| 1. |
- Hudson, Thomas J., et al.
(author)
-
International network of cancer genome projects
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Journal article (peer-reviewed)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 2. |
- Andersson, Ulrika, et al.
(author)
-
Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
- 2014
-
In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 16:10, s. 1333-1340
-
Journal article (peer-reviewed)abstract
- Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.
|
|
| 3. |
- Bogdanska, Jasna, et al.
(author)
-
Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
- 2011
-
In: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 284:1-3, s. 54-62
-
Journal article (peer-reviewed)abstract
- The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.
|
|
| 4. |
- Bogdanska, Jasna, et al.
(author)
-
Tissue distribution of S-35-labelled perfluorobutanesulfonic acid in adult mice following dietary exposure for 1-5 days
- 2014
-
In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 98, s. 28-36
-
Journal article (peer-reviewed)abstract
- Perfluorobutanesulfonyl fluoride (PBSF) has been introduced as a replacement for its eight-carbon homolog perfluorooctanesulfonyl fluoride (POSF) in the manufacturing of fluorochemicals. Fluorochemicals derived from PBSF may give rise to perfluorobutanesulfonic acid (PFBS) as a terminal degradation product. Although basic mammalian toxicokinetic data exist for PFBS, information on its tissue distribution has only been reported in one study focused on rat liver. Therefore, here we characterized the tissue distribution of PFBS in mice in the same manner as we earlier examined its eight-carbon homolog perfluorooctanesulfonate (PFOS) to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1,3 or 5 d to 16 mg S-35-PFBS kg(-1) d(-1), both scintillation counting and whole-body autoradiography (WBA) revealed the presence of PFBS in all of the 20 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. After 5 d of treatment the highest levels were detected in liver, gastrointestinal tract, blood, kidney, cartilage, whole bone, lungs and thyroid gland. WBA revealed relatively high levels of PFBS in male genital organs as well, with the exception of the testis. The tissue levels increased from 1 to 3 d of exposure but appeared thereafter to level-off in most cases. The estimated major body compartments were whole bone, liver, blood, skin and muscle. This exposure to PFBS resulted in 5-40-fold lower tissue levels than did similar exposure to PFOS, as well as in a different pattern of tissue distribution, including lower levels in liver and lungs relative to blood.
|
|
| 5. |
- Bolton, Kelly L., et al.
(author)
-
Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
-
In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
-
Journal article (peer-reviewed)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
|
|
| 6. |
- Borg, Daniel, et al.
(author)
-
Environmental and Health Risk Assessment of Perfluoroalkylated and Polyfluoroalkylated Substances (PFASs) in Sweden
- 2012
-
Reports (other academic/artistic)abstract
- Denna rapport sammanfattar resultatet av ett projekt för att ta fram information och ny kunskap gällande möjliga miljö- och hälsorisker av perfluoralkylerade och polyfluoralkylerade ämnen (PFAS) i Sverige. Projektet har utförts i form av en riskbedömning, bestående av en exponeringsbedömning med svenska monitoringdata för 23 utvalda PFAS i människor, däggdjur, fågel och fisk,en farobedömning med toxikologiska data på däggdjur, fågel och fisk för deutvalda ämnena och en riskkaraktärisering för människa, däggdjur, fågel ochfisk. Detta är den första hälso- och miljöriskbedömningen som undersöker ett stort antal PFAS, individuellt och i kombination. I den hälsorelaterade exponeringsbedömningen valdes två populationer ut– människor exponerade indirekt via miljön (dvs. allmänbefolkningen) och enyrkesexponerad grupp – professionella skidvallare. Exponeringsdata i form avPFAS-halter i blod och serum användes. Resultatet visade att de undersökta PFAS-kongenerna förekom i serum i låga ppb-halter (ng/ml) i allmänbefolkningen. I en liten subpopulation av allmänbefolkningen som ätit kontaminerad fisk kunde högre ppb-halter av PFOS uppmätas. I den yrkesexponerade gruppen förekom avsevärt högre koncentrationer av vissa kongener, t exPFNA och PFOA som uppmätts i höga ppb- eller låga ppm- halter (μg/ml),ca 125 och 200 gånger högre än i den allmänna befolkningen. Tidstrendstudieri den allmänna befolkningen visade att halterna av PFOS, PFDS, PFOSA ochPFOA i serum förefaller minska, medan halterna av PFBS, PFHxS, PFNA,PFDA och PFUnDA istället förefaller öka. I den hälsorelaterade farobedömningen användes främst data och slutsatser från redan existerande faro- eller riskbedömningar, som kompletterades med nytillkomna eller andra relevanta data. Två toxikologiska endpoints somidentifierades som gemensamma för PFAS användes: 1) levertoxicitet, och 2)reproduktions/utvecklingstoxicitet. För kongener som saknade toxikologiska data eller interndoser gjordes en ”read-across”, dvs. extrapolering av data, tillden närmaste mest potenta kongenern för respektive endpoint. Andra toxikologiskaendpoints som uppvisade lägre effektnivåer än lever- eller reproduktionstoxicitet beaktades också. Resultatet av farobedömningen visade att deolika PFAS-kongenerna var relativt lika avseende deras potens för lever- ochreproduktionstoxicitet, med utgångspunkter (på engelska ”point-of-departure”)på 4–89 μg/ml serum respektive 4–> 60 μg/ml serum. Användbara toxikologiskadata med interndoser fanns tillgängliga för 4 av 15 kongener i allmänbefolkningen och 5 av 17 kongener för de yrkesexponerade. För några kongenerkunde ytterligare toxikologiska endpoints identifieras (immuntoxicitet, påverkanpå bröstkörtelutveckling, fetma) vid väldigt låga effektnivåer – vid eller undernuvarande exponeringsnivåer för allmänbefolkningen. Epidemiologiska studiervisade motstridiga resultat.Riskkaraktäriseringen visade inte på någon risk1 för lever- eller reproduktionstoxiciteti allmänbefolkningen, vare sig för enskilda kongener eller i kombination. I den subpopulation som ätit kontaminerad fisk kunde däremot enrisk för levertoxicitet påvisas baserat på uppmätta PFOS-halter. För de yrkesexponeradeskidvallarna kunde en risk för levertoxicitet identifieras, baserat på enskilda kongener och i kombination, samt för reproduktionstoxicitet baserat på den samlade PFAS-exponeringen. Det bör dock understrykas attdenna grupp omfattar ett mycket begränsat antal människor i Sverige.I den miljörelaterade exponeringsbedömningen valdes 5 arter/grupper utmed följande vävnadsmatriser: 1) säl (lever), 2) utter (lever), 3) fågel (ägg),4) marin fisk (lever) och 5) högexponerad sötvattensfisk (muskel), baserat påförekomsten av PFAS i dessa arter. Alla dessa finns i, eller är kopplade till, denakvatiska miljön och visar på hur PFAS sprids till miljön. I de terrestra artersom granskades var halterna av PFAS signifikant lägre. PFOS var den dominerande kongenern i alla arter och kunde uppmätas i låga ppm-nivåer eller högappb-nivåer i säl och utter, fågelägg och högexponerad sötvattensfisk, och i lågappb-nivåer i marin fisk. I säl och utter kunde en nedåtgående trend för halterav sulfonater och en ökande trend för halter av karboxylater urskiljas. I äggfrån pilgrimsfalk var alla uppmätta kongener långkedjiga och en tidstrendstudievisade att nivåer av sulfonater var oförändrade eller nedåtgående, och att karboxylater med en kedjelängd av 11–15 kol minskar, men att PFNA ochPFDA ökar. I marin fisk innehåll alla detekterade kongener sex eller fler kolför sulfonater, och nio eller fler kol för karboxylater, vilket troligen återspeglar den högre biokoncentrationsfaktorn (BCF) för långkedjiga kongener. PFAShalterna var betydligt högre i högexponerad sötvattensfisk än i marin fisk. I den miljörelaterade farobedömningen användes för säl och utter samma toxikologiska endpoints och utgångspunkter som i den hälsorelaterade farobedömningen,baserat på deras gemensamma toxikologiska dataunderlag, menmed skillnad i de specifika kongener som undersökts samt att halter i leveranvändes som interdos istället för serum. Användbara toxikologiska data medinterndoser i lever var tillgängliga för 4 av 17 kongener, varav data för övrigakongener behövde extrapoleras. För fågel togs enbart data från reproduktionstoxicitetsstudiermed interndoser uppmätta i ägg i beaktande, vilka fannstillgängliga för 5 av 15 kongener, varav de övriga behövde extrapoleras. Få relevanta studier på reproduktionstoxicitet av PFAS i fågel fanns tillgängliga, och i dessa kunde endast effekter påvisas för PFOS. Dataunderlaget på PFAS i fågel kan därför anses osäkert med avseende på toxiska effekter, effektnivåeroch de extrapoleringar som gjorts. För fisk så fanns data tillgängliga för 5 av17 kongener och toxiska effektnivåer och utgångspunkter bör betraktas som högst osäkra beroende på att olika typer av studier, arter, och endpoints har använts, vilket gör dem väldigt svåra att jämföra mellan olika kongener. Dessa extrapoleringar är därför högst osäkra.Resultatet av riskkaraktäriseringen för säl och utter visade på risk för levertoxicitetoch reproduktionstoxicitet för enskilda kongener och/eller i kombination.Det bör poängteras att slutsatser gällande säl och utter är baserade pågenomsnittsnivåer av PFAS vid den sista tidpunkten i tidstrendstudier, och att nivåerna kan vara högre på individnivå, vilket skulle resultera i lägre säkerhetsmarginaler.För reproduktionstoxicitet i fågel kunde en risk påvisas, där de högsta halterna i pilgrimsfalksägg (provtagna 2006) översteg de halter iägg där en studie visat toxiska effekter, och där den genomsnittliga halten varnära de toxiska effektnivåerna. Det kan därför inte uteslutas att halterna av PFOS i dessa ägg kan ge upphov skadliga effekter. För marin och högexponerad sötvattensfisk indikerar tillgängliga data ingen risk för skadliga effekter. Det bör dock tydliggöras att data för fisk, monitoring såväl som toxicitetsdata och dess extrapoleringar är förknippade med en hög grad av osäkerhet p.g.a.brister i dataunderlaget.
|
|
| 7. |
- Borg, Daniel
(author)
-
Tissue distribution studies and risk assessment of perfluoroalkylated and polyfluoroalkylated substances (PFASs)
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Perfluoroalkylated and polyfluoroalkylated substances (PFASs) represent a large class of man-made chemicals. These substances have emerged as environmental contaminants due to their extraordinary resistance to degradation, potential for bioaccumulation, toxicity and a global presence in humans, wildlife and the environment. In the Swedish population 17 PFASs have so far been analyzed in blood. In animal studies, PFASs cause liver toxicity and reproductive/developmental toxicity as well as a range of other toxic effects. Detailed data on the tissue distribution of PFASs, which could contribute to better understanding of their toxicity, are limited. Also, health risk assessment information has been lacking for all PFASs except the most studied, perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). The aims of this thesis were to 1) generate detailed tissue distribution data on PFOS in perinatal and adult mice and on its replacement chemical perfluorobutane sulfonate (PFBS) in adult mice; and 2) and assess potential risks to human health associated with exposure to the 17 PFASs analyzed in the general Swedish population and occupationally exposed ski waxers, for all PFASs individually and in combination. The results of the experiments showed that following exposure of pregnant dams PFOS was readily transferred to mouse fetuses resulting in tissue levels similar to or higher than maternal blood levels. PFOS was markedly distributed to the perinatal and maternal lungs; showing the highest levels of the tissues analyzed in fetuses/pups on gestational day 20 and postnatal day 1. This finding may help to explain the respiratory distress seen in neonatal and adult rodents following exposure to PFOS. Further, in adult male mice after short-term dietary exposure to one environmentally relevant low dose and one experimentally relevant high dose, PFOS was recovered in all 19 examined tissues, with similar tissue distribution profiles at both doses, though with a higher tissue:blood ratio at the higher dose. The highest concentrations of PFOS were found in liver, lungs, blood, kidneys and whole bone and the major body compartments were liver, bone, blood, skin and muscle. Blood hemoglobin levels were markedly increased at the high dose which could be connected to the localization of PFOS in bone marrow. In a similar experiment PFBS was recovered in all 20 examined tissues in adult male mice after short-term dietary exposure to the same molar concentration as the high dose of PFOS. The distribution and compartment profiles were similar to those of PFOS with the exception of a remarkably high concentration in cartilage. Also, PFBS displayed significantly lower tissue concentrations and tissue: blood ratios than PFOS and a less marked erythropoietic effect. The risk assessment of PFASs showed that hepatotoxicity and reproductive/ developmental toxicity may be of concern for high local exposure and occupational exposure but indicated no risk for the general population. Concern for the less studied endpoints immunotoxicity and altered mammary gland development was identified for the general population and the occupationally exposed. A need of additional toxicological data for all investigated toxicological endpoints was recognized. Altogether, the work included in this thesis has generated experimental data that can be used to improve risk assessment of PFASs. It has also assessed the risks associated with current exposures to PFASs in Sweden and identified data needs.
|
|
| 8. |
- Breitholtz, Magnus, et al.
(author)
-
An evaluation of free water surface wetlands as tertiary sewage water treatment of micro-pollutants
- 2012
-
In: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 78, s. 63-71
-
Journal article (peer-reviewed)abstract
- Increased attention is currently directed towards potential negative effects of pharmaceuticals and other micro-pollutants discharged into the aquatic environment via municipal sewage water. A number of additional treatment technologies, such as ozonation, have therefore been suggested as promising tools for improving the removal efficiency of pharmaceuticals in existing Sewage Treatment Plants (STPs). Constructed wetlands are also capable of removing a variety of micro-pollutants, including some pharmaceuticals, and could hence be a resource efficient complement to more advanced treatment technologies. The purpose of the present study was therefore to increase the knowledge base concerning the potential use of constructed wetlands as a treatment step to reduce emissions of organic micro-pollutants from municipal sewage effluents. Under cold winter conditions, incoming and outgoing waters from four Swedish free water surface wetlands, operated as final treatment steps of sewage effluent from municipal STPs, were sampled and analyzed for levels of a set of 92 pharmaceuticals and 22 inorganic components as well as assessed using subchronic ecotoxicity tests with a macro-alga and a crustacean. Sixty-five pharmaceuticals were detected in the range from 1 ng L-1 to 7.6 mu g L-1 in incoming and outgoing waters from the four investigated wetlands. Although the sampling design used in the present study lacks the robustness of volume proportional to 24 h composite samples, the average estimated removal rates ranged from 42% to 52%, which correlates to previous published values. The effects observed in the ecotoxicity tests with the macro-alga (EC(50)s in the range of 7.5-46%) and the crustacean (LOECs in the range of 11.25-90%) could not be assigned to either pharmaceutical residues or metals, but in general showed that these treatment facilities release water with a relatively low toxic potential, comparable to water that has been treated with advanced tertiary treatments. From the present study it can be concluded that constructed wetlands may provide a complementary sewage treatment option, especially where other treatment is lacking today. To fully remove micro-pollutants from sewage effluent, however, other more advanced treatment technologies are likely needed.
|
|
| 9. |
- Goodwin, Richard J. A., et al.
(author)
-
Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation
- 2012
-
In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 75:16, s. 4912-4920
-
Journal article (peer-reviewed)abstract
- Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis.This article is part of a Special Issue entitled: Imaging Mass Spectrometry: A User's Guide to a New Technique for Biological and Biomedical Research.
|
|
| 10. |
- Martrat, Griselda, et al.
(author)
-
Exploring the link between MORF4L1 and risk of breast cancer
- 2011
-
In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
-
Journal article (peer-reviewed)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
|
|
| 11. |
- McDade, Lucinda A., et al.
(author)
-
Phylogenetic placement, delimitation, and relationships among genera of the enigmatic Nelsonioideae (Lamiales: Acanthaceae)
- 2012
-
In: Taxon. - : Wiley. - 0040-0262 .- 1996-8175. ; 61:3, s. 637-651
-
Journal article (peer-reviewed)abstract
- We took a two-tiered approach to test monophyly of Nelsonioideae and place the group within Lamiales, and to determine relationships among taxa within the group. Phylogenetic analysis of a molecular dataset (ndhF+trnL-F) for a broad sample of Lamiales supports monophyly of Nelsonioideae and places the clade with strong support as sister to a lineage composed of all other plants treated as Acanthaceae (Avicennia, Thunbergioideae, Acanthoideae). We propose to treat this entire group as Acanthaceae s.l. and hypothesize that indurate, explosively dehiscent capsules are a synapomorphy for the family, albeit with autapomorphic fruit types in Avicennia and Mendoncia. These results further support monophyly of family-level groups that have emerged from recent studies of Lamiales but are largely unsuccessful in resolving relationships among these groups, as also encountered by other workers. Our results contradict some aspects of relationships that have seemed resolved by earlier studies, notably among Byblidaceae, Scrophulariaceae, Thomandersia, and other Lamiales. Among Nelsonioideae, analysis of sequence data from rapidly evolving genic regions (trnS-G, ndhF-rpl32+rpl32-trnL((UAG)), nrITS) and a larger sample of nelsonioids (i.e., all genera and multiple taxa to represent the diversity of species-rich genera) indicates that Nelsonia and Elytraria are monophyletic with strong support, but with only moderate support for Nelsonia as the first branching clade and Elytraria sister to the remaining nelsonioids. An African clade comprising monospecific Saintpauliopsis sister to Anisosepalum (two of three species sampled) is sister to a clade that includes all sampled members of pantropical Staurogyne plus New World Gynocraterium and Asian Ophiorrhiziphyllon. Gynocraterium is sister to all sampled members of New World Staurogyne; this last clade is sister to a clade comprising the other sampled Staurogyne plus Ophiorrhiziphyllon, which is nested among Asian Staurogyne. The taxonomic implications of these patterns of relationship are discussed. Our results suggest that Nelsonioideae have a complex history of inter-continental dispersals compared to other lineages of Acanthaceae of similar to much larger size in terms of number of species, making it an interesting group for biogeographic study.
|
|
| 12. |
- Nik-Zainal, Serena, et al.
(author)
-
Mutational Processes Molding the Genomes of 21 Breast Cancers
- 2012
-
In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5, s. 979-993
-
Journal article (peer-reviewed)abstract
- All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
|
|
| 13. |
- Wu, Jun, et al.
(author)
-
Control of composition and morphology in InGaAs nanowires grown by metalorganic vapor phase epitaxy
- 2013
-
In: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248. ; 383, s. 158-165
-
Journal article (peer-reviewed)abstract
- InGaAs nanowires grown by Metalorganic Vapor Phase Epitaxy (MOVPE) are promising candidates in future device technologies. The control of the chemical composition of InGaAs nanowires is not trivial due to the In atom diffusion from the substrate, which causes significant variations in the chemical composition along the nanowire. In this work, we report on the growth of InGaAs nanowires on (111)B InAs substrates followed by the characterization using high-resolution x-ray diffraction (HRXRD), scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM) as well as scanning transmission electron microscopy (STEM) in combination with energy dispersive X-ray spectroscopy (EDS). By detailed analyses of the HRXRD spectra and their variations with nanowires grown for different times, fundamental insight was gained into tapering formation and chemical composition gradient of the nanowires. The measurements show that acceptable uniformity of In and Ga concentrations along InGaAs nanowires can be achieved, and the maximum achievable nanowire length without tapering depends on the nanowire density. Finally, by carefully choosing the growth conditions, the morphology of the InGaAs nanowire can be further optimized. (C) 2 013 Elsevier B.V. All rights reserved
|
|
