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  • 1
    Keywords: RISK ; MICE ; SUSCEPTIBILITY ; chemotherapy ; GEMCITABINE ; DUCTAL ADENOCARCINOMA ; GENE POLYMORPHISMS ; LUNG-CANCER PATIENTS ; MYOTUBULARIN-RELATED PROTEIN-2 ; SBF2
    Abstract: Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
    Type of Publication: Journal article published
    PubMed ID: 23180869
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  • 2
    Abstract: Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values 〈6 x 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 x 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP x MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.
    Type of Publication: Journal article published
    PubMed ID: 23423446
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  • 3
    Publication Date: 2012-03-01
    Description: The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292678/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292678/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Jennifer F -- Skaletsky, Helen -- Brown, Laura G -- Pyntikova, Tatyana -- Graves, Tina -- Fulton, Robert S -- Dugan, Shannon -- Ding, Yan -- Buhay, Christian J -- Kremitzki, Colin -- Wang, Qiaoyan -- Shen, Hua -- Holder, Michael -- Villasana, Donna -- Nazareth, Lynne V -- Cree, Andrew -- Courtney, Laura -- Veizer, Joelle -- Kotkiewicz, Holland -- Cho, Ting-Jan -- Koutseva, Natalia -- Rozen, Steve -- Muzny, Donna M -- Warren, Wesley C -- Gibbs, Richard A -- Wilson, Richard K -- Page, David C -- R01 HG000257/HG/NHGRI NIH HHS/ -- R01 HG000257-17/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 22;483(7387):82-6. doi: 10.1038/nature10843.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. jhughes@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22367542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Human, Y/*genetics ; Conserved Sequence/*genetics ; Crossing Over, Genetic/genetics ; *Evolution, Molecular ; Gene Amplification/genetics ; *Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Macaca mulatta/*genetics ; Male ; Models, Genetic ; Molecular Sequence Data ; Pan troglodytes/genetics ; Radiation Hybrid Mapping ; Selection, Genetic/genetics ; Time Factors ; Y Chromosome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2014 Mar 27;507(7493):407-8. doi: 10.1038/507407a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670737" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*legislation & jurisprudence ; Cannabidiol/analysis ; Cannabinol/analysis ; Cannabis/chemistry/classification/growth & development ; Child ; Colorado/epidemiology ; Data Collection/trends ; Dronabinol/analysis ; *Federal Government ; Female ; Humans ; Marijuana Smoking/economics/epidemiology/legislation & jurisprudence/psychology ; National Institute on Drug Abuse (U.S.) ; Pregnancy ; United States ; Washington/epidemiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Nature Publishing Group (NPG)
    Publication Date: 2015-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2015 Jun 25;522(7557):410-2. doi: 10.1038/522410a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26108835" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/physiology ; Autistic Disorder/drug therapy/metabolism ; Brain/drug effects/physiology ; Clinical Trials as Topic ; Female ; Labor Onset/drug effects ; Lactation/drug effects ; Maternal Behavior/drug effects ; Mice ; Oxytocin/pharmacology/*physiology/therapeutic use ; Pregnancy ; *Social Behavior
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2016 Feb 4;530(7588):24-6. doi: 10.1038/530024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842040" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomimetic Materials ; Biomimetics/*instrumentation/*methods/trends ; *Hardness ; Movement/physiology ; Octopodiformes/anatomy & histology/physiology ; Pliability ; Printing, Three-Dimensional ; Robotics/*instrumentation/methods/*trends
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2016 Apr 7;532(7597):135-6. doi: 10.1038/532135a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078570" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Automation/instrumentation/*methods ; Brain/*cytology/*physiology ; Imaging, Three-Dimensional ; Neurons/*physiology ; Patch-Clamp Techniques/*instrumentation/*methods ; Research Personnel ; Robotics/instrumentation/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2016 Mar 3;531(7592):129-31.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26942239" target="_blank"〉PubMed〈/a〉
    Keywords: Awards and Prizes ; Career Mobility ; Child ; Child Care/economics/supply & distribution ; Congresses as Topic/economics ; Divorce ; Fellowships and Scholarships/economics ; Female ; Financing, Organized/economics ; Humans ; *Laboratories ; Male ; Parental Leave ; Parenting/psychology ; *Research Personnel/economics/psychology ; *Single Parent/psychology ; *Social Support ; Travel/economics ; Work Schedule Tolerance/psychology ; *Workplace
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2011-12-24
    Description: A passive optical diode effect would be useful for on-chip optical information processing but has been difficult to achieve. Using a method based on optical nonlinearity, we demonstrate a forward-backward transmission ratio of up to 28 decibels within telecommunication wavelengths. Our device, which uses two silicon rings 5 micrometers in radius, is passive yet maintains optical nonreciprocity for a broad range of input power levels, and it performs equally well even if the backward input power is higher than the forward input. The silicon optical diode is ultracompact and is compatible with current complementary metal-oxide semiconductor processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fan, Li -- Wang, Jian -- Varghese, Leo T -- Shen, Hao -- Niu, Ben -- Xuan, Yi -- Weiner, Andrew M -- Qi, Minghao -- 1R01RR026273-01/RR/NCRR NIH HHS/ -- R01 GM103401/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):447-50. doi: 10.1126/science.1214383. Epub 2011 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22194410" target="_blank"〉PubMed〈/a〉
    Keywords: Equipment Design ; *Lasers, Semiconductor ; Optical Phenomena ; Semiconductors ; *Silicon
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2012-09-25
    Description: Animals locate and track chemoattractive gradients in the environment to find food. With its small nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behaviour. Extensive work on the nematode has identified the neurons that are necessary for the different locomotory behaviours underlying chemotaxis through the use of laser ablation, activity recording in immobilized animals and the study of mutants. However, we do not know the neural activity patterns in C. elegans that are sufficient to control its complex chemotactic behaviour. To understand how the activity in its interneurons coordinate different motor programs to lead the animal to food, here we used optogenetics and new optical tools to manipulate neural activity directly in freely moving animals to evoke chemotactic behaviour. By deducing the classes of activity patterns triggered during chemotaxis and exciting individual neurons with these patterns, we identified interneurons that control the essential locomotory programs for this behaviour. Notably, we discovered that controlling the dynamics of activity in just one interneuron pair (AIY) was sufficient to force the animal to locate, turn towards and track virtual light gradients. Two distinct activity patterns triggered in AIY as the animal moved through the gradient controlled reversals and gradual turns to drive chemotactic behaviour. Because AIY neurons are post-synaptic to most chemosensory and thermosensory neurons, it is probable that these activity patterns in AIY have an important role in controlling and coordinating different taxis behaviours of the animal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229948/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229948/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kocabas, Askin -- Shen, Ching-Han -- Guo, Zengcai V -- Ramanathan, Sharad -- DP1 MH099906/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 11;490(7419):273-7. doi: 10.1038/nature11431. Epub 2012 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA. akocabas@cgr.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23000898" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; Caenorhabditis elegans/*physiology ; Chemotaxis/*physiology ; Electric Stimulation ; Interneurons/physiology ; Neurons/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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