bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of lumps and dark–dark solitons in the multi-component long-wave–short-wave resonance interaction system
Authors: Rao Jiguang , Porsezian Kuppuswamy , He Jingsong , Kanna Thambithurai
Published: January 2018

General semi-rational solutions of an integrable multi-component (2+1)-dimensional long-wave–short-wave resonance interaction system comprising multiple short waves and a single long wave are obtained by employing the bilinear method. These solutions describe the interactions between various types of solutions, including line rogue waves, lumps, breathers and dark solitons. We only focus on the dynamical behaviours of the interactions between lumps and dark solitons in this paper. Our detailed study reveals two different types of excitation phenomena: fusion and fission. It is shown that the fundamental (simplest) semi-rational solutions can exhibit fission of a dark soliton into a lump and a dark soliton or fusion of one lump and one dark soliton into a dark soliton. The non-fundamental semi-rational solutions are further classified into three subclasses: higher-order, multi- and mixed-type semi-rational solutions. The higher-order semi-rational solutions show the process of annihilation (production) of two or more lumps into (from) one dark soliton. The multi-semi-rational solutions describe
N
(
N
≥2) lumps annihilating into or producing from
N
-dark solitons. The mixed-type semi-rational solutions are a hybrid of higher-order semi-rational solutions and multi-semi-rational solutions. For the mixed-type semi-rational solutions, we demonstrate an interesting dynamical behaviour that is characterized by partial suppression or creation of lumps from the dark solitons.
Coadaptation of mitochondrial and nuclear genes, and the cost of mother's curse
Authors: Connallon Tim , Camus M. Florencia , Morrow Edward H. , Dowling Damian K.
Published: January 2018

Strict maternal inheritance renders the mitochondrial genome susceptible to accumulating mutations that harm males, but are otherwise benign or beneficial for females. This ‘mother's curse’ effect can degrade male survival and fertility if unopposed by counteracting evolutionary processes. Coadaptation between nuclear and mitochondrial genomes—with nuclear genes evolving to compensate for male-harming mitochondrial substitutions—may ultimately resolve mother's curse. However, males are still expected to incur a transient fitness cost during mito-nuclear coevolution, and it remains unclear how severe such costs should be. We present a population genetic analysis of mito-nuclear coadaptation to resolve mother's curse effects, and show that the magnitude of the ‘male mitochondrial load’—the negative impact of mitochondrial substitutions on male fitness components—may be large, even when genetic variation for compensatory evolution is abundant. We also find that the male load is surprisingly sensitive to population size: male fitness costs of mito-nuclear coevolution are particularly pronounced in both small and large populations, and minimized in populations of intermediate size. Our results reveal complex interactions between demography and genetic constraints during the resolution of mother's curse, suggesting potentially widespread species differences in susceptibility to mother's curse effects.
The evolution, distribution and diversity and of endogenous circoviral elements
Authors: Dennis Tristan P.W , de Souza William Marciel , Marsile-Medun Soledad , Singer Joshua B. , Wilson Sam J. , Gifford Robert J.
Published: January 2018

Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe can provide unique, retrospective information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe.

Abbreviations

CVe

endogenous circoviral element

ORF

open reading frame

Cap

Capsid

Rep

Replicase

ssDNA

single-stranded DNA
Analysis of functional connectivity and oscillatory power using DICS: from raw MEG data to group-level statistics in Python
Authors: Vliet Marijn van , Liljeström Mia , Aro Susanna , Salmelin Riitta , Kujala Jan
Published: January 2018

Communication between brain regions is thought to be facilitated by the synchronization of oscillatory activity. Hence, large-scale functional networks within the brain may be estimated by measuring synchronicity between regions. Neurophysiological recordings, such as magnetoencephalography (MEG) and electroencephalography (EEG), provide a direct measure of oscillatory neural activity with millisecond temporal resolution. In this paper, we describe a full data analysis pipeline for functional connectivity analysis based on dynamic imaging of coherent sources (DICS) of MEG data. DICS is a beamforming technique in the frequency-domain that enables the study of the cortical sources of oscillatory activity and synchronization between brain regions. All the analysis steps, starting from the raw MEG data up to publication-ready group-level statistics and visualization, are discussed in depth, including methodological considerations, rules of thumb and tradeoffs. We start by computing cross-spectral density (CSD) matrices using a wavelet approach in several frequency bands (alpha, theta, beta, gamma). We then provide a way to create comparable source spaces across subjects and discuss the cortical mapping of spectral power. For connectivity analysis, we present a canonical computation of coherence that facilitates a stable estimation of all-to-all connectivity. Finally, we use group-level statistics to limit the network to cortical regions for which significant differences between experimental conditions are detected and produce vertex-and parcel-level visualizations of the different brain networks. Code examples using the MNE-Python package are provided at each step, guiding the reader through a complete analysis of the freely available openfMRI ds000117 “familiar vs. unfamiliar vs. scrambled faces” dataset. The goal is to educate both novice and experienced data analysts with the “tricks of the trade” necessary to successfully perform this type of analysis on their own data.
Non-linear transfer characteristics of stimulation and recording hardware account for spurious low-frequency artifacts during amplitude modulated transcranial alternating current stimulation (AM-tACS)
Authors: Kasten Florian H. , Negahbani Ehsan , Fröhlich Flavio , Herrmann Christoph S.
Published: January 2018

Amplitude modulated transcranial alternating current stimulation (AM-tACS) has been recently proposed as a possible solution to overcome the pronounced stimulation artifact encountered when recording brain activity during tACS. In theory, AM-tACS does not entail power at its modulating frequency, thus avoiding the problem of spectral overlap between brain signal of interest and stimulation artifact. However, the current study demonstrates how weak non-linear transfer characteristics inherent in stimulation and recording hardware can reintroduce spurious artifacts at the modulation frequency. The input-output transfer functions (TFs) of different stimulation setups were measured. The setups included basic recordings of signal-generator and stimulator outputs as well as M/EEG phantom measurements. 6th-degree polynomial regression models were fitted to model the input-output TFs of each setup. The resulting TF models were applied to digitally generated AM-tACS signals to predict the location of spurious artifacts in the spectrum. All four setups measured for the study exhibited low-frequency artifacts at the modulation frequency and its harmonics when recording AM-tACS. Fitted TF models showed non-linear contributions significantly different from zero (all p < .05) and successfully predicted the frequency of artifacts observed in AM-signal recordings. Results suggest that even weak non-linearities of stimulation and recording hardware can lead to spurious artifacts at the modulation frequency and its harmonics. Thus, findings emphasize the need for more linear stimulation devices for AM-tACS and careful analysis procedures, which take into account these low-frequency artifacts to avoid confusion with effects of AM-tACS on the brain.
Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition
Authors: Lax Elad , DoCarmo Sonia , Enuka Yehoshua , Sapozhnikov Daniel M. , Welikovitch Lindsay A. , Mahmood Niaz , Rabbani Shafaat A. , Wang Liqing , Britt Jonathan P. , Hancock Wayne W. , Yarden Yosef , Szyf Moshe
Published: January 2018

The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown.

Here we show that Mbd2-deficiency in mice (Mbd2−/−) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2−/− mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brains of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2−/− mice.

These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD individuals.
Emergent memory in cell signaling: Persistent adaptive dynamics in cascades can arise from the diversity of relaxation time-scales
Authors: Mitra Tanmay , Menon Shakti N. , Sinha Sitabhra
Published: January 2018

The mitogen-activated protein kinase (MAPK) signaling cascade, an evolutionarily conserved motif present in all eukaryotic cells, is involved in coordinating critical cell-fate decisions, regulating protein synthesis, and mediating learning and memory. While the steady-state behavior of the pathway stimulated by a time-invariant signal is relatively well-understood, we show using a computational model that it exhibits a rich repertoire of transient adaptive responses to changes in stimuli. When the signal is switched on, the response is characterized by long-lived modulations in frequency as well as amplitude. On withdrawing the stimulus, the activity decays over timescales much longer than that of phosphorylation-dephosphorylation processes, exhibiting reverberations characterized by repeated spiking in the activated MAPK concentration. The long-term persistence of such post-stimulus activity suggests that the cascade retains memory of the signal for a significant duration following its removal, even in the absence of any explicit feedback or cross-talk with other pathways. We find that the molecular mechanism underlying this behavior is related to the existence of distinct relaxation rates for the different cascade components. This results in the imbalance of fluxes between different layers of the cascade, with the repeated reuse of activated kinases as enzymes when they are released from sequestration in complexes leading to one or more spike events following the removal of the stimulus. The persistent adaptive response reported here, indicative of a cellular “short-term” memory, suggests that this ubiquitous signaling pathway plays an even more central role in information processing by eukaryotic cells.
Variation in Genome-wide NF-kappaB RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile
Authors: Borghini Lisa , Lu Jinhua , Hibberd Martin , Davila Sonia
Published: January 2018

NF-kB transcription factors are master regulators of the innate immune response. Activated downstream of pathogen recognition receptors, they regulate the expression of genes to help fighting infections as well as recruiting the adaptive immune system. NF-kB responds to a wide variety of signals, but the processes by which stimulus-specificity is attained remain unclear. Here, we characterized the response of one NF-kB member, RELA, to four stimuli mimicking infection in human nasopharyngeal epithelial cells. Comparing genome-wide RELA binding, we observed stimulus-specific sites, although most sites overlapped across stimuli. Specifically, the response to Poly I:C – mimicking viral dsRNA and signalling through TLR3 – induced a distinct RELA profile, binding in the vicinity of antiviral genes and correlating with corresponding gene expression. This group of binding sites was also enriched in Interferon Regulatory Factor (IRF) motifs and showed overlapping with IRFs binding sites. A novel NF-kB target, OASL was further validated and showed TLR3-specific activation. This work showed that some RELA DNA binding sites varied in activation response following different stimulations and that interaction with more specialized factors could help achieve this stimulus-specific activity. Our data provide a genomic view of regulated host response to different pathogen stimuli.
Homology Directed Repair by Cas9:Donor Co-localization in Mammalian Cells
Authors: Roche Philip J.R. , Gytz Heidi , Hussain Faiz , Cameron Christopher J.F. , Paquette Denis , Blanchette Mathieu , Dostie Josée , Nagar Bhushan , Akavia Uri David
Published: January 2018

Homology directed repair (HDR) induced by site specific DNA double strand breaks (DSB) with CRISPR/Cas9 is a precision gene editing approach that occurs at low frequency in comparison to indel forming non homologous end joining (NHEJ). In order to obtain high HDR percentages in mammalian cells, we engineered Cas9 protein fused to a high-affinity monoavidin domain to deliver biotinylated donor DNA to a DSB site. In addition, we used the cationic polymer, polyethylenimine, to deliver Cas9 RNP-donor DNA complex into the cell. Combining these strategies improved HDR percentages of up to 90% in three tested loci (CXCR4, EMX1, and TLR) in standard HEK293 cells. Our approach offers a cost effective, simple and broadly applicable gene editing method, thereby expanding the CRISPR/Cas9 genome editing toolbox.

Precision gene editing occurs at a low percentage in mammalian cells using Cas9. Colocalization of donor with Cas9MAV and PEI delivery raises HDR occurrence.
Whole Genome Sequencing and Rare Variant Analysis in Essential Tremor Families
Authors: Odgerel Zagaa , Hernandez Nora , Park Jemin , Ottman Ruth , Louis Elan D. , Clark Lorraine N.
Published: January 2018

Essential tremor (ET) is one of the most common movement disorders. The etiology of ET remains largely unexplained. Whole genome sequencing (WGS) is likely to be of value in understanding a large proportion of ET with Mendelian and complex disease inheritance patterns. In ET families with Mendelian inheritance patterns, WGS may lead to gene identification where WES analysis failed to identify the causative variant due to incomplete coverage of the entire coding region of the genome. Alternatively, in ET families with complex disease inheritance patterns with gene x gene and gene x environment interactions enrichment of functional rare coding and non-coding variants may explain the heritability of ET. We performed WGS in eight ET families (n=40 individuals) enrolled in the Family Study of Essential Tremor. The analysis included filtering WGS data based on allele frequency in population databases, rare variant classification and association testing using the Mixed-Model Kernel Based Adaptive Cluster (MM-KBAC) test and prioritization of candidate genes identified within families using phenolyzer. WGS analysis identified candidate genes for ET in 5/8 (62.5%) of the families analyzed. WES analysis in a subset of these families in our previously published study failed to identify candidate genes. In one family, we identified a deleterious and damaging variant (c.1367G>A, p.(Arg456Gln)) in the candidate gene,CACNA1G, which encodes the pore forming subunit of T-type Ca(2+) channels, CaV3.1, and is expressed in various motor pathways and has been previously implicated in neuronal autorhythmicity and ET. Other candidate genes identified includeSLIT3(family D), which encodes an axon guidance molecule and in three families, phenolyzer prioritized genes that are associated with hereditary neuropathies (family A,KARS, family B,KIF5Aand family F,NTRK1). This work has identified candidate genes and pathways for ET that can now be prioritized for functional studies.
Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics
Authors: Gopinath Smita , Kim Myoungjoo V. , Rakib Tasfia , Wong Patrick W. , van Zandt Michael , Barry Natasha A. , Kaisho Tsuneyasu , Goodman Andrew L. , Iwasaki Akiko
Published: January 2018

Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-β (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistancein vivo.
miR-10b Deficiency Affords Atherosclerosis Resistance
Authors: Nakahara Masako , Kobayashi Norihiko , Oka Masako , Nakano Kenta , Okamura Tadashi , Yuo Akira , Saeki Kumiko
Published: January 2018

Human vascular endothelial cells (ECs) are categorized into two groups; pro-stenotic (Type-I) and anti-stenotic (Type-II) ECs, and one of the master genes for a stress-induced “Type-II-to-Type-I” degeneration is Regulator of G-protein signaling 5 (RGS5). Here we show that miR-10b is a crucial downstream mediator in RGS5-dependent degeneration. We also demonstrated the miR-10bhigh Type-I EC exosome has a trans effect which suppresses anti-proliferative abilities of Type-II ECs. Moreover, we found miR-10b-deficient mice showed a resistance to experimental atherosclerosis, where high-fat-high-cholesterol-diet-fed mice were subjected to partial carotid ligation. Furthermore, we determined the key target of miR-10b was Latent transforming growth factor-β binding protein 1 (LTBP1), which is a regulator of TGF-β signaling. Compatible with a commonly accepted view that TGF-β creates the major growth-inhibitory signal against vascular smooth muscle cells, TGF-β inhibitor treatments abolished anti-proliferative functions of Type-II ECs. Therefore, RGS5/miR-10b/LTBP1/TGF-β axis plays a leading role in quality control of ECs.
Antagonistic regulation with a unique setpoint, integral and double integral action
Authors: Thorsen Kristian , Ruoff Peter , Drengstig Tormod
Published: January 2018

Several biochemical species are in organisms controlled in a pairwise manner i.e., two different species (e.g., hormone, enzyme, transporter protein) work to control the concentration of a third chemical species. Such pairs are often antagonistic, meaning that one of the controller species acts to increase whereas the other controller species acts to decrease the amount of the controlled species. How antagonistic systems interact to achieve regulation and to avoid competing against each other is not fully understood. An issue is how two antagonistic hormones can agree upon one common setpoint. We present here a new type of antagonistic regulatory system that has a single unique setpoint inherently defined by the system. The regulatory system controls the concentration of a chemical species with both integral and double integral action, achieving tight control. We show by the use of an analytical stability analysis, using the principle of vanishing perturbations, that the setpoint is asymptotically stable. Finally the prospect of treating the presented system as a part of a larger family of antagonistic regulatory systems with unique setpoints, integral and double integral action is discussed.
CityNet - Deep Learning Tools for Urban Ecoacoustic Assessment
Authors: Fairbrass A. J. , Firman M. , Williams C. , Brostow G. J. , Titheridge H. , Jones K. E.
Published: January 2018

Cities support unique and valuable ecological communities, but understanding urban wildlife is limited due to the difficulties of assessing biodiversity. Ecoacoustic surveying is a useful way of assessing habitats, where biotic sound measured from audio recordings is used as a proxy for biodiversity. However, existing algorithms for measuring biotic sound have been shown to be biased by non-biotic sounds in recordings, typical of urban environments.

We develop CityNet, a deep learning system using convolutional neural networks (CNNs), to measure audible biotic (CityBioNet) and anthropogenic (CityAnthroNet) acoustic activity in cities. The CNNs were trained on a large dataset of annotated audio recordings collected across Greater London, UK. Using a held-out test dataset, we compare the precision and recall of CityBioNet and CityAnthroNet separately to the best available alternative algorithms: four acoustic indices (AIs): Acoustic Complexity Index, Acoustic Diversity Index, Bioacoustic Index, and Normalised Difference Soundscape Index, and a state-of-the-art bird call detection CNN (bulbul). We also compare the effect of non-biotic sounds on the predictions of CityBioNet and bulbul. Finally we apply CityNet to describe acoustic patterns of the urban soundscape in two sites along an urbanisation gradient.

CityBioNet was the best performing algorithm for measuring biotic activity in terms of precision and recall, followed by bulbul, while the AIs performed worst. CityAnthroNet outperformed the Normalised Difference Soundscape Index, but by a smaller margin than CityBioNet achieved against the competing algorithms. The CityBioNet predictions were impacted by mechanical sounds, whereas air traffic and wind sounds influenced the bulbul predictions. Across an urbanisation gradient, we show that CityNet produced realistic daily patterns of biotic and anthropogenic acoustic activity from real-world urban audio data.

Using CityNet, it is possible to automatically measure biotic and anthropogenic acoustic activity in cities from audio recordings. If embedded within an autonomous sensing system, CityNet could produce environmental data for cites at large-scales and facilitate investigation of the impacts of anthropogenic activities on wildlife. The algorithms, code and pre-trained models are made freely available in combination with two expert-annotated urban audio datasets to facilitate automated environmental surveillance in cities.
Clinical and MRI changes ofpuborectalisandiliococcygeusafter a short period of intensive pelvic floor muscles training with or without instrumentation
Authors: Dierick Frédéric , Galtsova Ekaterina , Lauer Clara , Buisseret Fabien , Bouché Anne-France , Martin Laurent
Published: January 2018

Purpose

This study evaluates the impact of a 3-week period of intensive pelvic floor muscles training (PFMT), with or without instrumentation, on clinical and static magnetic resonance imaging (MRI) changes ofpuborectalis(PR) andiliococcygeus(IL) muscles.

Methods

24 healthy young 5 women were enrolled in the study and 17 achieved the 9 sessions of 30 minutes training exercises and conducted all assessments. Participants were randomly assigned in two training groups: voluntary contractions combined with hypopressive exercises (HYPO) or biofeedback exercises combined with transvaginal electrical stimulations (ELEC). Clinical and T2-weighted MRI assessments io were realized before and after training.

Results

Modified Oxford Grading System (MOGS) scores for left PR and perineal body significantly increased in the two groups (p=0.039,p=0.008), but MOGS score for right PR significantly increased only in HYPO (p=0.020). Muscle volumes of right and left IL significantly decreased (p=0.040,p=0.045) after training as well as signal i5 intensities of right and left PR (p=0.040,p=0.021) and thickness of right and left IL at mid-vagina location (p=0.012,p=0.011).

Conclusions

A short period of intensive PFMT induces clinical and morphological changes in PFMs at rest suggesting a decrease in IL volume and adipose content of PR. Given the difference in cost and accessibility between HYPO and ELEC approaches, PFMT should be based primarily on non-instrumented exercises.
Odd skipped-related 1 (Osr1) identifies muscle-interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury
Authors: Stumm Jürgen , Vallecíllo Garcia Pedro , vom Hofe-Schneider Sophie , Ollitrault David , Schrewe Heinrich , Economides Aris N. , Marazzi Giovanna , Sassoon David A. , Stricker Sigmar
Published: January 2018

Fibro-adipogenic progenitors (FAPs) are resident mesenchymal progenitors in adult skeletal muscle that support muscle repair, but also give rise to fibrous and adipose infiltration in response to disease and chronic injury. FAPs are currently identified using cell surface markers that do not distinguish between quiescent FAPs and FAPs actively engaged in the regenerative process. We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development. Here we show that adult FAPs express Osr1 at low levels and frequency, however upon acute injury FAPs reactivate Osr1 expression in the injured tissue. Osr1+ FAPs are enriched in proliferating and apoptotic cells demonstrating that Osr1 identifies activated FAPs. In vivo genetic lineage tracing shows that Osr1+ activated FAPs return to the resident FAP pool after regeneration as well as contribute to adipocytes after glycerol-induced fatty degeneration. In conclusion, reporter LacZ or eGFP-CreERt2 expression from the endogenous Osr1 locus serves as marker for FACS isolation and tamoxifen-induced manipulation of activated FAPs.

Summary statement

Expression of Osr1 specifically in muscle interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury provides a tool to isolate and trace this population.
MicroRNA-92a negatively regulates neurofibromin 2 and inhibits its tumor suppressive function
Authors: Alcantara Krizelle Mae M. , Garcia Reynaldo L.
Published: January 2018

Inactivation of the tumor suppressor Merlin leads to the development of benign nervous system tumors of neurofibromatosis type 2. Merlin deficiency is also observed in human malignancies including colorectal and lung cancers. Causes of Merlin inactivation include deleterious mutations in the encoding neurofibromin 2 gene (NF2) and aberrant Merlin proteasomal degradation. Here, we show that NF2 is also regulated by microRNAs (miRNAs) through interaction with evolutionarily conserved miRNA response elements (MREs) within its 3’-untranslated region (3‘UTR). Dual luciferase assays in HCT116 and A549 show downregulation of wild type NF2 by miR-92a via its 3’UTR but not NF2-3’UTR with mutated MRE. HCT116 cells transfected with miR-92a show significant downregulation of endogenous NF2 mRNA and protein levels, which were rescued by co-transfection of a target protector oligonucelotide specific for the miR-92a binding site within NF2-3’UTR. MiR-92a overexpression in HCT116 and A549 resulted in increased migration and proliferation, apoptosis resistance, and altered F-actin organization compared to controls. This study provides functional proof of the unappreciated role of miRNAs in NF2 regulation and tumor progression.
Leading after the boom: developing future leaders from a future leader’s perspective
Authors: Akers Katie Lynn
Published: January 2018

Purpose

This paper aims for an open discussion of new traits which are important to the success of future leaders. By understanding what is important to the new generations coming into leadership roles and how that differs from previous generations, a new set of leadership traits can be developed to help future leaders find success. The purpose of this paper is to challenge the current practices of leadership traits that are being developed and defined for making successful leaders.

Design/methodology/approach

This paper was designed to raise questions regarding what traits are being developed in current leaders to make them successful and provide two suggestions for new traits to be developed in future leaders. The bulk of the research was from books that analyzed leadership characteristics and the generational needs of the previous and current generations. The information was accompanied with personal experience working as and with the new generation of potential leaders.

Findings

This paper initiates the need for a discussion on why it is important to start discussing the development of the future generation of leaders. It suggests that the traits of curiosity and belief will be beneficial to the success and fulfillment of future leaders.

Research limitations/implications

Because of the newness of this concept in regards to curiosity and belief being leadership traits, the research comes from theories and a real life, relevant understanding of leadership development. Therefore, it is encouraged to continue to build upon the thoughts and ideas presented in the paper.

Practical implications

This paper includes implications that there is a need for leadership development and that through the development of future leader traits, based on what they want from the workforce, will help to make them successful and sustainable future leaders.

Originality/value

This paper fulfills a need to understand what areas future leaders will need to be developed to create a new generation of effective and successful leaders.
Proposing micro-macro HRM strategies to overcome challenges of workforce diversity and deviance in ASEAN
Authors: Malik Pooja , Lenka Usha , Sahoo Debashish Kumar
Published: January 2018

Purpose

The purpose of this paper is to propose a conceptual framework associating globalization, workforce diversity, and deviance and suggest micro-macro HRM strategies to overcome challenges associated with the workforce diversity and workplace deviance.

Design/methodology/approach

A systematic review of literature of past 25 years was carried out with the key word “globalization, workforce diversity, and deviance” from several electronic databases.

Findings

Findings propose micro-macro HRM strategies to be adopted by HR practitioners in Association of Southeast Asian Nations (ASEAN) organizations to manage workforce diversity and deviance in the age of globalization.

Research limitations/implications

The challenges due to workforce diversity may get worse because ASEAN is more incongruent in terms of phases of economic, social, cultural, and political advancement. Therefore, proposed model can be tested and compared in different ASEAN organizations.

Originality/value

There is a dearth of literature associating globalization, workforce diversity, and deviance. This paper bridges this gap by proposing a conceptual framework in the ASEAN context and suggests micro-macro HRM strategies to be adopted by HRM practitioners to overcome associated challenges with workforce diversity and deviance.
Effect of commitment and customers’ satisfaction on the relationship between service quality and customer retention in rural banks in Makassar, Indonesia
Authors: Sigit Parawansa Dian Anggraece
Published: January 2018

Purpose

The purpose of this paper is to investigate the effect of commitment and customer’s satisfaction on the relationship between service quality and customer retention.

Design/methodology/approach

The research was conducted on the entire customer rural banks (BPR) in Makassar, South Sulawesi Province; the sample size comprised 300 respondents. Analysis equipment used in this study is a quantitative approach that is inferential statistical analysis with structural equation modeling based variance is known as a method WarpPLS.

Findings

The results of the analysis show that there is significant influence between the variables of service quality, commitment, customer satisfaction, and customer retention. It was also found that the results of the variables commitment and customer satisfaction mediate the effect of service quality on customer’s retention.

Originality/value

The study showed the mediation effect (using the Sobel test) of service quality on customer retention using commitment and customer satisfaction as intervening variables in rural banks; and the study was conducted in the customer rural banks (BPR) in Makassar, South Sulawesi Province, where no such study for this relationship has been conducted previously.
A systematic review and classification of interventions for speech‐sound disorder in preschool children
Authors: Wren Yvonne , Harding Sam , Goldbart Juliet , Roulstone Sue
Published: January 2018

Background

Multiple interventions have been developed to address speech sound disorder (SSD) in children. Many of these have been evaluated but the evidence for these has not been considered within a model which categorizes types of intervention. The opportunity to carry out a systematic review of interventions for SSD arose as part of a larger scale study of interventions for primary speech and language impairment in preschool children.

Aims

To review systematically the evidence for interventions for SSD in preschool children and to categorize them within a classification of interventions for SSD.

Methods & Procedures

Relevant search terms were used to identify intervention studies published up to 2012, with the following inclusion criteria: participants were aged between 2 years and 5 years, 11 months; they exhibited speech, language and communication needs; and a primary outcome measure of speech was used. Studies that met inclusion criteria were quality appraised using the single case experimental design (SCED) or PEDro‐P, depending on their methodology. Those judged to be high quality were classified according to the primary focus of intervention.

Outcomes & Results

The final review included 26 studies. Case series was the most common research design. Categorization to the classification system for interventions showed that cognitive–linguistic and production approaches to intervention were the most frequently reported. The highest graded evidence was for three studies within the auditory–perceptual and integrated categories.

Conclusions & Implications

The evidence for intervention for preschool children with SSD is focused on seven out of 11 subcategories of interventions. Although all the studies included in the review were good quality as defined by quality appraisal checklists, they mostly represented lower‐graded evidence. Higher‐graded studies are needed to understand clearly the strength of evidence for different interventions.
Identification of stress‐related microRNA biomarkers in type 2 diabetes mellitus: A systematic review and meta‐analysis
Authors: Liang Ying‐Zhi , Li Jia‐Jiang‐Hui , Xiao Huan‐Bo , He Yan , Zhang Ling , Yan Yu‐Xiang
Published: January 2018

Background

Many studies have investigated microRNAs (miRNAs) in the detection of type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress‐related miRNAs used as biomarkers of T2DM are summarized and analyzed.

Methods

PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for case–control miRNA profiling studies about T2DM. A meta‐analysis under a random effect was performed. Subgroup analysis was conducted based on different tissues and species. Sensitivity analysis was conducted to confirm the robustness among studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence intervals (95% CIs), and P‐values.

Results

The present meta‐analysis included 39 case–control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in three or more studies and, of these, 18 were inconsistent in their direction of dysregulation. Two significantly dysregulated miRNAs (let‐7 g and miR‐155) were identified in the meta‐analysis. Four miRNAs (miR‐142‐3p, miR‐155, miR‐21, and miR‐34c‐5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR‐146a, miR‐199a‐3p, miR‐200b, miR‐29b and miR‐30e) were dysregulated in animal models of diabetes. In addition, two dysregulated miRNAs (miR‐146a and miR‐21) were highly cornea specific and heart specific. In sensitivity analysis, only miR‐155 was still significantly dysregulated after removing studies with small sample sizes.

Conclusions

The present meta‐analysis revealed that 16 stress‐related miRNAs were significantly dysregulated in T2DM. MiR‐148b, miR‐223, miR‐130a, miR‐19a, miR‐26b and miR‐27b were selected as potential circulating biomarkers of T2DM. In addition, miR‐146a and miR‐21 were identified as potential tissue biomarkers of T2DM.
Left sleeve lobectomy versus left pneumonectomy for the management of patients with non‐small cell lung cancer
Authors: Wang Liang , Pei YuQuan , Li ShaoLei , Zhang ShanYuan , Yang Yue
Published: January 2018

Background

The study was conducted to compare the outcomes of sleeve lobectomy (SL) and pneumonectomy (PN) for management of the left lung in patients with non‐small cell lung cancer (NSCLC).

Methods

One hundred and thirty‐five patients who underwent left SL (n = 87) or left PN (n = 48) for NSCLC from January 2006 to December 2011 were enrolled in this retrospective study. Left SL was performed when technically possible. The clinicopathological features and treatment outcomes in both groups were compared. Survival was evaluated using the Kaplan–Meier method, and significant differences were calculated using the log‐rank test. Multivariate analysis was conducted using the Cox proportional hazards model to analyze significant variables associated with the outcomes of left SL.

Results

There were no significant differences in general clinicopathological features (age, gender, lymph node metastasis, pathological stage, and complications of bronchial fistula) between patients who underwent left SL and left PN. The operation duration was markedly longer and the extent of bleeding was greater for left SL than left PN; however patients who underwent left SL achieved significantly longer overall survival than patients who underwent left PN. The outcomes of left SL were only associated with pathological stage.

Conclusions

Our results indicate that left SL may offer superior survival than left PN in selected patients. If anatomically feasible, left SL may be a preferred alternative to left PN for NSCLC patients. Pathological stage is an important factor to determine the outcome of SL.
Downregulation of BarH‐like homeobox 2 promotes cell proliferation, migration and aerobic glycolysis through Wnt/β‐catenin signaling, and predicts a poor prognosis in non‐small cell lung carcinoma
Authors: Chen Hao , Zhang Maowei , Zhang Wenhui , Li Yuanqin , Zhu Jiechen , Zhang Xiaojiao , Zhao Li , Zhu Shuyang , Chen Bi
Published: January 2018

Background

Human BarH‐like homeobox 2 (Barx2), a homeodomain factor of the Bar family, plays a critical role in cell adhesion and cytoskeleton remodeling, and has been reported in an increasing array of tumor types except non‐small cell lung carcinoma (NSCLC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in NSCLC.

Methods

Quantitative real‐time polymerase chain reaction, immunohistochemistry and western blot analysis were used to examine mRNA and protein expression, respectively. The relationships between Barx2 expression and clinicopathological variables were analyzed. Cell Counting Kit‐8 and plate colony formation assay were used to detect cell proliferation. Transwell assay was used to examine cell migration ability. Glucose uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were used to detect aerobic glycolysis.

Results

Barx2 is downregulated in NSCLC tissues compared with para‐carcinoma. Furthermore, Barx2 expression shows a negative correlation with advanced TNM stage and a high level of Ki‐67. Survival analysis reveals that Barx2 level is an independent prognostic factor for NSCLC patients. The Barx2 (low) Ki‐67 (high) group had the worst prognosis. Furthermore, the data indicate that downregulation of Barx2 expression promotes cell proliferation, migration, and aerobic glycolysis, including increased lactate dehydrogenase activity, glucose utilization, lactate production, and decreased intracellular adenosine triphospahte level. Furthermore, Barx2 acts as a negative regulator of the canonical Wnt/β‐catenin pathway. Reactivation of Wnt/β‐catenin pathway by LiCl can reverse the inhibiting effect of Barx2.

Conclusions

These findings reveal that Barx2 serving as a tumor suppressor gene could decrease cell proliferation, migration, and aerobic glycolysis through inhibiting the Wnt/β‐catenin signaling pathway, and predicts a good prognosis in NSCLC.
Analysis of haplotype networks: The randomized minimum spanning tree method
Authors: Paradis Emmanuel
Published: January 2018

Haplotype network construction is a widely used approach for analysing and visualizing the relationships among DNA sequences within a population or species. This approach has some problems such as how to quantify alternative links among sequences or how to plot efficiently networks to compare them easily.

In this paper, a new method is presented: the randomized minimum spanning tree method, based on randomizing the input order of the data in order to produce alternative branchings in the haplotype network. It is shown that this new method can produce, at least in some situations, networks with less alternative links than the minimum spanning network method.

A new graphical display of haplotype networks is introduced here. This is based on calculating the coordinates of the haplotypes from a multidimensional scaling of the haplotype distance matrix. The display can be done in two or three dimensions. The eigenvalues extracted from the multidimensional scaling analysis give an indication of the relevant number of dimensions.

These tools are illustrated with the analyses of published data on the leopard and on the jaguar. These analyses show interesting and contrasting patterns between these two species of big cats.

All tools are implemented in R and available in the package pegas.
The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High‐ and Low‐Flux Hemodialyzers
Authors: Schneditz Daniel , Sarikakis Georgios , Kontodima Maria , Sauseng Notburga
Published: January 2018

The aim of this study was to examine the relationship between hydrostatic trans‐membrane pressure (TMPh) and colloid osmotic pressure (COP) in low‐flux (LF) and high‐flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg) under constant dialysate flow and variable blood flow (Qb) ranging from 0 to 400 mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted, undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit, all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly increased with increasing Qb. The intercept of the linear TMPh to Qb relationship correlated with measured COP with an average bias of 1.00 ± 2.26 mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear TMPh to Qb relationship increased with increasing sample viscosity and was much larger in HF dialyzers under otherwise identical operating conditions, most likely because of increased internal filtration. The TMPh to Qb relationship measured in dialyzers in absence of UF can be described by the intercept related to measured COP and the slope related to internal filtration. This relationship could be of interest to estimate internal filtration and COP under in vivo conditions.
The five‐year survival of children with Down syndrome in Norway 1994–2009 differed by associated congenital heart defects and extracardiac malformations
Authors: Brodwall Kristoffer , Greve Gottfried , Leirgul Elisabeth , Klungsøyr Kari , Holmstrøm Henrik , Vollset Stein Emil , Øyen Nina
Published: January 2018

Aim

We investigated the prevalence of Down syndrome in a nationwide birth cohort, focusing on congenital heart defects (CHDs), their associations with extracardiac malformations (ECM) and survival.

Methods

National registers were used to identify Norwegian births (1994–2009) and deaths (1994–2014) and updated with hospital diagnoses. We estimated birth defect frequencies in Down syndrome and the general population, the association between CHDs and ECM and hazard ratios for death from different combinations of CHDs and ECM.

Results

Down syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no other malformations. The five‐year survival for Down syndrome increased from 91.8% (1994–1999) to 95.8% (2000–2009) (p = 0.006), and overall survival was 92.0% with CHD and 97.4% without. Compared with Down syndrome children without CHD or ECM, the five‐year mortality was similar for those with nonsevere CHDs, without or with ECM, but 4–7 times higher in those with severe CHDs without ECM and 13–28 times higher in those with severe CHDs and ECM.

Conclusion

Down syndrome childhood survival improved, but mortality remained high with severe CHDs and extracardiac defects.