Slip distribution and stress changes associated with the 1999 November 12, Duzce (Turkey) earthquake (M (w)=7.1)

The 1999 November 12 Duzce earthquake (M (w) = 7.1) was apparently the eastward extension of the August 17, Izmit earthquake (M (w) = 7.4). The Duzce event caused heavy damage and fatalities in the cities of Duzce and Bolu. Here a finite-fault inversion method with five discrete time windows is applied to derive the co-seismic slip distribution of the Duzce earthquake. The fault plane is best modelled as a 40 x 20 km(2) plane, with a strike of 262degrees and a dip of 65degrees to the north, and that the majority of slip occurred in two distinct patches on either side of the hypocentre, implying bilateral rupture. The possible triggering of this event by the Izmit earthquake is investigated using Coulomb stress modelling of all large events since 1943 with the inclusion of secular loading. The results show that although the Duzce rupture plane was in a stress shadow prior to the Izmit earthquake, that event caused a significant Coulomb stress load, taking the Duzce fault out of the stress shadow, which probably precipitated failure. A comparison of the mapped Coulomb stress change with the inferred slip shows no correlation between the two. Finally, the stress modelling indicates that the northern branch of the North Anatolian fault zone, beneath the Sea of Marmara towards the city of Istanbul, is presently the most highly loaded segment of the North Anatolian Fault Zone

Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies

AbstractObjective Many factors are involved in the osteoarthritic process. It is not yet known which are initiators, promoters or simply results. Thus, we have evaluated some of those potentially important factors in osteoarthritis (OA) as observed sequentially for the first time in synovial fluids.DesignSynovial fluids (SF) obtained between 1992–2002 were all routinely evaluated for gross appearance, leukocyte counts and microscopic examination of wet drop preparations. We used regular and polarized light and alizarin red s stains. We separated out all OA patients, then we looked for patients who had more than two synovial fluid analyses to get sequential information. Time between first and final aspiration ranged from 2 to 7 (3.6±1.6) years and number of analyses per patients from 3 to 6 (3.3±0.7). We related synovial fluid crystals, fibrils and white blood cell count (WBC) to age, sex, disease duration and radiographic assessment according to the Kellgren–Lawrence radiographic rating system.Results Of 4523 synovial fluid examinations, we found 855 in patients with knee OA; 330 patients with adequate clinical details for comparison were included in our study. Twenty-six patients (one woman and 25 men) had sequentially examined SF.We found that 52% of those OA patients with effusions studied had crystals identified in their synovial fluid. Twenty-one percent of all the patients had CPPD crystals, 47% had hydroxyapatite, also called basic calcium phosphate (BCP) crystals and 16% had both types of crystals. Microscopically identifiable fibrils were found in 60% of SF.In sequentially examined patients, CPPD crystals and apatite (BCP) were found in 19% and 23%, respectively, at the first aspiration and, in 34% and 58% at the final aspiration. Fibrils were seen in 54% at first examination and 85% later. Apatite and fibrils showed more significant correlation with time (r=0.51,r =0.92) than did CPPD (r=0.32). SF WBC correlated only with CPPD crystals and did not increase with OA duration or severity. CPPD, apatite and fibrils all correlated with higher radiographic grades of OA.Conclusions As noted before CPPD and apatite crystals were more common in patients with more severe OA. New findings are that our sequential cases showed that there were some patients with no crystals at onset but that crystals appeared with progression of the disease. Fibril presence in SF also correlated with progression of the disease.Copyright 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved

Vinculin Controls PTEN Protein Level by Maintaining the Interaction of the Adherens Junction Protein β-Catenin with the Scaffolding Protein MAGI-2

PTEN is a frequently mutated tumor suppressor in malignancies. Interestingly, some malignancies exhibit undetectable PTEN protein without mutations or loss of PTEN mRNA. The cause(s) for this reduction in PTEN is unknown. Cancer cells frequently exhibit loss of cadherin, beta-catenin, alpha-catenin and/or vinculin, key elements of adherens junctions. Here we show that F9 vinculin-null (vin(-/-)) cells lack PTEN protein despite normal PTEN mRNA levels. Their PTEN protein expression was restored by transfection with vinculin or by inhibition of PTEN degradation. F9 vin(-/-) cells express PTEN protein upon transfection with a vinculin fragment (amino acids 243-1066) that is capable of interacting with alpha-catenin but unable to target into focal adhesions. On the other hand, disruption of adherens junctions with an E-cadherin blocking antibody reduced PTEN protein to undetectable levels in wild-type F9 cells. PTEN protein levels were restored in F9 vin(-/-) cells upon transfection with an E-cadherin-alpha-catenin fusion protein, which targets into adherens junctions and interacts with beta-catenin in F9 vin(-/-) cells. beta-Catenin is known to interact with MAGI-2. MAGI-2 interaction with PTEN in the cell membrane is known to prevent PTEN protein degradation. Thus, MAGI-2 overexpression in F9 vin(-/-) cells restored PTEN protein levels. Moreover, expression of vinculin mutants that reinstated the disrupted interactions of beta-catenin with MAGI-2 in F9 vin(-/-) cells also restored PTEN protein levels. These studies indicate that PTEN protein levels are dependent on the maintenance of beta-catenin-MAGI-2 interaction, in which vinculin plays a critical role

Near-field propagation of tsunamis from megathrust earthquakes

We investigate controls on tsunami generation and propagation in the near-field of great megathrust earthquakes using a series of numerical simulations of subduction and tsunamigenesis on the Sumatran forearc. The Sunda megathrust here is advanced in its seismic cycle and may be ready for another great earthquake. We calculate the seafloor displacements and tsunami wave heights for about 100 complex earthquake ruptures whose synthesis was informed by reference to geodetic and stress accumulation studies. Remarkably, results show that, for any near-field location: (1) the timing of tsunami inundation is independent of slipdistribution on the earthquake or even of its magnitude, and (2) the maximum wave height is directly proportional to the vertical coseismic displacement experienced at that location. Both observations are explained by the dominance of long wavelength crustal flexure in near-field tsunamigenesis. The results show, for the first time, that a single estimate of vertical coseismic displacement might provide a reliable short-term forecast of the maximum height of tsunami waves

RhoA GTPase Activation by TLR2 and TLR3 Ligands: Connecting via Src to NF- B

Rho GTPases are essential regulators of signaling networks emanating from many receptors involved in innate or adaptive immunity. The Rho family member RhoA controls cytoskeletal processes as well as the activity of transcription factors such as NF-κB, C/EBP and serum response factor. The multifaceted host cell activation triggered by Toll-like receptors (TLRs) in response to soluble and particulate microbial structures includes rapid stimulation of RhoA activity. RhoA acts downstream of TLR2 in HEK-TLR2 and monocytic THP-1 cells, but the signaling pathway connecting TLR2 and RhoA is still unknown. It is also not clear if RhoA activation is dependent on a certain TLR adapter. Using lung epithelial cells, we demonstrate TLR2- and TLR3-triggered recruitment and activation of RhoA at receptor-proximal cellular compartments. RhoA activity was dependent on TLR-mediated stimulation of Src family kinases. Both Src family kinases and RhoA were required for NF-κB activation, while RhoA was dispensable for type I interferon generation. These results suggest that RhoA plays a role downstream of MyD88-dependent and -independent TLR signaling and acts as a molecular switch downstream of TLR-Src initiated pathways

Positive feedback between Cdc42 activity and H + efflux by the Na-H exchanger NHE1 for polarity of migrating cells

A fundamental feature of cell polarity in response to spatial cues is asymmetric amplification of molecules generated by positive feedback signaling. We report a positive feedback loop between the guanosine triphosphatase Cdc42, a central determinant in eukaryotic cell polarity, and H+ efflux by Na-H+ exchanger 1 (NHE1), which is necessary at the front of migrating cells for polarity and directional motility. In response to migratory cues, Cdc42 is not activated in fibroblasts expressing a mutant NHE1 that lacks H+ efflux, and wild-type NHE1 is not activated in fibroblasts expressing mutationally inactive Cdc42-N17. H+ efflux by NHE1 is not necessary for release of Cdc42–guanosine diphosphate (GDP) from Rho GDP dissociation inhibitor or for the membrane recruitment of Cdc42 but is required for GTP binding by Cdc42 catalyzed by a guanine nucleotide exchange factor (GEF). Data indicate that GEF binding to phosphotidylinositol 4,5–bisphosphate is pH dependent, suggesting a mechanism for how H+ efflux by NHE1 promotes Cdc42 activity to generate a positive feedback signal necessary for polarity in migrating cells

Effects of Glucose Control on Hematological Indices in Patients with Diabetes Mellitus

Aim: We aimed to investigate the effects of diabetes treatment modalities on haematological parameters and leukocyte formula in patients with type 2 diabetes mellitus.Materials and Methods: The study included 102 patients with type 2 diabetes, out of which 51 receiving insulin treatment and 51 receiving oral antidiabetics (OAD). Hemogram data of insulin and OAD treated groups were compared.Results HbA1c levels were 11.12 ± 2.09 mg/dl in insulin group and 7.94 ± 2.1 mg/dl in OAD group p=0.001. Platelet counts were 27866.67 ± 77693 109/L before treatment and 258941.18 ± 69068.2 109/L in OAD group at six months, p: 0.015 whereas; 293011.76 ± 73711.21 109/L before treatment and 289492.86 ± 82631.49 109/L in insulin group at six months p: 0.821. Monocyte counts were 0.47 ± 0.12 109/L before the treatment and 0.57 ± 0.12 109/L in mix insulin therapy subgroup at six months, p:0.004; monocyte percentage was % 6.11 ± 1.74 before the treatment and %7.51 ± 2.57 in mix insulin subgroup at six months p:0.039;  Basophiles counts were 0.1 ±  0.02 109/L before treatment and 0.09 ± 0.04 109/L in intensive insulin therapy subgroup at six months, p: 0.005; Lymphocyte and basophils counts were significantly decreased at six months insulin treatment as compared to the pretreatment values.Conclusion: This study showed that, glucose control effects; blood indices HbA1C, basophiles, eosinophils, platelets and lymphocytes counts

GEF-H1 Modulates Localized RhoA Activation during Cytokinesis under the Control of Mitotic Kinases

Formation of the mitotic cleavage furrow is dependent upon both microtubules and activity of the small GTPase RhoA. GEF-H1 is a microtubule-regulated exchange factor that couples microtubule dynamics to RhoA activation. GEF-H1 localized to the mitotic apparatus in HeLa cells, particularly at the tips of cortical microtubules and the midbody, and perturbation of GEF-H1 function induced mitotic aberrations, including asymmetric furrowing, membrane blebbing, and impaired cytokinesis. The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity. Dephosphorylation of GEF-H1 occurs just prior to cytokinesis, accompanied by GEF-H1-dependent GTP-loading on RhoA. Using a live cell biosensor, we demonstrate distinct roles for GEF-H1 and Ect2 in regulating Rho activity in the cleavage furrow, with GEF-H1 catalyzing Rho activation in response to Ect2-dependent localization and initiation of cell cleavage. Our results identify a GEF-H1-dependent mechanism to modulate localized RhoA activation during cytokinesis under the control of mitotic kinases