Antarctica: A Keystone in a Changing World

The 10th International Symposium on Antarctic Earth Sciences was convened at the University of California, Santa Barbara, where 350 researchers presented talks and posters on topics including climate change, biotic evolution, magmatic processes, surface processes, tectonics, geodynamics, and the cryosphere. The symposium resulted in 335 peer-reviewed papers, 225 of which are published online). A proceedings book will also be published by the National Academies Press. Advances in our understanding of Antarctic tectonics were many, often involving techniques that provide information under ice sheets or from proxies such as glacial till to provide clues on provenance. John Goodge (University of Minnesota-Duluth) and coworkers reported a 1440-million-year-old granite boulder from glacial till from the Nimrod Glacier that can be matched to North American Laurentian province granites, supporting the postulated (Southwest U.S.—East Antarctica (SWEAT) hypothesis) fit of East Antarctica and North America more than 1 billion years ago. Considerable debate concerned the formation of the Transantarctic Mountains and the role of plateau collapse

Decrease in natural marine hydrocarbon seepage near Coal Oil Point, California, associated with offshore oil production

Prolific natural hydrcarbon seepage occurs offshore of Coal Oil Point in the Santa Barbara Channel, California. Within the water column above submarine vents, plumes of hydrocarbon gas bubbles act as acoustic scattering targets. Using 3.5 kHz sonar data, seep distribution offshore of Coal Oil Point was mapped for August 1996, July 1995, and July 1973. Comparison of the seep distributions over time reveals more than 50% decrease in the areal extent of seepage, accompanied by declines in seep emission volume, in a 13 km2 area above a production oil reservoir. Declines in reservoir pressure and depletion of seep hydrocarbon sources associated with oil production are the mechanisms inferred to explain the declines in seep and emission volume

Von Willebrand factor delays liver repair after acetaminophen-induced acute liver injury in mice

Background &amp; Aim: Acetaminophen (APAP)-induced acute liver failure is associated with substantial alterations in the hemostatic system. In mice, platelets accumulate in the liver after APAP overdose and appear to promote liver injury. Interestingly, patients with acute liver injury have highly elevated levels of the platelet-adhesive protein von Willebrand factor (VWF), but a mechanistic connection between VWF and progression of liver injury has not been established. We tested the hypothesis that VWF contributes directly to experimental APAP-induced acute liver injury. Methods: Wild-type mice and VWF-deficient (Vwf−/−) mice were given a hepatotoxic dose of APAP (300 mg/kg, i.p.) or vehicle (saline). VWF plasma levels were measured by ELISA, and liver necrosis or hepatocyte proliferation was measured by immunohistochemistry. Platelet and VWF deposition were measured by immunofluorescence. Results: In wild-type mice, VWF plasma levels, high molecular weight (HMW) VWF multimers, and VWF activity decreased 24 h after APAP challenge. These changes coupled to robust hepatic VWF and platelet deposition, although VWF deficiency had minimal effect on peak hepatic platelet accumulation or liver injury. VWF plasma levels were elevated 48 h after APAP challenge, but with relative reductions in HMW multimers and VWF activity. Whereas hepatic platelet aggregates persisted in livers of APAP-challenged wild-type mice, platelets were nearly absent in Vwf−/− mice 48 h after APAP challenge. The absence of platelet aggregates was linked to dramatically accelerated repair of the injured liver. Complementing observations in Vwf−/− mice, blocking VWF or the platelet integrin αIIbβ3 during development of injury significantly reduced hepatic platelet aggregation and accelerated liver repair in APAP-challenged wild-type mice. Conclusion: These studies are the first to suggest a mechanistic link between VWF, hepatic platelet accumulation, and liver repair. Targeting VWF might provide a novel therapeutic approach to improve repair of the APAP-injured liver. Lay summary: Patients with acute liver injury due to acetaminophen overdose have highly elevated levels of the platelet-adhesive protein von Willebrand factor. It is not known whether von Willebrand factor plays a direct role in the progression of acute liver injury. We discovered that von Willebrand factor delays repair of the acetaminophen-injured liver in mice and that targeting von Willebrand factor, even in mice with established liver injury, accelerates liver repair.</p

What lies beneath? Interdisciplinary outcomes of the ANDRILL Coulman High Project site surveys on the Ross Ice Shelf

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, no. 3 (2012): 84-89, doi:10.5670/oceanog.2012.79.Extensive field operations were conducted on the northwestern Ross Ice Shelf in Antarctica from November 2010 through January 2011. A significant amount of equipment, supplies, and people safely traversed from McMurdo Station to establish a series of combined United States–New Zealand field camps at locations northeast of Ross Island. The ANDRILL (ANtarctic geological DRILLing) hot water drill system was used to melt multiple access holes through the ice shelf at each site to deploy a variety of sediment coring tools, cameras, and oceanographic instruments, as well as a remotely operated vehicle to characterize the ice shelf and sub-ice environment. These studies will contribute to future proposed geological drilling as part of the ANDRILL Coulman High Project.This work is funded by US NSF-OPP Grant ANT-0838914 and by the NZ Foundation for Research, Science and Technology

Contribution of Host-Derived Tissue Factor to Tumor Neovascularization

The role of host-derived tissue factor (TF) in tumor growth, angiogenesis and metastasis has hitherto been unclear, and was investigated in this study

Comparison of TNFα to Lipopolysaccharide as an Inflammagen to Characterize the Idiosyncratic Hepatotoxicity Potential of Drugs: Trovafloxacin as an Example

Idiosyncratic drug reactions (IDRs) are poorly understood, unpredictable, and not detected in preclinical studies. Although the cause of these reactions is likely multi-factorial, one hypothesis is that an underlying inflammatory state lowers the tolerance to a xenobiotic. Previously used in an inflammation IDR model, bacterial lipopolysaccharide (LPS) is heterogeneous in nature, making development of standardized testing protocols difficult. Here, the use of rat tumor necrosis factor-α (TNFα) to replace LPS as an inflammatory stimulus was investigated. Sprague-Dawley rats were treated with separate preparations of LPS or TNFα, and hepatic transcriptomic effects were compared. TNFα showed enhanced consistency at the transcriptomic level compared to LPS. TNFα and LPS regulated similar biochemical pathways, although LPS was associated with more robust inflammatory signaling than TNFα. Rats were then codosed with TNFα and trovafloxacin (TVX), an IDR-associated drug, and evaluated by liver histopathology, clinical chemistry, and gene expression analysis. TNFα/TVX induced unique gene expression changes that clustered separately from TNFα/levofloxacin, a drug not associated with IDRs. TNFα/TVX cotreatment led to autoinduction of TNFα resulting in potentiation of underlying gene expression stress signals. Comparison of TNFα/TVX and LPS/TVX gene expression profiles revealed similarities in the regulation of biochemical pathways. In conclusion, TNFα could be used in lieu of LPS as an inflammatory stimulus in this model of IDRs

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390–396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390–396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients

miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1

Cyclin T1 is a regulatory subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is also required for Tat transactivation of HIV-1 LTR-directed gene expression. Translation of Cyclin T1 mRNA has been shown to be repressed in human monocytes, and this repression is relieved when cells differentiate to macrophages. We identified miR-198 as a microRNA (miRNA) that is strongly down-regulated when monocytes are induced to differentiate. Ectopic expression of miR-198 in tissue culture cells reduced Cyclin T1 protein expression, and plasmid reporter assays verified miR-198 target sequences in the 3′ untranslated region (3′UTR) of Cyclin T1 mRNA. Cyclin T1 protein levels increased when an inhibitor of miR-198 was transfected into primary monocytes, and overexpression of miR-198 in primary monocytes repressed the normal up-regulation of Cyclin T1 during differentiation. Expression of an HIV-1 proviral plasmid and HIV-1 replication were repressed in a monocytic cell line upon overexpression of miR-198. Our data indicate that miR-198 functions to restrict HIV-1 replication in monocytes, and its mechanism of action appears to involve repression of Cyclin T1 expression

Bedmap2: improved ice bed, surface and thickness datasets for Antarctica

We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60 S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved datacoverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km3) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72m lower and the area of ice sheet grounded on bed below sea level is increased by 10 %. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets