bluuebunny/crossref_metadata_2025 huggingface dataset:
MeshMonk: Open-source large-scale intensive 3D phenotyping
Authors: White Julie D. , Ortega-Castrillón Alejandra , Matthews Harold , Zaidi Arslan A. , Ekrami Omid , Snyders Jonatan , Fan Yi , Penington Tony , Van Dongen Stefan , Shriver Mark D. , Claes Peter
Published: January 2019

In the post-genomics era, an emphasis has been placed on disentangling ‘genotype-phenotype’ connections so that the biological basis of complex phenotypes can be understood. However, our ability to efficiently and comprehensively characterize phenotypes lags behind our ability to characterize genomes. Here, we report a toolbox for fast and reproducible high-throughput dense phenotyping of 3D images. Given a target image, a rigid registration is first used to orient a template to the target surface, then the template is transformed further to fit the specific shape of the target using a non-rigid transformation model. As validation, we used N = 41 3D facial images registered with MeshMonk and manually landmarked at 19 locations. We demonstrate that the MeshMonk registration is accurate, with 0.62 mm as the average root mean squared error between the manual and automatic placements and no variation in landmark position or centroid size significantly attributable to landmarking method used. Though validated using 19 landmarks for comparison with traditional methods, MeshMonk allows for automatic dense phenotyping, thus facilitating more comprehensive investigations of 3D shape variation. This expansion opens up an exciting avenue of study in assessing genomic and phenomic data to better understand the genetic contributions to complex morphological traits.
Serodiagnostic potential of synthetic peptides derived from African swine fever virus putative protein pCP312R
Authors: Ochwo Sylvester , Atuhaire David Kalenzi , Afayoa Mathias , Kisseka Majid , Magambo Phillip Kimuda , Ndekezi Christian , Okuni Julius Boniface , Olaho-Mukani William , Ojok Lonzy
Published: January 2019

African swine fever (ASF) is a hemorrhagic disease of domestic swine, with often high mortality rates registered. To date there is still no vaccine produced against ASF, and disease management in countries including Uganda, where the disease is endemic is dependent on accurate and timely diagnosis programs and quarantine. This study aimed at contributing more knowledge towards ASF diagnosis by investigating the serodiagnostic potential of synthetic peptides of an ASF putative protein pCP312R. Antigenic regions of the pCP312R putative protein were identified using Kolaskar and Tongaonkar antigenicity prediction method and twelve (12) peptides were predicted, out of which four (4) peptides were selected and synthesised. An additional peptide derived from the carboxyl end of the ASFV p54 protein was also synthesised and used as a control. Polyclonal rabbit antibodies raised against each of the five peptides was used in immunohistochemistry, and each demonstrated ability to localize viral antigen in pig tissue albeit with slightly varying intensities, at a dilution of 1:200, with antibodies against peptides cpr1, cpr2, cpr3 and cpr4 all accurately staining infected macrophages. However all the peptides evaluated in this study performed moderately when used in indirect ELISA tests giving the following results; CP1; diagnostic sensitivity of 55% (95% CI, 0.3421-0.7418) and specificity of 96% (95% CI, 0.8046-0.9929), CP2; diagnostic sensitivity of 100% (95% CI, 0.8389-1) and specificity of 52% (95% CI, 0.335-0.6997), CP3; diagnostic sensitivity of 95% (95% CI, 76.39-99.11) and specificity of 88% (95% CI, 70.04-95.83), CP4; diagnostic sensitivity of 90% (95% CI: 0.699-0.9721) and specificity of 76% (95% CI: 0.5657-0.885) and p54; diagnostic sensitivity of 100% (95% CI, 0.8389-1) and specificity of 56% (95% CI, 0.3707-0.7333). This study presents the first time synthetic peptides have been successfully predicted, designed and evaluated for Serodiagnosis of African swine fever in domestic pigs. This study in addition showed that there is potential for use of polyclonal anti-peptide antibodies in the diagnosis of ASF using immunohistochemistry.
Gene Panel Sequencing in a Chinese High-risk Breast Cancer Cohort
Authors: Zhang Xianyu , Wang Xiaohong , Song Bingbing , Shao Kang , Li Guibo , Jian Wenjing , Lin Cong , Wang Min , Ye Xiaofei , Xie Jingjing , Xia Bingshu , Xu Shouping , Cao Boyang , Xiao Liyun , Zhang Zhao , Liu Meng , Fang Enhao , Jin Haoxuan , Wei Xiaofeng , Dean Michael , Wang Jian , Yang Huanming , Wang Xianming , Zhu Shida , Hou Yong , Pang Da
Published: January 2019

Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.

A total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.
Glycosylphosphatidylinositol Biosynthesis and Remodeling are Required for Neural Crest Cell, Cardiac and Neural Development
Authors: Lukacs Marshall , Roberts Tia , Chatuverdi Praneet , Stottmann Rolf W.
Published: January 2019

The glycosylphosphatidylinositol (GPI) anchor attaches nearly 150 proteins to the cell surface. Patients with pathogenic variants in GPI biosynthetic pathway genes display an array of phenotypes including seizures, developmental delay, dysmorphic facial features and cleft palate. There is virtually no mechanism to explain these phenotypes. we identified a novel mouse mutant (cleft lip/palate, edema and exencephaly; Clpex) with a hypomorphic mutation inPost-Glycophosphatidylinositol Attachment to Proteins-2 (Pgap2). Pgap2is one of the final proteins in the GPI biosynthesis pathway and is required for anchor maturation. We found theClpexmutation results in a global decrease in surface GPI expression. Surprisingly,Pgap2showed tissue specific expression with enrichment in the affected tissues of theClpexmutant. We found the phenotype inClpexmutants is due to apoptosis of neural crest cells (NCCs) and the cranial neuroepithelium, as is observed in the GPI anchoredFolate Receptor 1-/-mouse. We showed folinic acid supplementationin uterocan rescue the cleft lip phenotype inClpex. Finally, we generated a novel mouse model of NCC-specific total GPI deficiency in theWnt1-Crelineage. These mutants developed median cleft lip and palate demonstrating a cell autonomous role for GPI biosynthesis in NCC development.
On translational control by ribosome speed inS. cerevisiae
Authors: Kazana Eleanna , von der Haar Tobias
Published: January 2019

In addition to the widespread and well documented control of protein synthesis by translation initiation, recent evidence suggests that translation elongation can also control protein synthesis rates. One of the proposed mechanisms leading to elongation control is the interference of slow ribosome movement around the start codon with efficient translation initiation. Here we estimate the frequency with which this mode of control occurs in baker’s yeast growing in rich medium. Genome-wide data reveal that transcripts from around 20% of yeast genes show evidence of queueing ribosomes, which may be indicative of translation elongation control. Moreover, this subset of transcripts is sensitive to distinct regulatory signals compared to initiation-controlled mRNAs, and such distinct regulation occurs for example during the response to osmotic stress.

Note

the previous version 2 of this preprint contained a Decision-Tree based analysis where we attempted to relate mRNA features to the presence or absence of queueing ribosome peaks. Since releasing that version, we performed additional controls for this analysis which strongly sugest that its results are random and should be ignored. Specifically, both the overall predictability and the importance of individual features is very similar for a real dataset where genes are labelled as containing a second SSU peak or not, and for a simulated control dataset containing an equal proportion of randomly labelled genes. We have removed this figure from the current version. The analysis together with the additional control remains accessible on the accompanying Github repository (github.com/tobiasvonderhaar/ribosomespeedcontrol) in the file “Figure 3 Obsolete (Classification).ipynb”.
Altered Motor Development Following Late Gestational Alcohol and Cannabinoid Exposure in Rats
Authors: Breit Kristen R. , Zamudio Brandonn , Thomas Jennifer D.
Published: January 2019

Cannabis is the most commonly used illicit drug among pregnant women, and rates are likely to increase given recent legalization. In addition, half of pregnant women who report consuming cannabis also report drinking alcohol. However, little is known about the consequences of prenatal cannabis alone or combination with alcohol, particularly with cannabis products that are continually increasing in potency of the primary psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (THC). The current study investigated the effects of early exposure to cannabinoids during the brain growth spurt on early physical and motor development alone (Experiment 1) or in combination with alcohol (Experiment 2). In Experiment 1, Sprague-Dawley rat pups were exposed to a cannabinoid receptor agonist (CP-55,940 [CP]; 0.1, 0.25, 0.4 mg/kg/day), the drug vehicle, or a saline control from postnatal days (PD) 4-9. In Experiment 2, rat pups were exposed to CP (0.4 mg/kg/day) or the vehicle, and were additionally intubated with alcohol (11.9% v/v; 5.25 g/kg/day) or received a sham intubation. Subjects in both experiments were tested on a motor development task (PD 12-20) and a motor coordination task during adolescence (PD 30-32). Both developmental cannabinoid and alcohol exposure separately decreased body growth throughout development, and combined exposure exacerbated these effects, although only alcohol exposure induced long-term body weight reductions. Developmental cannabinoid exposure advanced early motor development, whereas alcohol exposure delayed development, and subjects given combined exposure did not differ from controls on some measures. Alcohol exposure impaired motor coordination later in life. In contrast, cannabinoid exposure, by itself did not significantly affect long-term motor coordination, but did exacerbate alcohol-related impairments in motor coordination among females. These results suggest that cannabinoid exposure may not only alter development by itself, but may exacerbate alcohol’s teratogenic effects in specific behavioral domains. These findings have important implications not only for individuals affected by prenatal exposure, but also for establishing public policy for women regarding cannabis use during pregnancy.
Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1 but is unnecessary during S phase for establishing cohesion
Authors: Srinivasan Madhusudhan , Petela Naomi J. , Scheinost Johanna C. , Collier James , Voulgaris Menelaos , Brunet-Roig Maurici , Beckouët Frederic , Hu Bin , Nasmyth Kim A.
Published: January 2019

Cohesin’s association with chromosomes is determined by loading dependent on the Scc2/4 complex and release due to Wapl. We show here that Scc2/4 is not merely a loading complex and that it actively maintains cohesin on chromosomes during G1. It does so by blocking a Wapl-independent release reaction that requires opening the cohesin ring at its Smc3/Scc1 interface as well as the D loop of Smc1’s ATPase. The Wapl-independent release mechanism is switched off as cells activate Cdk1 and enter G2/M and cannot be turned back on without cohesin’s dissociation from chromosomes. The latter phenomenon enabled us to show that cohesin that has already captured DNA in a Scc2-dependent manner before replication no longer requires Scc2 to capture sister DNAs during S phase.
Cooperation and Stability for Complex Systems in Resource-Limited Environments
Authors: Butler Stacey , O’Dwyer James
Published: January 2019

Resource-limited complex systems are ubiquitous in the natural world, as is the potential for instability in such systems. Classic models of interacting species have provided a basis for our understanding of stability in these systems, and suggest that stable coexistence requires weak, rare, and asymmetric interactions. But missing from these models is an explicit understanding of how resource exchange and resource limitation can drive or prevent instability. Here we show that systems based on general rules for the consumption and exchange of resources are guaranteed to be stable when exchange of resources is reciprocated by each pair of partners. These cooperative, mutualistic interactions can be arbitrarily strong and yet not disrupt stability. More general modes of exchange will lead to instability when supply rates are low, but when resource supply from outside the system is sufficiently high, arbitrary exchange is consistent with a stable equilibrium.
Modulation and recruitment of TRF2 at viral telomeres during human herpesvirus 6A/B infection
Authors: Gilbert-Girard Shella , Gravel Annie , Collin Vanessa , Wight Darren J. , Kaufer Benedikt B. , Lazzerini-Denchi Eros , Flamand Louis
Published: January 2019

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of host chromosomes. The HHV-6A/B genomes contain telomeric repeats essential for integration. Whether HHV-6A/B infections impact telomere homeostasis remains to be studied. We report that during infection, a massive increase in telomeric signals is observed. Such telomeric signals are detected in viral replication compartments (VRC) that colocalize with the viral IE2 and P41 proteins. Infection with HHV-6A mutants lacking telomeric repeats did not reproduce this phenotype. HHV-6A/B infections lead to increased expression of three shelterin genes, TRF1, TRF2 and TPP1. TRF2 was recruited to VRC and binding to the HHV-6A/B telomeric repeats demonstrated by chromatin immunoprecipitation and ELISA. Lastly, the HHV-6A IE2 protein colocalized with shelterin proteins at telomeres during infection. In summary, HHV-6A/B infections results in an excess of telomeric repeats that stimulates the expression of shelterin genes. TRF2 binds to viral telomeres during infection and localizes with HHV-6A IE2 protein. Our results highlight a potential role for shelterin complex proteins and IE2 during infection and possibly during integration of HHV-6A/B into host chromosomes.
Validating indicators of CNS disorders in a swine model of neurological disease
Authors: Swier Vicki J. , White Katherine A. , Meyerholz David K. , Chefdeville Aude , Khanna Rajesh , Sieren Jessica C. , Quelle Dawn E. , Weimer Jill M.
Published: January 2019

Genetically modified porcine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given their limited history, there remains a great need for proven reagents in swine tissue. To provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers. To validate these tools in a relevant model, we utilized a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is a tumor predisposition disorder, presenting with different type of tumors. Additionally, neurological associated symptomologies may include chronic pain, cognitive impairment, and behavioral abnormalities, making this miniswine model an ideal candidate for validating CNS-relevant antibodies. We validate antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4, Olig2, and myelin PLP), and neuron differentiation and neurotransmission (doublecortin, GAD67, and tyrosine hydroxylase) by examining cellular localization and brain region specificity. Additionally, we confirm the utility of anti-GFAP, anti-Iba1, and anti-MBP antibodies, previously validated in swine, by testing their immunoreactivity across multiple brain regions in mutant NF1 samples. These validated immunostaining protocols for CNS markers provide a useful resource, furthering the utility of the genetically modified miniswine for translational and clinical applications.
Systematic analysis of dark and camouflaged genes: disease-relevant genes hiding in plain sight
Authors: Ebbert Mark T. W. , Jensen Tanner D. , Jansen-West Karen , Sens Jonathon P. , Reddy Joseph S. , Ridge Perry G. , Kauwe John S. K. , Belzil Veronique , Pregent Luc , Carrasquillo Minerva M. , Keene Dirk , Larson Eric , Crane Paul , Asmann Yan W. , Ertekin-Taner Nilufer , Younkin Steven G. , Ross Owen A. , Rademakers Rosa , Petrucelli Leonard , Fryer John D.
Published: January 2019

Background

The human genome contains ‘dark’ gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations within these gene regions that may be relevant to human disease. Here, we identify regions that are ‘dark by depth’ (few mappable reads) and others that are ‘camouflaged’ (ambiguous alignment), and we assess how well long-read technologies resolve these regions. We further present an algorithm to resolve most camouflaged regions (including in short-read data) and apply it to the Alzheimer’s Disease Sequencing Project (ADSP; 13142 samples), as a proof of principle.

Results

Based on standard whole-genome lllumina sequencing data, we identified 37873 dark regions in 5857 gene bodies (3635 protein-coding) from pathways important to human health, development, and reproduction. Of the 5857 gene bodies, 494 (8.4%) were 100% dark (142 protein-coding) and 2046 (34.9%) were ≥5% dark (628 protein-coding). Exactly 2757 dark regions were in protein-coding exons (CDS) across 744 genes. Long-read sequencing technologies from 10x Genomics, PacBio, and Oxford Nanopore Technologies reduced dark CDS regions to approximately 45.1%, 33.3%, and 18.2% respectively. Applying our algorithm to the ADSP, we rescued 4622 exonic variants from 501 camouflaged genes, including a rare, ten-nucleotide frameshift deletion in CR1, a top Alzheimer’s disease gene, found in only five ADSP cases and zero controls.

Conclusions

While we could not formally assess the CR1 frameshift mutation in Alzheimer’s disease (insufficient sample-size), we believe it merits investigating in a larger cohort. There remain thousands of potentially important genomic regions overlooked by short-read sequencing that are largely resolved by long-read technologies.
Dual-site high-density 4Hz transcranial alternating current stimulation applied over auditory and motor cortical speech areas does not influence auditory-motor mapping
Authors: Preisig Basil , Sjerps Matthias J. , Kösem Anne , Riecke Lars
Published: January 2019

Background

Verbal repetition of auditory speech requires the mapping of a sensory acoustic input onto articulatory motor plans (auditory-motor mapping). Recent evidence indicates that auditory-motor mapping could rely on low frequency neural synchronization (i.e., theta oscillatory phase coupling) between sensory and motor speech areas.

Objective

In the present study, we apply dual-site high-density (HD) Transcranial Alternating Current Stimulation (TACS) above the auditory and motor cortex to induce, or disrupt, theta phase coupling between the two areas. We predicted that functionally coupling the two areas would strengthen auditory-motor mapping, compared with functionally decoupling them. We assessed the strength of auditory-motor mapping using a verbal repetition task.

Results

We found no significant effect of TACS-induced theta phase coupling on auditory-motor mapping as indexed by verbal repetition performance.

Conclusion

Auditory-motor mapping may rely on a different mechanism than we hypothesized, for example, oscillatory phase-coupling outside the theta range. Alternatively, modulation of interregional theta-phase coupling may require more effective stimulation protocols, for example, TACS at higher intensities.
An incremental training method with automated, extendible T-maze for training spatial behavioral tasks in rodents
Authors: Holleman Esther , Maka Jan , Schröder Tim , Battaglia Francesco
Published: January 2019

We present a training procedure and a T-maze equipped with sensors and automated feeders for training spatial behavioral tasks in rodents. The maze can be transformed from an enclosed box to a maze of variable dimensions. The modularity of the protocol and setup makes it highly flexible and suitable for training a wide variety of spatial tasks, and facilitates incremental training stages of increasing maze size for more efficient learning. The apparatus, in its software and hardware, is able to adapt to animal performance, adjusting task challenges and difficulty.

Two different methods of automatic behavioral scoring are evaluated against manual methods. Sensors embedded in the maze provide information regarding the order of reward locations visited and the time between the activation of the cue via the nose-poke and the activation of the reward location sensors. The distributions of these reaction times differ between correct and incorrect trials, providing an index of behavior and motivation. The automated maze system allows the trainer to operate and monitor the task away from the experimental set-up, minimizing human interference and improving the reproducibility of the experiment. We show that our method succeeds in training a binary forced-choice task in rats.
Sexual selection and the evolution of male and female cognition: a test using experimental evolution in seed beetles
Authors: Baur Julian , d’Amour Jean , Berger David
Published: January 2019

“The mating mind hypothesis”, originally aimed at explaining human cognition, holds that the socio-sexual environment shapes cognitive abilities among animals. Similarly, general sexual selection theory predicts that mate competition should benefit individuals carrying “good genes” with beneficial pleiotropic effects on general cognitive ability. However, few experimental studies have evaluated these related hypotheses due to difficulties of performing direct tests in most taxa. Here we harnessed the empirical potential of the seed beetle study system to investigate the role of sexual selection and mating system in the evolution of cognition. We evolved replicate lines of beetle under enforced monogamy (eliminating sexual selection) or polygamy for 35 generations and then challenged them to locate and discriminate among mating partners (male assays) or host seeds (female assays). To assess learning, the same beetles performed the task in three consecutive rounds. All lines learned the task, improving both within and between trails. Moreover, polygamous males outperformed monogamous males. However, there were no differences in the rate of learning between males of the two regimes, and polygamous females showed no improvement in host search, and even signs of reduced learning. Hence, while sexual selection was a potent factor that increased cognitive performance in mate search, it did not lead to the general increase in cognitive abilities expected under the “mating mind” hypothesis or general “good genes” theory. Our results highlight sexually antagonistic (balancing) selection as a potential force maintaining genetic variation in cognitive traits.
Tau-mediated Disruption of the Spliceosome Triggers Cryptic RNA-splicing and Neurodegeneration in Alzheimer’s Disease
Authors: Hsieh Yi-Chen , Guo Caiwei , Yalamanchili Hari K. , Abreha Measho , Al-Ouran Rami , Li Yarong , Dammer Eric B. , Lah James J. , Levey Allan I. , Bennett David A. , De Jager Philip L. , Seyfried Nicholas T. , Liu Zhandong , Shulman Joshua M.
Published: January 2019

In Alzheimer’s disease (AD), spliceosomal proteins with critical roles in RNA processing aberrantly aggregate and mislocalize to Tau neurofibrillary tangles. We test the hypothesis that Tau-spliceosome interactions disrupt pre-mRNA splicing in AD. In human postmortem brain with AD pathology, Tau coimmunoprecipitates with spliceosomal core components. InDrosophilamodels, pan-neuronal Tau expression triggers reductions in core and U1-specific spliceosomal proteins, and genetic disruption of these factors, including SmB, U1-70K, and U1A, enhances Tau-mediated neurodegeneration. We further show that loss-of-function inSmB, encoding a core spliceosomal protein, causes decreased survival, progressive locomotor impairment, and neuronal loss, independent of Tau toxicity. Lastly, RNA-sequencing reveals a similar profile of mRNA splicing errors inSmBmutant and Tau transgenic flies, including intron retention and non-annotated cryptic splice junctions. In human brains, we confirm cryptic splicing errors in association with neurofibrillary tangle pathologic burden. Our results implicate spliceosome disruption and perturbations of the neuronal transcriptome in Tau-mediated neurodegeneration in AD.
Attention hinges on tuned normalization strength within human visual cortex
Authors: Bloem Ilona M. , Ling Sam
Published: January 2019

Although attention is known to increase the gain of visuocortical responses, its underlying neural computations remain unclear. Here, we used fMRI to test the hypothesis that a neural population’s ability to be modulated by attention is dependent on divisive normalization. To do so, we leveraged the feature-tuned properties of normalization and found that visuocortical responses to stimuli sharing features normalized each other more strongly. Comparing these normalization measures to measures of attentional modulation, we discovered that subpopulations that exhibited stronger normalization also exhibited larger attentional benefits. In a converging experiment, we demonstrated that attentional benefits were greatest when a subpopulation was forced into a state of stronger normalization. We propose a tuned normalization model of attention that parsimoniously accounts for many properties of our results, suggesting that the degree to which a subpopulation exhibits normalization plays a role in dictating its potential for attentional benefits.
Perception of naturally dead conspecifics impairs health and longevity through serotonin signaling in Drosophila
Authors: Chakraborty Tuhin S. , Gendron Christi M. , Lyu Yang , Munneke Allyson S. , DeMarco Madeline N. , Hoisington Zachary W. , Pletcher Scott D.
Published: January 2019

Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. In humans, psychological trauma is often associated with the recognition of dead individuals, with chronic exposure leading to persistent mental health issues including depression and post-traumatic stress disorder. The mechanisms that link mental and physical health, and the degree to which these are shared across species, remain largely unknown. Here we show that the vinegar fly, Drosophila melanogaster, has the capability to perceive dead conspecifics in its environment and that this perceptive experience induces both short- and long-term effects on health and longevity. Death perception is mediated by visual and olfactory cues, and remarkably, its effects on aging are eliminated by targeted attenuation of serotonin signaling. Our results suggest a complex perceptive ability in Drosophila that reveals deeply conserved mechanistic links between psychological state and aging, the roots of which might be unearthed using invertebrate model systems.
Calcitriol and Non-Calcemic Vitamin D Analogue, 22-Oxacalcitriol, Attenuate Developmental and Pathological Ocular Angiogenesis Ex Vivo and In Vivo
Authors: Merrigan SL , Park B , Ali Z , Jensen LD , Corson TW , Kennedy BN
Published: January 2019

Aberrant ocular blood vessel growth can underpin vision loss in leading causes of blindness, including neovascular age-related macular degeneration, retinopathy of prematurity and proliferative diabetic retinopathy. Current pharmacological interventions require repeated invasive administrations, lack efficacy in some patients and are associated with poor patient compliance and tachyphylaxis. Small molecule vitamin D has de novo pro-differentiative, anti-proliferative, immunomodulatory, pro-apoptotic and anti-angiogenic properties. Here, our aim was to validate the anti-angiogenic activity of the biologically active form of vitamin D, calcitriol, and a selected vitamin D analogue, 22-oxacalcitriol, across a range of ocular angiogenesis models.

First, we validated the anti-angiogenic activity of calcitriol, showing calcitriol to significantly inhibit choroidal sprouting in an ex vivo mouse choroidal fragment sprouting assay. Viability studies in human RPE cell line, ARPE-19, suggested non-calcemic vitamin D analogues have the least off-target anti-proliferative activity compared to calcitriol and additional analogues. Thereafter, the ocular anti-angiogenic activity of non-calcemic vitamin D analogue, 22-oxacalcitriol, was demonstrated in the ex vivo mouse choroidal fragment sprouting assay. In zebrafish larvae, 22-oxacalcitriol was anti-angiogenic, inducing a dose-dependent reduction in choriocapillary angiogenesis. Inhibition of mouse retinal vasculature development was not induced by systemically delivered calcitriol. However, both calcitriol and 22-oxacalcitriol administered intraperitoneally significantly attenuate choroidal neovascularisation lesion volume in the laser-induced CNV mouse model. 22-oxacalcitriol presented with a more favourable safety profile than calcitriol.

In summary, calcitriol and 22-oxacalcitriol attenuate ex vivo and in vivo choroidal vasculature angiogenesis. Vitamin D has potential as a preventative or interventional treatment for ophthalmic neovascular indications.
Single-molecule live-cell imaging visualizes parallel pathways of prokaryotic nucleotide excision repair
Authors: Ghodke Harshad , Ho Han Ngoc , van Oijen Antoine M
Published: January 2019

In the model organismEscherichia coli, helix distorting lesions are recognized by the UvrAB damage surveillance complex in the global genomic nucleotide excision repair pathway (GGR). Alternately, during transcription-coupled repair (TCR), UvrA is recruited to Mfd at sites of RNA polymerases stalled or paused by lesions. Ultimately, damage recognition is mediated by UvrA, culminating in the loading of the damage verification enzyme UvrB. We set out to characterize the differences in the kinetics of interactions of UvrA with Mfd and UvrB. We followed functional, fluorescently tagged UvrA molecules in live cells and measured their residence times in TCR-deficient or wild-type cells. We demonstrate that the lifetimes of UvrA in Mfd-dependent or Mfd-independent interactions in the absence of exogenous DNA damage are comparable in live cells, and are governed by UvrB. Upon UV irradiation, we found that the lifetimes of UvrA strongly depended on, and matched those of Mfd. Here, we illustrate a non-perturbative, imaging-based approach to quantify the kinetic signatures of damage recognition enzymes participating in multiple pathways in cells.
The influence of image masking on object representations during rapid serial visual presentation
Authors: Robinson Amanda K. , Grootswagers Tijl , Carlson Thomas A.
Published: January 2019

Rapid image presentations combined with time-resolved multivariate analysis methods of EEG or MEG (rapid-MVPA) offer unique potential in assessing the temporal limitations of the human visual system. Recent work has shown that multiple visual objects presented sequentially can be simultaneously decoded from M/EEG recordings. Interestingly, object representations reached higher stages of processing for slower image presentation rates compared to fast rates. This fast rate attenuation is probably caused by forward and backward masking from the other images in the stream. Two factors that are likely to influence masking during rapid streams are stimulus duration and stimulus onset asynchrony (SOA). Here, we disentangle these effects by studying the emerging neural representation of visual objects using rapid-MVPA while independently manipulating stimulus duration and SOA. Our results show that longer SOAs enhance the decodability of neural representations, regardless of stimulus presentation duration, suggesting that subsequent images act as effective backward masks. In contrast, image duration does not appear to have a graded influence on object representations. Interestingly, however, decodability was improved when there was a gap between subsequent images, indicating that an abrupt onset or offset of an image enhances its representation. Our study yields insight into the dynamics of object processing in rapid streams, paving the way for future work using this promising approach.
Partial ligand-receptor engagement yields functional bias at the human complement receptor, C5aR1
Authors: Pandey Shubhi , Li Xaria X. , Srivastava Ashish , Baidya Mithu , Kumari Punita , Dwivedi Hemlata , Ghosh Eshan , Woodruff Trent M. , Shukla Arun K.
Published: January 2019

The human complement component, C5a, binds two different seven transmembrane receptors termed as C5aR1 and C5aR2. C5aR1 is a prototypical G protein-coupled receptor that couples to Gαi sub-family of heterotrimeric G proteins and β-arrestins (βarr) following C5a stimulation. Peptide fragments derived from the carboxyl-terminus of C5a can still interact with the receptor, albeit with lower affinity, and can act as agonists or antagonists. However, whether such fragments might display ligand bias at C5aR1 remains unexplored. Here, we compare C5a and a modified C-terminal fragment of C5a, C5apep, in terms of G protein coupling, βarr recruitment, endocytosis and ERK1/2 MAP kinase activation at the human C5aR1. We discover that C5apepacts as a full-agonist for G protein coupling, while only displaying partial agonism for βarr recruitment. We also observe that whilst C5apepis significantly less efficient in inducing C5aR1 endocytosis compared to C5a, it exhibits robust activation of ERK1/2 phosphorylation at levels similar to C5a. Interestingly, C5apepdisplays full-agonist efficacy with respect to inhibiting LPS induced IL-6 secretion in human macrophages, but its ability to induce human neutrophil migration is substantially lower compared to C5a. Taken together, our findings reveal ligand-bias at C5aR1, not only with respect to transducer-coupling and receptor trafficking but also in terms of cellular responses. Our findings therefore establish a framework to explore additional levels of biased signaling and biased ligands at C5aR1 with therapeutic potential. More generally, our findings may be extended to discover biased ligands for the broad sub-family of chemokine GPCRs which also interact with chemokine ligands through a biphasic mechanism.
Sample delivery for serial crystallography at free-electron lasers and synchrotrons
Authors: Grünbein Marie Luise , Nass Kovacs Gabriela
Published: January 2019

The high peak brilliance and femtosecond pulse duration of X-ray free-electron lasers (XFELs) provide new scientific opportunities for experiments in physics, chemistry and biology. In structural biology, one of the major applications is serial femtosecond crystallography. The intense XFEL pulse results in the destruction of any exposed microcrystal, making serial data collection mandatory. This requires a high-throughput serial approach to sample delivery. To this end, a number of such sample-delivery techniques have been developed, some of which have been ported to synchrotron sources, where they allow convenient low-dose data collection at room temperature. Here, the current sample-delivery techniques used at XFEL and synchrotron sources are reviewed, with an emphasis on liquid injection and high-viscosity extrusion, including their application for time-resolved experiments. The challenges associated with sample delivery at megahertz repetition-rate XFELs are also outlined.
Ethyl 4-chloro-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxylate
Authors: Rodriguez-Vega Gibran , Aguirre Gerardo , Chávez Daniel
Published: January 2019

In the title compound, C12H14ClNO3, the aliphatic ring of the hexahydroquinoline system adopts a half-chair conformation while the ethyl carboxylate substituent is inclined to the hexahydroquinoline ring system by 85.1 (2)°. In the crystal, a pair of N–H...O hydrogen bonds form an inversion dimer. The structure is further stabilized by C—H...O and C—H...Cl hydrogen bonds, forming a three-dimensional network.
Identification of a degradation of aerodynamic characteristics of a paraglider due to its flexibility from flight test
Authors: Kulhánek Robert
Published: January 2019

Purpose

Aerodynamics of paragliders is very complicated aeroelastic phenomena. The purpose of this work is to quantify the amount of aerodynamic drag related to the flexible nature of a paraglider wing.

Design/methodology/approach

The laboratory testing on scaled models can be very difficult because of problems in the elastic similitude of such a structure. Testing of full-scale models in a large facility with a large full-scale test section is very expensive. The degradation of aerodynamic characteristics is evaluated from flight tests of the paraglider speed polar. All aspects of the identification such as pilot and suspension lines drag and aerodynamics of spanwise chambered wings are discussed. The drag of a pilot in a harness was estimated by means of wind tunnel testing, computational fluid dynamics (CFD) solver was used to estimating smooth wing lift and drag characteristics.

Findings

The drag related to the flexible nature of the modern paraglider wing is within the range of 4-30 per cent of the total aerodynamic drag depending on the flight speed. From the results, it is evident that considering only the cell opening effect is sufficient at a low-speed flight. The stagnation point moves forwards towards the nose during the high speed flight. This causes more pronounced deformation of the leading edge and thus increased drag.

Practical implications

This paper deals with a detailed analysis of specific paraglider wing. Although the results are limited to the specific geometry, the findings help in the better understanding of the paraglider aerodynamics generally.

Originality/value

The data obtained in this paper are not affected by any scaling problems. There are only few experimental results in the field of paragliders on scaled models. Those results were made on simplified models at very low Reynolds number. The aerodynamic drag characteristics of the pilot in the harness with variable angles of incidence and Reynolds numbers have not yet been published.
Examining inter-organizational roles in Philippine post-disaster MHPSS delivery
Authors: Teng-Calleja Mendiola , Canoy Nico A. , Alianan Jr Arsenio Sze
Published: January 2019

Purpose

The purpose of this paper is to provide empirical grounding on the management of inter-organizational roles in the delivery of mental health and psychosocial services (MHPSS) through the experiences of three disaster-stricken localities. It describes challenges in the provision of MHPSS, and offered implications to post-disaster management practices in a developing country context.

Design/methodology/approach

In total, 28 individual interviews and four focus group discussions were conducted among key informants in the three localities that experienced destructive typhoons. Thematic analysis, following the procedures of Braun and Clarke (2006), was used to examine patterns in the data.

Findings

The results surfaced disparate perspectives in the role and scope of MHPSS, lack of clarity in inter-organizational roles and service standards as well as contextual challenges in post-disaster MHPSS delivery. Specific issues pertaining to the absence of inter-organizational role clarity in MHPSS post-disaster response include varying perspectives on the role of local government employees as survivors and MHPSS providers; local government as facilitator of MHPSS efforts; the Department of Health as the lead agency for MHPSS; and standards on who can deliver MHPSS and train MHPSS responders.

Research limitations/implications

The study is based on community accounts of MHPSS delivery during disasters. Future studies may focus on capturing longitudinal data that can further refine and enable the institutionalization of effective and sustainable MHPSS response.

Practical implications

The results suggest the importance of improving systems and structures for MHPSS response to enable effective multi-organization support in disaster scenarios. Findings also highlight the need to have guidelines anchored on international standards of MHPSS delivery that will be used by the designated agency leading and advocating MHPSS efforts. This lead agency may be tasked to operationally define MHPSS in a disaster context, develop guideposts and standards in MHPSS delivery as well as clarify roles and accountabilities of different organizations.

Originality/value

Existing literature often relied on the analysis of secondary evidence such as expert-driven state or national guidelines. This study provided rich empirical data from key organizational actors involved in MHPSS provision in disaster-stricken communities.
From rumor to release
Authors: Thompson Scott A. , Loveland James M. , Castro Iana A.
Published: January 2019

Purpose

This paper aims to investigate the impact of product release on word of mouth (WOM) behavior within and across rival online brand communities for technology products and evaluate competing predictions made by social identity theory and the group problem solving perspective of rumors.

Design/methodology/approach

In Study 1, 72,749 messages posted by 5,777 users over a 13-month period on two rival online brand forums were content analyzed using linguistic inquiry and word count, a linguistic content analysis program. In Study 2, two experiments were conducted to verify the theoretical explanation offered.

Findings

Marked differences were found as WOM transitioned from pre-release rumor to post-release facts. Prior to release, brand loyalists show an increased willingness to spread positive WOM about rival brands’ products. However, this willingness dissipated upon product release. This is in noted contrast to predictions made for experience goods.

Research limitations/implications

This study examines the uncertainty generated by a rival brand’s upcoming new product within a brand community. While centered on a technologically oriented consumer group, this study addresses a longstanding theoretical conundrum and provides interesting areas for future research.

Practical implications

Surprisingly, it is the most active and ostensibly loyal brand supporters who spread pre-release rumors about rival brands. Managers should not assume that “loyalists” will not seriously discuss the potential offerings of rival brands. Product rumors thus present rival marketers with a unique “move it or lose it” opportunity to spread positive buzz among rival brand loyalists. However, this window of opportunity closes rapidly upon product release.

Originality/value

This is the first paper to examine the nature of new product rumors at this scale, including both pre- and post-release WOM.
Psychometric evaluation of the Serbian adaptation of the individual entrepreneurial orientation scale
Authors: Popov Boris , Varga Suzana , Jelić Dragana , Dinić Bojana
Published: January 2019

Purpose

Entrepreneurial orientation (EO) at the organizational level refers to the process which includes methods, practices and decision-making styles which enhance the company’s approaches to business. At the individual level, EO is assessed using the individual entrepreneurial orientation (IEO: Bolton and Lane, 2012) scale, comprising three dimensions: risk-taking, innovativeness and proactiveness. The purpose of this paper is to evaluate and further validate the Serbian adaptation of the IEO scale among students.

Design/methodology/approach

Two independent studies were conducted on total of 685 students from Serbia. In Study 1, participants completed the IEO scale, proactive personality scales, reinforcement sensitivity questionnaire and academic performance questionnaire. In Study 2, participants completed the IEO scale, proactive personality scales, HEXACO-60 and risky-choice decision tasks.

Findings

Results supported the three-factor structure and satisfactory reliability of the IEO scale and its subscales. Omitting one item from the innovativeness scale led to better model fit, thus resulting in a nine-item solution. Convergent validity correlations were confirmed, showing that each IEO subscale obtained the expected correlations with similar constructs.

Research limitations/implications

A potential problem with divergent validity is discussed from the aspect of the adequacy of the constructs chosen for its testing. Overall findings indicate that the Serbian adaptation of the IEO scale is a brief instrument with adequate psychometric properties, which makes it suitable for both research and practical purposes. The limitations of the study and the instrument are also highlighted and discussed.

Originality/value

The study contributes to better understanding of the nature of EO and helps its accurate assessment.
Topic features for machine learning-based sentiment analysis in Indonesian tweets
Authors: Murfi Hendri , Siagian Furida Lusi , Satria Yudi
Published: January 2019

Purpose

The purpose of this paper is to analyze topics as alternative features for sentiment analysis in Indonesian tweets.

Design/methodology/approach

Given Indonesian tweets, the processes of sentiment analysis start by extracting features from the tweets. The features are words or topics. The authors use non-negative matrix factorization to extract the topics and apply a support vector machine to classify the tweets into its sentiment class.

Findings

The authors analyze the accuracy using the two-class and three-class sentiment analysis data sets. Both data sets are about sentiments of candidates for Indonesian presidential election. The experiments show that the standard word features give better accuracies than the topics features for the two-class sentiment analysis. Moreover, the topic features can slightly improve the accuracy of the standard word features. The topic features can also improve the accuracy of the standard word features for the three-class sentiment analysis.

Originality/value

The standard textual data representation for sentiment analysis using machine learning is bag of word and its extensions mainly created by natural language processing. This paper applies topics as novel features for the machine learning-based sentiment analysis in Indonesian tweets.