ALBERT

Description: Aberrant glycosylation by N -acetylgalactosaminyl transferases (GALNTs) is a well-described pathological alteration that is widespread in hereditary diseases, prominently including human cancers, familial tumoral calcinosis and hyperostosis-hyperphosphatemia. In this study, we integrated different computational tools to perform the in silico analysis of clinically significant mutations (nsSNPs/ single amino acid change) at both functional and structural levels, found in human GALNT3, GALNT8, GALNT12 and GALNT13 genes. From function and structure based insights, mutations encoding R162Q, T359K, C574G, G359D, R297W, Y396C & D313N substitutions were concordantly predicted highly deleterious for relevant GALNTs proteins. From intriguing findings, T359K- GALNT3 was simulated with high contribution for disease susceptibility (tumor calcinosis) as compared to its partner variant T272K [Ichikawa et al., 2006]. Similarly, the prediction of high damaging behavior, evolutionary conservation and structural destabilization for C574G were proposed as major contributing factors to regulate metabolic disorder underlying tumor calcinosis and hyperostosis-hyperphosphatemia syndrome. In case of R297W- GALNT12 , prediction of highly deleterious effect and disruption in ionic interactions were anticipated with reduction in enzymatic activity, associated with bilateral breast cancer and primary colorectal cancers. The second GALNT12 mutation (D303N)-known splice variant- was predicted with disease severity as a result of decrease in charge density and buried behavior neighboring the catalytic B domain. In the lack of adequate in silico data about systematic characterization of clinically significant mutations in GALNTs genes, current study can be used as a significant tool to interpret the role of GALNTs reaction chemistry in disease-association risks in body. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Objective To investigate whether crosstalk between RUNX2 and miRNAs is involved in tooth eruption regulated by dental follicle cells(DFCs) and the possible molecular mechanism. Methods Blood samples and embedded dental follicles were collected from patients with cleidocranial dysplasia (CCD), and RUNX2 gene mutations were analyzed, then RUNX2 +/m DFCs were isolated and identified. The characteristics of RUNX2 +/m DFCs were analyzed. The differential expression of miRNAs was detected between the RUNX2 +/m DFCs and RUNX2 +/+ DFCs by microarray, and target genes were predicted by miRGen. miR-146a was chosen for further investigation, and its effects in DFCs were analyzed by transfecting its mimics and inhibitors, and expression of genes involved in tooth eruption were detected. Results A novel insertion mutation (c.309_310insTG) of RUNX2 gene was identified which had an effect on the characteristics of DFCs. Compared with the RUNX2 +/+ DFCs, there were 69 microRNAs more than 2-fold up-regulated and 54 microRNAs more than 2-fold down-regulated in the RUNX2 +/m DFCs. Among these, miR-146a decreased significantly in RUNX 2 +/m DFCs, and expression of RUNX2, CSF-1,EGFR and OPG was significantly altered when miR-146a was over-expressed or inhibited. Conclusion RUNX2 gene mutation contributes to the characteristic change of dental follicle cells, and the crosstalk between RUNX2 gene and miRNAs may be one of the key regulatory mechanisms of differentiation of dental follicle cells. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Cancer stem cells (CSC) have a central role in driving tumor growth. Since metabolism is becoming an important diagnostic and therapeutic target, characterization of CSC line energetic properties is an emerging need. Embryonic and adult stem cells, compared to differentiated cells, exhibit a reduced mitochondrial activity and a stronger dependence on aerobic glycolysis. Here, we aimed to comparatively analyze bioenergetics features of the human osteosarcoma 3AB-OS CSC-like line, and the parental osteosarcoma MG63 cells, from which 3AB-OS cells have been previously selected. Our results suggest that 3AB-OS cells depend on glycolytic metabolism more strongly than MG63 cells. Indeed, growth in glucose shortage or in presence of galactose or pyruvate -mitochondrial specific substrates- leads to a significant reduction of their proliferation compared to MG63 cells. Accordingly, 3AB-OS cells show an increased expression of lactate dehydrogenase A (LDHA) and a larger accumulation of lactate in the culture medium. In line with these findings 3AB-OS cells as compared to MG63 cells present a reduced mitochondrial respiration, a stronger sensitivity to glucose depletion or glycolysis inhibition and a lessened sensitivity to oxidative phosphorylation inhibitors. Additionally, in contrast to MG63 cells, 3AB-OS display fragmented mitochondria, which become networked as they grow in glucose-rich medium, while almost entirely loose these structures growing in low glucose. Overall, our findings suggest that 3AB-OS CSCs energy metabolism is more similar to normal stem cells and to cancer cells characterized by a glycolytic anaerobic metabolism. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Areca chewing is an important environmental risk factor for development of oral premalignant lesions and cancer. Epidemiological evidence indicates that areca chewing is tightly linked to oral carcinogenesis. However, the pathogenetic impacts of areca nut extract (ANE) on normal human oral keratinocytes (HOKs) are unclear and possibly involve oxidative stress via redox imbalance. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that play an important role in regulating cellular reactive oxygen species (ROS) production. Recent studies have confirmed that ANE and other areca ingredients can induce ROS. In this study, we examined the role of SIRT3 in the regulation of ANE-induced ROS in HOK cells. We examined HOK cell viability following treatment with various ANE concentrations. ANE-induced cytotoxicity increased in a dose-dependent manner and was approximately 48% at a concentration of 50 μg/ml after 24 h. SIRT3 expression and enzyme activity were up-regulated in HOK cells by ANE-induced oxidative stress. Additionally, we identified that SIRT3 controls the enzymatic activity of mitochondrial proteins, such as forkhead box O3a (Foxo3a) transcription factor and antioxidant-encoding gene superoxide dismutase 2 (SOD2), by deacetylation in HOK cells. Moreover, SIRT3-mediated deacetylation and activation of Foxo3a promotes nuclear localization in vivo . These findings suggest that SIRT3 is an endogenous negative regulator in response to ANE-induced oxidative stress and demonstrate an essential role for redox balance in HOK cells. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Collagen is the most abundant structural protein in mammals and is expressed in various tissues. In recent years, sphingosine 1-phosphate receptors (S1PRs) have been proven to play an important role in the regulation of collagen expression. Our previous studies reported that S1PRs are involved in TGF-β1-induced collagen expression via up-regulating S1PR1/3 in mouse bone marrow-derived mesenchymal stem cells (BMSCs), and result in experimental mouse liver fibrogenesis. But it remains unclear whether this process happens in human bone marrow-derived mesenchymal stem cells (hMSCs). In this study, we provide evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of collagen in hMSCs using cellular and molecular approaches in vitro . We find that treatment of hMSCs with TGF-β1 up-regulated collagen expression in a dose- and time-dependent manner. Meanwhile, TGF-β1 inhibited the expression of S1PR1/3, but not S1PR2, in hMSCs in a time-dependent manner. Furthermore, either selective knock-down of S1PR1 or silencing S1PR3 induced collagen α1(I) and collagen α1(III) expression in hMSCs. In contrast, inhibition of S1PR2 by siRNA had no effects on the expression of collagen. Altogether, all these findings demonstrated that collagen expression was negatively regulated by S1PR1 and S1PR3 in hMSCs. This study highlights the differences between hMSCs and mouse BMSCs, provides a new regulation mechanism for collagen expression, and points out the risk of utilizing hMSCs in clinical applications. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  We investigated the evolution of seismicity and deformation in the unstable eastern flank of Etna volcano over a thirty-year period (from 1980 to 2012). A significant temporal correlation has been revealed between periods of flank acceleration and intensified seismic activity by comparing seismicity along the northern border (Pernicana fault system) of the sliding flank and the deformation of the eastern flank. Two marked phases have been observed in 1984-1986 and in the years following 2002. These two phases are separated by an intermediate phase from 1987 to 2001, in which the flank sliding slowed down and the seismicity dropped drastically. This common temporal evolution in the deformation rate and seismic release supports the hypothesis that the seismicity in the northern border can be viewed as a marker of the response to accommodate the stress exerted by the traction of the eastern flank sliding. This interplay has also been corroborated by Finite Element Method (FEM) numerical computations that highlight a good correlation between the seismicity pattern and areas of positive stress changes induced by the sliding surface. The two intense phases of flank acceleration are representative of two main different sources: volcano flank instability stretching the eastern sector in the first 1984-1986 phase and magmatic intrusions pushing the eastern flank seaward since the 2002-03 eruption. Establishing the relationship between flank acceleration and seismic activation, therefore, contributes to understanding Etna's mechanical behavior, and provides insights into the processes regulating the unstable flank response.

Description: [1]  Numerous studies in the Central Pyrenees have provided evidence for a rapid phase of exhumation of this mountain belt during the Late Eocene (37–30 Ma). Simultaneously, the closure of the Ebro foreland basin allowed the accumulation of sediments at the southern Piedmont, which partially covered the fold-and-thrust belt from Late Eocene ( e . g . when it was still actively deforming) to Miocene times. We aim here at understanding the consequences of such syn-tectonic sedimentation on the Southern Pyrenean fold-and-thrust belt by using a 2-D numerical model that reproduces the development of a thin-skinned wedge subject to different modes of sedimentation and erosion. The results show contrasting fold-and-thrust belt behavior when applying aggrading or prograding sedimentation, which we link to the critical state of the wedge. When the sediments are sourced from the hinterland (progradation), the thrusting propagates toward the foreland; whereas when the sediments aggrade from the basin, the thrusting sequence migrates backward. This latter mode shows patterns of deformation that compare favorably to the Pyrenean thrusting sequence observed during Eocene-Miocene times.

Description: [1]  In southern California, fault slip rate estimates along the San Andreas fault (SAF) and Garlock fault from geodetically-constrained kinematic models are systematically at the low end or lower than geologic slip rate estimates. The sum of geodetic model slip rates across the Eastern California Shear Zone is higher than the geologic sum. However, the ranges of reported model and geologic slip rate estimates in the literature are sufficiently large that it remains unclear whether these apparent discrepancies are real, or attributable to epistemic uncertainties in the two types of estimates. We further examine uncertainties in geodetically-derived slip rate estimates on major faults in southern California by conducting a suite of inversions with four kinematic models. Long-term-rigid elastic block models constrained by the geologic slip rates cannot fit the present-day GPS-derived velocity field. Deforming (permanent off-fault strain) elastic block models and viscoelastic earthquake cycle block models constrained by geologic slip rates can fit the present-day GPS-derived velocity field with 28-33% of the total geodetic moment rate occurring as distributed deformation off of the major faults. Models incorporating viscoelastic mantle flow predict systematically higher slip rates than purely elastic models on many of the the major southern California faults with ranges of (elastic/viscoelastic) 29-34/30-37 mm/yr for the Carrizo SAF segment, 20-24/20-32 mm/yr for the Mojave SAF segment, 14-17/18-22 mm/yr for the Coachella SAF segment, 13-19/14-22 mm/yr for the San Jacinto fault, and 5-11/5-11 mm/yr for the western Garlock fault.

Description: Lymph nodes are often the first target of metastatic cancer which can then remetastasize to distant organs. The progression of lymph node metastasis is dependent on sufficient blood supply provided by angiogenesis. In the present study, we have developed a color-coded imaging model to visualize angiogenesis of lymph nodes metastasis using green fluorescent protein (GFP) and red fluorescent protein (RFP). Transgenic mice carrying GFP under the control of the nestin second-intron enhancer (ND-GFP mice) were used as hosts. Nascent blood vessels express GFP in these mice. B16F10-RFP melanoma cells were injected into the efferent lymph vessel of the inguinal lymph node of the ND-GFP nude mice, whereby the melanoma cells trafficked to the axillary lymph node. Three days after melanoma implantation, ND-GFP-expressing nascent blood vessels were imaged in the axillary lymph nodes. Seven days after implantation, ND-GFP-expressing nascent blood vessels formed a network in the lymph nodes. ND-GFP-positive blood vessels surrounded the tumor mass by 14 days after implantation. However, by 28 days after implantation, ND-GFP expression was diminished as the blood vessels matured. Treatment with doxorubicin significantly decreased the mean nascent blood vessel length per tumor volume. These results show that the dual-color ND-GFP blood vessels/RFP-tumor model is a powerful tool to visualize and quantitate angiogenesis of metastatic lymph nodes as well as for evaluation of its inhibition. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  Determining the scale-length, magnitude, and distribution of heterogeneity in the lowermost mantle is crucial to understanding whole mantle dynamics, and yet it remains a much debated and ongoing challenge in geophysics. Common shortcomings of current seismically-derived lowermost mantle models are incomplete raypath coverage, arbitrary model parameterization, inaccurate uncertainty estimates, and an ad hoc definition of the misfit function in the optimization framework. In response, we present a new approach to global tomography. Apart from improving the existing raypath coverage using only high quality cross-correlated waveforms, the problem is addressed within a Bayesian framework where explicit regularization of model parameters is notrequired. We obtain high resolution images, complete with uncertainty estimates, of the lowermost mantle P-wave velocity structure using a hand-picked dataset of PKPab-df, PKPbc-df, and PcP-P differential traveltimes. Most importantly, our results demonstrate that the root mean square of the P-wave velocity variations in the lowermost mantle is approximately 0.87%, which is three times larger than previous global-scale estimates.

Description: The cytoplasmic signaling protein tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5), which was identified as a signal transducer for members of the TNF receptor super-family, has been implicated in several biological functions in T/B lymphocytes and the innate immune response against viral infection. However, the role of TRAF5 in cardiac hypertrophy has not been reported. In the present study, we investigated the effect of TRAF5 on the development of pathological cardiac hypertrophy induced by transthoracic aorta constriction (TAC) and further explored the underlying molecular mechanisms. Cardiac hypertrophy and function were evaluated with echocardiography, hemodynamic measurements, pathological and molecular analyses. For the first time, we found that TRAF5 deficiency substantially aggravated cardiac hypertrophy, cardiac dysfunction and fibrosis in response to pressure overload after 4 weeks of TAC compared to wild-type (WT) mice. Moreover, the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway was more activated in TRAF5-deficient mice than WT mice. In conclusion, our results suggest that as an intrinsic cardioprotective factor, TRAF5 plays a crucial role in the development of cardiac hypertrophy through the negative regulation of the MEK-ERK1/2 pathway. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: The SON protein is a ubiquitously expressed DNA- and RNA-binding protein primarily localized to nuclear speckles. Although several early studies implicated SON in DNA-binding, tumorigenesis and apoptosis, functional significance of this protein had not been recognized until recent studies discovered SON as a novel RNA splicing co-factor. During constitutive RNA splicing, SON ensures efficient intron removal from the transcripts containing suboptimal splice sites. Importantly, SON-mediated splicing is required for proper processing of selective transcripts related to cell cycle, microtubules/centrosomes maintenance, and genome stability. Moreover, SON regulates alternative splicing of RNAs from the genes involved in apoptosis and epigenetic modification. In addition to the role in RNA splicing, SON has an ability to suppress transcriptional activation at certain promoter/enhancer DNA sequences. Considering the multiple SON target genes which are directly involved in cell proliferation, genome stability and chromatin modifications, SON is an emerging player in gene regulation during cancer development and progression. Here, we summarize available information from several early studies on SON, and highlight recent discoveries describing molecular mechanisms of SON-mediated gene regulation. We propose that our future effort on better understanding of diverse SON functions would reveal novel targets for cancer therapy. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  The Dzhungarian strike-slip fault of Central Asia is one of a series of long, NW-SE right-lateral strike-slip faults that are characteristic of the northern Tien Shan region, and extends over 300 km from the high mountains into the Kazakh Platform. Our field-based and satellite observations reveal that the Dzhungarian fault can be characterised by three 100 km long sections based on variation in strike direction. Through morphological analysis of offset streams and alluvial fans, and through OSLdating, we find that the Dzhungarian fault has a minimum average late Quaternary slip rate of 2.2 ± 0.8 mm/yr and accommodates N-S shortening related to the India-Eurasia collision. This shortening may also be partly accommodated by counter-clockwise rotation about a vertical axis. Evidence for a possible paleo-earthquake rupture indicates that earthquakes up to at least Mw 7 can be associated with just the partitioned component of reverse slip on segments of the central section of the fault up to 30 km long. An event rupturing longer sections of the Dzhungarian fault has the potential to generate greater magnitude earthquakes ( Mw 8), however long time periods (e.g. thousands of years) are expected in order to accumulate enough strain to generate such earthquakes.

Description: Background Podocytes are a terminally differentiated and highly specialized cell type in the glomerulus that forms a crucial component of the glomerular filtration barrier. Recently, Myo1e was identified in the podocytes of glomeruli. Myo1e podocyte-specific knockout mice exhibit proteinuria, podocyte foot process effacement, glomerular basement membrane disorganization, signs of chronic renal injury, and kidney inflammation. Materials and Methods After overexpression of Myo1e in a conditionally immortalized mouse podocyte cell line (MPC5), podocyte migration was evaluated via transwell assay, endocytosis was evaluated using FITC-transferrin, and adhesion was evaluated using a detachment assay after puromycin aminonucleoside treatment. Results Myo1e overexpression significantly increased the adherence of podocytes. ANOVA analysis indicated significant differences for cell adhesion between the overexpression and control groups (overexpression vs. control, t = 11.3199, P = 0.005; overexpression vs. negative control, t = 12.0570, P = 0.0006). Overexpression of Myo1e inhibited puromycin aminonucleoside-induced podocyte detachment, and the number of cells remaining on the bottom of the culture plate increased. Cell migration was enhanced in Myo1e-overexpressing podocytes in the transwell migration assay. Internalization of FITC-transferrin also increased in Myo1e-overexpressing podocytes relative to control cells. Conclusions Overexpression of Myo1e can enhance podocyte migration ability, endocytosis, and attachment to the glomerular basement membrane. Restoration of Myo1e expression in podocytes may therefore strengthen their functional integrity against environmental and mechanical injury. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  We performed shock compression experiments on preheated forsterite liquid (Mg 2 SiO 4 ) at an initial temperature of 2273 K and have revised the equation of state (EOS) that was previously determined by shock melting of initially solid Mg 2 SiO 4 (300 K). The linear Hugoniot, U S  = 2.674 ± 0.188 + 1.64 ± 0.06 u p km/s, constrains the bulk sound speed within a temperature and composition space as yet unexplored by 1-bar ultrasonic experiments. We have also revised the EOS for enstatite liquid (MgSiO 3 ) to exclude experiments that may have been only partially melted upon shock compression and also the EOS for anorthite liquid, which now excludes potentially un-relaxed experiments at low pressure. The revised fits and the previously determined EOS of fayalite and diopside were used to produce isentropes in the multicomponent CaO-MgO-Al 2 O 3 -SiO 2 -FeO system at elevated temperatures and pressures. Our results are similar to those previously presented for peridotite and simplified “chondrite” liquids such that regardless of where crystallization first occurs, the liquidus solid sinks upon formation. This process is not conducive to the formation of a basal magma ocean. We also examined the chemical and physical plausibility of the partial melt hypothesis to explain the occurrence and characteristics of ultralow velocity zones. We determined that the ambient mantle cannot produce an equilibrium partial melt and residue that is sufficiently dense to be a ULVZ mush. The partial melt would need to be segregated from its equilibrium residue and combined with a denser solid component to achieve a sufficiently large aggregate density.

Description: [1]  High resolution sparker and crustal-scale airgun seismic reflection data, coupled with repeat bathymetric surveys, document a region of repeated coseismic uplift on the portion of the Alaska subduction zone that ruptured in 1964. This area defines the western limit of Prince William Sound. Differencing of vintage and modern bathymetric surveys shows that the region of greatest uplift related to the 1964 Great Alaska earthquake was focused along a series of sub-parallel faults beneath Prince William Sound and the adjacent Gulf of Alaska shelf. Bathymetric differencing indicates that 12 m of coseismic uplift occurred along two faults that reached the sea floor as submarine terraces on the Cape Cleare bank southwest of Montague Island. Sparker seismic reflection data provide cumulative Holocene slip estimates as high as 9 mm/yr along a series of splay thrust faults within both the inner wedge and transition zone of the accretionary prism. Crustal seismic data show that these megathrust splay faults root separately into the subduction zone décollement. Splay fault divergence from this megathrust correlates with changes in mid-crustal seismic velocity and magnetic susceptibility values, best explained by duplexing of the subducted Yakutat terrane rocks above Pacific plate rocks along the trailing edge of the Yakutat terrane. Although each splay fault is capable of independent motion, we conclude that the identified splay faults rupture in a similar pattern during successive megathrust earthquakes and that the region of greatest seismic coupling has remained consistent throughout the Holocene.

Description: [1]  We perform a time-lapse analysis of Rayleigh and Love wave anisotropy above an underground gas storage facility in the Paris Basin. The data were acquired with a three-component seismic array deployed during several days in April and November 2010. Phase velocity and back azimuth of Rayleigh and Love waves are measured in the frequency range 0.2-1.1 Hz using a three-component beamforming algorithm. In both snapshots, higher surface wave modes start dominating the signal above 0.4 Hz with a concurrent increase in back azimuth ranges. We fit anisotropy parameters to the array detections above 0.4 Hz using a bootstrap approach which also provides estimation uncertainty and enables significance testing. The isotropic phase velocity dispersion for Love and Rayleigh waves match for both snapshots. We also observe a stable fast direction of NNW-SSE for Love and Rayleigh waves which is aligned with the preferred orientation of known shallow (〈300 m) and deeper (~1000 m) fault systems in the area, as well as the maximum horizontal stress orientation. At lower frequencies corresponding to deeper parts of the basin, the anisotropic parameters exhibit higher magnitude in the November data. This may perhaps be caused by the higher pore-pressure changes in the gas reservoir in that depth range.

Description: [1]  Eruptive activity at the summit of Kilauea Volcano, Hawaii beginning in 2010 and continuing to the present time is characterized by transient outgassing bursts accompanied by very long period (VLP) seismic signals triggered by rockfalls from the vent walls impacting a lava lake in a pit within the Halemaumau pit crater. We use raw data recorded with a 11-station broadband network to model the source mechanism of signals accompanying two large rockfalls on August 29, 2012 and two smaller average rockfalls obtained by stacking over all events with similar waveforms to improve the signal-to-noise ratio. To determine the source centroid location and source mechanism, we minimize the residual error between data and synthetics calculated by the finite difference method for a point source embedded in a homogeneous medium that takes topography into account. We apply a new waveform inversion method that accounts for the contributions from both translation and tilt in horizontal seismograms through the use of Green's functions representing the seismometer response to translation and tilt ground motions. This method enables a robust description of the source mechanism over the period range 1-1000 s. The VLP signals associated with the rockfalls originate in a source region ~1 km below the eastern perimeter of the Halemaumau pit crater. The observed waveforms are well explained by a simple volumetric source with geometry composed of two intersecting cracks including an east striking crack (dike) dipping 80 ∘ to the north, intersecting a north striking crack (another dike) dipping 65 ∘ to the east. Each rockfall is marked by a similar step-like inflation trailed by decaying oscillations of the volumetric source, attributed to the efficient coupling at the source centroid location of the pressure and momentum changes induced by the rock mass impacting the top of the lava column. Assuming a simple lumped parameter representation of the shallow magmatic system, the observed pressure and volume variations can be modeled with the following attributes: rockfall volume (200 − 4500 m 3 ), length of magma column (120-210 m), diameter of pipe connecting the Halemaumau pit crater to the subjacent dike system (6 m), average thickness of the two underlying dikes (3 – 6 m), and effective magma viscosity (30–210 Pa s). Most rockfalls occur during episodes of sustained deflation of the Kilauea summit. The mass loss rate in the shallow magmatic system is estimated to be 1400  −  15, 000 kg s − 1 based on measurements of the temporal variation of VLP period in the two large rockfalls that occurred on August 29, 2012.

Description: Indoleamine 2,3-dioxygenase-1 (IDO1) catabolizes the essential amino acid tryptophan, acting as a modifier of inflammation and immune tolerance. Recent work has implicated IDO1 in many human diseases, including in cancer, chronic infection, autoimmune disorders and neurodegenerative disease, stimulating a major surge in preclinical and clinical studies of its pathogenic functions. In the mouse, IDO1 is expressed widely but in situ detection of the enzyme in murine tissues has been unreliable due to the lack of specific antibodies that do not also react with tissues from animals that are genetically deficient in IDO1. Such probes are crucial to establish cellular mechanisms since IDO1 appears to act in different cell types depending on disease context, but reliable probes have been elusive in the field. In this report, we address this issue with the development of IDO1 monoclonal antibody 4B7 which specifically recognizes the murine enzyme in tissue sections, offering a reliable tool for immunohistology in preclinical disease models. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation. Understanding the effects of nanotopography on cell adhesion and morphology and the consequences of cell shape changes in the nucleus, and consequently, gene expression offers new approaches to the elucidation and potential control of stem cell differentiation. In the current study we have used molecular approaches in combination with immunohistology and transcript analysis to understand the role of nanotopography on mesenchymal stem cell morphology and phenotype. Results demonstrate large changes in cell adhesion, nucleus and lamin morphologies in response to the different nanotopographies. Furthermore, these changes relate to alterations in packing of chromosome territories within the interphase nucleus. This, in turn, leads to changes in transcription factor activity and functional (phenotypical) signalling including cell metabolism. Nanotopography provides a useful, non-invasive tool for studying cellular mechanotransduction, gene and protein expression patterns, through effects on cell morphology. The different nanotopographies examined, result in different morphological changes in the cyto- and nucleo-skeleton. We propose that both indirect (biochemical) and direct (mechanical) signalling are important in these early stages of regulating stem cell fate as a consequence of altered metabolic changes and altered phenotype. The current studies provide new insight on cell–surface interactions and enhance our understanding of the modulation of stem cell differentiation with significant potential application in regenerative medicine. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to overcome oxidative damage by ROS/RNS all along its life cycle to survive and to establish a chronic infection. We propose that T. cruzi is able to survive, among other mechanisms of detoxification, by repair of its damaged DNA through activation of the DNA base excision repair (BER) pathway. BER is highly conserved in eukaryotes with apurinic/apirimidinic endonucleases (APEs) playing a fundamental role. Previous results showed that T. cruzi exposed to hydrogen peroxide and peroxinitrite significantly decreases its viability when co-incubated with methoxyamine, an AP endonuclease inhibitor. In this work the localization, expression and functionality of two T. cruzi APEs (TcAP1, Homo sapiens APE1 orthologous and TcAP2, orthologous to Homo sapiens APE2 and to Schizosaccaromyces pombe Apn2p) were determined. These enzymes are present and active in the two replicative parasite forms (epimastigotes and amastigotes) as well as in the non-replicative, infective trypomastigotes. TcAP1 and TcAP2 are located in the nucleus of epimastigotes and their expression is constitutive. Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are inhibited by methoxyamine. Overexpression of TcAP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent ROS/RNS exposition, mimicking nature conditions. Our results confirm that the BER pathway is involved in T. cruzi resistance to DNA oxidative damage and points to the participation of DNA AP endonucleases in parasite survival. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Active glutamine utilization is critical for tumor cell proliferation. Glutaminolysis represents the first and rate-limiting step of glutamine utilization and is catalyzed by glutaminase (GLS). Activation of ErbB2 is one of the major causes of breast cancers, the second most common cause of death for women in many countries. However, it remains unclear whether ErbB2 signaling affects glutaminase expression in breast cancer cells. In this study, we show that MCF10A-NeuT cell line has higher GLS1 expression at both mRNA and protein levels than its parental line MCF10A, and knockdown of ErbB2 decreases GLS1 expression in MCF10A-NeuT cells. We further show that in these cells, ErbB2-mediated upregulation of GLS1 is not correlated to c-Myc expression. Moreover, activation of neither PI3K-Akt nor MAPK pathway is sufficient to upregulate GLS1 expression. Interestingly, inhibition of NF-κB blocks ErbB2-stimulated GLS1 expression, whereas stimulation of NF-κB is sufficient to enhance GLS1 levels in MCF10A cells, suggesting a PI3K-Akt-independent activation of NF-κB upregulates GLS1 in ErbB2-positive breast cancer cells. Finally, knockdown or inhibition of GLS1 significantly decreased cell proliferation of breast cancer cells with high GLS1 levels. Taken together, our data indicate that ErbB2 activation promotes GLS1 expression via a PI3K-Akt-independent NF-κB pathway in breast cancer cells, identifying another oncogenic signaling pathway which stimulates GLS1 expression, and thus promoting glutamine utilization in cancer cells. These findings, if validated by in vivo model, may facilitate the identification of novel biochemical targets for cancer prevention and therapy. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Tissue injury and inflammation are associated with increased production of reactive oxygen species (ROS), which have the ability to induce oxidative injury to various biomolecules resulting in e.g. protein dysfunction or cell death. However, recent observations indicate that formation of hydrogen peroxide (H 2 O 2 ) during tissue injury is also an essential feature of the ensuing wound healing response, and functions as an early damage signal to control several critical aspects of the wound healing process. Because innate oxidative wound responses must be tightly coordinated to avoid chronic inflammation or tissue injury, a more complete understanding is needed regarding the origins and dynamics of ROS production, and their critical biological targets. This Prospect highlights the current experimental evidence implicating H 2 O 2 in early epithelial wound responses, and summarizes technical advances and approaches that may help distinguish its beneficial actions from its more deleterious actions in conditions of chronic tissue injury or inflammation. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  On 5 September 2012, a large thrust earthquake (M w 7.6) ruptured a densely-instrumented seismic gap on the shallow-dipping plate boundary beneath the Nicoya Peninsula, Costa Rica. Ground motion recordings directly above the rupture zone provide a unique opportunity to study the detailed source process of a large shallow megathrust earthquake using very nearby land observations. Hypocenter relocation using local seismic network data indicates that the event initiated with small emergent seismic waves from a hypocenter ~10 km offshore, 13 km deep on the megathrust. A joint finite-fault inversion using high-rate GPS, strong-motion ground velocity recordings, GPS static offsets, and teleseismic P waves reveals that the primary slip zone (slip 〉 1 m) is located beneath the peninsula. The rupture propagated down-dip from the hypocenter with a rupture velocity of ~3.0 km/s. The primary slip zone extends ~70 km along strike and ~30 km along dip, with an average slip of ~2 m. The associated static stress drop is ~3 MPa. The seismic moment is 3.5 x 10 20  Nm, giving M w  = 7.6. The co-seismic large-slip patch directly overlaps an onshore inter-seismic locked region indicated by geodetic observations, and extends down-dip to the intersection with the upper plate Moho. At deeper depths, below the upper plate Moho, seismic tremor and low frequency earthquakes have been observed. Most tremor locates in adjacent areas of the megathrust that have little co-seismic slip; a region of prior slow slip deformation to the southeast also has no significant co-seismic slip or aftershocks. An offshore locked patch indicated by geodetic observations does not appear to have experienced co-seismic slip, and aftershocks do not overlap this region, allowing the potential for a comparable size rupture offshore in the future.

Description: [1]  Seismic shear waves emitted by earthquakes can be modeled as plane (transverse) waves. When entering an anisotropic medium they can be split into two orthogonal components moving at different speeds. This splitting occurs along an axis, the fast polarization, that is determined by geologic conditions. We present here a comprehensive analysis of the Silver and Chan (1991) method, used to obtain shear wave splitting parameters, comprising theoretical derivations and statistical tests of the assumptions used to construct the standard errors. We find discrepancies in the derivations of equations in their article, with the most important being a mistake in how the standard errors are calculated. Our simulations suggest that the degrees of freedom are being overestimated by this method and consequently the standard errors are too small. Using a set of S waveforms from very similar shallow earthquakes on Reunion Island, we perform a statistical analysis on the noise of these replicates and find that the assumption of Gaussian noise does not hold. Further, the properties of background noise differ substantially from the noise obtained from the shear wave splitting analysis. However, we find that the standard errors for the fast polarization are comparable to the spread in the fast polarization parameters. Delay time errors appear to be comparable to delay time estimates once cycle skipping is accounted for. Future work using synthetic seismograms with simulated noise should be conducted to confirm this is the case for earthquakes in general.

Description: [1]  The sliver strike-slip Great Sumatra Fault (GSF) traverses mainland Sumatra from the Sunda Strait in the southeast to Banda Aceh in the northwest, and defines the present day plate boundary between the Sunda Plate in the north and the Burmese Sliver Plate in the south. It has been well studied on mainland Sumatra but poorly north of Banda Aceh in the Andaman Sea. Here we present deep seismic reflection images along the northward extension of the GSF over 700 km until it joins the Andaman Sea Spreading Centre and we interpret these images in the light of earthquake, gravity, and bathymetry data. We find that the GSF has two strands between Banda Aceh and Nicobar Island: a transpression in the south and a deep narrow active rift system in the north dotted with volcanoes in the center, suggesting that the volcanic arc is coincident with rifting. Further north of Nicobar Island, an active strike-slip fault, the Andaman-Nicobar Fault, cuts through a rifted deep basin until its intersection with the Andaman Sea Spreading Centre. The volcanic arc lies just east of the rift basin. The western margin of this basin seems to be a rifted continental margin, tilted westward, and flooring the Andaman-Nicobar forearc basin. The Andaman-Nicobar forearc basin is bounded in the west by backthrusts similar to the West Andaman and Mentawai faults. The cluster of seismicity after the 2004 great Andaman-Sumatra earthquake just north of Nicobar Island coincides with the intersection of two strike-slip fault systems.

Description: [1]  The Japan Tohoku-Oki earthquake (9.0 Mw) of 11 March 2011 has left signatures in the Earth's gravity field that are detectable by data of the GRACE mission. Because ESA's satellite gravity mission GOCE – launched in 2009 – aims at high spatial resolution, its measurements could complement the GRACE information on coseismic gravity changes, although time-variable gravity was not foreseen as goal of the GOCE mission. We modeled the coseismic earthquake geoid signal and converted this signal to vertical gravity gradients at GOCE satellite altitude. We combined the single gradient observations in a novel way reducing the noise level, required to detect the coseismic gravity change, subtracted a global gravity model, and applied tailored outlier detection to the resulting gradient residuals. Furthermore, the measured gradients were along-track filtered using different gradient bandwidths where in the space domain Gaussian smoothing has been applied. One year periods before and after earthquake occurrence have been compared with the modeled gradients. The comparison reveals that the earthquake signal is well above the accuracy of the vertical gravity gradients at orbital height. Moreover, the obtained signal from GOCE shows a 1.3 times higher amplitude compared with the modeled signal. Besides the statistical significance of the obtained signal, it has a high spatial correlation of ~0.7 with the forward modeled signal. We conclude therefore that the coseismic gravity change of the Japan Tohoku-Oki earthquake left a statistically significant signal in the GOCE measured gravity gradients.

Description: [1]  The Ninetyeast Ridge (NER), one of the longest linear volcanic features on the Earth, offers an excellent opportunity of understanding the isostatic response to the interactions of mantle plume with the migrating mid-ocean ridge. Bathymetry, geoid and gravity (ship-borne and satellite) data along 72 closely spaced transects and 17 overlapping grids on the NER are analyzed and modeled to determine the effective elastic thickness ( Te ) beneath the entire ridge. The results of 2-D and 3-D flexural modeling of the NER show large spatial variations in Te values ranging from 4 to 35 km, suggesting that the ridge was compensated along its length by different isostatic mechanisms. The southern (south of 22°S latitude) and northern (north of 2°N latitude) parts of the NER have Te values of 〉10 and 〉23 km, respectively, revealing that the southern part was emplaced on a lithosphere of intermediate strength possibly on flank of the Indian plate, whereas the northern part was emplaced in an intraplate setting. In contrast, in the central part of the NER (between latitudes 22°S and 2°N), highly variable Te values (4–22 km) are estimated. The scattered Te values in the central NER suggest that this part may have evolved due to the occurrence of more frequent ridge jumps caused by the interaction of Kerguelen hot spot with rapid northward migration of the Wharton spreading ridge. Residual Mantle Bouguer Anomaly (RMBA) map of the NER and adjacent basins reveals that the entire length of the NER is associated with a significant negative anomaly up to 200 mGal, indicating the presence of thickened crust or less dense mantle beneath the ridge. 3-D crustal thickness map of the NER, generated by inversion of the RMBA data, shows a thick crust ranging from 15 to 19 km. The present study clearly shows that NER possesses a highly segmented isostatic pattern with the occurrence of sub-crustal underplating or sub-surface loading.

Description: [1]  We conducted deep-sea magnetic measurements using autonomous underwater vehicles in the Bayonnaise knoll caldera, the Izu-Ogasawara island arc, which hosts the large Hakurei hydrothermal field. We improved the conventional correction method applied for removing the effect of vehicle magnetization, thus greatly enhancing the precision of the resulting vector anomalies. The magnetization distribution obtained from the vector anomaly data shows an ∼ 2-km-wide belt of high magnetization, trending NNW–SSE going through the caldera, and a low magnetization zone ∼ 300 m by ∼ 500 m in area, extending over the Hakurei site. Comparison between the results obtained using the vector anomaly and the total intensity anomaly shows that the magnetic field is determined more accurately, especially in areas of sparse data distribution, when the vector anomaly rather than the total intensity anomaly is used. We suggest a geologically motivated model that basaltic volcanism associated with the backarc rifting occurred after the formation of the caldera, resulting in the formation of the high magnetization belt underneath the silicic caldera. The Hakurei hydrothermal field lies in the intersection of the basaltic volcanism belt and the caldera wall fault, suggesting a mechanism that hot water generated by the heat of the volcanic activity has been spouting out through the caldera wall fault. The deposit apparently extends beyond the low magnetization zone, climbing up the caldera wall. This may indicate that hot water rising from the deep through the alteration zone is transported laterally when it comes near the seafloor along fissures and fractures in the caldera wall.

Description: [1]  Using multiple ScS reverberations we examine mantle reflectivity structure beneath northeast China and the northwest Pacific. We find several upper mantle discontinuities, including a melt layer with a mean thickness of 64 km atop the 410-km discontinuity, present on both sides of the subducting slab near the Nankai trench. The transition zone contains a split 520-km discontinuity in several paths, and tomographic images show stagnant slabs at this depth. We believe this may be slab-related based on experimental work (Saikia, A., Frost, D. J., Rubie, D. C., 2008. Splitting of the 520-kilometer seismic discontinuity and chemical heterogeneity in the mantle. Science 319 (5869), 1515–1518). A negative reflector is found in one path beneath the northeast China craton at a depth of 598 km. Mid-mantle reflectors are found in all of our paths and are present throughout a wide depth range (~750 – 1600 km).

Description: [1]  Three-dimensional P - and S -wave velocity (V P , V S ) models and high-resolution earthquake relocations are determined for the New Madrid Seismic Zone using double-difference local earthquake tomography. The data set consists of arrival times and differential times recorded by the Cooperative New Madrid Seismic Network (CNMSN) from 2000-2007 and the 1989-1992 Portable Array Network and Data Acquisition deployment. Waveform cross-correlation derived differential times for the CNMSN data are also incorporated. The velocity solutions are compatible with previous solutions centered on the active arms of seismicity and cover a broader area including mafic intrusions along the margin of the Reelfoot Rift. Major features include elevated V P and V S associated with the mafic plutons and reduced V P and V S along and southeast of the Axial fault (AF), a major arm of seismicity trending along the rift axis. Low V P extends to a depth of at least 20 km along the portion of the AF that extends south of the Missouri bootheel. A locally high V P /V S anomaly imaged along the central portion of the Reelfoot fault is spatially correlated with a significant change in fault trend and is interpreted as a region containing high pore pressure and/or water-filled microcracks.

Description: [1]  We present a catalog of InSAR constraints on deformation that occurred during earthquake sequences in southern Iran between 1992-2011, and explore the implications on the accommodation of large-scale continental convergence between Saudi Arabia and Eurasia within the Zagros Mountains. The Zagros Mountains, a salt-laden fold-and-thrust-belt involving ~10 km of sedimentary rocks overlying Precambrian basement rocks, have formed as a result of ongoing continental collision since 10-20 Ma that is currently occurring at a rate of ~3 cm/yr. We first demonstrate that there is a biased misfit in earthquake locations in global catalogs that likely results from neglect of 3D velocity structure. Previous work involving two M ~ 6 earthquakes with well-recorded aftershocks has shown that the deformation observed with InSAR may represent triggered slip on faults much shallower than the primary earthquake, which likely occurred within the basement rocks (〉10 km depth). We explore the hypothesis that most of the deformation observed with InSAR spanning earthquake sequences is also due to shallow, triggered slip above a deeper earthquake, effectively doubling the moment release for each event. We quantify the effects that this extra moment release would have on the discrepancy between seismically and geodetically constrained moment rates in the region, finding that even with the extra triggered fault slip, significant aseismic deformation during the interseismic period is necessary to fully explain the convergence between Eurasia and Saudi Arabia.

Description: [1]  The identification and evaluation of trigger mechanisms for volcano flank instabilities and/or collapse represent a key issue for risk assessment in densely populated volcanic areas, as well as in long distance settings, particularly in case of island or coastal volcanoes. Here, we address quantitatively the effects of external (seismic) and inner (magmatic) forcing on the stress-strain state associated to flank instabilities at Mt. Etna (Sicily, southern Italy) by means of a 2-D Finite-Difference-Method numerical modelling. Modelled seismic actions include strong near-field, strong far-field and low-magnitude near-field earthquakes. Magmatic actions consider the inner presssure changes induced by energetic lava fountains in the summit crater area, sub-vertical and oblique dyke ascent below the summit area. Model results are validated in light of available monitoring data and recent eruptive activity. Numerical results show that the main strain effects are produced by high-magnitude near-field earthquakes (expected return time of ~10 3  yrs), and by vertical uprise of a magma dyke below the volcano summit area. Maximum displacements in the order of tens of centimetres may involve the summit area, up to some 10 6  m 3 /m over some km laterally. Stress releases up to 10 7  Pa may affect a limited portion of the magmatic conduit, thus favouring major effusive flank eruptions. Major catastrophic events, such as volcano flank collapse, should not be expected by applying, either individually or combined, the aforementioned actions.

Description: [1]  Seismicity closely related to hydrological impacts has been observed in several locations worldwide; particularly in intraplate areas where tectonic stressing rates are small. The triggering mechanism is usually explained by a poroelastic response of the seismogenic crust to surface water flux, leading to pore pressure changes at depth. To explain the earthquake triggering in response of those small stress changes, however, the crust has to be near a critical state in which other transient processes might be significant. One of the prominent examples is the Mt. Hochstaufen in SW Germany, where seismicity is known to vary seasonally. A previous analysis showed that the seismicity in 2002 was highly correlated with model forecasts based on fluid diffusion and rate- and state-dependent frictional nucleation. Here we revisit this case by accounting additionally for poroelastic effects, as well as for thermoelastic and tidal stresses. We also test whether the model can explain the observations of the subsequent eight years between 2003 and 2010. Our analysis confirms that rainfall is the dominant driving force in this region. The model not only fits the year 2002 activity very well, but provides with the same parameters a reasonable fit to the subsequent period, with a probability gain of about 4 per event in comparison to a time-independent Poisson model.

Description: ABSTRACT [1]  The absolute magnitude of stress in the crust and the shear strength of faults are poorly known, yet fundamental quantities, in lithospheric dynamics. While stress magnitude cannot be measured directly, deviatoric stress state can be inferred indirectly from focal mechanism solutions collected before and after an earthquake. We extend a standard stress inversion for normalized stresses to invert for the 3D spatial distribution of absolute deviatoric stress and variation of fault strength with depth using focal mechanism solutions and coseismic stress changes produced by large earthquakes. We apply the method to the 2011 M9 Tohoku-oki, Japan earthquake. The northern Japan forearc crust between 5 and 15 km depth appears to be weak with fault strength of 40–90 MPa, consistent with a coefficient of friction of 0.2-0.5. The M9 Tohoku-oki coseismic stress change was large enough, relative to the ambient stress, to rotate the principal stress directions typically ~20° in the upper 20 km of the crust. The data from Japan require a heterogeneous ambient deviatoric stress field with short wavelength (~20-50 km) fluctions in principal stress orientations.

Description: [1]  We review marine heat flow data along the Nankai Trough and show that observations 〉 30 km seaward of the deformation front are 20% below conductive predictions (129–94 mW m -2 ) but consistent with the global heat flow average for oceanic crust of the same age (16-28 Ma). Heat flow values  〈  30 km seaward of the deformation front are generally 20% higher than conductive predictions. This heat flow pattern is consistent with the advection of heat by fluid flow in the subducting oceanic crust and explains both the high heat flux in the vicinity of the trench, 〉 200 and 〉 140 mW m -2 , and steep landward declines to values of approximately 60 mW m -2 over distances of 65 and 50 km along the Muroto and Kumano transects, respectively. Along the Ashizuri transect the lack of heat flow data preclude a definitive interpretation. We conclude that fluid flow in the subducting oceanic crust leads to temperatures that are generally 25 ° C higher near the toe of the margin wedge and 50 - 100 ° C lower near the downdip limit of the seismogenic zone than estimated by purely conductive models.

Description: Hepatocytes can be generated from embryonic stem cells (ESCs) using inducers such as chemical compounds and cytokines, but issues related to low differentiation efficiencies remain to be resolved. Recent work has shown that overexpression of lineage-specific transcription factors can directly cause cells phenotypic changes, including differentiation, trans-differentiation, and de-differentiation. We hypothesized that lentivirus-mediated constitutive expression of forkhead box A2 (Foxa2) and hepatocyte nuclear factor 4 alpha (Hnf4a) could promote inducing mouse ESCs to hepatocyte-likes cells. First, ESC lines that stably expressed Foxa2, Hnf4a or Foxa2/Hnf4a were constructed via lentiviral expression vectors. Second, observations of cell morphology changes were made during the cell culture process, followed by experiments examining teratoma formation. Then, the effects of constitutive expression of Foxa2 and Hnf4a on hepatic differentiation and maturation were determined by measuring the marker gene expression levels of Albumin, α-fetoprotein, Cytokeratin18, and α1-antitrypsin. The results indicate that constitutive expression of Foxa2 and Hnf4a does not affect ESCs culture, teratoma formation, or the expression levels of the specific hepatocyte genes under autonomous differentiation. However, with some assistance from inducing factors, Foxa2 significantly increased the hepatic differentiation of ESCs, whereas the expression of Hnf4a alone or Foxa2/Hnf4a could not. Differentiated CCE-Foxa2 cells were more superior in expressing several liver-specific markers and protein, storing glycogen than differentiated CCE cells. Therefore, our method employing the transduction of Foxa2 would be a valuable tool for the efficient generation of functional hepatocytes derived from ESCs. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: The definition of the secretome signature of a cancer cell line can be considered a potential tool to investigate tumor aggressiveness and a preclinical exploratory study required to optimize the search of cancer biomarkers. Dealing with a cell-specific secretome limits the contamination by the major components of the human serum and reduces the range of dynamic concentrations among the secreted proteins, thus favouring under-represented tissue-specific species. The aim of the present study is to characterize the secretome of two human colon carcinoma cell lines, CaCo-2 and HCT-GEO, in order to evaluate differences and similarities of two colorectal cancer model systems. In this study, we identified more than 170 protein species, 64 more expressed in the secretome of CaCo-2 cells and 54 more expressed in the secretome of HCT-GEO cells; 58 proteins were shared by the two systems. Among them, more than 50% were deemed to be secretory according to their Gene Ontology annotation and/or to their SignalP or SecretomeP scores. Such a characterization allowed to corroborate the potential of a cell culture-based model in order to describe the cell-specific invasive properties and to provide a list of putative cancer biomarkers. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: The cytoplasmic C-terminus of connexin43 (Cx43) interacts with numerous signaling complexes. We hypothesize that signal complex docking to the Cx43 C-terminus (CT) is required to propagate the molecules being shared by gap junctions. We have previously shown that Cx43 impacts the responsiveness of osteoblasts to FGF2 in a PKCδ- and ERK-dependent manner, converging on Runx2 activity. Here, we mapped the interaction domain of Cx43 and PKCδ to amino acids 243-302 of the Cx43 CT by GST pulldown assay. Using Runx2-responsive luciferase reporter assays, a Cx43 deletion construct (Cx43 S244Stop), which lacks the C-terminus (amino acids 244 to 382), failed to support the Cx43-dependent potentiation of transcription following FGF2 treatment in MC3T3 osteoblast-like cells. Similarly, overexpression of Cx43 S244Stop could not mimic the ability of the full length Cx43 to stimulate expression of osteoblast genes. In contrast to full length Cx43, overexpression of just the Cx43 CT (amino acids 236 to 382) inhibited both transcription from a Runx2 reporter and signaling via PKCδ and ERK. Inhibition of signaling by the CT did not occur in HeLa cells, which lack endogenous Cx43. In summary, the data support a model in which an intact Cx43 is required for both signal propagation/permeability (i.e., channel function) and local recruitment of signaling complexes to the CT (i.e., docking function) in order to mediate its cellular effects. Further, while the CT alone has channel independent activity, it is opposing to the effect of overexpression of the full length Cx43 channel. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by accelerating endothelial cell (EC) senescence and limiting the proliferative potential of these cells. Here we aimed to investigate the effect of stachydrine, a proline betaine present in considerable quantities in juices from fruits of the Citrus genus, on EC under high-glucose stimulation, and its underlying mechanism. The senescence model of EC was set up by treating cells with high-glucose (30 mM) for different times. Dose-dependent (0.001-1mM) evaluation of cell viability revealed that stachydrine does not affect cell proliferation with a similar trend up to 72 h. Noticeable, stachydrine (0.1 mM) significantly attenuated the high-glucose induced EC growth arrest and senescence. Indeed, co-treatment with high-glucose and stachydrine for 48 h kept the percentage of EC in the G 0 /G 1 cell cycle phase near to control values and significantly reduced cell senescence. Western blot analysis and confocal-laser scanning microscopy revealed that stachydrine also blocked the high-glucose induced upregulation of p16 INK4A and downregulation of SIRT1 expression and enzyme activity. Taken together, results here presented are the first evidence that stachydrine, a naturally occurring compound abundant in citrus fruit juices, inhibits the deleterious effect of high-glucose on EC and acts through the modulation of SIRT1 pathway. These results may open new prospective in the identification of stachydrine as an important component of healthier eating patterns in prevention of cardiovascular diseases. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Rett Syndrome (RTT) is one of most prevalent female neurodevelopmental disorders. De novo mutations in X-linked MECP2 are mostly responsible for RTT. Since the identification of MeCP2 as the underlying cause of RTT, murine models have contributed to understanding the pathophysiology of RTT and function of MeCP2. Reprogramming is a procedure to produce induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors. iPSCs obtain similar features as embryonic stem cells and are capable of self-renewing and differentiating into cells of all three layers. iPSCs have been utilized in modeling human diseases in vitro. Neurons differentiated from RTT-iPSCs showed the recapitulation of RTT phenotypes. Despite the early success, genetic and epigenetic instability upon reprogramming and ensuing maintenance of iPSCs raise concerns in using RTT-iPSCs as an accurate in vitro model. In this review, we update the current of iPSC-based RTT modeling, and concerns and challenges. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Background Mesangial cells (MCs) proliferation and accumulation of glomerular matrix proteins such as fibronectin (FN) are the early features of diabetic nephropathy, with MCs known to upregulate matrix protein synthesis in response to high glucose. Recently, it has been found that andrographolide has renoprotective effects on diabetic nephropathy. However, the molecular mechanism underlying these effects remains unclear. Methods Cell viability and proliferation was evaluated by MTT. FN expression was examined by immunofluorescence and immunoblotting. Activator protein-1 (AP-1) activation was assessed by immunoblotting, luciferase reporter and electrophoretic mobility shift assays. Results Andrographolide significantly decreased high glucose-induced cell proliferation and FN expression in MCs. Exposure of MCs to high glucose markedly stimulated the expression of phosphorylated c-jun, whereas the stimulation was inhibited by andrographolide. Plasmid pAP-1-Luc luciferase reporter assay showed that andrographolide blocked high glucose-induced AP-1 transcriptional activity. EMSA assay demonstrated that increased AP-1 binding to a AP-1 binding site at -1029 in the FN gene promoter upon high glucose stimulation, and the binding was disrupted by andrographolide treatment. Conclusions These data indicate that andrographolide suppresses high glucose-induced FN expression by inhibiting AP-1-mediated pathway. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Basic fibroblast growth factor (bFGF) and Notch signaling play critical roles in various cell behaviors. Here, we investigated the influence of bFGF and Notch signaling in alkaline phosphatase (ALP) expression and mineralization process in human periodontal ligament-derived mesenchymal stem cells (PDLSCs) and stem cells isolated from human exfoliated deciduous teeth (SHEDs). PDLSCs and SHEDs were cultured in osteogenic medium supplemented with bFGF or on the immobilized Notch ligands, JAGGED1. The ALP mRNA and protein expression were measured by quantitative reverse transcriptase polymerase chain reaction and enzymatic activity assay, respectively. Mineral deposition was determined using alizarin red S staining. The results showed that the addition of bFGF resulted in the decrease of ALP mRNA expression and enzymatic activity. In addition, the attenuation of mineralization was noted. These phenomenons were blocked by the addition of a fibroblast growth factor receptor inhibitor (SU5402) or a MEK inhibitor (PD98059). Interestingly, bFGF supplementation also decreased the Notch signaling component mRNA levels. Thus, to evaluate effect of Notch signaling in mineralization process, PDLSCs and SHEDs were exposed to JAGGED1 modified surface. The ALP mRNA and protein expression were significantly upregulated and the mineral deposition was markedly increased. These results could be reversed by the addition of a γ-secretase inhibitor. In addition, bFGF could attenuate the Notch-signaling-induced mineralization in both PDLSCs and SHEDs. These results suggest that mineralization was enhanced by Notch signaling but attenuated by bFGF signaling. This knowledge can be further utilized to control PDLSCs and SHEDs mineralization for tissue regeneration purpose. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  We investigate whether predictions of mantle structure from tectonic reconstructions are in agreement with a detailed tomographic image of seismic P-wave velocity structure under the Caribbean region. In the upper mantle, positive seismic anomalies are imaged under the Lesser Antilles and Puerto Rico. These anomalies are interpreted as remnants of Atlantic lithosphere subduction and confirm tectonic reconstructions that suggest at least 1100 km of convergence at the Lesser Antilles island arc during the past ~45 Myr. The imaged Lesser-Antilles slab consists of a northern and southern anomaly, separated by a low velocity anomaly across most of the upper mantle, which we interpret as the subducted North America-South America plate boundary. The southern edge of the imaged Lesser Antilles slab agrees with vertical tearing of South America lithosphere. The northern Lesser Antilles slab is continuous with the Puerto Rico slab along the northeastern plate boundary. This results in an amphitheatre-shaped slab and it is interpreted as westward subducting North America lithosphere that remained attached to the surface along the northeastern boundary of the Caribbean plate. At the Muertos Trough, however, material is imaged until a depth of only 100 km, suggesting a small amount of subduction. The location and length of the imaged South Caribbean slab agrees with proposed subduction of Caribbean lithosphere under the northern South America plate. An anomaly related to proposed Oligocene subduction at the Nicaragua rise is absent in the tomographic model. Beneath Panama, a subduction window exists across the upper mantle, which is related to the cessation of subduction of the Nazca plate under Panama since 9.5 Ma and possibly the preceding subduction of the extinct Cocos-Nazca spreading center. In the lower mantle two large anomaly patterns are imaged. The westernmost anomaly agrees with the subduction of Farallon lithosphere. The second lower mantle anomaly is found east of the Farallon anomaly and is interpreted as a remnant of the late Mesozoic subduction of North and South America oceanic lithosphere at the Greater Antilles, Aves ridge and Leeward Antilles. The imaged mantle structure does not allow us to discriminate between an ‘Intra-Americas’ origin and a ‘Pacific origin’ of the Caribbean plate.

Description: Cell penetrating peptides (CPPs) are a series of promising carriers for delivering exogenous DNA to living cells. Among them, the combination of the human immunodeficiency virus TAT protein (TAT) with the SV40 large T protein nuclear localization signal (NLS) to form NLS-TAT performs well. In the present study, we took advantage of this new carrier to deliver transforming growth factor-beta 3 (TGFβ3) genes. TGFβ3 was expressed by the pEGFP-N1 vector following transfection of rat precartilaginous stem cells (PSCs), which promoted hTGFβ3 protein self-expression. At 24 h, 48 h, 72 h and 120 h after transfection, the expression levels of hTGFβ3 were found to be elevated as compared with the control. The expression of hTGFβ3 was found to mediate the chondrogenic effect of PSCs. Thus, we determined the expression of the chondrogenesis-related genes type II collagen, Sox 9 and aggrecan in PSCs at 24 h, 48 h, 72 h and 120 h after transfection. We found that their transcription and translation was augmented, which indicated a trend of active chondrogenesis in the PSCs. Our results demonstrated that NLS-TAT had the ability to deliver exogenous DNA into rat PSCs and could be actively expressed. This process successfully promoted PSC chondrogenesis. Additionally, PSC, may represent a new type of stem cells, and thus show great potential in regenerative repair following cartilage injury. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  We have measured interseismic deformation across the Ashkabad strike-slip fault using 13 Envisat interferograms covering a total effective timespan of ~30 years. Atmospheric contributions to phase delay are significant and variable due to the close proximity of the Caspian Sea. In order to retrieve the pattern of strain accumulation, we show it is necessary to use data from Envisat's Medium Resolution Imaging Spectrometer (MERIS) instrument, as well numerical weather model outputs from the European Centre for Medium-Range Weather Forecasting (ECMWF), to correct interferograms for differences in water vapour and atmospheric pressure respectively. This has enabled us to robustly estimate the slip rate and locking depth for the Ashkabad fault using a simple elastic dislocation model. Our data are consistent with a slip rate of 5–12 mm/yr below a locking depth of 5.5–17 km for the Ashkabad fault, and synthetic tests support the magnitude of the uncertainties on these estimates. Our estimate of slip rate is 1.25–6 times higher than some previous geodetic estimates, with implications for both seismic hazard and regional tectonics, in particular supporting fast relative motion between the South Caspian Block and Eurasia. This result reinforces the importance of correcting for atmospheric contributions to interferometric phase for small strain measurements. We also attempt to validate a recent method for atmospheric correction based on ECMWF ERA-Interim model outputs alone and find that this technique does not work satisfactorily for this region when compared to the independent MERIS estimates.

Description: Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase (ALP) activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPARγ), adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  The seafloor within the Perth Abyssal Plain (PAP), offshore Western Australia, is the only section of crust that directly records the early spreading history between India and Australia during the Mesozoic breakup of Gondwana. However, this early spreading has been poorly constrained due to an absence of data, including marine magnetic anomalies and data constraining the crustal nature of key tectonic features. Here, we present new magnetic anomaly data from the PAP that shows that the crust in the western part of the basin was part of the Indian Plate – the conjugate flank to the oceanic crust immediately offshore the Perth margin, Australia. We identify a sequence of M2 and older anomalies in the west PAP within crust that initially moved with the Indian Plate, formed at intermediate half-spreading rates (35 mm/yr) consistent with the conjugate sequence on the Australian Plate. More speculatively, we reinterpret the youngest anomalies in the east PAP, finding that the M0-age crust initially formed on the Indian Plate was transferred to the Australian Plate by a westward jump or propagation of the spreading ridge shortly after M0 time. Samples dredged from the Gulden Draak and Batavia Knolls (at the western edge of the PAP) reveal that these bathymetric features are continental fragments rather than igneous plateaus related to Broken Ridge. These microcontinents rifted away from Australia with Greater India during initial breakup at ~130 Ma, then rifted from India following the cessation of spreading in the PAP (~101-103 Ma).

Description: [1]  We develop a three-step Maximum-A-Posteriori probability (MAP) method for coseismic rupture inversion, which aims at maximizing the a posterior probability density function (PDF) of elastic deformation solutions of earthquake rupture. The method originates from the Fully Bayesian Inversion (FBI) and Mixed linear-nonlinear Bayesian inversion (MBI) methods, shares the same posterior PDF with them, while overcoming difficulties with convergence when large numbers of low-quality data are used and greatly improving the convergence rate using optimization procedures. A highly-efficient global optimization algorithm, Adaptive Simulated Annealing (ASA), is used to search for the maximum of a posterior PDF (" mode " in statistics) in the first step. The second step inversion approaches the " true" solution further using the Monte Carlo Inversion (MCI) technique with positivity constraints, with all parameters obtained from step one as the initial solution. Then slip artifacts are eliminated from slip models in the third step using the same procedure of the second step, with fixed fault geometry parameters. [2]  We first design a fault model with 45°-dip angle and oblique slip, and produce corresponding synthetic InSAR datasets to validate the reliability and efficiency of the new method. We then apply this method to InSAR data inversion for the coseismic slip-distribution of the April 14, 2010 Mw 6.9 Yushu, China earthquake. Our preferred slip model is composed of three segments with most of the slip occurring within 15 km depth and the maximum slip reaches 1.38 m at the surface. The seismic moment released is estimated to be 2.32e + 19 Nm, consistent with the seismic estimate of 2.50e + 19 Nm.

Description: We have previously demonstrated that the ultraviolet (UV) light is effective against a variety of cancer cells in vivo as well as in vitro. In the present report, we imaged the DNA damage repair response of minimal cancer after UVC irradiation. DNA-damage repair response to UV irradiation was imaged on tumors growing in 3-D culture and in superficial tumors grown in vivo . UV-induced DNA damage repair was imaged with GFP fused to the DNA damage response (DDR)-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. Three-dimensional culture and in vivo imaging enabled 53BP1-GFP nuclear foci to be observed within one hour after UVC irradiation, indicating the onset of DNA damage repair response. A clonogenic assay showed that UVC inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, while UVA and UVB showed little effect on cell proliferation. Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40 µm in 3D-culture of MiaPaCa-2 cells. The MiaPaCa-2 cells irradiated by UVC light in a skin-flap mouse model had a significant decrease of tumor growth compared to untreated controls. Our results also demonstrate that 53BP1-GFP is an imageable marker to UV-induced DNA damage repair response of minimal cancer and that UVC is a useful tool for the treatment of residual cancer since UVC can kill superficial cancer cells without damage to deep tissue. In this study, using 53BP1-GFP as a marker of early response to DNA damage, we investigated the efficacy and limitation of UV light as a therapeutic modality for MRC. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Endochondral ossification is essential for new bone formation and remodeling during the distraction stage. Endochondral ossification is attributed to chondrocyte maturation, which is induced by various factors, such as the cellular environment, gene transcription, and growth factor expression. Cartilage oligomeric matrix protein (COMP)-angiopoietin 1 (Ang1) is more soluble, stable, and potent than endogenous Ang1, and COMP-Ang1 treatment has osteogenic and angiogenic effects in an in vivo model of bone fracture healing. Although the osteogenic effects of COMP-Ang1 have been demonstrated, the precise mechanism by which COMP-Ang1 induces chondrocyte maturation and triggers endochondral ossification is not understood. Here, we investigated the possible mechanism by which COMP-Ang1 induces chondrocyte maturation. First, using a WST assay, we found that COMP-Ang1 is nontoxic in rat chondrocytes. Then, we isolated total RNA from COMP-Ang1–treated rat chondrocytes, and analyzed the decrease in chondrogenic gene expression and the increase in osteogenic gene expression using real-time RT-PCR. Gene and protein expression of heme oxygenase-1 (HO-1), which maintains chondrocytes in an immature stage, decreased in a dose-dependent manner upon COMP-Ang1 treatment. To clarify the relationship between HO-1 and COMP-Ang1 in chondrocyte maturation, we used cobalt protoporphyrin IX (CoPP IX), an HO-1 inducer, and tin protoporphyrin IX (SnPP-IX), an HO-1 inhibitor. Treatment with various combinations of CoPP IX, SnPP IX, and COMP-Ang1 confirmed that COMP-Ang1 accelerates chondrocyte maturation by reducing HO-1. In conclusion, our results suggest that COMP-Ang1 accelerates chondrocyte maturation by interacting with HO-1. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  We conducted total magnetic field and Bouguer gravity measurements to investigate the shallow structure beneath the summit caldera of Kīlauea Volcano, Hawai‘i. Two significant and distinctive magnetic anomalies were identified within the caldera. One is interpreted to be associated with a long-lived pre-historic eruptive centre, the Observatory vent, located ~1 km east of the Hawaiian Volcano Observatory. The second magnetic anomaly corresponds to a set of eruptive fissures that strike northeast from Halema‘uma‘u Crater, suggesting this is an important transport pathway for magma. The Bouguer gravity data were inverted to produce 3D models of density contrasts in the upper 2 km beneath Kīlauea. The models detect 3.0 km 3 of material, denser than 2800 kg m -3 , beneath the caldera that may represent an intrusive complex centred northeast of Halema‘uma‘u. Recent temporal gravity studies indicate continual addition of mass beneath the caldera during 1975–2008 centred west of Halema‘uma‘u and suggest this is due to filling of void space. The growth of a large intrusive complex, apparent cyclical caldera formation, and continual mass addition without inflation, however, can also be explained by extensional rifting caused by the continual southward movement of Kīlauea's unstable south flank.

Description: [1]  The 2006-2007 doublet of M W  〉 8 earthquakes in the Kuril subduction zone caused postseismic transient motion in the asthenosphere, which we observed on the Kuril GPS Array in 2007–2011. Here we show that the Maxwell asthenospheric viscosity that best fits the geodetic data increased by nearly an order of magnitude over the interval of four years, from 2 × 10 17 to 1 × 10 18  Pa s. These effective values of viscosity can be explained by a power-law rheology for which strain rate is proportional to stress raised to a power n  〉 1. The apparent change in viscosity can also be caused by other factors such as coupling between afterslip and viscoelastic flow. The open and intriguing question in connection with postseismic data after the Kuril earthquake doublet is the magnitude of the long-term asthenospheric viscosity, which shall be revealed by continued observations. An asthenosphere with viscosity of about 1 × 10 19  Pa s is favored by the postseismic deformation still observed several decades after the 1960 Chile and 1964 Alaska M W ~9 earthquakes. However, postseismic deformation associated with the 1952 southern Kamchatka M W ~9 earthquake currently is not observed in the northern Kurils, an indication that the long-term asthenospheric viscosity in the Kurils is lower than in Chile and Alaska.

Description: [1]  The region of central Chile offers a unique opportunity to study the links between the subducting Juan Fernandez Ridge, the flat slab, the Double Seismic Zone (DSZ) and the absence of modern volcanism. Here, we report the presence and characteristics of the first observed DSZ within the intermediate-depth Nazca slab using two temporary seismic catalogues (OVA99 and CHARSME). The lower plane of seismicity (LP) is located 20–25 km below the upper plane (UP), begins at 50 km depth and merges with the lower plane at 120 km depth, where the slab becomes horizontal. Focal mechanism analysis and stress tensor calculations indicate that the slab's state of stress is dominantly controlled by plate convergence and overriding crust thickness: Above 60–70 km depth, the slab is in horizontal compression, and below, it is in horizontal extension, parallel to plate convergence, which can be accounted for by vertical loading of the overriding lithosphere. Focal mechanisms below 60–70 km depth are strongly correlated with offshore outer rise bend faults, suggesting the reactivation of pre-existing faults below this depth. The large interplane distances for all Nazca DSZs can be related to the slab's unusually cold thermal structure with respect to its age. Since LPs globally seem to mimic mantle mineral dehydration paths, we suggest that fluid migration and dehydration embrittlement provide the mechanism necessary to weaken the rock and that the stress field determines the direction of rupture.

Description: One of the most frequent chromosomal translocation found in patients with acute myeloid leukemia (AML) is the t(8;21). This translocation involves the RUNX1 and ETO genes. The breakpoints regions for t(8;21) are located at intron 5 and intron 1 of the RUNX1 and ETO gene respectively. To date, no homologous sequences have been found in these regions to explain their recombination. The breakpoint regions of RUNX1 gen are characterized by the presence of DNasaI hypersensitive sites and topoisomerase II cleavage sites, but no information exists about complementary regions of ETO gene. Here we report analysis of chromatin structure of ETO breakpoint regions. Chromatin immunoprecipitation (ChIP) were performed with antibodies specific to acetylated histone H3, H4 and total histone H1. Nucleosomal distribution at the ETO locus was evaluated by determining total levels of histone H3. Our data show that in myeloid cells, the breakpoint regions at the ETO gene are enriched in hyperacetylated histone H3 compared to a control region of similar size where no translocations have been described. Moreover, acetylated H4 associates with both the whole ETO breakpoint regions as well as the control intron. Interestingly, we observed no H1 association either at the breakpoint regions or the control region of the ETO gene. Our data indicate that a common chromatin structure enriched in acetylated histones is present in breakpoint regions involved in formation of (8;21) leukemic translocation. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: PU.1 is an Ets family transcription factor involved in the myelo-lymphoid differentiation. We have previously demonstrated that PU.1 is also expressed in the adipocyte lineage. However, the expression levels of PU.1 mRNA and protein in preadipocytes do not match the levels in mature adipocytes. PU.1 mRNA level is higher in preadipocytes, whereas its protein is expressed in the adipocytes but not in the preadipocytes. The underlying mechanism remains elusive. Here, we find that miR-155 knockdown or overexpression has no effect on the levels of PU.1 mRNA and protein in preadipocytes or adipocytes. MiR-155 regulates adipogenesis not through PU.1, but via C/EBPβ which is another target of miR-155. We also checked the expression levels of PU.1 mRNA and antisense long non-coding RNA (AS lncRNA). Interestingly, compared with the level of PU.1 mRNA, the level of PU1 AS lncRNA is much higher in preadipocytes, whereas it is opposite in the adipocytes. We further discover that PU.1 AS lncRNA binds to its mRNA forming an mRNA/AS lncRNA compound. The knockdown of PU.1 AS by siRNA inhibits adipogenesis and promotes PU.1 protein expression in both preadipocytes and adipocytes. Furthermore, the repression of PU.1 AS decreases the expression and secretion of adiponectin. We also find that the effect of retroviral-mediated PU.1 AS knockdown on adipogenesis is consistent with that of PU.1 AS knockdown by siRNA. Taken together, our results suggest that PU.1 AS lncRNA promotes adipogenesis through preventing PU.1 mRNA translation via binding to PU.1 mRNA to form mRNA/AS lncRNA duplex in preadipocytes. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  Among the different types of waves embedded in seismic noise, body waves present appealing properties but are still challenging to extract. Here we first validate recent improvements in numerical modeling of microseismic compressional ( P ) body waves and then show how this tool allows fast detection and location of their sources. We compute sources at ~ 0.2 Hz within typical P teleseismic distances (30-90 degrees) from the South California Seismic Network (SCSN) and analyze the most significant discrete sources. The locations and relative strengths of the computed sources are validated by the good agreement with beam-forming analysis. These ~75 noise sources exhibit a highly heterogeneous distribution, and cluster along the usual storm tracks in the Pacific and Atlantic oceans. They are mostly induced in the open ocean, at or near water depths of 2800 and 5600 km, most likely within storms or where ocean waves propagating as swell meet another swell or wind sea. We then emphasize two particularly strong storms to describe how they generate noise sources in their wake. We also use these two specific noise bursts to illustrate the differences between microseismic body- and surface-waves in terms of source distribution and resulting recordable ground motion. The different patterns between body- and surface-waves result from distinctive amplification of ocean wave-induced pressure perturbation and different seismic attenuation. Our study demonstrates the potential of numerical modeling to provide fast and accurate constraints on where and when to expect microseismic body waves, with implications for seismic imaging and climate studies.

Description: [1]  Earthquakes that rupture across steps between faults can be larger than those predicted from individual fault lengths, making understanding multifault events critical to assessing earthquake hazard. Empirical data from earthquake surface ruptures suggest that the distances between faults that rupture together can range from 〈1 km to 5 km. Dynamic and quasi-static models of planar faults determine similar distances. However, studies of interactions between realistic, 3D non-planar faults are few. A general comparison of quasi-static stress perturbations and triggering potentials with mechanical models incorporating either planar or non-planar faults highlight the sensitivity of planar fault models to model parameters and reveal no clear relationship between mean fault slip and triggering potential. More specifically, planar fault models predict triggering across a 3 km extensional step, while models incorporating non-planar faults indicate that a connecting fault is necessary to transfer slip through a 3 km step along the 1992 Landers, California earthquake rupture. The mechanical approach taken captures the stress changes as well as the total stress following fault slip, improving the criterion used to determine triggered failure potential. This underscores the need for additional constraint on fault strength and cohesion. The focus on complex fault geometry restricts analyses to the quasi-static realm, limiting the application of results to fault interactions over the short distances and slow rupture velocities for which the quasi-static stress field is relevant or approximates the dynamic stress field.

Description: [1]  Batch and flow-through experiments were performed on quartz-feldspar granular aggregates and sandstone samples to investigate time-dependent effects of fluid-rock interactions on fluid and rock conductivity, respectively. The experiments were conducted at temperatures up to 164, at confining and pore pressures up to 10 and 5 MPa, respectively, and for up to 136 days. It showed that changes in rock conductivity were unequivocally related to changes in pore fluid conductivity. It is inferred that these changes were dependent on kinetically controlled dissolution reactions between the mineral grains and the fluid. The time-dependent signature of rock conductivity implied a detectable transition from initial dissolution towards some state of equilibrium. The response of rock conductivity to temperature changes followed an Arrhenius-type behavior. An exploratory kinetic evaluation of the conductivity data for sandstone samples yielded an apparent activation energy of approximately 32 kJ/mol. A concurrent chemical fluid analysis showed that this is an integrated value over all reactions occurring in parallel within a sample. These reactions namely concern silica and silicate dissolutionbut also the dissolution of accessory salt minerals. It is concluded that measuring the evolution of rock conductivity in combination with chemical pore fluid analysis constitutes a powerful and quantitative tool for monitoring time-dependent changesin pore fluid chemistry and thus fluid-rock interactions in real time.

Description: [1]  We describe a multi-parameter experiment at Erebus volcano, Antarctica, employing Doppler radar, video, acoustic, and seismic observations to estimate the detailed energy budget of large (up to 40-m-diameter) bubble bursts from a persistent phonolite lava lake. These explosions are readily studied from the crater rim at ranges of less than 500 m, and present an ideal opportunity to constrain the dynamics and mechanism of magmatic bubble bursts that can drive Strombolian and Hawaiian eruptions. We estimate the energy budget of the first second of a typical Erebus explosion as a function of time and energy type, and constrain gas pressures and forces using an analytic model for the expansion of a gas bubble above a conduit that incorporates conduit geometry and magma and gas parameters. The model, consistent with video and radar observations, invokes a spherical bulging surface with a base diameter equal to that of the lava lake. The model has no ad hoc free parameters, and geometrical calculations predict zenith height, velocity and acceleration during shell expansion. During explosions, the energy contained in hot over-pressured gas bubbles is freed and partitioned into other energy types, where by far the greatest non-thermal energy component is the kinetic and gravitational potential energy of the accelerated magma shell (〉10 9 J). Seismic source energy created by explosions is estimated from radar measurements and is consistent with source energy determined from seismic observations. For the generation of the infrasonic signal, a dual mechanism incorporating a terminally disrupted slug is proposed, which clarifies previous models and provides good fits to observed infrasonic pressures. A new and straightforward method is presented for determining gas volumes from slug explosions at volcanoes from remote infrasound recordings.

Description: [1]  We explore the application of GPS data to earthquake early warning and investigate whether the co-seismic ground deformation can be used to provide fast and reliable magnitude estimations and ground shaking predictions. We use an algorithm to extract the permanent static offset from GPS displacement time series and invert for the slip distribution on the fault plane, which is discretized into a small number of rectangular patches. We developed a completely “self-adapting” strategy in which the initial fault plane model is built based on a quick, approximate magnitude estimation, and is then allowed to increase in size based on the evolutionary magnitude estimation resulting from the slip inversion. Two main early warning outputs are delivered in real-time: magnitude and the along-strike extent of the rupture area. These are finally used to predict the expected ground shaking due to the finite source. We tested the proposed strategy by simulating real-time environments for three earthquakes. For the Mw 9.0, 2011 Tohoku-Oki earthquake our algorithm provides the first magnitude estimate of 8.2 at 39 sec after the origin time, and then gradually increases to 8.9 at 120 sec. The estimated rupture length remains constant from the outset at ~360 km. For the Mw 8.3, 2003 Tokachi-Oki earthquake the initial magnitude estimate is 8.5 at 24 sec and drops to 8.2 at 40 sec with a rupture length of 290 km. Finally, for the Mw 7.2, 2010 El Mayor-Cucapah earthquake the magnitude estimate is 7.0 from the outset with a rupture length of 140 km. The accuracy of the ground shaking prediction using the GPS-based magnitude and finite extent is significantly better than existing seismology-based point source approaches. This approach would also facilitate more rapid tsunami warnings

Description: ABSTRACT [1]  Analysis of Lake Bonneville shorelines using LIDAR digital elevation data challenges accepted models of Wasatch fault deformation since the late Pleistocene. While footwall deformation of the Weber segment of the Wasatch fault is consistent with back-rotation of the footwall block and greatest displacement rate towards the center of the segment, shorelines along the footwall of the Salt Lake City segment decrease in elevation towards the interior and are highest at the segment boundaries, an opposite pattern of footwall deformation than predicted for boundaries arresting or strongly inhibiting displacement during earthquakes. The spatial pattern of footwall rebound implies that some of the proposed persistent fault segment boundaries do not stop earthquake ruptures that originate on adjacent fault segments, nor constrain ruptures initiated within the Salt Lake City segment. Net vertical fault displacement at the boundary between the Salt Lake and Provo segments is 16—20 m over the past 16.3—18.5 ka, corresponding to a vertical displacement rate of 0.8—1.2 mm/yr, a net fault slip rate of 2.0—2.8 mm/yr and horizontal extension rate of 1.8—2.6 mm/yr on the 25 o west-southwest dipping fault that forms the southern Salt Lake City segment boundary. Shoreline analysis suggests isostatic rebound caused by a drop in lake level was concentrated during a relatively short (~2000 yr) time period following the Bonneville flood at ~16 ka. LIDAR-derived topography in conjunction with robust geomorphic datums improves our ability to map deformation associated with lithospheric flexure and faulting while demonstrating the limitation of lacustrine shorelines in this type of analysis.

Description: [1]  We use recent results on statistical analysis of seismicity to present a robust method for comprehensive detection and analysis of earthquake clusters. The method is based on nearest-neighbor distances of events in space-time-energy domain. The method is applied to a 1981–2011 relocated seismicity catalog of southern California having 111,981 events with magnitudes m  ≥ 2, and corresponding synthetic catalogs produced by the Epidemic Type Aftershock Sequence (ETAS) model. Analysis of the ETAS model demonstrates that the cluster detection results are accurate and stable with respect to (i) three numerical parameters of the method, (ii) variations of the minimal reported magnitude, (iii) catalog incompleteness, and (iv) location errors. Application of the method to the observed catalog separates the 111,981 examined earthquakes into 41,393 statistically significant clusters comprised of foreshocks , mainshocks and aftershocks . The results reproduce the essential known statistical properties of earthquake clusters, which provide overall support for the proposed technique. In addition, systematic analysis with our method allows us to detect several new features of seismicity that include (i) existence of a significant population of single-event clusters ; (ii) existence of foreshock activity in natural seismicity that exceeds expectation based on the ETAS model; and (iii) dependence of all cluster properties, except area, on the magnitude difference of events from mainshocks but not on their absolute values. The classification of detected clusters into several major types, generally corresponding to singles, burst-like and swarm-like sequences, and correlations between different cluster types and geographic locations is addressed in a companion paper.

Description: [1]  For the first time, we report the amplitude variation with angle (AVA) pattern of bottom simulating reflectors (BSRs) beneath fracture-filled gas hydrate deposits when the effective medium is anisotropic. The common depth point (CDP) gathers of two mutually perpendicular multi-channel seismic profiles, located in the vicinity of Site NGHP-01-10, are appropriately processed such that they are fit for AVA analysis. AVA analysis of the BSR shows normal-incidence reflection coefficients of -0.04 to -0.11 with positive gradients of 0.04 to 0.31 indicating class IV pattern. The acoustic properties from isotropic rock physics model predict class III AVA pattern which cannot explain the observed class IV AVA pattern in Krishna-Godavari basin due to the anisotropic nature of fracture-filled gas hydrate deposits. [2]  We modeled the observed class IV AVA of the BSR by assuming that the gas hydrate bearing sediment can be represented by horizontally transversely isotropic (HTI) medium after accounting for anisotropic wave propagation effects on BSR amplitudes. The effective medium properties are estimated using Backus averaging technique and the AVA pattern of BSRs is modeled using the properties of overlying HTI and underlying isotropy/HTI media with or without free gas. Anisotropic AVA analysis of the BSR from the inline seismic profile shows 5–30 % gas hydrate concentration (equivalent to fracture density) and the azimuth of fracture system (fracture orientation) with respect to the seismic profile is close to 45°. Free gas below the base of gas hydrate stability zone is interpreted in the vicinity of fault system (F1).

Description: ABSTRACT Obesity is now a major health problem due to its rapidly increasing incidence worldwide and severe consequences.Among many conditions associated with obesity aresome cancers including melanoma.Both genetic defects and environmental risk factors are involved in the carcinogenesis of melanoma. Activation of multiple signal pathways such as the PI3K/Akt and MAPK pathways are necessary for the initiation of melanoma. Activation of the MAPK pathway as a result of activating mutations in BRAF is commonly seen in melanoma though it alone is not sufficient to cause malignant transformation of melanocytes. Obesity can result in the activation of many signal pathways including PI3K/Akt, MAPK and STAT3. The activation of these pathways may have a synergistic effect with the genetic defects thereby increasing the incidence of melanoma. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: A normal fertilized human zygote contains two pronuclei, but zygotes may also display one, three, or even more pronuclei resulting from irregular insemination or meiotic division. Today diploid and triploid human embryonic stem cell (hESC) lines have been derived from tripronuclear (3PN) triploid zygotes, and an in-vitro fertilization (IVF) baby was born from a rescued diploid zygote by removing the extra male pronucleus of the 3PN zygote. However, whether hESCs can be derived from a rescued 3PN zygote is still unknown. Here, by microsurgical pronuclear removal, we restored 61 diploid zygotes from 3PN zygotes donated by 35 couples, and 11 blastocysts developed with a blastocyst rate of 18.0%, which seems higher than that of nonrescued 3PN zygotes according to previous reports. After the whole zona pellucida free embryos were plated onto feeder cells to grow and passage, 2 hESC lines (CCRM-hESC-22 and CCRM-hESC-23) were generated and both carried normal karyotype (46, XY). The hESC lines were then characterized by morphology, expansion in vitro , and expression of specific markers of alkaline phosphatase, OCT4, SSEA4, TRA-1-60 and TRA-1-81. Furthermore, the pluripotency of these 2 hESC lines was confirmed by in vitro embryoid body formation and in vivo teratoma production. Our study indicates that depronucleared 3PN zygotes can improve the blastocysts formation rate, and normal hESC lines can be derived from those corrected 2PN embryos. Based on their multi-directional differentiation potential in vitro , the established hESC lines could be applied to the developmental risk assessment for IVF babies born from restored zygotes. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  Sequestration of large amounts of CO 2 within deep underground reservoirs has been proposed as a potential approach for reducing atmospheric emissions of greenhouse gases. A CO 2 sequestration project should address the associated environmental and safety issues and, in this respect, the importance of geomechanics has recently been widely recognized. Geomechanics is even more important when fluid injection is planned in faulted reservoirs. How much CO 2 can be safely injected into multi-compartment reservoirs? Are geomechanical constraints more restrictive than flow-dynamic constraints? These and other questions are addressed in the present study using a three-dimensional Finite Element - Interface Element geomechanical model. We simulate the possible mechanical failure in both the injected formation and the caprock, the fault/thrust reactivation, and the ground surface displacement in a faulted reservoir of the off-shore northern Italy, where seismic surveys provided an accurate characterization of the faulted geological structure. Based on reliable petrophysical/geomechanical properties from well-logs and pore overpressure as predicted by a fluid-dynamic model, the results show that the injection of 1 × 10 6  ton/a of CO 2 may be performed over a few years only. Thereafter part of the injected formation fails by shear stress. A number of parametric scenarios are investigated to address the major uncertainties on the geomechanical response to CO 2 injection. The modeling outcome suggests that shear failure and faults/thrusts reactivation can occur much before attaining the hydraulic fracturing pressure, hence representing two major constraints for a safe and permanent containment.

Description: [1]  We present numerical subduction models to investigate overriding plate deformation at subduction zones. All models show forearc shortening, resulting predominantly from shear stresses at the subduction zone interface and opposite-sense mantle shear stresses at the base of the forearc lithosphere. Models dominated by backarc extension show that it results from trench-normal positive velocity gradients in the mantle below the overriding plate. Such gradients result from toroidal mantle flow induced by slab rollback, with velocities below the leading part of the backarc faster than the overriding plate velocity. The velocity gradients induce basal shear stresses that increase trenchward and cause trenchward overriding plate motion at a velocity ( v OP⊥ ) whose spatial average is below the trench retreat velocity ( v T⊥ ). The combination of basal shear stresses and average v OP⊥ 〈 v T⊥ causes trench-normal deviatoric tension in the backarc and backarc extension. Models dominated by backarc shortening show that it results from a relatively immobile subduction hinge and trenchward overriding plate motion driven by poloidal mantle flow. The poloidal mantle flow is induced by downdip slab sinking and causes the average v OP⊥ 〉 v T⊥ . This results in trench-normal deviatoric compression and shortening in the leading part of the overriding plate as it collides with the subduction hinge. Ultimately, the geodynamic models demonstrate that backarc extension is favored for narrow slabs and near lateral slab edges, and is driven by rollback induced toroidal mantle flow, while backarc shortening is favored for the center of wide slabs, and is driven by poloidal mantle flow resulting from downdip slab motion.

Description: [1]  The Gamburtsev Subglacial Mountains (GSM), located near the center of East Antarctica, remain one of the most enigmatic mountain ranges on earth. A lack of direct geologic samples renders theirtectonic history almost totally unconstrained. We utilize teleseismic Rayleigh wave data from a two-year deployment of broadband seismic stations across the region to image shear velocity structure and analyze the lithospheric age of the GSM and surrounding regions. We solve for 2-D phase velocitiesand invert these results for 3-D shear velocity structure. We perform a Monte Carlo simulation to improve constraints of crustal thickness and shear velocity structure.Beneath the core of the GSM, we find crustal thickness in excess of 55 km.Mantle shear velocities remain faster than global average models to a depth of approximately 250 km, indicating a thick lithospheric root. Thinner crust and slower upper mantle velocities are observed beneath the Lambert Rift System and the Polar Subglacial Basin.When compared with phase velocity curves corresponding to specific tectonothermal ages elsewhere in the world, average phase velocity results for the GSM are consistent with regions of Archean – Paleoproterozoic origin. Combined with radiometric ages of detrital zircons found offshore, these results indicate a region of old crust that has undergone repeated periods of uplift and erosion, most recently during the Mesozoic breakup of Gondwana. Lower crustal seismic velocities imply a moderately dense lower crust beneath the core of the GSM, but with lower density than suggested by recent gravity models.

Description: [1]  This is a second paper in a study of statistical identification and classification of earthquake clusters using a relocated catalog of 1981–2011 seismicity in southern California and synthetic catalogs produced by the ETAS model. Here we focus on classification of event families – statistically significant clusters comprised of foreshocks , mainshocks and aftershocks – that are detected with the methodology discussed in part I of the study. The families are analyzed using their representation as time oriented tree graphs. The results (i) demonstrate that the clustering associated with the largest earthquakes, m  〉 7, is statistically different from that of small-to-medium earthquakes; (ii) establish the existence of two dominant types of small-to-medium magnitude earthquake families– burst-like and swarm-like sequences – and a variety of intermediate cluster forms obtained as a mixture of the two dominant types; (iii) suggest a simple new quantitative measure for identifying the cluster type based on its topological structure; (iv) demonstrate systematic spatial variability of the cluster characteristics on a scale of tens of kilometers in relation to heat flow and other properties governing the effective viscosity of a region; and (v) establish correlation between the family topological structure and a dozen of metric properties traditionally considered in the literature (number of aftershocks, duration, spatial properties, b -value, parameters of Omori-Utsu and Båth law, etc .). The burst-like clusters likely reflect highly-brittle failures in relatively cold regions, while the swarm-like clusters are likely associated with mixed brittle-ductile failures in regions with relatively high temperature and/or fluid content. The results of this and paper I may be used to develop improved region-specific hazard estimates and earthquake forecasts.

Description: Transplantation of functional insulin-producing cells (IPCs) provides a novel mode for insulin replacement, but is often accompanied by many undesirable side effects. Our previous studies suggested that IPCs could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. To obtain a better method through which to acquire more similar IPCs, we compared the difference between IPCs of the GLP-1 group and IPCs of the non-GLP-1 group in the morphological features in cellular level and physiological function. The levels of insulin secretion were measured by ELISA. The insulin and Glucagon-like peptide-1 (GLP-1) mRNA gene expression was determined by real-time quantitative PCR. The morphological features were detected by atomic force microscopy (AFM)and laser confocal scanning microscopy (LCSM). Intracellular Ca 2+ levels and Glucagon-like peptide-1 Receptor (GLP-1R) levels were determined by flow cytometer (FCM).We found that IPCs of the GLP-1group had bigger membrane particle size and average roughness (Ra) than IPCs of the non-GLP-1 group but still smaller than normal human pancreatic beta cells. The physiology function of IPCs of the GLP-1 group were much closer to normal human pancreatic beta cells than IPCs of the non-GLP-1 group. GLP-1 could improve the similarity of insulin-producing cells from human adipose tissue-derived mesenchymal stem cells and pancreatic beta cells in cellular ultrastructure and function. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: ABSTRACT Glutathione has traditionally been considered as an antioxidant that protects cells against oxidative stress. Hence, the loss of reduced glutathione and formation of glutathione disulfide is considered a classical parameter of oxidative stress that is increased in diseases. Recent studies have emerged that demonstrate that glutathione plays a more direct role in biological and pathophysiological processes through covalent modification to reactive cysteines within proteins, a process known as S-glutathionylation. The formation of an S-glutathionylated moiety within the protein can lead to structural and functional modifications. Activation, inactivation, loss of function, and gain of function have all been attributed to S-glutathionylation. In pathophysiological settings, S-glutathionylation is tightly regulated. This perspective offers a concise overview of the emerging field of protein thiol redox modifications. We will also cover newly developed methodology to detect S-glutathionylation in situ , which will enable further discovery into the role of S-glutathionylation in biology and disease. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Paget's disease of bone (PDB) is a chronic focal skeletal disorder characterized by excessive bone resorption followed by disorganized new bone formation. Measles virus nucleocapsid (MVNP) is implicated in pathogenesis of PDB. RANK ligand (RANKL), a critical osteoclastogenic factor expressed on bone marrow stromal/preosteoblast cells is upregulated in PDB. We recently demonstrated that fibroblast growth factor-2 (FGF-2) which induces RANKL expression is elevated in PDB. In this study, we hypothesized that FGF-2 modulates suppressors of cytokine signaling (SOCS) to induce RANKL expression in PDB. We identified increased levels of SOCS-1/3 mRNA expression in bone marrow mononuclear cells derived from patients with PDB compared to normal subjects. Interestingly, conditioned media obtained from MVNP transduced osteoclast progenitor cells significantly increased SOCS-1/3 mRNA expression in stromal/preosteoblast cells. We next examined if SOCS participates in FGF-2 signaling to modulate RANKL gene expression. We showed that FGF-2 stimulation significantly increased SOCS-1/3 expression in human bone marrow stromal/preosteoblast cells. In addition, co-expression of SOCS-1/3 with hRANKL gene promoter-luciferase reporter plasmid in marrow stromal cells demonstrated a significant increase in promoter activity without FGF-2 stimulation. Furthermore, siRNA inhibition of STAT-1 suppresses FGF-2 increased SOCS-1/3 expression in these cells. Thus, our results suggest that SOCS participates in FGF-2 modulation of RANKL expression in PDB. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: The molecular mechanisms linking A β to the onset of neurotoxicity are still largely unknown, but several lines of evidence point to reactive oxygen species, which are produced even under the effect of nanomolar concentrations of soluble A β -oligomers. The consequent oxidative stress is considered as the mediator of a cascade of degenerative events in many neurological disorders. Epidemiological studies indicate that dietary habits and antioxidants from diet can influence the incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In the recent years, a number of reviews have reported on neuroprotective effects of polyphenols in cell and animal models. However, the majority of these studies have focused only on the anti-oxidant properties of these compounds and less on the mechanism/s of action at cellular level. In this work we investigated the effect of cocoa polyphenolic extract on a human AD in vitro model. The results obtained, other than confirming the anti-oxidant properties of cocoa, demonstrate that cocoa polyphenols triggers neuroprotection by activating BDNF survival pathway, both on Aß plaque treated cells and on Aß oligomers treated cells, resulting in the counteraction of neurite dystrophy. On the light of the results obtained the use of cocoa powder as preventive agent for neurodegeneration is further supported. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Micro RNA (miRNA) is a small non-coding posttranscriptional RNA regulator that is involved in a variety of biological events. In order to specify the role of miRNAs in cartilage metabolism, we comparatively analyzed the expression profile of known miRNAs in chicken sternum chondrocytes representing early and late differentiation stages. Interestingly, none of the miRNAs displaying strong expression levels showed remarkable changes along with differentiation, suggesting their roles in maintaining the homeostasis rather than cytodifferentiation of chondrocytes. Among these miRNAs, miR-181a, which is known to play critical roles in a number of tissues, was selected and was further characterized. Human microarray analysis revealed remarkably stronger expression of miR-181a in human HCS-2/8 cells, which strongly maintained a chondrocytic phenotype, than in HeLa cells, indicating its significant role in chondrocytes. Indeed, subsequent investigation indicated that miR-181a repressed the expression of 2 genes involved in cartilage development. One was CCN family member 1 (CCN1), which promotes chondrogenesis; and the other, the gene encoding the core protein of aggrecan, a major cartilaginous proteoglycan, aggrecan. Based on these findings, negative feedback system via miR-181a to conserve the integrity of the cartilaginous phenotype may be proposed. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: ABSTRACT Phosphoinositide 3-kinase proteins are composed by a catalytic p110 subunit and a regulatory p85 subunit. There are three classes of PI3K, named class I, II and III, on the bases of the protein domain constituting and determining their specificity. The first one is the best characterized and includes a number of key elements for the integration of different cellular signals. Regulatory p85 subunit shares with the catalytic p110 subunit, a N-terminal SH3 domain showing homology with the protein domain Rho-GTP-ase. After cell stimulation, all class I PI3Ks are recruited to the inner face of the plasma membrane, where they generate phosphatidylinositol-3,4,5-trisphosphate by direct phosphorylation of phosphatidylinositol-4,5-bisphosphate. All pathways trigger the control of different phenomena such as cell growth, proliferation, apoptosis, adhesion and migration through various downstream effectors. We have previously provided direct evidences that a Serine in position 83, adjacent to the N-terminal SH3 domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work is to confirm the role of p85αPI3KSer83 in regulating cell proliferation, migration and invasion in prostate cancer cells LNCaP. To this purpose cells were transfected with mutant forms of p85, where Serine was replaced by Alanine, where phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated residue. The findings of this study suggest that identifying a peptide mimicking the sequence adjacent to Ser 83 may be used to produce antibodies against this residue that can be proposed as usefool tool for prognosis by correlating phosphorylation at Ser83 with tumor stage. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: [1]  Paleoseismologic data from the southern Panamint Valley fault (PVF) reveal evidence of at least four surface ruptures during late Holocene time (0.33-0.48 ka, 0.9-3.0 ka, 3.3-3.6 ka and 〉4.1 ka). These paleo-earthquake ages indicate that the southern PVF has ruptured at least once and possibly twice during the ongoing (≤1.5 ka) seismic cluster in the Mojave section of the eastern California shear zone (ECSZ). The most recent event (MRE) on the PVF is also similar in age to the 1872 Owens Valley earthquake and the geomorphically youthful MRE on the Death Valley fault. The timing of the three oldest events at our site shows that the PVF ruptured at least once and possibly thrice during the well-defined 2-5 ka seismic lull in the Mojave section of the ECSZ. Interestingly, the 3.3-3.6 ka age of Event 3 overlaps with the 3.3-3.8 ka age of the penultimate (i.e., pre-1872) rupture on the central Owens Valley fault. These new PVF data support the notion that earthquake occurrence in the ECSZ may be spatially and temporally complex, with earthquake clusters occurring in different regions at different times. Coulomb Failure Function modeling of the Panamint Valley and Garlock faults reveals significant stress interactions between these two faults that may influence future earthquake occurrence. Specifically, our models suggest a possible rupture sequence whereby an event on the southern Panamint Valley fault can lead to the potential triggering of an event on the Garlock fault, which in turn could trigger the Mojave section of the San Andreas Fault.

Description: [1]  The lithospheric structure of the Indian plate has been investigated using converted wave techniques (P and S receiver functions, RFs) and a novel stacking analysis technique (without using deconvolution) applied to a large seismological dataset from permanent and temporary broadband seismic stations. We observe coherent energy from at least two seismic discontinuities i.e. the crust-mantle (Moho) and lithosphere-asthenosphere boundary (LAB) in the uppermost mantle. Here, we provide a novel seismic image of the Indian lithosphere showing definitive evidence of its flexure, which is interpreted to be primarily caused by the hard collision at ~55My resulting in the world's highest mountain chain - the Himalayas and the Tibetan plateau. Results from geoidal and gravity studies do suggest post-collisional flexuring of the Indian plate; however, the flexure lacks observational constraints. The observed wavelength of the flex is ~1000 km with the thickness of the Indian plate varying from ~70 km to 140 km; such a low value for a continent implies that the Indian plate has been reworked in the past. The plate deepens in the Himalayan region to a depth of ~150 km. Further, the converted phases are interpreted to be resulting from the bottom of the lithosphere. We clearly demonstrate that these are distinct and different from the mid-lithospheric discontinuity. For a large number of stations, the MLD and LAB are clearly separated in depth. Our observations suggest that the Archaean lithosphere is no longer intact and is prone to deformation.

Description: [1]  Studying heat transfer processes in sedimentary crustal rocks requires the correct thermal conductivity of the respective rock type. Often a single value is used for a given rock type, obtained from the measurements on homogenous samples. We demonstrate how variations in rock layering and micro-fractures on the sub-centimeter scale may influence thermal conductivity values at much larger scale. We obtain thermal conductivity images from lab measurements on two different, heterogeneous samples performed with an optical thermal conductivity scanner in two directions. We study different spatial averaging methods for parameterizing the structural heterogeneities and the associated variation of thermal conductivity within the samples. For each of these structural simplifications we set up a numerical model for a numerical heat transfer experiment in order to determine effective thermal conductivity values in two directions. We compare these values and the mean thermal conductivities obtained from different mixing laws and find that, in heterogeneous rocks, effective and mean thermal conductivity may differ substantially. This may cause significant errors in reservoir-scale simulations of heat transfer with associated severe consequences for estimated heat flow and temperatures.

Description: [1]  We analyze teleseismic P-waves from four Mw ≥ 6.5 earthquakes recorded by a petroleum industry survey in Long Beach, California. The survey used a 2-D array with up to 5200 seismometers, 120 m mean spacing, and 7 – 10 km aperture. At frequencies near 1 Hz P-wave travel-times and amplitudes exhibit coherent lateral variations over scales as short as ~400 m, including locally delayed travel-times and increased amplitudes at the crest of the Long Beach anticline. Deeper heterogeneity is indicated by P-wave phase velocities that deviate from reference model predictions for events from southwestern azimuths. We postulate that a sharp northeastward increase in Moho depth from the Inner Borderland (IB) to mainland southern California causes the anomalous phase velocities. Elastic forward modeling finds the travel-times are fit well by a Moho that dips 65° to the northeast and flattens ~10 km southwest of the Newport-Inglewood fault zone. Constraining the felsic thickness of mainland crust to 28 km requires an 8 km thick layer with a P-velocity of 7 km/s beneath it, which could result from basal accretion of former Farallon ocean crust or magmatic underplating during Miocene volcanism. Forward models with a 65° Moho dip predict a P-to-s conversion with a phase velocity of ~5 km/s. Deconvolution of the array's mean P-wave signal isolates a similar later arriving phase. The steep crust thickness transition supports a locally abrupt boundary to IB rifting. Our results highlight the utility of dense short-period arrays for passive imaging at near surface to uppermost mantle depths.

Description: [1]  In this study we present new high-resolution, regional-scale, Vp and Vp/Vs models of the northern-central Apennines along with accurate 3D locations of a large set of local earthquakes. The main velocity anomalies are consistent with the surface geology in the shallow layers and present evidence for fluids stored within the basement at greater depths beneath the extensional belt. The Adria and Tyrrhenian mantle are defined by positive velocity anomalies below 30 km depth, while a low Vp, high Vp/Vs region in between indicates the existence of an hydrated wedge. The results yield new constraints on active processes in the Apennines and more generally envisage the evolution of a post-collisional belt. Velocity anomalies and earthquakes are consistent with a complex system of delamination and sinking of the Adria continental lithosphere, with the peeling of the crust identified by intermediate-depth seismicity. Change of seismicity and structural patterns along the belt indicates that this tectonic process is diachronous and that fluids, released by sunken lithosphere, are stored within the crust conditioning the occurrence of seismicity and the onset of extension.

Description: Annonaceous acetogenins (ACGs) are a group of fatty acid-derivatives with potent anticancer effects. In the present study, we found desacetyluvaricin (Dau) exhibited notable in vitro antiproliferative effect on SW480 human colorectal carcinoma cells with IC 50 value of 14 nM. The studies on the underlying mechanisms revealed that Dau inhibited the cancer cell growth through induction of S phase cell cycle arrest from 11.3% (control) to 33.2% (160 nM Dau), which was evidenced by the decreased protein expression of cyclin A Overproduction of superoxide, intracellular DNA damage, and inhibition of MEK/ERK signaling pathway, were also found involved in cells exposed to Dau. Moreover, pre-treatment of the cells with ascorbic acid significantly prevented the Dau-induced overproduction of superoxide, DNA damage and cell cycle arrest. Taken together, our results suggest that Dau induces S phase arrest in cancer cells by firstly superoxide overproduction and subsequently the involvement of various signaling pathways. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Obesity is a major risk factor for the development of asthma, and causes severe, uncontrolled disease that responds poorly to therapy. The obese state alters early onset allergic asthma, and leads to the development of a novel form of late onset asthma secondary to obesity. The presentation of early onset allergic asthma is altered through effects on immune function. Factors such as mechanical loading, effects of adipokines on airways, altered diet, insulin resistance and altered metabolism of nitric oxide likely all contribute to increased airway reactivity in obesity, causing late onset asthma in obesity. Obesity also alters responses to environmental factors such as ozone and particulate matter. Focused studies to understand the importance of these factors in the pathogenesis of airway disease in obesity will be essential to develop therapies to intervene in this new epidemic of airway disease. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Angiogenesis, the process of new blood vessel formation and growth from already existing venules is critical in vascular development and homeostasis controlled by the balance of pro- and anti-angiogenic factors. Emerging evidence indicates the development, progression and metastasis of various human cancers are strongly relied on angiogenesis. However, molecular mechanisms that underlie the complex regulation of angiogenic processes are still not fully elucidated. Recent studies revealed that microRNAs (miRNAs) were important regulators of tumor angiogenesis and the entire research in this area has entered into a so-called “miRNAs era”. Thus, miRNAs might be important therapeutic targets or biomarkers for cancer. Due to the complexity of miRNA regulating mechanisms, how specific miRNAs intersect with and modulate tumor angiogenesis is still unclear. The conflicting results of the same miRNAs from different groups indicated that miRNAs might possess potent activity in a cell type or cell context specific manner. Here, we present a summary of latest advances in understanding the roles of angiogenic miRNAs as potential tools or targets in cancer therapy. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Description: Secreted phosphoprotein 24 kDa (Spp24) is an apatite- and BMP/TGF-β cytokine-binding phosphoprotein found in serum and many tissues, including bone. N-terminally intact degradation products ranging in size from 14 kDa to 23 kDa have been found in bone. The cleavage sites in Spp24 that produce these short forms have not been definitively identified, and the biological activities and mechanisms of action of Spp24 and its degradation products have not been fully elucidated. We found that the C-terminus of Spp24 is labile to proteolysis by furin, kallikrein, lactoferrin, and trypsin, indicating that both extracellular and intracellular proteolytic events could account for the generation of biologically-active Spp18, Spp16, and Spp14. We determined the effects of these truncation products on kinase-mediated signal transduction, gene expression, and osteoblastic differentiation in W-20-17 bone marrow stromal cells cultured in basal or pro-osteogenic media. After culturing for five days, all forms inhibited BMP-2-stimulated osteoblastic differentiation, assessed as induction of alkaline phosphatase activity, in basal, but not pro-osteogenic media. After 10 days, they also inhibited BMP-2-stimulated mineral deposition in pro-osteogenic media. Spp24 had no effect on Erk1/2 phosphorylation, but Spp18 stimulated short-term Erk1/2, MEK 1/2, and p38 phosphorylation. Pertussis toxin and a MEK1/2 inhibitor ablated Spp18-stimulated Erk 1/2 phosphorylation, indicating a role for G i proteins and MEK1/2 in the Spp18-stimulated Erk1/2 phosphorylation cascade. Truncation products, but not full-length Spp24, stimulated RUNX2, ATF4, and CSF1 transcription. This suggests that Spp24 truncation products have effects on osteoblastic differentiation mediated by kinase pathways that are independent of exogenous BMP/TGF-β cytokines. This article is protected by copyright. All rights reserved

Description: Sarcopenia and osteoporosis have recently been noted for their relationship with locomotive syndrome and increased number of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which may be associated with frailty. Several clinical data have indicated that increased muscle mass is related to increased bone mass and reduced fracture risk. Genetic, endocrine and mechanical factors as well as inflammatory and nutritional states concurrently affect muscle tissues and bone metabolism. Several genes, including myostatin and α-actinin 3, have been shown in a genome-wide association study (GWAS) to be associated with both sarcopenia and osteoporosis. Vitamin D, growth hormone and testosterone as well as pathological disorders, such as an excess in glucocorticoid and diabetes, affect both muscle and bone. Basic and clinical research of bone metabolism and muscle biology suggests that bone interacts with skeletal muscle via signaling from local and humoral factors in addition to their musculoskeletal function. However, the physiological and pathological mechanisms related to muscle and bone interactions remain unclear. We found that Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage. We also reported that osteoglycin and FAM5C might be muscle-derived humoral osteogenic factors. Other factors, including myostatin, osteonectin, insulin-like growth factor I, irisin and osteocalcin, may be associated with the interactions between muscle tissues and bone metabolism. This article is protected by copyright. All rights reserved

Description: In this study, rock friction ‘stick-slip’ experiments are used to develop constraints on models of earthquake recurrence. Constant-rate loading of bare rock surfaces in high quality experiments produces stick-slip recurrence that is periodic at least to second order. When the loading rate is varied, recurrence is approximately inversely proportional to loading rate. These laboratory events initiate due to a slip rate-dependent process that also determines the size of the stress drop and as a consequence, stress drop varies weakly but systematically with loading rate. This is especially evident in experiments where the loading rate is changed by orders of magnitude, as is thought to be the loading condition of naturally occurring, small repeating earthquakes driven by afterslip, or low-frequency earthquakes loaded by episodic slip. As follows from the previous studies referred to above, experimentally observed stress drops are well described by a logarithmic dependence on recurrence interval that can be cast as a non-linear slip-predictable model. The fault's rate dependence of strength is the key physical parameter. Additionally, even at constant loading rate the most reproducible laboratory recurrence is not exactly periodic, unlike existing friction recurrence models. We present example laboratory catalogs that document the variance and show that in large catalogs, even at constant loading rate, stress drop and recurrence co-vary systematically. The origin of this covariance is largely consistent with variability of the dependence of fault strength on slip rate. Laboratory catalogs show aspects of both slip and time predictability and successive stress drops are strongly correlated indicating a ‘memory’ of prior slip history that extends over at least one recurrence cycle.

Description: We derive equations for HTI and orthorhombic symmetries to analyze fluid substitution effects in porous fractured media. The derivations are based on the anisotropic Gassmann equation and linear slip theory. We assess the influence of fluid substitution (gas, brine, and oil), on elastic moduli, velocities, anisotropy, and azimuthal amplitude variations. We find that in the direction normal to fractures, P-wave moduli increase as much as 56% and P-wave velocity increases up to 19% for gas-to-brine substitution. For the direction parallel to fractures, P-wave velocity remains almost constant when porosity is low (5%), but can increase up to 4% if porosity is high (25%). Since P-waves in two different directions have different sensitivities to fluids and fractures, the Thomsen's parameters (defined for HTI and orthorhombic symmetries), ε and δ , are sensitive to fluid types and fractures. We also found that δ is sensitive to porosity for liquid saturation, but insensitive to porosity for the case of gas saturation. Gassmann assumes (and as has been observed) that shear modulus does not depend on fluids. And we observe no changes in shear-wave splitting ( γ ) for different fluids. The azimuthal amplitude variation is dependent on fluid types, fractures and porosity. We observe up to 12% increase in azimuthal amplitude variation for low porosity gas sands after brine saturation, and 6% decrease for high porosity gas sands. We find that the percentage changes in gas-to-oil substitution are about half that of the gas-to-brine case. The equations we have derived provide a useful tool to quantitatively evaluate the effects of fluid substitution on seismic anisotropy.

Description: In the central part of Fennoscandia the crust is currently rising, because of the delayed response of the viscous mantle to melting of the Late Pleistocene ice sheet. This process, called Glacial Isostatic Adjustment (GIA), causes a negative anomaly in the present-day static gravity field as isostatic equilibrium has not been reached yet. Several studies have tried to use this anomaly as a constraint on models of GIA, but the uncertainty in crustal and upper mantle structures has not been fully taken intoaccount. Therefore, our aim is to revisit this using improved crustal models and compensation techniques. We find that, in contrast with other studies, the effect of crustal anomalies on the gravity field cannot be effectively removed, because of uncertainties in the crustal and upper mantle density models. Our second aim is to estimate the effects on geophysical models, which assume isostatic equilibrium, after correcting the observed gravity field with numerical models for GIA. We show that correcting for GIA in geophysical modelling can give changes of several km in the thickness of structural layers of modeled lithosphere, which is a small but significant correction. Correcting the gravity field for GIA prior to assuming isostatic equilibrium and inferring density anomalies might be relevant in other areas with ongoing post-glacial rebound such as North America and the polar regions.

Description: Large variability of earthquake stress drops and scaled energy has been commonly reported in the literature, but it is difficult to assess how much of this variability is caused by underlying physical source processes rather than simply observational uncertainties. Here, we examine a variety of dynamically realistic rupture scenarios for circular and elliptical faults and investigate to what extent the variability in seismically estimated stress drops and scaled energy comes from differences in source geometry, rupture directivity, and rupture speeds. We numerically simulate earthquake source scenarios using a cohesive-zone model with the small-scale yielding limit, where the solution approaches a singular crack model with spontaneous healing of slip. Compared to symmetrical circular source models, asymmetrical models result in larger variability of estimated corner frequencies and scaled energy over the focal sphere. The general behavior of the spherical averages of corner frequencies and scaled energy in the subshear regime extends to the supershear regime, although shear Mach waves generated by the propagation of supershear rupture lead to much higher corner-frequency and scaled-energy estimates locally. Our results suggest that at least a factor of two difference in the spherical average of corner frequencies is expected in observational studies simply from variability in source characteristics almost independent of the actual stress drops, translating into a factor ofeight difference in estimated stress drops. Furthermore, radiation efficiency estimates derived from observed seismic spectra should not be directly interpreted as describing rupture properties unless there are independent constraints on rupture speed and geometry.

Description: Tumor cells display different bioenergetic profiles when compared to normal cells. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin A in breast cancer cells representing different stages of aggressiveness and metabolic profile. When testing the effect of NaB and TSA on viability of cells, it was shown that non-tumorigenic MCF-10A cells were less affected by increasing doses of the drugs than the tumorigenic, hormone dependent, tightly cohesive MCF-7, T-47D and the highly metastatic triple-negative MDA-MB 231 cells. T-47D cells were the most sensitive to treatment with both, NaB and TSA. Experiments measuring anchorage- independent growth of tumor cells showed that MCF-7, T-47D, and MDA-MB-231 cells were equally sensitive to the treatment with NaB. The NaB induced an attenuation of glycolysis, reflected by a decrease in lactate release in MCF-7 and T47D lines. Pyruvate kinase activity was significantly enhanced by NaB in MDA-MB-231 cells only. In contrast, the inhibitor enhanced lactate dehydrogenase activity specifically in T-47 D cells. Glucose-6-phosphate dehydrogenase activity was shown to be differentially modulated by NaB in the cell lines investigated: the enzyme was inhibited in MCF-7 cells, whereas in T-47D and MDA-MB-231 cells, G6PDH was activated. NaB and TSA were able to significantly increase the oxygen consumption by MDA-MB-231 and T-47D cells. Collectively the results show that epigenetic changes associated to acetylation of proteins in general affect the energy metabolism in all cancer cell lines and that mitochondria may occupy a central role in metastasis. This article is protected by copyright. All rights reserved

Description: Petrophysical properties of rocks and their applicability at larger scale are a challenging topic in Earth sciences. Petrophysical properties of rocks are severely affected by: boundary conditions, rock fabric/microstructure, and tectonics that require a multi-scale approach to be properly defined. Here we: (1) report laboratory measurements of density, porosity, permeability and P-wave velocities at increasing confining pressure conducted on Miocene foredeep sandstones (Frosinone Fm.); (2) compare the laboratory results with larger-scale geophysical investigations; (3) discuss the effect of thrusting on the properties of sandstones. At ambient pressure, laboratory porosity varied from 2.2% to 13.8% and P-wave velocities (Vp) from 1.5 km/s to 2.7 km/s. The P-wave velocity increased with confining pressure, reaching between 3.3 km/s to 4.7 km/s at 100 MPa. In situ Vp profiles, measured using sonic logs, matched the ultrasonic laboratory measurement well. The permeability varied between 1.4 × 10 -15  m 2 to 3.9 × 10 -15  m 2 and was positively correlated with porosity. The porosity and permeability of samples taken at various distances to the Olevano-Antrodoco fault plane progressively decreased with distance while P-wave velocity increased. At about 1 km from the fault plane, the relative variations reached 43%, 65% and 20% for porosity, permeability and P-wave velocity, respectively. This suggests that tectonic loading changed the petrophysical properties inherited from sedimentation and diagenesis. Using field constraints and assuming overburden-related inelastic compaction in the proximity of the fault plane, we conclude that the fault reached the mechanical condition for rupture in compression at differential stress of 64.8 MPa at a depth of 1500 m.

Description: We discuss an innovation in traveltime tomography that combines wavelet-based, multiscale parameterization and finite-frequency theory to solve two outstanding issues that inevitably arise from uneven source station distributions and from the three-dimensional (3-D) nature of wavefront healing: how to objectively address the intrinsically multiscale nature of data coverage while simultaneously maintain model resolution at each scale level. We apply the new, integrated methodology to investigate 3-D variations of P and S wave speeds (δlnVP and δlnVS) beneath the Himalayan-Tibetan orogen. In particular, we are able to constrain variations in the Poisson's ratio via δln(VP/VS). The formulation is naturally data adaptive, resolving features at each scale only if the required data converge is available. The very first, long-wavelength feature that emerges is a clear anomaly of high δlnV that extends over more than 500 km beyond the northern edge of the Lhasa terrane at places. Farther northward, a strong negative anomaly underlies the region where recent volcanism occurs in northern Tibet. Regions of negative δln(VP/VS) delineate a slab-like, subhorizontal feature concentrated between depths of ∼100–250 km. Such characteristics are consistent with the notion that chemically refractory, and therefore buoyant, mantle lithosphere of the Indian shield (“Greater India”) has advanced subhorizontally northward far beyond the surficial Bangong-Nujiang suture. In the crust, two isolated regions of low δlnV, each extending to depths near 100 km, occur along the Lunggar and the Yadong-Gulu active rifts in southern Tibet. Deep penetrating rifts imply that only a limited amount of horizontal displacement is being accommodated on subvertical structures.

Description: We present results of detailed paleomagnetic investigations on deep-sea cores from sediment drifts located along the Pacific continental margin of the Antarctic Peninsula. High-resolution magnetic measurements on u channel samples provide detailed age models for three cores collected from drift 7, which document an age of 122 ka for the oldest sediments recovered near the drift crest at site SED-07 and a high sedimentation rate (11 cm/kyr) at site SED-12 located close to the Alexander Channel system. Low- and high-temperature magnetic measurements in conjunction with microscopic and mineralogic observations from drifts 4, 5 and 7 indicate that pseudosingle-domain detrital titanomagnetite (partially oxidized and with limited Ti substitution) is the dominant magnetic mineral in the drift sediments. The titanomagnetite occurs in two magnetic forms: (1) a low-coercivity form similar to laboratory-synthesized titanomagnetite and (2) a high-coercivity form (Bcr 〉 60 mT). These two forms vary in amount and stratigraphic distribution across the drifts. We did not find evidence for diagenetic magnetic iron sulfides as has been previously suggested for these drift deposits. The observed change of magnetic mineralogy in sediments deposited during Heinrich events on drift 7 appears to be related to warming periods, which temporarily modified the normal glacial transport pathways of glaciogenic detritus to and along the continental rise and thus resulted in deposition of sediments with a different provenance. Understanding this sediment provenance delivery signature at a wider spatial scale should provide information about ice sheet dynamics in West Antarctica over the last ∼100 kyr.

Description: The origin of pulverized rocks (PR) in surface outcrops adjacent to the fault cores of the San Andreas and other major faults in Southern California is not clear, but their structural context indicates that they are clearly associated with faulting. An understanding of their origin might allow inferences to be drawn about the nature of dynamic slip on faults, including rupture mechanisms and their speed during earthquakes. In the present study, we use split Hopkinson bar recovery experiments to investigate whether PR can be produced under dynamic stress wave loading conditions in the laboratory and whether PR is diagnostic of any particular process of formation. The results of the study indicate that in Westerly granite for transition from sparse fracture to pervasive pulverization requires high strain rates in excess of 250/s and that the formation of PR may be inhibited at the larger burial depths. The constraint imposed by field observations of the relatively low strains (1–3%) in PR recovered from the field and the laboratory derived threshold for the critical strain rate (∼250/s and higher) together indicate that a dynamic supershear-type rupture may be necessary for the origin of pulverized rocks at distances of tens of meters away from the fault plane as observed in the field for both large strike-slip-type and the relatively small dip-slip-type fault ruptures in nature.

Description: This study investigates the spatial and temporal distribution of energy release of large, intermediate-depth earthquakes using a modified back projection technique first used to study the 2004 Sumatra-Andaman megathrust event. Multiple seismic phases are included in the back projection analysis, which provides the capability to determine the energy distribution with respect to depth and time. A total of 22 intermediate-depth earthquakes with moment magnitudes greater than or equal to 6.5 are investigated with hypocentral depths between 100 and 300 km. For most of these events, the vertical extent of energy release is either below the resolution of this study (≤5 km) or slightly above (≤15 km). This observation agrees with previous studies that find large, intermediate-depth earthquakes have subhorizontal rupture planes. The results also show a significant portion of the events have multiple rupture planes that are well separated in depth. The closeness in time of the ruptures on separate planes and the distance between the planes suggest dynamic triggering where the P waves from the first rupture initiate rupture on the second plane. We propose that a dehydration embrittlement mechanism combined with preferentially hydrated subhorizontal faults can explain the observations of dominant subhorizontal rupture planes and the frequent occurrence of rupture complexity involving multiple subevents.

Description: We have synthesized phase D at 24 GPa and at temperatures of 1250–1100°C in a multianvil press under conditions of high silica activity. The compressibility of this high-silica-activity phase D (Mg1.0Si1.7H3.0O6) has been measured up to 55.8 GPa at ambient temperature by powder X-ray diffraction. The volume (V) decreases smoothly with increasing pressure up to 40 GPa, consistent with the results reported in earlier studies. However, a kink is observed in the trend of V versus pressure above ∼40 GPa, reflecting a change in the compression behavior. The data to 30 GPa fit well to a third-order Birch-Murnaghan equation of state (EoS), yielding Vo = 85.1 ± 0.2 Å3; Ko = 167.9 ± 8.6 GPa; and K′o = 4.3 ± 0.5, similar to results for Fe-Al-free phase D reported by Frost and Fei (1999). However, these parameters are larger than those reported for Fe-Al-bearing phase D and for Fe-Al-free phase D. The abnormal volume change in this study may be attributed to the reported hydrogen bond symmetrization in phase D. Fitting a third-order Birch-Murnaghan EoS to the data below 30 GPa yields a bulk modulus Ko = 173 (2) GPa for the hydrogen-off-centered (HOC) phase and Ko = 212 (15) GPa for the data above 40 GPa for the hydrogen-centered (HC) phase, assuming K′o is 4. The calculated bulk modulus Ko of the HC phase is 18% larger than the bulk modulus Ko of the HOC phase.

Description: Knowledge of the mechanical properties of gas-hydrate-bearing sediments is essential for simulating the geomechanical response to gas extraction from a gas-hydrate reservoir. In this study, drained triaxial compression tests were conducted on artificial methane-hydrate-bearing sediment samples under hydrate-stable temperature-pressure conditions. Toyoura sand (average particle size: D50 = 0.230 mm), number 7 silica sand (D50 = 0.205 mm), and number 8 silica sand (D50 = 0.130 mm) were used as the skeleton of each specimen. Axial loading was conducted at an axial strain rate of 0.1% min−1 at a constant temperature of 278 K. The cell and pore pressures were kept constant during axial loading. We found that the strength and stiffness of the hydrate-sand specimens increased with methane hydrate saturation and with the effective confining pressure, and the secant Poisson's ratio decreased with the effective confining pressure. The stiffness depends on the type of sand forming the skeleton of the specimens, although the strength has little dependence on the type of sand. According to an earlier work, hydrate-sand specimens are thought to contract in the early stage of axial loading before starting to expand owing to the dilatancy effect, as is the case for many other geological materials. The test results in this study are discussed in relation to the deformation mechanism proposed in an earlier work.