bluuebunny/crossref_metadata_2025 huggingface dataset:
A Parametric Blueprint for Optimum Cochlear Outer Hair Cell Design
Authors: Rabbitt Richard D. , Bidone Tamara C.
Published: October 2022

The present work examines the hypothesis that cochlear outer hair cell (OHC) properties vary in precise proportions along the tonotopic map to optimize electro-mechanical power conversion. We tested this hypothesis using a very simple model of a single isolated OHC driving a mechanical load. Results identify three nondimensional ratios that are predicted to optimize power conversion: the ratio of the resistive-capacitive (RC) corner to the characteristic frequency (CF), the ratio of nonlinear to linear capacitance, and the ratio of OHC stiffness to cochlear load stiffness. Optimum efficiency requires all three ratios to be universal constants, independent of CF and species. The same ratios are cardinal control parameters that maximize power output by positioning the OHC operating point on the edge of a dynamic instability. Results support the hypothesis that OHC properties evolved to optimize electro-mechanical power conversion. Identification of the RC corner frequency as a control parameter reveals a powerful mechanism used by medial olivocochlear efferent system to control OHC power output. Results indicate the upper frequency limit of OHC power output is not constrained by the speed of the motor itself, but instead is likely limited by the size of the nucleus and membrane surface area available for ion-channel expression.
Staphylococcus lugdunensisand Coagulase-Negative Staphylococci species characterisation in a tropical climate
Authors: Howes Matthew , Baird Rob
Published: October 2022

Coagulase negative staphylococci (CoNS) are a heterogeneous group of colonising organisms that have historically been differentiated from Staphyloccocus aureus but are now known to cause invasive disease. We characterised the CoNS species from a single tropical centre to compare with previous studies. 1262 isolates were collected with 203 from blood stream samples over an 18 month period. S. lugdunensis was the second most isolated CoNS comprising 15.9% of isolates, much greater than comparative studies. A single blood stream infection with S. lugdunensis was identified over this time period, comprising a much lower ratio of blood to swab isolates than in previous studies.
Residential clustering of COVID-19 cases and efficiency of building-wide compulsory testing notices as a transmission control measure in Hong Kong
Authors: Young Benjamin R. , Yang Bingyi , Wu Peng , Adam Dillon C. , Wong Jessica Y. , Ho Faith , Gao Huizhi , Lau Eric H. Y. , Leung Gabriel M. , Cowling Benjamin J.
Published: October 2022

Background

Despite relatively few reports of residential case clusters of COVID-19, building-wide compulsory testing notices on residential apartment blocks are frequently applied in Hong Kong with the aim of identifying cases and reducing transmission.

Methods

We aimed to describe the frequency of residential case clusters and the efficiency of compulsory testing notices in identifying cases. The residences of locally infected COVID-19 cases in Hong Kong were grouped to quantify the number of cases per residence.

Buildings targeted in compulsory testing notices were matched with the residence of cases to estimate the number of cases identified.

Results

We found that most of the residential buildings (4246/7688, 55.2%) with a confirmed COVID-19 case had only one reported case. In the fourth and the fifth epidemic wave in Hong Kong, we estimated that compulsory testing notices detected 29 cases (95% confidence interval: 26, 32) and 46 cases (44, 48) from every 100 buildings tested (each with hundreds of residents), respectively. Approximately 13% of the daily reported cases were identified through compulsory testing notices.

Conclusions

Compulsory testing notices can be an essential method when attempting to maintain local elimination (‘zero covid’) and most impactful early in an epidemic when the benefit remains of stemming a new wave. Compulsory testing therefore appears to be a relatively inefficient control measure in response to sustained community transmission in the community.
Transcriptomic diversity of cell types across the adult human brain
Authors: Siletti Kimberly , Hodge Rebecca , Mossi Albiach Alejandro , Hu Lijuan , Lee Ka Wai , Lönnerberg Peter , Bakken Trygve , Ding Song-Lin , Clark Michael , Casper Tamara , Dee Nick , Gloe Jessica , Keene C. Dirk , Nyhus Julie , Tung Herman , Yanny Anna Marie , Arenas Ernest , Lein Ed S. , Linnarsson Sten
Published: October 2022

The human brain directs a wide range of complex behaviors ranging from fine motor skills to abstract intelligence and emotion. However, the diversity of cell types that support these skills has not been fully described. Here we used high-throughput single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain in three postmortem donors. We sampled over three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins. We found area-specific cortical neurons, as well as an unexpectedly high diversity of midbrain and hindbrain neurons. Astrocytes also exhibited regional diversity at multiple scales, comprising subtypes specific to the telencephalon and to more precise anatomical locations. Oligodendrocyte precursors comprised two distinct major types specific to the telencephalon and to the rest of the brain. Together, these findings demonstrate the unique cellular composition of the telencephalon with respect to all major brain cell types. As the first single-cell transcriptomic census of the entire human brain, we provide a resource for understanding the molecular diversity of the human brain in health and disease.
Enhancer/gene relationships: need for more reliable genome-wide reference sets
Authors: Hoellinger Tristan , Mestre Camille , Aschard Hugues , Goff Wilfried Le , Foissac Sylvain , Faraut Thomas , Djebali Sarah
Published: October 2022

Differences in cells’ functions arise from differential action of regulatory elements, in particular enhancers. Like promoters, enhancers are genomic regions bound by transcription factors (TF) that activate the expression of one or several genes by getting physically close to them in the 3D space of the nucleus. As there is increasing evidence that variants associated with common diseases are located in enhancers active in cell types relevant to these diseases, knowing the set of enhancers and more importantly the sets of genes activated by each enhancer (the so-called enhancer/gene or E/G relationships) in a cell type, will certainly help understanding these diseases.

There are three broad approaches for the genome-wide identification of E/G relationships in a cell type: (1) genetic link methods or eQTL, (2) functional link methods based on 1D functional data such as open chromatin, histone mark and gene expression and (3) spatial link methods based on 3D data such as HiC. Since (1) and (3) are costly, there has been a focus on developing functional link methods and using data from (1) and (3) to evaluate them, however there is still no consensus on the best functional link method to date.

For this reason we decided to start from the two latest benchmarks of the field, namely from the CRISPRi-FlowFISH (CRiFF) technique and from 3D and eQTL data inBENGI, and to evaluate the two methods claimed to be the best one on each of these benchmark studies, namely theABC modeland theAverage-Rankmethod respectively, on the other method’s reference data. Not only did we manage to reproduce the results of the two benchmarks but we also saw that none of the two methods performed best on the two reference data. WhileCRiFFreference data are very reliable, it is not genome-wide and is mostly available on a cancer cell type. On the other handBENGIis genome-wide but may contain many false positives. This study therefore calls for new reliable and genome-wide E/G reference data rather than new functional link E/G identification methods.
A Generalizable Nanopore Sensor for Highly Specific Protein Detection at Single-Molecule Precision
Authors: Ahmad Mohammad , Ha Jeung-Hoi , Mayse Lauren A. , Presti Maria F. , Wolfe Aaron J. , Moody Kelsey J. , Loh Stewart N. , Movileanu Liviu
Published: October 2022

Protein detection and biomarker profiling have wide-ranging implications in many areas of basic research and molecular diagnostics. Substantial progress has been made in protein analytics using nanopores and the resistive-pulse technique. Yet, a long-standing challenge is implementing specific binding interfaces for detecting proteins without the steric hindrance of the pore interior. To overcome this technological difficulty, we formulate a new class of sensing elements made of a programmable antibody-mimetic binder fused to a monomeric protein nanopore. This way, such a modular design significantly expands the utility of nanopore sensors to numerous proteins while preserving their architecture, specificity, and sensitivity. We prove the power of this approach by developing and validating nanopore sensors for protein analytes that drastically vary in size, charge, and structural complexity. These analytes produce unique electrical signatures that depend on their identity and quantity and the binder-analyte assembly at the nanopore tip. From a practical point of view, our sensors unambiguously probe protein recognition events without the necessity of using any additional exogenous tag. The outcomes of this work will impact biomedical diagnostics by providing a fundamental basis and tools for protein biomarker detection in biofluids.
Atypical B cells and impaired SARS-CoV-2 neutralisation following booster vaccination in the elderly
Authors: Ferreira Isabella A.T.M. , Lee Colin Y.C. , Foster William , Abdullahi Adam , Tuong Zewen Kelvin , Stewart Benjamin J , Ferdinand John R. , Guillaume Stephane , Potts Martin O.P. , Perera Marianne , Krishna Benjamin A. , Alonso Ana P. , Cabantous Mia , Kemp Steven A. , Ceron-Gutierrez Lourdes , Ebrahimi Soraya ,   The CITIID-NIHR BioResource COVID-19 Collaboration, Lyons Paul , Smith Kenneth GC , Bradley John , Collier Dami A. , Teichmann Sarah A. , McCoy Laura E. , MacAry Paul A. , Doffinger Rainer , Wills Mark R. , Linterman Michelle , Clatworthy Menna R. , Gupta Ravindra K.
Published: October 2022

Age is a major risk factor for hospitalization and death after SARS-CoV-2 infection, even in vaccinees. Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here we show that individuals 70 or older who received a primary two dose schedule with AZD1222 and booster third dose with mRNA vaccine achieved significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared to those younger than 70. One month after the booster neither the concentration of serum binding anti spike IgG antibody, nor the frequency of spike-specific B cells showed differences by age grouping. However, the impaired neutralization potency and breadth post-third dose in the elderly was associated with enrichment of circulating “atypical” spike-specific B cells expressing CD11c and FCRL5. Single cell RNA sequencing confirmed an expansion ofTBX21-, ITGAX-expressing B cells in the elderly that enriched for B cell activation/receptor signalling pathway genes. Importantly we also observed impaired T cell responses to SARS-CoV-2 spike peptides in the elderly post-booster, both in terms of IFNgamma and IL2 secretion, as well as a decrease in T cell receptor signalling pathway genes. This expansion of atypical B cells and impaired T cell responses may contribute to the generation of less affinity-matured antibodies, with lower neutralizing capacity post-third dose in the elderly. Altogether, our data reveal the extent and potential mechanistic underpinning of the impaired vaccine responses present in the elderly after a booster dose, contributing to their increased susceptibility to COVID-19 infection.
Protocol for the development of a meta-core outcome set for stillbirth prevention and bereavement care following stillbirth
Authors: Dube Kushupika , Ayebare Elizabeth , Bakhbakhi Danya , Bedwell Carol , Chandriah Savitha , Chaudhry Nasim , Chilinda Ides , Chimwaza Angela , Goshomi Unice , Laisser Rose , Lavender Tina , Mills Tracey A , Fattepur Sudhindrashayana , Vwalika Bellington , Wakasiaka Sabina , Kirkham Jamie J
Published: October 2022

Introduction

A stillbirth is the death of a baby before or during birth and accounts for about 14 in every 1,000 births globally with the highest rates seen in Sub-Saharan Africa and South Asia. Stillbirth prevention and bereavement care following stillbirth remains a challenge, particularly in Low-Middle Income Countries (LMiC). One approach to improvement is the prioritisation of women/family-centred care. However, there are a large variety of outcomes measured in stillbirth studies and consensus on the outcomes that matter most to women and families is often lacking, which can impact on the ability to make informed decisions about improved care practices. To help mitigate this problem, a core outcome set (COS) has been developed for stillbirth prevention and another COS has recently been finalised for care after stillbirth. Despite the majority of stillbirths occurring in LMiC involvement in these studies is ‘tokenistic’ and therefore the outcomes may not reflect the needs of parents or communities in these settings. The aim is to develop standard sets of outcomes for use in all interventional studies for stillbirth prevention and bereavement care using participants from predominantly Sub-Saharan Africa and South Asia, where the burden of stillbirth is highest.

Methods/Design

This study will involve three stages in the development of the COS: (1) a list of outcomes will be identified from multiple sources, specifically existing reviews of outcomes and a targeted qualitative literature review of studies that have interviewed parents who have experienced stillbirth and healthcare professionals working in this field across Sub-Saharan Africa and South Asia. (2) The list of outcomes will first be reviewed by in-country leads and scored by multiple stakeholder groups in a real-time online Delphi survey. (3) The results of the Delphi will be summarised and discussed at a face-to-face or virtual consensus meeting with representation from all stakeholder groups.

Discussion

As well as improving the consistency of outcomes for future research in an LMiC setting, these COS will harmonise with the existing COS in this field developed in a high income setting. The final output will be a global ‘meta-COS’, a recommended set of outcomes that can be used in stillbirth research worldwide.
Ultrasound versus fluoroscopy as imaging guidance for percutaneous nephrolithotomy: A systematic review and meta-analysis
Authors: Bahri Razman Arabzadeh , maleki Saba , Shafiee Arman , Shobeiri Parnian
Published: October 2022

Objectives

To determine whether the outcomes of ultrasound-guided percutaneous nephrolithotomy (UG-PCNL), an alternative to traditional fluoroscopy-guided percutaneous nephrolithotomy (FG-PCNL), are comparable.

Methods

A systematic search of PubMed, Embase, and the Cochrane Library was carried out to discover investigations comparing UG-PCNL to FG-PCNL, and accordingly, a meta-analysis of those studies was performed. The primary outcomes included the stone-free rate (SFR), overall complications based on Clavien-Dindo classification, duration of surgery, duration of patients’ hospitalization, and hemoglobin (Hb) drop during the surgery. All statistical analyses and visualizations were implemented utilizing R software.

Results

Nineteen studies, including eight randomized clinical trials (RCTs) and eleven observational cohorts, comprising 3016 patients (1521 UG-PCNL patients) and comparing UG-PCNL with FG-PCNL met the inclusion criteria of the current study. Considering SFR, overall complications, duration of surgery, duration of hospitalization, and Hb drop, our meta-analysis revealed no statistically significant difference between UG-PCNL and FG-PCNL patients, with p-values of 0.29, 0.47, 0.98, 0.28, and 0.42, respectively. Significant differences were discovered between UG-PCNL and FG-PCNL patients in terms of the length of time they were exposed to radiation (p-value< 0.0001). Moreover, FG-PCNL had shorter access time than UG-PCNL (p-value= 0.04).

Conclusion

UG-PCNL provides the advantage of requiring less radiation exposure while being just as efficient as FG-PCNL; thus, this study suggests prioritizing the use of UG-PCNL.
WITHDRAWN: Molecular characterization of enolase fromHaemaphysalis longicornistick
Authors: Haque Md. Samiul , Rahman Md. Khalesur , Islam Mohammad Saiful , You Myungjo
Published: October 2022

Withdrawal Statement

The authors have withdrawn their manuscript owing tofor more improvement in our research work and need to revise our manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
SARS-CoV-2 infection in domestic rats after transmission from their infected owner
Authors: Montagutelli Xavier , Decaudin Bérénice , Beretta Maxime , Mouquet Hugo , Simon-Lorière Etienne
Published: October 2022

We report the transmission of SARS-CoV-2 Omicron variant from a COVID-19 symptomatic individual to two domestic rats, one of which developed severe symptoms. Omicron carries several mutations which permit rodent infection. This report demonstrates that pet, and likely wild, rodents could therefore contribute to SARS-CoV-2 spread and evolution.
A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike
Authors: Dadonaite Bernadeta , Crawford Katharine H D , Radford Caelan E , Farrell Ariana G , Yu Timothy C , Hannon William W , Zhou Panpan , Andrabi Raiees , Burton Dennis R , Liu Lihong , Ho David D. , Neher Richard A. , Bloom Jesse D
Published: October 2022

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here we describe a new deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We demonstrate this new platform by making libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ~7000 distinct amino-acid mutations in the context of up to ~135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ~105combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.
In silicocharacterization of cysteine-stabilized αβ defensins from neglected unicellular microeukaryotes
Authors: Senra Marcus Vinicius Xavier
Published: October 2022

Background

The emergence of multi-resistant pathogens have increased dramatically in recent years, becoming a major public-health concern. Among other promising antimicrobial molecules with potential to assist in this worldwide struggle, cysteine-stabilized αβ (CS-αβ) defensins are attracting attention due their efficacy, stability, and broad spectrum against viruses, bacteria, fungi, and protists, including many known human pathogens.

Results

Here, 23 genomes of ciliated protists were screened and three CS-αβ defensins with a likely antifungal activity were identified and characterized using bioinformatics from two freshwater and culturable speciesLaurentiellasp. (LsAMP-1 and LsAMP-2) andEuplotes focardii(EfAMP-1). Although any potential cellular ligand could be predicted for LsAMP-2 and EfAMP-1; evidences from structural, molecular dynamics, and docking analyses suggest that LsAMP-1 may form stably associations with phosphatidylinositol 4,5-bisphosphates (PIP2), a phospholipid found on many eukaryotic cells, which could, in turn, represent an anchorage mechanism within plasma membrane of targeted cells.

Conclusion

These data stress that more biotechnology-oriented studies should be conducted on neglected protists, such ciliates, which could become valuable sources of novel bioactive molecules for therapeutic uses.
Chimeric MerR-Family Regulators and Logic Elements for the Design of Metal Sensitive Genetic Circuits inBacillus subtilis
Authors: Ghataora Jasdeep S. , Gebhard Susanne , Reeksting Bianca J.
Published: October 2022

Whole-cell biosensors are emerging as promising tools for monitoring environmental pollutants such as heavy metals. These sensors constitute a genetic circuit comprising a sensing module and an output module, such that a detectable signal is produced in the presence of the desired analyte. The MerR family of metal-responsive regulators offers great potential for the construction of metal sensing circuits, due to their high sensitivity, tight transcription control and large diversity in metal-specificity. However, the sensing diversity is broadest in Gram-negative systems, while chassis organisms are often selected from Gram-positive species, particularly sporulating bacilli. This can be problematic, because Gram-negative biological parts, such as promoters, are frequently observed to be non-functional in Gram-positive hosts. Herein, we combined construction of synthetic genetic circuits and chimeric MerR regulators, supported by structure-guided design, to generate metal-sensitive biosensor modules that are functional in the biotechnological work-horse speciesBacillus subtilis. These chimeras consist of a constant Gram-positive derived DNA-binding domain fused to variable metal binding domains of Gram-negative origins. To improve the specificity of the whole-cell biosensor, we developed a modular ‘AND gate’ logic system based on theB. subtilisnatively split σ-factor, SigO-RsoA, designed to maximise future use for synthetic biology applications inB. subtilis. This work provides insights into the use of modular regulators, such as the MerR family, in the design of synthetic circuits for the detection of heavy metals, with potential wider applicability of the approach to other systems and genetic backgrounds.
Inhibition of Microbial Methane Oxidation by 2-Chloro-6-Methylpyridine
Authors: O’Loughlin Edward J. , Antonopoulos Dionysios A. , Arend Kristin K. , Flynn Theodore M. , Koval Jason C. , Owens Sarah M.
Published: October 2022

Several pyridine derivatives including the pesticide nitrapyrin [2-chloro-6-(trichloromethyl) pyridine] are strong inhibitors of methane monooxygenase, a key enzyme of aerobic methane (CH4) oxidation. In this study we examined the effects of 2-chloro-6-methylpyridine (2C6MP) concentration on aerobic CH4oxidation and the development of populations of putative methanotrophs in sediment from Old Woman Creek, a freshwater estuary in Huron Co., Ohio. Experimental systems were prepared in serum bottles containing minimal medium with a headspace containing 20% O2and 10% CH4. The microcosms were spiked with 2C6MP to achieve concentrations of 0, 0.1, 1, or 10 mM and inoculated with sediment. When headspace CH4concentrations decreased from 10% to < 2%, subsamples were taken for DNA extraction and sequencing of 16S rRNA gene amplicons. There was minimal effect of 2C6MP on CH4oxidation at concentrations of 0.1, and 1 mM, but complete inhibition for > 20 months was observed at 10 mM. ANOSIM of weighted UniFrac distances between groups of triplicate samples supported a primary distinction of the inoculum relative to the enrichments (R=0.999) and a secondary distinction between bottles containing 2C6MP versus those without (R=0.464 [0.1 mM]; R=0.894 [1 mM]). The inoculum was dominated by members of theProteobacteria(49.9±1.5%), and to a lesser extent byBacteroidetes(8.8±0.2%),Acidobacteria(8.9±0.4%), andVerrucomicrobia(4.4±0.3%). In enrichments with or without 2C6MP,Proteobacteriaexpanded to comprise 65–70% of the total. In the absence of inhibitor, members of theMethylococcaceaeandMethylophilaceaeincreased in relative abundance from < 0.1% of the inoculum to 8.5±1.0% and 13.4±2.3%, of the total community respectively. At both 0.1 and 1 mM concentrations of the inhibitor, theMethylococcaceaewere much less abundant, representing 3.3±0.5% and 2.8±3.3% respectively. No inhibition of theMethylophilaceaewas seen at the lower concentration of 2C6MP, but at the higher concentration this taxon was only 7.8±1.1% of the total. In contrast, members of theCrenotrichaceae, another group of methane oxidizers, increased in relative abundance with greater amounts of inhibitor, representing 8.6±3.6% of the total at 0.1 mM and 12.0±4.5% at 1 mM, compared to only 4.1±0.4% when no inhibitor was present. These results clearly show changes in the populations of putative aerobic methanotrophs relative to the amount of 2C6MP present.
PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration
Authors: Chen Jinghao , Holt Jesse R. , Evans Elizabeth L. , Lowengrub John S. , Pathak Medha M.
Published: October 2022

The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1’s contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration.

Author summary

During the healing of a wound, cells called keratinocytes that make up the outer layer of the skin migrate collectively to close the wound gap. The mechanically activated ion channel PIEZO1 was previously found to inhibit wound closure. Here, through a combined modeling and experimental approach, we investigate the role of PIEZO1 in regulating collective migration. Specialized cells called leader cells, which typically form along the wound edge, are important for guiding the migration of neighboring cells. These leader cells dictate the coordinated directionality, or the cohesiveness of the migration direction between neighboring cells, through the transmission of mechanical and biochemical cues. We find that PIEZO1 activity inhibits the formation of these leader cells and, as a result, inhibits cell coordinated directionality causing the collective movement of cells to become disorganized and less effective in closing the wound. Our findings shed light on the complex mechanisms underlying collective migration, providing valuable insight into how mechanical cues affect the movement of cells during wound closure.
Improved Protocol for Single-Nucleus RNA-sequencing of Frozen Human Bladder Tumor Biopsies
Authors: Schmøkel Sofie S. , Nordentoft Iver , Lindskrog Sia V. , Lamy Philippe , Knudsen Michael , Jensen Jørgen Bjerggaard , Dyrskjøt Lars
Published: October 2022

This paper provides a laboratory workflow for single-nucleus RNA-sequencing (snRNA-seq) including a protocol for gentle nuclei isolation from fresh frozen tumor biopsies, making it possible to analyze biobanked material. To develop this protocol, we used non-frozen and frozen human bladder tumors and cell lines. We tested different lysis buffers (IgePal and Nuclei EZ) and incubation times in combination with different approaches for tissue and cell dissection; sectioning, semi-automated dissociation, manual dissociation with pestles, and semi-automated dissociation combined with manual dissociation with pestles. Our results showed a combination of IgePal lysis buffer, tissue dissection by sectioning and short incubation time was the best conditions for gentle nuclei isolation applicable for snRNA-seq, and we found limited confounding transcriptomic changes based on the isolation procedure. This protocol makes it possible to analyze biobanked material from patients with well described clinical and histopathological information and known clinical outcomes with snRNA-seq.
Analysis of Skin Cancers from Xeroderma Pigmentosum Patients Reveals Heterogeneous UV-Induced Mutational Profiles Shaped by DNA Repair
Authors: Yurchenko Andrey A. , Rajabi Fatemeh , Braz-Petta Tirzah , Fassihi Hiva , Lehmann Alan , Nishigori Chikako , Padioleau Ismael , Gunbin Konstantin , Panunzi Leonardo , Morice-Picard Fanny , Laplante Pierre , Robert Caroline , Kannouche Patricia L. , Menck Carlos F. M. , Sarasin Alain , Nikolaev Sergey I.
Published: October 2022

Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase η (V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors and experiments withPOLH-KO cell line revealed the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.
DNMT1 inhibition by pUG-fold quadruplex RNA
Authors: Jansson-Fritzberg Linnea I. , Sousa Camila I. , Smallegan Michael J. , Song Jessica J. , Gooding Anne R. , Kasinath Vignesh , Rinn John L. , Cech Thomas R.
Published: October 2022

Aberrant DNA methylation is one of the earliest hallmarks of cancer. DNMT1 is responsible for methylating newly replicated DNA, but the precise regulation of DNMT1 to ensure faithful DNA methylation remains poorly understood. A link between RNA and chromatin-associated proteins has recently emerged, and several studies have shown that DNMT1 can be regulated by a variety of RNAs. In this study we have confirmed that human DNMT1 indeed interacts with multiple RNAs, including its own nuclear mRNA. Unexpectedly, we found that DNMT1 exhibits a strong and specific affinity for GU-rich RNAs that form a pUG-fold, a non-canonical G-quadruplex. We find that pUG-fold-capable RNAs inhibit DNMT1 activity by inhibiting binding of hemimethylated DNA, and additionally provide evidence for multiple RNA binding modes with DNMT1. Together, our data indicates that a human chromatin-associated protein binds to and is regulated by pUG-fold RNA.
Arts marketing during COVID-19: a critical review and theoretical integration
Authors: Fillis Ian , Lehman Kim , Rentschler Ruth , Lee Boram
Published: October 2022

Purpose

This paper aims to provide clarity on arts marketing during COVID-19 by undertaking a critical review and theoretical integration of published cultural and creative industries (CCIs) data on the pandemic.

Design/methodology/approach

The study draws on the findings from a content analysis of published refereed journal articles and research reports, between 2020 and 2022.

Findings

This study clarifies how scholars in the arts marketing field have examined the concept and identified core dimensions. It also brings together these conceptual categories into an integrative multilevel framework of relevance for arts marketing during COVID-19. The framework outlines interconnected processes as well as dualities, such as digitisation, monetisation and sustainability of the CCIs and poses a future centred on entrepreneurial actions.

Originality/value

The originality of the paper is that it provides clear-cut evidence for new frontiers for research in the field during a period of discontinuous change due to COVID-19, through a literature review that has not been undertaken previously. It links the need to be entrepreneurial as a means for the CCIs to survive and thrive during and after a global crisis.
Market competition, capital regulation and cost of financial intermediation: an empirical study on the banking sector of Bangladesh
Authors: Mia MD. Rasel
Published: October 2022

Purpose

This study aims to examine the impact of market competition, and capital regulation on the cost of financial intermediation of banks of the Bangladesh banking industry.

Design/methodology/approach

This study has used a balanced panel dataset comprised of 340 firm-year observations for 34 commercial banks in the Bangladesh banking industry from 2011 to 2020. The Prais Winsten panel estimator has been used to assess the impact of market competition and capital regulation on the cost of financial intermediation of banks.

Findings

Based on the regression results, this study has documented that greater market competition results in a lower cost of financial intermediation for banks. Similarly, an increase in the regulatory capital of banks increases the cost of financial intermediation of banks. The main findings of this study are found robust by using alternative proxies for the cost of financial intermediation, market competition and capital regulation. The regression results also suggest that private commercial banks tend to have a higher cost of financial intermediation than state-owned commercial banks.

Research limitations/implications

The regulatory reforms should aim to foster sustainable and optimal market competition for the Bangladesh banking industry to regulate the market power of banks to reduce the cost of financial intermediation. The regulatory authority of Bangladesh should find the optimal policy measures for implementing the capital regulation in the banking industry which would reduce the cost of financial intermediation margin of banks.

Originality/value

Unlike previous studies which have used structural market competition measures, this study has used non-structural market competition measures to assess the relationship between market competition and cost of financial intermediation in the Bangladesh banking industry.
Thermal behavior of a conical antenna cooled with nanofluid saturated porous media: effects of the cavity’s inclination and aspect ratio
Authors: Alilat Nacim , Martin Elena B. , Sastre Francisco , Millán García Jose Antonio , Baïri Abderrahmane
Published: October 2022

Purpose

The aim of this work is to determine the average surface temperature of a conical antenna. Its cooling is ensured by means of a nanofluid-saturated porous structure. The volume fraction of the H2O–Cu nanofluid ranges between 0% (pure water) and 5%, whereas the ratio between the thermal conductivity of the used porous materials and that of water (fluid base) varies in the wide 4–41.2 range. The antenna is contained in a coaxial conical closed cavity with a variable distance between the cones, leading to an aspect ratio varying between 0.2 and 0.6. The axis of the assembly is also inclined with respect to the gravity field by an angle varying between 0° (a vertical axis with top of the cone oriented upwards) and 180° (a vertical axis with top of the cone oriented downwards).

Design/methodology/approach

Simulations have been done by means of the volume control method based on the SIMPLE algorithm.

Findings

Results of the numerical approach show that the cavity’s aspect ratio and inclination with respect to the gravity field significantly affect the thermal behavior of the active cone. Otherwise, the work confirms that the Maxwell and Brinkman models used to determine the nanofluid’s effective thermal conductivity and viscosity, respectively, are adapted to the considered assembly.

Originality/value

A new correlation is proposed, allowing the determination of the average surface temperature of the active cone and its correct thermal sizing. This correlation could be used in various engineering fields, including electronics, examined in the present study.
Linking organizational exploitation to extra-role behaviors: a conservation of resources perspective
Authors: Cheng Xuan-Mei , Lyu Yijing , Ye Yijiao
Published: October 2022

Purpose

Drawing on conservation of resources (COR) theory, this study aims to explore how perceived organizational exploitation affects hospitality employees’ extra-role customer service behaviors by investigating the mediating role of depressed mood at work and the moderating role of reappraisal.

Design/methodology/approach

This study tested all of the hypotheses using multilevel path analyses with a sample of 340 supervisor–subordinate dyads.

Findings

The results show that perceived organizational exploitation is indirectly associated with hospitality employees’ extra-role customer service through depressed mood at work and that employees’ reappraisal may help mitigate the negative effect of organizational exploitation.

Practical implications

First, policies and rules should be established in advance to prevent organizational exploitation. Second, we suggest that hospitality organizations should pay special attention to employees who have low levels of reappraisal, and reappraisal training could be provided to enhance their emotion regulation skills. Third, hospitality organizations could nurture a healthy and supportive emotional climate to create positive emotions in the workplace, in case that depressed mood at work contributes to employees’ extra-role behaviors.

Originality/value

First, the authors go beyond previous studies to focus on a new behavioral outcome of perceived organizational exploitation, i.e. extra-role customer service. Second, it applies a new perspective of COR theory to determine the underlying mechanism of perceived organizational exploitation. Third, to the best of the authors’ knowledge, this study is one of the first to explore the boundary conditions under which the destructive effects of perceived organizational exploitation can be mitigated.
Coordinating multi-level collective action: how intermediaries and digital governance can help supply chains tackle grand challenges
Authors: Rosca Eugenia , Tate Wendy L. , Bals Lydia , Huang Feigao , Ciulli Francesca
Published: October 2022

Purpose

Driven by increasing concerns for sustainable development and digitalization, intermediaries have emerged as relevant actors who can help supply chains tackle grand societal challenges. They can also trigger significant changes in structure, shape and governance models of supply chains. The goal of this research is to advance the understanding of supply chain intermediation and digital governance as coordinating mechanisms for enabling multi-level collective action to address the world's grand challenges.

Design/methodology/approach

This is a conceptual research paper that uses a vignette approach, where real examples are described to help question and expand theoretical insights and provide a basis for future research. The examples are drawn from past and ongoing extensive primary and secondary data collection efforts in diverse types of supply chains.

Findings

Three contexts are proposed to illustrate how intermediaries and digital governance can play a key role in helping supply chains tackle grand challenges. The first and second context highlight the differences between material and support flow intermediaries in a triadic supply chain relationship. The third context illustrates intermediation within a multi-level network which can be industry-specific or span across industries. The three contexts are evaluated on the level of intervention, the focus on material or support flows, and traditional or digital governance. The specific Sustainable Development Goals which can be tackled through intermediary intervention are also indicated.

Originality/value

Intermediaries are often hidden actors in global supply chains and have received limited attention in the academic literature. The conceptual foundation provided in this manuscript serves as the basis for future research opportunities. Three main avenues for further research in this domain are proposed: (1) novel forms of intermediation beyond economic and transactional arrangements; (2) novel forms of digital governance; and (3) translating multi-level collective action into sustainable development outcomes. Research on intermediation driven by sustainable development and digitalization trends can spur empirical advances in sustainable supply chain and operations management with important societal impact.
Advance selling of uncertain demand in low-carbon supply chain
Authors: Jia Haicheng , Li Jing , Liang Ling , Peng Weicai , Xie Jiqing , Xie Jiaping
Published: October 2022

Purpose

The development of low-carbon production is impeded by the investment costs of green technology research and development (R&D) and carbon emission reduction while facing the uncertain risk of emission reduction investment. With the government's carbon emission constraints, green manufacturers implement the advance selling strategy to increase both profit and reduction level. However, few studies consider the consumer's green preference and emission constraints in advance selling market and spot market independently. The authors' paper investigates the optimal strategies of advance selling pricing and reduction effort for green manufacturers to maximize profits.

Design/methodology/approach

The authors' paper designs a stochastic model and investigates the manufacturer's optimal strategies of advance selling price and emission reduction efforts by categorizing different purchasing periods of low-carbon consumers. With the challenges of uncertain demand and government's emission constraints, the authors' develop the non-linear optimization model to investigate the manufacturer's profit-oriented decisions.

Findings

The results show the government's carbon constraints cannot influence the manufacturer's profit, but the consumer's low-carbon preference in the advance selling period can. Interestingly, the manufacturer will make fewer reduction efforts even when the consumers have stronger environmental awareness. In addition, the increasing consumer price sensitivity will exacerbate the profit loss from mandatory emissions reduction. Overall, for achieving a win–win situation between emission reduction and profit growth, green manufacturers should not only consider the sales strategies, market demand, and government constraints in a low-carbon market, but also pay attention to the uncertainty of green technology innovation.

Originality/value

With the consideration of the government's carbon emission constraints, uncertain demand, and low-carbon consumer's preferences, the authors' study innovatively incorporates the joint impacts of advance selling strategy and emission reduction effort strategy and then differentiates between two cases that pertain to the diverse carbon emission regulations.
Preliminary investigation on the self-propulsion performance of wedge-shaped functional surfaces
Authors: Li Qianqian , Zhang Bo , Yang Tao , Dai Qingwen , Huang Wei , Wang Xiaolei
Published: October 2022

Purpose

The purpose of this paper is to artificially construct a functional surface with self-propulsion flow characteristics for the directional transportation of propellant in surface tension tanks.

Design/methodology/approach

In this study, a method to enhance the propulsion efficiency by using functional surfaces of self-propulsion performance was proposed. Superhydrophilic wedged-groove with the superhydrophobic background was fabricated and the self-propulsion capacity was verified.

Findings

It is found that the self-propulsion capacity is related to the divergence angle of the wedged-groove in the hydrophilic area, and the velocity of the droplets on the deflector plate is the largest with the divergence angle of 4°; the temperature gradient field formed by the condensing device at the nozzle can accelerate the droplet outflow from the tank.

Originality/value

Realization of this idea provides an accurate control strategy for the complex flow process of propellant in plate surface tension tanks, which could enhance the efficiency of the tension tank significantly.
Perceived determinants for modifying littering behavior – a study testing the influence of perceived behavioral control, environmental factors and intention
Authors: Kaur Ranjit , Singh Jagwinder
Published: October 2022

Purpose

The purpose of the paper is to empirically examine the impact of environmental factors and perceived behavioral control (PBC) in addition to the intention on modified littering behavior.

Design/methodology/approach

The present study followed a quantitative approach. The empirical data for the present study were drawn from 750 individuals across the states of Delhi and Punjab in India. The predictors of the antecedents of the modified behavior have been examined using confirmatory factor analysis in AMOS 21.0. The hypothesized relationships were tested using structural equation modeling.

Findings

The results of the current research found that the modified littering behavior was significantly influenced by intention, PBC and environmental factors. Among these predictor variables, environmental factors have been found influencing the modified littering behavior to the highest extent.

Practical implications

Considering the highest influence of environmental factors, social marketing interventions need to focus on cleaning the already littered areas, convenient placement of trash bins, regular cleanliness, sanitization and emptying of trash bins.

Originality/value

Looking at the uniqueness of the present study in the Indian context, this paper is the first to empirically examine the predictive ability of environmental factors and PBC in addition to the intention that may help close the intention–behavior gap.