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Wiley takes measures to target plagiarism

September 18, 2014

With one in three editors encountering plagiarism on a regular basis, it remains a real problem in scientific publishing, and open access is no exception. And the problem isn’t improving, there has been a recent increase in article retractions and problems with published work tarnished by plagiarism or even complete fabrication. However, the growth of retractions can also point to more screening, and more propensity on the part of editorial offices to retract. In response, Wiley has rolled out automatic reports upon submission using the iThenticate anti-plagiarism software (part of the Crosscheck service) across all Wiley Open Access journals using ScholarOneManuscripts.

So, what are Crosscheck and iThenticate how do they work?
The CrossCheck service offers a continuously updated database of current and archival scholarly literature. The second part of this service, the iThenticate tool, then compares authored work against the content in the database and highlights matching or similar text for further editorial review. The software produces a report for each manuscript, which includes a percentage score, called a ‘Similarity Index’. This index indicates how much of the document matches other sources, and sentences or paragraphs that are duplicates of those in previous publications are highlighted, with links to the previous articles included. In addition to the internet, manuscripts are checked against more than 37 million published research articles from over 500 global scientific, technical and medical publishers.

iThenticate identifies unoriginal content in three steps:

1.Document is uploaded to iThenticate.
2.The document is compared against a vast content database for plagiarism, using advanced plagiarism checker technology.
3.The results of the report, containing any detected matched materials or unattributed text, are ready in minutes.

To clarify, a high Similarity Index does not necessarily indicate plagiarism. It could be the result of small text overlaps with many individual sources, or a large overlap with a single source. The latter case would be more of a problem if the author had lifted a whole page from a previous manuscript, for example. Repetition can sometimes be difficult to avoid – after all, there are only so many ways to talk about a specific experimental technique. Similarly, you might expect review articles to contain higher levels of overlap compared to original research papers; so editors will always take into account the whole report, rather than relying on one ‘magic’ number.

What are the advantages of using iThenticate?
To begin with, the use of iThenticate across Wiley Open Access journals will go some way towards setting a standard for dealing with ethics issues. Wiley is committed to providing the best possible service for its authors and the use of this software on all submissions will vastly improve the submission and review process, while ensuring that Wiley Open Access journals meet the high ethical standards expected by our authors and society partners.

Because documents are screened by iThenticate at the submission stage, editors and editorial assistants will have been made aware of any possible ethical issues at the beginning of the peer review process. This allows plenty of time to address any problems during peer review, making for a much more efficient process. Additionally, editors are able to request any changes that need to be made as a result of the iThenticate report at the recommendation stage, so any textual overlap revision requests can be combined with all of the usual revision requests based on reviewer comments and/or English language revisions.

Of course, not all plagiarism is intentional. The iThenticate software makes it much easier for authors to identify and properly attribute any material that might contain unintended plagiarism. Authors can therefore ensure that they have cited their sources sufficiently, and that their finished submissions are of the highest possible standard.

The use of iThenticate across the majority of Wiley Open Access journals will help to ensure that the best ethical practices are used across the program, enhancing the reputation of the journals while benefiting editors and authors alike.

Molecular Genetics & Genomic Medicine Volume 2 Issue 5 is Published!

September 10, 2014

Molecular Genetics & Genomic Medicine has now published its next issue. Editor-in-Chief: Max Muenke introduces his editorial highlights: “This issue includes an Invited Commentary on the evolution of comparative genomics and also features the next article in our series, “Genetics and Genomic Medicine around the World“, this month focusing on Saudi Arabia. Highlights of the issue include articles focusing on craniofacial morphometric analysis in X-linked hypohidrotic ectodermal dysplasia, coding region analysis in centenarians, next generation sequencing for Usher syndrome and polycystic kidney disease.”

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia by Alice F. Goodwin, Jacinda R. Larson, Kyle B. Jones, Denise K. Liberton, Maya Landan, Zhifeng Wang, Anne Boekelheide, Margaret Langham, Vagan Mushegyan, Snehlata Oberoi, Rosalie Brao, Timothy Wen, Ramsey Johnson, Kenneth Huttner, Dorothy K. Grange, Richard A. Spritz, Benedikt Hallgrímsson, Andrew H. Jheon and Ophir D. Klein.
Abstract: Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

Disease variants in genomes of 44 centenarians by Yun Freudenberg-Hua, Jan Freudenberg, Vladimir Vacic, Avinash Abhyankar, Anne-Katrin Emde, Danny Ben-Avraham, Nir Barzilai, Dayna Oschwald, Erika Christen, Jeremy Koppel, Blaine Greenwald, Robert B. Darnell, Soren Germer, Gil Atzmon and Peter Davies.
Abstract: To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30× coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as “pathogenic” or “likely pathogenic” based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE ε4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer’s disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions.

Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome by Peter M. Krawitz, Daniela Schiska, Ulrike Krüger, Sandra Appelt, Verena Heinrich, Dmitri Parkhomchuk, Bernd Timmermann, Jose M. Millan, Peter N. Robinson, Stefan Mundlos, Jochen Hecht and Manfred Gross.
Abstract: Usher syndrome is an autosomal recessive disorder characterized both by deafness and blindness. For the three clinical subtypes of Usher syndrome causal mutations in altogether 12 genes and a modifier gene have been identified. Due to the genetic heterogeneity of Usher syndrome, the molecular analysis is predestined for a comprehensive and parallelized analysis of all known genes by next-generation sequencing (NGS) approaches. We describe here the targeted enrichment and deep sequencing for exons of Usher genes and compare the costs and workload of this approach compared to Sanger sequencing. We also present a bioinformatics analysis pipeline that allows us to detect single-nucleotide variants, short insertions and deletions, as well as copy number variations of one or more exons on the same sequence data. Additionally, we present a flexible in silico gene panel for the analysis of sequence variants, in which newly identified genes can easily be included. We applied this approach to a cohort of 44 Usher patients and detected biallelic pathogenic mutations in 35 individuals and monoallelic mutations in eight individuals of our cohort. Thirty-nine of the sequence variants, including two heterozygous deletions comprising several exons of USH2A, have not been reported so far. Our NGS-based approach allowed us to assess single-nucleotide variants, small indels, and whole exon deletions in a single test. The described diagnostic approach is fast and cost-effective with a high molecular diagnostic yield.

Diagnosis of autosomal dominant polycystic kidney disease using efficient PKD1 and PKD2 targeted next-generation sequencing by Daniel Trujillano, Gemma Bullich, Stephan Ossowski, José Ballarín, Roser Torra, Xavier Estivill and Elisabet Ars.
Abstract: Molecular diagnostics of autosomal dominant polycystic kidney disease (ADPKD) relies on mutation screening of PKD1 and PKD2, which is complicated by extensive allelic heterogeneity and the presence of six highly homologous sequences of PKD1. To date, specific sequencing of PKD1 requires laborious long-range amplifications. The high cost and long turnaround time of PKD1 and PKD2 mutation analysis using conventional techniques limits its widespread application in clinical settings. We performed targeted next-generation sequencing (NGS) of PKD1 and PKD2. Pooled barcoded DNA patient libraries were enriched by in-solution hybridization with PKD1 and PKD2 capture probes. Bioinformatics analysis was performed using an in-house developed pipeline. We validated the assay in a cohort of 36 patients with previously known PKD1 and PKD2 mutations and five control individuals. Then, we used the same assay and bioinformatics analysis in a discovery cohort of 12 uncharacterized patients. We detected 35 out of 36 known definitely, highly likely, and likely pathogenic mutations in the validation cohort, including two large deletions. In the discovery cohort, we detected 11 different pathogenic mutations in 10 out of 12 patients. This study demonstrates that laborious long-range PCRs of the repeated PKD1 region can be avoided by in-solution enrichment of PKD1 and PKD2 and NGS. This strategy significantly reduces the cost and time for simultaneous PKD1 and PKD2 sequence analysis, facilitating routine genetic diagnostics of ADPKD.

The journal also publishes Genetics and Genomic Medicine around the World. Below is the second article of this type, this month focusing on Saudi Arabia.

Genetics and genomic medicine in Saudi Arabia” by Fowzan S. Alkuraya.

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Wiley and the Royal Geographical Society (with IBG) launch Geo!

July 24, 2014

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Wiley and the Royal Geographical Society (with IBG) are thrilled to announce the launch this week of Geo: Geography and Environment. The journal will be the Society’s first fully open access journal, and positions the RGS-IBG and Wiley as world leaders in the publication of geographical research.

Geo is one of the first journals of its kind, publishing high-quality, original articles from across the spectrum of geographical and environmental enquiry. It has an interdisciplinary approach that spans the sciences, social sciences and humanities. The journal will focus on work of international significance, and welcomes submissions that bring new understanding to geographical research agendas, foster methodological development, and address contemporary geographical issues.

‘We are extremely pleased to partner with Wiley to offer a journal that will be at the forefront of many of the exciting developments within geographical and environmental research’ said Dr Catherine Souch, Head of Research and Higher Education at the RGS-IBG. ‘By offering an open access journal, the RGS-IBG is strengthening its commitment to publish and disseminate high-quality research reaching the widest possible audience’.

Geo is edited by Professor Gail Davies, of the University of Exeter, and Professor Anson Mackay, of University College London. ‘Growing imperatives for openness in science present both exciting opportunities and significant challenges for research’, said Professor Davies, ‘Openness has many meanings and the ethos of open access is still at issue. The RGS-IBG is actively shaping these debates and I am delighted to be editing Geo.’

Geo will publish articles under a choice of Creative Commons licenses, allowing authors to be fully compliant with open access requirements of funding organisations where they apply. For more information, and to find out how to submit an article, please visit the website here.

Molecular Genetics & Genomic Medicine Volume 2 Issue 4 is Published!

July 15, 2014

Molecular Genetics & Genomic Medicine has now published its next issue. Editor-in-Chief: Max Muenke introduces his editorial highlights: “This issue includes an Invited Commentary on the genomics and epigenomics of substance use disorders and also features the third article in our series, “Genetics and Genomic Medicine around the World”, this month focusing on Brazil. Highlights of the issue include the articles, “Telomere Length, Family History and Paternal Age in Schizophrenia“, “Association of the c.385C>A (p.Pro129Thr) Polymorphism of the Fatty Acid Amide Hydrolase Gene with Anorexia Nervosa in the Japanese Population”, and “46,XY Disorder of Sexual Development Resulting from a Novel Monoallelic Mutation (p.Ser31Phe) in the Steroid 5α-Reductase Type-2 (SRD5A2) Gene”.

Telomere length, family history, and paternal age in schizophrenia by Dolores Malaspina, Roberta Dracxler, Julie Walsh-Messinger, Susan Harlap, Raymond R. Goetz, David Keefe and Mary C. Perrin.
Abstract: Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.

Association of the c.385C>A (p.Pro129Thr) Polymorphism of the Fatty Acid Amide Hydrolase Gene with Anorexia Nervosa in the Japanese Population by Tetsuya Ando, Naho Tamura, Takashi Mera, Chihiro Morita, Michiko Takei, Chiemi Nakamoto, Masanori Koide, Mari Hotta, Tetsuro Naruo, Keisuke Kawai, Toshihiro Nakahara, Chikara Yamaguchi, Toshihiko Nagata, Kazuyoshi Ookuma, Yuri Okamoto, Takao Yamanaka, Nobuo Kiriike, Yuhei Ichimaru, Toshio Ishikawa, Gen Komaki and The Japanese Genetic Research Group For Eating Disorders.
Abstract: The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653–0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557–0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

46,XY Disorder of Sexual Development Resulting from a Novel Monoallelic Mutation (p.Ser31Phe) in the Steroid 5α-Reductase Type-2 (SRD5A2) Gene by Bertha Chávez, Luis Ramos, Rita Gómez and Felipe Vilchis.
Abstract: Inactivating mutations of the 5α-steroid reductase type-2 (SRD5A2) gene result in a broad spectrum of masculinization defects, ranging from a male phenotype with hypospadias to a female phenotype with Wolffian structures. Molecular studies of the SRD5A2 revealed a new heterozygous gene variant within the coding region that results in phenotypic expression. A c.92C>T transition changing serine to phenylalanine at codon 31 of exon 1 (p.Ser31Phe) was identified in a patient with 46,XY disorder of sexual development who displayed glandular hypospadias with micropenis and bilateral cryptorchidism. The restoration of the p.Ser31Phe mutation by site-directed mutagenesis and transient expression assays using cultured HEK-293 cells showed that this novel substitution does not abolish but does deregulate the catalytic efficiency of the enzyme. Thus, the maximum velocity (Vmax) value was higher for the mutant enzyme (22.5 ± 6.9 nmol DHT mg protein−1 h−1) than for the wild-type enzyme (9.8 ± 2.0 nmol DHT mg protein−1 h−1). Increased in vitro activity of the p.Ser31Phe mutant suggested an activating effect. This case provides evidence that heterozygous missense mutations in SRD5A2 may induce the abnormal development of male external genitalia..

The journal also publishes Genetics and Genomic Medicine around the World. Below is the second article of this type, this month focusing on Brazil.

Genetics and genomics in Brazil: a promising future” by Maria Rita Passos-Bueno, Debora Bertola, Dafne Dain Gandelman Horovitz, Victor Evangelista de Faria Ferraz and Luciano Abreu Brito.

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Good news- new editor for latest AGU open access journal announced!

May 23, 2014

ESS2 thumbnail 2 The American Geophysical Union (AGU) today announced that John Orcutt, a distinguished professor of Geophysics at the Scripps Institution of Oceanography and former president of AGU, will serve as the inaugural editor of its newest open access, peer-reviewed journal, Earth and Space Science. The journal will begin accepting papers in late summer 2014, and the first articles will be available in late fall 2014.

Earth and Space Science reflects the expansive range of science AGU represents, including all of the Earth, planetary, and space sciences, as well as related fields in environmental science, geoengineering, space engineering, and biogeochemistry. It will also include papers describing and presenting data, observations, instrumentation and methods that are important for advancing these fields. In addition to direct submissions, it will accept, via referral from other journals, articles that meet AGU’s high standards of excellence, but that do not fit the unique criteria of those journals.

Earth and Space Science is unique in the breadth of science it represents and its goal to contribute to a broader scientific understanding of the Earth and its environment, as well as our solar system and beyond. To make such an ambitious effort successful, we knew that we needed the guidance of a skilled and innovative editor who could help bring forth, peer-reviewed science and data that are important for societal decision making at all scales,” said AGU President Carol Finn. “I’m pleased to say that John Orcutt’s background makes him perfect for tackling this assignment, and I am happy to welcome him into AGU’s editorial community. Under his leadership I am sure that Earth and Space Science will quickly join the ranks of AGU’s other award-winning journals.”

Orcutt has published more than 175 scientific papers and book chapters. His research interests include the exploitation of information technology for the collection and processing of real-time environmental data, as well as seismology in the oceans and on land and marine geophysics. He is the principal investigator for the National Science Foundation’s MRE-FC Ocean Observatories Initiative Cyberinfrastructure program, and a participant in the National Research Council’s (NRC) study entitled Fukushima, Lessons Learned. Orcutt recently completed a review of hydroacoustics monitoring by the United Nation’s Comprehensive Test Ban Treaty in the Indian Ocean, and he chaired the NRC’s reviews of Ocean Exploration, the National Oceanic and Atmospheric Administration’s Tsunami Warning System, and the Ocean Panel of the Climate, Energy and National Security Committee.

“For many years the Earth and space science community has lacked a space for publishing work on models, data from experiments and observatories, observational methodologies, instrumentation, and the complexities of integrating technologies for stable and long-term observations related to critical issues including climate and hazards. This has presented a significant barrier to scientific progress,” said Orcutt. Earth and Space Science will offer a timely and reputable solution to this dilemma, and as an open access journal, it will ensure that high-quality research is shared as widely as possible. It is only fitting that AGU, as the leading society for Earth and space science, is the home for this innovative and exciting new journal . . . and I am honored to be a part of its inception.”

A recipient of the U.S. Navy/AGU’s Ewing Medal, the American Association for the Advancement of Science’s Newcomb-Cleveland Prize, and the Marine Technology Society’s LockheedMartin Award for Ocean Science and Technology, Orcutt received a Secretary of the Navy/Chief of Naval Operations Chair in 1996. He is a member of the National Academy of Engineering, a member of the American Philosophical Society and a Fellow and Past President of AGU. Orcutt received his bachelor’s in mathematics and physics from U.S. Naval Academy, his master’s in physical chemistry as a Fulbright Scholar at the University of Liverpool, and his Ph.D. in Earth sciences from the Scripps Institution of Oceanography/University of California, San Diego.

Molecular Genetics & Genomic Medicine Volume 2 Issue 3 is Published!

May 15, 2014

Molecular Genetics & Genomic Medicine has now published its next issue. Editor-in-Chief: Max Muenke introduces his editorial highlights: “This issue includes an Invited Commentary on the Future of Genomic Medicine, HLA haplotyping, Papillon-Lefèvre syndrome, and association of THAP1 mutations with Primary Dystonia. It also features the second article in our series Genetics and Genomic Medicine around the World, this month focusing on Thailand. Highlights of the issue include the articles, “Novel IRF6 Mutations in Families with Van Der Woude Syndrome and Popliteal Pterygium Syndrome from Sub-Saharan Africa”, and “Mutations of NOTCH3 in childhood pulmonary arterial hypertension”.

Novel IRF6 Mutations in Families with Van Der Woude Syndrome and Popliteal Pterygium Syndrome from Sub-Saharan Africa by Azeez Butali, Peter A. Mossey, Wasiu L. Adeyemo, Mekonen A. Eshete, LauRen A. Gaines, Dee Even, Ramat O. Braimah, Babatunde S. Aregbesola, Jennifer V. Rigdon, Christian I. Emeka, Olutayo James, Mobolanle O. Ogunlewe, Akinola L. Ladeinde, Fikre Abate, Taye Hailu, Ibrahim Mohammed, Paul E. Gravem, Milliard Deribew, Mulualem Gesses, Adebowale A. Adeyemo and Jeffrey C. Murray.
Abstract: Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families.

Mutations of NOTCH3 in childhood pulmonary arterial hypertension by Ayako Chida, Masaki Shintani, Yoshihisa Matsushita, Hiroki Sato, Takahiro Eitoku, Tomotaka Nakayama, Yoshiyuki Furutani, Emiko Hayama, Yoichi Kawamura, Kei Inai, Shinichi Ohtsuki, Tsutomu Saji, Shigeaki Nonoyama and Toshio Nakanishi.
Abstract: Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis.

The journal also publishes Genetics and Genomic Medicine around the World. Below is the second article of this type, this month focusing on Thailand.

Genetics and genomics in Thailand: challenges and opportunities” by Vorasuk Shotelersuk, Chanin Limwongse and Surakameth Mahasirimongkol

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