Species richness is the most commonly used but controversial biodiversity metric in studies on aspects of community stability such as structural composition or productivity. The apparent ambiguity of ...theoretical and experimental findings may in part be due to experimental shortcomings and/or heterogeneity of scales and methods in earlier studies. This has led to an urgent call for improved and more realistic experiments. In a series of experiments replicated at a global scale we translocated several hundred marine hard bottom communities to new environments simulating a rapid but moderate environmental change. Subsequently, we measured their rate of compositional change (re-structuring) which in the great majority of cases represented a compositional convergence towards local communities. Re-structuring is driven by mortality of community components (original species) and establishment of new species in the changed environmental context. The rate of this re-structuring was then related to various system properties. We show that availability of free substratum relates negatively while taxon richness relates positively to structural persistence (i.e., no or slow re-structuring). Thus, when faced with environmental change, taxon-rich communities retain their original composition longer than taxon-poor communities. The effect of taxon richness, however, interacts with another aspect of diversity, functional richness. Indeed, taxon richness relates positively to persistence in functionally depauperate communities, but not in functionally diverse communities. The interaction between taxonomic and functional diversity with regard to the behaviour of communities exposed to environmental stress may help understand some of the seemingly contrasting findings of past research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Typical psychometric paradigm factors appear to have greater explanatory power for individual participants than previously envisaged. It is possible to acquire interpretable information about single ...participants using two factors (catastrophic potential and social and personal exposure) from aggregated participant-focused data. Our results suggest that the classical psychometric model originated by Fischhoff and Slovic in the early 1980s to explain differences among hazards may also be capable of accounting for differences among participants. While socio-demographic conditions on their own do not have substantial explanatory power, they are statistically significant and appear to dictate the position of participants within the factor space obtained using a participant-focused analysis. One of the principal criticisms of the psychometric paradigm has been its lack of interpretability when using disaggregated data, but incorporating socio-demographic variables overcomes this limitation.
Summary
Background
Tachykinins‐like substance P (SP) have been shown to play an important role in initiating and perpetuating airway inflammation. Furthermore, they are supposed to be released into ...tissues in response to stress.
Objective
The aim of this study was to investigate the effects of stress alone or in combination with allergic airway inflammation on SP expression in sensory neurons innervating the mouse airways.
Methods
Balb/c mice were systemically sensitized to ovalbumin (OVA), followed by allergen aerosol exposure, and compared with non‐sensitized controls. Additionally, OVA‐sensitized and ‐challenged and non‐sensitized mice were exposed to sound stress. SP expression in airway‐specific and overall vagal sensory neurons of the jugular and nodose ganglion complex was analysed using retrograde neuronal tracing in combination with immunohistochemistry. Preprotachykinin A (PPT‐A) mRNA, the precursor for SP, was quantified in lung tissue by real‐time PCR. Bronchoalveolar lavage (BAL) fluid was obtained, and cell numbers and differentiation were determined.
Results
Stress and/or allergic airway inflammation significantly increased SP expression in retrograde‐labelled vagal sensory neurons from the mouse lower airways compared with controls stress: 15.7±0.8% (% of retrograde‐labelled neurons, mean±SEM); allergen: 17.9±0.4%; allergen/stress: 13.1±0.7% vs. controls: 6.3±0.3%. Similarly, SP expression increased in overall vagal sensory neurons identified by the neuronal marker protein gene product (PGP) 9.5 stress: 9.3±0.6% (% of PGP 9.5‐positive neurons, means±SEM); allergen: 12.5±0.4%; allergen/stress: 10.2±0.4% vs. controls: 5.1±0.3%. Furthermore, stress significantly increased PPT‐A mRNA expression in lung tissue from OVA‐sensitized and ‐challenged animals, and immune cells were identified as an additional source of SP in the lung by immunohistochemistry. Associated with enhanced neuronal SP expression, a significantly higher number of leucocytes were found in the BAL following allergen exposure. Further, stress significantly increased allergen‐induced airway inflammation identified by increased leucocyte numbers in BAL fluids.
Conclusion
The central event of sound stress leads to the stimulation of SP expression in airway‐specific neurons. However, in sensitized stressed mice an additional local source of SP (probably inflammatory cells) might enhance allergic airway inflammation.
The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive ...factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 86-118 mg/dL vs. 76 54-88 mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.
Background
Next‐generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding ...in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies.
Methods
Next‐generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug‐related rearrangements, were prepared from 39 tumors (paraffin‐embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines.
Results
The platform detects single‐nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy‐number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent.
Conclusion
With an adequate methodology, it is possible to translate to the clinical practice the latest advances in precision oncology, integrating under the same platform the identification of somatic and germline genomic alterations.
This work describes the development, validation and clinical application of a novel molecular diagnostics platform based on targeted NGS, specifically designed to comprehensively identify, in a single test, both (1) somatic alterations linked to sensitivity or resistance to approved cancer therapies and (2) germline mutations predisposing to familial cancer. We also propose an innovative framework for analysis, interpretation and reporting of results, which adapts to different combinatorial situations regarding the nature of the request, the availability of tumor/normal samples and the scope of the informed consent. The analytical sensitivity and specificity of the platform for detecting SNVs and indels are >99.5% and its application to patient samples identified targeted therapeutic opportunities, revealed one case of misdiagnosis and detected germline pathogenic mutations.
Ureteral herniation is a rare entity. We report the first case of extraperitoneal ureteral herniation in a pediatric en bloc renal graft causing obstructive uropathy. A 70‐year‐old, obese patient ...with an en bloc renal transplant was found to have ureterohydronephrosis in the right renal graft on magnetic resonance imaging. Nephrostomy with insertion of a double‐J catheter confirmed the presence of a ureteral loop within the inguinal tract. Surgery confirmed herniation of the ureter through the internal inguinal ring, crossing over the spermatic cord. We performed release, resection, ureteral reimplantation and hernioplasty. Four months later, renal function was normal and urinary tract dilation had diminished. This case illustrates an unusual cause of obstructive uropathy in a transplanted kidney. Apart from obesity, two other factors may have contributed to its development: presence of a redundant ureter, and the fact that the ureter had been placed over, rather than under, the spermatic cord.
We report the mass stranding of 46 false killer whales in the Strait of Magellan in February 2013. We present observation-based information about body size, sex, dental formula and necropsies. Sexual ...dimorphism in body length was clear, with males being significantly larger than females. Dental formula coincided with previous reports for the species, with asymmetry present in females. Individuals showed normal body conditions without any signs of apparent disease. The cause of the stranding remains unknown, however the coastal morphology hypothesis is a possible explanation.
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