bluuebunny/crossref_metadata_2025 huggingface dataset:
Macropinocytosis and autophagy crosstalk in nutrient scavenging
Authors: Florey Oliver , Overholtzer Michael
Published: December 2018

Adaptive strategies used by cells to scavenge and recycle essential nutrients are important for survival in nutrient-depleted environments such as cancer tissues. Autophagy and macropinocytosis are two major mechanisms that promote nutrient recycling and scavenging, which share considerable, yet poorly understood, cross-regulation. Here we review recent findings that connect these starvation response mechanisms and discuss the implications of their crosstalk.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
The origins and evolution of macropinocytosis
Authors: King Jason S. , Kay Robert R.
Published: December 2018

In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers
Authors: Fan Shicai , Tang Jianxiong , Li Nan , Zhao Ying , Ai Rizi , Zhang Kai , Wang Mengchi , Du Wei , Wang Wei
Published: December 2018

The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450K BeadChip (Illumina 450K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in the majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, TRIM59, showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.
Zebrafish DANA retroposon can form large zebrafish sequence in human Hepg2 and 293T cell lines
Authors: Cao Zheming , Ding Weidong , Qiang Jun , Bing Xuwen , Xu Pao
Published: December 2018

In this study, we cloned small zebrafish retroposon DANA from zebrafish genome and constructed the lentiviral expression vector pEB-GFP (T2A)PURO. Three human cell lines including 293T, Hepg2 and LO2 were selected as infection targets. After detecting the expression of DANA, we found that the expression of DANA retroposon in three cells had different effects on cell lines through chromosome walking. Among these cells, LO2 showed no DANA retrotrans-position, while 293T and Hepg2 cell lines displayed retrotrans-position with the formation of some zebrafish genome fragments. Thereafter, we constructed a mutant of DANA retroposon and infected it in 293T cells, but no retrotrans-position was found after chromosome walking. Re-sequencing of the two cell lines (293T and Hepg2) showed that a large number of zebrafish genome fragments were found in the genomes of both cell lines, which could be divided into four types. The first type was zebrafish microsatellite sequence, accounting for 79.23% and 74.45% in 293T cell line and Hepg2 cell line, respectively. The second type was the sequence with a small amount of poly A or T, and the third type was the sequence with poly G or C, and the second and third types accounted very low proportion. The fourth type was composed of coding sequence and non-coding sequence, with large difference and very low proportion of common sequences between the two cell lines. Taken together, this study indicated that zebrafish DANA retroposon can result in retrotrans-position using the retrotrans system of human cell lines.
Adaptation of Acinetobacter baumannii to colistin exposure: Laboratory mimicking of a clinical case
Authors: Oralkan Ezgi , Keske Şiran , Ergonul Onder , Can Fusun
Published: December 2018

Adaptation of Acinetobacter baumannii to colistin use on a disease course of a patient was described. Effects of colistin was mimicked in the laboratory conditions. The colistin resistant isolate was identified from the patient after 25 days of colistin treatment. In the laboratory, the expressions of pmrCAB were the highest at the generation which was corresponded to the duration of therapy. A. baumannii can develop a stable colistin-resistant phenotype after three weeks of colistin exposure.
Spatial and Temporal Influences on Discrimination of Vibrotactile Stimuli on The Arm
Authors: Shah Valay A , Casadio Maura , Scheidt Robert A , Mrotek Leigh
Published: December 2018

Body-machine interfaces (BMIs) provide a non-invasive way to use and control external devices such as powered wheelchairs. Vibrotactile stimulation has been proposed as a way for BMIs to provide device performance feedback to the user, thereby reducing visual demands of closed-loop control. To advance the goal of developing a compact, multivariate vibrotactile display for BMIs, we performed two 2-alternative, forced choice experiments to determine the extent to which vibrotactile perception might vary across multiple stimulation sites. The first experiment assessed vibrotactile discrimination of sequentially presented stimuli within each of four dermatomes of the arm (C5, C7, C8, T1) and on the ulnar head. The second compared discrimination when pairs of vibrotactile stimuli were presented simultaneously vs. sequentially both within and across dermatomes. Although the first experiment found small but statistically significant differences across dermatomes C7 and T1, discrimination thresholds at the other three locations did not differ one from another or from those at either C7 or T1. These results suggest that stimuli applied to each of the sites may be able to convey approximately the same amount of information. The second experiment found that sequential delivery of vibrotactile stimuli resulted in better discrimination than simultaneous delivery, independent of whether the pairs were located within the same dermatome or across dermatomes. Taken together, our results suggest that the arm may be a viable site to transfer multivariate information via vibrotactile feedback for body-machine interfaces. However, user training may be needed to overcome the perceptual disadvantage of simultaneous vs. sequentially-presented stimuli.
Inhibition Of Nitric Oxide Synthesis By Dexamethasone Increases Survival Rate In Plasmodium berghei-Infected Mice
Authors: Moreira Danilo Reymão , Uberti Ana Carolina MG , Gomes Antonio Rafael Q , Ferreira Michelli Erica Souza , Santos Rogério Silva , Green Michael Dean , Vieira José Ricardo dos Santos , Dolabela Maria Fani , Percario Sandro
Published: December 2018

Malaria still presents great epidemiologic importance by its high incidence in the world and potential clinical severity. Plasmodium parasites are highly susceptible to changes in the redox balance and the relationship between the redox state of the parasite and host cells is very complex and involves nitric oxide (NO) synthesis. Thus, the present study is aimed at evaluating the effects of NO synthesis on the redox status, parasitemia evolution and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and submitted to the stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice and data suggested the participation of oxidative stress in brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of iNOS caused a decrease of parasitemia and increased survival rate of infected animals, suggesting that the synthesis of NO may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.
Genome-wide association meta-analysis identifies novel GP2 gene risk variants for pancreatic cancer in the Japanese population
Authors: Lin Yingsong , Nakatochi Masahiro , Ito Hidemi , Kamatani Yoichiro , Inoko Akihito , Sakamoto Hiromi , Kinoshita Fumie , Kobayashi Yumiko , Ishii Hiroshi , Ozaka Masato , Sasaki Takashi , Matsuyama Masato , Sasahira Naoki , Morimoto Manabu , Kobayashi Satoshi , Fukushima Taito , Ueno Makoto , Ohkawa Shinichi , Egawa Naoto , Kuruma Sawako , Mori Mitsuru , Nakao Haruhisa , Adachi Yasushi , Okuda Masumi , Osaki Takako , Kamiya Shigeru , Wang Chaochen , Hara Kazuo , Shimizu Yasuhiro , Miyamoto Tatsuo , Hayashi Yuko , Hosono Yasuyuki , Ebi Hiromichi , Kohmoto Tomohiro , Imoto Issei , Murakami Yoshinori , Akiyama Masato , Ishigaki Kazuyoshi , Matsuda Koichi , Hirata Makoto , Shimada Katsuaki , Okusaka Takuji , Kawaguchi Takahisa , Takahashi Meiko , Watanabe Yoshiyuki , Kuriki Kiyonori , Kadota Aya , Wakai Kenji , Yamaji Taiki , Iwasaki Motoki , Sawada Norie , Tsugane Shoichiro , Kinoshita Kengo , Fuse Nobuo , Katsuoka Fumiki , Shimizu Atsushi , Nishizuka Satoshi S. , Tanno Kozo , Suzuki Ken , Okada Yukinori , Horikoshi Momoko , Yamauchi Toshimasa , Kadowaki Takashi , Yoshida Teruhiko , Matsuda Fumihiko , Kubo Michiaki , Kikuchi Shogo , Matsuo Keitaro
Published: December 2018

The etiology of pancreatic cancer remains largely unknown. Here, we report the results of a meta-analysis of three genome-wide association studies (GWASs) comprising 2,039 pancreatic cancer cases and 32,592 controls, the largest sample size in the Japanese population. We identified 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P<5.0×10-8) and 4 suggestive loci (P<1.0×10-6) for pancreatic cancer. Of these risk loci, 16p12.3 is novel; the lead SNP maps to rs78193826 (odds ratio (OR)=1.46, 95% CI=1.29-1.66, P=4.28×10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant predicted to be highly deleterious. Additionally, the gene-based GWAS identified a novel gene, KRT8, which is linked to exocrine pancreatic and liver diseases. The identified GP2 gene variants were pleiotropic for multiple traits, including type 2 diabetes, hemoglobin A1c (HbA1c) levels, and pancreatic cancer. Mendelian randomization analyses corroborated causality between HbA1c and pancreatic cancer. These findings suggest that GP2 gene variants are associated with pancreatic cancer susceptibility in the Japanese population, prompting further functional characterization of this locus.
A Nanopore-based method for generating complete coding region sequences of dengue virus in resource-limited settings
Authors: Stubbs Samuel , Blacklaws Barbara , Yohan Benediktus , Yudhaputri Frisalita A , Schwem Brian , Salvaña Edsel M , Destura Raul V , Myint Khin S , Sasmono R. Tedjo , Frost Simon D W
Published: December 2018

Dengue virus (DENV) sequencing is a vital tool for surveillance and epidemiology studies. However, the current methods employed for sequencing DENV are expensive, laborious and technically demanding, often due to intra- and inter-serotype variability. Therefore, on-site DENV sequencing is not feasible in many of the areas where DENV is endemic. Surveillance in these areas can only be performed by shipping samples to well-equipped central laboratories for sequencing. However, long periods of inadequate storage and unreliable shipping conditions mean that such samples can arrive degraded, rendering sequence recovery difficult. We therefore aimed to develop an approach that is simple, portable and effective, to be used for on-site DENV sequencing in limited resource settings.

To achieve this, we first used the ‘Primal Scheme’ primer design tool to develop a simple and robust protocol for generating multiple short amplicons, covering the complete coding-region of DENV isolates. We then paired this method with the Nanopore MinION, a portable and affordable sequencing device, well-suited to minimal resource settings.

The multiplex PCR method produced full-coding-region coverage of all DENV samples tested with no optimisation required, and Nanopore sequencing of the short amplicons generated consensus sequences with high accuracy (99.52 - 99.92 %). Phylogenetic analysis of the consensus sequences generated using the new method showed that they formed monophyletic clusters with those produced by the current, long-amplicon, Illumina method, thus demonstrating that the two approaches are comparable. The multiplex method’s simplicity and portability compared to the current DENV sequencing approach make it well-suited for use in resource-limited, DENV-endemic regions. Deployment of the method in these regions would increase the capacity for DENV surveillance and has the potential to provide vital resolution for future DENV epidemiology studies.
A counterselectable sucrose sensitivity marker permits efficient and flexible mutagenesis in Streptococcus agalactiae
Authors: Hooven Thomas Alexander , Bonakdar Maryam , Chamby Anna B , Ratner Adam J.
Published: December 2018

Streptococcus agalactiae (group B Streptococcus; GBS) is a cause of severe infections, particularly during the newborn period. While methods exist for generating chromosomal mutations in GBS, they are cumbersome and inefficient and present significant challenges if the goal is to study subtle mutations such as single base pair polymorphisms. To address this problem, we have developed an efficient and flexible GBS mutagenesis protocol based on sucrose counterselection against levansucrase (SacB) expressed from a temperature-selective shuttle vector. GBS containing the SacB expression cassette demonstrate lethal sensitivity to supplemental sucrose whether the plasmid DNA is replicating outside of the chromosome or has been integrated during a crossover event. Transmission electron microscopy shows that SacB-mediated lethal sucrose sensitivity results from accumulation of inclusion bodies that eventually lead to complete degradation of normal cellular architecture and subsequent lysis. We used this new mutagenesis technique to generate an in-frame, allelic exchange knockout of the GBS sortase gene srtA, demonstrating that >99% of colonies that emerge from our protocol had the expected knockout phenotype and that among a subset tested by sequencing, 100% had the correct genotype. We also generated barcoded nonsense mutations in the cylE gene in two GBS strains, showing that the approach can be used to make small, precise chromosomal mutations.
miR-216b-5p is Down-Regulated in Human Breast Cancer and Inhibits Proliferation and Progression by Targeting HDAC8 Oncogene
Authors: Menbari Mohammad-Nazir , Rahimi Karim , Ahmadi Abbas , Mohammadi-Yeganeh Samira , Elyasi Anvar , Darvishi Nikoo , Hosseini Vahedeh , Abdi Mohammad
Published: December 2018

Background: Previous studies showed the role of histone deacetylases (HDACs) on the progression of some malignancies. Recently, there is more attention to therapeutic applications of epigenetic factors such as microRNAs (miRs). To the best of our knowledge, there are no other results regarding the contribution of miR-216b-5p and its potential target, HDAC8, in the progression of cancer.
Aim: In the present study, we investigated the role of miR-216b-5p on HDAC8 and there following impacts on breast cancer (BC) progression.
Methods: Human BC specimens and noncancerous tissues were acquired from Iran Tumor Bank (I.T.B). The MDA-MB-231, MCF-7 and MCF-10A BC cell lines were also prepared. The tissue and cell line expression levels of miR-216b-5p and HDAC8 were determined by quantitative real-time PCR (qPCR). Protein levels of HDAC8 were also measured by Western blotting assay. The cell cycle, cell proliferation and colony formation assay were determined and the role of HDAC8 was investigated using a knockout vector. Targeting the 3' untranslated region (3'UTR) of HDAC8 by miR-216b-5p were confirmed using a luciferase reporter assay.
Results: Our results show the significant decline in miR-216b-5p and highly increase in HDAC8 levels in human breast cancer tissues and cell lines. Overexpression of miR-216b-5p in BC cell lines inhibited cellular proliferation and progression and inhibition of miR-216b-5p reverse these effects. We also confirmed that HDAC8 is directly down-regulated by miR-216b-5p. Knockout of HDAC8 had also the effects as miR-216b-5p overexpression. Furthermore, we found that lower levels of miR-216b-5p are negatively correlated with lymph node metastasis and advanced tumor size.
Conclusion: Taken together, our data showed that targeted overexpression of miR-216b-5p can suppress the growth of BC cells down-regulation of HDAC8. Therefore, inhibition of HDAC8 by miR-216b-5p will be helpful in developing newer therapies for the effective treatment of BC.
SBOL-OWL: An ontological approach for formal and semantic representation of synthetic genetic circuits
Authors: Misirli Goksel , Taylor Renee , Goni-Moreno Angel , McLaughlin James Alastair , Myers Chris , Gennari John H , Lord Phillip , Wipat Anil
Published: December 2018

Standard representation of data is key for the reproducibility of designs in synthetic biology. The Synthetic Biology Open Language (SBOL) has already emerged as a data standard to represent genetic circuit designs, and it is based on capturing data using graphs. The language provides the syntax using a free text document which is accessible to humans only. Here, we provide SBOL-OWL, an ontology for a machine understandable definition of SBOL. This ontology acts as a semantic layer for genetic circuit designs. As a result, computational tools can understand the meaning of design entities in addition to parsing structured SBOL data. SBOL-OWL not only describes how genetic circuits can be constructed computationally, it also facilitates the use of several existing Semantic Web tooling for synthetic biology. Here, we demonstrate some of these features, for example, to validate designs and check for inconsistencies. Through the use of SBOL-OWL, queries are simplified and become more intuitive. Moreover, existing reasoners can be used to infer information about genetic circuit designs that can't be directly retrieved using existing querying mechanisms. This ontological representation of the SBOL standard provides a new perspective to the verification, representation and querying of information about synthetic genetic circuits and is important to incorporate complex design information via the integration of biological ontologies.
A Constant Proportion in Protein Structure
Authors: Lobo-Cabrera Francisco Javier
Published: December 2018

The principles governing protein structure are largely unknown. Here, a structural proportion universal (R2 = 0.978) among proteins is reported. The model variance is shown to be independent from protein size, secondary structure composition, compactness or relative surface area. The structural characteristic under study --named here QUILLO-- quantifies residue-type spatial clustering. In this way, polar, hydrophobic, acidic and basic residues are evaluated individually and their values added up. For the analysis, all X-Ray currently determined structures deposited in the Protein Data Bank were studied. The QUILLO proportion offers for the first time an a priori protein prediction quality-check. Indeed, predictions with unexpected proportion values correspond to low ranks in the CASP12 experiment. The reason behind a specific, constant rule for protein folding remains unknown.
Boosting learning efficacy with non-invasive brain stimulation in intact and brain-damaged humans
Authors: Herpich Florian , Melnick Michael D , Agosta Sara , Huxlin Krystel , Tadin Duje , BATTELLI Lorella
Published: December 2018

Numerous behavioral studies have shown that visual function can improve with training, although perceptual refinements generally require weeks to months of training to attain. This, along with questions about long-term retention of learning, limits practical and clinical applications of many such paradigms. Here, we show for the first time that just 10 days of visual training coupled with transcranial random noise stimulation (tRNS) over visual areas causes dramatic improvements in visual motion perception. Relative to control conditions and anodal stimulation, tRNS-enhanced learning was at least twice as fast, and, crucially, it persisted for 6 months after the end of training and stimulation. Notably, tRNS also boosted learning in patients with chronic cortical blindness, leading to recovery of motion processing in the blind field after just 10 days of training, a period too short to elicit enhancements with training alone. In sum, our results reveal a remarkable enhancement of the capacity for long-lasting plastic and restorative changes when a neuromodulatory intervention is coupled with visual training.
Learning of pathogenic bacteria in adult C. elegans bidirectionally regulates pathogen response in the progeny
Authors: Pereira Ana , Gracida Xicotencatl , Kagias Konstantinos , Zhang Yun
Published: December 2018

Parental experience can generate adaptive changes in the behavioral and physiological traits of the offspring. However, the biological properties of this intergenerational regulation and the underlying molecular and cellular mechanisms are not well understood. Here, we show that the experience of learning to avoid pathogenic bacteria in C. elegans alters the behavioral response to the pathogen in the progeny through the endogenous RNA interference (RNAi) pathway. We previously show that the adult C. elegans learns to avoid the smell of pathogenic bacteria, such as the Pseudomonas aeruginosa strain PA14, after feeding on the pathogen for a few hours. Here, we report that this learning experience can bidirectionally regulate the olfactory response to PA14 in the progeny that are never directly exposed to the pathogen. The olfactory preference for PA14 in these progeny is linearly correlated with the learned avoidance of PA14 in their mothers. If the mothers show strong learning of PA14, their progeny avoid PA14; intriguingly, if the mothers show weak learning of PA14, the progeny prefer PA14, suggesting that the PA14-trained mothers transmit both the negative and positive information of PA14 to their progeny. The intergenerational behavioral effect results from an altered behavioral decision regulated by an olfactory sensorimotor neural circuit. Learning to avoid the pathogen also influences the development of the progeny, which is regulated independently from the behavioral change. Animals mutated for the RRF-3/RNA-directed RNA polymerase, a master regulator for the synthesis of the small interfering RNAs that are maternally inherited or in the soma, display the normal naive and learned response to PA14 but are defective in regulating the olfactory response to PA14 in their progeny. Our results characterize an intergenerational effect that allows the progeny to rapidly adapt to an environmental condition that is critical for survival.
Massively Parallel FPGA Hardware for Spike-By-Spike Networks
Authors: Rotermund David , Pawelzik Klaus R.
Published: December 2018

While inspired by the brain, currently successful artificial neural networks lack key features of the biological original. In particular, the deep convolutional networks (DCNs) neither use pulses as signals exchanged among neurons, nor do they include recurrent connections which are both core properties of real neuronal networks. This not only puts to question the relevance of DCNs for explaining information processing in nervous systems but also limits their potential for modeling natural intelligence.

Spike-By-Spike (SbS) networks are a promising new approach that combines the computational power of artificial networks with biological realism. Instead of separate neurons they consist of neuronal populations performing inference. Even though the underlying equations are rather simple implementations of such networks on currently available hardware are several orders of magnitude slower than for comparable non-spiking deep networks.

Here, we develop and investigate a framework for SbS networks on chip. Thanks to the communication via spikes, already moderately sized deep networks based on the SbS approach allows a parallelization into thousands of simple and fully independent computational cores. We demonstrate the feasibility of our design on a Xilinx Virtex 6 FPGA while avoiding proprietary cores (except block memory) that cannot be realized on a custom-designed ASIC. We present memory access optimized circuits for updating the internal variables of the neurons based on incoming spikes as well as for learning the connection’s strength. The optimized computational circuits as well as the representation of variables fully exploit the non-negative properties of all data in the SbS approach. We compare the sizes of the arising circuits for floating and fixed point numbers. In addition we show how to minimize the number of components that are required for the computational cores by reusing their components for different functions.
Invasive DNA elements modify nuclear architecture by KNOT-Linked Silencing in plants
Authors: Grob Stefan , Grossniklaus Ueli
Published: December 2018

Background

The three-dimensional (3D) organization of chromosomes is linked to epigenetic regulation and transcriptional activity. However, only few functional features of 3D chromatin architecture have been described to date. The KNOT is a 3D chromatin structure in Arabidopsis, comprising 10 interacting genomic regions termed KNOT ENGAGED ELEMENTs (KEEs). KEEs are enriched in transposable elements and small RNAs, suggesting a function in transposon biology.

Results

Here, we report the KNOT’s involvement in regulating invasive DNA elements. Transgenes can specifically interact with the KNOT, leading to perturbations of 3D nuclear organization, which correlates with the transgene’s expression: high KNOT-contact frequencies are associated with transgene silencing. KNOT-Linked Silencing (KLS) cannot readily be connected to canonical silencing mechanisms, such as RNA-directed DNA methylation and post-transcriptional gene silencing, as both cytosine methylation and small RNA abundance do not correlate with KLS. Furthermore, KLS exhibits paramutation-like behavior, as silenced transgenes can lead to the silencing of active transgenes in trans.

Conclusion

Transgene silencing can be readily connected to a specific feature of Arabidopsis 3D nuclear organization, namely the KNOT. KLS likely acts either independent or prior canonical silencing mechanisms and, hence, its characterization promises to not only contribute to our understanding of chromosome folding but moreover provides valuable insight into how genomes are defended against invasive DNA elements.
Signals from the brood modulate the sleep of brood tending bumblebee workers
Authors: Nagari Moshe , Gera Ariel , Jonsson Sara , Bloch Guy
Published: December 2018

Sleep is ubiquitous in vertebrates and invertebrates, and its chronic lost is typically associated with reduced performance, health, or survival. Nevertheless, some animals can give up sleep in order to increase survival or mating opportunities. We studied the interplay between sleep and brood care in the social bumblebeeBombus terrestris. We first used video recording and detailed behavioral analyses to confirm that the bumblebee shows the essential behavioral characteristics of sleep. Based on these analyses we next used immobility bouts of >5′ as proxy for sleep in automatic activity monitoring records, and found that sleep is severely reduced in the presence of larvae that require feeding or pupae that are not fed. Reduced sleep was correlated with wax pot building, which is a behavior typical to nest founding mother queens. Sleep was also reduced in the presence of empty cocoons, but this effect was transient and reduced with time. This observation that is consistent with the presence of a sleep modulating pheromonal signal. These results provide the first evidence for brood modulation of sleep in an insect, and are consistent with the hypothesis that plasticity in sleep can evolve as a mechanism to improve care for dependent juveniles.
Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution
Authors: Pollen Alex A , Bhaduri Aparna , Andrews Madeline G , Nowakowski Tomasz J , Meyerson Olivia S , Mostajo-Radji Mohammed A , Di Lullo Elizabeth , Alvarado Beatriz , Bedolli Melanie , Dougherty Max L , Fiddes Ian T , Kronenberg Zev N , Shuga Joe , Leyrat Anne A , West Jay A , Bershteyn Marina , Lowe Craig B , Pavolvic Bryan J , Salama Sofie R , Haussler David , Eichler Evan , Kriegstein Arnold A
Published: December 2018

Direct comparisons of human and non-human primate brain tissue have the potential to reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is largely inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. First, we systematically evaluated the fidelity of organoid models to primary human and macaque cortex, finding organoid models preserve gene regulatory networks related to cell types and developmental processes but exhibit increased metabolic stress. Second, we identified 261 genes differentially expressed in human compared to chimpanzee organoids and macaque cortex. Many of these genes overlap with human-specific segmental duplications and a subset suggest increased PI3K/AKT/mTOR activation in human outer radial glia. Together, our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.
The C-terminal Helix 9 motif regulates cannabinoid receptor type 1 trafficking and surface expression
Authors: Fletcher-Jones Alexandra , Hildick Keri L , Evans Ashley J , Nakamura Yasuko , Wilkinson Kevin , Henley Jeremy M
Published: December 2018

Cannabinoid type 1 receptor (CB1R) is only stably surface expressed in axons, where it downregulates neurotransmitter release. How this tightly regulated axonal surface polarity is established and maintained is unclear. To address this question, we used time-resolved imaging to determine the trafficking of CB1R from biosynthesis to mature polarised localisation. We show that the secretory pathway delivery of CB1R is axonally biased and that surface expressed CB1R is more stable in axons than in dendrites. This dual mechanism is mediated by the CB1R C-terminal and involves the Helix 9 (H9) domain. Removal of the H9 domain increases dendrite secretory pathway delivery and decreases in surface stability. Furthermore, CB1RΔH9 is more sensitive to agonist-induced internalisation and less efficient at downstream signalling than CB1RWT. Together, these results shed new light on how polarity of CB1R is mediated and indicate that the C-terminal H9 domain plays key roles in this process.
De novo Design of Translational RNA Repressors
Authors: Carlson Paul D. , Glasscock Cameron J. , Lucks Julius B.
Published: December 2018

A central goal of synthetic biology is the development of methods for the predictable control of gene expression. RNA is an attractive substrate by which to achieve this goal because the relationship between its sequence, structure, and function is being uncovered with increasing depth. In addition, design approaches that use this relationship are becoming increasingly effective, as evidenced by significant progress in the de novo design of RNA-based gene regulatory mechanisms that activate transcription and translation in bacterial cells. However, the design of synthetic RNA mechanisms that are efficient and versatile repressors of gene expression has lagged, despite their importance for gene regulation and genetic circuit construction. We address this gap by developing two new classes of RNA regulators, toehold repressors and looped antisense oligonucleotides (LASOs), that repress translation of a downstream gene in response to an arbitrary input RNA sequence. Characterization studies show that these designed RNAs robustly repress translation, are highly orthogonal, and can be multiplexed with translational activators. We show that our LASO design can repress endogenous mRNA targets and distinguish between closely-related genes with a high degree of specificity and predictability. These results demonstrate significant yet easy-to-implement improvements in the design of synthetic RNA repressors for synthetic biology, and point more broadly to design principles for repressive RNA interactions relevant to modern drug design.
Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment
Authors: Abdallah Chadi , Averill Christopher , Ramage Amy , Averill Lynnette , Alkin Evelyn , Krystal John , Roache John , Resick Patricia , Young-McCaughan Stacey , Peterson Alan , Fox Peter
Published: December 2018

BACKGROUND: In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging (fMRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment.
METHODS: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed fMRI at rest and during symptom provocation using subject-specific script imagery. Then, participants with PTSD received 6 weeks (12 sessions) of group cognitive processing therapy (CPT) or present-centered therapy (PCT). At week 8, all participants repeated the fMRI scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations post-treatment in PTSD participants compared to controls.
RESULTS: Over the treatment period, PCT significantly reduced salience GBCr (p = .02). Compared to controls, salience GBCr was high pretreatment (PCT, p = .01; CPT, p = .03) and normalized post-PCT (p = .53), but not post-CPT (p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in PTSD participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following CPT treatment (p = .01).
CONCLUSION: The results support previous models relating CPT to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of PCT treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection.
The USTC co-opts an ancient machinery to drive piRNA transcription in C. elegans
Authors: Weng Chenchun , Kosalka Joanna , Berkyurek Ahmet C. , Stempor Przemyslaw , Feng Xuezhu , Mao Hui , Zeng Chenming , Li Wen-Jun , Yan Yong-Hong , Dong Meng-Qiu , Morero Natalia Rosalía , Zuliani Cecilia , Barabas Orsolya , Ahringer Julie , Guang Shouhong , Miska Eric A.
Published: December 2018

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In Caenorhabditis elegans, most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis, the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC contains piRNA silencing-defective 1 (PRDE-1), SNPC-4, twenty-one-U fouled-up 4 (TOFU-4), and TOFU-5. The USTC forms unique piRNA foci in germline nuclei and coats the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and forming the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other noncoding RNA genes. These results reveal the USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defense against transposons.
PRC1 preserves epidermal tissue integrity independently of PRC2
Authors: Cohen Idan , Zhao Dejian , Menon Gopinathan , Nakayama Manabu , Koseki Haruhiko , Zheng Deyou , Ezhkova Elena
Published: December 2018

Polycomb-repressive complex 1 (PRC1) and PRC2 are critical chromatin regulators of gene expression and tissue development. Here, we show that despite extensive genomic cobinding, PRC1 is essential for epidermal integrity, whereas PRC2 is dispensable. Loss of PRC1 resulted in blistering skin, reminiscent of human skin fragility syndromes. Conversely, PRC1 does not restrict epidermal stratification during skin morphogenesis, whereas PRC2 does. Molecular dissection demonstrated that PRC1 functions with PRC2 to silence/dampen expression of adhesion genes. In contrast, PRC1 promotes expression of critical epidermal adhesion genes independently of PRC2-mediated H3K27me3. Together, we demonstrate a functional link between epigenetic regulation and skin diseases.
Fabrication and characterization of ZnMgO nanowalls grown on 4H-SiC by molecular beam epitaxy
Authors: Pietrzyk Mieczyslaw A. , Wierzbicka Aleksandra , Stachowicz Marcin , Jarosz Dawid , Kozanecki Adrian
Published: December 2018

Control of nanostructure growth is a prerequisite for the development of electronic and optoelectronic devices. This paper reports the growth conditions and structural properties of ZnMgO nanowalls grown on the Si face of 4H-SiC substrates by molecular beam epitaxy without catalysts and buffer layers. Images from scanning electron microscopy revealed that the ZnMgO nanowalls are arranged in parallel rows following the stripe morphology of the SiC surface, and their thickness is around 15 nm. The crystal quality of the structures was evaluated by X-ray diffraction measurements.
Microstrain-assisted polymorphic phase transitions in (Eu1−x
La
x
)2O3
Authors: Irshad K. A. , Saikumaran A. , Srihari V. , Kalavathi S. , Chandra Shekar N. V.
Published: December 2018

Solid solutions, (Eu1−x
La
x
)2O3 (0 ≤ x ≤ 1), of the rare earth sesquioxides Eu2O3 and La2O3 have been prepared by a simple soft chemistry approach. The composition and morphology of the as-synthesized oxides have been characterized using energy-dispersive spectroscopy and scanning electron microscopy. The particles are of irregular shape and submicrometre size. In order to understand the structural evolution as a function of composition, angle-dispersive X-ray diffraction measurements have been carried out and the structural parameters have been obtained through Rietveld refinement. A structural phase transition from the cubic (C-type) to the monoclinic (B-type) structure and subsequently to the hexagonal (A-type) structure was observed with an increasing substitution of La. A detailed analysis of the transition boundaries in terms of the average cationic radius, R
RE, shows that the onset of the C → B transition is at R
RE = 0.980 Å, whereas the B → A transition occurs at R
RE = 1.025 Å. A biphasic region of cubic and monoclinic structures is observed for 0.2 ≤ x ≤ 0.4 and one of monoclinic and hexagonal structures is observed for 0.5 ≤ x ≤ 0.6. The microstrain induced by the difference in size of the rare earth cations introduces a substitutional disorder in the crystal structure, which is a plausible cause of the observed phase transitions in these oxides.
Numerical study on flow over a confined oscillating cylinder with a splitter plate
Authors: Ghiasi Arya , Razavi Seyed Esmaeil , Rouboa Abel , Mahian Omid
Published: December 2018

Purpose

This study aims to investigate the effect of the simultaneous usage of active and passive methods (which in this case are rotational oscillation and attached splitter plate, respectively) on the flow and temperature fields to find an optimum situation which this combination results in heat transfer increment and drag reduction.

Design/methodology/approach

The method of the solution was based on finite volume discretization of Navier–Stokes equations. A dynamic grid is coupled with the solver by the arbitrary Lagrangian–Eulerian (ALE) formulation for modeling cylinder oscillation. Parametric studies were performed by altering oscillation frequency, splitter plate length and Reynolds number.

Findings

Oscillation in different frequencies was found to be complicated. Higher frequencies provide more heat transfer, but in the lock-on region, they bring remarkable increment to the drag coefficient. It was observed that simultaneous usage of oscillation and splitter plate may have both positive and negative effects on drag reduction and heat transfer increment. Finally F = 2 and L = 0.5 were chosen as an optimum combination.

Originality/value

In this study, the laminar incompressible flow and heat transfer from a confined rotationally oscillating circular cylinder with an attached splitter plate are investigated. Parametric studies are performed by changing oscillation frequency, splitter plate length and Reynolds number.
Stability analysis, solition solutions and Gaussian solitons of the generalized nonlinear Schrödinger equation with higher order terms
Authors: Wang Hui , Zhang Tian-Tian
Published: December 2018

Purpose

The purpose of this paper is to study stability analysis, solition solutions and Gaussian solitons of the generalized nonlinear Schrödinger equation with higher order terms, which can be used to describe the propagation properties of optical soliton solutions.

Design/methodology/approach

The authors apply the ansatz method and the Hamiltonian system technique to find its bright, dark and Gaussian wave solitons and analyze its modulation instability analysis and stability analysis solution.

Findings

The results imply that the generalized nonlinear Schrödinger equation has bright, dark and Gaussian wave solitons. Meanwhile, the authors provide the graphical analysis of such solutions to better understand their dynamical behavior. Some constraint conditions are provided which can guarantee the existence of solitons. The authors analyze its modulation instability analysis and stability analysis solution.

Originality/value

These results may help us to further study the local structure and the interaction of solutions in generalized nonlinear Schrödinger -type equations. The authors hope that the results provided in this work can help enrich the dynamic behavior of the generalized nonlinear Schrödinger--type equations.
Asymmetric sensitivities of house prices to housing fundamentals: evidence from UK regions
Authors: Alqaralleh Huthaifa
Published: December 2018

Purpose

This paper aims to examine asymmetries in the house price cycle and to understand the dynamic of housing prices, incorporating macroeconomic variables at regional and country level, namely, housing affordability, the unemployment rate, mortgage rate and inflation rate.

Design/methodology/approach

To highlight significant differences in the asymmetric patterns of house prices between regions, the STAR model is adopted.

Findings

The authors highlight significant differences in the asymmetric patterns of house prices between regions, in which some areas showed asymmetric response over the housing cycle; here the LSTAR model outperforms other models. In contrast, some regions (the South West and the North West) showed symmetric properties in the tails of the cycle; therefore, the ESTAR model was adopted in their case.

Practical implications

Being limited to a few fundamentals, this study opens an avenue for further research to investigate this dynamic using in addition such demand-supply factors as land supply, construction cost and loans made for housing. These findings can also be used to examine whether other models such as ARIMA, exponential smoothing or artificial neural networks can more accurately forecast housing prices.

Originality/value

The present paper aims to highlight housing affordability as a cause of asymmetric behaviour in house prices. Put differently, the authors seek to understand the dynamics of housing prices with other fundamentals incorporating macroeconomic variables in regions and country level data as a means of achieving a more concise result.
“You get what you appreciate”
Authors: Hassi Abderrahman
Published: December 2018

Purpose

The purpose of this study is to examine the influences of transactional and transformational leadership styles on employee job satisfaction, employee affective commitment and organisational citizenship behaviour (OCB) within Moroccan organisations.

Design/methodology/approach

Data were gathered from a sample of 219 employees working in seven different industries in Morocco and analysed using Structural Equations Modelling (SEM).

Findings

SEM analyses reveal that employee job satisfaction, affective commitment and OCB are only impacted by thepersonal recognitiondimension of the transformational leadership style. The study indicates thatcharismaandintellectual stimulation(transformational leadership) as well ascontingent rewardandmanagement-by-exception(transactional leadership) did not yield significant results.

Research limitations/implications

The use of a cross-sectional research design limits establishing cause-and-effect relationships.

Practical implications

The results of the current study may be of use and interest for organisations in designing effective leadership training programs, as it takes into account how managers and/or practitioners tap into their subordinates’ effective behaviour.

Originality/value

With insights derived from a non-Western perspective, the major theoretical contribution of the present study lies in exploring the effects of transactional and transformational leadership styles on employee job satisfaction, employee affective commitment and OCB in Morocco.