bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Volumetric Assessment of Hepatocellular Carcinoma Response to Sorafenib: A Pilot Study
Authors: Fuentes David , Ahmed Kareem , Lin Jonathan S. , Abdel-Wahab Reham , Kaseb Ahmed O. , Hassan Manal , Szklaruk Janio , Morshid Ali , Hazle John D. , Qayyum Aliya , Elsayes Khaled M.
Published: May 2019

Purpose

This pilot study evaluates the feasibility of automated volumetric quantification of hepatocellular carcinoma (HCC) as an imaging biomarker to assess treatment response for sorafenib.

Methods

In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, a training database of manually labeled background liver, enhancing and nonenhancing tumor tissue was established using pretherapy and first posttherapy multiphasic computed tomography images from a registry of 13 HCC patients. For each patient, Hounsfield density and geometry-based feature images were generated from registered multiphasic computed tomography data sets and used as the input for a random forest–based classifier of enhancing and nonenhancing tumor tissue. Leave-one-out cross-validation of the dice similarity measure was applied to quantify the classifier accuracy. A Cox regression model was used to confirm volume changes as predictors of time to progression (TTP) of target lesions for both manual and automatic methods.

Results

When compared with manual labels, an overall classification accuracy of dice similarity coefficient of 0.71 for pretherapy and 0.66 posttherapy enhancing tumor labels and 0.45 for pretherapy and 0.59 for posttherapy nonenhancing tumor labels was observed. Automated methods for quantifying volumetric changes in the enhancing lesion agreed with manual methods and were observed as a significant predictor of TTP.

Conclusions

Automated volumetric analysis was determined to be feasible for monitoring HCC response to treatment. The information extracted using automated volumetrics is likely to reproduce labor-intensive manual data and provide a good predictor for TTP. Further work will extend these studies to additional treatment modalities and larger patient populations.
Update on PET imaging biomarkers in the diagnosis of neuropsychiatric disorders
Authors: Hellwig Sabine , Domschke Katharina
Published: May 2019

Purpose of review

To give an update on recent imaging studies probing positron emission tomography (PET) as a tool for improving biomarker-guided diagnosis of neuropsychiatric disorders.

Recent findings

Several studies confirmed the value of imaging of regional neuronal activity and imaging of dopaminergic, serotonergic, and other neuroreceptor function in the diagnostic process of neuropsychiatric disorders, particularly schizophrenia, depression/bipolar disorder, substance use disorders, obsessive compulsive disorders (OCD), and attention-deficit/hyperactivity disorder. Additionally, imaging brain microglial activation using translocator protein 18 kDa (TSPO) radiotracer allows for unique in-vivo insights into pathophysiological neuroinflammatory changes underlying schizophrenia, affective disorders, and OCD.

The role of PET imaging in the biomarker-guided diagnostic process of neuropsychiatric disorders has been increasingly acknowledged in recent years. Future prospective studies are needed to define the value of PET imaging for diagnosis, treatment decisions, and prognosis in neuropsychiatric disorders.
The source and engine of coronal mass ejections
Authors: Georgoulis Manolis K. , Nindos Alexander , Zhang Hongqi
Published: May 2019

Coronal mass ejections (CMEs) are large-scale expulsions of coronal plasma and magnetic field propagating through the heliosphere. Because CMEs are observed by white-light coronagraphs which, by design, occult the solar disc, supporting disc observations (e.g. in EUV, soft X-rays, Halpha and radio) must be employed for the study of their source regions and early development phases. We review the key properties of CME sources and highlight a certain causal sequence of effects that may occur whenever a strong (flux-massive and sheared) magnetic polarity inversion line develops in the coronal base of eruptive active regions (ARs). Storing non-potential magnetic energy and helicity in a much more efficient way than ARs lacking strong polarity inversion lines, eruptive regions engage in an irreversible course, making eruptions inevitable and triggered when certain thresholds of free energy and helicity are crossed. This evolution favours the formation of pre-eruption magnetic flux ropes. We describe the steps of this plausible path to sketch a picture of the pre-eruptive phase of CMEs that may apply to most events, particularly the ones populating the high end of the energy/helicity distribution, that also tend to have the strongest space-weather implications.

This article is part of the theme issue ‘Solar eruptions and their space weather impact’.
Predicting the geoeffective properties of coronal mass ejections: current status, open issues and path forward
Authors: Vourlidas A. , Patsourakos S. , Savani N. P.
Published: May 2019

Much progress has been made in the study of coronal mass ejections (CMEs), the main drivers of terrestrial space weather thanks to the deployment of several missions in the last decade. The flow of energy required to power solar eruptions is beginning to be understood. The initiation of CMEs is routinely observed with cadences of tens of seconds with arc-second resolution. Their inner heliospheric evolution can now be imaged and followed routinely. Yet relatively little progress has been made in predicting the geoeffectiveness of a particular CME. Why is that? What are the issues holding back progress in medium-term forecasting of space weather? To answer these questions, we review, here, the measurements, status and open issues on the main CME geoeffective parameters; namely, their entrained magnetic field strength and configuration, their Earth arrival time and speed, and their mass (momentum). We offer strategies for improving the accuracy of the measurements and their forecasting in the near and mid-term future. To spark further discussion, we incorporate our suggestions into a top-level draft action plan that includes suggestions for sensor deployment, technology development and modelling/theory improvements.

This article is part of the theme issue ‘Solar eruptions and their space weather impact’.
Ionospheric response to solar and interplanetary disturbances: a Swarm perspective
Authors: Balasis G. , Papadimitriou C. , Boutsi A. Z.
Published: May 2019

The ionospheric response to solar and interplanetary disturbances has been the subject of intense study for several decades. For 5 years now, the European Space Agency's Swarm fleet of satellites surveys the Earth's topside ionosphere, measuring magnetic and electric fields at low-Earth orbit with unprecedented detail. Herein, we study
in situ
the ionospheric response in terms of the occurrence of plasma instabilities based on 2 years of Swarm observations. Plasma instabilities are an important element of space weather because they include irregularities like the equatorial spread F events, which are responsible for the disruption of radio communications. Moreover, we focus on three out of the four most intense geospace magnetic storms of solar cycle 24 that occurred in 2015, including the St Patrick's Day event, which is the strongest magnetic storm of the present solar cycle. We examine the associated ionospheric response at Swarm altitudes through the estimation of a Swarm Dst-like index. The newly proposed Swarm derived Dst index may be suitable for space weather applications.

This article is part of the theme issue ‘Solar eruptions and their space weather impact’.
The emergence of magnetic flux and its role on the onset of solar dynamic events
Authors: Archontis V. , Syntelis P.
Published: May 2019

A plethora of solar dynamic events, such as the formation of active regions, the emission of jets and the occurrence of eruptions is often associated with the emergence of magnetic flux from the interior of the Sun to the surface and above. Here, we present a short review on the onset, driving and/or triggering of such events by magnetic flux emergence. We briefly describe some key observational examples, theoretical aspects and numerical simulations, towards revealing the mechanisms that govern solar dynamics and activity related to flux emergence. We show that the combination of important physical processes like shearing and reconnection of magnetic fieldlines in emerging flux regions or at their vicinity can power some of the most dynamic phenomena in the Sun on various temporal and spatial scales. Based on previous and recent observational and numerical studies, we highlight that, in most cases, none of these processes alone can drive and also trigger explosive phenomena releasing considerable amount of energy towards the outer solar atmosphere and space, such as flares, jets and large-scale eruptions (e.g. coronal mass ejections). In addition, one has to take into account the physical properties of the emerging field (e.g. strength, amount of flux, relative orientation to neighbouring and pre-existing magnetic fields, etc.) in order to better understand the exact role of magnetic flux emergence on the onset of solar dynamic events.

This article is part of the theme issue ‘Solar eruptions and their space weather impact’.
Direct visualization of human myosin II force generation using DNA origami-based thick filaments
Authors: Fujita Keisuke , Ohmachi Masashi , Ikezaki Keigo , Yanagida Toshio , Iwaki Mitsuhiro
Published: May 2019

Muscle contraction can be explained by the swinging lever-arm model. However, the dynamic features of how the myosin head swings the lever-arm and its initial interactions with actin are not well understood even though they are essential for the muscle force generation, contraction speed, heat production, and response to mechanical perturbations. This is because myosin heads during force generation have not been directly visualized. Here, we engineered thick filaments composed of DNA origami and recombinant human muscle myosin, and directly visualized the heads during force generation using nanometer-precision single-molecule imaging. We found that when the head diffuses, it weakly interacts with actin filaments and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the head two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. These results can explain all mechanical characteristics of muscle contraction and suggest that our DNA origami-based assay system can be used to dissect the mechanistic details of motor proteins.
Antibiotics and food in the American press
Authors: Bridier-Nahmias Antoine , Badau Estera , Nyvall-collen Pi , Andremont Antoine , Arquembourg Jocelyne
Published: May 2019

The emergence of antimicrobial resistant infections from food is well documented in the scientific literature but, in this kind of matter, the public opinion is an important policy driver and is vastly forged by traditional media. Here, we propose a text mining study through about 500 articles from two reference daily U.S. newspapers to assess the media coverage of this issue. Our results indicate that, since the middle of the 80s, the two journals considered here adopted a very different narrative around the issue, echoing civil society concerns in one case and the official discourse in the other.
Girdin: an essential component of pre-replicative complex in human cells
Authors: Wu Lihong , Hua Yu , Chang Feiran , Kong Daochun
Published: May 2019

A central event in the initiation of DNA replication in eukaryotes is the assembly of pre-replicative complex (pre-RC) on specific chromatin sites known as DNA replication origins. The pre-RC assembly process differs between budding and fission yeasts. In fission yeast, Sap1 directly participates in pre-RC assembly, together with the four initiation factors: ORC, Cdc18/Cdc6, Cdt1, and MCM. In metazoans, the nature of DNA replication origins is not defined and the mechanism of pre-RC assembly remains incompletely known. In this study, Girdin was identified as an essential replication initiation factor in human cells. Similar to the activity of Sap1, human Girdin binds to DNA origins, interacts with ORC, and is required for pre-RC assembly due to its essential role in recruitment of Cdc6 to DNA origins. Thus, DNA origins in human or metazoans are defined as including two elements, one bound by ORC and the other bound by Girdin.
Increasing objective cardiometabolic burden associated with attenuations in the P3b event-related potential component in older adults
Authors: Keage Hannah A.D. , Feuerriegel Daniel , Greaves Danielle , Tregoweth Emma , Coussens Scott , Smith Ashleigh E.
Published: May 2019

Cardiometabolic diseases and risk factors increase the risk of late-life cognitive impairment and dementia, and have also been associated with detrimental grey and white matter changes. However the functional brain changes associated with cardiometabolic health in late-life are unclear. We sought to characterise these functional changes by recording event-related potentials (ERPs) during a n-back working memory task (0, 1 and 2 back) in 85 adults (60% female) between 50 and 80 years of age. Due to a stratified recruitment approach, participants varied widely regarding cognitive function and cardiometabolic health. Standard and objective cut-offs for high blood glucose, waist to hip ratio (i.e. obesity), high blood cholesterol, and hypertension were employed to generate a summative score for cardiometabolic burden (none, one, or two or more above cut-off). Mixed effects modelling (covarying for age and gender) revealed no statistically significant associations between cardiometabolic burden and visual P1 and N1 component amplitudes. There was a significant effect for the P3b component: as cardiometabolic burden increased, P3b amplitude decreased. We show that cardiometabolic factors related to the development of cognitive impairment and dementia in late-life associate with functional brain activity, as recorded via ERPs. Findings have relevance for the monitoring of lifestyle interventions (typically targeting cardiometabolic factors) in ageing, as ERPs may provide a more sensitive measure of change than cognitive performance. Further, our results raise questions related to the findings of a broad range of ERP studies where the groups compared may differ in their cardiometabolic health status (not only in psychological symptomatology).
Permissive Fatty Acid Incorporation in Host Environments Promotes Staphylococcal Adaptation to FASII Antibiotics
Authors: Kénanian Gérald , Morvan Claire , Weckel Antonin , Pathania Amit , Anba-Mondoloni Jamila , Halpern David , Solgadi Audrey , Dupont Laetitia , Henry Céline , Poyart Claire , Fouet Agnès , Lamberet Gilles , Gloux Karine , Gruss Alexandra
Published: May 2019

Development of fatty acid synthesis pathway (FASII) inhibitors against the major human pathogen Staphylococcus aureus hinges on the accepted but unproven postulate that an endogenously synthesized branched chain fatty acid is required to complete membrane phospholipids. Evidence for anti-FASII efficacy in animal models supported this view. However, restricted test conditions used previously to show FASII antibiotic efficacy led us to investigate these questions in a broader, host-relevant context. We report that S. aureus rapidly adapts to FASII antibiotics without FASII mutations when exposed to host environments. Treatment with a lead FASII antibiotic upon signs of infection, rather than just after inoculation as commonly practiced, failed to eliminate S. aureus from infected organs in a septicemia model. In vitro, addition of serum facilitated rapid S. aureus FASII bypass by environmental fatty acid (eFA) replacement in phospholipids. Serum lowers membrane stress, leading to increased retention of the two substrates required for exogenous fatty acid (eFA) utilization. In these conditions, eFA occupy both phospholipid positions 1 and 2, regardless of anti-FASII selection. This study revises conclusions on S. aureus fatty acid requirements by disproving the postulate of fatty acid stringency, and reveals an Achilles’ heel for using FASII antibiotics to treat infection in monotherapy.

Significance statement

Antibiotic discovery to overcome treatment failure has huge socio-medical and economic stakes. The fatty acid synthesis (FASII) pathway is considered an ideal druggable target against the human pathogen Staphylococcus aureus, based on evidence of anti-FASII efficacy in infection models, and the postulate that S. aureus synthesizes an irreplaceable fatty acid. We report that S. aureus alters its behavior in host-relevant conditions. Administering FASII antibiotics upon signs of infection, rather than just after inoculation as frequently practiced, failed to clear septicemic infections. In serum, S. aureus rapidly overcomes FASII antibiotics by incorporating alternative fatty acids. We conclude that previously, premature antibiotic treatments and experimental constraints masked S. aureus antibiotic adaptation capacity. These findings should help streamline future drug development programs.
Spatial domain analysis predicts risk of colorectal cancer recurrence and infers associated tumor microenvironment networks
Authors: Uttam Shikhar , Stern Andrew M. , Furman Samantha , Pullara Filippo , Spagnolo Daniel , Nguyen Luong , Gough Albert , Sevinsky Christopher J. , Ginty Fiona , Taylor D. Lansing , Chennubhotla S. Chakra
Published: May 2019

An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. We have developed a transformational spatial analytics (SpAn) computational and systems biology platform that predicts clinical outcomes and captures emergent spatial biology that can potentially inform therapeutic strategies. Here we apply SpAn to primary tumor tissue samples from a cohort of 432 chemo-naïve colorectal cancer (CRC) patients iteratively labeled with a highly multiplexed (hyperplexed) panel of fifty-five fluorescently tagged antibodies. SpAn predicted the 5-year risk of CRC recurrence with a mean area under the ROC curve of 88.5% (SE of 0.1%), significantly better than current state-of-the-art methods. SpAn also inferred the emergent network biology of the tumor spatial domains revealing a synergistic role of known features from CRC consensus molecular subtypes that will enhance precision medicine.
Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity
Authors: Johnson Bryan A. , Hage Adam , Kalveram Birte , Mears Megan , Plante Jessica A. , Rodriguez Sergio E. , Ding Zhixia , Luo Xuemei , Bente Dennis , Bradrick Shelton S. , Freiberg Alexander N. , Popov Vsevolod , Rajsbaum Ricardo , Rossi Shannan , Russell William K. , Menachery Vineet D.
Published: May 2019

Enteric viruses exploit bacterial components including lipopolysaccharides (LPS) and peptidoglycan (PG) to facilitate infection in humans. With origins in the bat enteric system, we wondered if severe acute respiratory syndrome-coronavirus (SARS-CoV) or Middle East respiratory syndrome-CoV (MERS-CoV) also use bacterial components to modulate infectivity. To test this question, we incubated CoVs with LPS and PG and evaluated infectivity finding no change following LPS treatment. However, PG from B. subtilis reduced infection >10,000-fold while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol solvent transferred inhibitory activity to the wash and mass spectrometry revealed surfactin, a cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose- and temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin disrupts CoV virion integrity and surfactin treatment of the virus inoculum ablated infection in vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity and the inhibitory effect of surfactin extended broadly to enveloped viruses including influenza, Ebola, Zika, Nipah, Chikungunya, Una, Mayaro, Dugbe, and Crimean-Congo hemorrhagic fever viruses. Overall, our results indicate that peptidoglycan-associated surfactin has broad virucidal activity and suggest bacteria byproducts may negatively modulate virus infection.

Importance

In this manuscript, we considered a role for bacteria in shaping coronavirus infection. Taking cues from studies of enteric viruses, we initially investigated how bacterial surface components might improve CoV infection. Instead, we found that peptidoglycan-associated surfactin is a potent viricidal compound that disrupts virion integrity with broad activity against enveloped viruses. Our results indicate that interactions with commensal bacterial may improve or disrupt viral infections highlighting the importance of understanding these microbial interactions and their implications for viral pathogenesis and treatment.
Detailed profiles of histone modification in male germ line cells of the young and aged mice
Authors: Tatehana Misako , Kimura Ryuichi , Mochizuki Kentaro , Osumi Noriko
Published: May 2019

Human epidemiological studies have shown paternal aging as one of the risks for neurodevelopmental disorders such as autism in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence biology of offspring. Here we are focusing on epigenetic alterations in sperm that can influence offspring developmental programs. In this study, we qualitatively and semi-quantitatively evaluated histone modification patterns in male germ line cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months) and aged (12 months) old mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, H3K9me3 was decreased in the male germ line cells in the aged testis, while H3K27me2/3 was increased. The intensity of H3K27ac, an active mark, was relatively low in the aged testis. Interestingly, H3K27ac was detected in putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germ line cells in the aged testis. H3K79me3 was contrastingly increased and accumulated on the sex chromosomes at M-phase spermatocytes. Therefore, aging induced alterations in the amount of histone modifications, of which patterns were different in individual histone modifications. Moreover, histone modification seems to be differentially regulated by aging on the sex chromosomes and on others. These findings would help elucidate epigenetic mechanisms underlying influence of paternal aging on offspring's development.
Interspecific introgression mediates adaptation to whole genome duplication
Authors: Marburger Sarah , Monnahan Patrick , Seear Paul J. , Martin Simon H. , Koch Jordan , Paajanen Pirita , Bohutínská Magdalena , Higgins James D. , Schmickl Roswitha , Yant Levi
Published: May 2019

Adaptive gene flow is a consequential evolutionary phenomenon across all kingdoms of life. While recognition of widespread gene flow is growing, examples lack of bidirectional gene flow mediating adaptations at specific loci that cooperatively manage core cellular processes. We previously described concerted molecular changes among physically interacting members of the meiotic machinery controlling crossover number and distribution upon adaptation to whole genome duplication (WGD) inArabidopsis arenosa. Here we conduct a population genomic study to test the hypothesis that escape from extinction following the trauma of WGD was mediated by adaptive gene flow betweenA. arenosaand its congenerArabidopsis lyrata. We show thatA. lyrataunderwent WGD more recently thanA. arenosa, indicating that specific pre-adapted alleles donated byA. arenosaunderwent selection and rescued the nascentA. lyratatetraploids from early extinction. At the same time, we detect specific signals of gene flow in the opposite direction at other functionally interacting gene coding loci that display dramatic signatures of selective sweep in both tetraploid species. Cytological analysis shows that A. lyrata tetraploids exhibit similar levels of meiotic stability asA. arenosatetraploids. Taken together, these data indicate that bidirectional gene flow allowed for an escape from extinction of the young autopolyploids, especially the rare tetraploidA. lyrata, and suggest that the merger of these species is greater than the sum of their parts.
A large-scale resource for tissue-specific CRISPR mutagenesis inDrosophila
Authors: Port Fillip , Strein Claudia , Stricker Mona , Rauscher Benedikt , Heigwer Florian , Zhou Jun , Beyersdörffer Celine , Frei Jana , Hess Amy , Kern Katharina , Malamud Roberta , Pavlovic Bojana , Rädecke Kristin , Schmitt Lukas , Voos Lukas , Valentini Erica , Boutros Michael
Published: May 2019

Genetic screens are powerful tools for the functional annotation of genomes. In the context of multicellular organisms, interrogation of gene function is greatly facilitated by methods that allow spatial and temporal control of gene abrogation. Here, we describe a large-scale transgenic short guide (sg) RNA library for efficient CRISPR-based disruption of specific target genes in a constitutive or conditional manner. The library consists currently of more than 2600 plasmids and 1600 fly lines with a focus on targeting kinases, phosphatases and transcription factors, each expressing two sgRNAs under control of the Gal4/UAS system. We show that conditional CRISPR mutagenesis is robust across many target genes and can be efficiently employed in various somatic tissues, as well as the germline. In order to prevent artefacts commonly associated with excessive amounts of Cas9 protein, we have developed a series of novel UAS-Cas9 transgenes, which allow fine tuning of Cas9 expression to achieve high gene editing activity without detectable toxicity. Functional assays, as well as direct sequencing of genomic sgRNA target sites, indicates that the vast majority of transgenic sgRNA lines mediate efficient gene disruption. Furthermore, we conducted the so far largest fully transgenic CRISPR screen in any metazoan organism, which further supported the high efficiency and accuracy of our library and revealed many so far uncharacterized genes essential for development.
Structural state recognition facilitates tip tracking of EB1 at growing microtubule ends in cells
Authors: Reid Taylor A. , Coombes Courtney , Mukherjee Soumya , Goldblum Rebecca R. , White Kyle , Parmar Sneha , McClellan Mark , Zanic Marija , Courtemanche Naomi , Gardner Melissa K.
Published: May 2019

The microtubule binding protein EB1 specifically targets the growing ends of microtubules in cells, where EB1 facilitates the interactions of cellular proteins with microtubule plus-ends. Microtubule end targeting of EB1 has been attributed to high affinity binding of EB1 to GTP-tubulin that is present at growing microtubule ends. However, our 3D single-molecule diffusion simulations predicted a ∼6000% increase in EB1 arrivals to open, tapered microtubule tip structures relative to closed lattice conformations. Using quantitative fluorescence, single-molecule, and electron microscopy experiments, we found that the binding of EB1 onto opened, structurally disrupted microtubules was dramatically increased relative to closed, intact microtubules, regardless of hydrolysis state. Correspondingly, in cells, the conversion of growing microtubule ends from a tapered into a blunt configuration resulted in reduced EB1 targeting. Together, our results suggest that microtubule structural recognition, based on a fundamental diffusion-limited binding model, facilitates the tip tracking of EB1 at growing microtubule ends.
Parkin deficiency perturbs striatal circuit dynamics
Authors: Baaske Magdalena K. , Kramer Edgar R. , Meka Durga Praveen , Engler Gerhard , Engel Andreas K. , Moll Christian K.E.
Published: May 2019

Loss-of-function mutations in the parkin-encoding PARK2 gene cause young-onset, autosomal recessive Parkinson’s disease (PD). Here, we investigated how parkin mutations affect cortico-basal ganglia circuit dynamics and cell-type-specific functional connectivity by recording simultaneously from motor cortex, striatum and globus pallidus (GP) in anesthetized parkin-mutant mice.

While ongoing activity of presumed striatal spiny projection neurons and their downstream counterparts in the GP was not different from controls, parkin deficiency had a differential impact on striatal interneurons: In parkin-mutant mice, tonically active neurons displayed elevated activity levels. Baseline firing of transgenic striatal fast spiking interneurons (FSI), on the contrary, was reduced and the correlational structure of the FSI microcircuitry was disrupted. The entire transgenic striatal microcircuit showed enhanced and phase-shifted phase coupling to slow (1-3Hz) cortical population oscillations. Unexpectedly, local field potentials recorded from striatum and GP of parkin-mutant mice robustly displayed amplified beta oscillations (∼22Hz), phase-coupled to cortex. Moreover, parkin deficiency selectively increased spike-field coupling of FSIs to beta oscillations.

Our findings suggest that loss of parkin function leads to amplifications of synchronized cortico-striatal oscillations and intrastriatal reconfiguration of interneuronal circuits. This presymptomatic disarrangement of dynamic functional connectivity may precede nigro-striatal neurodegeneration and predispose to imbalance of striatal outflow accompanying symptomatic PD.
Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
Authors: Vassilopoulos Stéphane , Gibaud Solène , Jimenez Angélique , Caillol Ghislaine , Leterrier Christophe
Published: May 2019

Recent super-resolution microscopy studies have unveiled a periodic scaffold of actin rings regularly spaced by spectrins under the plasma membrane of axons. However, ultrastructural details are unknown, limiting a molecular and mechanistic understanding of these enigmatic structures. Here, we combine platinum-replica electron and optical super-resolution microscopy to investigate the cortical cytoskeleton of axons at the ultrastructural level. Immunogold labeling and correlative super-resolution/electron microscopy allow us to unambiguously resolve actin rings as braids made of two long, intertwined actin filaments connected by a dense mesh of aligned spectrins. This molecular arrangement contrasts with the currently assumed model of actin rings made of short, capped actin filaments. Along the proximal axon, we resolved the presence of phospho-myosin light chain and the scaffold connection with microtubules via ankyrin G. We propose that braided rings explain the observed stability of the actin-spectrin scaffold and ultimately participate in preserving the axon integrity.
PRAM: a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments
Authors: Liu Peng , Soukup Alexandra A. , Bresnick Emery H. , Dewey Colin N. , Keleş Sündüz
Published: May 2019

Publicly available RNA-seq data is routinely used for retrospective analysis to elucidate new biology. Novel transcript discovery enabled by joint examination of large collections of RNA-seq datasets has emerged as one such analysis. Current methods for transcript discovery rely on a ‘2-Step’ approach where the first step encompasses building transcripts from individual datasets, followed by the second step that merges predicted transcripts across datasets. To increase the power of transcript discovery from large collections of RNA-seq datasets, we developed a novel ‘1-Step’ approach named Pooling RNA-seq and Assembling Models (PRAM) that builds transcript models from pooled RNA-seq datasets. We demonstrate in a computational benchmark that ‘1-Step’ outperforms ‘2-Step’ approaches in predicting overall transcript structures and individual splice junctions, while performing competitively in detecting exonic nucleotides. Applying PRAM to 30 human ENCODE RNA-seq datasets identified unannotated transcripts with epigenetic and RAMPAGE signatures similar to those of recently annotated transcripts. In a case study, we discovered and experimentally validated new transcripts through the application of PRAM to mouse hematopoietic RNA-seq datasets. Notably, we uncovered new transcripts that share a differential expression pattern with a neighboring genePik3cgimplicated in human hematopoietic phenotypes, and we provided evidence for the conservation of this relationship in human. PRAM is implemented as an R/Bioconductor package and is available athttps://bioconductor.org/packages/pram.
HA Nanocarriers Mediate HepG2 Vaccine Induction of hGM-CSF Gene Antitumor effect study
Authors: Robert Leah , Gupta David
Published: May 2019

This report developed a novel method to observe the anti-tumor effect of HA nanoparticle carrier-mediated HepG2 cell vaccine transfected with hGM-CSF gene in vitro, and provide evidence for the clinical application of hGM-CSF gene-modified HepG2 cell vaccine. HA nanoparticle-mediated hGM-CSF gene transfection of HepG2 cells was used to prepare HepG2 cell vaccine transfected with GMCSF gene. Human PBMC were isolated by density gradient centrifugation and human PBMC were induced in vitro. The proliferative activity of PBMC and the killing effect on HepG2 cells were determined by WST-1 method. The positive expression rates of CD4+ and CD8+ were analyzed by flow cytometry, and the secretion of INF-γ was determined by ELISA. WST-1 results showed that the transgenic HepG2 vaccine induced PBMC proliferation, and its proliferation rate was better than that of wild-type vaccine. The induced PBMC had a higher killing rate against HepG2 than the wild-type vaccine group and each blank. In the control group, FCM results showed that the positive expression rates of CD4+ and CD8+ in the transgenic HepG2 vaccine group were higher than those in the wild-type vaccine group and each blank control group. The ELISA results showed that the IFN-γ content in the transgenic PBMC culture supernatant was 1989.76. +/− 254.21 pg/ml, higher than the wild-type vaccine group and each blank control group.
Social foraging extends associative odor-food memory expression in an automated learning assay for Drosophila
Authors: Sehdev Aarti , Mohammed Yunusa G. , Tafrali Cansu , Szyszka Paul
Published: May 2019

Animals socially interact during foraging and share information about the quality and location of food sources. The mechanisms of social information transfer during foraging have been mostly studied at the behavioral level, and its underlying neural mechanisms are largely unknown. The fruit fly Drosophila melanogaster has become a model for studying the neural bases of social information transfer, as fruit flies show a rich repertoire of social behaviors and provide a well-developed genetic toolbox to monitor and manipulate neuronal activity. Social information transfer has already been characterized for fruit flies’ egg laying, mate choice, foraging and aversive associative learning, however the role of social information transfer on associative odor-food learning during foraging are unknown. Here we present an automated learning and memory assay for walking flies that allows studying the effect of group size on social interactions and on the formation and expression of associative odor-food memories. We found that both inter-fly attraction and the duration of odor-food memory expression increase with group size. We discuss possible behavioral and neural mechanisms of this social effect on odor-food memory expression. This study opens up opportunities to investigate how social interactions are relayed in the neural circuitry of learning and memory expression.
In Silico Analysis of Ixodid Tick Aqauporin-1 Protein as a Candidate Anti-Tick Vaccine Antigen
Authors: Ndekezi Christian , Nkamwesiga Joseph , Ochwo Sylvester , Kimuda Magambo Phillip , Mwiine Frank Norbert , Tweyongyere Robert , Amanyire Wilson , Muhanguzi Dennis
Published: May 2019

Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Ticks are largely controlled by acaricide application. However, acaricide efficacy is hampered by high cost, the need for regular application and selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on integration of rational acaricide application and other methods such as vaccination. To contribute to systematic research-guided efforts to produce anti-tick vaccines, we carried out an in silico tick Aquaporin-1 protein (AQP1) analysis to identify unique tick AQP1 peptide motifs that can be used in future peptide anti-tick vaccine development. We used multiple sequence alignment (MSA), motif analysis, homology modeling, and structural analysis to identify unique tick AQP1 peptide motifs. BepiPred, Chou & Fasman-Turn, Karplus & Schulz Flexibility and Parker-Hydrophilicity prediction models were used to asses these motifs’ abilities to induce antibody mediated immune responses. Tick AQP1 (MK334178) protein homology was largely similar to the bovine AQP1 (PDB:1J4N) (23% sequence similarity; Structural superimposition RMS=1.475). The highest similarities were observed in the transmembrane domains while differences were observed in the extra and intra cellular protein loops. Two unique tick AQP1 (MK334178) motifs, M7 (residues 106-125, p=5.4e-25) and M8 (residues 85-104, p=3.3e-24) were identified. These two motifs are located on the extra-cellular AQP1 domain and showed the highest Parker-Hydrophilicity prediction immunogenic scores of 1.153 and 2.612 respectively. The M7 and M8 motifs are a good starting point for the development of potential peptide-based anti-tick vaccine. Further analyses such as in vivo immunization assays are required to validate these findings.
Exploring family business decline with socioemotional wealth perspective
Authors: Llanos-Contreras Orlando Antonio , Jabri Muayyad
Published: May 2019

Purpose

The purpose of this paper is to determine how family and business priorities influence organisational decline and turnaround in a family business.

Design/methodology/approach

Following critical realism as philosophical orientation, this research is based on an exploratory single case study.

Findings

This research identified specific socioemotional wealth priorities driving this organisation decline and turnaround. The study also determined how the family and business dynamic leads to decisions that first trigger the organisational decline and then explain the successful implementation of turnaround strategies.

Research limitation/implications

Findings of this research provide limited and contingent theoretical generalisation. Accordingly, replication and further quantitative research is required for a better understanding of this phenomenon.

Practical implications

Managers can benefit from this paper by noting which behaviour could lead to organisational decline and which factors could lead to a turnaround. Similarly, managers can learn about the importance of the alignment of socioemotional wealth priorities as a critical response factor to determine whether to follow exit strategies or turnaround (succession) actions.

Originality value

The study contributes to the organisational decline literature and family business literature. It advances the understanding of how family businesses should balance family and business priorities to avoid organisational decline and identify strategies successfully implemented for turning around.
Resilience in Talcahuano, Chile: appraising local disaster response
Authors: Engel Karen Elisabeth , Warner Jeroen Frank
Published: May 2019

Purpose

The purpose of this paper is to present the findings of a qualitative and exploratory study aimed at learning more about the local forms of resilience that emerged in two localities (one rural and one urban locality) in Talcahuano, Chile, in response to the major earthquake and devastating tsunami that hit them on February 27, 2010.

Design/methodology/approach

To ensure that people’s experiences remained leading throughout the study, data were collected in the field by the first author over a period of 13 months using a variety of qualitative methods. The primary methods were observation, participation and semi-structured interviews with a variety of actors, ranging from community members to local leaders and emergency professionals. For the analysis, a scheme was used that categorizes manifested resilience using two dimensions: damage and responsiveness. Since this scheme has been mostly used to evaluate tree populations, it was adapted to fit the appraisal of a social system.

Findings

The findings suggest that damage levels in the two communities were similar, but that the responsiveness was not. One locality revealed high levels of resilience, while the other exposed increased susceptibility to future similar events.

Originality/value

This research initiative was relevant because it exposed actual resilience. Also, the specificities of the findings enable insights about prevalent vulnerability, in particular the local capacity of response, and that can be used to elaborate concrete earthquake/tsunami disaster scenarios and design local disaster risk reduction interventions.
An exploratory temporal analysis of the lodging market and state economic recovery from Hurricane Sandy (The lodging market recovery from Hurricane Sandy)
Authors: Choi Danny Woosik , Lee Seoki , Singal Manisha
Published: May 2019

Purpose

The purpose of this study is to examine how the lodging market and the state economy affected by Hurricane Sandy have recovered from the damages sustained. Specifically, this study examines and predicts the influence of revenue management key performance indicators (KPIs) on recovery and lodging revenue in the affected states and the states’ economies. These KPIs include average daily rate (ADR), occupancy and revenue per available room (RevPAR).

Design/methodology/approach

Secondary financial data were collected for the states most damaged by Hurricane Sandy. Subsequently, pooled Ordinary Least Square (OLS) regression was conducted combining time and non-time dependent variables based on the states and radius from the landfall.

Findings

The results indicate that although the lodging market and the state economies have recovered since the onslaught of Hurricane Sandy, certain KPIs still need to improve.

Practical implications

Managerial implications are suggested in terms of dynamic pricing, market-based recovery, the KPIs, federal aid and facility management.

Originality/value

Despite its importance, research on the effects of climate change in the hospitality context has not actively progressed after Hurricane Katrina. Time and non-time dependent variables are combined in this analysis to gain a richer understanding of the impacts and recovery of KPIs on the revenue in the lodging market and the revenue on states’ economies. Additional analysis based on the radius from the landfall of the hurricane was performed to examine the impact and recovery based on geographical proximity.
An analysis of emerging trends and transformations in global healthcare
Authors: Yeganeh Hamid
Published: May 2019

Purpose

The purpose of this paper is to analyze the main global transformations of the healthcare sector and their underlying causes and effects.

Design/methodology/approach

The study focuses on several important trends including the increasing life expectancy and aging, the rise of non-communicable diseases, the risks of pandemics, medication expenditure, the globalization of healthcare and technological innovations such as digitization, robotic and nanomedicine.

Findings

The analysis indicates that the world populations will be much older in the near future and the healthcare sector will witness significant growth opportunities. The aging populations will put more pressure on healthcare systems and increase the incidence of non-communicable diseases. In a globalized world, the risks of global pandemics are expected to increase. The surge in the medication expenditure will put much pressure on healthcare systems, insurers, patients, employers and providers. The healthcare sector is characterized by its above-average growth in the USA and much of the developed world. Therefore, the share of healthcare in gross domestic product will continue to rise. The digitization and globalization of healthcare may involve major disruptions in the location and the type of care. New materials particularly nanoparticles will be used to enhance the precision, quality and efficacy of diagnostics, medications and treatments.

Originality/value

The paper touches on several areas including demographic, clinical, financial, managerial and technological transformations and examines their implications for the healthcare sector.
Market reactions to changes in the Dow Jones industrial average index
Authors: Biktimirov Ernest N. , Xu Yuanbin
Published: May 2019

Purpose

The purpose of this paper is to examine changes in stock returns, liquidity, institutional ownership, analyst following and investor awareness for companies added to and deleted from the Dow Jones Industrial Average (DJIA) index. Previous studies report conflicting evidence regarding the market reactions to changes in the DJIA index membership.

Design/methodology/approach

This study uses the event-study methodology to calculate abnormal returns and trading volume around the announcement and effective days of DJIA index changes from 1929 to 2015. It also tests for significant changes in liquidity, institutional ownership, analyst following and investor awareness in the 1990–2015 period. Multivariate regressions are used to perform a simultaneous analysis of competing hypotheses.

Findings

This study resolves the mixed results of previous DJIA index papers by documenting different stock price and trading volume reactions over the 1929–2015 period. Focusing on the most recent period, 1990–2015, the study finds that stocks added to (deleted from) the index experience a significant permanent stock price gain (loss). The observed stock price reaction seems to be associated with changes in liquidity proxies thus lending support for the liquidity hypothesis.

Research limitations/implications

Limited data availability for the periods prior to 1990 prevents this study from identifying the exact reasons for different stock price and trading volume reactions across subperiods of the 1929–2015 period.

Originality/value

This study provides the most comprehensive examination of market reactions to changes in the DJIA index and resolves the mixed results of previous studies. A better understanding of market reactions around the DJIA index changes can help both individual and institutional investors with developing effective trading strategies and index managing companies with designing optimal announcement policies.