bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia
Authors: Miller Brandi D. , Tallman Christopher T. , Boone Timothy B. , Khavari Rose
Published: July 2019

Objectives

Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS.

Methods

Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values.

Results

The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%.

Conclusions

The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS.
Nonfatal motor vehicle related injuries among deployed US Service members: Characteristics, trends, and risks for limb amputations
Authors: Schweizer Marc A. , Janak Jud C. , Graham Brock , Mazuchowski Edward L. , Gurney Jennifer M. , Shackelford Stacy A. , Stockinger Zsolt T. , Monchal Tristan
Published: July 2019

BACKGROUND

Motor vehicle-related (MVR) incidents are important causes of morbidity among deployed US service members (SMs). Nonbattle MVR injuries are usually similar to civilian MVR injuries, while battle MVR injuries are often unique due to the blast effects from precipitating explosive mechanisms. Our primary objective was to describe the characteristics and trends of nonfatal MVR injuries sustained by deployed US SMs. A second objective was to assess the association between mechanism of injury (i.e., explosive vs. nonexplosive) and limb amputation.

METHODS

We conducted a retrospective cross-sectional analysis using data from the Department of Defense Trauma Registry collected from October 2001 to December 2018. Descriptive statistics were reported stratified by mechanism of injury (explosive vs. nonexplosive). The association between mechanism of injury and limb amputation was assessed using logistic regression models.

RESULTS

There were 3,119 US casualties who sustained nonfatal MVR injuries, 2,380 (76.3%) SMs sustained nonexplosive MVR injuries while 739 (23.7%) sustained explosive MVR injuries. Of all MVR casualties, 2,085 (66.9%) were in Iraq or Syria and 1034 (33.1%) in Afghanistan. The annual prevalence of nonfatal MVR battle casualties was highest in Iraq and Syria from 2003 to 2009 and Afghanistan from 2009 to 2014, ranging overall 15 to 50 MVR casualties per 1,000 wounded in action. There were 92 limb amputations associated with MVR incidents. Compared with nonexplosive MVR mechanisms, explosive MVR mechanisms had higher association with limb amputation (adjusted odds ratio, 2.6; confidence interval, 1.7–3.9), even after adjusting for injury year and Injury Severity Score (AOR, 2.1; confidence interval: 1.4–3.4).

CONCLUSION

Motor vehicle-related incidents are an important cause of injury in US military operations. Compared with nonexplosive MVR incidents, explosive MVR incidents result in more severe injuries, and have a higher associated risk of limb amputation. Continued efforts to improve injury prevention through protective equipment and medical training specific to MVR injuries are needed.

LEVEL OF EVIDENCE

Prognostic and epidemiological study, Level III.
Effect of partial and complete aortic balloon occlusion on survival and shock in a swine model of uncontrolled splenic hemorrhage with delayed resuscitation
Authors: Kauvar David S. , Schechtman David W. , Thomas Sarah B. , Prince M. Dale , De Guzman Rodolfo , Polykratis I. Amy , Kheirabadi Bijan S. , Dubick Michael A.
Published: July 2019

BACKGROUND

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is accepted as a resuscitation adjunct and bridge to definitive hemostasis. The ischemic burden of REBOA may be mitigated by a partial REBOA (P-REBOA) strategy permitting longer occlusion times and military use for combat trauma. We evaluated REBOA and P-REBOA in a swine multiple trauma model with uncontrolled solid organ hemorrhage and delayed resuscitation and surgical hemostasis.

METHODS

Anesthetized swine (51.9 ± 2.2 kg) had 20 mL/kg hemorrhage and closed femur fracture. Splenic transection was performed and free bleeding permitted for 10 minutes. Controls (n = 5) were hemorrhaged but had no REBOA, REBOA (n = 8) had 60 minutes complete zone 1 occlusion, P-REBOA (n = 8) had 15 minutes complete occlusion and 45 minutes 50% occlusion. Splenectomy was performed and plasma (15 mL/kg) resuscitation initiated 5 minutes prior to deflation. Resuscitation goal was 80 mm Hg systolic with epinephrine as needed. Animals were monitored for 6 hours.

RESULTS

An initial study with 120-minute occlusion had universal fatality in three REBOA (upon deflation) and three P-REBOA animals (after 60 minutes inflation). With 60-minute occlusion, mortality was 100%, 62.5%, and 12.5% in the control, REBOA, and P-REBOA groups, respectively (p < 0.05). Survival time was shorter in controls (120 ± 89 minutes) than REBOA and P-REBOA groups (241 ± 139, 336 ± 69 minutes). Complete REBOA hemorrhaged less during inflation (1.1 ± 0.5 mL/kg) than Control (5.6 ± 1.5) and P-REBOA (4.3 ± 1.4), which were similar. Lactate was higher in the REBOA group compared with the P-REBOA group after balloon deflation, remaining elevated. Potassium increased in REBOA after deflation but returned to similar levels as P-REBOA by 120 minutes.

CONCLUSION

In a military relevant model of severe uncontrolled solid organ hemorrhage 1-hour P-REBOA improved survival and mitigated hemodynamic and metabolic shock. Two hours of partial aortic occlusion was not survivable using this protocol due to ongoing hemorrhage during inflation. There is potential role for P-REBOA as part of an integrated minimally invasive field-expedient hemorrhage control and resuscitation strategy.
Resilience and long-term outcomes after trauma: An opportunity for early intervention?
Authors: Nehra Deepika , Herrera-Escobar Juan P. , Al Rafai Syeda S. , Havens Joaquim , Askari Reza , Nitzschke Stephanie , Velmahos George , Kasotakis George , Brasel Karen J. , Levy-Carrick Nomi , Salim Ali , Haider Adil
Published: July 2019

BACKGROUND

Resilience, or the ability to cope with difficulties, influences an individual's response to life events including unexpected injury. We sought to assess the relationship between patient self-reported resilience traits and functional and psychosocial outcomes 6 months after traumatic injury.

METHODS

Adult trauma patients 18 years to 64 years of age with moderate to severe injuries (Injury Severity Score, ≥9) admitted to one of three Level I trauma centers between 2015 and 2017 were contacted by phone at 6 months postinjury and asked to complete a validated Trauma Quality of Life (T-QoL) survey and PTSD screen. Patients were classified into “low” and “high” resilience categories. Long-term outcomes were compared between groups. Adjusted logistic regression models were built to determine the association between resilience and each of the long-term outcomes.

RESULTS

A total of 305 patients completed the 6-month interview. Two hundred four (67%) of the 305 patients were classified as having low resilience. Mean age was 42 ± 14 years, 65% were male, 91% suffering a blunt injury, and average Injury Severity Score was 15.4 ± 7.9. Patients in the low-resilience group had significantly higher odds of functional limitations in activities of daily living (odds ratio [OR], 4.81; 95% confidence interval [CI], 2.48–9.34). In addition, patients in the lower resilience group were less likely to have returned to work/school (OR, 3.25; 95% CI, 1.71–6.19), more likely to report chronic pain (OR, 2.57; 95% CI, 1.54–4.30) and more likely to screen positive for PTSD (OR, 2.96; 95% CI, 1.58–5.54).

CONCLUSION

Patients with low resilience demonstrated worse functional and psychosocial outcomes 6 months after injury. These data suggest that screening for resilience and developing and deploying early interventions to improve resilience-associated traits as soon as possible after injury may hold promise for improving important long-term functional outcomes.

LEVEL OF EVIDENCE

Prognostic, level II.
Artifact Mimicking Ictal Epileptiform Activity in EEG
Authors: McKay Jake H. , Tatum William O.
Published: July 2019

Although the EEG is designed to record cerebral activity, it also frequently records activity from extracerebral sources, leading to artifact. Differentiating rhythmical artifact from true electrographic ictal activity remains a substantial challenge to even experienced electroencephalographers because the sources of artifact able to mimic ictal activity on EEG have continued to increase with the advent of technology. Knowledge of the characteristics of the polarity and physiologic electrical fields of the brain, as opposed to those generated by the eyes, heart, and muscles, allows the electroencephalographer to intuitively recognize noncerebrally generated waveforms. In this review, we provide practical guidelines for the EEG interpreter to correctly identify physiologic and nonphysiologic artifacts capable of mimicking electrographic seizures. In addition, we further elucidate the common pitfalls in artifact interpretation and the costly impact of epilepsy misdiagnosis due to artifact.
Alternative Splicing of MR1 regulates antigen presentation to MAIT cells
Authors: Narayanan Gitanjali A. , Nellore Abhinav , Tran Jessica G. , Worley Aneta H. , Meermeier Erin W. , Karamooz Elham , Huber Megan , Kurapova Regina , Tafesse Fikadu , Harriff Melanie J. , Lewinsohn David M.
Published: July 2019

Mucosal Associated Invariant T (MAIT) cells can sense intracellular infection by a broad array of pathogens. These cells are activated upon encountering microbial antigen(s) displayed by MR1 on the surface of an infected cell. Human MR1 undergoes alternative splicing. The full length isoform, MR1A, can activate MAIT cells, while the function of the isoforms, MR1B and MR1C, are not well characterized.

In this report, we sought to characterize these splice variants. Using a transcriptomic analysis in conjunction with qPCR, we find that that MR1A and MR1B transcripts are widely expressed. Despite the widespread expression of MR1A and MR1B, only MR1A can present mycobacterial antigen to MAIT cells. Coexpression of MR1B with MR1A serves to decrease MAIT cell activation following bacterial infection. However, expression of MR1B prior to MR1A lowers total MR1A abundance, suggesting competition between MR1A and MR1B for either ligands or chaperones required for folding and/or trafficking. Finally, we evaluated CD4/CD8 double positive thymocytes expressing surface MR1. RelativeMR1A/MR1Bexpression in MR1-expressing thymocytes is associated with their prevalence.

Our results suggest alternative splicing of MR1 represents a means of regulating MAIT activation in response to microbial ligand.

Funding

This work was supported by NIH T32HL083808 (EK, GAN, EM), VA Merit Award I01CX001562 (MJH), NIH R01AI29976 (MJH), NIH R01AI048090 (DML), NIH R21AI124225-01A1 (FT) and VA Merit Award I01BX000533 (DML). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
Ultraconserved non-coding DNA within insect phyla
Authors: Brody Thomas , Yavatkar Amar , Kuzin Alexander , Odenwald Ward F.
Published: July 2019

Presence of ultra-conserved sequence elements in vertebrate enhancers suggest that transcription factor regulatory interactions are shared across phylogenetically diverse species. To date evidence for similarly conserved elements among evolutionarily distant insects such as flies, mosquitos, ants and bees, has been elusive. This study has taken advantage of the availability of the assembled genomic sequence of these insects to explore the presence of ultraconserved sequence elements in these phylogenetic groups. To investigate the integrity of fly regulatory sequences across ~100 million years of evolutionary divergence from the fruitfly Drosophila melanogaster, we compared Drosophila non-coding sequences to those of Ceratitis capitata, the Mediterranean fruit fly and Musca domestica, the domestic housefly. Using various alignment techniques, Blastn, Clustal, Blat, EvoPrinter and Needle, we show that many of the conserved sequence blocks (CSBs) that constitute Drosophila cis-regulatory DNA, recognized by EvoPrinter alignment protocols, are also conserved in Ceratitis and Musca. We term the sequence elements shared among these species ultraconserved CSBs (uCSBs). The position of the uCSBs with respect to flanking genes is also conserved. The results suggest that CSBs represent the point of interaction of multiple trans-regulators whose functions and interactions are conserved across divergent genera. Blastn alignments also detect putative cis-regulatory sequences shared among evolutionarily distant mosquitos Anopheles gambiae and Culex pipiens and Aedes aegypti. We have also identified conserved sequences shared among bee species. Side by side comparison of bee and ant EvoPrints identify uCSBs shared between the two taxa, as well as more poorly conserved CSBs in either one or the other taxon but not in both. Analysis of uCSBs in dipterans, mosquitos and bees will lead to a greater understanding of their evolutionary origin and the function of their conserved sequences.
DIALib: an automated ion library generator for data independent acquisition mass spectrometry analysis of peptides and glycopeptides
Authors: Phung Toan K. , Zacchi Lucia F , Schulz Benjamin L.
Published: July 2019

Data Independent Acquisition (DIA) Mass Spectrometry (MS) workflows allow unbiased measurement of all detectable peptides from complex proteomes, but require ion libraries for interrogation of peptides of interest. These DIA ion libraries can be theoretical or built from peptide identification data from Data Dependent Acquisition (DDA) MS workflows. However, DDA libraries derived from empirical data rely on confident peptide identification, which can be challenging for peptides carrying complex post-translational modifications. Here, we present DIALib, software to automate the construction of peptide and glycopeptide Data Independent Acquisition ion Libraries. We show that DIALib theoretical ion libraries can identify and measure diverse N- and O-glycopeptides from yeast and mammalian glycoproteins without prior knowledge of the glycan structures present. We present proof-of-principle data from a moderately complex yeast cell wall glycoproteome and a simple mixture of mammalian glycoproteins. We also show that DIALib libraries consisting only of glycan oxonium ions can quickly and easily provide a global compositional glycosylation profile of the detectable “oxoniome” of glycoproteomes. DIALib will help enable DIA glycoproteomics as a complementary analytical approach to DDA glycoproteomics.
Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology
Authors: Li Qiang , Nan Kewang , Le Floch Paul , Lin Zuwan , Sheng Hao , Liu Jia
Published: July 2019

Tissue-wide electrophysiology with single-cell and millisecond spatiotemporal resolution is critical for heart and brain studies, yet issues arise from invasive, localized implantation of electronics that destructs the well-connected cellular networks within matured organs. Here, we report the creation of cyborg organoids: the three-dimensional (3D) assembly of soft, stretchable mesh nanoelectronics across the entire organoid by cell-cell attraction forces from 2D-to-3D tissue reconfiguration during organogenesis. We demonstrate that stretchable mesh nanoelectronics can grow into and migrate with the initial 2D cell layers to form the 3D structure with minimal interruptions to tissue growth and differentiation. The intimate contact of nanoelectronics to cells enables us to chronically and systematically observe the evolution, propagation and synchronization of the bursting dynamics in human cardiac organoids through their entire organogenesis.
Systematic Description of 3q29 Duplication Syndrome Reveals New Syndromic Phenotypes: Results from the 3q29 Registry
Authors: Pollak Rebecca M , Zinsmeister Michael C , Murphy Melissa M , Zwick Michael E ,   the Emory 3q29 Project, Mulle Jennifer G
Published: July 2019

3q29 duplication syndrome (3q29Dup) is a rare genomic disorder caused by the reciprocal duplication of the 1.6 Mb 3q29 deletion syndrome region. Case reports indicate the 3q29Dup is likely to be pathogenic, but because no systematic study of the syndrome exists, the full range of manifestations is not well-understood. To develop a better understanding of 3q29 duplication syndrome, we used the 3q29 registry (https://3q29deletion.patientcrossroads.org/) to ascertain 31 individuals with 3q29Dup, the largest cohort ever surveyed in a systematic way. For comparison, we ascertained 117 individuals with the reciprocal 3q29 deletion syndrome (3q29Del) and 64 typically developing controls. We used a custom medical and demographic questionnaire to assess physical and developmental phenotypes, and two standardized instruments, the Social Responsiveness Scale (SRS) and Achenbach Behavior Checklists (CBCL/ABCL), to assess social disability. We find that our 3q29Dup participants report a high rate of problems in the first year of life (80.6%), including feeding problems (58%), failure to gain weight (42%), hypotonia (39%), and respiratory distress (29%). In early childhood, learning problems (87.1%) and seizures (25.8%) are common. Additionally, we find a rate of self-reported ASD diagnoses (39%) similar to that previously identified in 3q29Del (29%), and the granular characteristics of social disability measured using the SRS and CBCL/ABCL are comparable between 3q29Dup and 3q29Del. This is the most comprehensive description of 3q29Dup to date. Our findings can be used to develop evidence-based strategies for early intervention and management of 3q29 duplication syndrome.
PACVr: Plastome Assembly Coverage Visualization in R
Authors: Gruenstaeudl Michael , Jenke Nils
Published: July 2019

Background

The circular, quadripartite structure of plastid genomes which includes two inverted repeat regions renders the automatic assembly of plastid genomes challenging. The correct assembly of plastid genomes is a prerequisite for the validity of subsequent analyses on plastid genome structure and evolution. Plastome-based phylogenetic or population genetic investigations, for example, require the precise identification of DNA sequence and length to determine the location of nucleotide polymorphisms. The average coverage depth of a genome assembly is often used as an indicator for assembly quality. Visualizing coverage depth across a draft genome allows users to inspect the quality of the assembly and, where applicable, identify regions of reduced assembly confidence. Based on such visualizations, users can conduct a local re-assembly or other forms of targeted error correction. Few, if any, contemporary software tools can visualize the coverage depth of a plastid genome assembly while taking its quadripartite structure into account, despite the interplay between genome structure and assembly quality. A software tool is needed that visualizes the coverage depth of a plastid genome assembly on a circular, quadripartite map of the plastid genome.

Results

We introduce ‘PACVr’, an R package that visualizes the coverage depth of a plastid genome assembly in relation to the circular, quadripartite structure of the genome as well as to the individual plastome genes. The tool allows visualizations on different scales using a variable window approach and also visualizes the equality of gene synteny in the inverted repeat regions of the plastid genome, thus providing an additional measure of assembly quality. As a tool for plastid genomics, PACVr provides the functionality to identify regions of coverage depth above or below user-defined threshold values and helps to identify non-identical IR regions. To allow easy integration into bioinformatic workflows, PACVr can be directly invoked from a Unix shell, thus facilitating its use in automated quality control. We illustrate the application of PACVr on two empirical datasets and compare the resulting visualizations with alternative software tools for displaying plastome sequencing coverage.

Conclusions

PACVr provides a user-friendly tool to visualize (a) the coverage depth of a plastid genome assembly on a circular, quadripartite plastome map and in relation to individual plastome genes, and (b) the equality of gene synteny in the inverted repeat regions. It, thus, contributes to optimizing plastid genome assemblies and increasing the reliability of publicly available plastome sequences, especially in light of incongruence among the visualization results of alternative software tools. The software, example datasets, technical documentation, and a tutorial are available with the package at https://github.com/michaelgruenstaeudl/PACVr.
StructureDistiller: Structural relevance scoring increases resilience of contact maps to false positive predictions
Authors: Bittrich Sebastian , Schroeder Michael , Labudde Dirk
Published: July 2019

Protein folding and structure prediction are two sides of the same coin. We propose contact maps and the related techniques of constraint-based structure reconstruction as unifying aspect of both processes. The presented Structural Relevance (SR) score quantifies the contribution of individual contacts and residues to structural integrity.

It is demonstrated that entries of a contact map are not equally relevant for structural integrity. Structure prediction methods should explicitly consider the most relevant contacts for optimal performance because they effectively double resilience toward false positively predicted contacts. Furthermore, knowledge of the most relevant contacts significantly increases reconstruction fidelity on sparse contact maps by 0.4 Å.

Protein folding is commonly characterized with spatial and temporal resolution: some residues are Early Folding while others are Highly Stable with respect to unfolding events. Using the proposed SR score, we demonstrate that folding initiation and structure stabilization are distinct processes.
Cross-kingdom recognition of bacterial small RNAs induces transgenerational pathogenic avoidance
Authors: Kaletsky Rachel , Moore Rebecca S. , Parsons Lance L. , Murphy Coleen T.
Published: July 2019

We recently discovered that C. elegans can pass on a learned avoidance of pathogenic Pseudomonas aeruginosa (PA14) to four generations of its progeny. This transgenerational inheritance is bacterial species-specific, but how C. elegans recognizes and distinguishes different bacteria and transmits this information to future generations is not apparent. Here we show that small RNAs purified from pathogenic PA14 are sufficient not only to induce avoidance of pathogens in mothers, but also to confer transgenerational inheritance of this species-specific behavior for four generations, all without direct contact with pathogenic bacteria. This behavior requires the small RNA transporters SID-1 and SID-2, RNA interference pathway components, the piRNA Piwi/Argonaute pathway, a functioning germline, and TGF-β ligand daf-7 expression in the ASI sensory neuron. Our results suggest that C. elegans “reads” small RNAs expressed by pathogenic bacteria, and uses this information to induce an escape behavior that lasts for four additional generations. C. elegans may have evolved this trans-kingdom signaling system to avoid pathogens in abundant classes of bacteria in its environment and its microbiome.
Classification of columnar and salt-and-pepper organization in mammalian visual cortex
Authors: Jang Jaeson , Song Min , Paik Se-Bum
Published: July 2019

In mammalian visual cortex, neural tuning to stimulus orientation is organized in either columnar1 or salt- and-pepper2 patterns across species. This is often considered to reflect disparate mechanisms of cortical development across mammalian taxa. However, it is unknown whether different cortical architectures are generated by species-specific mechanisms3,4, or simply originate from the variation of biological parameters within a universal principle of development5–8. We analysed neural parameters in eight mammalian species and found that cortical organization is predictable by a single factor: the retino-cortical mapping ratio. We show that a Nyquist sampling model explains parametric division of the patterns with high accuracy and that simulations of controlled mapping conditions reproduce both types of organization. Our results explain the origin of distinct cortical circuits under a universal development process.
Dynamic regulation of chromatin accessibility by pluripotency transcription factors across the cell cycle
Authors: Friman Elias T. , Deluz Cédric , Meireles-Filho Antonio C.A. , Govindan Subashika , Gardeux Vincent , Deplancke Bart , Suter David M.
Published: July 2019

The pioneer activity of transcription factors allows for opening of inaccessible regulatory elements and has been extensively studied in the context of cellular differentiation and reprogramming. In contrast, the function of pioneer activity in self-renewing cell divisions and across the cell cycle is poorly understood. Here we assessed the interplay between OCT4 and SOX2 in controlling chromatin accessibility of mouse embryonic stem cells. We found that OCT4 and SOX2 operate in a largely independent manner even at co-occupied sites, and that their cooperative binding is mostly mediated indirectly through regulation of chromatin accessibility. Controlled protein degradation strategies revealed that the uninterrupted presence of OCT4 is required for post-mitotic re-establishment and interphase maintenance of chromatin accessibility, and that highly OCT4-bound enhancers are particularly vulnerable to transient loss of OCT4 expression. Our study sheds light on the constant pioneer activity required to maintain the dynamic pluripotency regulatory landscape in an accessible state.
Negative Regulation of Autophagy by UBA6-BIRC6–Mediated Ubiquitination of LC3
Authors: Jia Rui , Bonifacino Juan S.
Published: July 2019

Although the process of autophagy has been extensively studied, the mechanisms that regulate it remain insufficiently understood. The ability to manipulate autophagy is important not only for addressing fundamental biological questions, but also for its possible application to the treatment of various human diseases. To identify novel regulators of autophagy, we performed a whole-genome CRISPR/Cas9 knockout screen in H4 human neuroblastoma cells gene-edited to express the endogenous autophagy effector LC3B fused to a tandem of GFP and mCherry. Using this methodology, we identified the ubiquitin-activating (E1) enzyme UBA6 and the hybrid ubiquitin-conjugating (E2)/ubiquitin-ligase (E3) enzyme BIRC6 as important autophagy regulators. We found that these two enzymes cooperate to monoubiquitinate LC3B on lysine-51, targeting it for degradation by the proteasome. Knockout of UBA6 or BIRC6 increased the levels of LC3B as well as autophagic flux under conditions of nutrient deprivation or protein synthesis inhibition. Moreover, depletion of UBA6 or BIRC6 KO decreased the formation of aggresome-like induced structures in H4 cells, and aggregates of an α-synuclein mutant in the axon of rat hippocampal neurons. These findings demonstrate that UBA6 and BIRC6 negatively regulate autophagy by limiting the availability of LC3B, possibly to prevent the deleterious effects of excessive autophagy. Inhibition of UBA6 or BIRC6, on the other hand, could be used to enhance autophagic clearance of protein aggregates in neurodegenerative disorders.
HBMITool: a user-friendly software for labeling Human Brain Microscopy Images
Authors: Wang Hungju , Grinberg Lea T , Alegro Maryana
Published: July 2019

One of the most popular tools for quantifying protein expression is Immunofluorescence (IF). Although IF is widely applied in drug discovery research and assessing disease mechanisms, it has great room for improvement on the task of analyzing human postmortem brain samples. IF analysis of postmortem human tissue relies mostly on manual interaction, which is often error-prone and leading to low inter and intra-observer reproducibility. The high level of autofluorescence caused by accumulation of lipofuscin pigment during aging impedes systematic analyses of human postmortem brain samples. A method for automating cell counting and classification in IF microscopy of human postmortem brains was proposed before, which speeds up the quantification task while improving reproducibility. To correct for misclassified cells by the algorithm, we created HBFMTool, a software package that ease the process of editing the result produced by cell detection/classification algorithm.
Differential expansion microscopy
Authors: Pernal Sebastian P. , Liyanaarachchi Asiri , Gatti Domenico L. , Formosa Brent , Pulvender Rishika , Kuhn Eric R. , Ramos Rafael , Naik Akshata R. , George Kathleen , Arslanturk Suzan , Taatjes Douglas J. , Jena Bhanu P.
Published: July 2019

Expansion microscopy (ExM) involves the use of hydration-competent polymers to physically expand biological specimens approximately 4-fold linear increase to achieve 70 nanometer resolution using an ordinary diffraction limited optical microscope. Optimal conditions however for antigen retention during the expansion process and the relative expansion between organelles within cells has remained unclear. It is reported that different tissues expand to different extents, suggesting that although isotropic expansion is believed to occur, different subcellular compartments with different composition would undergo anisotropic or differential expansion (DiEx). Consequently, there would be distortion of the native shape and size of subcellular compartments upon expansion, parameters which are critical in assessing cellular states in health and disease. Here we report optimal fixation and expansion conditions that retain structural integrity of cells while exhibiting up to 8-fold linear and therefore 512-fold volumetric expansion. Anisotropic expansion is observed not just between tissues, but between different subcellular compartments and even within subcellular compartments. Combining image analysis and machine learning, we provide an approach for the rapid and precise measurement of cellular and subcellular structures in expanded tissue. Using both manual and computation assessment of morphometric parameters, we demonstrate expansion to be anisotropic and name this method differential expansion microscopy (DiExM).
The tumor immune response is not compromised by mesenchymal stromal cells in humanized mice
Authors: Moquin-Beaudry Gaël , Colas Chloé , Li Yuanyi , Bazin Renée , Guimond Jean V. , Haddad Elie , Beauséjour Christian
Published: July 2019

Therapeutic uses of mesenchymal stromal cells (MSCs) have emerged over the past decade. Yet, their effect on tumor growth remains highly debated, particularly in an immune competent environment. Here, we wanted to investigate the impact of human umbilical cord MSCs (hUC-MSCs) on tumor growth in humanized mice generated by the adoptive transfer of peripheral blood mononuclear cells (Hu-AT) or the co-transplantation of hematopoietic stem cells and human thymic tissue (Hu-BLT). Our results showed that the growth and immune rejection of engineered human tumors was not altered by the injection of hUC-MSCs in immune-deficient or humanized mice respectively. This was observed whether tumor cells were injected subcutaneously or intravenously and independently of the injection route of the hUC-MSCs. Moreover, only in Hu-BLT mice did hUC-MSCs have some effects on the tumor immune infiltrate, yet without altering tumor growth. These results demonstrate that hUC-MSCs do not promote tumor growth and neither do they prevent tumor infiltration and rejection by immune cells in humanized mice.
Automated serial rotation electron diffraction combined with cluster analysis: an efficient multi-crystal workflow for structure determination
Authors: Wang Bin , Zou Xiaodong , Smeets Stef
Published: July 2019

Serial rotation electron diffraction (SerialRED) has been developed as a fully automated technique for three-dimensional electron diffraction data collection that can run autonomously without human intervention. It builds on the previously established serial electron diffraction technique, in which submicrometre-sized crystals are detected using image processing algorithms. Continuous rotation electron diffraction (cRED) data are collected on each crystal while dynamically tracking the movement of the crystal during rotation using defocused diffraction patterns and applying a set of deflector changes. A typical data collection screens up to 500 crystals per hour, and cRED data are collected from suitable crystals. A data processing pipeline is developed to process the SerialRED data sets. Hierarchical cluster analysis is implemented to group and identify the different phases present in the sample and to find the best matching data sets to be merged for subsequent structure analysis. This method has been successfully applied to a series of zeolites and a beam-sensitive metal–organic framework sample to study its capability for structure determination and refinement. Two multi-phase samples were tested to show that the individual crystal phases can be identified and their structures determined. The results show that refined structures obtained using automatically collected SerialRED data are indistinguishable from those collected manually using the cRED technique. At the same time, SerialRED has lower requirements of expertise in transmission electron microscopy and is less labor intensive, making it a promising high-throughput crystal screening and structure analysis tool.
X-ray photon correlation spectroscopy of protein dynamics at nearly diffraction-limited storage rings
Authors: Möller Johannes , Sprung Michael , Madsen Anders , Gutt Christian
Published: July 2019

This study explores the possibility of measuring the dynamics of proteins in solution using X-ray photon correlation spectroscopy (XPCS) at nearly diffraction-limited storage rings (DLSRs). We calculate the signal-to-noise ratio (SNR) of XPCS experiments from a concentrated lysozyme solution at the length scale of the hydrodynamic radius of the protein molecule. We take into account limitations given by the critical X-ray dose and find expressions for the SNR as a function of beam size, sample-to-detector distance and photon energy. Specifically, we show that the combined increase in coherent flux and coherence lengths at the DLSR PETRA IV yields an increase in SNR of more than one order of magnitude. The resulting SNR values indicate that XPCS experiments of biological macromolecules on nanometre length scales will become feasible with the advent of a new generation of synchrotron sources. Our findings provide valuable input for the design and construction of future XPCS beamlines at DLSRs.
Fluid-structure interaction analysis of transient convection heat transfer in a cavity containing inner solid cylinder and flexible right wall
Authors: Alsabery Ammar I. , Saleh Habibis , Ghalambaz Mohammad , Chamkha Ali J. , Hashim Ishak
Published: July 2019

Purpose

This paper aims to investigate the fluid structure interaction analysis of conjugate natural convection in a square containing internal solid cylinder and flexible right wall.

Design/methodology/approach

The right wall of the cavity is flexible, which can be deformed due to the interaction with the natural convection flow in the cavity. The top and bottom walls of the cavity are insulated while the right wall is cold and the left wall is partially heated. The governing equations for heat, flow and elastic wall, as well as the grid deformation are written in Arbitrary Lagrangian–Eulerian formulation. The governing equations along with their boundary conditions are solved using the finite element method.

Findings

The results of the present study show that the presence of the solid cylinder strongly affects the transient solution at the initial times. The natural convection flow changes the shape of the flexible right wall of the cavity into S shape wall due to the interaction of the flow and the structure. It is found that the increase of the flexibility of the right wall increases the average Nusselt number of the hot wall up to 2 per cent.

Originality/value

To the best of the authors' knowledge, the unsteady natural convection in an enclosure having a flexible wall and inner solid cylinder has never been reported before.
Comparison of the experimental and numerical analyses of silver nanofluid under influence of strong magnetic field
Authors: Fornalik-Wajs Elzbieta , Roszko Aleksandra , Donizak Janusz , Kraszewska Anna
Published: July 2019

Purpose

Nanofluids’ properties made them interesting for various areas like engineering, medicine or cosmetology. Discussed here, research pertains to specific problem of heat transfer enhancement with application of the magnetic field. The main idea was to transfer high heat rates with utilization of nanofluids including metallic non-ferrous particles. The expectation was based on changed nanofluid properties. However, the results of experimental analysis did not meet it. The heat transfer effect was smaller than in the case of base fluid. The only way to understand the process was to involve the computational fluid dynamics, which could help to clarify this issue. The purpose of this research is deep understanding of the external magnetic field effect on the nanofluids heat transfer.

Design/methodology/approach

In presented experimental and numerical studies, the water and silver nanofluids were considered. From the numerical point of view, three approaches to model the nanofluid in the strong magnetic field were used: single-phase Euler, Euler–Euler and Euler–Lagrange. In two-phase approach, the momentum transfer equations for individual phases were coupled through the interphase momentum transfer term expressing the volume force exerted by one phase on the second one.

Findings

Therefore, the results of numerical simulation predicted decrease of convection heat transfer for nanofluid with respect to pure water, which agreed with the experimental results. The experimental and numerical results are in good agreement with each other, which confirms the right choice of two-phase approach in analysis of nanofluid thermo-magnetic convection.

Originality/value

The Euler–Lagrange exhibit the best matching with the experimental results.
Numerical simulation of the interaction between a vortex ring and a bubble plume
Authors: Nguyen Van Luc , Degawa Tomohiro , Uchiyama Tomomi
Published: July 2019

Purpose

This paper aims to provide discussions of a numerical method for bubbly flows and the interaction between a vortex ring and a bubble plume.

Design/methodology/approach

Small bubbles are released into quiescent water from a cylinder tip. They rise under the buoyant force, forming a plume. A vortex ring is launched vertically upward into the bubble plume. The interactions between the vortex ring and the bubble plume are numerically simulated using a semi-Lagrangian–Lagrangian approach composed of a vortex-in-cell method for the fluid phase and a Lagrangian description of the gas phase.

Findings

A vortex ring can transport the bubbles surrounding it over a distance significantly depending on the correlative initial position between the bubbles and the core center. The motion of some bubbles is nearly periodic and gradually extinguishes with time. These bubble trajectories are similar to two-dimensional-helix shapes. The vortex is fragmented into multiple regions with high values of Q, the second invariant of velocity gradient tensor, settling at these regional centers. The entrained bubbles excite a growth rate of the vortex ring's azimuthal instability with a formation of the second- and third-harmonic oscillations of modes of 16 and 24, respectively.

Originality/value

A semi-Lagrangian–Lagrangian approach is applied to simulate the interactions between a vortex ring and a bubble plume. The simulations provide the detail features of the interactions.
Estimation of building heat transfer coefficients from in-use data
Authors: Li Matthew , Allinson David , Lomas Kevin
Published: July 2019

Purpose

The purpose of this paper is to identify the impact of traditionally unmonitored energy sources and sinks on assessment of the as-built thermal performance of occupied homes. The analysis aims to demonstrate the potential scale of uncertainties introduced in a heat balance estimation of the heat transfer coefficient (HTC) when using in-use monitored data.

Design/methodology/approach

Energy flows for two UK homes – one a 1930s dwelling with high heat loss, the second a higher-performing 2014-built home – are predicted using the UK Government’s standard assessment procedure (SAP) and visualised using Sankey diagrams. Selected modelled energy flows are used as inputs in a quasi-steady state heat balance to calculate in-use HTCs as if from measured data sets gathered in occupied homes. The estimated in-use HTCs are compared against SAP-calculated values to illustrate the impact of including or omitting various heat sources and sinks.

Findings

The results demonstrate that for dwellings with low heat loss, the increased proportion of heating demand met by unmetered internal and solar gains informs a greater sensitivity of a heat balance estimation of the HTC to their omission. While simple quasi-steady state heat balance methods may be appropriate for dwellings with very high heat loss, alternative approaches are likely to be required for those with lower heat loss.

Originality/value

A need to understand the impacts of unmetered heat flows on the accuracy with which a building’s thermal performance may be inferred from in-use monitored data is identified: this paper illustrates the scale of these impacts for two homes at opposite ends of the energy performance scale.
The effect of fellow customer on complaining behaviors: the moderating role of gender
Authors: Joe Sungjun , Choi Choongbeom
Published: July 2019

Purpose

This paper aims to examine the joint effect of the focal customer’s gender and fellow customer’s gender in influencing voice complaint intentions and intention to convey negative word of mouth (NWOM).

Design/methodology/approach

Participants were randomly assigned to one of the two dining conditions (same-gender fellow customer vs opposite-gender fellow customer). Their intention to voice a complaint and to spread NWOM were measured after reading a scenario describing a service failure. A 2 (focal customer gender: male vs female) × 2 (fellow customer: same gender vs opposite gender) between-subjects quasi-experimental design was conducted to test the hypotheses.

Findings

The results demonstrate that female customers’ voice complaint intentions were significantly higher when a fellow customer’s gender was female rather than male. In contrast, regardless of the fellow customer’s gender, no significant differences in voice complaint intentions were found among male customers. The results further indicate that voice complaint intentions mediate the impact of a fellow customer’s gender on intention to spread NWOM among female customers. However, both female and male participants show equally high levels of voice complaint intentions in the context of fine-dining restaurant.

Practical implications

This study broadens the understanding of customer complaining behavior and also provides insights to practitioners on how to manage customers who are in same- and mixed-gender situations.

Originality/value

This research extends the literature on agency–communal theory and complaining behaviors by examining the role of a fellow customer’s gender influencing the focal customer’s intentions to voice complaints and to spread NWOM.
Investigating the role of contextual factors in effectively executing communication evaluation and measurement
Authors: Romenti Stefania , Murtarelli Grazia , Miglietta Angelo , Gregory Anne
Published: July 2019

Purpose

Evaluation and measurement (E&M) remains a critical and debated topic among communication scholars and practice. Substantial research and professional efforts have been devoted to discussing what should be measured and which methods should be applied. Most of the E&M models seem to carry a positivist imprint. But, in real-life, organizations could not have clear aims, enough resources, or adequate informative systems to support E&M. Moreover, several contextual factors could affect the implementation of E&M management processes. The communication literature rarely highlights these factors. To fulfill this gap, the purpose of this paper is to theorize the contextual factors relevant to the management of the evaluation process.

Design/methodology/approach

A scoping literature review was carried out exploring the role of contextual factors and impact of contextual factors on E&M management processes. More specifically, the review examines the contribution provided by program evaluation and performance measurement (PM) fields of research.

Findings

The paper provides a scoping review of program evaluation and PM approaches. Additionally, it explains how both streams of thought argued the importance of contextual factors, such as organizational, relational, cultural and communicative factors, for the success of any evaluation processes. The study underlined that the main evaluation models used in the field of communication have overlooked these studies and put on evidence the role of contextual factors in effectively executing communication E&M.

Originality/value

The paper enriches the dominant rationale concerning the E&M management processes by incorporating literature on: program evaluation; and PM. The analysis could provide useful insights also from a professional perspective, by helping practitioners for a contextual assessment of strategic communication programs and activities.