Genomics of Divergence along a Continuum of Parapatric Population Differentiation

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1)

HFE variants and the expression of iron-related proteins in breast cancer-associated lymphocytes and macrophages

Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264664/The association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients’ HFE genotype. Within the group of patients with invasive carcinoma, those carrying the p.Cys282Tyr variant in heterozygosity presented a higher expression of hepcidin in lymphocytes and macrophages than wild-type or p.His63Asp carriers. An increased expression of TfR1 was also observed in all the cell types analyzed but only in p.Cys282Tyr/p.His63Asp compound heterozygous patients. A differential impact of the two HFE variants was further noticed with the observation of a significantly higher percentage of p.Cys282Tyr heterozygous patients presenting tissue iron deposition in comparison to p.His63Asp heterozygous. In the present cohort, no significant associations were found between HFE variants and classical clinicopathological markers of breast cancer behavior and prognosis. Although limited by a low sampling size, our results provide a new possible explanation for the previously reported impact of HFE major variants on breast cancer progression, i.e., not by influencing systemic iron homeostasis but rather by differentially modulating the local cellular expression of iron-related proteins and tissue iron deposition.OM is a recipient of the PhD grant SFRH/BD/2011/78184 from Fundação para a Ciência e Tecnologia (FCT). The authors also acknowledge financial support from ICBAS/AI&NSUMIB and by national funds through FCT and Ministério da Educação e Ciência (MEC) and when applicable co-funded by FEDER funds within the partnership agreement PT2020 related with the research unit number 4293.info:eu-repo/semantics/publishedVersio

XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox) gene

BACKGROUND: X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. METHODS: Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. RESULTS: A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families – MRX29, MRX32, MRX33 and MRX38 – were found to have this particular gene mutation. CONCLUSION: We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

The use of quality information by general practitioners: does it alter choices? A randomized clustered study

Background: Following the introduction of elements of managed competition in the Netherlands in 2006, General Practitioners (GPs) and patients were given the role to select treatment hospital using public quality information. In this study we investigate to what extent hospital preferences of GP's are affected by performance indicators on medical effectiveness and patient experiences. We selected three conditions: breast cancer, cataract surgery, and hip and knee replacement. Methods. After an inquiry 26 out of 226 GPs in the region signed up to participate in our study. After a 2:1 randomization, we analyzed the referral patterns in the region using three groups of GPs: GPs (n=17) who used the report cards and received personal clarification, GPs that signed up for the study but were assigned to the control group (n=9), and the GPs outside the study (n=200).We conducted a difference in differences analysis where the choice for a particular hospital was the dependent variable and time (2009 or 2010), the sum score of the CQI, the sum score of the PI's and dummy variables for the individual hospitals were used as independent variables. Results: The analysis of the conditions together and cataract surgery and hip and knee replacement separately, showed no significant relationships between the scores on the report cards and the referral patterns of the GPs. For breast cancer our analysis revealed that GPs in the intervention group refer 1.0% (p=0.01) more to hospitals that score one percent point better on the indicators for medical effectiveness. Conclusion: Our study provides empirical evidence that GP referral patterns were unaffected by the available quality information, except for the outcome indicators for breast cancer care that were presented. This finding was surprising since our study was designed to identify changes in hospital preference (1) amongst the most motivated GP's, (2) that received personal clarification of the performance indicators, and (3) selected indicators/conditions from a large set of indicators that they believed were most important. This finding may differ when quality information is based on outcome indicators with a clinically relevant difference, as shown by our indicators for breast cancer treatment. We believe that the current set of (largely process) hospital quality indicators do not serve the GP's information needs and consequently quality plays little role in the selection of hospitals for treatment. © 2013 Ikkersheim and Koolman; licensee BioMed Central Ltd

Speciation Along Environmental Gradients

Traditional discussions of speciation are based on geographical patterns of species ranges. In allopatric speciation, long-term geographical isolation generates reproductively isolated and spatially segregated descendant species. In the absence of geographical barriers, diversification is hindered by gene flow. Yet a growing body of phylogenetic and experimental data suggests that closely related species often occur in sympatry or have adjacent ranges in regions over which environmental changes are gradual and do not prevent gene flow. Theory has identified a variety of evolutionary processes that can result in speciation under sympatric conditions, with some recent advances concentrating on the phenomenon of evolutionary branching. Here we establish a link between geographical patterns and ecological processes of speciation by studying evolutionary branching in spatially structured populations. We show that along an environmental gradient, evolutionary branching can occur much more easily than in non-spatial models. This facilitation is most pronounced for gradients of intermediate slope. Moreover, spatial evolutionary branching readily generates patterns of spatial segregation and abutment between the emerging species. Our results highlight the importance of local processes of adaptive divergence for geographical patterns of speciation, and caution against pitfalls of inferring past speciation processes from present biogeographical patterns

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Self-administered questionnaire versus interview as a screening method for intimate partner violence in the prenatal setting in Japan: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) is a serious social issue in Japan. In order to start effective interventions for abused women, the appropriate method of screening for IPV in healthcare settings needs clarifying. The objective of this study was to compare the effectiveness of a face-to-face interview with a self-administered questionnaire. We used the Violence Against Women Screen (VAWS), a Japanese screening instrument for intimate partner violence (IPV), for identifying pregnant women who have experienced abuse.</p> <p>Methods</p> <p>We conducted a randomised controlled trial to screen participants at three points in time in a prenatal clinic in Tokyo, Japan. There were 328 consenting women between 14 and 25 weeks of pregnancy who were consecutively selected and randomly assigned to either the interview or self-administered questionnaire group. Both groups completed the same screening instrument three times during their pregnancy. The primary outcome was the total number of women identified by each screening method and the secondary outcome was the effect of the screening as measured by the women's comfort level and their expressed need to consult with the nurse.</p> <p>Results</p> <p>For all three screenings, the identification rate in the interview group was significantly lower than that for the self-administered questionnaire group (relative risk 0.66, 95% CI 0.46 to 0.97), even after controlling for smoking (adjusted odds ratio 0.59, 95% CI 0.35 to 0.98). The two groups did not differ for secondary outcomes.</p> <p>Conclusions</p> <p>The self-administered questionnaire identified more IPV than the face-to-face interview when screening pregnant women in a Japanese prenatal clinic.</p> <p>Trial Registration</p> <p>UMIN-CTRC000000353</p