bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers of Targeted Therapy and Immuno-Oncology in Cancers Metastatic to the Breast
Authors: Vranic Semir , Senarathne Wijendra , Stafford Phillip , Poorman Kelsey , Pockaj Barbara A. , Gatalica Zoran
Published: September 2019

The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.
Multidimensional screening for predicting pain problems in adults: a systematic review of screening tools and validation studies
Authors: Veirman Elke , Van Ryckeghem Dimitri M. L. , De Paepe Annick , Kirtley Olivia J. , Crombez Geert
Published: September 2019

Screening tools allowing to predict poor pain outcomes are widely used. Often these screening tools contain psychosocial risk factors. This review (1) identifies multidimensional screening tools that include psychosocial risk factors for the development or maintenance of pain, pain-related distress, and pain-related disability across pain problems in adults, (2) evaluates the quality of the validation studies using Prediction model Risk Of Bias ASsessment Tool (PROBAST), and (3) synthesizes methodological concerns. We identified 32 articles, across 42 study samples, validating 7 screening tools. All tools were developed in the context of musculoskeletal pain, most often back pain, and aimed to predict the maintenance of pain or pain-related disability, not pain-related distress. Although more recent studies design, conduct, analyze, and report according to best practices in prognosis research, risk of bias was most often moderate. Common methodological concerns were identified, related to participant selection (eg, mixed populations), predictors (eg, predictors were administered differently to predictors in the development study), outcomes (eg, overlap between predictors and outcomes), sample size and participant flow (eg, unknown or inappropriate handling of missing data), and analysis (eg, wide variety of performance measures). Recommendations for future research are provided.
Spinal cord stimulation prevents paclitaxel-induced mechanical and cold hypersensitivity and modulates spinal gene expression in rats
Authors: Sivanesan Eellan , Stephens Kimberly E. , Huang Qian , Chen Zhiyong , Ford Neil C. , Duan Wanru , He Shao-Qui , Gao Xinyan , Linderoth Bengt , Raja Srinivasa N. , Guan Yun
Published: September 2019

Introduction:

Paclitaxel-induced peripheral neuropathy (PIPN) is a common dose-limiting side effect of this cancer treatment drug. Spinal cord stimulation (SCS) has demonstrated efficacy for attenuating some neuropathic pain conditions.

Objective:

We aim to examine the inhibitory effect of SCS on the development of PIPN pain and changes of gene expression in the spinal cord in male rats after SCS.

Methods:

We examined whether traditional SCS (50 Hz, 6–8 h/session daily for 14 consecutive days) administered during paclitaxel treatment (1.5 mg/kg, i.p.) attenuates PIPN-related pain behavior. After SCS treatment, we performed RNA-seq of the lumbar spinal cord to examine which genes are differentially expressed after PIPN with and without SCS.

Results:

Compared to rats treated with paclitaxel alone (n = 7) or sham SCS (n = 6), SCS treatment (n = 11) significantly inhibited the development of paclitaxel-induced mechanical and cold hypersensitivity, without altering open-field exploratory behavior. RNA-seq showed that SCS induced upregulation of 836 genes and downregulation of 230 genes in the spinal cord of paclitaxel-treated rats (n = 3) as compared to sham SCS (n = 5). Spinal cord stimulation upregulated immune responses in paclitaxel-treated rats, including transcription of astrocyte- and microglial-related genes, but repressed transcription of multiple gene networks associated with synapse transmission, neuron projection development, γ-aminobutyric acid reuptake, and neuronal plasticity.

Conclusion:

Our findings suggest that traditional SCS may attenuate the development of pain-related behaviors in PIPN rats, possibly by causing aggregate inhibition of synaptic plasticity through upregulation and downregulation of gene networks in the spinal cord.
Utility of Longitudinal Measurement of the Liver With Ultrasound in Comparison to Computed Tomography Liver Volume in Assessing Hepatomegaly
Authors: Surasi Devaki Shilpa Sudha , Jazbeh Sammer , Nicek Zachary S. , Zanabria Rosemarie G. , Wells Richard T. , Patel Aashka , Alhyari Laith , Wagner Jason M.
Published: September 2019

The purpose of the study is to retrospectively compare the longitudinal measurement of the liver on ultrasound (US) with liver volume as measured on computed tomography (CT). This institutional review board–approved retrospective study with prospective image analysis included adult patients with US examinations of the liver and CT examinations of the abdomen performed within 2 weeks of each other from January 1, 2010, to April 30, 2016. We recorded the dome-to-tip longitudinal length measurement of the right lobe of the liver on the US study. The liver volume was calculated using manual 3-dimensional segmentation of the CT data set. Additional linear liver measurements and qualitative assessments were retrospectively made on the US and CT images. Hepatomegaly was defined as a liver volume 2000 mL or greater. The sample had 302 patients including 140 males and 162 females. Liver length measured on US had a moderate positive correlation with liver volume measured on CT, with a Pearson correlation coefficient of 0.7078. The optimum cutoff of liver length (US) was found to be 17 cm by Youden index, with a sensitivity of 76.0% and specificity of 73.4% for hepatomegaly. Additional linear measurements and qualitative assessments of the liver did not significantly improve the diagnosis of hepatomegaly. In conclusion, liver length measured with US has only a moderate correlation with liver volume. Commonly used US liver length maximum values of 16 to 18 cm produce a significant number of false-negatives and false-positives for the diagnosis of hepatomegaly.
Opioid Prescriptions for Female Pelvic Reconstructive Surgery Patients Before and After Implementation of Tennessee State Legislation
Authors: Samimi Parisa , Panza Joseph , Heft Jessica , Wang Li , Adam Rony
Published: September 2019

Objectives

Limited data exist regarding the impact of state legislation on opioid-prescribing patterns, particularly in states with the highest opioid-prescribing rates in the nation. Our primary objective was to examine the change in the amount of opioid morphine equivalents (OMEs) prescribed at discharge to patients undergoing female pelvic reconstructive surgery after the implementation of state legislation created in response to the opioid crisis.

Methods

At our institution, state legislation went into effect on July 1, 2018, implementing limitations on OMEs prescribed to patients. This retrospective cohort study examines all adult women undergoing female pelvic reconstructive surgery from January 1, 2018, to December 31, 2018. The study compares prescribing practices 6 months before and 6 months after the state law was enacted.

Results

In total, 346 patients met inclusion criteria. The 2 groups had similar demographics. Surgical procedures were well distributed, with 52% of cases occurring in the first 6 months of the calendar year. At the time of discharge, 324 (96.7%) patients received an opioid prescription, with an overall average of 197 OMEs. After the implementation of state legislation on July 1, 2018, the amount of OMEs prescribed at discharge significantly decreased, from a median of 210 mg (interquartile range, 150–225) to 150 mg (interquartile range 135–225; P = 0.02).

Conclusions

State legislation was associated with a significant decrease in prescribed OMEs at the time of discharge in patients undergoing female pelvic reconstructive surgery. These results support ongoing legislative efforts to address the current opioid crisis.
Behaviors Characteristic of Autism Spectrum Disorder in a Geriatric Cohort With Mild Cognitive Impairment or Early Dementia
Authors: Rhodus Elizabeth K. , Barber Justin , Abner Erin L. , Duff Danielle M.C. , Bardach Shoshana H. , Caban-Holt Allison , Lightner Donita , Rowles Graham D. , Schmitt Frederick A. , Jicha Gregory A.
Published: September 2019

Introduction:

Autism spectrum disorder (ASD) represents a heterogenous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has been poorly explored.

Methods:

To more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in mild cognitive impairment and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2.

Results:

Participants with high autism index ratings (autism “possible/very likely,” n=23) reported significantly (statistically and clinically) younger age at the onset of cognitive impairment than those who scored in the autism “unlikely” range (n=119): 71.14±10.9 vs. 76.65±8.25 (P=0.034). In addition, those in the autism “possible/very likely” group demonstrated advanced severity of cognitive impairment, indicated by the Clinical Dementia Rating Scale Sum of Boxes scores.

Discussion:

Data demonstrate that ASD behaviors may seem de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.
Insomnia-related Memory Impairment in Individuals With Very Complex Chronic Pain
Authors: Bothelius Kristoffer , Hysing Eva-Britt , Filén Tove , Lundeborg Linnea , Gordh Torsten
Published: September 2019

Objective:

To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain.

Background:

Individuals with insomnia disorder or chronic pain often experience cognitive deficits, with both conditions appearing to correlate with impairments in neuropsychological functions. As insomnia often occurs comorbid with chronic pain, distinguishing the differential effects of these two syndromes on an individual’s neuropsychological functioning can be challenging. Comorbid depressive symptoms in these individuals, which may also affect cognitive function, may further obscure the associations between chronic pain, insomnia, and the neuropsychological profile.

Methods:

The neuropsychological function of 22 individuals with very complex chronic pain was assessed using specialized tests examining aspects of memory and executive functioning. The severity of insomnia, depression, and anxiety was measured using questionnaires, and pain levels were assessed using a visual analog scale. Pain medications were transformed to the morphine-equivalent daily dose.

Results:

Insomnia severity was found to predict memory function, accounting for 32.4% of the variance: A 1 SD increase in insomnia severity decreased memory function by 0.57 SD. The negative correlation between insomnia and memory was significant even after controlling for pain level, morphine-equivalent daily dose, and comorbid levels of anxiety and depression.

Conclusions:

Insomnia severity independently predicted memory function in patients with very complex chronic pain, even after controlling for other factors known to impair cognitive function. Insomnia may possibly explain some of the cognitive impairments related to chronic pain; thus, screening for, and treating, sleep disturbances may be a central aspect of chronic pain rehabilitation.
The Dynamic Strength of the Hair-Cell Tip Link Reveals Mechanisms of Hearing and Deafness
Authors: Mulhall Eric M. , Ward Andrew , Yang Darren , Koussa Mounir A. , Corey David P. , Wong Wesley P.
Published: September 2019

Our senses of hearing and balance rely on the extraordinarily sensitive molecular machinery of the inner ear to convert deflections as small as the width of a single carbon atom1,2 into electrical signals that the brain can process3. In humans and other vertebrates, transduction is mediated by hair cells4, where tension on tip links conveys force to mechanosensitive ion channels5. Each tip link comprises two helical filaments of atypical cadherins bound at their N-termini through two unique adhesion bonds6–8. Tip links must be strong enough to maintain a connection to the mechanotransduction channel under the dynamic forces exerted by sound or head movement—yet might also act as mechanical circuit breakers, releasing under extreme conditions to preserve the delicate structures within the hair cell. Previous studies have argued that this connection is exceptionally static, disrupted only by harsh chemical conditions or loud sound9–12. However, no direct mechanical measurements of the full tip-link connection have been performed. Here we describe the dynamics of the tip-link connection at single-molecule resolution and show how avidity conferred by its double stranded architecture enhances mechanical strength and lifetime, yet still enables it to act as a dynamic mechanical circuit breaker. We also show how the dynamic strength of the connection is facilitated by strong cis-dimerization and tuned by extracellular Ca2+, and we describe the unexpected etiology of a hereditary human deafness mutation. Remarkably, the connection is several thousand times more dynamic than previously thought, challenging current assumptions about tip-link stability and turnover rate, and providing insight into how the mechanotransduction apparatus conveys mechanical information. Our results reveal fundamental mechanisms that underlie mechanoelectric transduction in the inner ear, and provide a foundation for studying multi-component linkages in other biological systems.
Visual properties of human retinal ganglion cells
Authors: Reinhard Katja , Münch Thomas A.
Published: September 2019

The retinal output is the sole source of visual information for the brain. Studies in non-primate mammals estimate that this information is carried by several dozens of retinal ganglion cell types, each informing the brain about different aspects of a visual scene. Even though morphological studies of primate retina suggest a similar diversity of ganglion cell types, research has focused on the function of only a few cell types. In human retina, recordings from individual cells are anecdotal or focus on a small subset of identified types. Here, we present the first systematic ex-vivo recording of light responses from 342 ganglion cells in human retinas obtained from donors. We find a great variety in the human retinal output in terms of preferences for positive or negative contrast, spatio-temporal frequency encoding, contrast sensitivity, and speed tuning. Some human ganglion cells showed similar response behavior as known cell types in other primates, while we also recorded light responses that have not been described previously. This first extensive description of the human retinal output should facilitate interpretation of primate data and comparison to other mammalian species, and it lays the basis for the use of ex-vivo human retina for in-vitro analysis of novel treatment approaches.
A new strategy for selection of crop cultivated varieties based on yield factors driving and meteorological prediction
Authors: Zhu Rongsheng , Sun Kai , Yan Xuehui , Xin Dawei , Jiang Hongwei , Zhang Zhanguo , Li Yang , Hu Zhenbang , Qi Zhaoming , Yang Chunming , Chen Qingshan
Published: September 2019

Meteorological conditions, as an uncontrollable factor, have a direct impact on the growth and yield of crops in the field. It’s particularly important to choose the cultivated varieties suitable for environmental change. As for this problem, a new strategy for selection of crop cultivated varieties is proposed in this paper. The experiment selected Harbin pilot (Heilongjiang, China) and Changchun pilot (Jilin, China). In the experiment, the cultivated varieties suitable for forecasting meteorological conditions in 2015 could be provided according to the meteorological data of 2005-2014 years and the yield data of different soybean varieties in Harbin pilot. The same method was also taken in Changchun pilot. The results showed that the recommended varieties of Harbin pilot and Changchun pilot had 70% and 50% probability respectively for selection of soybean cultivated varieties when the yield evaluation trait was 100-seed-weight. As for seed weight per plant, the possibility of more than 60% of the recommended varieties in two pilots is to provide prejudgment. Therefore, this method can help to improve the current situation of the impact of uncontrollable meteorological conditions on crop yield and also can be applied to the selection of any other crops cultivated varieties under a certain environment.
Osteoporosis- and obesity-risk interrelationships: An epigenetic analysis of GWAS-derived SNPs at the developmental geneTBX15
Authors: Zhang Xiao , Ehrlich Kenneth C. , Yu Fangtang , Hu Xiaojun , Deng Hong-Wen , Shen Hui , Ehrlich Melanie
Published: September 2019

A major challenge in translating findings from genome-wide association studies (GWAS) to biological mechanisms is pinpointing functional variants because only a very small percentage of variants associated with a given trait actually impact the trait. We used an extensive epigenetics, transcriptomics, and genetics analysis of theTBX15/WARS2neighborhood to prioritize this region’s best-candidate causal variants for the genetic risk of osteoporosis (estimated bone density, eBMD) and obesity (waist-hip ratio or waist circumference adjusted for body mass index).TBX15encodes a transcription factor that is important in bone development and adipose biology. Manual curation of 692 GWAS-derived variants gave eight strong candidates for causal SNPs that modulateTBX15transcription in subcutaneous adipose tissue (SAT) or osteoblasts, which highly and specifically express this gene. None of these SNPs were prioritized by Bayesian fine-mapping. The eight regulatory causal SNPs were in enhancer or promoter chromatin seen preferentially in SAT or osteoblasts atTBX15intron-1 or upstream. They overlap strongly predicted, allele-specific transcription factor binding sites. Our analysis suggests that these SNPs act independently of two missense SNPs inTBX15. Remarkably, five of the regulatory SNPs were associated with eBMD and obesity and had the same trait-increasing allele for both. We found thatWARS2obesity-related SNPs can be ascribed to high linkage disequilibrium withTBX15intron-1 SNPs. Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tuneTBX15expression and, thereby, affect both obesity and osteoporosis risk.
Basal forebrain parvalbumin neurons mediate arousals from sleep induced by hypercarbia or auditory stimuli
Authors: McKenna James T. , Thankachan Stephen , Uygun David S , Shukla Charu , Cordeira Joshua , McNally James M. , Katsuki Fumi , Zant Janneke , Gamble Mackenzie C. , Deisseroth Karl , McCarley Robert W. , Brown Ritchie E. , Strecker Robert E. , Basheer Radhika
Published: September 2019

Brief arousals from sleep in patients with sleep apnea and other disorders prevent restful sleep, and contribute to cognitive, metabolic and physiologic dysfunction. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system. These inputs include the brainstem parabrachial neurons which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia, but which cell types within the BF mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here using optogenetic techniques in mice, we show that BF parvalbumin (PV) neurons fulfill several criteria for a system mediating brief arousals from sleep. Optical stimulation of BF PV neurons during the light period, when mice normally sleep, caused rapid transitions to wakefulness and increased wake bout durations. Unlike many other ascending arousal systems, arousals induced by stimulation of BF PV neurons were brief, resulting in only a small (13.6%) increase in the total amount of wakefulness. Bilateral optical inhibition of BF PV neurons increased the latency to arousal produced by hypercarbia or auditory stimuli. Thus, BF PV neurons are an important component of the brain circuitry which generates brief arousals from sleep in response to internal and external sensory stimuli.
Optimal design of single-cell RNA sequencing experiments for cell-type-specific eQTL analysis
Authors: Mandric Igor , Schwarz Tommer , Majumdar Arunabha , Perez Richard , Subramaniam Meena , Ye Chun Jimmie , Pasaniuc Bogdan , Halperin Eran
Published: September 2019

Single-cell RNA-sequencing (scRNA-Seq) is a compelling approach to simultaneously measure cellular composition and state which is impossible with bulk profiling approaches. However, it has not yet become a widely used tool in population-scale analyses, due to its prohibitively high cost. Here we show that given the same budget, the statistical power of cell-type-specific expression quantitative trait loci (eQTL) mapping can be increased through low-coverage per-cell sequencing of more samples rather than high-coverage sequencing of fewer samples. We also show that multiple experimental designs with different numbers of samples, cells per sample and reads per cell could have similar statistical power, and choosing an appropriate design can yield large cost savings especially when multiplexed workflows are considered. Finally, we provide a practical approach on selecting cost-effective designs for maximizing cell-type-specific eQTL power.
2D-HELS-AA MS Seq: Direct sequencing of tRNA reveals its different isoforms and multiple dynamic base modifications
Authors: Zhang Ning , Shi Shundi , Wang Xuanting , Ni Wenhao , Yuan Xiaohong , Duan Jiachen , Jia Tony Z. , Yoo Barney , Ziegler Ashley , Russo James J. , Li Wenjia , Zhang Shenglong
Published: September 2019

We report a direct method for sequencing tRNAPhewithout cDNA by combining 2-dimensional hydrophobic RNA end-labeling with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNAPhewas sequenced and the identity, location and abundance of all 11 base modifications were determined. Changes in ratios of wybutosine and its depurinated form under different conditions were quantified, pointing to the ability of our technology to determine dynamic changes of nucleotide modifications. Two truncated isoforms at 3’CCA tail of the tRNAPhe(75 nt CC, 80% and 74 nt C, 3%) were identified in addition to the 76 nt tRNAPhewith a full-length 3’CCA tail (17%). We also discovered a new isoform with A-G transitions at both the 44 and 45 positions in the tRNAPhevariable loop.

One Sentence Summary

Direct 2D-HELS-AA MS Seq of tRNA reveals different isoforms and base modifications
Orb-weaving spiders show a correlated syndrome of morphology and web structure in the wild
Authors: Fisher David N. , Yeager Justin , Pruitt Jonathan N.
Published: September 2019

Extended phenotypes are traits that exist outside the physical body of the organism. Despite their potential role in the lives of both the organisms that express them and other organisms that can be influenced by extended phenotypes, the consistency and covariance with morphological and behaviour traits of extended phenotypes is rarely evaluated, especially in wild organisms. We repeatedly measured an extended phenotype that directly influences an organism’s prey acquisition, the web structure, of wild orb-weaving spiders (Micrathena vigorsii), which re-build their webs each day. We related web structure traits to behavioural traits and body size (length). Both web diameter and web density were repeatably different among individuals, while reaction to a predation threat was slightly so, but response to a prey stimulus and web symmetry were not. There was a syndrome between morphology and web structure traits, where larger spiders spun webs that were wider, had webs with increased thread spacing, and the spider tended to react more slowly to a predation threat. When a spider built a relatively larger web it was also relatively a less dense and less symmetrical web. The repeatability of web construction and relationship with spider body size we found may be common features of intra-population variation in web structure in spiders. Individual variation along the morphology and web structure syndrome could represent variation in individual foraging strategies, or age-based correlated changes. By estimating the consistency and covariances of extended phenotypes we can begin to evaluate what maintains their variation and how they might evolve.
IdentifyingClostridioides difficile-inhibiting gut commensals using culturomics, phenotyping, and combinatorial community assembly
Authors: Ghimire Sudeep , Roy Chayan , Wongkuna Supapit , Antony Linto , Fenske Gavin , Maji Abhijit , Keena Mitchel Chan , Foley Andrew , Scaria Joy
Published: September 2019

A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious level. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1590 isolates belonging to 102 species. Estimated by metagenomic sequencing of fecal samples used for culture, this culture collection represents 50.73% of taxonomic diversity and 70% functional capacity. Using whole genome sequencing we characterized species representatives from this collection, and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profile and short chain fatty acid (SCFA) production. When screened using a co-culture assay, 66 species in our culture collection inhibitedC. difficile. Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol or succinate correlated withC. difficileinhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory toC. difficile. When 256 combinations were tested, we found both species composition and blend size to be important in inhibition. Our results show that the interaction of bacteria with each other in a mix and with other members of gut commensals must be investigated for designing defined bacterial mixes for inhibitingC. difficile in vivo.

IMPORTANCE

Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, allowing pathogens such asC. difficileto colonize, causing recurrent infection and mortality. Although fecal microbiome transplantation has shown to be an effective treatment forC. difficileinfection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria.C. difficile-inhibiting species and bacterial combinations we identify herein improve our understanding of the ecological interactions controlling colonization resistance againstC. difficile, and could aid the design of defined bacteriotherapy as a non-antibiotic alternative against CDI.
A high-quality reference genome assembly of the saltwater crocodile,Crocodylus porosus, reveals patterns of selection in Crocodylidae
Authors: Ghosh Arnab , Johnson Matthew G. , Osmanski Austin B. , Louha Swarnali , Bayona-Vásquez Natalia J. , Glenn Travis C. , Gongora Jaime , Green Richard E. , Isberg Sally , Stevens Richard D. , Ray David A.
Published: September 2019

Crocodilians are an economically, culturally, and biologically important group. To improve researchers’ ability to study genome structure, evolution, and gene regulation in the clade, we generated a high-qualityde novogenome assembly of the saltwater crocodile,Crocodylus porosus, from Illumina short read data from genomic libraries andin vitroproximity-ligation libraries. The assembled genome is 2,123.5 Mb, with N50 scaffold size of 17.7 Mb and N90 scaffold size of 3.8 Mb. We then annotated this new assembly, increasing the number of annotated genes by 74%. In total, 96% of 23,242 annotated genes were associated with a functional protein domain. Furthermore, multiple non-coding functional regions and mappable genetic markers were identified. Upon analysis and overlapping the results of branch length estimation and site selection tests for detecting potential selection, we found 16 putative genes under positive selection in crocodilians, ten inC. porosusand six inA. mississippiensis. The annotatedC. porosusgenome will serve as an important platform for osmoregulatory, physiological and sex determination studies, as well as an important reference in investigating the phylogenetic relationships of crocodilians, birds, and other tetrapods.
A Pairwise Distance Distribution Correction (DDC) algorithm to eliminate blinking-caused artifacts in super-resolution microscopy
Authors: Bohrer Christopher H. , Yang Xinxing , Weng Xiaoli , Tenner Brian , Thakur Shreyasi , McQuillen Ryan , Ross Brian , Wooten Matthew , Chen Xin , Lakadamyali Melike , Zhang Jin , Roberts Elijah , Xiao Jie
Published: September 2019

In single-molecule localization based super-resolution microscopy (SMLM), a fluorophore stochastically switches between fluorescent- and dark-states, leading to intermittent emission of fluorescence, a phenomenon known as blinking. Intermittent emissions create multiple localizations belonging to the same molecule, resulting in blinking-artifacts within SMLM images. These artifacts are often interpreted as true biological assemblies, confounding quantitative analyses and interpretations. Multiple methods have been developed to eliminate these artifacts, but they either require additional experiments, arbitrary thresholds, or specific photo-kinetic models. Here we present a method, termed Distance Distribution Correction (DDC), to eliminate blinking-caused repeat localizations without any additional calibrations. The approach relies on the finding that the true pairwise distance distribution of different fluorophores in an SMLM image can be naturally obtained from the imaging sequence by using distances between localizations separated by a time much longer than the average fluorescence survival time. We show that using the true pairwise distribution we can define and then maximize the likelihood of obtaining a particular set of localizations void of blinking-artifacts, generating an accurate reconstruction of the underlying cellular structure. Using both simulated and experimental data, we show that DDC surpasses all previous existing blinking-artifact correction methodologies, resulting in drastic improvements in obtaining the closest estimate of the true spatial organization and number of fluorescent emitters in a wide range of applications. The simplicity and robustness of DDC will allow it to become the field standard in SMLM imaging, enabling the most accurate reconstruction and quantification of SMLM images to date.
Folding latency of fluorescent proteins affects the mitochondrial localization of fusion proteins
Authors: Kashiwagi Sayaka , Fujioka Yoichiro , Satoh Aya O. , Yoshida Aiko , Fujioka Mari , Nepal Prabha , Tsuzuki Atsushi , Aoki Ozora , Paudel Sarad , Sasajima Hitoshi , Ohba Yusuke
Published: September 2019

The discovery of fluorescent proteins (FPs) has revolutionized cell biology. The fusion of targeting sequences to FPs enables the investigation of cellular organelles and their dynamics; however, occasionally, such fluorescent fusion proteins (FFPs) exhibit behavior different from that of the native proteins. Here, we constructed a color pallet comprising different organelle markers and found that FFPs targeted to the mitochondria were mislocalized when fused to certain types of FPs. Such FPs included several variants of Aequorea victoria green FP (aqGFP) and a monomeric variant of the red FP. Because the FFPs that are mislocalized include FPs with faster maturing or folding mutations, the increase in the maturation rate is likely to prevent their expected localization. Indeed, when we reintroduced amino acid substitutions so that the FP sequences were equivalent to that of wild-type aqGFP, FFP localization to the mitochondria was significantly enhanced. Moreover, similar amino acid substitutions improved the localization of mitochondria-targeted pHluorin, which is a pH-sensitive variant of GFP, and its capability to monitor pH changes in the mitochondrial matrix. Our findings demonstrate the importance of selecting FPs that maximize FFP function.
The ATG5 Interactome Links Clathrin Vesicular Trafficking With The ATG8 Lipidation Machinery For Autophagosome Assembly
Authors: Baines Kiren , Lane Jon D.
Published: September 2019

Autophagosome formation involves the sequential actions of conserved ATG family proteins that regulate the lipidation of the ubiquitin-like modifier ATG8 at the nascent isolation membrane. Although the molecular steps driving this process are well understood, the source of membranes supplied for the expanding autophagosome and their mode of delivery remain uncertain. Here, we have used quantitative SILAC-based proteomics to identify proteins that associate with the ATG12∼ATG5 conjugate that is crucial for ATG8 lipidation. Our datasets reveal a strong enrichment of regulators of clathrin-mediated vesicular trafficking, including clathrin heavy and light chains, and several clathrin adaptors. Also identified were PIK3C2A (a phosphoinositide 3-kinase involved in clathrin-mediated endocytosis) and HIP1R (a component of clathrin vesicles), and the absence of either of these proteins caused defects in autophagic flux in cell-based starvation assays. To determine whether the ATG12∼ATG5 conjugate reciprocally influences trafficking within the endocytic compartment, we captured the cell surface proteomes of autophagy-competent and autophagy-incompetent mouse embryonic fibroblasts under fed and starved conditions. Proteins whose surface expression increased contingent on autophagic capability included EPHB2, SLC12A4, and JAG1. Those whose surface expression was decreased included CASK, SLC27A4 and LAMP1. These data provide evidence for direct regulatory coupling between the ATG12∼ATG5 conjugate and the clathrin membrane trafficking system, and suggest candidate membrane proteins whose trafficking within the cell may be modulated by the autophagy machinery.
Service ecosystem well-being: conceptualization and implications for theory and practice
Authors: Frow Pennie , McColl-Kennedy Janet R. , Payne Adrian , Govind Rahul
Published: September 2019

Purpose

This paper aims to conceptualize and characterize service ecosystems, addressing calls for research on this important and under-researched topic.

Design/methodology/approach

The authors draw on four meta-theoretical foundations of S-D logic – resource integration, resource density, practices and institutions – providing a new integrated conceptual framework of ecosystem well-being. They then apply this conceptualization in the context of a complex healthcare setting, exploring the characteristics of ecosystem well-being at the meso level.

Findings

This study provides an integrated conceptual framework to explicate the nature and structure of well-being in a complex service ecosystem; identifies six key characteristics of ecosystem well-being; illustrates service ecosystem well-being in a specific healthcare context, zooming in on the meso level of the ecosystem and noting the importance of embedding a shared worldview; provides practical guidance for managers and policy makers about how to manage complex service ecosystems in their quest for improving service outcomes; and offers an insightful research agenda.

Research limitations/implications

This research focuses on service ecosystems with an illustration in one healthcare context, suggesting additional studies that explore other industry contexts.

Practical implications

Practically, the study indicates the imperative for managing across mutually adapting levels of the ecosystem, identifying specific new practices that can improve service outcomes.

Social implications

Examining well-being in the context of a complex service ecosystem is critical for policymakers charged with difficult decisions about balancing the demands of different levels and actors in a systemic world.

Originality/value

The study is the first to conceptualize and characterize well-being in a service ecosystem, providing unique insights and identifying six specific characteristics of well-being.
White sanctuaries: race and place in art museums
Authors: Embrick David G. , Weffer Simón , Dómínguez Silvia
Published: September 2019

Purpose

This paper examines the Art Institute of Chicago – a nationally recognized museum – as a white sanctuary, i.e., a white institutional space within a racialized social system that serves to reassure whites of their dominant position in society. The purpose of this paper is to highlight how museums create and maintain white spaces within the greater context of being an institution for the general public.

Design/methodology/approach

The empirical analysis of this study is based on collaborative ethnographic data collected over a three-year period of time conducted by the first two authors, and consists of hundreds of photos and hundreds of hours of participant observations and field notes. The data are analyzed using descriptive methods and content analyses.

Findings

The findings highlight three specific racial mechanisms that speak to how white spaces are created, recreated and maintained within nationally and internationally elite museums: spatiality, the policing of space, and the management of access.

Research limitations/implications

Sociological research on how white spaces are maintained in racialized organizations is limited. This paper extends to museums’ institutional role in maintaining white supremacy, as white sanctuaries.

Originality/value

This paper adds to the existing literature on race, place and space by highlighting three specific racial mechanisms in museum institutions that help to maintain white supremacy, white normality(ies), and serve to facilitate a reassurance to whites’ anxieties, fears and fragilities about their group position in society – that which helps to preserve their psychological wages of whiteness in safe white spaces.
Factors explaining a cost-based pricing essence
Authors: Amaral Juliana Ventura , Guerreiro Reinaldo
Published: September 2019

Purpose

Empirical studies have found that cost-based pricing remains dominant in pricing practice and suggest that practice conflicts with marketing theory, which recommends value-based prices. However, empirical studies have yet to examine whether cost-plus formulas represent the pricing approach or essence.

Design/methodology/approach

This study aims to address the factors that explain price setting whereby the cost-plus formula is not just the pricing approach but also the pricing essence. This examination is grounded in a survey conducted on 380 Brazilian industrial companies.

Findings

The results show that, for price-makers, the cost-based pricing essence is positively associated with four factors (two obstacles to deploying value-based pricing, company size and differentiation), but it is negatively related to one factor (premium pricing strategy). For price-takers, the cost-based pricing essence is positively associated with four factors (two obstacles to deploying value-based pricing, coercive isomorphism and use of full costs), but it is negatively related to five factors (one obstacle to deploying value-based pricing, company size, competitors’ ability to copy, normative isomorphism and experience).

Originality/value

The key contribution of this paper is demonstrating that cost-plus formulas do not go against the incorporation of competitors and value information. This study reveals that it is possible to set prices based on either value or competitors’ prices while simultaneously preserving the simplicity of the cost-plus formulas. Via the margin, firms may connect costs to information about competition and value. The authors also demonstrate the drawbacks of not segregating companies into price-makers and price-takers and an excessive focus on the pricing approach at the expense of pricing essence.
Organizational prerequisites for knowledge creation and sharing: empirical evidence from Serbia
Authors: Stojanović-Aleksić Vesna , Erić Nielsen Jelena , Bošković Aleksandra
Published: September 2019

Purpose

Being mindful of the importance of organizational structure and organizational culture for knowledge management in companies, the purpose of this study is to investigate the organizational prerequisites for creating and sharing knowledge. The goals are to determine whether and to what extent the attributes of organic structure contribute to the creation and sharing of knowledge and to show that an organizational culture which supports knowledge stimulates the processes of knowledge creation and sharing.

Design/methodology/approach

The data for the empirical study was obtained through a survey of 150 respondents, employed in 30 companies from several industries, in the Republic of Serbia. The questionnaire was adapted to the needs of the study and was developed based on the theoretical knowledge and findings of several previous studies on processes of knowledge creation and knowledge sharing. A regression method was used to test all hypotheses.

Findings

The results show that both the organic structure and the organizational culture that support knowledge have positive effects on knowledge creation, while knowledge sharing is positively influenced only by the knowledge supporting culture of an organization.

Originality/value

This study contributes to organization studies and knowledge management theory because of the holistic approach taken with regards to the issue involved and the fact that it takes into account a large number of the significant characteristics of organizational structure and culture that are relevant to knowledge management processes. The findings could prove useful to managers when structuring an organization and shaping its culture to enhance knowledge management.
Paradoxes and partnerships: a study of knowledge exploration and exploitation in international development programmes
Authors: Lannon John , Walsh John N.
Published: September 2019

Purpose

This paper aims to look at how organisational partnerships balance knowledge exploration and exploitation in contexts that are rife with paradoxes. It draws on paradox theory to examine the partnership’s response to the explore-exploit relationship.

Design/methodology/approach

A multiple interpretive case study was used to examine international partnerships in three African countries. These partnerships were between international (Northern-based) non-governmental organisations and local African non-governmental organisations.

Findings

The research finds that within the partnership, knowledge exploration and exploitation exist as a duality rather than a dualism. This is supported by the acceptance and confrontation of paradoxes of performing and belonging. However, macro-level paradoxes of organising linked to power, culture and epistemologies inhibit further effective confrontation of the explore-exploit paradox.

Practical implications

The findings can help managers working in international development organisations to understand how learning is enabled and constrained in partnership-based programmes.

Originality/value

The study provides a novel contribution to knowledge management by applying the paradox perspective to the explore-exploit relationship. This paper extends previous work by drawing on the levels and repertoires present in the paradox perspective to understand how knowledge exploration and exploitation can be mutually reinforcing and can exist as a duality.
Improving travellers' trust in restaurant review sites
Authors: Anaya-Sánchez Rafael , Molinillo Sebastian , Aguilar-Illescas Rocío , Liébana-Cabanillas Francisco
Published: September 2019

Purpose

This paper aims to focus on understanding how restaurant review sites generate trust among travellers and the effect of trust on the intention to visit and recommend restaurants while travelling.

Design/methodology/approach

The research model was assessed with data from a sample of 439 Spanish tourists using partial least squares structural equation modelling (PLS-SEM).

Findings

Information quality and source credibility are key for generating website trust. Website quality does not influence trust. Website trust is a key variable for explaining both intention to visit and recommend a restaurant, offline and online. Age is a significant moderator.

Research limitations/implications

This study expands the literature by assessing the antecedents and consequences of travellers’ trust in restaurant review sites during their trips.

Practical implications

Strategies are suggested for review sites, restaurants and destination managers.

Originality/value

This research enhances the knowledge of how consumers perceive restaurant review sites, and their behavioural intention while travelling.
The science of complexity in the tourism domain: a perspective article
Authors: Baggio Rodolfo
Published: September 2019

Purpose

This paper aims to examine the complexity science approach to the tourism domain.

Design/methodology/approach

This study is a personal perspective

Findings

The study is an analysis of past and future applications.

Originality/value

Historical considerations