bluuebunny/crossref_metadata_2025 huggingface dataset:
NanoStringNormCNV: pre-processing of NanoString CNV data
Authors: Sendorek Dorota H , Lalonde Emilie , Yao Cindy Q , Sabelnykova Veronica Y , Bristow Robert G , Boutros Paul C
Published: November 2017

The NanoString System is a well-established technology for measuring RNA and DNA abundance. Although it can estimate copy number variation, relatively few tools support analysis of these data. To address this gap, we created NanoStringNormCNV, an R package for pre-processing and copy number variant calling from NanoString data. This package implements algorithms for pre-processing, quality-control, normalization and copy number variation detection. A series of reporting and data visualization methods support exploratory analyses. To demonstrate its utility, we apply it to a new dataset of 96 genes profiled on 41 prostate tumour and 24 matched normal samples.

Availability and implementation

NanoStringNormCNV is implemented in R and is freely available at http://labs.oicr.on.ca/boutros-lab/software/nanostringnormcnv.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess
Authors: Bowen Asha C , Carapetis Jonathan R , Currie Bart J , Fowler Vance , Chambers Henry F , Tong Steven Y C
Published: November 2017

Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus, including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus, supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.
Endovascular Coil Retrieval Using Dual Synchronous Solitaire Revascularization Devices
Authors: Nerva John D , Morton Ryan P , Kelly Cory M , Hallam Danial K , Levitt Michael R
Published: November 2017

BACKGROUND AND IMPORTANCE

Coil migration is a potential complication of endovascular aneurysm treatment. Dislodged coils into the parent artery require retrieval to prevent thromboembolic complications. A variety of techniques for coil retrieval have been described, including the use of single stentrievers and aspiration catheters.

CLINICAL PRESENTATION

The use of 2 stentrievers, as opposed to a single device, was thought to be advantageous in coil removal by the additional point of friction due to the extensive length of coil stretching and earlier failure of a single device.

CONCLUSION

In this report, 2 synchronous Solitaire FR Revascularization Devices (Covidien/Medtronic, Dublin, Ireland) were deployed, 1 distal and 1 proximal, to retrieve an inadvertently deployed coil.
Alteration of Bile Acid and Cholesterol Biosynthesis and Transport by Perfluorononanoic Acid (PFNA) in Mice
Authors: Zhang Yue , Zhang Youcai , Klaassen Curtis D , Cheng Xingguo
Published: November 2017

Perfluorochemicals produce hepatotoxic effects via activation of peroxisome proliferator-activated receptor alpha (PPARα) and constitutive androstane receptor (CAR) nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice. PFNA caused cholestasis in the WT mice, indicated by increased serum alanine aminotransferase, hyperbilirubinemia, elevated BA concentrations in mouse serum, and appearance of bile plugs in mouse liver. In addition, PFNA decreased total and some individual BAs in mouse liver. PFNA increased the concentrations of total and taurine-conjugated, as well as some individual BAs in the serum of WT and CAR-null mice but not in PPARα-null mice, indicating a PPARα-dependent mechanism. PFNA decreased mRNA expression of most BA-related transporters (sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide [Oatp]1a1, Oatp1b2, and bile salt export pump) and BA biosynthetic enzymes (Cyp7a1, 7b1, 8b1, and 27a1) in mouse liver, but increased mRNA expression of some efflux transporters (breast cancer resistance protein, multidrug resistance transporter 2, multidrug resistance-associated protein [Mrp] 2, Mrp3, and Mrp4), primarily via a PPARα-dependent mechanism. Moreover, PFNA increased free and total cholesterol in mouse liver but not in mouse serum. Furthermore, PFNA increased mRNA expression of sterol transporters, namely Abca1, g1, g5/g8, and steroidogenic acute regulatory protein via PPARα. In conclusion, PFNA produced cholestasis in mouse liver, and the activation of PPARα plays a central role in regulating BA and cholesterol metabolism and transport in mouse serum and liver.
An Improved Detached-Leaf Assay for Phenotyping Net Blotch of Barley Caused by Pyrenophora teres
Authors: El-Mor I. M. , Fowler R. A. , Platz G. J. , Sutherland M. W. , Martin A.
Published: November 2017

Net blotch, caused by Pyrenophora teres, is a major barley (Hordeum vulgare) leaf disease worldwide. P. teres occurs as two forms—P. teres f. teres, and P. teres f. maculata—inducing net and spot-like symptoms, respectively. An intact-seedling assay, where entire seedlings are inoculated by spraying with a conidial suspension, is frequently used for phenotyping net blotch. However, this presents a biosecurity risk in the glasshouse when nonlocal isolates are being screened. Alternatively, a detached-leaf assay (DLA-droplet method) can be used in which leaf segments laid out in a covered tray are inoculated with droplets of a conidial suspension, confining the inoculum. However, using this method, net and spot form symptoms cannot be distinguished from each other. We have developed an improved DLA (DLA-spray method) in which detached whole leaves are sprayed with the inoculum to produce distinct lesions. We compare the results for the three phenotyping methods above using four isolates from both net and spot forms of the disease to inoculate a standard set of eight barley genotypes. Results indicate that the DLA-spray method is a functional, informative and rapid test that readily differentiates the two forms of the pathogen in a biosecure environment.
Electrographic and Clinical Natural History of Lateralized Periodic Discharges
Authors: Punia Vineet , Vakani Ravi , Burgess Richard , Hantus Stephen
Published: November 2017

Purpose:

The long-term electrographic features of lateralized periodic discharges (LPD) and their impact on clinical management are unclear. The authors investigated routine EEGs (rEEG) to analyze the delayed natural history of LPDs, and studied the clinical care of these patients.

Methods:

After IRB approval, the prospectively maintained continuous EEG (cEEG) database was searched to identify patients fulfilling the following criteria: LPDs on cEEG, age ≥18 years, no epilepsy history, and rEEG completed within 1 to 12 months of hospital discharge. Their rEEGs were reviewed followed by clinical data extraction. Appropriate statistical tools were used for data analysis.

Results:

Thirty-nine patients (20 females) with a mean age of 63.3 ± 16.8 years at the time of cEEG fulfilled the study criteria. Thirty-three (85%) had associated electrographic seizures. rEEG was performed 4.7 ± 3.5 months after cEEG. Seven (18%) patients had interictal epileptiform discharges (IEDs) on the rEEG. The LPDs on cEEG of these patients were more often continuous, with an amplitude >2 times their background compared with 10 (26%) patients with normal rEEGs findings. After a mean follow-up of 19.8 ± 9.9 months, 11 (31%) patients developed epilepsy, but only 3 had IEDs on their rEEG. Majority (86%) of patients were on AEDs at the time of last follow-up.

Conclusions:

LPDs lead to markers of epileptogenicity in around 18% of patients. One-third of the study population developed epilepsy. rEEG findings were not found to be good indicators of epilepsy development in our small, retrospective study limited by its sampling bias. Indiscriminate, long-term use of AEDs in these patients is a concerning finding.
Germline loss of MBD4 predisposes to leukaemia due to a mutagenic cascade driven by 5mC
Authors: Sanders Mathijs A. , Chew Edward , Flensburg Christoffer , Zeilemaker Annelieke , Miller Sarah E. , al Hinai Adil S. , Bajel Ashish , Luiken Bram , Rijken Melissa , Mclennan Tamara , Hoogenboezem Remco M. , Kavelaars François G. , Blewitt Marnie E. , Bindels Eric M. , Alexander Warren S. , Löwenberg Bob , Roberts Andrew W. , Valk Peter J.M. , Majewski Ian J.
Published: November 2017

Cytosine methylation is essential for normal mammalian development, yet also provides a major mutagenic stimulus. Methylcytosine (5mC) is prone to spontaneous deamination, which introduces cytosine to thymine transition mutations (C>T) upon replication1. Cells endure hundreds of 5mC deamination events each day and an intricate repair network is engaged to restrict this damage. Central to this network are the DNA glycosylases MBD42 and TDG3,4, which recognise T:G mispairing and initiate base excision repair (BER). Here we describe a novel cancer predisposition syndrome resulting from germline biallelic inactivation of MBD4 that leads to the development of acute myeloid leukaemia (AML). These leukaemias have an extremely high burden of C>T mutations, specifically in the context of methylated CG dinucleotides (CG>TG). This dependence on 5mC as a source of mutations may explain the remarkable observation that MBD4-deficient AMLs share a common set of driver mutations, including biallelic mutations in DNMT3A and hotspot mutations in IDH1/IDH2. By assessing serial samples taken over the course of treatment, we highlight a critical interaction with somatic mutations in DNMT3A that accelerates leukaemogenesis and accounts for the conserved path to AML. MBD4-deficiency was also detected, rarely, in sporadic cancers, which display the same mutational signature. Collectively these cancers provide a model of 5mC-dependent hypermutation and reveal factors that shape its mutagenic influence.
Germline determinants of the somatic mutation landscape in 2,642 cancer genomes
Authors: Waszak Sebastian M , Tiao Grace , Zhu Bin , Rausch Tobias , Muyas Francesc , Rodríguez-Martín Bernardo , Rabionet Raquel , Yakneen Sergei , Escaramis Georgia , Li Yilong , Saini Natalie , Roberts Steven A , Demidov German M , Pitkänen Esa , Delaneau Olivier , Heredia-Genestar Jose Maria , Weischenfeldt Joachim , Shringarpure Suyash S , Chen Jieming , Nakagawa Hidewaki , Alexandrov Ludmil B , Drechsel Oliver , Dursi L Jonathan , Segre Ayellet V , Garrison Erik , Erkek Serap , Habermann Nina , Urban Lara , Khurana Ekta , Cafferkey Andy , Hayashi Shuto , Imoto Seiya , Aaltonen Lauri A , Alvarez Eva G , Baez-Ortega Adrian , Bailey Matthew , Bosio Mattia , Bruzos Alicia L , Buchhalter Ivo , Bustamante Carlos D. , Calabrese Claudia , DiBiase Anthony , Gerstein Mark , Holik Aliaksei Z , Hua Xing , Huang Kuan-lin , Letunic Ivica , Klimczak Leszek J , Koster Roelof , Kumar Sushant , McLellan Mike , Mashl Jay , Mirabello Lisa , Newhouse Steven , Prasad Aparna , Rätsch Gunnar , Schlesner Matthias , Schwarz Roland , Sharma Pramod , Shmaya Tal , Sidiropoulos Nikos , Song Lei , Susak Hana , Tanskanen Tomas , Tojo Marta , Wedge David C , Wright Mark , Wu Ying , Ye Kai , Yellapantula Venkata D , Zamora Jorge , Butte Atul J , Getz Gad , Simpson Jared , Ding Li , Marques-Bonet Tomas , Navarro Arcadi , Brazma Alvis , Campbell Peter , Chanock Stephen J , Chatterjee Nilanjan , Stegle Oliver , Siebert Reiner , Ossowski Stephan , Harismendy Olivier , Gordenin Dmitry A , Tubio Jose MC , Vega Francisco M De La , Easton Douglas F , Estivill Xavier , Korbel Jan O ,   on behalf of the PCAWG Germline Working group%,   and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: November 2017

Cancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic resource to study genetic determinants of somatic mutagenesis across 39 cancer types. Our analyses implicate damaging germline variants in a variety of cancer predisposition and DNA damage response genes with specific somatic mutation patterns. Mutations in the MBD4 DNA glycosylase gene showed association with elevated C>T mutagenesis at CpG dinucleotides, a ubiquitous mutational process acting across tissues. Analysis of somatic structural variation exposed complex rearrangement patterns, involving cycles of templated insertions and tandem duplications, in BRCA1-deficient tumours. Genome-wide association analysis implicated common genetic variation at the APOBEC3 gene cluster with reduced basal levels of somatic mutagenesis attributable to APOBEC cytidine deaminases across cancer types. We further inferred over a hundred polymorphic L1/LINE elements with somatic retrotransposition activity in cancer. Our study highlights the major impact of rare and common germline variants on mutational landscapes in cancer.
Size-reduced embryos reveal a gradient scaling based mechanism for zebrafish somite formation
Authors: Ishimatsu Kana , Hiscock Tom W. , Collins Zach M. , Sari Dini Wahyu Kartika , Lischer Kenny , Richmond David L. , Bessho Yasumasa , Matsui Takaaki , Megason Sean G.
Published: November 2017

Little is known about how the sizes of animal tissues are controlled. A prominent example is somite size which varies widely both within an individual and across species. Despite intense study of the segmentation clock governing the timing of somite generation, how it relates to somite size is poorly understood. Here we examine somite scaling and find that somite size at specification scales with the length of the presomitic mesoderm (PSM) despite considerable variation in PSM length across developmental stages and in surgically size-reduced embryos. Measurement of clock period, axis elongation speed, and clock gene expression patterns demonstrate that existing models fail to explain scaling. We posit a “clock and scaled gradient” model, in which somite boundaries are set by a dynamically scaling signaling gradient across the PSM. Our model not only explains existing data, but also makes a unique prediction that we experimentally confirm—the formation of periodic “echoes” in somite size following perturbation of the size of one somite. Our findings demonstrate that gradient scaling plays a central role both in progression and size control of somitogenesis.

Summary statement

By comparing patterning in zebrafish embryos of different size we show that a dynamically scaling gradient in the presomitic mesoderm regulates somite size control.
A note on measuring natural selection on principal component scores
Authors: Chong Veronica K. , Fung Hannah F. , Stinchcombe John R.
Published: November 2017

Measuring natural selection through the use of multiple regression has transformed our understanding of selection, although the methods used remain sensitive to the effects of multicollinearity due to highly correlated traits. While measuring selection on principal component scores is an apparent solution to this challenge, this approach has been heavily criticized due to difficulties in interpretation and relating PC axes back to the original traits. We describe and illustrate how to transform selection gradients for PC scores back into selection gradients for the original traits, addressing issues of multicollinearity and biological interpretation. We demonstrate this approach with empirical data and examples from the literature, highlighting how selection estimates for PC scores can be interpreted while reducing the consequences of multicollinearity.
Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies
Authors: Zhou Wei , Nielsen Jonas B. , Fritsche Lars G. , Dey Rounak , Gabrielsen Maiken E. , Wolford Brooke N. , LeFaive Jonathon , VandeHaar Peter , Gagliano Sarah A. , Gifford Aliya , Bastarache Lisa A. , Wei Wei-Qi , Denny Joshua C. , Lin Maoxuan , Hveem Kristian , Kang Hyun Min , Abecasis Goncalo R. , Willer Cristen J. , Lee Seunggeun
Published: November 2017

In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, linear mixed model and the recently proposed logistic mixed model, perform poorly – producing large type I error rates – in the analysis of phenotypes with unbalanced case-control ratios. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation (SPA) to calibrate the distribution of score test statistics. This method, SAIGE, provides accurate p-values even when case-control ratios are extremely unbalanced. It utilizes state-of-art optimization strategies to reduce computational time and memory cost of generalized mixed model. The computation cost linearly depends on sample size, and hence can be applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 white British European-ancestry samples for >1400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness.
Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes
Authors: Knowles David A , Burrows Courtney K , Blischak John D , Patterson Kristen M , Ober Carole , Pritchard Jonathan K , Gilad Yoav
Published: November 2017

Anthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes for cancer patients, with almost half of patients expected to ultimately develop congestive heart failure given high drug doses. However, the genetic basis of sensitivity to anthracyclines such as doxorubicin remains unclear. To begin addressing this, we created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24h exposure to varying levels of doxorubicin. The transcriptomic response to doxorubicin is substantial, with the majority of genes being differentially expressed across treatments of different concentrations and over 6000 genes showing evidence of differential splicing. Overall, our observations indicate that splicing fidelity decreases in the presence of doxorubicin. We detect 376 response-expression QTLs and 42 response-splicing QTLs, i.e. genetic variants that modulate the individual transcriptomic response to doxorubicin in terms of expression and splicing changes respectively. We show that inter-individual variation in transcriptional response is predictive of cell damage measuredin vitrousing a cardiac troponin assay, which in turn is shown to be associated within vivoACT risk. Finally, the molecular QTLs we detected are enriched in lower ACT GWASp-values, further supporting thein vivorelevance of our map of genetic regulation of cellular response to anthracyclines.
Natural selection interacts with the local recombination rate to shape the evolution of hybrid genomes
Authors: Schumer Molly , Xu Chenling , Powell Daniel L. , Durvasula Arun , Skov Laurits , Holland Chris , Sankararaman Sriram , Andolfatto Peter , Rosenthal Gil G. , Przeworski Molly
Published: November 2017

While hybridization between species is increasingly appreciated to be a common occurrence, little is known about the forces that govern the subsequent evolution of hybrid genomes. We considered this question in three independent, naturally-occurring hybrid populations formed between swordtail fish speciesXiphophorus birchmanniandX. malinche.To this end, we built a fine-scale genetic map and inferred patterns of local ancestry along the genomes of 690 individuals sampled from the three populations. In all three cases, we found hybrid ancestry to be more common in regions of high recombination and where there is linkage to fewer putative targets of selection. These same patterns are also apparent in a reanalysis of human-Neanderthal admixture. Our results lend support to models in which ancestry from the “minor” parental species persists only where it is rapidly uncoupled from alleles that are deleterious in hybrids, and show the retention of hybrid ancestry to be at least in part predictable from genomic features. Our analyses further indicate that in swordtail fish, the dominant source of selection on hybrids stems from deleterious combinations of epistatically-interacting alleles.

One sentence summary

The persistence of hybrid ancestry is predictable from local recombination rates, in three replicate hybrid populations as well as in humans.
Neural mechanisms of speed-accuracy tradeoff of visual search: Saccade vigor, targeting errors, superior colliculus and frontal eye field
Authors: Reppert Thomas R. , Servant Mathieu , Heitz Richard P. , Schall Jeffrey D.
Published: November 2017

Balancing the speed-accuracy tradeoff (SAT) is necessary for successful behavior. Using a visual search task with interleaved cues emphasizing speed or accuracy, we recently reported diverse contributions of frontal eye field (FEF) neurons instantiating salience evidence and response preparation. Here we report replication of visual search SAT performance in two macaque monkeys, new information about variation of saccade dynamics with SAT, extension of the neurophysiological investigation to describe processes in the superior colliculus, and description of the origin of search errors in this task. Saccade vigor varied idiosyncratically across SAT conditions and monkeys, but tended to decrease with response time. As observed in the FEF, speed-accuracy tradeoff was accomplished through several distinct adjustments in the superior colliculus. Visually-responsive neurons modulated baseline firing rate and the time course of salience evidence. Unlike FEF, the magnitude of visual responses in SC did not vary across SAT conditions, but the time to locate the target was longer in Accurate as compared to Fast trials. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Search errors occurred when visual salience neurons in FEF and SC treated distractors as targets, even in the Accurate condition. Saccade-related neural activity in SC but less FEF varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT.

Significance statement

Neurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This paper reports the first replication of SAT performance in nonhuman primates, the first report of variation of saccade dynamics with SAT, the first description of superior colliculus contributions to SAT, and the first description of the origin of errors during SAT. These results inform and constrain new models of distributed decision-making.
Cross-Site Comparison of Ribosomal Depletion Kits for Illumina RNAseq Library Construction
Authors: Herbert Zachary T. , Kershner Jamie P. , Butty Vincent L. , Thimmapuram Jyothi , Choudhari Sulbha , Alekseyev Yuriy O. , Fan Jun , Podnar Jessica W. , Wilcox Edward , Gipson Jenny , Gillaspy Allison , Jepsen Kristen , BonDurant Sandra Splinter , Morris Krystalynne , Berkeley Maura , LeClerc Ashley , Simpson Stephen D. , Sommerville Gary , Grimmett Leslie , Adams Marie , Levine Stuart S.
Published: November 2017

Ribosomal RNA (rRNA) comprises at least 90% of total RNA extracted from mammalian tissue or cell line samples. Informative transcriptional profiling using massively parallel sequencing technologies requires either enrichment of mature poly-adenylated transcripts or targeted depletion of the rRNA fraction. The latter method is of particular interest because it is compatible with degraded samples such as those extracted from FFPE and also captures transcripts that are not poly-adenylated such as some non-coding RNAs. Here we provide a cross-site study that evaluates the performance of ribosomal RNA removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded RNA samples. We find that all of the kits are capable of performing significant ribosomal depletion, though there are differences in their ease of use. All kits were able to remove ribosomal RNA to below 20% with intact RNA and identify ∼14,000 protein coding genes from the Universal Human Reference RNA sample at >1FPKM. Analysis of differentially detected genes between kits suggests that transcript length may be a key factor in library production efficiency. These results provide a roadmap for labs on the strengths of each of these methods and how best to utilize them.
Species and Cell-Type Properties of Classically Defined Human and Rodent Neurons and Glia
Authors: Xu Xiao , Stoyanova Elitsa I. , Lemiesz Agata , Xing Jie , Mash Deborah C. , Heintz Nathaniel
Published: November 2017

Determination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species, including postmortem human brain. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions.
Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development
Authors: Thomas Anna C. , Heux Pauline , Santos Chloe , Arulvasan Wisenave , Solanky Nita , Carey Magalie E. , Gerrelli Dianne , Kinsler Veronica A. , Etchevers Heather C.
Published: November 2017

Background

MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk.MC1Rmutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentationin uteroalter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight.

Methods and Results

Byin situhybridization, RT-PCR and immunohistochemistry, we show thatMC1Ris widely expressed during human, chick and mouse embryonic and fetal stages in many somatic tissues, particularly in the musculoskeletal and nervous systems, and conserved across evolution in these three amniotes. Its dynamic pattern differs from that ofTUBB3, a gene overlapping the same locus in humans and encoding class III β-tubulin. The αMSH peptide and the transcript for its precursor, pro-opiomelanocortin (POMC), are similarly present in numerous extra-cutaneous tissues.MC1Rgenotyping of variants p.(V60M) and p.(R151C) was undertaken for 867 healthy children from the Avon Longitudinal Study of Parent and Children (ALSPAC) cohort, and birthweight modelled using multiple logistic regression analysis. A significant positive association initially found between R151C and birth weight, independent of known birth weight modifiers, was not reproduced when combined with data from an independent genome-wide association study of 6,459 additional members of the same cohort.

Conclusions

These data clearly show a new and hitherto unsuspected role for MC1R in non-cutaneous solid tissues before birth.
Post-catalytic spliceosome structure reveals mechanism of 3'-splice site selection
Authors: Wilkinson Max E. , Fica Sebastian M. , Galej Wojciech P. , Norman Christine M. , Newman Andrew J. , Nagai Kiyoshi
Published: November 2017

Introns are removed from eukaryotic mRNA precursors by the spliceosome in two transesterification reactions – branching and exon ligation. Following branching, the 5'-exon remains paired to U5 snRNA loop 1, but the mechanism of 3'-splice site recognition during exon ligation has remained unclear. Here we present the 3.7Å cryo-EM structure of the yeast P complex spliceosome immediately after exon ligation. The 3'-splice site AG dinucleotide is recognised through non-Watson-Crick pairing with the 5'-splice site and the branch point adenosine. A conserved loop of Prp18 together with the α-finger and the RNaseH domain of Prp8 clamp the docked 3'-splice site and 3'-exon. The step 2 factors Prp18 and Slu7 and the C-terminal domain of Yju2 stabilise a conformation competent for 3'-splice site docking and exon ligation. The structure accounts for the strict conservation of the GU and AG dinucleotides of the introns and provides insight into the catalytic mechanism of exon ligation.
A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery
Authors: Ngo Thuy T. M. , Moufarrej Mira N. , Rasmussen Marie-Louise H. , Camunas-Soler Joan , Pan Wenying , Okamoto Jennifer , Neff Norma F. , Liu Keli , Wong Ronald J. , Downes Katheryne , Tibshirani Robert , Shaw Gary M. , Skotte Line , Stevenson David K. , Biggio Joseph R. , Elovitz Michal A. , Melbye Mads , Quake Stephen R.
Published: November 2017

We performed a high time-resolution, longitudinal study of normal pregnancy development by measuring cell-free RNA (cfRNA) in blood from women during each week of pregnancy. Analysis of tissue-specific transcripts in these samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific responses of the maternal immune system to pregnancy. We established a “clock” for normal pregnancy development and enabled a direct molecular approach to determine expected delivery dates with comparable accuracy to ultrasound, creating the basis for a portable, inexpensive fetal dating method. We also identified a related gene set that accurately discriminated women at risk for spontaneous preterm delivery up to two months in advance of labor, forming the basis of a potential screening test for risk of preterm delivery.
Parent-based early childhood interventions do make a difference! A rebuttal to See and Gorard (2015a)
Authors: Goldstein Keith , Vatalaro Angela , Yair Gad
Published: November 2017

Purpose

The purpose of this paper is to refute See and Gorard’s paper published in this journal in 2015 which argues that parent-based interventions for school readiness are ineffective.

Design/methodology/approach

Methods and results from 107 studies that were cited in See and Gorard (2015a) and associated reports were reviewed. Evaluations were made based on comparing the original studies with the summaries of those studies in the publication.

Findings

In this rebuttal, the authors show how See and Gorard erred to correctly report methods, sample sizes, outcomes measured, and the actual results of prior research.

Practical implications

The authors suggest that See and Gorard do not provide solid evidence within their article to back up their claims about parent intervention programs. This rigorous review of See and Gorard’s primary sources reveals that the empirical evidence stands contrary to the claims being made. See and Gorard inaccurately reviewed publications which contradict their conclusions, and they relied on a vast amount of unpublished papers by students to support their claims.

Originality/value

The authors demonstrate how See and Gorard misapplied their own standards of evaluation; the authors claim that their source materials contradict the “finding” they purport to present; and the authors argue that they chose lesser known studies when more reputable ones were available.
The impact of mentoring and pedagogy on mitigation of library stress of undergraduate students
Authors: Alazemi Huwayah M. , Alharbi Awadh
Published: November 2017

Purpose

This paper aims to justify the relevance of student-centred teaching – learning in influencing their motivation to shed library fear, source resources, attain higher-order learning, garner intellectual prowess and invent new theories.

Design/methodology/approach

To assess the validity of association between guidance, pedagogy, library access and intellectual prowess, a close-ended questionnaire is used. This questionnaire was administered on 350 undergraduate students in Kuwait. The step helped to gather their responses and initiate correlation analysis. Also, correlation analysis was used to review the association between the items selected in the questionnaire, interpret outcomes and draw valid inferences.

Findings

The outcome highlights that such students show keen interest to learn when faculty members give credence to educational psychology, teaching-learning quality, knowledge transfer and their transformation into knowledge seekers. The realization of such scholastic capabilities makes it possible for them to shed library fear and search disappointments, circumvent procedural complexities and pay least importance to size of library structure. Such mental state heightens their desire to use library services optimally, learn and contribute to new knowledge.

Originality/value

Few attempts have been made to study the impact of mentoring and pedagogy on mitigation of library stress undergraduate students.
How does social sustainability feature in studies of supply chain management? A review and research agenda
Authors: Nakamba Christine Chanda , Chan Paul W. , Sharmina Maria
Published: November 2017

Purpose

The purpose of this paper is to examine how social sustainability is considered in the study of supply chain management, thereby identifying key areas for future researchers to develop.

Design/methodology/approach

A systematic literature review of 109 studies is conducted. The papers have been analysed with a particular focus on their definition of social sustainability, research methods used, the central themes covered and the evolution of the debate including theories and the main findings.

Findings

Findings show that, first, researchers have thus far focused on principles for managing social change, developing measures for performance, identifying drivers and barriers, with few studies considering the social practices, particularly at the micro level and in the context of small and medium-sized enterprises. Second, findings also reveal that there is less consideration of the suppliers’, as opposed to the buyers’, perspective.

Research limitations/implications

This review focuses only on social sustainability within supply chain management, without considering the economic and environmental dimensions.

Practical implications

This review provides the key themes and areas for managers/practitioners to consider when implementing social sustainability in supply chains. It also provides insights into under-researched areas together with the need for future researchers to move beyond frameworks and develop more tools and instruments for measuring social performance in practice.

Originality/value

This paper is one of the few studies that consider the social dimension of sustainability exclusively within the context of supply chains, providing insights and implications for further research.
New modified selective platinum electrode based on poly (ethylene glycol) for Iron (III) detection in real water
Authors: Mecheri Nacira , Benounis Messaoud , Barhoumi Houcine
Published: November 2017

Purpose

This work aims to determine iron (III) in real water by using a new amperometric sensor on the basis of polyethylene glycol (PEG) to test and characterize a new modified selective platinum electrode.

Design/methodology/approach

In this review, the authors focus on testing and characterizing several polymeric membranes by using cyclic voltammetry and square-wave voltammetry (SWV) methods to differentiate the nature of plasticizers (2-Nitrophenyl octyl ether [NPOE], Di-n-octyl phthalate, Bis (2-ethylhexyl) sebacate, PEG. The authors have evaluated the possibility of using crown ether and three zeolite ionophore (faujasite [FAU], Chabazite and ZSM-5) matrixes as novel materials for the selective determination of iron (III) using SWV for the best membranes.

Findings

The results demonstrated that the modified platinum electrode presents linear dependence of amperometric signal with a wide linear range of 10−9to 10−4mol.L−1for iron determination, revealing a detection limit of 10−10mol.L−1and amperometric sensibility of 58.58 µA/mol.L−1. The slope of the membrane plasticized with PEG calibration curve is six times higher than that of the other membranes. It was noticed that when the crown ether and the three zeolite ionophores were used, as a new detective material for iron with the membrane plasticized with PEG, the expected results were highly proven. The modified platinum electrode showed high selectivity to iron (III) when the heavy metal ions such as Ni (II), Al (III), Zn (III), Cd (II), Gd (II) and Cu (II) were present.

Originality/value

The utility of the method and the efficiency of the best membrane sensor have been accurately tested by the determination of iron in real water samples of Hassi Messaoud, south of Algeria.
Critical disease windows shaped by stress exposure alter allocation trade‐offs between development and immunity
Authors: Kirschman Lucas J. , Crespi Erica J. , Warne Robin W.
Published: November 2017

Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested.

We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade‐offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians.

We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection.

Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment.

Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae.

Interactions between stress exposure (via glucocorticoid actions) and infection impose resource trade‐offs that shape optimal allocation between development and somatic function. As a result, critical disease windows are likely shaped by stress exposure because any conditions that induce changes in differentiation rates will alter the duration and susceptibility of organisms to stressors or disease.
The neuronal and endocrine roles of RCAN1 in health and disease
Authors: Peiris Heshan , Keating Damien J.
Published: November 2017

The regulator of calcineurin 1 (RCAN1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down syndrome individuals. Increased expression of RCAN1 has been linked with not only Down syndrome‐associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN1 expression is also increased. RCAN1 has additionally been demonstrated to affect other cell types including endocrine cells, with links to the pathogenesis of β‐cell dysfunction in type 2 diabetes. The primary functions of RCAN1 relate to the inhibition of the phosphatase calcineurin, and to the regulation of mitochondrial function. Various forms of cellular stress such as reactive oxygen species and hyperglycaemia cause transient increases in RCAN1 expression. The short term (hours to days) induction of RCAN1 expression is generally thought to have a protective effect by regulating the expression of pro‐survival genes in multiple cell types, many of which are mediated via the calcineurin/NFAT transcriptional pathway. However, strong evidence also supports the notion that chronic (weeks‐years) overexpression of RCAN1 has a detrimental effect on cells and that this may drive pathophysiological changes in neurons and endocrine cells linked to Down syndrome, Alzheimer's Disease and type 2 diabetes. Here we review the evidence related to these roles of RCAN1 in neurons and endocrine cells and their relationship to these human health disorders.
Furan Levels and Sensory Profiles of Commercial Coffee Products Under Various Handling Conditions
Authors: Han Jeesoo , Kim Mina K. , Lee Kwang‐Geun
Published: November 2017

In this study, the levels of furan in coffee with consideration towards common coffee consumption was investigated. The concentration of furan in brewed coffee was the highest among the coffee types studied, with an average of 110.73 ng/mL, followed by canned coffee (28.08 ng/mL) and instant coffee (8.55 ng/mL). In instant and brewed coffee, the furan levels decreased by up to an average of 20% and 22%, after 5 min of pouring in a cup without a lid. The degree of reduction was greater when coffee was served without a lid, regardless of coffee type (P < 0.05). In canned coffee, the level of furan decreased by an average of 14% after storage at 60 °C without a lid, and the degree of furan reduction in coffee was greater in coffee served warm (60 °C) than in coffee served cold (4 °C). A time‐dependent intensities of sensory attributes in commercial coffees with various handling condition were different (P < 0.05), suggesting that coffee kept in a cup with lid closed, holds the aroma of coffee longer than coffee in a cup without a lid.

Practical Application

Consumption of coffee has increased rapidly in Korea over the past few years. Consequently, the probability of exposure to chemical hazards presence in coffee products increases. Furan is a heterocyclic compound, formed mainly from Maillard reaction, therefore present in coffee products. This work demonstrated the strategy to reduce the levels of furan in coffee products at individual consumer level, by investigating the levels of furan served in common handling scenarios of coffee in Korea: canned coffee, instant coffee, and brewed coffee. Findings of this study can practically guide industry, government, and consumer agencies to reduce the risk exposure to furan during coffee consumptions.
Effect of House Cricket (Acheta domesticus) Flour Addition on Physicochemical and Textural Properties of Meat Emulsion Under Various Formulations
Authors: Kim Hyun‐Wook , Setyabrata Derico , Lee YongJae , Jones Owen G. , Kim Yuan H. Brad
Published: November 2017

The objective of this study was to determine the effect of house cricket (Acheta domesticus) flour addition on physicochemical and textural properties of meat emulsion under various formulations. As an initial marker of functionality, protein solubility, water absorption, emulsifying capacity, and gel formation ability of house cricket flour were determined at pH (2 to 10) and NaCl concentrations (0 to 2.10 M). Control emulsion was formulated with 60% lean pork, 20% back fat, and 20% ice. Six treatment emulsions were prepared with replacement of lean pork and/or back fat portions with spray‐dried house cricket flour at 5% and 10% levels, based on a total sample weight. The protein solubility of house cricket flour (67 g protein/100 g) was significantly altered depending upon pH (P < 0.0001) and NaCl concentration (P = 0.0421). Similar water absorption capacity, emulsifying capacity, and gel formation ability of house cricket flour were found between 0 and 2.10 M NaCl concentration (P > 0.05). The replacement of lean meat/fat portion with house cricket flour within 10% level could fortify protein and some micronutrients (phosphorus, potassium, and magnesium) in meat emulsion, without negative impacts on cooking yield and textural properties. Our results suggest that house cricket flour can be used as an effective nonmeat functional ingredient to manufacture emulsified meat products.

Practical Application

To better utilize house cricket flour as a food ingredient in wide application, understanding its technological properties in various pH, and ionic strength conditions is a pivotal step. Protein solubility of house cricket flour would be considerably affected by the varying pH and NaCl concentrations of applied conventional foods. In the case of meat emulsion, within 10% lean meat and/or fat portions could be successfully substituted with house cricket flour without detectable adverse impacts on technological properties associated with cooking yield and instrumental analysis of texture. Thus, our findings suggest that house cricket flour possess the necessary physical properties to be used as an alternative nonmeat ingredient for incorporation within emulsified meat products, which could be further explored in subsequent sensory‐based studies.