bluuebunny/crossref_metadata_2025 huggingface dataset:
The Alignment of the Nose in Rhinoplasty: Fix Down Concept
Authors: Taş Süleyman
Published: November 2019

Background:

The current literature on rhinoplasty focuses mainly on the nasal profile (sagittal plane); however, the nose is a three-dimensional structure, and alignment of the nose in consideration of other aspects is important to achieve an aesthetic result. The author aimed to introduce the fix down concept, which includes fix down technique and the adjunct maneuvers for achieving alignment of the nose in three anatomical planes and improving the results of rhinoplasty in terms of symmetry.

Methods:

Between March of 2017 and December of 2017, a total of 102 patients (78 women and 24 men), 13 revision and 89 primary cases, underwent septorhinoplasty with the fix down concept. The noses were evaluated in coronal, sagittal, and axial planes and classified according to their deformities.

Results:

The functional and aesthetic results were satisfactory for the patients, examiners, and surgeon. No revisions were necessary during the follow-up period. In addition to the fix down technique, ethmoid bone grafting (16 patients), fix up technique (eight patients), dissection of the levator labii superioris alaeque nasi muscle (14 patients), plication of this muscle (four patients), superior-based transposition flap (39 patients), rim grafts (17 patients), mucosa grafts (12 patients), double-layer grafts (nine patients), maxillary deepening (five patients), maxillary augmentation with cartilage/bone grafts (21 patients), and supratip onlay grafts (seven patients) were used as adjunctive maneuvers to achieve symmetry in the frontal, base, and profile views.

Conclusion:

The presented fix down concept will help to provide three-dimensional symmetric noses for rhinosurgeons.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Interventions to reduce acute hepatitis C virus in HIV-positive MSM
Authors: Elliott Tamara , Cooke Graham S. , Garvey Lucy
Published: November 2019

Purpose of review

The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets.

Recent findings

With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing.

Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
Facing increased sexually transmitted infection incidence in HIV preexposure prophylaxis cohorts: what are the underlying determinants and what can be done?
Authors: Kenyon Chris , Van Dijck Christophe , Florence Eric
Published: November 2019

Purpose of review

The combined incidence of chlamydia, gonorrhoea and syphilis in MSM PrEP (preexposure prophylaxis) cohorts now frequently exceeds 100 per 100 person years. The efficacy of antiretroviral PrEP in reducing HIV transmission has led to efforts to find similar biomedical ways reduce sexually transmitted infection (STI) incidence. We review the recent evidence for these and other strategies.

Recent findings

Doxycycline PrEP/postexposure prophylaxis has been shown to reduce the incidence of syphilis and chlamydia but not gonorrhoea. A meningococcal vaccine has been found to result in a lower incidence of gonorrhoea. Novel insights into the role of the pharynx in the transmission of gonorrhoea have led to clinical trials of oral antiseptics to reduce the spread of gonorrhoea. Intensified STI screening has been introduced in a number of clinics. Serious concerns have however been raised about the emergence of resistance to each of these strategies. This is particularly true for doxycycline PrEP which is not advocated by any guidelines we reviewed.

Randomized controlled trials are urgently required to ascertain the benefits and risks of interventions to reduce STIs in MSM PrEP cohorts.
Comparison of Quantitative Perfusion and Function Parameters of Gated-SPECT Myocardial Perfusion Imaging in Patients With Concordant and Discordant Left Bundle-Branch Block
Authors: Ghaedian Tahereh , Behbudnia Tuba , Dehghani Pooyan
Published: November 2019

Background

Patients with left bundle-branch block (LBBB) can be classified to discordant LBBB (dLBBB) and concordant LBBB (cLBBB) according to T-wave orientation in lateral leads. This classification indicates different functional left ventricular (LV) parameters with worse prognosis in dLBBB patients. However, there are no data regarding the impact of this classification on perfusion status of the left ventricle. The aim of this study is to evaluate and compare the SPECT myocardial perfusion imaging (MPI) findings of LV perfusion and function between dLBBB and cLBBB patients.

Methods

All patients who were referred for SPECT MPI during an 11 months' period were evaluated. Patients with evidence of LBBB on standard baseline 12-lead ECG were included, and their demographic, medical history, and imaging data were recorded. Quantitative perfusion and function parameters of LV included summed stress score, summed rest score, summed difference score, total perfusion deficit (TPD) at both phases with delta TPD, ejection fraction, end-diastolic volume, end-systolic volume, summed motion score, summed thickening score, phase SD, and phase histogram bandwidth. All baseline ECGs were further assessed by a cardiologist to categorize patients as the cLBBB or dLBBB group according to concordance of the T wave with QRS complex in lateral leads.

Results

Finally, 97 patients with 46 cLBBB and 51 dLBBB cases were included. Baseline characteristics and cardiovascular risk factors including diabetes mellitus, hypertension, hyperlipidemia, history of coronary artery disease (CAD), family history of CAD, and smoking were not significantly different between the 2 groups. However, summed stress score (12.2 vs 6.7), summed difference score (4.0 vs 2.6), stress TPD (11.0 vs 6.4), and delta TPD (4.8 vs 3.9) were significantly higher in dLBBB patients. In addition, functional parameters were also significantly worse in dLBBB patients with lower ejection fraction and higher end-diastolic volume, end-systolic volume, summed motion score, and summed thickening score in these patients. Mean phase SD and phase histogram bandwidth were also significantly higher in dLBBB patients.

Conclusions

This study revealed that LBBB patients with discordant T wave in lateral leads have significantly higher ischemic scores and worse functional parameters with more dyssynchrony in gated SPECT MPI.
Solitary Bone Langerhans Cell Histiocytosis Demonstrated on Multimodality Imaging in an Adult
Authors: Zhao Yu , Zhou Yi , Tian Rong , Su Minggang
Published: November 2019

Multimodality imaging was performed on a 53-year-old woman who was suspected with malignant bone tumor in her left femoral midshaft on radiograph. An MRI demonstrated the lesion showed hypointensity on T1-weighted and high intensity on T2-weighted fat-saturated images. It was more extensive on MRI than that on radiograph, especially in bone marrow and parosteal soft tissue. The lesion accumulated radiotracer on bone scan and 18F-FDG PET/CT. Finally, a Langerhans cell histiocytosis was confirmed after surgery. The case cautions us Langerhans cell histiocytosis should be in the differential diagnosis spectrum in an adult with unexplained unifocal bone lesion on 18F-FDG PET/CT.
Adrenocortical Scintigraphy With SPECT/CT for the Diagnosis of Hepatic Adrenal Rest
Authors: Kawasaki Masako , Yoshimura Mana , Sugimoto Katsutoshi , Takeuchi Hirohito , Saito Kazuhiro
Published: November 2019

Hepatic adrenal rest include ectopic adrenal tissue in the liver and adrenohepatic fusion. Long-lasting hyperstimulation of that tissue induces hyperplasia sometimes simulating true tumors. True autonomic tumors originating from ectopic adrenal tissue with or without hyperfunction are rare. Hepatic adrenal rest sometimes has similar imaging findings to lipid-rich hepatocellular carcinoma or angiomyolipoma, containing obvious lipid component. But in our cases, tumors showed hypervascular patterns similar to hepatocellular adenoma or carcinoma. Therefore, adrenocortical scintigraphy with SPECT/CT should be taken into consideration to diagnose tumoral lesions in the posterior segment of the right hepatic lobe with or without an obvious lipid component.
Nivolumab-Induced Subcutaneous Fat Necrosis
Authors: Bhargava Peeyush , Flynt Lesley , Marcal Leonardo
Published: November 2019

A 59-year-old woman with history of metastatic melanoma, currently on nivolumab, presents for a restaging FDG PET/CT scan. New subcutaneous hypermetabolic foci are seen in bilateral lower extremities, suggestive of recurrent melanoma. She is referred for percutaneous image-guided biopsy for definitive diagnosis of progressive disease. Ultrasound shows the subcutaneous foci to be hyperechoic (fat density), and biopsy of the right thigh nodule shows fat necrosis with no evidence of tumor. Fat necrosis, an immune-related adverse event, can be FDG-avid and mimic malignancy on PET/CT scan.
Feasibility and Accuracy of Different Methods for Collecting Data on Falls Among Older People With Dementia
Authors: Adamczewska Natalia , Vassallo Michael , Thomas Peter W. , Thomas Sarah , Barrado-Martín Yolanda , Nyman Samuel R.
Published: November 2019

This study compared different methods for collecting data on falls among people with dementia to identify which is most feasible and accurate. Eighty-three dyads, comprised of a community-dwelling person with dementia and their informal carer, participated in the TAi ChI for people with demenTia (TACIT) trial. Falls were collected prospectively over 6 months using monthly calendars, weekly and monthly telephone interviews, and 3-monthly telephone interviews with the carer. Unique falls identified across the reporting methods were combined, and this total was compared against each reporting method in isolation and combinations. A higher frequency of falls indicated greater accuracy. Falls data collection was most feasible with weekly telephone interviews (84%), and most accurate with the combination of weekly telephone interviews with monthly calendars (96%). For the greatest completeness and accuracy of falls data with community-dwelling people with dementia, researchers should use both weekly telephone interviews and monthly calendars.
Patent foramen ovale and stroke: current evidence and treatment options
Authors: Favilla Christopher G. , Messé Steven R.
Published: November 2019

Purpose of review

Recent data have changed the landscape of patent foramen ovale (PFO) closure for secondary stroke prevention. This review synthesizes the data and provides a framework for optimal management of stroke patients with PFO.

Recent findings

The cumulative evidence indicates that PFO closure reduces the risk of recurrent stroke in carefully selected young cryptogenic stroke patients, with an annualized risk reduction of ∼0.6%. The benefit of PFO closure is particularly evident in patients with embolic appearing strokes, large right-to-left shunt, or an associated atrial septal aneurysm. There may be little or no benefit in patients with small deep infarcts, a small PFO, or an indication for long-term anticoagulation. Closure is accompanied by a small risk of major procedural complication and atrial fibrillation.

The annual risk of stroke from PFO is low relative to other stroke mechanisms, but the life-time cumulative risk in young patients who have experienced a prior stroke may be substantial, in which case the absolute benefit of closure is likely impactful. PFO is highly prevalent in the general population, present in about one in four adults, and should not be considered to be the cause of the stroke until a thorough workup has excluded alternative mechanisms.
A guide to machine learning for bacterial host attribution using genome sequence data
Authors: Lupolova Nadejda , Lycett Samantha J. , Gally David L.
Published: November 2019

With the ever-expanding number of available sequences from bacterial genomes, and the expectation that this data type will be the primary one generated from both diagnostic and research laboratories for the foreseeable future, then there is both an opportunity and a need to evaluate how effectively computational approaches can be used within bacterial genomics to predict and understand complex phenotypes, such as pathogenic potential and host source. This article applied various quantitative methods such as diversity indexes, pangenome-wide association studies (GWAS) and dimensionality reduction techniques to better understand the data and then compared how well unsupervised and supervised machine learning (ML) methods could predict the source host of the isolates. The study uses the example of the pangenomes of 1203

Salmonella enterica

serovar Typhimurium isolates in order to predict 'host of isolation' using these different methods. The article is aimed as a review of recent applications of ML in infection biology, but also, by working through this specific dataset, it allows discussion of the advantages and drawbacks of the different techniques. As with all such sub-population studies, the biological relevance will be dependent on the quality and diversity of the input data. Given this major caveat, we show that supervised ML has the potential to add real value to interpretation of bacterial genomic data, as it can provide probabilistic outcomes for important phenotypes, something that is very difficult to achieve with the other methods.
Multi-site clonality analyses uncovers pervasive subclonal heterogeneity and branching evolution across melanoma metastases
Authors: Rabbie Roy , Ansari-Pour Naser , Cast Oliver , Lau Doreen , Scott Francis , Welsh Sarah J. , Parkinson Christine , Khoja Leila , Moore Luiza , Tullett Mark , Wong Kim , Ferreira Ingrid , Martínez Gómez Julia M. , Levesque Mitchell , Gallagher Ferdia A. , Jiménez-Sánchez Alejandro , Riva Laura , Miller Martin L. , Allinson Kieren , Campbell Peter J. , Corrie Pippa , Wedge David C. , Adams David J.
Published: November 2019

Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal that metastatic cells may depart the primary tumour very early in the disease course and follow a branched pattern of evolution. Truncal UV-induced mutations that often swamp downstream analyses of heterogeneity, were found to be replaced by APOBEC-associated mutations in the branches of the evolutionary tree. Multi-sample analyses from a further 7 patients confirmed that branched evolution was pervasive, representing an important mode of melanoma dissemination. Our analyses illustrate that combining cancer cell fraction estimates across multiple metastases provides higher resolution phylogenetic reconstructions relative to single sample analyses and highlights the limitations of accurately inferring inter-tumoural heterogeneity from a single biopsy.
Age-related differences in structural and functional prefrontal networks during a logical reasoning task
Authors: Ziaei Maryam , Bonyadi Mohammad Reza , Reutens David C.
Published: November 2019

In logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. No study to date, however, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief load. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) during conclusion stage. Our functional connectivity results suggest that while older adults engaged the ACC network to overcome their intuitive responses for believable inferences, the IFG network contributed to higher control over responses during both believable and unbelievable conditions. Our functional results were further supported by structure-function-behavior analyses indicating the importance of cingulum bundle and uncinate fasciculus integrity in rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for decision making where currently-held beliefs and given assumptions are in conflict.
Whole genome sequencing analysis of the cardiometabolic proteome
Authors: Gilly Arthur , Park Young-Chan , Png Grace , Barysenka Andrei , Fischer Iris , Bjornland Thea , Southam Lorraine , Suveges Daniel , Neumeyer Sonja , Rayner N. William , Tsafantakis Emmanouil , Karaleftheri Maria , Dedoussis George , Zeggini Eleftheria
Published: November 2019

The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5x) whole-genome sequencing (WGS) in 1,328 individuals. We discover 131 independent sequence variant associations (P<7.45×10−11) across the allele frequency spectrum, all of which replicate in an independent cohort (n=1,605, 18.4x WGS). We identify for the first time replicating evidence for rare-variantcis-acting protein quantitative trait loci for five genes, involving both coding and non-coding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets.
Evaluating molecular modeling tools for thermal stability using an independently generated dataset
Authors: Huang Peishan , Chu Simon K. S. , Frizzo Henrique N. , Connolly Morgan P. , Caster Ryan W. , Siegel Justin B.
Published: November 2019

Engineering proteins to enhance thermal stability is a widely utilized approach for creating industrially relevant biocatalysts. Computational tools that guide these engineering efforts remain an active area of research with new data sets and develop algorithms. To aid in these efforts, we are reporting an expansion of our previously published data set of mutants for a β-glucosidase to include both measures of TM and ΔΔG, to complement the previously reported measures of T50 and kinetic constants (kcat and KM). For a set of 51 mutants, we found that T50 and TM are moderately correlated with a Pearson correlation coefficient (PCC) of 0.58, indicated the two methods capture different physical features. The performance of predicted stability using five computational tools are also evaluated on the 51 mutants dataset, none of which are found to be strong predictors of the observed changes in T50, TM, or ΔΔG. Furthermore, the ability of the five algorithms to predict the production of isolatable soluble protein is examined, which revealed that Rosetta ΔΔG, ELASPIC, and DeepDDG are capable of predicting if a mutant could be produced and isolated as a soluble protein. These results further highlight the need for new algorithms for predicting modest, yet important, changes in thermal stability as well as a new utility for current algorithms for prescreening designs for the production of soluble mutants.
Thermodynamic modelling of synthetic communities predicts minimum free energy requirements for sulfate reduction and methanogenesis
Authors: Delattre Hadrien , Chen Jing , Wade Matthew , Soyer Orkun S
Published: November 2019

Microbial communities are complex dynamical systems harbouring many species interacting together to implement higher-level functions. Among these higher-level functions, conversion of organic matter into simpler building blocks by microbial communities underpins biogeochemical cycles and animal and plant nutrition, and is exploited in biotechnology. A prerequisite to predicting the dynamics and stability of community-mediated metabolic conversions, is the development and calibration of appropriate mathematical models. Here, we present a generic, extendable thermodynamic model for community dynamics accounting explicitly for metabolic activities of composing microbes, system pH, and chemical exchanges. We calibrate a key parameter of this thermodynamic model, the minimum energy requirement associated with growth-supporting metabolic pathways, using experimental population dynamics data from synthetic communities composed of a sulfate reducer and two methanogens. Our findings show that accounting for thermodynamics is necessary in capturing experimental population dynamics of these synthetic communities that feature relevant species utilising low-energy growth pathways. Furthermore, they provide the first estimates for minimum energy requirements of methanogenesis and elaborates on previous estimates of lactate fermentation by sulfate reducers. The open-source nature of the developed model and demonstration of its use for estimating a key thermodynamic parameter should facilitate further thermodynamic modelling of microbial communities.
Satellite cell depletion in early adulthood attenuates muscular dystrophy pathogenesis
Authors: Boyer Justin G. , Han Sarah , Prasad Vikram , Khalil Hadi , Vagnozzi Ronald J. , Molkentin Jeffery D.
Published: November 2019

Satellite cells are skeletal muscle resident stem cells that regenerate adult myofibers following an acute injury to muscle. Despite the assumption that the loss of satellite cells would be detrimental in a chronic regeneration-inducing muscle disease such as muscular dystrophy, this assumption has never been tested using mouse genetics. Here we generated a novel model of satellite cell ablation and crossed it with mouse models of muscular dystrophy to directly investigate how critical these cells are in maintaining muscle during a chronic degenerative disorder. Satellite cell deletion in 2-week-old young dystrophic mice provided noticeable improvements in histopathology and function, although at this early timepoint it was utimately detrimental because muscle size was not sufficient to permit survival. However, depletion of satellite cells beginning at 2 months of age in dystrophic mice provided similar histological and functional improvements but without compromising muscle size. The improved profile showed fewer damaged fibers, less myofiber central nucleation, increased sarcolemma integrity, decreased fibrosis and a dramatic size increase in the remaining myofibers. At the functional level, young adult dystrophic mice lacking satellite cells performed significantly better than those with satellite cells when exercised on a treadmill. Thus, loss of satellite cells during early adulthood in dystrophic mice produces an unexpected protective effect.
Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism
Authors: McCausland Joshua W. , Yang Xinxing , Squyres Georgia R. , Lyu Zhixin , Bruce Kevin E. , Lamanna Melissa M. , Söderström Bill , Garner Ethan C. , Winkler Malcolm E. , Xiao Jie , Liu Jian
Published: November 2019

FtsZ, a highly conserved bacterial tubulin GTPase homolog, is a central component of the cell division machinery in nearly all walled bacteria. FtsZ polymerizes at the future division site and recruits greater than 30 proteins to assemble into a macromolecular complex termed the divisome. Many of these divisome proteins are involved in septal cell wall peptidoglycan (sPG) synthesis. Recent studies found that FtsZ polymers undergo GTP hydrolysis-coupled treadmilling dynamics along the circumference the division site, driving the processive movement of sPG synthesis enzymes. How FtsZ’s treadmilling drives the directional transport of sPG enzymes and what its precise role is in bacterial cell division are unknown. Combining theoretical modeling and experimental testing, we show that FtsZ’s treadmilling drives the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism, where the shrinking end of FtsZ polymers introduces an asymmetry to rectify diffusions of single sPG enzymes into persistent end-tracking movement. Furthermore, we show that the processivity of this directional movement is dependent on the binding potential between FtsZ and the enzyme, and hinges on the balance between the enzyme’s diffusion and FtsZ’s treadmilling speed. This interplay could provide a mechanism to control the level of available enzymes for active sPG synthesis both in time and space, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacterial species.
Targeting DDR1 and DDR2 overcomes matrix-mediated melanoma cell adaptation to BRAF-targeted therapy
Authors: Berestjuk Ilona , Lecacheur Margaux , Diazzi Serena , Rovera Christopher , Prod’homme Virginie , Mallavialle Aude , Larbret Frédéric , Pisano Sabrina , Audebert Stéphane , Passeron Thierry , Gaggioli Cédric , Girard Christophe A. , Deckert Marcel , Tartare-Deckert Sophie
Published: November 2019

Resistance to BRAF and MEK inhibitors in BRAFV600Emutant melanomas remains a major obstacle that limits patient benefit. Microenvironment components including the extracellular matrix (ECM) can support tumor cell adaptation and tolerance to targeted therapies, however the underlying mechanisms remain poorly understood. Here, we investigated the process of matrix-mediated drug resistance (MM-DR) in response to BRAF inhibition in melanoma. We demonstrate that physical and structural cues from fibroblast-derived ECM abrogate anti-proliferative responses to BRAF/MEK inhibition. MM-DR is mediated by the drug-induced clustering of DDR1 and DDR2, two tyrosine kinase collagen receptors. Genetic depletion and pharmacological inhibition of DDR1 and DDR2 overcome ECM-mediated resistance to BRAF inhibition. In melanoma xenografts, targeting DDRs by Imatinib enhances BRAF inhibitor efficacy, counteracts drug-induced collagen remodeling and delays tumor relapse. Mechanistically, DDR-mediated MM-DR fosters a targetable pro-survival NIK/IKKα/NF-κB2 pathway. Our study reveals a novel role of collagen-rich matrix and DDRs in tumor cell adaptation and therapy resistance, thus providing important insights into environment-mediated drug resistance and a pre-clinical rationale for targeting DDR1/2 signaling in combination with BRAF-targeted therapy in melanoma.
Regulator of Gene Silencing-Calmodulin associates with mRNA granules and the autophagy protein ATG8
Authors: Craig Conner W. , Lokdarshi Ansul , Roberts Daniel M.
Published: November 2019

Abstract

Regulator-of-gene-silencing calmodulins (rgsCaM) represent a phylogenetic subfamily of calmodulin-like calcium sensors that are targets of viral induced suppression of posttranscriptional gene silencing by secondary siRNAs. The present work shows that a stress (hypoxia) that induces mRNP granule formation also induces the relocalization of rgsCaM to cytosolic granule-like foci that interact with the surface of stress granule and processing body structures. Co-expression of rgsCaM and its binding protein Suppressor of Gene Silencing 3 causes re-localization and integration of rgsCaM into stress granule structures. RgsCaMs contain a conserved topology that consists for four EF hand like domains (three functional and one divergent) that are separated into two calcium binding lobes with an extended amino terminal region. RgsCaM also contains an “ATG8 family interacting motif” (AIM) within its amino-terminal domain that is characteristic of selective autophagy cargo receptors. Co-localization experiments and ratiometric BiFC analyses inNicotiana benthamianasupport the hypothesis that rgsCaM binds directly to ATG8e through this conserved AIM domain, and the two proteins co-localize with mRNP granule markers. Previous reports show that rgsCaM mediates the suppression of gene silencing, at least in part, via turnover of SGS3 via autophagy. A model is proposed for rgsCaM-like proteins as potential mediators of selective autophagy of RNA granules in response to biotic and abiotic stresses.
FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination during DNA repair
Authors: Alcón Pablo , Shakeel Shabih , Patel Ketan J. , Passmore Lori A.
Published: November 2019

Vertebrate DNA crosslink repair is a crucial process that excises toxic replication-blocking DNA interstrand crosslinks1. This pathway fails in the inherited human disease Fanconi anemia (FA), resulting in abnormal development, loss of blood production, and marked cancer susceptibility2. Numerous factors involved in crosslink repair have been identified, and mutations in their corresponding genes cause FA3. A biochemical description of how FA gene products might initiate the removal of DNA crosslinks is now emerging. However, structural insight into this vital process has been limited. Here, we use electron cryomicroscopy (cryoEM) to determine the structure of a key DNA crosslink repair factor – FANCD2 heterodimerized with FANCI (D2-I). Recombinant chicken D2-I adopts a conformation that is in agreement with the structure of its murine counter-part4. In contrast, the activated monoubiquitinated form of D2-I (ubD2-I) adopts an alternative closed conformation, creating a channel that encloses double-stranded DNA. Ubiquitin is positioned at the interface of FANCD2 and FANCI, and acts as a molecular pin to trap ubD2-I in the closed conformation, clamped on DNA. The new solvent-exposed interface around the monoubiquitination site is likely a platform for recruitment of other DNA repair factors. We also find that isolated FANCD2 is a dimer, but it adopts a closed conformation that is unable to bind DNA. When incubated with free FANCI, the FANCD2 homodimer exchanges to D2-I, acquiring DNA binding properties. This suggests an autoinhibitory mechanism that prevents FANCD2 activation on DNA until after assembly with FANCI. Together, our cryoEM and biochemical analysis suggests that D2-I is a clamp that is locked onto DNA by ubiquitin, and provides unanticipated new insight into the regulation and the initiation of DNA cross-link repair.
CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus
Authors: Graziano Vincent R. , Walker Forrest C. , Kennedy Elizabeth A. , Wei Jin , Ettayebi Khalil , Simões Madison S. , Filler Renata B. , Hassan Ebrahim , Hsieh Leon L. , Kolawole Abimbola O. , Wobus Christiane E. , Lindesmith Lisa C. , Baric Ralph S. , Estes Mary K. , Orchard Robert C. , Baldridge Megan T. , Wilen Craig B.
Published: November 2019

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. Thebona fidereceptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infectionin vitro. Here we explored whether CD300lf is the sole physiologic receptorin vivoand whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strainsin vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responsesin vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. However, after high dose intraperitoneal challenge with MNoV inCd300lf−/−Stat1−/−mice a single amino acid mutation in the MNoV capsid protein emerged. This substitution did not alter receptor utilizationin vitro. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.

Author Summary

Human norovirus is the leading cause of non-bacterial gastroenteritis causing up to 200,000 deaths each year. How human norovirus enters cells is unknown. Because human norovirus is difficult to grow in the laboratory and in small animals, we use mouse or murine norovirus as a model system. We recently discovered that murine norovirus can use the either CD300ld or CD300lf as a receptorin vitro. We also showed that CD300lf deficient mice were resistant to oral challenge with a single virus strain. Here we determined that CD300lf is essential for infection of diverse murine norovirus strains in cell lines and in mice with normal immune systems demonstrating it’s the primary physiologic receptor for diverse murine norovirus strains independent of infection route. However, in immunodeficient mice injected with high dose virus directly into the abdominal cavity, we observed a norovirus mutant that enabled CD300lf-independent infection. Finally, we demonstrated that human CD300lf is not the elusive receptor for human norovirus.
Combined X-ray and neutron single-crystal diffraction in diamond anvil cells
Authors: Grzechnik Andrzej , Meven Martin , Paulmann Carsten , Friese Karen
Published: November 2019

It is shown that it is possible to perform combined X-ray and neutron single-crystal studies in the same diamond anvil cell (DAC). A modified Merrill–Bassett DAC equipped with an inflatable membrane filled with He gas has been developed. It can be used on laboratory X-ray and synchrotron diffractometers as well as on neutron instruments. The data processing procedures and a joint structural refinement of the high-pressure synchrotron and neutron single-crystal data are presented and discussed for the first time.
Implementing evaluation for positive organizational changes: IBA-public school Sukkur, Pakistan
Authors: Umrani Waheed Ali , Solangi Rukhman , Ali Memon Mumtaz , Hadeesa Asmaa , Khoso Soonhan
Published: November 2019

Learning outcomes

Learning outcomes are as follows: Understand performance appraisal process and tools; apply theory X and Theory Y in managing resistance to performance evaluation; identify the causes and symptoms of resistance; identify and apply managing resistance approaches.

Case overview/synopsis

After attaining the height of success in terms of imparting quality education and contributing to the creation of many learned persons of the society, Public school Sukkur was facing the downward trending success for many reasons. After the takeover of management control by Sukkur IBA University, the school was upward trending for quality education, state of the art infrastructure, advanced educational lab, modern teaching methodologies. With such a change, resistance was a must. Both Active and Passive resistance from the stakeholders was impeding the success of newly named IBA-Public School Sukkur. Particularly, the resistance against the implementation of the Performance Appraisal tool and its administration. With the resistance from employees, Chang, Principal IBA Public School Sukkur had to come up a solution for the smooth administration and implementation of Performance Appraisal and manage the resistance from the employees and ensure the continuous improvement through performance appraisal.

Complexity academic level

Case study is applicable for the MBA students.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 7: Management Science.
Bike Wala – A To Zee Distribution
Authors: Shaikh Abdul Rehman , Qazi Asad Ali
Published: November 2019

Learning outcomes

Learning outcomes are as follows: to understand the influence of external factors in operations planning; to understand the importance of contingency planning in new initiatives; to analyze financial and non-financial gains of the new project; to analyze and visualize the unexpected challenges in post-implementation of project; and to critically analyze the ethical consideration in decision-making.

Case overview/synopsis

After joining A to Zee Distribution, Shaikh had brought up several improvements to distribution operations and had suggested various cost-saving initiatives. He had also developed and implemented the distribution KPIs for the first time in the organization. One of the recent initiatives that he took was the start of a new project named ‘Bike Wala’. This project not only increased the market base for A to Zee but also significantly reduced their operations expenses. However, after around two months of the project, the delivery officers reported several incidents and accidents. These accidents included several injuries due to unbalancing bikes and excess load/weight in delivery boxes. The owner has asked Shaikh to close the project on humanitarian grounds and revert back to delivery vans. However, Shaikh is confused and willing for the project to continue. Shaikh had to choose from either his own career and initiative or safety and security of employees and the company’s assets.

Complexity academic level

BBA and MBA.

Supplementary materials

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Subject Code

CSS 9: Operations and Logistics.
Estimating the impact of crime risk on housing prices in Malaysia
Authors: Wong Woei-Chyuan , Azhari Adilah , Abdullah Nur Adiana Hiau , Yip Chee Yin
Published: November 2019

Purpose

The purpose of this study is to examine the impact of crime risk on housing prices at a national level in Malaysia during the period from 1988 to 2016.

Design/methodology/approach

A hedonic regression approach was used to estimate the Malaysian households’ valuation for crime risk. Specifically, the state-level property index on the state-level reported crime rate was regressed while controlling for state-level socioeconomic variables. The macroeconomic panel nature of the data set provides the merit to use a panel dynamic model instead of the traditional static panel data techniques (fixed effects or first difference).

Findings

Panel dynamic estimators consistently show a negative impact of crime risks on housing prices. The estimated elasticity of housing prices with respect to crime risks ranges from −0.141 to −0.166, in line with existing literature using micro level data. In fact, householders in crime hotspot states are willing to pay more for crime reduction compared to householders in non-hotspot states. The willingness to pay has also increased since the implementation of nationwide crime reduction plans in 2010.

Research limitations/implications

This is the first study that has examined the Malaysian people’s willingness to pay to reduce crime. This information is important in determining the optimal level of government expenditures for public safety.

Originality/value

This is the first study to examine the relationship between crime rates and housing prices in Malaysia. This study contributes to the literature by examining the impact of crime rates on housing prices at a national level by using panel dynamic models. The macro level data results are consistent and complement the existing literature based on micro level data.
Building conservation and the circular economy: a theoretical consideration
Authors: Huuhka Satu , Vestergaard Inge
Published: November 2019

Purpose

The purpose of this paper is to discuss the relation between building conservation and circular economy (CE), which are often erroneously seen as inherently contradictory to one another.

Design/methodology/approach

The work draws from a comparative approach. The paper reviews a body of literature on architectural conservation and CE to establish an understanding on the state-of-the-art for both disciplines separately. Then, the relation between thereof is developed through a theoretical discourse.

Findings

Both architectural conservation and CE aim at safeguarding value, although they define “value” differently. Fabric-focused conservation and CE favor minimal intervention to material, albeit they arrive at this conclusion from different bases. Consequently, both approaches struggle with the low cost of virgin resource extraction and waste production and the high cost of human labor in contemporary Western societies. CE could be harnessed for building conservation by adopting its vocabulary and methodology, such as lifecycle assessment and material flow analysis. Transitioning toward CE can help increase the preservation of built heritage while redefining what is meant by “heritage” and “waste.”

Originality/value

Prior to this paper, there have been no articles addressing the relationship of the concepts explicitly and to this extent. The paper provides a theoretical basis for further discourse and outlines some implications of CE for the construction and built heritage disciplines.
Flow effect and resonance effect: group emotional contagion in service failure encounters
Authors: Du Jiangang , Yang Mengya , Liu Jianhua
Published: November 2019

Purpose

The purpose of this paper is to explore the two effects (flow effect and resonance effect) during a group complaint based on the emotional contagion theory.

Design/methodology/approach

This study uses an experimental research design in which participants’ negative emotions dynamically change driven by group emotional interactions when they are experiencing a group complaint.

Findings

Flow effect and resonance effect can occur during the process of group emotional contagion. Specifically, when group customers’ negative emotional similarity is low in a group complaint, group emotional contagion leads to flow effect (i.e. negative emotions flow from customers with higher levels of negative emotions to those with lower levels of negative emotions). By contrast, when group customers’ negative emotional similarity is high in a group complaint, group emotional contagion leads to resonance effect (i.e. group customers’ negative emotions increase significantly).

Originality/value

Most of the previous research studies the process of emotional contagion from one with higher levels of emotional displays to the other with lower levels of emotional displays, which is named as the “flow effect” of emotional contagion. However, when two individuals with the same levels of negative emotional displays interact with each other, the flow effect of emotional contagion is very likely not to occur. It is interesting to find that both individuals’ negative emotions increase significantly during the process of emotional contagion. The authors propose the “resonance effect” of emotional contagion to explain this phenomenon.
Forklift truck performance simulation and fuel consumption estimation
Authors: d'Apolito Luigi , Hong Hanchi
Published: November 2019

Purpose

Forklift trucks are generally operated with frequent accelerations and stops, reverse and operations of load handling. This way of operation increases the energy losses and consequently the need for reduction of fuel consumption from forklift customers. This study aims to build a model to replicate the performance of forklifts during real operations and estimate fuel consumption without building a real prototype.

Design/methodology/approach

AVL Cruise has been used to simulate forklift powertrain and hydraulic circuit. The driving cycles used for this study were in accordance with the standard VDI 2198. Artificial neural networks (ANNs), trained by the results of AVL Cruise simulations, have been used to forecast the fuel consumption for a large set of possible driving cycles.

Findings

The comparison between simulated and experimental data verified that AVL Cruise model was able to simulate the performance of real forklifts, but the results were only valid for the specified driving cycle. The ANNs, trained by the results of AVL Cruise for a certain number of driving cycles, have been found effective to forecast the fuel consumption of a larger number of driving cycles following the prescriptions of the standard VDI 2198.

Originality/value

A new method based on ANN, trained by AVL Cruise simulation results, has been introduced to forecast the forklift fuel consumption, reducing the computational time and the cost of experimental tests.
Personalized TMS: role of RNA genotyping
Authors: Chan Shawna , Bota Robert
Published: November 2019

Purpose

Noninvasive brain stimulation (NIBS) such a transcranial magnetic stimulation, intermittent theta burst stimulation, transcranial direct current stimulation and electroconvulsive therapy have emerged as an efficacious and well-tolerated therapy for treatment-resistant psychiatric disorders. While novel NIBS techniques are an exciting addition to the current repertoire of neuropsychiatric therapies, their success is somewhat limited by the wide range of treatment responses seen among treated patients.

Design/methodology/approach

In this study, the authors will review the studies on relevant genetic polymorphisms and discuss the role of RNA genotyping in personalizing NIBS.

Findings

Genome studies have revealed several genetic polymorphisms that may contribute for the heterogeneity of treatment response to NIBS where the presence of certain single nucleotide polymorphisms (SNPs) are associated with responders versus nonresponders.

Originality/value

Historically, mental illnesses have been arguably some of the most challenging disorders to study and to treat because of the degree of biological variability across affected individuals, the role of genetic and epigenetic modifications, the diversity of clinical symptomatology and presentations and the interplay with environmental factors. In lieu of these challenges, there has been a push for personalized medicine in psychiatry that aims to optimize treatment response based on one’s unique characteristics.