The Endoplasmic Spreading Mechanism of Fibroblasts: Showcasing the Integrated Cytoskeleton

Cell motility is an essential process that depends on a coherent, cross-linked cytoskeleton that physically coordinates the actions of numerous structural and signaling molecules. In culture, a common feature of cells is the coherent movement of the endoplasmic reticulum and membranous organelles toward the periphery during substrate adhesion and spreading. The actin cross-linking protein, filamin (Fln), has been implicated in the support of three-dimensional cortical actin networks capable of both maintaining cellular integrity and withstanding large forces. Although numerous studies have examined cells lacking one of the multiple Fln isoforms, compensatory mechanisms can mask novel phenotypes only observable by further Fln depletion. Indeed, shRNA-mediated knockdown of FlnA in FlnB-/- mouse embryonic fibroblasts (MEFs) causes a novel endoplasmic spreading deficiency as detected by endoplasmic reticulum markers. Microtubule (MT) extension rates are also decreased but not by peripheral actin flow, because this is also decreased in the Fln-depleted system. Additionally, Fln-depleted MEFs exhibit decreased adhesion stability that leads to increased ruffling of the cell edge, reduced adhesion size, transient traction forces, and decreased stress fibers. FlnA-/- MEFs, but not FlnB-/- MEFs, also show a moderate defect in endoplasm spreading, characterized by initial extension followed by abrupt retractions and stress fiber fracture. FlnA localizes to actin linkages surrounding the endoplasm, adhesions, and stress fibers. Thus I suggest that Flns have a major role in the maintenance of actin-based mechanical linkages that enable endoplasmic spreading and MT extension as well as sustained traction forces and mature focal adhesions. I also report that treatment with the calpain inhibitor N-[N-(N-Acetyl-L-leucyl)-L-leucyl]- L-norleucine (ALLN) restores endoplasmic spreading and focal adhesion (FA) maturation in the absence of Fln. Further, expression of calpain-uncleavable talin, but not full-length talin, also rescues endoplasmic spreading in Fln-depleted cells and indicates a crucial role for stable, mature FAs in endoplasmic spreading. Because FA maturation involves the vimentin intermediate filament (vIF) network, I also examined the role of vIFs in endoplasmic spreading. Wild-type cells expressing a dominant-negative vimentin variant incapable of vIF polymerization exhibit deficient endoplasmic spreading as well as defects in FA maturation. ALLN treatment restores FA maturation despite the lack of vIFs, but does not restore endoplasmic spreading. Consistent with a role for vIFs in endoplasmic spreading, adhesive structures do not contain vIFs when the endoplasm does not spread. Fln-depleted cells also exhibit a microtubule-dependent mistargeting of vIFs. Thus, I propose a model in which cellular force generation and interaction of vIFs with mature FAs are required for endoplasmic spreading. Additionally, I discuss future lines of investigation concerning the role of FlnA in the endoplasmic spreading mechanism as well as mechanosensitive functions of FlnA. Finally, I speculate on a potential application of endoplasmic spreading deficiencies as hallmarks of metastatic breast cancer

Predicting New Jersey High School Proficiency Test Results in Mathematics and Language Arts Using Community Demographic Data

This study examined the relationship between the 2013 New Jersey High School Proficiency Assessment (HSPA) Language Arts and Mathematics scores and school level data related to family human capital and community social capital found in the extant literature to influence student achievement on high-stakes standardized assessments. School level data included percentage of families in poverty for 12 months, percentage of lone-parent households (total), and percentage of population with some college. Final analysis utilized hierarchical linear regression and the application of a mathematical algorithm found in extant literature. The study incorporated New Jersey high schools that (a) tested more than 25 students in the 11th grade, (b) had valid 2013 NJ HSPA results in the Language Arts and Mathematics sections, and (c) complete census data existed for the communities they served. The final sample size included 168 towns in the state of New Jersey. The final Language Arts model was able to accurately predict 125 of the 168 (74%) passing rates within 4 percentage points, factoring for the model’s standard error of the estimate. The final Mathematics model was able to accurately predict 131 of the 168 (78%) passing rates within 8 percentage points, factoring for the model’s standard error of the estimate

Variations in teaching of removable partial dentures in Spanish dental schools

Objectives: Despite the increasing demand for implant-based treatments, removable partial dentures (RPDs) are frequently used in the oral rehabilitation of partially dentate patients. Furthermore, the Bologna Declaration Agreement (1999) promotes the freedom of movement both of students among dental schools and of graduates across the European Union (EU). Given that inconsistency in teaching among dental schools may lead to confusion, this study aimed to evaluate the status of teaching and clinical experience reached by undergrad uate dentalstudents in Spanish dental schools in relation to RPDs. Study design: A questionnaire seeking information on the preclinical and clinical teaching of RPDs was emailed to all Spanish dental schools (11 public, 4 private) with complete undergraduate degree dental programmes in November 2009. Descriptive statistical data analysis was performed. Results: A 100% response rate was obtained. The average duration of the preclinical course in Spain was 44 hours (38 hours in the public chools and 60.5 hours in the private schools). However, public schools reported a greater number of RPDs made per student prior to graduation, with an average of 3.4 acrylic (range: 1-20) and 3.4 cobaltchromium (range: 1-20) RPDs. The corresponding means for private schools were 1 acrylic (range: 0-2) and 2.3 cobalt-chromium (range: 1-4). One public school (9%) stated that they were teaching RPDs using Problem-Based- Learning.Conclusions: Similar to that noted in previously surveyed countries, variations in teaching programmes and clinical experience concerning RPDs achieved by Spanish dental students were evident. While diversity of teaching is often considered to be of benefit, dental students must be adequately trained to ensure that they meet the needs of the patients they will serve during their careers. © Medicina Oral S. L

Sampling Bias Overestimates Climate Change Impacts on Forest Growth in the Southwestern United States

Climate−tree growth relationships recorded in annual growth rings have recently been the basis for projecting climate change impacts on forests. However, most trees and sample sites represented in the International Tree-Ring Data Bank (ITRDB) were chosen to maximize climate signal and are characterized by marginal growing conditions not representative of the larger forest ecosystem. We evaluate the magnitude of this potential bias using a spatially unbiased tree-ring network collected by the USFS Forest Inventory and Analysis (FIA) program. We show that U.S. Southwest ITRDB samples overestimate regional forest climate sensitivity by 41–59%, because ITRDB trees were sampled at warmer and drier locations, both at the macro- and micro-site scale, and are systematically older compared to the FIA collection. Although there are uncertainties associated with our statistical approach, projection based on representative FIA samples suggests 29% less of a climate change-induced growth decrease compared to projection based on climate-sensitive ITRDB samples

Effect of alloy type and casting technique on the fracture strength of implant-cemented structures

Objectives: To evaluate the influence of alloy type and casting procedure on the fracture strength (FS) of metallic frameworks for implant-supported fixed prostheses. Study design: Thirty three-unit structures for lower posterior bridges were waxed-up and randomly assigned to two groups (n=15) according to alloy type and casting technique: Group 1 (C): cobalt-chromium cast in a centrifugal machine (TS1, Degussa-Hüls); Group 2 (T): titanium cast in a pressure-differential device (Cyclarc II, Morita). Each structure was cemented onto two prefabricated abutments under a constant seating pressure. After 6 months of water aging, samples were loaded in a static universal testing machine (EFH/5/FR, Microtest) until fracture. Axial compressive loads were applied at the central fossa of the pontics. FS data were recorded and surface topography of the fractured connectors was SEM-analyzed. A Chi-Square test was performed to assess the dependence of pores on the alloy type and casting procedure. ANOVA and Student-Newman-Keuls (SNK) tests were run for FS comparisons (p<0.05). Results: One third of the C structures showed pores inside the fractured connectors. T frameworks demonstrated higher FS than that of C specimens exhibiting pores (p=0.025). C samples containing no pores recorded the greatest mean FS (p<0.001). Conclusions: Fracture strength of metallic frameworks depended on the alloy type and casting procedure. Cobalt-chromium casts often registered pores inside the connectors, which strongly decreased the fracture resistance. An accurate casting of titanium with a pressure-differential system may result in the most predictable technique under the tested experimental conditions. © Medicina Oral S. L

A randomised controlled study on the effects of different surface treatments and adhesive self-etch functional monomers on the immediate repair bond strength and integrity of the repaired resin composite interface

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Hypothermia: an unusual indication for gastric lavage.

BACKGROUND: Previous reports suggest that gastric lavage holds many risks and is not routinely indicated for decontamination of the overdose patient. OBJECTIVE: To present a case of overdose with concurrent accidental hypothermia where gastric decontamination was utilized. CASE REPORT: A 50-year-old hypothermic, comatose patient was transported to the Emergency Department with a concurrent, massive medication ingestion diagnosed incidentally on a routine abdominal computed tomography scan. Both active and passive rewarming measures, in conjunction with gastric lavage and retrieval of multiple pill fragments, were performed, and the patient survived to hospital discharge without sequelae. Interestingly, the patient admitted to an intentional ingestion of both labetalol and lorazepam. CONCLUSION: Due to hypothermia-mediated changes in metabolism, including gastric atony and decreased hepatic metabolism, gastric lavage may provide additional benefit in the management of severely hypothermic patients with potentially lethal, massive pill ingestions

A Generative Model of the Mutual Escalation of Anxiety Between Religious Groups

We propose a generative agent-based model of the emergence and escalation of xenophobic anxiety in which individuals from two different religious groups encounter various hazards within an artificial society. The architecture of the model is informed by several empirically validated theories about the role of religion in intergroup conflict. Our results identify some of the conditions and mechanisms that engender the intensification of anxiety within and between religious groups. We define mutually escalating xenophobic anxiety as the increase of the average level of anxiety of the agents in both groups overtime. Trace validation techniques show that the most common conditions under which longer periods of mutually escalating xenophobic anxiety occur are those in which the difference in the size of the groups is not too large and the agents experience social and contagion hazards at a level of intensity that meets or exceeds their thresholds for those hazards. Under these conditions agents will encounter out-group members more regularly, and perceive them as threats, generating mutually escalating xenophobic anxiety. The model\u27s capacity to grow the macro-level emergence of this phenomenon from micro-level agent behaviors and interactions provides the foundation for future work in this domain

A zinc-doped endodontic cement facilitates functional mineralization and stress dissipation at the dentin surface

The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (?). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan ? values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan ? after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface