Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN).

In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future

Adoption of practice guidelines and assessment tools in substance abuse treatment

<p>Abstract</p> <p>Background</p> <p>The gap between research and practice limits utilization of relevant, progressive and empirically validated strategies in substance abuse treatment.</p> <p>Methods</p> <p>Participants included substance abuse treatment programs from the Northeastern United States. Structural equation models were constructed with agency level data to explore two outcome variables: adoption of practice guidelines and assessment tools at two points in time; models also included organizational, staffing and service variables.</p> <p>Results</p> <p>In 1997, managed care involvement and provision of primary care services had the strongest association with increased use of assessment tools, which, along with provision of counseling services, were associated with a greater use of practice guidelines. In 2001, managed care involvement, counseling services and being a stand-alone drug treatment agency were associated with a greater use of assessment tools, which was in turn related to an increase in the use of practice guidelines.</p> <p>Conclusions</p> <p>This study provides managers, clinicians and policy-makers with a framework for understanding factors related to the adoption of new technologies in substance abuse treatment.</p

Microarrays for global expression constructed with a low redundancy set of 27,500 sequenced cDNAs representing an array of developmental stages and physiological conditions of the soybean plant

BACKGROUND: Microarrays are an important tool with which to examine coordinated gene expression. Soybean (Glycine max) is one of the most economically valuable crop species in the world food supply. In order to accelerate both gene discovery as well as hypothesis-driven research in soybean, global expression resources needed to be developed. The applications of microarray for determining patterns of expression in different tissues or during conditional treatments by dual labeling of the mRNAs are unlimited. In addition, discovery of the molecular basis of traits through examination of naturally occurring variation in hundreds of mutant lines could be enhanced by the construction and use of soybean cDNA microarrays. RESULTS: We report the construction and analysis of a low redundancy 'unigene' set of 27,513 clones that represent a variety of soybean cDNA libraries made from a wide array of source tissue and organ systems, developmental stages, and stress or pathogen-challenged plants. The set was assembled from the 5' sequence data of the cDNA clones using cluster analysis programs. The selected clones were then physically reracked and sequenced at the 3' end. In order to increase gene discovery from immature cotyledon libraries that contain abundant mRNAs representing storage protein gene families, we utilized a high density filter normalization approach to preferentially select more weakly expressed cDNAs. All 27,513 cDNA inserts were amplified by polymerase chain reaction. The amplified products, along with some repetitively spotted control or 'choice' clones, were used to produce three 9,728-element microarrays that have been used to examine tissue specific gene expression and global expression in mutant isolines. CONCLUSIONS: Global expression studies will be greatly aided by the availability of the sequence-validated and low redundancy cDNA sets described in this report. These cDNAs and ESTs represent a wide array of developmental stages and physiological conditions of the soybean plant. We also demonstrate that the quality of the data from the soybean cDNA microarrays is sufficiently reliable to examine isogenic lines that differ with respect to a mutant phenotype and thereby to define a small list of candidate genes potentially encoding or modulated by the mutant phenotype

Extracting a stroke phenotype risk factor from Veteran Health Administration clinical reports: an information content analysis

In the United States, 795,000 people suffer strokes each year; 10-15 % of these strokes can be attributed to stenosis caused by plaque in the carotid artery, a major stroke phenotype risk factor. Studies comparing treatments for the management of asymptom

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

Abstract Background Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Results Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Conclusion Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. Trial Registration ClinicalTrials.gov NCT0029074

Does the level of expressed emotion (LEE) questionnaire have the same factor structure for adolescents as it has for adults?

Background The level of expressed emotion (LEE) is a four-factor questionnaire that measures expressed emotion (EE) as perceived by the recipient. These factors are: perceived lack of emotional support, perceived intrusiveness, perceived irritation, and perceive criticism. The four factors of the LEE has previously been found to be related to psychological disorders and has good psychometric properties for adults. However, it has not previously been studied in adolescent populations. Methods A total of 311 adolescents participated in this study. Using structural equation modeling, confirmatory factor analyses were conducted to examine if the LEE also had the same four-factor structure for adolescents as it does for adults. Results The confirmatory factor analyses demonstrated that the LEE's four-factor structure also applied to adolescents. The internal consistency of the scales were good and all the inter-correlations between the scales were significant. Additionally, the factors were significantly correlated to adolescent depressive and anxiety symptom score dimensions. Conclusion These findings seem to indicate that the LEE may be a good instrument in the measurement of adolescents perceived EE

Variability in the Dynamics of Mortality and Immobility Responses of Freshwater Arthropods Exposed to Chlorpyrifos

The species sensitivity distribution (SSD) concept is an important probabilistic tool for environmental risk assessment (ERA) and accounts for differences in species sensitivity to different chemicals. The SSD model assumes that the sensitivity of the species included is randomly distributed. If this assumption is violated, indicator values, such as the 50% hazardous concentration, can potentially change dramatically. Fundamental research, however, has discovered and described specific mechanisms and factors influencing toxicity and sensitivity for several model species and chemical combinations. Further knowledge on how these mechanisms and factors relate to toxicologic standard end points would be beneficial for ERA. For instance, little is known about how the processes of toxicity relate to the dynamics of standard toxicity end points and how these may vary across species. In this article, we discuss the relevance of immobilization and mortality as end points for effects of the organophosphate insecticide chlorpyrifos on 14 freshwater arthropods in the context of ERA. For this, we compared the differences in response dynamics during 96 h of exposure with the two end points across species using dose response models and SSDs. The investigated freshwater arthropods vary less in their immobility than in their mortality response. However, differences in observed immobility and mortality were surprisingly large for some species even after 96 h of exposure. As expected immobility was consistently the more sensitive end point and less variable across the tested species and may therefore be considered as the relevant end point for population of SSDs and ERA, although an immobile animal may still potentially recover. This is even more relevant because an immobile animal is unlikely to survive for long periods under field conditions. This and other such considerations relevant to the decision-making process for a particular end point are discussed

Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

<p>Abstract</p> <p>Background</p> <p>Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR) are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor.</p> <p>Results</p> <p>MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice), it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis.</p> <p>Conclusion</p> <p>During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.</p

The Effect of DNA-Dependent Protein Kinase on Adeno-Associated Virus Replication

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs