bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation inCaenorhabditis elegans
Authors: Ardiel Evan L. , McDiarmid Troy A. , Timbers Tiffany A. , Lee Kirsten C. Y. , Safaei Javad , Pelech Steven L. , Rankin Catharine H.
Published: November 2018

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented—animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematodeCaenorhabiditis elegansto identify the first molecules that modulate habituation in an ISI-dependent manner. We show that theCaenorhabditis elegansorthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, bothcmk-1andogt-1mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type). Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
Miniaturization technologies for cost-effective AmpliSeq library preparation for next generation sequencing
Authors: Ogiso-Tanaka Eri , Kaga Akito , Hajika Makita
Published: November 2018

Purpose

AmpliSeq technology, the target enrichment method for next-generation sequencing (NGS), enables quick and easy detection of the genomic “hot spot” region frequently mutated in species. Even though the cost of NGS has decreased, library preparation cost accounts for a more significant proportion of the total cost. If AmpliSeq library can be prepared at a lower cost, large-scale precision oncology can be more easily carried out. Furthermore, this technology can be widely applied not only to medical research, but also to polymorphism detection in biology. This study aimed to reduce the cost of AmpliSeq library preparation by adopting miniaturization technology.

Methods

We used approximately 10 ng of genomic DNA for ultra-multiplex PCR of 384, 768, 1152, 1920, and 3072 amplicons. Multiplex PCR was performed in a total volume of 1.6, 2.0, and 2.4 μL, using a nano-liter liquid handler, for library preparation.

Results

The success rate of library construction decreased with decreasing total multiplex PCR reaction volume. Using 1.6-, 2.0-, and 2.4-μL reactions, the success rates of ultra-multiplex PCR were 25%, 95%, and 100%, respectively. We could stably create libraries of the correct amplicon size, with an amplicon number of approximately 1500 or less. As a result of NGS, uniformity of PCR amplification and read length of quality-checked libraries were hardly affected by the number of amplicons.

Conclusion

Here, we show that the minimum volume for a stable reaction was 2.4 μL and the maximum number of amplicons obtained was approximately 1500. The protocol saved 86.8% in reagent usage and reduced handling time by 85% compared to that required by the manual protocol. Therefore, miniaturization technologies could reduce the cost of AmpliSeq library preparation through minimization of reagents.
Quantified ensemble 3D surface features modeled as a window on centric diatom valve morphogenesis
Authors: Pappas Janice L.
Published: November 2018

Morphological surface features are a record of genetic and developmental processes as well as environmental influences. The 3D geometric “terrain” of the surface consists of slopes via tangents, peaks and valleys via normals, smoothness of the transition between peaks and valleys, and point connections as flatness or curvature among all features. Such geometric quantities can be used to indicate morphological changes in valve formation over time. Quantified 3D surface features as geometric pattern ensembles may be representative of structural snapshots of the morphogenetic process.

For diatoms, valve formation and pattern morphogenesis has been modeled using Turing-like and other algorithmic techniques to mimic the way in which diatoms exhibit the highly diverse patterns on their valve surfaces. How the created surface features are related to one another is not necessarily determined via such methods. With the diatom valve face structure of layered areolae, cribra, and other morphological characters, valve formation exhibits different combined geometries unfolding as 3D structural ensembles in particular spatial arrangements. Quantifying ensemble 3D surface geometries is attainable via models devised using parametric 3D equations and extracting surface features via partial derivatives for slopes, peaks and valleys, smoothness, and flatness as feature connectedness. Differences in ensemble 3D surface features may be used to assess structural differences among selected diatom genera as indicators of different valve formation sequences in surface generation and morphogenesis.
Genetic selection for small molecule production in competitive microfluidic droplets
Authors: Millet Larry J. , Velez Jessica M. , Michener Joshua K.
Published: November 2018

Biosensors can be used to screen or select for small molecule production in engineered microbes. However, mutations to the biosensor that interfere with accurate signal transduction are common, producing an excess of false positives. Strategies have been developed to avoid this limitation by physically separating the production pathway and biosensor, but these approaches have only been applied to screens, not selections. We have developed a novel biosensor-mediated selection strategy using competition between co-cultured bacteria. When applied to biosynthesis ofcis,cis-muconate, we show that this strategy yields a selective advantage to producer strains that outweighs the costs of production. By encapsulating the competitive co-cultures into microfluidic droplets, we successfully enriched for muconate-producing strains from a large population of control non-producers. Facile selections for small molecule production will increase testing throughput for engineered microbes and allow for the rapid optimization of novel metabolic pathways.
Enzymatic and structural characterization of the Naegleria fowleri glucokinase
Authors: Milanes Jillian E. , Suryadi Jimmy , Abendroth Jan , Van Voorhis Wesley C. , Barrett Kayleigh F. , Dranow David M. , Phan Isabelle Q. , Patrick Stephen L. , Rozema Soren D. , Khalifa Muhammad M. , Golden Jennifer E. , Morris James C.
Published: November 2018

Infection with the free-living amoeba Naegleria fowleri leads to life-threatening primary amoebic meningoencephalitis. Efficacious treatment options for these infections are limited and the mortality rate is very high (~98%). Parasite metabolism may provide suitable targets for therapeutic design. Like most other organisms, glucose metabolism is critical for parasite viability, being required for growth in culture. The genome of the parasite encodes a single glucose phosphorylating enzyme, a glucokinase (Glck). The products of this enzyme are required for both glycolysis and the pentose phosphate pathway. The N. fowleri Glck (NfGlck) shares limited (25%) amino acid identity with the mammalian host enzyme (HsGlck), suggesting that parasite-specific inhibitors with anti-amoeba activity could be generated. Following heterologous expression, NfGlck was found to have a limited hexose substrate range, with greatest activity observed with glucose. The enzyme had apparent Km values of 42.5 ± 7.3 μM and 141.6 ± 9.9 μM for glucose and ATP, respectively. The NfGlck structure was determined and refined to 2.2 Å resolution, revealing that the enzyme shares greatest structural similarity with the Trypanosoma cruzi Glck. These similarities include binding modes and binding environments for substrates. To identify inhibitors of NfGlck, we screened a small collection of inhibitors of glucose phosphorylating enzymes and identified several small molecules with IC50 values < 1 μM that may prove useful as hit chemotypes for further lead and therapeutic development against N. fowleri.
Family reunion via error correction: An efficient analysis of duplex sequencing data
Authors: Stoler Nicholas , Arbeithuber Barbara , Povysil Gundula , Heinzl Monika , Salazar Renato , Makova Kateryna , Tiemann-Boege Irene , Nekrutenko Anton
Published: November 2018

Duplex sequencing is the most accurate approach for identification of sequence variants present at very low frequencies. Its power comes from pooling together multiple descendants of both strands of original DNA molecules, which allows distinguishing true nucleotide substitutions from PCR amplification and sequencing artifacts. This strategy comes at a cost—sequencing the same molecule multiple times increases dynamic range but significantly diminishes coverage, making whole genome duplex sequencing prohibitively expensive. Furthermore, every duplex experiment produces a substantial proportion of singleton reads that cannot be used in the analysis and are, technically, thrown away. In this paper we demonstrate that a significant fraction of these reads contains PCR or sequencing errors within duplex tags. Correction of such errors allows “reuniting” these reads with their respective families increasing the output of the method and making it more cost effective. Additionally, we combine error correction strategy with a number of algorithmic improvements in a new version of the duplex analysis software, Du Novo 2.0, readily available through Galaxy, Bioconda, and as the source code.
Open Humans: A platform for participant-centered research and personal data exploration
Authors: Tzovaras Bastian Greshake , Angrist Misha , Arvai Kevin , Dulaney Mairi , Estrada-Galiñanes Vero , Gunderson Beau , Head Tim , Lewis Dana , Nov Oded , Shaer Orit , Tzovara Athina , Bobe Jason , Ball Mad Price
Published: November 2018

Background

Many aspects of our lives are now digitized and connected to the internet. As a result, individuals are now creating and collecting more personal data than ever before. This offers an unprecedented chance for human-participant research ranging from the social sciences to precision medicine. With this potential wealth of data come practical problems (such as how to merge data streams from various sources), as well as ethical problems (such as how to best balance risks and benefits when enabling personal data sharing by individuals).

Results

To begin to address these problems in real time, we present Open Humans, a community-based platform that enables personal data collections across data streams, giving individuals more personal data access and control of sharing authorizations, and enabling academic research as well as patient-led projects. We showcase data streams that Open Humans combines (e.g. personal genetic data, wearable activity monitors, GPS location records and continuous glucose monitor data), along with use cases of how the data facilitates various projects.

Conclusions

Open Humans highlights how a community-centric ecosystem can be used to aggregate personal data from various sources as well as how these data can be used by academic and citizen scientists through practical, iterative approaches to sharing that strive to balance considerations with participant autonomy, inclusion, and privacy.
CAT tails drive on- and off-ribosome degradation of stalled polypeptides
Authors: Sitron Cole S. , Brandman Onn
Published: November 2018

Stalled translation produces incomplete, ribosome-associated polypeptides that Ribosome-associated Quality Control (RQC) targets for degradation via the ubiquitin ligase Ltn1. During this process, the Rqc2 protein and large ribosomal subunit elongate stalled polypeptides with carboxy-terminal alanine and threonine residues (CAT tails). Failure to degrade CAT-tailed proteins disrupts global protein homeostasis, as CAT-tailed proteins aggregate and sequester chaperones. Why cells employ such a potentially toxic process during RQC is unclear. Here, we developed quantitative techniques to assess how CAT tails affect stalled polypeptide degradation in Saccharomyces cerevisiae. We found that CAT tails improve Ltn1’s efficiency in targeting structured polypeptides, which are otherwise poor Ltn1 substrates. If Ltn1 fails, CAT tails undergo a backup route of ubiquitylation off the ribosome, mediated by the ubiquitin ligase Hul5. Thus, CAT tails functionalize the carboxy-termini of stalled polypeptides to drive their degradation on and off the ribosome.
Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq
Authors: Wienert Beeke , Wyman Stacia K , Richardson Christopher D , Yeh Charles D , Akcakaya Pinar , Porritt Michelle J , Morlock Michaela , Vu Jonathan T , Kazane Katelynn R , Watry Hannah L , Judge Luke M , Conklin Bruce R , Maresca Marcello , Corn Jacob E
Published: November 2018

Genome editing using nucleases such as CRISPR-Cas induces programmable DNA damage at a target genomic site but can also affect off-target sites. Here, we develop a powerful, sensitive assay for the unbiased identification of off-target sites that we term DISCOVER-Seq. This approach takes advantage of the recruitment of endogenous DNA repair factors for genome-wide identification of Cas-induced double-strand breaks. One such factor, MRE11, is recruited precisely to double-strand breaks, enabling molecular characterization of nuclease cut sites with single-base resolution. DISCOVER-Seq detects off-targets in cellular models and in vivo upon adenoviral gene editing of mouse livers, paving the way for real-time off-target discovery during therapeutic gene editing. DISCOVER-Seq is furthermore applicable to multiple types of Cas nucleases and provides an unprecedented view of events that precede repair of the affected sites.
Geocoding genomic databases using GBIF
Authors: Page Roderic D. M.
Published: November 2018

Many nucleotide sequences in the publicly available genomics databases lack spatial information, such as the latitude and longitude coordinates for the locality where the sample for sequencing was taken. In this note I discuss several approaches to geocoding sequence records. The ﬁrst method uses the Global Biodiversity Information Facility (GBIF: https://gbif.org) as a gazetter. The availability of a simple full text search across GBIF data makes it possible to rapidly geocode locality information simply by searching for matching records within GBIF. Hence if a sequence lacks coordinates but has some locality information it could be rapidly geocoded. The second method matches voucher specimen code for sequences with the corresponding specimen records in GBIF, which may be geocoded even if the sequence obtained from that specimen is not. Lastly, there will be cases where sequence records lack either locality or specimen information, but that information is available elsewhere, such as in the published literature or in supplementary data files. The possibility of publishing geocoded sequence records using Github is discussed.
Discovery of volatile biomarkers of Parkinson’s disease from sebum
Authors: Trivedi Drupad K , Sinclair Eleanor , Xu Yun , Sarkar Depanjan , Liscio Camilla , Banks Phine , Milne Joy , Silverdale Monty , Kunath Tilo , Goodacre Royston , Barran Perdita
Published: November 2018

Parkinson’s disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic test (1–3). We have serendipitously identified a hyperosmic individual, a ‘Super Smeller’ that can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects(4). Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained non-invasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort, identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our ‘Super Smeller’.

1 sentence summary

Metabolomics identifies volatile odorous compounds from patient sebum that associate with the smell of Parkinson’s.
Cell-type-specific genomics reveals histone modification dynamics in mammalian meiosis
Authors: Gabriel Lam Kwan-Wood , Brick Kevin , Cheng Gang , Pratto Florencia , Camerini-Otero R. Daniel
Published: November 2018

Meiosis is the specialized cell division during which parental genomes recombine to create genotypically unique gametes. Despite its importance, mammalian meiosis cannot be studiedin vitro, greatly limiting mechanistic studies.In vivo, meiocytes progress asynchronously through meiosis and therefore the study of specific stages of meiosis is a challenge. Here, we describe a method for isolating pure sub-populations of nuclei that allows for detailed study of meiotic sub-stages. Interrogating the H3K4me3 landscape revealed dynamic chromatin transitions between sub-stages of meiotic prophase I, both at sites of genetic recombination and at gene promoters. We also leveraged this method to perform the first comprehensive, genome-wide survey of histone marks in meiotic prophase, revealing a heretofore unappreciated complexity of the epigenetic landscape at meiotic recombination hotspots. Ultimately, this study presents a straightforward, scalable framework for interrogating the complexities of mammalian meiosis.
SVXplorer: Identification of structural variants through overlap of discordant clusters
Authors: Kathuria Kunal , Ratan Aakrosh
Published: November 2018

Motivation

The identification of structural variants using short-read data remains challenging. Most approaches ignore signatures of complex variants such as those generated by trans-posable elements. This can result in lower precision and sensitivity in identification of the more common structural variants such as deletions and duplications.

Results

We present SVXplorer, which uses a streamlined sequential approach to integrate discordant paired-end alignments with split-reads and read depth information. We show that it outperforms several existing approaches in both reproducibility and accuracy on real and simulated datasets.

Availability

SVXplorer is available at https://github.com/kunalkathuria/SVXplorer.
Classifying Asian Rice Cultivars (Oryza sativa L.) into Indica and Japonica Using Logistic Regression Model with Publicly Available Phenotypic Data
Authors: Kim Bongsong
Published: November 2018

This article introduces how to implement the logistic regression model (LRM) with phenotypic variables for classifying Asian rice (Oryza sativa L.) cultivars into two pivotal subpopulations, indica and japonica. This study took advantage of publicly available data attached to a previous paper. The classification accuracy was assessed using an area under curve (AUC) of a receiver operating characteristic (ROC) curve. Given 24 phenotypic variables for 280 indica/japonica accessions, the LRMs were fitted with up to six phenotypic variables of all possible combinations; the highest AUC accounts for 0.9977, obtained with six variables including panicle number per plant, seed number per panicle, florets per panicle, panicle fertility, straighthead susceptibility and blast resistance. Overall, the more variables there are, the higher the resulting AUCs are. The ultimate purpose of this study is to demonstrate the indica/japonica prediction ability of the LRM when applied to unclassified Asian rice cultivars. To estimate the indica/japonica prediction accuracy, ten-fold cross-validations were conducted 100 times with the 280 indica/japonica accessions using the LRM with parameters that yielded the highest AUC. The resulting prediction accuracy accounted for 0.9779. This suggests that the LRM promises to be a highly effective indica/japonica prediction tool using phenotypic variables in Asian cultivated rice.
PTPN14 Degradation by High-Risk Human Papillomavirus E7 Limits Keratinocyte Differentiation and Contributes to HPV-Mediated Oncogenesis
Authors: Hatterschide Joshua , Bohidar Amelia E. , Grace Miranda , Nulton Tara J. , Windle Brad , Morgan Iain M. , Munger Karl , White Elizabeth A.
Published: November 2018

High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate RB1 but cannot degrade PTPN14 we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion ofPTPN14from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation andPTPN14deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV-positive but not HPV-negative cancers exhibit a gene expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.

Significance Statement

Human papillomaviruses uncouple proliferation from differentiation in order to enable virus replication in epithelial cells. HPV E7 proteins are well established to promote proliferation by binding to and inactivating retinoblastoma family proteins and other cell cycle inhibitors. However, mechanisms by which high-risk HPV oncoproteins inhibit differentiation have not been defined. This paper identifies the first mechanism by which high-risk HPV E7 inhibit keratinocyte differentiation. The inhibition of differentiation requires degradation of the cellular protein PTPN14 by high-risk HPV E7 and this degradation is related to the ability of high-risk HPV oncoproteins to immortalize keratinocytes and to cause cancer.
Integrative Pharmacogenomics Analysis of Patient Derived Xenografts
Authors: Mer Arvind Singh , Ba-alawi Wail , Smirnov Petr , Wang Yi Xiao , Brew Ben , Ortmann Janosch , Tsao Ming-Sound , Cescon David , Goldenberg Anna , Haibe-Kains Benjamin
Published: November 2018

One of the key challenges in cancer precision medicine is finding robust biomarkers of drug response. Patient-derived tumor xenografts (PDXs) have emerged as reliable preclinical models since they better recapitulate tumor response to chemo- and targeted therapies. However, the lack of standard tools poses a challenge in the analysis of PDXs with molecular and pharmacological profiles. Efficient storage, access and analysis is key to the realization of the full potential of PDX pharmacogenomic data. We have developed Xeva (XEnograft Visualization & Analysis), an open-source software package for processing, visualization and integrative analysis of a compendium ofin vivopharmacogenomic datasets. The Xeva package follows the PDX minimum information (PDX-MI) standards and can handle both replicate-based and 1×1×1 experimental designs. We used Xeva to characterize the variability of gene expression and pathway activity across passages. We found that only a few genes and pathways have passage specific alterations (median intraclass correlation of 0.53 for genes and positive enrichment score for 92.5% pathways). For example, activity of the mRNA 3’-end processing and elongation arrest and recovery pathways were strongly affected by model passaging (gene set enrichment analysis false discovery rate [FDR] <5%). We then leveraged our platform to link the drug response and the pathways whose activity is consistent across passages by mining the Novartis PDX Encyclopedia (PDXE) data containing 1,075 PDXs spanning 5 tissue types and 62 anticancer drugs. We identified 87 pathways significantly associated with response to 51 drugs (FDR < 5%), including associations such as erlotinib response and signaling by EGFR in cancer pathways and MAP kinase activation in TLR cascade and binimetinib response. Among the significant pathway-drug associations, we found novel biomarkers based on gene expressions, Copy Number Aberrations (CNAs) and mutations predictive of drug response (concordance index > 0.60; FDR < 0.05). Xeva provides a flexible platform for integrative analysis of preclinicalin vivopharmacogenomics data to identify biomarkers predictive of drug response, a major step toward precision oncology.
Ecological occurrence and plant regeneration of embryoid of the endangered and endemic plantDysosma versipellisin China
Authors: Tan Xiao-Ming , Zhou Ya-Qin , Wu Pei-Bin , Wei Ying , Yang Shi-Lin , Tang Hong-Zhen
Published: November 2018

In this study, the effective callus culture, somatic embryogenesis, and plant regeneration system ofDysosma versipellis, which is an endangered and endemic plant in China, were established under specific culture conditions. Using theD.versipellisleaves, petioles, and roots as explants, DPS software orthogonal design method and SPSS Duncan’s multiple range test were used to investigate their effects ofD.versipellison callus formation, embryoid induction, and plant regeneration by adding different phytohormones. Results showed that leaves and petioles were the most suitable materials in inducing callus. The effect of phytohormone on callus formation followed the order of 2,4-dichlorophenoxyacetic acid (2,4-D)>thidiazuron (TDZ)> kinetin>naphthylacetic acid (NAA)>2-ip. The best medium for callus formation was MS+2,4-D 1 mg/L+NAA 0.05 mg/L+TDZ 0.5 mg/L+2-ip 1 mg/L. The optimal medium to induce the formation of granular callus embryoid was MS+0.5 mg/L 6-BA+0.1 mg/L NAA, and the induction rate was 71.33%. The embryoid rooting and plant regeneration medium was MS+0.5 mg/L IBA+0.5 mg/L GA3. The optimal medium formula obtained in this study was suitable for the rapid induction of callus, embryoid, and plant regeneration ofD. versipellisunder in vitro culture conditions. Further study on the action mechanism, signal regulation mechanism, and artificial seed production of fungal elicitors affecting the accumulation of podophyllotoxin is important.
CRISPR/Cas9-mediated mutagenesis of phytoene desaturase in diploid and octoploid strawberry
Authors: Wilson Fiona , Harrison Kate , Armitage Andrew D. , Simkin Andrew J. , Harrison Richard J.
Published: November 2018

Gene editing using CRISPR/Cas9 is a simple and powerful tool for elucidating genetic controls and for crop improvement. We demonstrate use of CRISPR/Cas methodology in diploid Fragaria vesca ssp. vesca ‘Hawaii 4’ and octoploid F. x ananassa ‘Calypso’ by targeting the visible endogenous marker gene PDS (phytoene desaturase). Agrobacterium-mediated transformation of leaf and petiole explants was used for efficient stable integration of constructs expressing plant codon-optimised Cas9 and single guide sequences under control of either the Arabidopsis U6-26 consensus promoter and terminator or Fragaria vesca U6III regulatory sequences. More than 80% (‘Hawaii 4’) and 50% (‘Calypso’) putative transgenic shoot lines exhibited mutant phenotypes. Of mutant shoot lines selected for molecular analysis, approximately 55% (‘Calypso’) and 75% (‘Hawaii 4’) included albino regenerants with bi-allelic target sequence variants. Our results indicate the PDS gene is functionally diploid in ‘Calypso’ and clearly demonstrate that CRISPR/Cas9 can be used to edit single copy genes at high frequency within the genome of the diploid and the same target in octoploid strawberry.
Spindle checkpoint silencing at kinetochores with submaximal microtubule occupancy
Authors: Etemad Banafsheh , Vertesy Abel , Kuijt Timo E.F. , Sacristan Carlos , van Oudenaarden Alexander , Kops Geert J.P.L.
Published: November 2018

The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by monitoring kinetochore-microtubule interactions. SAC proteins are shed from kinetochores once stable attachments are achieved. Human kinetochores consist of hundreds of SAC protein recruitment modules and bind up to 20 microtubules, raising the question how the SAC responds to intermediate attachment states. We show that the ‘RZZS-MAD1/2’ module of the SAC is removed from kinetochores at low microtubule occupancy and remains absent at higher occupancies, while the ‘BUB1/R1’ module is retained at substantial levels irrespective of attachment states. Artificially tuning the affinity of kinetochores for microtubules further shows that ~50% occupancy is sufficient to shed MAD2 and silence the SAC. Kinetochores thus responds as a single unit to shut down SAC signaling at submaximal occupancy states, but retains one SAC module. This may ensure continued SAC silencing on kinetochores with fluctuating occupancy states while maintaining the ability for fast SAC re-activation.
Whole-genome and transcriptome profiling of a metastatic thyroid-like follicular renal cell carcinoma
Authors: Ko Jenny J. , Grewal Jasleen K. , Ng Tony , Lavoie Jean-Michel , Thibodeau My Linh , Shen Yaoqing , Mungall Andrew J. , Taylor Greg , Schrader Kasmintan A. , Jones Steven J.M. , Kollmannsberger Christian , Laskin Janessa , Marra Marco A.
Published: November 2018

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: CDK6 (81st percentile), MYC (99th percentile), AR (100th percentile), PDGFRA and PDGFRB (99th and 100th percentiles, respectively), and MAP2K2 (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors’ knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.
Investigation of `glitches' in the energy spectrum induced by single-crystal diamond compound X-ray refractive lenses
Authors: Zhang Qiuyuan , Polikarpov Maxim , Klimova Nataliya , Larsen Helge B. , Mathiesen Ragnvald , Emerich Hermann , Thorkildsen Gunnar , Snigireva Irina , Snigirev Anatoly
Published: November 2018

Single-crystal diamond stands out among all the candidate materials that could be exploited to fabricate compound refractive lenses (CRLs) owing to its extremely stable properties. Among all related experimental features, beam divergence, χ-angles relative to the incoming beam in Eulerian geometry and different positions of the X-ray beam relative to the lens geometry may influence the transmission energy spectrum of CRLs. In addition, the orientation of the single-crystal diamond sample may also affect the glitches significantly. To verify these initial assumptions, two experiments, an energy scan and an ω-scan, were set up by employing a polished diamond plate consisting of five biconcave lenses. The results show that beam divergence does not affect the spectrum, nor do χ-angles when ω is set to zero. Nevertheless, different incident positions have an appreciable effect on the transmission spectrum, in particular the `strengths' of the glitches. This is attributed to absorption. The ω-scan setup is capable of determining the so-called orientation matrix, which may be used to predict both `energy positions' and `strengths' of the glitches.
2-Amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one
Authors: Lahmidi Sanae , El Hafi Mohamed , Sebbar Nada kheira , Abad Nadeem , Essassi El Mokhtar , Mague Joel T.
Published: November 2018

The asymmetric unit of the title compound, C6H7N5O, consists of two molecules with almost identical conformations. In the crystal, inversion dimers linked by pairs of N—H...N hydrogen bonds occur for both molecules; further N—H...N and N—H...O hydrogen bonds connect the dimers into a three-dimensional network.
Stemming the tide of work-related stress: it’s not rocket science, it’s neuroscience
Authors: Chase Maria Alexis
Published: November 2018

Purpose

This paper aims to illuminate how the findings from neuroscience, translate into simple, elegant, and easily applied tools which offer highly effective strategies to help stem the rising tide of stress in global work-forces.

Design/methodology/approach

Focusing on how current working practices inadvertently activate the brains primal survival mechanism, this paper details the brain’s main organizing principle and the negative effect this has on performance and productivity.

Findings

Exemplifying why, how, and when this automated stress response is triggered, the paper suggests practical, real-world solutions to overcome the primal fight, flight, and freeze mechanism. As this mechanism is responsible for the majority of work-related stress, it discusses the brains capacity to re-wire and change behavioral responses to stress at an individual and organizational level

Originality/value

This study seeks to introduce the concept of aligning work place practices with biological processes. Hoping to open a debate around shifting cultural perceptions of what constitutes the real well-being of work forces, it offers a unique and fresh perspective into the machinery of the mind.
Contextual layers of service experience in professional business services
Authors: Still Johanna , Komulainen Hanna , Nätti Satu
Published: November 2018

Purpose

This study provides us with new knowledge in the form of conceptual framework of the contextual layers of service experience within professional business services. This study aims to answer the following questions: What kinds of contextual layers can be identified influencing service experience? How specific characteristics of professional service context may influence customer experience at these different layers?

Design/methodology/approach

The framework is based on extensive literature review considering research in the fields of service and relationship perspectives, likewise professional services.

Findings

The framework is based on extensive literature review in the fields of service and relationship perspectives, likewise professional services.

Originality/value

Only a limited number of studies seem to address the highly topical context of professional/knowledge-intensive business services and relationships. The authors tie the discussion concerning different contextual layers of service experience to this specific operating context with the aim of identifying their importance and influence in service experience. Related to this context, this study highlights the importance of understanding role of individuals in service experience, rarely emphasized in B2B dyadic setting. The framework also contributes to current discussion regarding service experience and “zooms in” to the context and its detailed levels.
Placing social capital in business networks: conceptualisation and research agenda
Authors: Bondeli Julia V. , Havenvid Malena Ingemansson , Solli-Sæther Hans
Published: November 2018

Purpose

This paper aims to refine conceptual treatment of the social facet in business relationships and reinforce its significance in the industrial marketing and purchasing (IMP) research tradition by integrating the concept of social capital in its original interpretation into the actor-resource-activity (ARA) model.

Design/methodology/approach

The paper begins by indicating some typical conceptual challenges associated with application of social capital in IMP. This is followed by a conceptual clarification that explores the origin and the essence of social capital in economic sociology. Finally, the paper proposes integrating social capital in its original interpretation into IMP’s ARA model and presents four propositions on how social capital is created in interaction between business actors.

Findings

The paper shows how bridging Bourdieu’s theory of social capital with the IMP approach may solve the identified conceptual challenges. This paper’s main contribution is a cyclical model depicting how social capital is created in business networks. It is integrated into the ARA model and designed specifically for studying the social facet of business relationships.

Research limitations/implications

The paper is expected to aid IMP researchers in empirical contexts where the social component in business relationships is particularly prominent. As such, the novel approach presented could be used to further understand how social exchange processes are related to relationship governance, relationship initiation and development.

Originality/value

The proposed model shows how social capital is generated through the dynamic interplay in the social facets of actor, activity and resource dimensions, emphasising its creation dynamics. The model integrates insights from the classic works in economic sociology to strengthen the social side of IMP’s socioeconomic interface and is intended to be used as a tool for empirical application.
Algorithm applied in corporate sustainability
Authors: Barcellos de Paula Luciano , Gil-Lafuente Anna Maria
Published: November 2018

Purpose

Scientific studies indicate that stakeholder’s engagement is a key factor for the creation of sustainable value in companies. This paper aims to evaluate the sustainability of a sports company and propose a tool to prioritize the relevant issues that this company should consider in its operations.

Design/methodology/approach

Stakeholder theory and Global Reporting Initiative (GRI) are considered, and, from the Fuzzy Logic, the paper proposes a decision-making tool to establish the relevant issues. The “Experton Method” is used in this paper.

Findings

The algorithm used can help decision makers in processes that include the stakeholder’s opinions. In this case, a tool that treats qualitative data in a reliable manner is required. The methodology used allowed knowing the stakeholders expectations and to define priorities in sustainability issues. The results were captured in a materiality matrix. The manuscript concludes that including stakeholders in the decision-making process, the company generates trust and legitimacy of its stakeholders. This participatory approach and the use of algorithm help companies in materiality assessment, definition of priority issues and management of resources.

Practical implications

In terms of managerial implications, this paper presents a useful tool that can help entrepreneurs in the decision-making to manage their suppliers. Using an algorithm of fuzzy logic applied in the supply chain management, it is indicated how to set priorities to build a consistent corporate social responsibility (CSR) plan to achieve corporation success. This methodology allows reducing subjectivity; it generates greater precision and decreases the risk in decision-making. At the same time, it promotes dialogue and collaboration among stakeholders to create value for stakeholders and CSR, and collaborate to have a responsible company performance. Furthermore, this paper provides theoretical applications in terms of the literature review on corporate sustainability, indicating that companies must consider the stakeholder’s engagement in its strategies. Based on the bibliometric study, there are knowledge gaps on the subject. For these reasons, an important contribution is observed at the academic level that allows expanding the frontier of knowledge on the subject.

Originality/value

A tool for decision-making is presented with great utility for entrepreneurs in the processes of dialogue and stakeholder’s engagement, being a contribution for the creation of sustainable value. In addition, there is an important scientific contribution because the paper identifies in the literature the knowledge gaps on the subject.
The effect of tempeh intake on spatial memory in prediabetic rats
Authors: Ayuningtyas Annisa , Murbawani Etisa Adi , Nuryanto Nuryanto
Published: November 2018

Purpose

Prediabetes can affect the central nervous system and lead to changes including impaired cognition and spatial memory. Isoflavones, especially genistein and daidzein, can increase spatial memory. Tempeh is a soy product with high levels of genistein and daidzein. The purpose of this paper is to determine the effect of tempeh on spatial memory of prediabetic Wistar rat.

Design/methodology/approach

A pre-and post-test randomised control group design was used. In total, 15 male Wistar rats were divided into three equal groups, Treatment 1 (T1), Treatment 2 (T2) and Treatment 3 (T3). All rats were injected with alloxan (120 mg/Kg body weight) to induce prediabetes. T1 was maintained on a diet of standard food for 14 days. T2 and T3 were given 9 g/200 g body weight and 18 g/200 g body weight of tempeh, respectively, for 14 days. The Morris water maze (MWM) test was used to test spatial memory.

Findings

While there were no statistically significant differences between the treatment groups, there was a difference with the tempeh-treated rats improving their spatial memory following tempeh ingestion with a decrease in the travel time to negotiate the MWM [T1(−8.36), T2 (−5.48) and T3 (3.66)]. Differences of travel time of the three groups was not significant (p = 0.677).

Originality/value

The result of the study indicates that tempeh may act as a functional food in reducing cognitive impairment associated with prediabetes and diabetes. However, as the result is not statistically significant, further research using animal models and human studies is warranted.
Ageing in an herbaceous plant: Increases in mortality and decreases in physiology and seed mass
Authors: Quarles Brandie M. , Roach Deborah Ann
Published: November 2018

Little is known about plant age‐dependent trait expression and how environmental conditions might affect ageing in the wild. This study evaluates age variation in multiple traits of a short‐lived perennial herb using a manipulative field experimental design.

Two different‐aged cohorts were followed in a field plot for over a year to evaluate trait expression in response to a competition treatment and seasonal stress. Traits measured included size, mortality, reproduction, and physiology, including photosynthetic efficiency and chlorophyll content (SPAD). We hypothesized that the stress of competition and seasonal changes would accentuate age‐dependent trait declines in older plants.

The results highlight consistent age differences in plant size, mortality, and seed size with older plants being smaller, more likely to die, and producing smaller seeds. Some of the ageing declines were sensitive to environmental conditions such that it was only during certain seasons when older plants had higher mortality, lower photosynthetic efficiency, and lower chlorophyll content than young plants. Age‐dependent trait expression also varied in response to competition such that age differences in size were only present in the “no competition treatment,” and old individuals in the competition treatment had a higher mortality than all other age‐environment combinations.

Synthesis. These findings show that ageing in plants is a complex phenotype where declines in traits are uncoordinated and can be, but are not always, sensitive to environmental conditions. This study shows age‐dependent maternal effects on offspring quality which, together with the decline in performance of older individuals, may have impacts on an individual’s fitness and on natural population demography.
Reconceptualizing developmental language disorder as a spectrum disorder: issues and evidence
Authors: Lancaster Hope S. , Camarata Stephen
Published: November 2018

Background

There is considerable variability in the presentation of developmental language disorder (DLD). Disagreement amongst professionals about how to characterize and interpret the variability complicates both the research on understanding the nature of DLD and the best clinical framework for diagnosing and treating children with DLD. We describe and statistically examine three primary possible models for characterizing the variability in presentation in DLD: predictable subtypes; individual differences; and continuum/spectrum.

Aims

To test these three models of DLD in a population‐based sample using two distinct types of cluster analyses.

Methods & Procedures

This study included children with DLD (n = 505) from the US Epidemiological Study of Language Impairment database. All available language and cognitive measures were included. Two cluster methods were used: Ward's method and K‐means. Optimal cluster sizes were selected using Bayesian information criteria (BIC). Bootstrapping and permutation methods were used to evaluate randomness of clustering.

Outcomes & Results

Both clustering analyses yielded more than 10 clusters, and the clusters did not have spatial distinction: many of these clusters were not clinically interpretable. However, tests of random clustering revealed that the cluster solutions obtained did not arise from random aggregation.

Conclusions & Implications

Non‐random clustering coupled with a large number of non‐interpretable subtypes provides empirical support for the continuum/spectrum and individual differences models. Although there was substantial support for the continuum/spectrum model and weaker support for the individual differences model, additional research testing these models should be completed. Based on these results, clinicians working with children with DLD should focus on creating treatment plans that address the severity of functioning rather than seeking to identify and treat distinct subtypes. Additional consideration should be given to reconceptualizing DLD as a spectrum condition.
Attribute Specific Impacts of Stated Non‐Attendance in Choice Experiments
Authors: Mohanty Suva Kanta , Balcombe Kelvin , Bennett Richard , Nocella Giuseppe , Fraser Iain
Published: November 2018

In this paper, we generalise existing approaches to the treatment of stated attribute non‐attendance data in discrete choice experiments by allowing attribute specific impacts. We implement this approach by employing an extended hierarchical Bayes logit model specification. To illustrate this approach, we consider data collected to examine Indian consumers’ preferences for traditional aromatic rice varieties. Our results regarding stated attribute non‐attendance reveal that, our new approach shrinks marginal utilities of non‐attenders substantially compared to stated attenders, with significant differences in the shrinkage between some of the attributes. In addition, our results reveal the way in which non‐attendance of attributes interact with each other and the impact that this has on the distribution of willingness to pay estimates.