bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells
Authors: Neavin Drew , Nguyen Quan , Daniszewski Maciej S. , Liang Helena H. , Chiu Han Sheng , Senabouth Anne , Lukowski Samuel W , Crombie Duncan E. , Lidgerwood Grace E. , Hernández Damián , Vickers James C. , Cook Anthony L. , Palpant Nathan J. , Pébay Alice , Hewitt Alex W. , Powell Joseph E.
Published: June 2020

The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) - cells that can be differentiated into any cell type of the three germ layers - has provided a foundation forin vitrohuman disease modelling1,2, drug development1,2, and population genetics studies3,4. In the majority of instances, the expression levels of genes, plays a critical role in contributing to disease risk, or the ability to identify therapeutic targets. However, while the effect of the genetic background of cell lines has been shown to strongly influence gene expression, the effect has not been evaluated at the level of individual cells. Differences in the effect of genetic variation on the gene expression of different cell-types, would provide significant resolution for in vitro research using preprogramed cells. By bringing together single cell RNA sequencing15–21and population genetics, we now have a framework in which to evaluate the cell-types specific effects of genetic variation on gene expression. Here, we performed single cell RNA-sequencing on 64,018 fibroblasts from 79 donors and we mapped expression quantitative trait loci (eQTL) at the level of individual cell types. We demonstrate that the large majority of eQTL detected in fibroblasts are specific to an individual sub-type of cells. To address if the allelic effects on gene expression are dynamic across cell reprogramming, we generated scRNA-seq data in 19,967 iPSCs from 31 reprogramed donor lines. We again identify highly cell type specific eQTL in iPSCs, and show that that the eQTL in fibroblasts are almost entirely disappear during reprogramming. This work provides an atlas of how genetic variation influences gene expression across cell subtypes, and provided evidence for patterns of genetic architecture that lead to cell-types specific eQTL effects.
Exposure to artificial light at night accelerates but does not override latitude-dependent seasonal reproductive response in dark-eyed juncos
Authors: Singh D. , Montoure J. , Ketterson E.D.
Published: June 2020

In the modern era of industrialization, illuminated nights have become a common defining feature of human-occupied environments, particularly cities. Artificial light at night (ALAN) imposes several known negative impacts on the neuroendocrine system, metabolism, and seasonal reproduction of species living in the wild. However, we know little about the impact of ALAN on populations of birds that either live year-round in the same location or move to different latitudes across seasons. To test whether ALAN has differing impact on reproductive timing of the bird populations that winter in sympatry but breed at different latitudes, we monitored sedentary and migratory male dark-eyed juncos that were or were not exposed to low intensity (~2.5 ± 0.5 lux) ALAN. All groups were held in common conditions and day length was gradually increased to mimic natural day length changes (NDL). We assessed seasonal reproductive response from initiation to termination of the breeding cycle. As expected based on earlier research, the sedentary birds exhibited earlier gonadal recrudescence and terminated breeding later than the migratory birds. In addition, resident and migrant birds exposed to ALAN initiated gonadal recrudescence earlier and terminated reproduction sooner as compared to their conspecifics experiencing NDL. Importantly, the difference in the reproductive timing of sedentary and migratory populations was maintained even when exposed to ALAN. This variation in the seasonal reproductive timing may likely have a genetic ground or early developmental effects imposed due to different latitude of origin. This study reveals first that latitude-dependent variation in reproductive timing is maintained despite exposure to ALAN, and second that ALAN accelerated reproductive development across both migrants and residents. The results corroborating relationship between latitude, population, and ALAN impact on seasonal reproductive timing, may provide a potential mechanism to test the fitness of a population and its range expansion to exploit urban environment.
Non-canonical immune response to the inhibition of DNA methylation via stabilization of endogenous retrovirus dsRNAs
Authors: Ku Yongsuk , Park Joo-Hwan , Cho Ryeongeun , Lee Yongki , Park Hyoung-Min , Kim MinA , Hur Kyunghoon , Byun Soo Young , Liu Jun , Shum David , Shin Dong-Yeop , Koh Youngil , Cho Je-Yoel , Yoon Sung-Soo , Hong Junshik , Kim Yoosik
Published: June 2020

5-Aza-2′-deoxycytidine, also known as decitabine, is a DNA-methyltransferase inhibitor (DNMTi) used to treat acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERV), which can induce an immune response by acting as cellular double-stranded RNAs (dsRNAs). Here, we employ an image-based screening platform to identify dsRNA-binding factors that mediate the downstream effect of ERV induction. We find that Staufen1 (Stau1) knockdown decreases the interferon signature and rescues decitabine-mediated cell death. Moreover, Stau1 directly binds to ERV RNAs and stabilizes them, together with a long non-coding RNA TINCR. We further show that TINCR enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that AML patients with low Stau1 and TINCR expressions exhibits inferior treatment outcomes to the DNMTi therapy. Our study reveals that decitabine-mediated cell death is a consequence of complex interactions among different dsRNA-binding proteins for access to their common dsRNA targets.

HIGHLIHGTS

Image-based RNAi screening reveals multiple dsRBPs regulate response to decitabine

Stau1 binds to ERV RNAs and affects their stability and subcellular localization

TINCR binds to Stau1 and enhances Stau1-ERV interactions

AML/MDS patients with low Stau1 and TINCR expressions show poor response to DNMTis
Statins attenuate antiviral IFN-β and ISG expression via inhibiting IRF3/JAK/STAT signaling in poly(I:C)-treated hyperlipidemic mice and macrophages
Authors: Koike Atsushi , Tsujinaka Kaito , Fujimori Ko
Published: June 2020

Viral infection is a significant burden to healthcare worldwide. Statins, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, are widely used as cholesterol-lowering drugs. Recently, long term statin therapy was shown to reduce the antiviral immune response; however, the underlying molecular mechanisms are unclear. Here, we found that simvastatin decreased polyinosinic-polycytidylic acid [poly(I:C)]-induced expression of antiviral interferon (IFN)-β and IFN-stimulated genes (ISGs) in the bronchoalveolar lavage fluid and lungs of mice with high-fat diet-induced hyperlipidemia. As macrophages were the dominant cell type in the bronchoalveolar lavage fluid of poly(I:C)-treated mice, we examined the molecular mechanisms of statin-mediated inhibition of antiviral gene expression using murine J774.1/JA-4 macrophages. Simvastatin and pitavastatin decreased poly(I:C)-induced expression of IFN-β and ISGs. Moreover, they repressed poly(I:C)-induced phosphorylation of IFN regulatory factor (IRF) 3 and signal transducers and activators of transcription (STAT) 1, which is involved in Janus kinase (JAK)/STAT signaling. Mevalonate and geranylgeranylpyrophosphate (GGPP), but not cholesterol, counteracted the negative effect of statins on IFN-β and ISG expression and phosphorylation of IRF3 and STAT1. These results suggest that statins suppressed the expression of IFN-β and ISGs in poly(I:C)-treated hyperlipidemic mice and murine macrophages, and that these effects occured through the inhibition of IRF3-mediated JAK/STAT signaling in macrophages. Furthermore, GGPP recovered the statin-suppressed IRF3/JAK/STAT signaling pathway in poly(I:C)-treated macrophages.
Absence of heme at the catalytic site of heme oxygenase-2 triggers its lysosomal degradation
Authors: Liu Liu , Dumbrepatil Arti B. , Fleischhacker Angela S. , Marsh E. Neil G. , Ragsdale Stephen W.
Published: June 2020

Heme oxygenase-2 (HO2) and −1 (HO1) catalyze heme degradation to biliverdin, CO, and iron, forming an essential link in the heme metabolism network. Tight regulation of the cellular levels and catalytic activities of HO1 and HO2 is important for maintaining heme homeostasis. While transcriptional control of HO1 expression has been well-studied, how the cellular levels and activity of HO2 are regulated remains unclear. Here, the mechanism of post-translational regulation of cellular HO2 level by heme is elucidated. Under heme deficient conditions, HO2 is destabilized and targeted for degradation. In HO2, three heme binding sites are potential targets of heme-dependent regulation: one at its catalytic site; the others at its two heme regulatory motifs (HRMs). We report that, in contrast to other HRM-containing proteins, the cellular protein level and degradation rate of HO2 are independent of heme binding to the HRMs. Rather, under heme deficiency, loss of heme binding to the catalytic site destabilizes HO2. Consistently, a HO2 catalytic site variant that is unable to bind heme exhibits a constant low protein level and an enhanced protein degradation rate compared to the wild-type HO2. However, cellular heme overload does not affect HO2 stability. Finally, HO2 is degraded by the lysosome through chaperone-mediated autophagy, distinct from other HRM-containing proteins and HO1, which are degraded by the proteasome. These results reveal a novel aspect of HO2 regulation and deepen our understanding of HO2’s role in maintaining heme homeostasis, paving the way for future investigation into HO2’s pathophysiological role in heme deficiency response.
Genetic influences on hub connectivity of the human connectome
Authors: Arnatkevičiūtė Aurina , Fulcher Ben D. , Oldham Stuart , Tiego Jeggan , Paquola Casey , Gerring Zachary , Aquino Kevin , Hawi Ziarih , Johnson Beth , Ball Gareth , Klein Marieke , Deco Gustavo , Franke Barbara , Bellgrove Mark , Fornito Alex
Published: June 2020

Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.
Universal Features of Epidemic Models Under Social Distancing Guidelines
Authors: Sadeghi Mahdiar , Greene James M. , Sontag Eduardo D.
Published: June 2020

Social distancing as a form of nonpharmaceutical intervention has been enacted in many countries as a form of mitigating the spread of COVID-19. There has been a large interest in mathematical modeling to aid in the prediction of both the total infected population and virus-related deaths, as well as to aid government agencies in decision making. As the virus continues to spread, there are both economic and sociological incentives to minimize time spent with strict distancing mandates enforced, and/or to adopt periodically relaxed distancing protocols, which allow for scheduled economic activity. The main objective of this study is to reduce the disease burden in a population, here measured as the peak of the infected population, while simultaneously minimizing the length of time the population is socially distanced, utilizing both a single period of social distancing as well as periodic relaxation. We derive a linear relationship among the optimal start time and duration of a single interval of social distancing from an approximation of the classic epidemicSIRmodel. Furthermore, we see a sharp phase transition region in start times for a single pulse of distancing, where the peak of the infected population changes rapidly; notably, this transition occurs wellbeforeone would intuitively expect. By numerical investigation of more sophisticated epidemiological models designed specifically to describe the COVID-19 pandemic, we see that all share remarkably similar dynamic characteristics when contact rates are subject to periodic or one-shot changes, and hence lead us to conclude that these features areuniversalin epidemic models. On the other hand, the nonlinearity of epidemic models leads to non-monotone behavior of the peak of infected population under periodic relaxation of social distancing policies. This observation led us to hypothesize that an additional single interval social distancing at aproper timecan significantly decrease the infected peak of periodic policies, and we verified this improvement numerically. While synchronous quarantine and social distancing mandates across populations effectively minimize the spread of an epidemic over the world, relaxation decisions should not be enacted at the same time for different populations.
Transferability of Brain decoding using Graph Convolutional Networks
Authors: Zhang Yu , Bellec Pierre
Published: June 2020

Transfer learning has been a very active research topic in natural image processing. But few studies have reported notable benefits of transfer learning on medical imaging. In this study, we sought to investigate the transferability of deep artificial neural networks (DNN) in brain decoding, i.e. inferring brain state using fMRI brain response over a short window. Instead of using pretrained models from ImageNet, we trained our base model on a large-scale neuroimaging dataset using graph convolutional networks (GCN). The transferability of learned graph representations were evaluated under different circumstances, including knowledge transfer across cognitive domains, between different groups of subjects, and among different sites using distinct scanning sequences. We observed a significant performance boost via transfer learning either from the same cognitive domain or from other task domains. But the transferability was highly impacted by the scanner site effect. Specifically, for datasets acquired from the same site using the same scanning sequences, using transferred features highly improved the decoding performance. By contrast, the transferability of representations highly decreased between different sites, with the performance boost reducing from 20% down to 7% for the Motor task and decreasing from 15% to 5% for Working-memory tasks. Our results indicate that in contrast to natural images, the scanning condition, instead of task domain, has a larger impact on feature transfer for medical imaging. With other advanced tools such as layer-wise fine-tuning, the decoding performance can be further improved through learning more site-specific high-level features while retaining the transferred low-level representations of brain dynamics.
microRNA-19b regulates proliferation & patterning in the avian forebrain
Authors: Mishra Archita , Sindhu Suvimal Kumar , Udaykumar Niveda , Sen Jonaki
Published: June 2020

Unlike the six-layered organization of neurons in the mammalian neocortex, the avian pallium features spatially-segregated neuronal clusters with partially conserved gene expression. While efforts to uncover similarities between the avian pallium and mammalian neocortex have persisted, the mechanisms of pallial development in birds have not been comprehensively explored. Here, we have established the role of a highly conserved microRNA, miR-19b, in controlling proliferation in the embryonic avian forebrain, by regulating the expression of E2f8, a cell-cycle inhibitor and NeuroD1, a neuronal differentiation factor. Further, investigation revealed that there exists a proliferation-dependent specification of pallial neurons in birds, similar to that in mammals. In summary, these findings suggest a profound role of miR-19b in shaping the avian pallium and indicate a closer resemblance of developmental mechanisms between the avian pallium and the mammalian neocortex.
TMT-Based Quantitative Proteomic Analysis of Intestinal Organoids Infected byListeria monocytogeneswith Different Virulence
Authors: Huang Jie , Zhou Cong , Zhou Guanghong , Ye Keping
Published: June 2020

Listeria monocytogenes (Lm)is an opportunistic food-borne pathogen that cause listeriosis.L. monocytogenesbelonged to different serovars presents with different virulence in the host and caused different host reactions. To investigate the remodeling of host proteome by differently toxic strains, the cellular protein responses of intestinal organoids were analyzed using TMT labeling and high performance liquid chromatography-mass spectrometry. Quantitative proteomic analysis revealed 6564 differentially expressed proteins, of which 5591 proteins were quantified. The fold-change cutoff was set at 1.3 (Lmvs control), the virulent strain caused 102 up-regulated proteins and 52 down-regulated proteins, while the low virulent strain caused 188 up-regulated proteins and 25 down-regulated proteins. These identified proteins were involved in the regulation of essential processes such as biological metabolism, energy metabolism, and immune system process. Some selected proteins were screened by Real-time PCR and Western blotting. These results revealed that differently toxicL. monocytogenesinduced similar biological functions and immune responses while had different regulation on differential proteins in the pathway.
PRKCA overexpression is frequent in young oral tongue squamous cell carcinoma patients and is associated with poor prognosis
Authors: Parzefall Thomas , Schnoell Julia , Monschein Laura , Foki Elisabeth , Liu David Tianxiang , Frohne Alexandra , Grasl Stefan , Pammer Johannes , Lucas Trevor , Kadletz Lorenz , Brunner Markus
Published: June 2020

Oral tongue squamous cell carcinoma (OTSCC) have an increasing incidence in young patients and many have an aggressive course of disease. The molecular mechanisms for this increase are unknown and biologic markers to identify high risk patients are lacking.

In an unbiased data screening for differential protein expression of younger (≤45 years) and older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n=98) we identified Protein kinase C alpha (PRKCA), to be significantly more frequently overexpressed in younger versus older patients (p=0.0001). These results were experimentally validated and confirmed in an independent Austrian OTSCC patient sample (n=34) by immunohistochemistry (p=0.0026). PRKCA upregulation was associated with negative anamnesis for alcohol consumption (p=0.009) and tobacco smoking (p=0.02). Univariate and multivariate analysis of overall survival (OS) and disease-free survival (DFS) showed a significantly worse prognosis in patients with tumors overexpressing PRKCA regarding OS (univariate p= 0.04, multivariate p< 0.01). In the young subgroup both OS and DFS were significantly decreased in PRKCA positive patients (both p< 0.001). TCGA messenger RNA enrichment analysis showed 24 mRNAs with significant differential expression in PRKCA positive OTSCC (all p≤ 0.05 after Benjamini-Hochberg correction).

Our findings suggest the potential existence of a distinct molecular subtype of alcohol and tobacco negative, high risk OTSCC in a significant proportion of early onset individuals. Our findings warrant validation in additional OTSCC patient cohorts. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA overexpressing OTSCC.
Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion
Authors: Gallais Floriane , Velay Aurélie , Wendling Marie-Josée , Nazon Charlotte , Partisani Marialuisa , Sibilia Jean , Candon Sophie , Fafi-Kremer Samira
Published: June 2020

Background

In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results.

Methods

Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls.

Results

All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection.

Conclusion

Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus.
Bacterial retrons encode tripartite toxin/antitoxin systems
Authors: Bobonis Jacob , Mateus André , Pfalz Birgit , Garcia-Santamarina Sarela , Galardini Marco , Kobayashi Callie , Stein Frank , Savitski Mikhail M. , Elfenbein Johanna R. , Andrews-Polymenis Helene , Typas Athanasios
Published: June 2020

Retrons are genetic retroelements, commonly found in bacterial genomes and recently repurposed as genome editing tools. Their encoded reverse transcriptase (RT) produces a multi-copy single-stranded DNA (msDNA). Despite our understanding of their complex biosynthesis, the function of msDNAs and therefore, the physiological role of retrons has remained elusive. We establish that the retron-Sen2 inSalmonellaTyphimurium encodes a toxin, which we have renamed as RcaT (Retron cold-anaerobic Toxin). RcaT is activated when msDNA biosynthesis is perturbed and its toxicity is higher at ambient temperatures or during anaerobiosis. The RT and msDNA form together the antitoxin unit, with the RT binding RcaT, and the msDNA enabling the antitoxin activity. Using anotherE. coliretron, we establish that this toxin/antitoxin function is conserved, and that RT-toxin interactions are cognate. Altogether, retrons constitute a novel family of tripartite toxin/antitoxin systems.
Synergistic epistasis enhances cooperativity of mutualistic interspecies interactions
Authors: Turkarslan Serdar , Stopnisek Nejc , Thompson Anne W , Arens Christina E , Valenzuela Jacob J , Wilson James , Hunt Kristopher A , Hardwicke Jessica , Lim Sujung , Seah Yee Mey , Fu Ying , Wu Liyou , Zhou Jizhong , Hillesland Kristina L , Stahl David A , Baliga Nitin S
Published: June 2020

Frequent fluctuations in sulfate availability rendered syntrophic interactions between the sulfate reducing bacteriumDesulfovibrio vulgaris(Dv) and the methanogenic archaeonMethanococcus maripaludis(Mm) unsustainable. By contrast, prolonged laboratory evolution in obligate syntrophy conditions improved the productivity of this community but at the expense of erosion of sulfate respiration (SR). Hence, we sought to understand the evolutionary trajectories that could both increase the productivity of syntrophic interactions and sustain SR. We combined a temporal and combinatorial survey of mutations accumulated over 1000 generations of 9 independently-evolved communities with analysis of the genotypic structure for one community down to the single-cell level. We discovered a high level of parallelism across communities despite considerable variance in their evolutionary trajectories and the perseverance of a rare SR+Dvlineage within many evolution lines. An in-depth investigation revealed that synergistic epistasis acrossDvandMmgenotypes had enhanced cooperativity within SR- and SR+ assemblages, allowing their co-existence asr- andK-strategists, respectively.
Critical information thresholds underlying concurrent face recognition functions
Authors: Quek Genevieve L. , Rossion Bruno , Liu-Shuang Joan
Published: June 2020

Humans rapidly and automatically recognise faces on multiple different levels, yet little is known about how the brain achieves these manifold categorisations concurrently. We bring a new perspective to this emerging issue by probing the relative informational dependencies of two of the most important aspects of human face processing: categorisation of the stimulusas a face(generic face recognition) and categorisation of its familiarity (familiar face recognition). Recording electrophysiological responses to a large set of natural images progressively increasing in image duration (Expt. 1) or spatial frequency content (Expt. 2), we contrasted critical sensory thresholds for these recognition functions as driven by the same face encounters. Across both manipulations, individual observer thresholds were consistently lower for distinguishing faces from other objects than for distinguishing familiar from unfamiliar faces. Moreover, familiar face recognition displayed marked inter-individual variability compared to generic face recognition, with no systematic relationship evident between the two thresholds. Scalp activation was also more strongly right-lateralised at the generic face recognition threshold than at the familiar face recognition threshold. These results suggest that high-level recognition of a faceas a facearises based on minimal sensory input (i.e., very brief exposures/coarse resolutions), predominantly in right hemisphere regions. In contrast, the amount of additional sensory evidence required to access face familiarity is highly idiosyncratic and recruits wider neural networks. These findings underscore the neurofunctional distinctions between these two recognition functions, and constitute an important step forward in understanding how the human brain recognises various dimensions of a face in parallel.

Significance Statement

The relational dynamics between different aspects of face recognition are not yet well understood. We report relative informational dependencies for two concurrent, ecologically relevant face recognition functions: distinguishing faces from objects, and recognising people we know. Our electrophysiological data show that for a given face encounter, the human brain requires less sensory input to categorise that stimulus as a face than to recognise whether the face is familiar. Moreover, where sensory thresholds for distinguishing faces from objects are remarkably consistent across observers, they vary widely for familiar face recognition. These findings shed new light on the multifaceted nature of human face recognition by painting a more comprehensive picture of the concurrent evidence accumulation processes initiated by seeing a face.
Flower initiates a positive feedback loop upon PIP2enrichment at periactive zones to control bulk endocytosis
Authors: Li Tsai-Ning , Chen Yu-Jung , Wang You-Tung , Lin Hsin-Chieh , Yao Chi-Kuang
Published: June 2020

Synaptic vesicle (SV) endocytosis is coupled to exocytosis to maintain SV pool size and thus neurotransmitter release. Intense stimulation induces activity-dependent bulk endocytosis (ADBE) to recapture large quantities of SV constituents in large endosomes from which SVs reform. How these consecutive processes are spatiotemporally coordinated remains unknown. Here, we show that the Flower Ca2+channel-dependent phosphatidylinositol 4,5-bisphosphate (PIP2) compartmentalization governs such control. Strong stimuli trigger PIP2microdomain formation at periactive zones. Upon exocytosis Flower translocates from SVs to periactive zones, where it increases PIP2levels via Ca2+influxes. Remarkably, PIP2directly enhances Flower channel activity, thereby establishing a positive feedback loop for PIP2microdomain compartmentalization. The PIP2microdomains drive ADBE and SV reformation from bulk endosomes. PIP2further sorts Flower to bulk endosomes, thereby terminating endocytosis. Hence, we propose that the interplay between Flower and PIP2is the crucial spatiotemporal cue that couples exocytosis to ADBE and subsequent SV reformation.
Advancing capacity to adapt to climate change: addressing information needs in the Australian property industry
Authors: Warren-Myers Georgia , Hurlimann Anna , Bush Judy
Published: June 2020

Purpose

The purpose of this paper is to understand the sources of climate change information used and trusted by key stakeholders in the Australian property industry, their information needs and their capacity to translate that information into decision-making.

Design/methodology/approach

Qualitative research applying in-depth interviews with 24 key stakeholders from a diverse range of property/real estate companies in Australia.

Findings

This research identified a wide range of information types used by key stakeholders, ranging from reliance on unsophisticated mass media reporting to detailed analysis of scientific research. The capacity of stakeholders to translate this information for their organisation was polarised; 11 of the 24 interviewees indicated they had the capacity, while the other 13 indicated they did not, often owing to time horizons or lack of current interest within the organisation or from clients.

Research limitations/implications

This research was limited to 24 in-depth interviews and is not intended to be a representative sample. However, this limitation is offset by the fact that a diverse range of stakeholders were interviewed and an in-depth and rich understanding has been provided about their approach to climate change.

Practical implications

The results can inform the development of better communication channels for climate change for the property industry by supporting science-practice collaborations in the timely and effective dissemination of research. This is important to understand given the identified need to bridge the gap among research, policy and practice.

Social implications

Climate change poses significant challenges and risks for built environments. The property industry, as a key stakeholder, has great potential to influence current practices. The results reported here assist in addressing these challenges.

Originality/value

At present, limited research globally has been conducted about climate change actions in the property industry. This research responds to this gap.
Outcome of slip features on the peristaltic flow of a Rabinowitsch nanofluid in an asymmetric flexible channel
Authors: Imran Naveed , Javed Maryiam , Sohail Muhammad , Farooq S. , Qayyum Mubashir
Published: June 2020

Purpose

Naturally, all the materials are not viscous (i.e. milk, mayonnaise, blood, vaccines, syrups, cosmetics, oil reservoirs, paints, etc.). Here present analysis focuses on the usage of non-Newtonian fluid rheological properties enhancing, damping tools, protection apparatus individuals and in various distinct mechanical procedures. Industrial applications of non-Newtonian liquids include minimum friction, reduction in oil-pipeline friction, scale-up, flow tracers and in several others. The peristaltic mechanism is used as a non-Newtonian material carrier here. This mechanism occurs because of continuous symmetrical and asymmetrical propulsion of smooth channel walls. Peristalsis is a very significant mechanism for carrying drugs and other materials during sensitive diseases treatments.

Design/methodology/approach

Keeping in mind the considered problem assumptions (Rabinowitsch fluid model, thermal Grashof number, Prandtl number, density Grashof number, wall properties, etc.), it is found that the modeled equations are coupled and nonlinear. Thus here, analytical results are quite challenging to acquire and very limited to extremely venerated circumstances unsettled to their nonlinearity. Hence various developments found in computing proficiencies, numerical procedures that provides accurate, stable and satisfying solutions for non-Newtonian material flows exclusively in complex dimensions play a significant role. Here BVP4C numerical technique is developed to evaluate the nonlinear coupled system of equations with appropriate boundary constraints.

Findings

Due to convectively heated surface fluid between the walls having a small temperature. Sherwood and Nusselt numbers both deduce for fixed radiation values and different Rabinowitsch fluid quantity. Skin friction is maximum in the case of Newtonian, while minimum in case of dilatant model and pseudoplastic models. The influence of numerous parameters associated with flow problems such as thermal Grashof number, density Grashof number, Hartman number, Brownian motion, thermophoresis motion factor and slip parameters are also explored in detail and plotted for concentration profile, temperature distribution and velocity. From this analysis, it is concluded that velocity escalates for larger

Originality/value

The work reported in this manuscript has not been investigated so far by any researcher.
Hall and ion slip current’s impact on magneto-sodium alginate hybrid nanoliquid past a moving vertical plate with ramped heating, velocity slip and Darcy effects
Authors: Ali A. , Banerjee Soma Mitra , Das S.
Published: June 2020

Purpose

The purpose of this study is to analyze an unsteady MHD Darcy flow of nonNewtonian hybrid nanoliquid past an exponentially accelerated vertical plate under the influence of velocity slip, Hall and ion slip effects in a rotating frame of reference. The fluids in the flow domain are assumed to be viscously incompressible electrically conducting. Sodium alginate (SA) has been taken as a base Casson liquid. A strong uniform magnetic field is applied under the assumption of low magnetic Reynolds number. Effect of Hall and ion-slip currents on the flow field is examined. The ramped heating and time-varying concentration at the plate are taken into consideration. First-order homogeneous chemical reaction and heat absorption are also considered. Copper and alumina nanoparticles are dispersed in base fluid sodium alginate to be formed as hybrid nanoliquid.

Design/methodology/approach

The model problem is first formulated in terms of partial differential equations (PDEs) with physical conditions. Laplace transform method (LTM) is used on the nondimensional governing equations for their closed-form solution. Based on these results, expressions for nondimensional shear stresses, rate of heat and mass transfer are also determined. Graphical presentations are chalked out to inspect the impacts of physical parameters on the pertinent physical flow characteristics. Numerical values of the shear stresses, rate of heat and mass transfer at the plate are tabulated for various physical parameters.

Findings

Numerical exploration reveals that a significant increase in the secondary flow (i.e. crossflow) near the plate is guaranteed with an augmenting in Hall parameter or ion slip parameter. MHD and porosity have an opposite effect on velocity component profiles for both types of nanoliquids. Result addresses that both shear stresses are strongly enhanced by the Casson effect. Also, hybrid nanosuspension in Casson fluid (sodium alginate) exhibits a lower rate of heat transfer than usual nanoliquid.

Social implications

This model may be pertinent in cooling processes of metallic infinite plate in bath and hybrid magnetohydrodynamic (MHD) generators, metallurgical process, manufacturing dynamics of nanopolymers, magnetic field control of material processing, synthesis of smart polymers, making of paper and polyethylene, casting of metals, etc.

Originality/value

The originality of this study is to obtain an analytical solution of the modeled problem by using the Laplace transform method (LTM). Such an exact solution of nonNewtonian fluid flow, heat and mass transfer is rare in the literature. It is also worth remarking that the influence of Hall and ion slip effects on the flow of nonNewtonian hybrid nanoliquid is still an open question.
A novel apparatus to measure the biomechanical properties of blood vessels
Authors: Guo Zhanshe , Zhang Taiyi , Liang Xiangdang , Wang Yutong
Published: June 2020

Purpose

The study of vascular mechanics is important. The purpose of this paper is to present an apparatus to measure the biomechanical properties of blood vessels, which can be used for tensile test and fatigue test.

Design/methodology/approach

This equipment consists of a mechanical test platform, a hardware circuit based on FPGA and control software. The torque generated by stepper motor is converted to axial force by ball screw, and the vascular specimen is stretched axially. The tension is measured by a load cell, and the displacement is recorded by a grating displacement sensor.

Findings

According to the results of calibration experiment and stability experiment, the linearity error of the system is 0.251, the hysteresis error is 0.047, the repeatability error is 0.185, the comprehensive error is 0.315 and the standard deviation of the output is less than 0.01 N. A test of animal vascular mechanical properties was carried out, and the results are consistent with the theory.

Originality/value

This apparatus is designed to measure biomechanical properties of blood vessels, and the results of experiments indicate that it is stable and reliable. This work is valuable for studying vascular disease and testing artificial blood vessels.
Modelling Financial Contagion Using High Frequency Data
Authors: Yao Wenying , Dungey Mardi , Alexeev Vitali
Published: June 2020

This paper develops a methodology for detecting and measuring contagion using high‐frequency data which disentangles continuous and discontinuous price movements. We demonstrate its finite‐sample properties using Monte Carlo simulation, focusing on the empirically plausible parameter space. Decisions to extend the role of financial regulation around the world to the supervision of insurers in the wake of the global financial crisis have been met with literature which supports both the systemic importance of insurers and contrasting evidence that insurers are rather the `victims' of shocks transmitted via banks. We contribute to this debate by considering the time‐varying evidence for contagion at both the firm level and the sector level. A number of insurance companies exhibit bank‐like characteristics. Our evidence for contagion effects from banks to the real economy, with similar impact from the insurers, supports the view that financial regulation on banks does need to be extended to the insurance sector.
Effectiveness of mandatory peer review to reduce antipsychotic prescriptions for Medicaid‐insured children
Authors: Akincigil Ayse , Mackie Thomas I. , Cook Sharon , Hilt Robert J. , Crystal Stephen
Published: June 2020

Background

Prior authorization of prescription medications is a policy tool that can potentially impact care quality and patient safety.

Objective

To examine the effectiveness of a mandatory peer‐review program in reducing antipsychotic prescriptions among Medicaid‐insured children, accounting for secular trends that affected antipsychotic prescribing nationally.

Data Source

Medicaid Analytical eXtracts (MAX) with administrative claims for health services provided between January 2006 and December 2011.

Study Design

This retrospective, observational study examined prescription claims records from Washington State (Washington) and compared them to a synthetic control drawing from 20 potential donor states that had not implemented any antipsychotic prior authorization program or mandatory peer review for Medicaid‐insured children during the study period. This method provided a means to control for secular trends by simulating the antipsychotic use trajectory that the program state would have been expected to experience in the absence of the policy implementation.

Principal Findings

Before the policy implementation, antipsychotic use prevalence closely tracked those of the synthetic control (6.17 per 1000 in Washington vs. 6.21 in the synthetic control group). Within two years after the policy was implemented, prevalence decreased to 4.04 in Washington and remained stable in the synthetic control group (6.47), corresponding to an approximately 38% decline.

Conclusion

Prior authorization program designs and implementations vary widely. This mandatory peer‐review program, with an authorization window and two‐stage rollout, was effective in moving population level statistics toward safe and judicious use of antipsychotic medications in children.
The Analysis of 3D Printer Dust for Forensic Applications,,
Authors: Brinsko‐Beckert Kelly , Palenik Christopher S.
Published: June 2020

3D printers are becoming increasingly efficient and economical, and thus more widespread and easily accessible to consumers and businesses. They have been used to print nefarious objects such as guns and suppressors. Previous research has documented the release of dust particles during the printing process; however, little has been written about the morphology and chemical features that define the dust emitted by these printers. This study was undertaken to recover, analyze, and identify the dust produced during the printing process in the context of forensic trace evidence analysis. Samples were collected from a variety of 3D fused deposition modeler printers, representing both consumer and commercial grade models. This work focused on printers that use thermoplastic filaments composed of acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA), two of the most commonly used filament polymers. Swabs were used to collect dust within the printer chamber and then processed to isolate the dust particles. Particles produced from ABS filaments are most easily recognized via light microscopy through a combination of color, morphology, and fluorescence. The composition of these particles can be confirmed through analysis by either FTIR or Raman microspectroscopy. These methods can also be used to identify ABS fillers and pigments within the printer dust particles. In contrast, dust from PLA printers consistently contained finer, submicron‐sized particles that could be observed by field emission scanning electron microscopy. Because the size of the particles precludes their identification using vibrational spectroscopy methods, pyrolysis‐GC‐MS was used to confirm the presence of PLA.
Finger thoracostomy in patients with chest trauma performed by paramedics on a helicopter emergency medical service
Authors: Hannon Liam , St Clair Toby , Smith Karen , Fitzgerald Mark , Mitra Biswadev , Olaussen Alexander , Moloney John , Braitberg George , Judson Rodney , Teague Warwick , Quinn Nuala , Kim Yesul , Bernard Stephen
Published: June 2020

Objective

To determine the frequency of finger thoracostomy performed by intensive care flight paramedics after the introduction of a training programme in this procedure and complications of the procedure that were diagnosed after hospital arrival.

Methods

This was a retrospective cohort study of adult and paediatric trauma patients undergoing finger thoracostomy performed by paramedics on a helicopter emergency medical service between June 2015 and May 2018. Hospital data were obtained through a manual search of the medical records at each of the three receiving major trauma services. Additional data were sourced from the Victorian State Trauma Registry.

Results

The final analysis included 103 cases, of which 73.8% underwent bilateral procedures with a total of 179 finger thoracostomies performed. The mean age of patients was 42.8 (standard deviation 21.4) years and 73.8% were male. Motor vehicle collision was the most common mechanism of injury accounting for 54.4% of cases. The median Injury Severity Score was 41 (interquartile range 29–54). There were 30 patients who died pre‐hospital, with most (n = 25) having finger thoracostomy performed in the setting of a traumatic cardiac arrest. A supine chest X‐ray was performed prior to intercostal catheter insertion in 38 of 73 patients arriving at hospital; of these, none demonstrated a tension pneumothorax. There were three cases of potential complications related to the finger thoracostomy.

Conclusion

Finger thoracostomy was frequently performed by intensive care flight paramedics. It was associated with a low rate of major complications and given the deficiencies of needle thoracostomy, should be the preferred approach for chest decompression.
Necrotising fasciitis from fulminant pyelonephritis
Authors: Bong Christopher Y. , Burstow Matthew J. , Yuide Peter J. , Chua Terence C.
Published: June 2020

Emphysematous pyelonephritis (EPN) is a severe urinary tract infection (UTI) that causes kidney necrosis by gas‐producing bacteria. Escherichia coli is most implicated. Type‐2 diabetes mellitus (T2DM) is a common predisposing factor. Necrotising fasciitis (NF) is an uncommon complication of EPN that has severe consequences. It is easily missed due to rarity. We present the case of an 82‐year‐old female nursing home resident with T2DM that presents with NF of the left flank following EPN of the left kidney that has penetrated through the superior lumbar triangle. This is the first time this anatomical pathway has been implicated in NF secondary to EPN in the English literature.
Reimbursement for therapeutic apheresis devices and procedures for using the healthcare insurance system in Japan
Authors: Kusaoi Makio , Murayama Go , Tamura Naoto , Yamaji Ken
Published: June 2020

The aim of this paper was to explain the insurance coverage status of therapeutic apheresis (excluding CHDF) in Japan, alongside the social system of medical reimbursement and concerns regarding the future sustainability of the healthcare system. Insurance schemes and premiums differed for individuals at different levels in the society (eg, municipal residents, employees, and public servants). Insurance premiums and their rates varied depending on the total household income, the number of people living together, age, and the place of residence. In addition, the medical expense subsidies for children through public expenditure were also described. Japan's generous insurance system and multiple medical expense subsidies provide financial support for patients. With Japan's history of medical expense subsidies based on the policy of supporting intractable diseases, we have established an environment where all citizens can receive therapeutic apheresis when needed if they are affected by a disease for which insurance coverage is indicated.