Genetic Basis for Red Coloration in Birds Lopes, Ricardo J.; Johnson, James D.; Toomey, Matthew B. ...
CB/Current biology,
06/2016, Letnik:
26, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The yellow and red feather pigmentation of many bird species 1 plays pivotal roles in social signaling and mate choice 2, 3. To produce red pigments, birds ingest yellow carotenoids and endogenously ...convert them into red ketocarotenoids via an oxidation reaction catalyzed by a previously unknown ketolase 4–6. We investigated the genetic basis for red coloration in birds using whole-genome sequencing of red siskins (Spinus cucullata), common canaries (Serinus canaria), and “red factor” canaries, which are the hybrid product of crossing red siskins with common canaries 7. We identified two genomic regions introgressed from red siskins into red factor canaries that are required for red coloration. One of these regions contains a gene encoding a cytochrome P450 enzyme, CYP2J19. Transcriptome analysis demonstrates that CYP2J19 is significantly upregulated in the skin and liver of red factor canaries, strongly implicating CYP2J19 as the ketolase that mediates red coloration in birds. Interestingly, a second introgressed region required for red feathers resides within the epidermal differentiation complex, a cluster of genes involved in development of the integument. Lastly, we present evidence that CYP2J19 is involved in ketocarotenoid formation in the retina. The discovery of the carotenoid ketolase has important implications for understanding sensory function and signaling mediated by carotenoid pigmentation.
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•Two genomic regions are required for red ketocarotenoid-based coloration in canaries•The first region contains CYP2J19, a cytochrome P450 family member•CYP2J19 is implicated as the ketolase required for ketocarotenoid formation in birds•The second region maps to a cluster of genes involved in epidermal differentiation
To produce red coloration of bills and feathers, birds convert yellow dietary carotenoids to red ketocarotenoids via the action of an unknown enzyme. Lopes et al. use whole-genome sequencing of yellow and red canaries to implicate CYP2J19 as the ketolase that catalyzes this conversion.
P-Glycoprotein (Pgp) is one of the best characterized ABC transporters, often involved in the multidrug-resistance phenotype overexpressed by several cancer cell lines. Experimental studies ...contributed to important knowledge concerning substrate polyspecificity, efflux mechanism, and drug-binding sites. This information is, however, scattered through different perspectives, not existing a unifying model for the knowledge available for this transporter. Using a previously refined structure of murine Pgp, three putative drug-binding sites were hereby characterized by means of molecular docking. The modulator site (M-site) is characterized by cross interactions between both Pgp halves herein defined for the first time, having an important role in impairing conformational changes leading to substrate efflux. Two other binding sites, located next to the inner leaflet of the lipid bilayer, were identified as the substrate-binding H and R sites by matching docking and experimental results. A new classification model with the ability to discriminate substrates from modulators is also proposed, integrating a vast number of theoretical and experimental data.
Objective
In current management paradigms of rheumatoid arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced ...therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role.
Methods
This was a cross‐sectional, single‐center study including consecutive ambulatory RA patients. Data collection comprised swollen 28‐joint count (SJC28), tender 28‐joint count (TJC28), C‐reactive protein (CRP) level, PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorized using American College of Rheumatology/European League Against Rheumatism Boolean‐based criteria: remission, near‐remission (only PGA >1), and nonremission. A binary definition without PGA (3v‐remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state.
Results
A total of 309 patients were included (remission 9.4%, near‐remission 37.2%, and nonremission 53.4%). Patients in near‐remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in nonremission. In multivariable analyses, PGA in near‐remission was explained (R2adjusted = 0.50) by fatigue, pain, anxiety, and function. Fatigue and pain had no relationship with disease activity measures.
Conclusion
In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP level ≤1) does not equate to low disease impact: a large proportion of these patients are considered in nonremission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This consideration suggests that clinical practice should be guided by 2 separate remission targets: inflammation (3v‐remission) and disease impact.
P-Glycoprotein (P-gp) is often involved in multidrug resistance (MDR) to the pharmacological action of a wide number of anticancer agents. In this article, a series of molecular dynamics simulations ...of murine’s P-gp were developed, elucidating the importance of the lipid membrane and linker sequence in the protein structure stability. The behavior of several molecules inside the drug-binding pocket revealed a striking difference between substrates or modulators, and motion patterns were identified that could be correlated with conformational alterations due to substrate binding, corresponding to the initial step in the efflux mechanism. Only one “entrance gate” to the drug-binding pocket was found and, in the presence of a substrate, leads to changes in the motion patterns of the transporter into an efflux-like movement.
To identify and synthesise the best available evidence on the accuracy of the currently available tools for predicting fracture risk.
We systematically searched PubMed MEDLINE, Embase and Cochrane ...databases to 2014. Two reviewers independently selected articles, collected data from studies, and carried out a hand search of the references of the included studies. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) checklist was used, and the primary outcome was the area under the curve (AUC) and 95% CIs, obtained from receiver operating characteristic (ROC) analyses. We excluded tools if they had not been externally validated or were designed for specific disease populations. Random effects meta-analyses were performed with the selected tools.
Forty-five studies met inclusion criteria, corresponding to 13 different tools. Only three tools had been tested more than once in a population-based setting: FRAX (26 studies in 9 countries), GARVAN (6 studies in 3 countries) and QFracture (3 studies in the UK, 1 also including Irish participants). Twenty studies with these three tools were included in a total of 17 meta-analyses (for hip or major osteoporotic fractures; men or women; with or without bone mineral density).
Most of the 13 tools are feasible in clinical practice. FRAX has the largest number of externally validated and independent studies. The overall accuracy of the different tools is satisfactory (>0.70), with QFracture reaching 0.89 (95% CI 0.88 to 0.89). Significant methodological limitations were observed in many studies, suggesting caution when comparing tools based solely on the AUC.
It is very well known that the incorporation of fillers into polymers increases their viscosity in a molten state; however, results contrary to this have been reported when graphite (Gr), graphite ...oxide (GrO), and graphene oxide (GO) among other carbonaceous fillers are used. Many authors have justified the reduction in polymer viscosity due to the slipping interlayers of the Gr, GrO, and GO fillers. The slipping interlayer cannot explain the reduction in polymer viscosity since the shear stresses produced or applied during rheological tests are lower than the interlayer shear strength of these fillers. Here, rheological experiments with two types of polyethylenes and Gr, GrO, and GO as fillers were carried out to elucidate this phenomenon. Remarkably, it was observed that the viscosity reduction occurs due to the presence of agglomerates in the composites. The agglomerates contain many flake–flake contacts out of registry (superlubricity state), which have very low slipping resistance. The slipping of these contacts promotes the reduction in polymer viscosity during rheological tests. The elucidation of the superlubricity state phenomenon proposed here may contribute to the understanding of the carbonaceous filler influence during the deformation of polymer composites.
To update the European League Against Rheumatism (EULAR) recommendations for the role of the nurse in the management of chronic inflammatory arthritis (CIA) using the most up to date evidence. The ...EULAR standardised operating procedures were followed. A task force of rheumatologists, health professionals and patients, representing 17 European countries updated the recommendations, based on a systematic literature review and expert consensus. Higher level of evidence and new insights into nursing care for patients with CIA were added to the recommendation. Level of agreement was obtained by email voting. The search identified 2609 records, of which 51 (41 papers, 10 abstracts), mostly on rheumatoid arthritis, were included. Based on consensus, the task force formulated three overarching principles and eight recommendations. One recommendation remained unchanged, six were reworded, two were merged and one was reformulated as an overarching principle. Two additional overarching principles were formulated. The overarching principles emphasise the nurse's role as part of a healthcare team, describe the importance of providing evidence-based care and endorse shared decision-making in the nursing consultation with the patient. The recommendations cover the contribution of rheumatology nursing in needs-based patient education, satisfaction with care, timely access to care, disease management, efficiency of care, psychosocial support and the promotion of self-management. The level of agreement among task force members was high (mean 9.7, range 9.6-10.0). The updated recommendations encompass three overarching principles and eight evidence-based and expert opinion-based recommendations for the role of the nurse in the management of CIA.
Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new ...atomistic model for the MDR-related ABCG2 efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of the ABCG5/G8 heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of the ABCG2 homodimer was obtained. The role of important residues and motifs in the structural stability of the transporter was comprehensively studied and was found to be in good agreement with the available experimental data published in literature. Moreover, structural motifs potentially involved in signal transmission were identified, along with two symmetrical drug-binding sites that are herein described for the first time, in a rational attempt to better understand how drug binding and recognition occurs in ABCG2 homodimeric transporters.
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