bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal-type adenocarcinoma of the sinonasal tract: an update
Authors: Rampinelli Vittorio , Ferrari Marco , Nicolai Piero
Published: February 2018

Purpose of review

Intestinal-type adenocarcinoma (ITAC) is one of the most frequent sinonasal tumors, especially in European countries. The purpose of this article is to review the most recent literature, with special emphasis on biological and genetic profile and treatment guidelines.

Recent findings

Results on large series support transnasal endoscopic surgery as the technique of choice in the large majority of patients with ITAC. Adjuvant radiotherapy is recommended in advanced-stage and high-grade lesions. More robust data are required to confirm that early-stage, low-grade lesions can be treated with exclusive surgery. The efficacy of new chemotherapy and biotherapy regimens and the added value of heavy particle radiotherapy are currently under evaluation. With a 5-year overall survival ranging between 53 and 83%, which is mainly impacted by local recurrences, ITAC requires a more detailed understanding of its biology. Genetic and biological studies have identified alterations in the molecular pathways of EGFR, MET, and H-RAS which might be considered as potential targets for biotherapy.

Surgery still plays a key role in the treatment of ITAC, but multidisciplinary management is mandatory. Although further validation is needed, the role of nonsurgical treatment strategies is rising, in agreement with the progresses made in the biological profiling of the disease.
Progression of chronic kidney disease in children – role of glomerular hemodynamics and interstitial fibrosis
Authors: Oliveira Eduardo A. , Mak Robert H.
Published: February 2018

Purpose of review

The aim of this review is to provide an overview of the current advances in the understanding of the mechanisms involved in the progression of chronic kidney disease (CKD) with emphasis on the role of glomerular hemodynamics and tubulointerstitial fibrosis.

Recent findings

Despite the varied causes of CKD, the progressive destruction of renal tissue processes through a complex common pathway. Current studies have highlighted both the role of the abnormal intrarenal hemodynamics and of the activation of fibrogenic biochemical pathway in the replacement of normal renal structure by extracellular matrix and ultimately by fibrosis. Molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney has been identified.

There is a clear need to understand and elucidate the mechanisms of progression of CKD to develop efficient therapeutic strategies to halt decline of renal function in children.
Artificial Intelligence in Surgery: Promises and Perils
Authors: Hashimoto Daniel A. , Rosman Guy , Rus Daniela , Meireles Ozanan R.
Published: February 2018

Objective:

The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments.

Summary Background Data:

AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers.

Methods:

A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed.

Results:

Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed.

Conclusions:

Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.
Orally Administered Combination of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin in the Prevention of Postcoital Recurrent Urinary Tract Infections: Analysis of 98 Women in Reproductive Age After 6 Months of Treatment
Authors: Schiavi Michele Carlo , Porpora Maria Grazia , Vena Flaminia , Prata Giovanni , Sciuga Valentina , D’Oria Ottavia , Di Tucci Chiara , Savone Delia , Aleksa Natalia , Giannini Andrea , Nusiner Maria Paola , Zullo Marzio Angelo , Muzii Ludovico , Benedetti Panici Pierluigi
Published: February 2018

Objective

The aim of this study is to assess the efficacy of orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin for the prevention of postcoital recurrent urinary tract infection (UTI) in reproductive age women.

Methods

Ninety-eight consecutive patients in reproductive age affected by UTI were considered for the study. All 98 patients received a combination of HA, CS, curcumin, and quercetin two tablets per diem for the first month and one tablet every day for the next 5 months. We investigate recurrence of UTI with the Urinary Tract Infection Symptoms Assessment and the Pelvic Pain and Urinary Urgency Frequency. The quality of life and sexual function were valued using 36-Item Short Form Survey, Female Sexual Function Index, and the Female Sexual Distress Scale questionnaires. The same investigations were performed at the first visit and after 6 months of treatment.

Results

The symptoms associated with UTI significantly decreased after 6 months of treatment, in particular dysuria episodes diminished and number of voiding decreased (P < 0.0001). During the treatment period, only seven patients (7.1%) experienced a UTI recurrence, confirmed by positive urine culture with bacteriuria of greater than 105 colony forming units/mL. The Pelvic Pain and Urinary Urgency Frequency, Female Sexual Function Index, Female Sexual Distress Scale, and 36-Item Short Form Survey showed a statistically significant improvement after 6 months.

Conclusions

Oral administration of a combination of HA, CS, curcumin, and quercetin is a valid and well-tolerated nonantibiotic treatment for prevention of postcoital UTI in reproductive age women.
The Impact of Language Experience on Language and Reading
Authors: Seidenberg Mark S. , MacDonald Maryellen C.
Published: February 2018

This article reviews the important role of statistical learning for language and reading development. Although statistical learning—the unconscious encoding of patterns in language input—has become widely known as a force in infants' early interpretation of speech, the role of this kind of learning for language and reading comprehension in children has received less attention. In fact, the implicit learning of co-occurrences of words, sentence structures, and other components of language forms a critical part of children's language comprehension and fluent reading. Beyond introducing basic information about language statistics, the article offers a discussion of how variability in the amount and nature of language experience can affect language development and literacy, including variation owing to the amount of language input in the child's linguistic environment and the variable nature of input for children who are exposed to multiple languages or multiple dialects.
Clinical trials in autism spectrum disorder: evidence, challenges and future directions
Authors: Anagnostou Evdokia
Published: February 2018

Purpose of review

The purpose of this manuscript is to review the evidence generated by clinical trials of pharmaceuticals in autism spectrum disorder (ASD), describe challenges in the conduct of such trials, and discuss future directions

Recent findings

Clinical trials in ASD have produced several compounds to adequately support the pharmacological treatment of associated symptom domains: attention deficit hyperactivity disorder (methylphenidate, atomoxetine, and alpha agonists), irritability/aggression (risperidone and aripiprazole), sleep (melatonin), and weight gain associated with atypical antipsychotic use (metformin). However, there is no evidence yet to support the routine use of pharmaceuticals for the treatment of core symptom domains. Challenges in the field include biological heterogeneity within ASD, lack of biomarkers that clarify biological heterogeneity or predict response to treatment, lack of data across the lifespan, and suboptimal outcome measures.

Several compounds have evidence for the treatment of co-occurring symptoms in children and youth with ASD, although pharmacological interventions for core symptoms are still lacking. Identifying the various biologies underling ASD and developing biomarkers that stratify biologically homogeneous populations are both necessary to realize the promise of precision medicine in ASD.
Characterization of rhinovirus C from a 4-year-old boy with acute onset dilated cardiomyopathy in Jakarta, Indonesia
Authors: Wiyatno Ageng , Febrianti E. S. Zul , Dewantari Aghnianditya Kresno , Myint Khin Saw , Safari Dodi , Idris Nikmah Salamia
Published: February 2018

Introduction. Myocarditis, inflammation of the heart muscle, can be caused by infections, autoimmune disease or exposure to toxins. The major cause of myocarditis in the paediatric population is viral infection, including coxsackievirus B3, adenovirus, herpesvirus, parvovirus, influenza A and B, and hepatitis. Here, we report the detection of rhinovirus C in a boy with a clinical presentation of myocarditis, suggesting a possible causative role of this virus in this case.

Case presentation. A previously well 4.5-year-old boy presented with increasing breathlessness for a week prior to admission. He also had upper respiratory tract infection a few days before the event. An echocardiogram revealed severe left ventricle (LV) systolic dysfunction with dilation of the LV. RNA was extracted from serum and two nasal swabs, and tested with conventional PCR at the family level for viruses including enterovirus, dengue, chikungunya, influenza, herpesvirus, paramyxovirus and coronavirus. Further characterization of the enterovirus group was carried out using PCR with primers targeting the VP4/VP2 gene, followed by sequencing. Molecular tests showed the presence of rhinovirus C genetic material in both serum and swab samples. Phylogenetic analysis of the VP4/VP2 region showed 96–97 % similarity with the closest strain isolated in Ulaanbaatar (Mongolia) and Japan in 2012.

Conclusion. We report the possible association of rhinovirus C and myocarditis in a child presenting with acute onset of dilated cardiomyopathy.
Streptomyces coelicolor strains lacking polyprenol phosphate mannose synthase and protein O-mannosyl transferase are hyper-susceptible to multiple antibiotics
Authors: Howlett Robert , Read Nicholas , Varghese Anpu , Kershaw Charles , Hancock Y. , Smith Margaret C. M.
Published: February 2018

Polyprenol phosphate mannose (PPM) is a lipid-linked sugar donor used by extra-cytoplasmic glycosyl tranferases in bacteria. PPM is synthesiszed by polyprenol phosphate mannose synthase, Ppm1, and in most Actinobacteria is used as the sugar donor for protein O-mannosyl transferase, Pmt, in protein glycosylation. Ppm1 and Pmt have homologues in yeasts and humans, where they are required for protein O-mannosylation. Actinobacteria also use PPM for lipoglycan biosynthesis. Here we show that ppm1 mutants of Streptomyces coelicolor have increased susceptibility to a number of antibiotics that target cell wall biosynthesis. The pmt mutants also have mildly increased antibiotic susceptibilities, in particular to β-lactams and vancomycin. Despite normal induction of the vancomycin gene cluster, vanSRJKHAX, the pmt and ppm1 mutants remained highly vancomycin sensitive indicating that the mechanism of resistance is blocked post-transcriptionally. Differential RNA expression analysis indicated that catabolic pathways were downregulated and anabolic ones upregulated in the ppm1 mutant compared to the parent or complemented strains. Of note was the increase in expression of fatty acid biosynthetic genes in the ppm1-
mutant. A change in lipid composition was confirmed using Raman spectroscopy, which showed that the ppm1
- mutant had a greater relative proportion of unsaturated fatty acids compared to the parent or the complemented mutant. Taken together, these data suggest that an inability to synthesize PPM (ppm1) and loss of the glycoproteome (pmt-
mutant) can detrimentally affect membrane or cell envelope functions leading to loss of intrinsic and, in the case of vancomycin, acquired antibiotic resistance.
Transmission of and susceptibility to seasonal influenza in Switzerland from 2003–2015
Authors: Brugger Jon , Althaus Christian L.
Published: February 2018

Understanding the seasonal patterns of influenza transmission is critical to help plan public health measures for the management and control of epidemics. Mathematical models of infectious disease transmission have been widely used to quantify the transmissibility of and susceptibility to past influenza seasons in many countries. The objective of this study was to obtain a detailed picture of the transmission dynamics of seasonal influenza in Switzerland from 2003-2015. To this end, we developed a compartmental influenza transmission model taking into account social mixing between different age groups and seasonal forcing. We applied a Bayesian approach using Markov chain Monte Carlo (MCMC) methods to fit the model to the reported incidence of influenza-like-illness (ILI) and virological data from Sentinella, the Swiss Sentinel Surveillance Network. The maximal basic reproduction number, R0, ranged from 1.46 to 1.81 (median). Median estimates of susceptibility to influenza ranged from 29% to 98% for different age groups, and typically decreased with age. We also found a decline in ascertainability of influenza cases with age. Our study illustrates how influenza surveillance data from Switzerland can be integrated into a Bayesian modeling framework in order to assess age-specific transmission of and susceptibility to influenza.
Bayesian model comparison for rare variant association studies
Authors: Venkataraman Guhan Ram , DeBoever Christopher , Tanigawa Yosuke , Aguirre Matthew , Ioannidis Alexander G. , Mostafavi Hakhamanesh , Spencer Chris C. A. , Poterba Timothy , Bustamante Carlos D. , Daly Mark J. , Pirinen Matti , Rivas Manuel A.
Published: February 2018

Whole genome sequencing studies applied to large populations or biobanks with extensive phenotyping raise new analytic challenges. The need to consider many variants at a locus or group of genes simultaneously and the potential to study many correlated phenotypes with shared genetic architecture provide opportunities for discovery and inference that are not addressed by the traditional one variant, one phenotype association study. Here, we introduce a Bayesian model comparison approach that we refer to as MRP (Multiple Rare-variants and Phenotypes) for rare-variant association studies that considers correlation, scale, and direction of genetic effects across a group of genetic variants, phenotypes, and studies. The approach requires only summary statistic data. To demonstrate the efficacy of MRP, we apply our method to exome sequencing data (N = 184,698) across 2,019 traits from the UK Biobank, aggregating signals in genes. MRP demonstrates an ability to recover previously-verified signals such as associations between PCSK9 and LDL cholesterol levels. We additionally find MRP effective in conducting meta-analyses in exome data. Notable non-biomarker findings include associations between MC1R and red hair color and skin color, IL17RA and monocyte count, IQGAP2 and mean platelet volume, and JAK2 and platelet count and crit (mass). Finally, we apply MRP in a multi-phenotype setting; after clustering the 35 biomarker phenotypes based on genetic correlation estimates into four clusters, we find that joint analysis of these phenotypes results in substantial power gains for gene-trait associations, such as in TNFRSF13B in one of the clusters containing diabetes and lipid-related traits. Overall, we show that the MRP model comparison approach is able to improve upon useful features from widely-used meta-analysis approaches for rare variant association analyses and prioritize protective modifiers of disease risk.
Leveraging allele-specific expression to refine fine-mapping for eQTL studies
Authors: Zou Jennifer , Hormozdiari Farhad , Jew Brandon , Ernst Jason , Sul Jae Hoon , Eskin Eleazar
Published: February 2018

Many disease risk loci identified in genome-wide association studies are present in non-coding regions of the genome. It is hypothesized that these variants affect complex traits by acting as expression quantitative trait loci (eQTLs) that influence expression of nearby genes. This indicates that many causal variants for complex traits are likely to be causal variants for gene expression. Hence, identifying causal variants for gene expression is important for elucidating the genetic basis of not only gene expression but also complex traits. However, detecting causal variants is challenging due to complex genetic correlation among variants known as linkage disequilibrium (LD) and the presence of multiple causal variants within a locus. Although several fine-mapping approaches have been developed to overcome these challenges, they may produce large sets of putative causal variants when true causal variants are in high LD with many non-causal variants. In eQTL studies, there is an additional source of information that can be used to improve fine-mapping called allele-specific expression (ASE) that measures imbalance in gene expression due to different alleles. In this work, we develop a novel statistical method that leverages both ASE and eQTL information to detect causal variants that regulate gene expression. We illustrate through simulations and application to the Genotype-Tissue Expression (GTEx) dataset that our method identifies the true causal variants with higher specificity than an approach that uses only eQTL information. In the GTEx dataset, our method achieves the median reduction rate of 11% in the number of putative causal variants.

Contact

JaeHoonSul@mednet.ucla.edu, eeskin@cs.ucla.edu
Attention seeking in a spatially explicit game of mate choice and the evolution of dimorphic ornaments
Authors: Számadó Szabolcs
Published: February 2018

The evolution of conspicuous signals fascinated biologist ever since Darwin. The Handicap Principle was dominant explanation in the last decades; it proposed that exaggerated and conspicuous signals are costly signals of quality. There are other less popular explanations however, one them is that conspicuous signals function to call the attention of potential receivers. These ‘attention seeking displays’ need not reveal the quality of the signaller. There are many empirical examples and recently the idea was modelled in terms of a simple action-response game. However, action-response games model an interaction of a pair of signaller and receiver, thus they omit potential competition between signallers, which could be a crucial force behind the evolution of attention-seeking displays. Here I model this competition in a spatially explicit model of mate choice where males can give a continuous signal to call the attention of potential mates. The results show that attention-seeking displays readily evolve to the allowed maximum when the cost of signalling is low. However, dimorphism evolves when the cost of signalling is high. The population consist of two types of males at this dimorphic state: males that do not give a signals and males that give the highest intensity signal possible. The results show that variation in quality is not a necessary requirement for the evolution of dimorphic traits.
The plasma miR-122 basal levels respond to circulating catecholamines in rats
Authors: Peng Xu , Li Qiao , Lu Song , He Xueling , Yu Sisi , Zhang Zhihui , Xu Guohui , Li Lu , Yang Tinghan , Zhu Jiang , Zhu Wenli , Wu Zhigang , Luo Delun , Zhu Jie , Xu Binghe , Huang Jian , Yin Hailin , Xu Kai
Published: February 2018

miR-122 in circulation is a promising non-invasive biomarker as a replacement or supplement of current serum biomarkers for liver injuries. But the concept was questioned by recent studies, mainly due to its release from hepatocytes in absence of overt cellular injuries. In this study, we reported that the hepatic metabolism of circulating catecholamines resulted in the release of hepatocyte-specific miR-122. Acute stress-induced hepatocellular deformation was histopathologically different from drug-induced liver injury with significant increases of plasma miR-122 levels. The basal levels of human plasma miR-122 could be significantly altered by emotional responses. Interday variances of plasma miR-122 measurements were reduced effectively by stress-relief measures. The metabolism of basal circulating norepinephrine and epinephrine in liver might contribute to the basal levels of plasma miRNAs expressed in hepatocytes.
Conservation of sex-linked markers among conspecific populations of a viviparous skink, Niveoscincus ocellatus, exhibiting genetic and temperature dependent sex determination
Authors: Hill Peta , Burridge Christopher P. , Ezaz Tariq , Wapstra Erik
Published: February 2018

Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whilst in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater divergence of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems (GSD and TSD-like systems) can be facilitated by subtle genetic differences.
Bounded Rationality in C. elegans
Authors: Cohen Dror , Volovich Meshi , Zeevi Yoav , Elbaum Lilach , Louie Kenway , Levy Dino J , Rechavi Oded
Published: February 2018

Rational choice theory assumes optimality in decision-making. Violations of a basic axiom of economic rationality known as “Independence of Irrelevant Alternatives” (IIA), have been demonstrated in both humans and animals, and could stem from common neuronal constraints. We developed tests for IIA in the nematode Caenorhabditis elegans, an animal with only 302 neurons, using olfactory chemotaxis assays. We found that in most cases C. elegans make rational decisions. However, by probing multiple neuronal architectures using various choice sets, we show that asymmetric sensation of odor options by the AWCON neuron can lead to violations of rationality. We further show that genetic manipulations of the asymmetry between the AWC neurons can make the worm rational or irrational. Last, a normalization-based model of value coding and gain control explains how particular neuronal constraints on information coding give rise to irrationality. Thus, we demonstrate that bounded rationality could arise due to basic neuronal constraints.
Regulation of (p)ppGpp hydrolysis by a conserved archetypal regulatory domain
Authors: Ronneau Séverin , Caballero-Montes Julien , Mayard Aurélie , Garcia-Pino Abel , Hallez Régis
Published: February 2018

Sensory and regulatory domains allow bacteria to adequately respond to environmental changes. The regulatory ACT domains are mainly found in metabolic-related proteins as well as in long (p)ppGpp synthetase/hydrolase (SD/HD) enzymes. Here, we investigate the functional role of the ACT domain of SpoT, the only (p)ppGpp SD/HD ofCaulobacter crescentus. We show that SpoT requires the ACT domain to hydrolyse ppGpp in an efficient way. In addition, ourin vivoandin vitrodata show that the phosphorylated version of EIIANtr(EIIANtr~P) interacts directly with the ACT to inhibit the hydrolase activity of SpoT. Finally, we highlight the conservation of the ACT-dependent interaction between EIIANtr~P and SpoT/Rel along with the PTSNtr-dependent regulation of (p)ppGpp accumulation upon nitrogen starvation inSinorhizobium meliloti, a plant-associated α-proteobacterium. Thus, this work suggests that α-proteobacteria might have inherited from a common ancestor, a PTSNtrdedicated to modulate (p)ppGpp levels.
A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy
Authors: Nikopoulos Konstantinos , Cisarova Katarina , Quinodoz Mathieu , Koskiniemi-Kuending Hanna , Miyake Noriko , Farinelli Pietro , Ur Rehman Atta , Imran Khan Muhammad , Prunotto Andrea , Akiyama Masato , Kamatani Yoichiro , Terao Chikashi , Miya Fuyuki , Ikeda Yasuhiro , Ueno Shinji , Fuse Nobuo , Murakami Akira , Wada Yuko , Terasaki Hiroko , Sonoda Koh-Hei , Ishibashi Tatsuro , Kubo Michiaki , Cremers Frans P. M. , Kutalik Zoltán , Matsumoto Naomichi , Nishiguchi Koji M. , Nakazawa Toru , Rivolta Carlo
Published: February 2018

Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e. a 3.5-fold enrichment; p-value = 9.2×10−5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation, in trans with the Alu insertion, but might also cause disease in association with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.
ANIMA: Association Network Integration for Multiscale Analysis
Authors: Deffur Armin , Wilkinson Robert J , Mayosi Bongani M , Mulder Nicola
Published: February 2018

Contextual functional interpretation of -omics data derived from clinical samples is a classical and difficult problem in computational systems biology. The measurement of thousands of datapoints on single samples has become routine but relating ‘big data’ datasets to the complexities of human pathobiology is an area of ongoing research. Complicating this is the fact that many publically available datasets use bulk transcriptomics data from complex tissues like blood. The most prevalent analytic approaches derive molecular ‘signatures’ of disease states or apply modular analysis frameworks to the data. Here we show, using a network-based data integration method using clinical phenotype and microarray data as inputs, that we can reconstruct multiple features (or endophenotypes) of disease states at various scales of organization, from transcript abundance patterns of individual genes through co-expression patterns of groups of genes to patterns of cellular behavior in whole blood samples, both in single experiments as well as in a meta-analysis of multiple datasets.
Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer
Authors: Hsu Chih-Chao , Shi Jiejun , Yuan Chao , Zhao Dan , Jiang Shiming , Lyu Jie , Wang Xiaolu , Li Haitao , Wen Hong , Li Wei , Shi Xiaobing
Published: February 2018

Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for “reader” proteins. The bromodomain (BRD) has long been thought to be the sole protein module that recognizes acetylated histones. Recently, we identified the YEATS domain of AF9 (ALL1 fused gene from chromosome 9) as a novel acetyl-lysine-binding module and showed that the ENL (eleven-nineteen leukemia) YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias. The human genome encodes four YEATS domain proteins, including GAS41, a component of chromatin remodelers responsible for H2A.Z deposition onto chromatin; however, the importance of the GAS41 YEATS domain in human cancer remains largely unknown. Here we report that GAS41 is frequently amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell proliferation, survival, and transformation. Biochemical and crystal structural studies demonstrate that GAS41 binds to histone H3 acetylated on H3K27 and H3K14, a specificity that is distinct from that of AF9 or ENL. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) analyses in lung cancer cells reveal that GAS41 colocalizes with H3K27ac and H3K14ac on the promoters of actively transcribed genes. Depletion of GAS41 or disruption of the interaction between its YEATS domain and acetylated histones impairs the association of histone variant H2A.Z with chromatin and consequently suppresses cancer cell growth and survival both in vitro and in vivo. Overall, our study identifies GAS41 as a histone acetylation reader that promotes histone H2A.Z deposition in NSCLC.
One-Tube Isolation of DNA from Mouse Tails
Authors: Green Michael R. , Sambrook Joseph
Published: February 2018

This protocol describes a variation of a simple method for isolation of DNA from mouse tails that uses commercially available gel-barrier tubes to eliminate the tedious transfer of samples during serial extractions with organic solvents. This variant is useful when processing very large numbers of samples.
Electroporation of Postimplantation Mouse Embryos In Utero
Authors: Huang Cheng-Chiu , Carcagno Abel
Published: February 2018

Gene transfer by electroporation is possible in mouse fetuses within the uterus. As described in this protocol, the pregnant female is anesthetized, the abdominal cavity is opened, and the uterus with the fetuses is exteriorized. A solution of plasmid DNA is injected through the uterine wall directly into the fetus, typically into a cavity like the brain ventricle, guided by fiber optic illumination. Electrodes are positioned on the uterus around the region of the fetus that was injected, and electrical pulses are delivered. The uterus is returned to the abdominal cavity, the body wall is sutured closed, and the female is allowed to recover. The manipulated fetuses can then be collected and analyzed at various times after the electroporation. This method allows experimental access to later-stage developing mouse embryos.
Inhibiting miRNA Function by Antisense Oligonucleotides in Drosophila S2 Cells
Authors: Li Chengjian , Zamore Phillip D.
Published: February 2018

This protocol describes methods to transfect antisense oligonucleotides (ASOs) into Drosophila S2 cells for suppression of miRNA function. The effects of ASOs on the miRNA are evaluated by measuring the protein level of the putative miRNA target or the activity of a reporter bearing a 3′ UTR derived from the putative miRNA target.
Caring for Escherichia coli
Authors: Green Michael R. , Sambrook Joseph
Published: February 2018

The bacterial strain E. coli K-12 has played an indisputably important role over the past century—in biology overall and in molecular biology in particular. Strains of E. coli (either untransformed or transformed with a plasmid) are usually sent through the mail as agar stab cultures. All strains must be validated as soon as they enter the laboratory, before they are used in experiments. This protocol provides guidelines for validation and storage of E. coli and plasmids.
High-Throughput Quantitative Genetic Interaction Mapping in the Fission Yeast Schizosaccharomyces pombe
Authors: Roguev Assen , Ryan Colm J. , Hartsuiker Edgar , Krogan Nevan J.
Published: February 2018

Epistasis mapping, in which the phenotype that emerges from combining pairs of mutations is measured quantitatively, is a powerful tool for unbiased study of gene function. When performed at a large scale, this approach has been used to assign function to previously uncharacterized genes, define functional modules and pathways, and study their cross talk. These experiments rely heavily on methods for rapid sampling of binary combinations of mutant alleles by systematic generation of a series of double mutants. Epistasis mapping technologies now exist in various model systems. Here we provide an overview of different epistasis mapping technologies, including the pombe epistasis mapper (PEM) system designed for the collection of quantitative genetic interaction data in fission yeast Schizosaccharomyces pombe. Comprising a series of high-throughput selection steps for generation and characterization of double mutants, the PEM system has provided insight into a wide range of biological processes as well as facilitated evolutionary analysis of genetic interactomes across different species.
Buffers
Authors: Green Michael R. , Sambrook Joseph
Published: February 2018

Biological reactions work well only within a narrow concentration range of hydrogen ions. Paradoxically, however, many of these reactions themselves generate or consume protons. Buffers are substances that undergo reversible protonation within a particular pH range and therefore maintain the concentration of hydrogen ions within acceptable limits. This introduction describes standard buffers used in molecular cloning, including Tris buffers, Good buffers, and phosphate buffers.
Strategic foresight for organizational agility at Nedbank Area Collaboration
Authors: Oosthuizen Marius , Scheepers Caren
Published: February 2018

Subject area

The case study uses a strategic foresight method, scenario-planning, to examine the strategic options for a financial services firm. As such, it covers the fields of strategy, environment of business, innovation, digital disruption and organizational change as they relate to the firm’s ability to adapt to changes in the environment of business in an emerging market context.

Study level/applicability

The case was developed with master's-level students in mind, particularly those seeking a master of business administration, masters in strategic foresight or related management degrees.

Case overview

The case of NEDBANK, a longstanding and successful financial services firm based in South Africa is confronted with major challenges from competitors because of technological change in the industry as well as having to expand their market penetration across Africa. A rising regulatory burden, tough economic conditions and the need to access low income markets, provide a significant organizational development challenge as a decades-old bank, known for a relational approach to banking, has to navigate the new domains of “fintech”, micro-lending and public sector banking.

Expected learning outcomes

Students will gain comprehensive insight into the industry environment in emerging markets, understand the strategic management challenge before financial services firms in this environment and be able to consider the alternative strategic interventions that may be used to ensure corporate sustainability amid these challenges. Simultaneously, the case provides a comprehensive view into the use and application of scenario-planning for strategic management.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS: 11: Strategy
An innovative work behaviour-enhancing employability model moderated by age
Authors: Stoffers Jol M.M. , Van der Heijden Béatrice I.J.M.
Published: February 2018

Purpose

This study aims to empirically validate an innovative work behaviour-enhancing model of employability in small- and medium-sized enterprises (SMEs), and to examine possible moderating effects of age.

Design/methodology/approach

Data have been collected from 487 pairs of employees and their immediate supervisors who worked in 151 SMEs. Structural equation modelling (SEM) has been used to investigate the predictive validity of employability on innovative work behaviour using a multi-source approach. The moderating effect of employee age on the relationship between, on the one hand, self-ratings and supervisor ratings of employability, and, on the other hand, innovative work behaviour has been tested using multi-group SEM.

Findings

Results suggest that self-rated employability correlates positively with supervisor-rated innovative work behaviour, and that supervisor-rated employability correlates positively with self-rated innovative work behaviour. Age appeared to have a weak influence on the relationship between employability and innovative work behaviour; more specifically, in case of a higher age, the relationship was stronger.

Research limitations/implications

The cross-sectional design is a limitation of this study. Another limitation relates to the generalizability of the study findings outside the context in which the research has been undertaken. The relational meaning of employee age might be different in other cultures.

Practical implications

Supervisors appear to play an essential role in providing an age-friendly working life for employees. Moreover, as SMEs often do not employ professionals to manage human resources, supervisors themselves have to carry the responsibility to encourage aging employees to develop themselves the enhancing innovative work behaviour.

Originality/value

This study is the first to investigate the predictive validity of employability on innovative work behaviour and the effects of age on this relationship.
Factors influencing price premiums of Australian wine in the UK market
Authors: Shane Elyse , Murad MD Wahid , Freeman Susan
Published: February 2018

Purpose

The purpose of this paper is to determine and analyse that factors that could potentially influence price premiums of Australian wine in the UK market. The authors integrated the economic-based hedonic pricing theory and marketing export pricing literature. The authors demonstrate a potential solution to limitations in knowledge of market-level data and industry wide competition, currently lacking in export pricing studies.

Design/methodology/approach

Using data extracted from wine-searcher.com and using multiple regression as the main analytical technique, the authors examined the relationships between actual retail prices UK consumers pay for Australian wine and product attributes. The authors compared the moderating influence of distribution channel (retail choice) on these relationships.

Findings

The results provide insights in export pricing literature, and the authors support better theoretical explanations for hedonic pricing studies in export marketing. The authors found two types of wine attributes – “brand” and “region of origin” – that attract price premiums. While relationships between variety and retail price, as well as age and retail price are less clear, the authors provide some support.

Research limitations/implications

One limitation of this hedonic pricing study is the inability to explain why certain relationships between product attributes and price premiums exist. Studies such as these could be improved by utilising both consumer- and firm-level data.

Practical implications

Whilst final prices paid by consumers are beyond the control of producers, understanding the relationships between retail prices, retail choices and product attributes are of strategic importance. Understanding the role consumer preferences play in determining prices they ultimately pay is of great value when determining export/retail pricing strategies.

Social implications

Consumers and firm managers are jointly able to provide comprehensive explanations on why certain attributes attract price premiums. The integration of economic and consumer-based theories provides a holistic understanding of the influence of retail choices and product attributes on retail prices.

Originality/value

The authors drew on the hedonic pricing theory linking product attributes with retail prices, which is vital for understanding market share and brand image. The authors identified which product attributes and which distribution channels (retail choices) are valuable to consumers. Deeper understanding of these issues is important for producers.
Consumers’ willingness to pay for local muscadine wine
Authors: Everett Connie , Jensen Kimberly , Boyer Christopher , Hughes David
Published: February 2018

Purpose

This paper aims to identify factors influencing the likelihood of consumers trying muscadine wines and among those who have tried them, willingness to pay (WTP) for an in-state produced muscadine wine.

Design/methodology/approach

The study uses a 2015 survey of wine consumers residing in Tennessee (TN). The survey presented respondents with a referendum choice experiment between a ‘base’ wine (represented by a North Carolina (NC) muscadine wine) and a TN muscadine wine. The study uses probit regressions to estimate factors influencing the probability of trying muscadine, and those influencing TN muscadine wine choice. Estimates of WTP for TN muscadine wine are derived from the model coefficients.

Findings

Older age, living in non-metro households being a weekly wine consumer, preferring red wines, and having visited a winery in the past year positively influence trying muscadines. Older age, liking muscadines and lower product price positively influence TN muscadine choice. Greater importance of wines being local and premiums paid for local foods have positive influences on trying muscadines and WTP for TN muscadine wine. A premium WTP for a TN muscadine over a NC muscadine exists among TN consumers. Among the most influential reasons why consumers chose the TN muscadine were beliefs that purchasing local wines helps local wine grape growers and local economies.

Originality/value

This study provides the muscadine wine industry with estimates of WTP for locally produced muscadines and demonstrates that attitudes toward local wines and premium paid for local foods positively influence trying muscadine wine and WTP for locally produced muscadine.
Intangible resources influencing the international performance of professional service SMEs in an emerging market
Authors: Radulovich Lori , Javalgi Rajshekhar (Raj) G. , Scherer Robert F.
Published: February 2018

Purpose

The purpose of this paper is to empirically examine the relationships between the drivers of economic growth in emerging markets to include entrepreneurial orientation (EO), human capital (HC), relational capital (RC), and international performance (IP).

Design/methodology/approach

Data were collected from 199 small- to medium-sized Indian professional service entrepreneurs that employ less than 500 employees and engage in international business. Given the multidimensional nature of IP, structural equation modeling (SEM) was used to test the measurement and substantive models.

Findings

SEM and mediation tests confirmed significant relationships among the constructs in the model and indicated that HC can be leveraged for international growth using RC to deliver new professional services across borders. EO, the strongest predictor, along with HC and RC, directly influenced IP. The effect of HC is mediated by an EO and RC.

Research limitations/implications

By design, only successful professional service firms in India were studied, which limited generalizability.

Practical implications

Entrepreneurs can enhance the likelihood of international expansion success by utilizing highly skilled HC and developing strong network relationships. Entrepreneurial managers should leverage their professional service resources through judicious investments in personnel and relationship-building skills to develop RC.

Originality/value

This study examined entrepreneurial professional HC and RC as related to international entrepreneurship emerging market research. Data collection in India contributes to empirical research on internationalization from emerging markets.
Managerial support for development and turnover intention
Authors: Kumar Manish , Jauhari Hemang , Rastogi Ashish , Sivakumar Sandeep
Published: February 2018

Purpose

The purpose of this paper is to integrate learnings from social exchange theory, organizational support theory and JD-R model to explore the relationship among support for development, work engagement (WE), job satisfaction (JS) and turnover intention (TI). It was hypothesized that the relationship between managerial support for development (MSD) and TI would be explained through organizational support for development (OSD), WE and overall job satisfaction (OJS).

Design/methodology/approach

A cross-sectional survey on a sample of 5,088 service industry employees undergoing organizational change and working in the business-to-business context was employed. Reponses were analyzed using IBM® SPSS® AMOSTM 20.

Findings

The findings were along the hypothesized lines. The study found support for mediation by OSD, WE and OJS, respectively of MSD and TI relationship. Similarly, the mediation of MSD-OJS relationship by OSD and WE, respectively were also supported. Furthermore, OSD mediated the relationship between MSD and WE; while the relationship between OSD and TI was mediated by WE and OJS, respectively and additionally, the OSD-OJS relationship was mediated by WE. Lastly, the mediation of WE-TI relationship by OJS was also supported. Therefore, the sequence of MSD-OSD-WE-OJS-TI partial mediation model was supported.

Research limitations/implications

While the sample size (n=5,088) is large, the respondents belong to one business unit of an organization, constraining generalizability. Additionally, the study is limited by cross-sectional design. Finally, the study was restricted by the choices of perceptual measures of study variables and non-quantitative evaluation of discretion/job demand.

Originality/value

Using learnings from multiple theories, the present study examined the roles of two sources of support for development (organizational and managerial) and two job-related states (WE and JS) in relating with TI. Interestingly, all the expected relationships were true in a context signifying the discretionary nature of organization. Further, testing of alternate models gives additional credence to the findings.