of at least 200 bp. Thus, most of the generated STS-markers can easily be integrated into multilocus assays covering a broader separation spectrum. Linkage mapping results of the markers indicate their potential immediate use in QTL studies to further dissect trait associated chromosomal regions. Conclusion: The sequencing strategy described in this study provides a targeted, inexpensive and fast method to develop microsatellites from large-insert libraries. It is well suited to generate polymorphic markers for selected chromosomal regions, contigs of overlapping clones and yields sufficient high quality sequence data to develop amplicons greater than 250 base

Targeted oligonucleotide-mediated microsatellite identification (TOMMI) from large-insert library clones

BACKGROUND: In the last few years, microsatellites have become the most popular molecular marker system and have intensively been applied in genome mapping, biodiversity and phylogeny studies of livestock. Compared to single nucleotide polymorphism (SNP) as another popular marker system, microsatellites reveal obvious advantages. They are multi-allelic, possibly more polymorphic and cheaper to genotype. Calculations showed that a multi-allelic marker system always has more power to detect Linkage Disequilibrium (LD) than does a di-allelic marker system [1]. Traditional isolation methods using partial genomic libraries are time-consuming and cost-intensive. In order to directly generate microsatellites from large-insert libraries a sequencing approach with repeat-containing oligonucleotides is introduced. RESULTS: Seventeen porcine microsatellite markers were isolated from eleven PAC clones by targeted oligonucleotide-mediated microsatellite identification (TOMMI), an improved efficient and rapid flanking sequence-based approach for the isolation of STS-markers. With the application of TOMMI, an average of 1.55 (CA/GT) microsatellites per PAC clone was identified. The number of alleles, allele size distribution, polymorphism information content (PIC), average heterozygosity (H(T)), and effective allele number (N(E)) for the STS-markers were calculated using a sampling of 336 unrelated animals representing fifteen pig breeds (nine European and six Chinese breeds). Sixteen of the microsatellite markers proved to be polymorphic (2 to 22 alleles) in this heterogeneous sampling. Most of the publicly available (porcine) microsatellite amplicons range from approximately 80 bp to 200 bp. Here, we attempted to utilize as much sequence information as possible to develop STS-markers with larger amplicons. Indeed, fourteen of the seventeen STS-marker amplicons have minimal allele sizes of at least 200 bp. Thus, most of the generated STS-markers can easily be integrated into multilocus assays covering a broader separation spectrum. Linkage mapping results of the markers indicate their potential immediate use in QTL studies to further dissect trait associated chromosomal regions. CONCLUSION: The sequencing strategy described in this study provides a targeted, inexpensive and fast method to develop microsatellites from large-insert libraries. It is well suited to generate polymorphic markers for selected chromosomal regions, contigs of overlapping clones and yields sufficient high quality sequence data to develop amplicons greater than 250 bases

Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice

The prototypic protein disulfide isomerase (PDI), encoded by the P4HB gene, has been described as a survival factor in ischemic cardiomyopathy. However, the role of protein disulfide isomerase associated 6 (PDIA6) under hypoxic conditions in the myocardium remains enigmatic, and it is unknown whether the gut microbiota influences the expression of PDI and PDIA6 under conditions of acute myocardial infarction. Here, we revealed that, in addition to the prototypic PDI, the PDI family member PDIA6, a regulator of the unfolded protein response, is upregulated in the mouse cardiomyocyte cell line HL-1 when cultured under hypoxia. In vivo, in the left anterior descending artery (LAD) ligation mouse model of acute myocardial infarction, similar to PDI, PDIA6 protein expression was enhanced in the infarcted area (LAD ) relative to uninfarcted sham tissue or the neighbouring area at risk (LAD–) of C57BL/6J mice. Interestingly, we found that ex-germ-free (ex-GF) mice subjected to the LAD ligation model for 24 h had a reduced ejection fraction compared with their conventionally raised (CONV-R) SPF controls. Furthermore, the LAD area in the infarcted heart of ex-GF mice showed reduced PDIA6 expression relative to CONV-R controls, suggesting that the presence of a gut microbiota enhanced LAD ligation-triggered PDIA6 expression. Collectively, our results demonstrate that PDIA6 is upregulated in cardiomyocytes as a consequence of hypoxia. In the LAD mouse model, PDIA6 was also increased in the infarcted area under in vivo conditions, but this increase was suppressed in ex-GF mice relative to CONV-R controls