1. |
- Kirchhoff, Tomas, et al.
(author)
-
Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
-
In: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
-
Journal article (peer-reviewed)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
|
|
2. |
- Stevens, Kristen N, et al.
(author)
-
19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
-
Journal article (peer-reviewed)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
|
|
3. |
- Barata-Morgado, Rute, et al.
(author)
-
Theoretical study of the conformational equilibrium of 1,4-dioxane in gas phase, neat liquid, and dilute aqueous solutions
- 2013
-
In: Theoretical Chemistry accounts. - : Springer Science and Business Media LLC. - 1432-881X .- 1432-2234. ; 132:10, s. 1390-
-
Journal article (peer-reviewed)abstract
- The conformational equilibrium of 1,4-dioxane in the gas phase, in the pure liquid, and in aqueous solution has been studied by means of the Average Solvent Electrostatic Potential from Molecular Dynamics (ASEP/MD) method and the Integral Equation Formalism for the Polarizable Continuum Model (IEF-PCM). The dioxane molecule was described at the DFT(B3LYP)/aug-cc-pVTZ level. In the three phases, the equilibrium is almost completely shifted toward the chair conformer, with populations of the twist-boat conformers lower than 0.01 %. The equilibrium is dominated by the internal energy of the molecule, as the solute-solvent interaction free energies are very similar in the three conformers considered (chair, 1,4 twist-boat, and 2,5 twist-boat). In the pure liquid, where the dioxane-dioxane interaction is dominated by the Lennard-Jones term, the structure is characteristic of a van der Waals liquid. However, the decrease in the C-H distance from gas phase to solution, the increase in the C-H vibrational frequencies, and the presence of a shoulder in the O-Haxial pair radial distribution function point to the presence of a weak C-H-O hydrogen bond. The analysis of the occupancy maps of water oxygen and hydrogen atoms around the 1,4-dioxane molecule confirms this conclusion. Contrary to what is found in small water-dioxane clusters, in the liquid, there is a preference for oxygen atoms to interact with axial hydrogen atoms to form C-H-O hydrogen bonds. Comparison of ASEP/MD and IEF-PCM results indicates that including specific interactions is very important for an adequate description of the solute-solvent interaction; however, the influence of these interactions does not translate in changes in the relative stability of the conformers because it cancels out when energy differences are calculated.
|
|
4. |
- Corchado, José C., et al.
(author)
-
Theoretical Study of Solvent Effects on the Ground and Low-Lying Excited Free Energy Surfaces of a Push–Pull Substituted Azobenzene
- 2014
-
In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 118:43, s. 12518-12530
-
Journal article (peer-reviewed)abstract
- The ground and low-lying excited free energy surfaces of 4-amino-4'-cyano azobenzene, a molecule that has been proposed as building block for chiroptical switches, are studied in gas phase and a variety of solvents (benzene, chloroform, acetone, and water). Solvent effects on the absorption and emission spectra and on the cistrans thermal and photo isomerizations are analyzed using two levels of calculation: TD-DFT and CASPT2/CASSCF. The solvent effects are introduced using a polarizable continuum model and a QM/MM method, which permits one to highlight the role played by specific interactions. We found that, in gas phase and in agreement with the results found for other azobenzenes, the thermal cistrans isomerization follows a rotation-assisted inversion mechanism where the inversion angle must reach values close to 180 degrees but where the rotation angle can take almost any value. On the contrary, in polar solvents the mechanism is controlled by the rotation of the CN=NC angle. The change in the mechanism is mainly related to a better solvation of the nitrogen atoms of the azo group in the rotational transition state. The photoisomerization follows a rotational pathway both in gas phase and in polar and nonpolar solvents. The solvent introduces only small modifications in the n pi* free energy surface (S-1), but it has a larger effect on the pi pi* surface (S-2) that, in polar solvents, gets closer to S-1. In fact, the S-2 band of the absorption spectrum is red-shifted 0.27 eV for the trans isomer and 0.17 eV for the cis. In the emission spectrum the trend is similar: only S-2 is appreciably affected by the solvent, but in this case a blue shift is found.
|
|
5. |
- Lisa Pinardi, Anna, et al.
(author)
-
Tailored Formation of N-Doped Nanoarchitectures by Diffusion-Controlled on-Surface (Cyclo)-Dehydrogenation of Heteroaromatics
- 2013
-
In: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 7:4, s. 3676-3684
-
Journal article (peer-reviewed)abstract
- Surface-assisted cyclodehydrogenation and dehydrogenative polymerization of polycyclic (hetero)aromatic hydrocarbons (PAH) are among the most important strategies for bottom-up assembly of new nanostructures from their molecular building blocks. Although diverse compounds have been formed in recent years using this methodology, a limited knowledge on the molecular machinery operating at the nanoscale has prevented a rational control of the reaction outcome. We show that the strength of the PAH-substrate interaction rules the competitive reaction pathways (cyclodehydrogenation versus dehydrogenative polymerization). By controlling the diffusion of N-heteroaromatic precursors, the on-surface dehydrogenation can lead to monomolecular triazafullerenes and diazahexabenzocoronenes (N-doped nanographene), to N-doped oligomeric or polymeric networks, or to carbonaceous monolayers. Governing the on-surface dehydrogenation process is a step forward toward the tailored fabrication of molecular 2D nanoarchitectures distinct from graphene and exhibiting new properties of fundamental and technological interest.
|
|
6. |
- Rinaldi, Sabina, et al.
(author)
-
Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies
- 2010
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:7, s. 1702-1715
-
Journal article (peer-reviewed)abstract
- Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.
|
|
7. |
|
|
8. |
- Schulte, Peter, et al.
(author)
-
The Chicxulub Asteroid Impact and Mass Extinction at the Cretaceous-Paleogene Boundary
- 2010
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 327:5970, s. 1214-1218
-
Journal article (peer-reviewed)abstract
- The Cretaceous-Paleogene boundary similar to 65.5 million years ago marks one of the three largest mass extinctions in the past 500 million years. The extinction event coincided with a large asteroid impact at Chicxulub, Mexico, and occurred within the time of Deccan flood basalt volcanism in India. Here, we synthesize records of the global stratigraphy across this boundary to assess the proposed causes of the mass extinction. Notably, a single ejecta-rich deposit compositionally linked to the Chicxulub impact is globally distributed at the Cretaceous-Paleogene boundary. The temporal match between the ejecta layer and the onset of the extinctions and the agreement of ecological patterns in the fossil record with modeled environmental perturbations (for example, darkness and cooling) lead us to conclude that the Chicxulub impact triggered the mass extinction.
|
|
9. |
- Goicoechea, Noemi, et al.
(author)
-
Recovering phylogenetic signal from frog mating calls
- 2010
-
In: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 39:2, s. 141-154
-
Journal article (peer-reviewed)abstract
- Few studies have tried to analyse the phylogenetic information contained in frog mating calls. While some of those studies suggest that sexual selection deletes any phylogenetic signal, others indicate that frog calls do retain phylogenetic informative characters. Discordant results can be the outcome of disparate rates of character evolution and evolutionary plasticity of call characters in different groups of frogs, but also the result of applying different coding methods. No study to date has compared the relative performance of different coding methods in detecting phylogenetic signal in calls, hampering thus potential consilience between previous results. In this study, we analyse the strength of phylogenetic signal in 10 mating call characters of 11 related species of frogs belonging to three genera of Andean and Amazonian frogs (Anura: Terrarana: Strabomantidae). We use six quantitative characters (number of notes per call, note length, call length, number of pulses per note, fundamental frequency and dominant frequency) and four qualitative ones (presence/absence of: pseudopulses, frequency modulation in notes, amplitude modulation in notes and amplitude modulation in pulses). We code quantitative characters using four different coding and scaling methods: (i) gap-coding, (ii) fixed-scale, (iii) step-matrix gap-weighting with between-characters scaling, and (iv) step-matrix gap-weighting with between-states scaling. All four coding methods indicate that frog calls contain phylogenetic information. These results suggest that divergent selection on frog mating calls may not always be strong enough to eliminate phylogenetic signal. However, coding methods strongly affect the amount of recoverable information. Step-matrix gap-weighting with between-characters scaling and gap-coding are suggested as the best methods available for coding quantitative characters of frog calls. Also, our results indicate that the arbitrariness in selecting character states and the method for scaling transitions weights, rather than the number of character states, is what potentially biases phylogenetic analyses with quantitative characters.
|
|
10. |
- Koehler, Joern, et al.
(author)
-
Systematics of Andean gladiator frogs of the Hypsiboas pulchellus species group (Anura, Hylidae)
- 2010
-
In: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 39:6, s. 572-590
-
Journal article (peer-reviewed)abstract
- We revisit the taxonomic status of Andean species and populations of frogs of the Hypsiboas pulchellus group using multiple lines of evidence potentially indicative of evolutionary lineage divergence in anurans: differences in qualitative morphological or bioacoustic character states, no overlap in quantitative characters of advertisement calls, and monophyly of gene genealogies. We found qualitative and quantitative morphological characters to be extremely variable among species and populations of the group and thus of very limited use in assessing lineage divergence. In contrast, phylogenetic analyses based on 16S rRNA and cytochrome b sequences resolved highly supported clades that are in concordance with bioacoustic differences. The results support the specific distinctness of most nominal species recognized in the group, including the Bolivian Hypsiboas balzani and Hypsiboas callipleura, two species that were considered to be synonymous, and revealed the presence of an undescribed species from southern Peru, which is here described as Hypsiboas gladiator sp. n. In contrast, Hypsiboas andinus and Hypsiboas riojanus were mutually paraphyletic, and showed no differences in morphology and acoustic characters. Consequently, we regard the former as a junior synonym of the latter. However, we discovered that populations of H. riojanus from central Bolivia exhibit some degree of genetic differentiation and advertisement call differences with respect to Argentine populations, but sampling of these Bolivian populations is too sparse to draw taxonomic conclusions. Our phylogenetic results support the hypothesis that ancestral lineages of the Andean H. pulchellus group experienced successive splitting events along a latitudinal gradient from north to south.
|
|
11. |
- Kvist, Laura, et al.
(author)
-
Endangered subspecies of the Reed Bunting (Emberiza schoeniclus witherbyi and E. s. lusitanica) in Iberian Peninsula have different genetic structures.
- 2011
-
In: Journal of Ornithology. - : Springer Science and Business Media LLC. - 2193-7192 .- 2193-7206. ; 152:3, s. 681-693
-
Journal article (peer-reviewed)abstract
- In the Iberian Peninsula, populations of two subspecies of the Reed Bunting Emberiza schoeniclus have become increasingly fragmented during the last decades when suitable habitats have been lost and/or the popula- tions have gone extinct. Presently, both subspecies are endangered. We estimated the amount of genetic variation and population structure in order to define conservation units and management practices for these populations. We found that the subspecies lusitanica has clearly reduced genetic variation in nuclear and mitochondrial markers, has a drastically small effective population size and no genetic differentiation between populations. In contrast, the sub- species witherbyi is significantly structured, but the popu- lations still hold large amounts of variation even though the effective population sizes are smaller than in the non- endangered subspecies schoeniclus. We suggest several management units for the Iberian populations. One unit includes subspecies lusitanica as a whole; the other three units are based on genetically differentiated populations of witherbyi. The most important genetic conservation mea- sure in the case of lusitanica is to preserve the remaining habitats in order to at least maintain the present levels of gene flow. In the case of the three management units within witherbyi, the most urgent conservation measure is to improve the habitat quality to increase the population sizes.
|
|
12. |
- Padial, José M., et al.
(author)
-
A response to recent proposals for integrative taxonomy
- 2010
-
In: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 101:3, s. 747-756
-
Journal article (peer-reviewed)abstract
- Several proposals have been launched under the new concept 'integrative taxonomy' to frame the future development of species discovery and description. We consider that some of those proposals have failed to be truly integrative, by not acknowledging the limitations of operational definitions of species, by defending some kinds of evidence as universally superior, by considering taxonomy to be irreconcilable with population genetics, or by ignoring that the heterogeneity of evolutionary processes often precludes full character congruence in species. Here we defend a taxonomy where species exist, but not in any particular way everyone might want them to exist; a taxonomy open to data and methods from population biology, phylogeography and phylogenetics, as well as any other discipline providing evidence about the origin and evolution of species. This new taxonomy embraces all the consequences of considering species as lineages of reproductive populations, encouraging the use of as many lines of evidence as possible, but without negating that a single line may also be the only one providing evidence for a particular species. Species cannot only be those reproductive populations showing broad character congruence and/or reproductive isolation, due to the different degrees of character congruence, as well as of reproductive isolation, that result from the heterogeneity of evolutionary processes causing lineage splitting and divergence. Also, any kind of character - and not only those established by tradition or fashion - is potentially relevant as evidence of lineage divergence. To conciliate the authors who only see species supported by broad character congruence as good species hypotheses, we explain how a hypothesis can gain corroboration using single or multiple lines of evidence, even in cases of discordance with other lines of evidence. Finally, we propose guidelines to identify the expected degree of stability (preliminary, unstable, and stable) of species hypotheses. (C) 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 747-756.
|
|
13. |
- Padial, José M., et al.
(author)
-
The integrative future of taxonomy
- 2010
-
In: Frontiers in Zoology. - : Springer Science and Business Media LLC. - 1742-9994. ; 7, s. 16-
-
Research review (peer-reviewed)abstract
- Background: Taxonomy is the biological discipline that identifies, describes, classifies and names extant and extinct species and other taxa. Nowadays, species taxonomy is confronted with the challenge to fully incorporate new theory, methods and data from disciplines that study the origin, limits and evolution of species. Results: Integrative taxonomy has been proposed as a framework to bring together these conceptual and methodological developments. Here we review perspectives for an integrative taxonomy that directly bear on what species are, how they can be discovered, and how much diversity is on Earth. Conclusions: We conclude that taxonomy needs to be pluralistic to improve species discovery and description, and to develop novel protocols to produce the much-needed inventory of life in a reasonable time. To cope with the large number of candidate species revealed by molecular studies of eukaryotes, we propose a classification scheme for those units that will facilitate the subsequent assembly of data sets for the formal description of new species under the Linnaean system, and will ultimately integrate the activities of taxonomists and molecular biologists.
|
|
14. |
- Prasetyo, Endry Nugroho, et al.
(author)
-
Polymerization of lignosulfonates by the laccase-HBT (1-hydroxybenzotriazole) system improves dispersibility
- 2010
-
In: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 101:14, s. 5054-5062
-
Journal article (peer-reviewed)abstract
- The ability of laccases from Trametes villosa (TvL), Myceliophthora thermophila (MtL), Trametes hirsuta (ThL) and Bacillus subtilis (BsL) to improve the dispersion properties of calcium lignosulfonates 398 in the presence of HBT as a mediator was investigated. Size exclusion chromatography showed an extensive increase in molecular weight of the samples incubated with TvL and ThL by 107% and 572% from 28400 Da after 17 h of incubation, respectively. Interestingly, FTIR spectroscopy. C-13 NMR and Py-GC/MS analysis of the treated samples suggested no substantial changes in the aromatic signal of the lignosulfonates, a good indication of the ability of TvL/ThL-HBT systems to limit their effect on functional groups without degrading the lignin backbone. Further, the enzymatic treatments led to a general increase in the dispersion properties, indeed a welcome development for its application in polymer blends. (C) 2010 Elsevier Ltd. All rights reserved.
|
|
15. |
- Yilmaz, Mehmet B., et al.
(author)
-
Renal Effects of Levosimendan : A Consensus Report
- 2013
-
In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 27:6, s. 581-590
-
Research review (peer-reviewed)abstract
- Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K-ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).
|
|