A critical role of tropomyosins in TGF-beta regulation of the actin cytoskeleton and cell motility in epithelial cells

We have investigated transforming growth factor beta (TGF-beta)-mediated induction of actin stress fibers in normal and metastatic epithelial cells. We found that stress fiber formation requires de novo protein synthesis, p38Mapk and Smad signaling. We show that TGF-beta via Smad and p38Mapk up-regulates expression of actin-binding proteins including high-molecular-weight tropomyosins, alpha-actinin and calponin h2. We demonstrate that, among these proteins, tropomyosins are both necessary and sufficient for TGF-beta induction of stress fibers. Silencing of tropomyosins with short interfering RNAs (siRNAs) blocks stress fiber assembly, whereas ectopic expression of tropomyosins results in stress fibers. Ectopic-expression and siRNA experiments show that Smads mediate induction of tropomyosins and stress fibers. Interestingly, TGF-beta induction of stress fibers was not accompanied by changes in the levels of cofilin phosphorylation. TGF-beta induction of tropomyosins and stress fibers are significantly inhibited by Ras-ERK signaling in metastatic breast cancer cells. Inhibition of the Ras-ERK pathway restores TGF-beta induction of tropomyosins and stress fibers and thereby reduces cell motility. These results suggest that induction of tropomyosins and stress fibers play an essential role in TGF-beta control of cell motility, and the loss of this TGF-beta response is a critical step in the acquisition of metastatic phenotype by tumor cells

Patterns and Predictors of Local Health Department Accreditation in Missouri

Background: The Healthy People 2020 goal for the public health system is “to ensure that Federal, State, Tribal, and local health agencies have the necessary infrastructure to effectively provide essential public health services.” To address this goal, Missouri established the first statewide, voluntary accreditation program of local health departments (LHDs) and began accrediting the LHDs in 2003. The purpose of this study was to identify organizational, structural, and workforce factors related to accreditation status of LHDs in Missouri. Methods: Using data from the National Association of County & City Health Officials (2010) and the Missouri Department of Health & Senior Services (2012), binary logistic regression analysis was performed to predict accreditation status of LHDs. Likelihood ratio tests were used to examine whether the addition of each predictor added significantly to the model compared with a model including total revenues alone. Adjusted odds ratios (aORs), 95% confidence intervals, the significance level of the likelihood ratio test, and the overall Nagelkerke pseudo-R2 for each model are reported. Results: Having a community health improvement plan (aOR = 6.2), a strategic plan (aOR = 7.9), evaluating programs (aOR = 3.6), being in a region with a high proportion of accredited LHDs (aOR = 5.5), and participating in multijurisdictional collaborations (aOR = 6.4) all increased the likelihood of accreditation. Barriers of time (aOR = 0.1) and cost (aOR = 0.3) were negatively associated with accreditation. Conclusions: Accredited LHDs were more likely to have completed the prerequisites for accreditation and collaborate with other LHDs. These activities help LHDs meet the accreditation standards. In addition, with shrinking budgets, LHDs will need additional financial and technical support to achieve accreditation. Assisting LHDs to find ways to increase the staff is important. Through collaborations with other LHDs, regional or multicounty positions can be created. Also collaborations with universities, specifically colleges or schools of public health, can provide opportunities for internships at LHDs giving practical experience while providing important assistance to LHDs

Characterisation of indeterminate focal breast lesions on grey-scale ultrasound: role of ultrasound elastography.

PURPOSE: This study was undertaken to evaluate the role of ultrasound (US) elastography in characterising focal breast lesions classified as indeterminate on B-mode US. MATERIALS AND METHODS: Eighty-four focal breast lesions, 64 benign and 20 malignant (mean diameter, 15.1 mm), detected but not characterised on B-mode US in 72 women, Breast Imaging Reporting and Data System (BI-RADS) US category 3 (n=56) or category 4 (n=28), were studied with US elastography and classified in consensus by two radiologists according to a five-point colour scale. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) of US elastography compared with conventional US were calculated in relation to microhistology (n=67) and cytology (n=17), which were used as the reference standard. RESULTS: A total of 65/84 (77.4%) lesions were correctly classified as benign or malignant using US elastography, whereas the remaining 19/84 (22.6%) were incorrectly assessed. There were no statistically significant differences between US elastography and B-mode US with regard to sensitivity (70% vs. 68.4%), specificity (79.6% vs. 78.5%), PPV (51.8% vs. 48.1%) and NPV 89% vs. 89.5% (p>0.5). By contrast, a statistically significant difference was noted in the evaluation of BI-RADS 3 lesions, in which US elastography had 50% sensitivity, 86% specificity, 30% PPV and 93.5% NPV compared with BI-RADS 4 lesions (78.6%, 57.1%, 64.7% and 72.7%) (p<0.5). CONCLUSIONS: The high NPV of US elastography may help reduce the use of biopsy in BI-RADS 3 lesions, but its low PPV in BI-RADS 4 lesions does not allow avoidance of biopsy on the basis of the US elastographic score alone in this group of lesions

Dietary studies in birds: testing a non-invasive method using digital photography in seabirds

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Dietary studies give vital insights into foraging behaviour, with implications for understanding changing environmental conditions and the anthropogenic impacts on natural resources. Traditional diet sampling methods may be invasive or subject to biases, so developing non-invasive and unbiased methods applicable to a diversity of species is essential. We used digital photography to investigate the diet fed to chicks of a prey-carrying seabird and compared our approach (photo-sampling) to a traditional method (regurgitations) for the greater crested tern Thalasseus bergii. Over three breeding seasons, we identified >24 000 prey items of at least 48 different species, more than doubling the known diversity of prey taken by this population of terns. We present a method to estimate the length of the main prey species (anchovy Engraulis encrasicolus) from photographs, with an accuracy <1 mm and precision ~ 0·5 mm. Compared to regurgitations at two colonies, photo-sampling produced similar estimates of prey composition and size, at a faster species accumulation rate. The prey compositions collected by two researchers photo-sampling concurrently were also similar. Photo-sampling offers a non-invasive tool to accurately and efficiently investigate the diet composition and prey size of prey-carrying birds. It reduces biases associated with observer-based studies and is simple to use. This methodology provides a novel tool to aid conservation and management decision-making in the light of the growing need to assess environmental and anthropogenic change in natural ecosystems.Department of Science and Technology, South Afric

Facilitates Chromatin Transcription Complex Is an “Accelerator” of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

SummaryThe facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACT’s role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses

Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors

BACKGROUND: This phase II study investigated whether targeting the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy. METHODS: Patients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure. RESULTS: Enrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1–NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72–3.25). The most commonly reported all‐grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%). CONCLUSION: BEZ235 treatment in mTOR inhibitor‐naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile

The Real maccoyii: Identifying Tuna Sushi with DNA Barcodes – Contrasting Characteristic Attributes and Genetic Distances

BACKGROUND:The use of DNA barcodes for the identification of described species is one of the least controversial and most promising applications of barcoding. There is no consensus, however, as to what constitutes an appropriate identification standard and most barcoding efforts simply attempt to pair a query sequence with reference sequences and deem identification successful if it falls within the bounds of some pre-established cutoffs using genetic distance. Since the Renaissance, however, most biological classification schemes have relied on the use of diagnostic characters to identify and place species. METHODOLOGY/PRINCIPAL FINDINGS:Here we developed a cytochrome c oxidase subunit I character-based key for the identification of all tuna species of the genus Thunnus, and compared its performance with distance-based measures for identification of 68 samples of tuna sushi purchased from 31 restaurants in Manhattan (New York City) and Denver, Colorado. Both the character-based key and GenBank BLAST successfully identified 100% of the tuna samples, while the Barcode of Life Database (BOLD) as well as genetic distance thresholds, and neighbor-joining phylogenetic tree building performed poorly in terms of species identification. A piece of tuna sushi has the potential to be an endangered species, a fraud, or a health hazard. All three of these cases were uncovered in this study. Nineteen restaurant establishments were unable to clarify or misrepresented what species they sold. Five out of nine samples sold as a variant of "white tuna" were not albacore (T. alalunga), but escolar (Lepidocybium flavorunneum), a gempylid species banned for sale in Italy and Japan due to health concerns. Nineteen samples were northern bluefin tuna (T. thynnus) or the critically endangered southern bluefin tuna (T. maccoyii), though nine restaurants that sold these species did not state these species on their menus. CONCLUSIONS/SIGNIFICANCE:The Convention on International Trade Endangered Species (CITES) requires that listed species must be identifiable in trade. This research fulfills this requirement for tuna, and supports the nomination of northern bluefin tuna for CITES listing in 2010

From the Eye of the Albatrosses: A Bird-Borne Camera Shows an Association between Albatrosses and a Killer Whale in the Southern Ocean

Albatrosses fly many hundreds of kilometers across the open ocean to find and feed upon their prey. Despite the growing number of studies concerning their foraging behaviour, relatively little is known about how albatrosses actually locate their prey. Here, we present our results from the first deployments of a combined animal-borne camera and depth data logger on free-ranging black-browed albatrosses (Thalassarche melanophrys). The still images recorded from these cameras showed that some albatrosses actively followed a killer whale (Orcinus orca), possibly to feed on food scraps left by this diving predator. The camera images together with the depth profiles showed that the birds dived only occasionally, but that they actively dived when other birds or the killer whale were present. This association with diving predators or other birds may partially explain how albatrosses find their prey more efficiently in the apparently ‘featureless’ ocean, with a minimal requirement for energetically costly diving or landing activities