bluuebunny/crossref_metadata_2025 huggingface dataset:
A functional variant ofCD40modulates clearance of hepatitis B virus in hepatocytes via regulation of the ANXA2/CD40/BST2 axis
Authors: Chen Jiaxuan , Chen Haitao , Mai Haoming , Lou Shuang , Luo Mengqi , Xie Haisheng , Zhou Bin , Hou Jinlin , Jiang De-Ke
Published: November 2022

More than 250 million people in the world are chronically infected with hepatitis B virus (HBV), which causes serious complications. Host genetic susceptibility is essential for chronic hepatitis B (CHB), and our previous genome-wide association study identified a single-nucleotide polymorphism (SNP), rs1883832, in the 5′ untranslated region of CD40 predisposing to chronic HBV infection, but the underlying mechanism remains undefined. This study aimed to investigate whether rs1883832 was the real functional SNP (fSNP) of CD40 and how it modulated HBV clearance in hepatocytes. We determined the fSNP of CD40 and its regulatory protein(s) using luciferase reporter assays, electrophoretic mobility shift assay, flanking restriction enhanced pulldown and chromatin immunoprecipitation. The potential anti-HBV activity of CD40 and its downstream molecule BST2 was assessed in HBV-transfected and HBV-infected hepatoma cells and HBV-infected primary human hepatocytes. Moreover, the mechanism of CD40 was investigated by mRNA sequencing, quantitative real-time polymerase chain reaction, immunofluorescence and western blot. We revealed rs1883832 as the true fSNP of CD40 and identified ANXA2 as a negative regulatory protein that preferentially bound to the risk allele T of rs1883832 and hence reduced CD40 expression. Furthermore, CD40 suppressed HBV replication and transcription in hepatocytes via activating the JAK–STAT pathway. BST2 was identified to be the key IFN-stimulated gene regulated by CD40 after activating JAK–STAT pathway. Inhibition of JAK/STAT/BST2 axis attenuated CD40-induced antiviral effect. In conclusion, a functional variant of CD40 modulates HBV clearance via regulation of the ANXA2/CD40/BST2 axis, which may shed new light on HBV personalized therapy.
Application of health belief model in the assessment of factors affecting exercise behaviours in preventing osteoporosis
Authors: Ong Siew Chin , Low Joo Zheng , Ooi Guat See
Published: November 2022

Objectives

Osteoporosis is a skeletal disorder associated with weak and brittle bones, and more susceptible to fracture. Osteo-protective behaviours, such as exercise, may prevent osteoporosis. Therefore, this study aimed to assess the factors influencing the exercise behaviour in Malaysian adults and to assess their health beliefs and self-regulation in preventing osteoporosis.

Methods

A cross-sectional, self-administered questionnaire was conducted throughout Malaysia through a web-based or physical-based survey. The questionnaire consisted of three sections: demographic data, ten questions regarding social and family history related to osteoporosis and 38 questions with seven subdomains (i.e. susceptibility, seriousness, barriers, benefits, health motivation, self-efficacy and self-regulation) which measured the health belief scores and self-regulation using 5-point Likert scale. Descriptive, inferential analysis and linear regression were used to analyse the data.

Key findings

A total of 679 participants completed the questionnaire. The mean health belief score was 63.7%, which was moderate. Most participants (64.4%) perceived low susceptibility to osteoporosis [mean score = 47.0%, standard deviation (SD) = 16.2]. Participants with age 18–27 years (44.8%), single (45.0%) and monthly income <RM 1000 (45.2%), perceived significant lower susceptibility to osteoporosis. Participants’ perception scores were high on the benefits of exercise (75.7%, SD = 16.4), health motivation (74.9%, SD = 17.1) and perceived low barriers to exercise (71.7%, SD = 14.9). Respondents who were at risk of osteoporosis and with family and friends diagnosed with osteoporosis obtained a higher score than those who did not.

Conclusions

The health belief score in the Malaysian population was moderate. However, the majority of participants were unaware of the susceptibility and seriousness of osteoporosis. Efforts need to be taken to break the barriers associated with exercise in preventing osteoporosis.
Pitavastatin attenuates neuropathic pain induced by partial sciatic nerve in Wistar rats
Authors: Goel Radha , Kumar Nitin , Kumar Saxena Prasoon , Pratap Singh Alok , Bana Sweeti
Published: November 2022

Objectives

Pitavastatin is a competitive HMG-CoA reductase inhibitor for lowering of cholesterol level and low density lipoprotein cholesterol. This study was designed to evaluate the effect of pitavastatin in neuropathic pain induced by partial sciatic nerve ligation along with neuronal changes in Wister rats.

Methods

Pitavastatin was started three days prior to the surgery and continued for 14 days The pain was determined by thermal hyperalgesia and cold allodynia. The biochemical changes were estimated at the end of the study. The levels of cytokines were measured using an ELISA test. Western blot analysis was used to detect levels of expression of JNK, p-JNK, ERK, p-ERK, p38MAPK, p-p38MAPK. The sciatic nerve was investigated histopathologically.

Key findings

Pitavastatin significantly ameliorated nerve pain induced by PSNL and also attenuated the biochemical changes in a dose-dependent manner. The levels of inflammatory mediators were inhibited by pitavastatin. There was significant improvement in sciatic nerve fibres histology. The levels of p-38, p-ERK, and p-JNK and their associated phosphorylated proteins were reduced after treatment with pitavastatin.

Conclusion

The present study indicates that treatment with pitavastatin reversed the PSNL-induced neuropathy in Wister rats and may be an additional therapeutic strategy in the management of neuropathic pain.
Recursive rules with aggregation: a simple unified semantics
Authors: Liu Yanhong A , Stoller Scott D
Published: November 2022

Complex reasoning problems are most clearly and easily specified using logical rules, but require recursive rules with aggregation such as count and sum for practical applications. Unfortunately, the meaning of such rules has been a significant challenge, leading to many disagreeing semantics. This paper describes a unified semantics for recursive rules with aggregation, extending the unified founded semantics and constraint semantics for recursive rules with negation. The key idea is to support simple expression of the different assumptions underlying different semantics, and orthogonally interpret aggregation operations using their simple usual meaning. We present a formal definition of the semantics, prove important properties of the semantics and compare with prior semantics. In particular, we present an efficient inference over aggregation that gives precise answers to all examples we have studied from the literature. We also apply our semantics to a wide range of challenging examples, and show that our semantics is simple and matches the desired results in all cases. Finally, we describe experiments on the most challenging examples, exhibiting unexpectedly superior performance over well-known systems when they can compute correct answers.
The environments and hosts of metal absorption at z > 5
Authors: Doughty Caitlin C , Finlator Kristian M
Published: November 2022

A growing population of metal absorbers are observed at z > 5, many showing strong evolution in incidence approaching the epoch of hydrogen reionization. Follow-up surveys examining fields around these metals have resulted in galaxy detections but the direct physical relationship between the detected galaxies and absorbers is unclear. Upcoming observations will illuminate this galaxy–absorber relationship, but the theoretical framework for interpreting these observations is lacking. To inform future z > 5 studies, we define the expected relationship between metals and galaxies using the Technicolor Dawn simulation to model metal absorption from z = 5 to 7, encompassing the end of reionization. We find that metal absorber types and strengths are slightly better associated with their environment than with the traits of their host galaxies, as absorption system strengths are more strongly correlated with the local galaxy overdensity than the stellar mass of their host galaxy. For redshifts prior to the end of the epoch of reionization, strong high-ionization transitions like C iv are more spatially correlated with brighter galaxies on scales of a few hundred proper kpc than are low-ionization systems, due to the former’s preference for environments with higher ultraviolet background amplitudes and those ions’ relative rarity at z > 6. Post-reionization, the galaxy counts near these high-ionization ions are reduced, and increase surrounding certain low-ionization ions due to a combination of their relative abundances and preferred denser gas phase. We conclude that galaxy–absorber relationships are expected to evolve rapidly such that high-ionization absorbers are better tracers of galaxies pre-reionization, while low-ionization absorbers are better post-reionization.
DirectRMDB: a database of post-transcriptional RNA modifications unveiled from direct RNA sequencing technology
Authors: Zhang Yuxin , Jiang Jie , Ma Jiongming , Wei Zhen , Wang Yue , Song Bowen , Meng Jia , Jia Guifang , de Magalhães João Pedro , Rigden Daniel J , Hang Daiyun , Chen Kunqi
Published: November 2022

With advanced technologies to map RNA modifications, our understanding of them has been revolutionized, and they are seen to be far more widespread and important than previously thought. Current next-generation sequencing (NGS)-based modification profiling methods are blind to RNA modifications and thus require selective chemical treatment or antibody immunoprecipitation methods for particular modification types. They also face the problem of short read length, isoform ambiguities, biases and artifacts. Direct RNA sequencing (DRS) technologies, commercialized by Oxford Nanopore Technologies (ONT), enable the direct interrogation of any given modification present in individual transcripts and promise to address the limitations of previous NGS-based methods. Here, we present the first ONT-based database of quantitative RNA modification profiles, DirectRMDB, which includes 16 types of modification and a total of 904,712 modification sites in 25 species identified from 39 independent studies. In addition to standard functions adopted by existing databases, such as gene annotations and post-transcriptional association analysis, we provide a fresh view of RNA modifications, which enables exploration of the epitranscriptome in an isoform-specific manner. The DirectRMDB database is freely available at: http://www.rnamd.org/directRMDB/.
Passing the buck!—how credible are self-reported measures of confidence in public institutions?
Authors: Chatterjee Somdeep
Published: November 2022

Measures of confidence in public institutions are self-reported and therefore, susceptible to heterogeneity arising out of individual perceptions. In this article, I explore the possibility of individuals reporting lower levels of confidence in public institutions depending on their personal economic conditions, for which these institutions cannot be solely held responsible. Using nationally representative Indian data, I exploit exogenous sources of indebtedness in an instrumental variables regression approach to identify the causal effects of personal economic hardships on confidence in public institutions. The identification strategy relies on exogenous variation in the measure of indebtedness generated by a large monetary loss arising out of natural calamities such as accident, fire, or drought. I find that estimated coefficients from two-stage least square regressions are negative and statistically significant suggesting that an increase in indebtedness is associated with an erosion in confidence measures.
Academic achievements and brain volume development in children and adolescents
Authors: Hashimoto Teruo , Matsuzaki Yutaka , Yokota Susumu , Kawashima Ryuta
Published: November 2022

Children are expected to acquire both basic and numeric skills. Achievement of higher levels of reading, writing, arithmetic, and vocabulary are favorable and desirable. The relationship between each literacy skill and neural development has been investigated; however, association between brain development and the 4 literacy skills has not been examined. This longitudinal, structural, neuroimaging study explored the contribution of higher academic achievement in reading, writing, arithmetic, and vocabulary to neural development. The brain volumes of children and adolescents aged 9–16 years were measured in the first test. Approximately 2.6 years later, the brain volumes and 4 academic achievement scores of 77 participants were measured in the second test. Changes in the gray matter volume in the left fusiform gyrus were associated with vocabulary scores, whereas those in the left striatum were associated with arithmetic scores. The reading and writing scores showed no statistically significant relationship with changes in brain volume. The current vocabulary score correlated with current gray matter volume, while brain volumes in the first test showed no association with any achievement scores. These results suggest that academic achievement may modulate brain plasticity in various ways.
Development of Colloidal Gold Immunochromatography and Reverse-Transcription Loop-Mediated Isothermal Amplification Assays to Detect Lychnis Mottle Virus
Authors: Jin Weijie , Zhang Yubao , Su Xuesi , Wang Ruoyu , Xie Zhongkui , Wang Yajun , Qiu Yang
Published: November 2022

Lychnis mottle virus (LycMoV; genus Unassigned, family Secoviridae) infection of Angelica sinensis produces mottle and mosaic symptoms, damaging the host. Early detection of relevant pathogens is the most critical step in preventing the potential transmission of infectious disease. Polyclonal antibodies with high potency and high specificity were prepared using the recombinant LycMoV capsid protein as an antigen. Here, we developed and optimized a rapid colloidal gold immunochromatography assay (GICA) detection system for LycMoV using this antibody. Under optimum conditions, GICA specifically detected (up to 10,000-fold) positive LycMoV samples. A real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) system was also established by selecting the primers with high sensitivity and specificity to LycMoV. The RT-LAMP detection threshold was 1.42 fg/μl (291 copies/μl). A GICA-RT-LAMP assay system was further established and optimized. The minimum GICA detection line was calculated at 1.52 × 10−2 ng/μl. Although GICA did not detect positive samples after capturing virus at 2.53 × 10−3 ng/μl, GICA-LAMP and GICA-RT-PCR did, whose sensitivity was comparatively greater than sixfold. This is the first report showing that GICA-RT-LAMP is a cost-effective approach for use in detecting LycMoV without extracting nucleic acids. These sensitive assays will help improve virus disease management in A. sinensis crops.
Complete Genome Sequence Resource of the Pathogen Pectobacterium cacticida CFCC 10813T Causing Soft Rot Diseases of Cactus Plants
Authors: Xie Ting , Zhu Huajie , Liao Tianlan , Liang Yan , An Qianli
Published: November 2022

Pectobacterium cacticida (formerly Erwinia cacticida) causes soft rot disease of cactus plants. Its taxonomic status within the genus Pectobacterium remains questionable because no whole genome sequence of this species is available in public databases for reliable taxonomic analyses. Here, we present the complete genome sequence of the P. cacticida type strain CFCC 10813T (=1-12T = ATCC 49481T). P. cacticida can be classified into the genus Pectobacterium because it is on the deepest basal phylogenomic branch of the genus Pectobacterium, and its genome relatedness to other Pectobacterium species is at the border for the genus delimitation boundaries. This complete genome sequence provides the genome resource for elucidating P. cacticida pathogenicity and adaptation to plant hosts and environments.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs
Authors: Ibrahim John , Mahmood Burhan , DiGeronimo Robert , Rintoul Natalie E. , Hamrick Shannon E. , Chapman Rachel , Keene Sarah , Seabrook Ruth B. , Billimoria Zeenia , Rao Rakesh , Daniel John , Cleary John , Sullivan Kevin , Gray Brian , Weems Mark , Dirnberger Daniel R. ,   for the CHNC ECMO Focus Group
Published: November 2022

OBJECTIVES:

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs).

DESIGN:

Cross-sectional electronic survey.

SETTING:

Email-based Research Electronic Data Capture survey.

PATIENTS:

Neonates undergoing ECMO for respiratory failure at level IV NICUs.

INTERVENTIONS:

A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children’s Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals.

MEASUREMENTS AND MAIN RESULTS:

Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16–20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9–10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10–15 (60%), and Fio
2 22–30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6–7 (45%), PIP of 21–25 (55%), and tidal volume 5–5.9 mL/kg (50%).

CONCLUSIONS:

The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients.
Assessment of visual field progression in glaucoma
Authors: Chen Rebecca I. , Gedde Steven J.
Published: November 2022

Purpose of review

Perimetry plays an important role in the diagnosis and management of glaucoma. This article discusses the assessment of visual field progression in patients with glaucoma.

Recent findings

Selecting the best visual field test strategy and establishing a baseline of visual fields will assist clinicians in the detection of glaucomatous progression. Repeat testing serves to confirm or refute changes on visual field testing. More frequent testing after initial diagnosis is recommended to establish a baseline and to identify patients with rapid progression who may need more aggressive management. Statistically significant changes on event analysis can prompt examination of a patient's trend analysis to determine whether clinically significant deterioration may be occurring. Future applications of machine learning can complement existing methods of visual field interpretation.

Many treated patients with glaucoma will experience visual field progression. Optimal utilization of visual field testing strategy and analytical software can help clinicians identify patients with glaucomatous progression likely to cause functional visual disability.
Hybrid Ga-68 prostate-specific membrane antigen PET/MRI in the detection of skeletal metastasis in patients with newly diagnosed prostate cancer: Contribution of each part to the diagnostic performance
Authors: Asa Sertac , Ozgur Eren , Uslu-Besli Lebriz , Ince Burak , Sager Sait , Demirdag Cetin , Guner Ekrem , Sayman Haluk B. , Bakir Baris , Sonmezoglu Kerim
Published: November 2022

Purpose

Bone metastasis is essential in patients with prostate cancer (PCa) as it determines prognosis and survival. Hybrid PET/MRI allows simultaneous acquisition of PET and MRI data, thus combining the strength of both technologies allows the detection of bone marrow metastases that are missed by PET/CT. In this retrospective study, we aimed to evaluate the diagnostic efficiency of hybrid PET/MRI with Ga-68 prostate-specific membrane antigen (PSMA) in detecting skeletal metastases in newly diagnosed PCa patients and compared the effectiveness of stand-alone PSMA PET reviewing versus stand-alone whole-body (WB) MRI evaluation. We also investigated the effect of the interpretation of all PET/MR data together on clinical management.

Methods

We studied 74 newly diagnosed PCa patients who underwent PSMA PET/MRI for staging purposes. At first, PET and MRI were evaluated separately for bone lesions on a patient-and-lesion basis and then a further joint PSMA PET/MRI interpretation was made.

Results

Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy analysis for bone metastasis was, respectively, 1.0, 0.83, 0.54, 1.0, 0.86 for PET; 0.75, 0.96, 0.81, 0.95, 0.93 for WB MRI and 0.91, 0.95, 0.78, 0,98, 0.94 for PET/MRI. The combined PET/MRI evaluation changed the clinical impact in 13.5% of patients (eight correct and two wrong decisions) compared to PET stand-alone interpretation.

Conclusion

PSMA PET imaging showed superior sensitivity to WB MRI in detecting bone metastases in newly diagnosed PCa patients, whereas WB MRI has superior specificity and PPV. Furthermore, the specificity and PPV of joint PET/MRI evaluation are better than PSMA PET alone. Despite the longer acquisition period, adding WB MRI sequences to PSMA PET imaging appears beneficial for PCa patient management.
The great team: A recipe
Authors: Rosengart Matthew R.
Published: November 2022

When do the many become one? Why does one join with others? In his political writings of self-government, Rousseau proposes “when the obstacles to their self-preservation in the state of nature are too great to be overcome by the forces each individual is capable of exerting to maintain himself in that state.” Few obstacles are more threatening to an individual than disease and death, and our response as a civilization is the institution of healthcare. The impetus for this perspective piece budded from personal experience and a resultant sentiment that emerged from more deliberate contemplation. It is purposed to conjure in the reader a certain joy of that which can be accomplished through collaboration, but concomitantly, to offer perspective as to characteristics opined to be vital to creating and maintaining a great team.
Response to ‘Comment on “Quantum correlations are weaved by the spinors of the Euclidean primitives”’
Authors: Christian Joy
Published: November 2022

In this paper, I respond to a critique of one of my papers previously published in the
Royal Society Open Science
entitled ‘Quantum correlations are weaved by the spinors of the Euclidean primitives.’ Without engaging with the geometrical framework presented in my paper, the critique incorrectly claims that there are mathematical errors in it. I demonstrate that the critique is based on a series of misunderstandings, and refute each of its claims of error. I also bring out a number of logical, mathematical and conceptual errors from the critique and the critiques it relies on.
Eco-hydrological modelling of channel network dynamics—part 1: stochastic simulation of active stream expansion and retraction
Authors: Durighetto Nicola , Bertassello Leonardo E. , Botter Gianluca
Published: November 2022

Dynamic changes in the active portion of stream networks represent a phenomenon common to diverse climates and geologic settings. However, mechanistically describing these processes at the relevant spatiotemporal scales without huge computational burdens remains challenging. Here, we present a novel stochastic framework for the effective simulation of channel network dynamics capitalizing on the concept of ‘hierarchical structuring of temporary streams’—a general principle to identify the activation/deactivation order of network nodes. The framework allows the long-term description of event-based changes of the river network configuration starting from widely available climatic data (mainly rainfall and evapotranspiration). Our results indicate that climate strongly controls temporal variations of the active length, influencing not only the preferential configuration of the active channels but also the speed of network retraction during drying. Moreover, we observed that—while the statistics of wet length are mainly dictated by the underlying climatic conditions—the spatial patterns of active reaches and the size of the largest connected patch of the network are strongly controlled by the spatial correlation of local persistency. The proposed framework provides a robust mathematical set-up for analysing the multi-faceted ecological legacies of channel network dynamics, as discussed in a companion paper.
The Madelung constant in
N
dimensions
Authors: Burrows Antony , Cooper Shaun , Schwerdtfeger P.
Published: November 2022

We introduce two convergent series expansions (direct and recursive) in terms of Bessel functions and the number of representations of an integer as a sum of squares for

N

-dimensional Madelung constants,

M
N

(
s
)

, where

s

is the exponent of the Madelung series (usually chosen as

s
=
1

/

2

). The convergence of the Bessel function expansion is discussed in detail. Values for

M
N

(
s
)

for

s
=

1
2

,

3
2

,
3

and 6 for dimension up to

N
=
20

are presented. This work extends Zucker’s original analysis on

N

-dimensional Madelung constants for even dimensions up to

N
=
8

.
Female dewlap ornaments are evolutionarily labile and associated with increased diversification rates in
Anolis
lizards
Authors: Yuan Michael L. , Westeen Erin P. , Wogan Guinevere O. U. , Wang Ian J.
Published: November 2022

The evolution of costly signalling traits has largely focused on male ornaments. However, our understanding of ornament evolution is necessarily incomplete without investigating the causes and consequences of variation in female ornamentation. Here, we study the
Anolis
lizard dewlap, a trait extensively studied as a male secondary sexual characteristic but present in females of several species. We characterized female dewlaps for 339 species to test hypotheses about their evolution. Our results did not support the hypothesis that female dewlaps are selected against throughout the anole phylogeny. Rather, we found that female dewlaps were evolutionary labile. We also did not find support for the adaptive hypothesis that interspecific competition drove the evolution of female dewlaps. However, we did find support for the pleiotropy hypothesis as species with larger females and reduced sexual size dimorphism were more likely to possess female dewlaps. Lastly, we found that female dewlap presence influenced diversification rates in anoles, but only secondarily to a hidden state. Our results demonstrate that female ornamentation is widespread in anoles and the traditional hypothesis of divergent selection between the sexes does not fully explain their evolution. Instead, female ornamentation is likely to be subject to complex adaptive and non-adaptive evolutionary forces.
Non-parametric GWAS: Another View on Genome-wide Association Study
Authors: Hu Xiaoyue , Yu Shizhou , Jiang Hangjin
Published: November 2022

Genome-wide association study (GWAS) is a fundamental step for understanding the genetic link to traits (phenotypes) of interest, such as disease, BMI and height. Typically, GWAS estimates the effect of SNP on the phenotype using a linear model by coding SNP as working code, {0, 1, 2}, according to the minor allele frequency. Looking inside the linear model, we find that the coding strategy of SNP plays a key role in detecting SNPs contributed to the phenotype. Specifically, a partial mismatch between the order of the working code and that of the underlying true code will lead to false negatives, which has been ignored for a long time. Motivated by this phenomenon, we propose an indicator of possible false negatives and several non-parametric GWAS methods independent of coding strategy. Results from both simulations and real data analysis show the advantages of new methods in identifying significant loci, indicating their important complementary role in GWAS.
Buffering role of HSP shapes the molecular evolution of mammalian and human genomes at short and long-term scales
Authors: Timonina Valeriia , Tretiakov Evgenii , Goncharov Andrey , Gunbin Konstantin , Fellay Jacques , Popadin Konstantin
Published: November 2022

Heat shock proteins in parallel with their main and originally discovered function – maintenance of folded proteins under stressful conditions, can play also background buffering role – by folding proteins with an excess of slightly-deleterious nonsynonymous variants (SDNV). Here we tested several scenarios of this buffering role. On the comparative species scale, we demonstrated that low-Ne species are characterized by a higher expression level of hsp90 which can be explained by the excess of SDNV. On the comparative tissue level, we showed that long-lived tissues have also a higher hsp90 expression level, which can be advantageous to maintain the functionality of proteins. On the comparative gene level, we demonstrated that purifying selection of hsp90 in low-Ne-species did not relax as strongly as it happens for control genes, similar to hsp90. Additionally, we demonstrated that hsp clients versus non-clients are characterised by decreased level of selective constraints; demonstrate stronger relaxation of purifying selection in low-Ne species; have an excess of slightly-deleterious variants associated with complex disease phenotypes in humans; have an excess of pathological variants associated with clinical phenotypes in humans, suggesting that clients, being buffered by hsp90 can degenerate a bit more as compared to non-clients. Altogether, our results show that the secondary role of hsp, buffering of SDNV, is widespread and universal affecting properties of species, tissues and genes. A deep understanding of the buffering role of hsp90 will help to predict the deleterious effect of each variant in the human genome more precisely as well as will extend the application of the effectively-neutral theory of molecular evolution.
Computational Design of a New Aflatoxin B1 Aptamerin lieuof SELEX Technique
Authors: Ahmad Ghazy Mohamad Yasser
Published: November 2022

Mycotoxins are extremely dangerous, and their detection in our environment, food and feed is becoming increasingly important. Biosensors are being implemented heavily in mycotoxin detection along with other significant applications. Aptamers have numerous beneficial advantages as biorecognition molecules and are being used as the biorecognition part of biosensors (Aptasensors). The development of aptamers does not require inducing immune response against the target, but the SELEX method is used. The SELEX method is laborious, time consuming and can be expensive at times. Various efforts were done to replace that method with a computational alternative to reduce the effort, time and money needed to develop and design aptamers. One of the most significant efforts to achieve that was the MAWS algorithm. We used the MAWS algorithm to develop a new aptamer against aflatoxin B1, the most dangerous mycotoxin. The MAWS algorithm failed to function properly, and molecular modelling and molecular docking was used alternatively to achieve the same goal. A new pipeline for predicting ssDNA aptamers was proposed, a new aptamer against aflatoxin B1 was obtained and recommendations for further future research directions were given.
Viral Airway Injury Promotes Cell Engraftment in anIn VitroModel of Cystic Fibrosis Cell Therapy
Authors: Lee Rhianna E. , Mascenik Teresa M. , Major Sidra C. , Lewis Catherine A. , Bear James E. , Pickles Raymond J. , Randell Scott H.
Published: November 2022

Cell therapy is a potential treatment for cystic fibrosis (CF). However, cell engraftment into the airway epithelium is challenging. Here, we model cell engraftmentin vitrousing the air-liquid interface (ALI) culture system by injuring well-differentiated CF ALI cultures and delivering non-CF cells at the time of peak injury. Engraftment efficiency was quantified by measuring chimerism by droplet digital PCR and functional ion transport in Ussing chambers. Using this model, we found that human bronchial epithelial cells (HBECs) engraft more efficiently when they are cultured by conditionally reprogrammed cell (CRC) culture methods. Cell engraftment into the airway epithelium requires airway injury, but the extent of injury needed is unknown. We compared three injury models and determined that severe injury with partial epithelial denudation facilitates long-term cell engraftment and functional CFTR recovery up to 20% of wildtype function. The airway epithelium promptly regenerates in response to injury, creating competition for space and posing a barrier to effective engraftment. We examined competition dynamics by time-lapse confocal imaging and found that delivered cells accelerate airway regeneration by incorporating into the epithelium. Irradiating the repairing epithelium granted engrafting cells a competitive advantage by diminishing resident stem cell proliferation. Intentionally causing severe injury to the lungs of people with CF would be dangerous. However, naturally occurring events like viral infection can induce similar epithelial damage with patches of denuded epithelium. We found that viral preconditioning promoted effective engraftment of cells primed for viral resistance.
Formation process of the twinning β-form anhydrous guanine platelets in the scallop eyes
Authors: Guo Dongmei , Liu Yiqun , Hou Xiubin , Wang Xubo , Fan Chenge , Bao Lixia , He Xinpeng , Zhang Hongmei , Ma Yurong
Published: November 2022

Square shaped twinning guanine microplates with high symmetry are assembled into highly ordered layered patterns and function as image-forming mirrors in the scallop eyes. However, the formation process and biomineralization mechanism of twinning guanine microplatelets are still unclear. Herein, the eyes of juvenileYessoscallops were investigated to understand the formation mechanism of the twinning β-form anhydrous guanine (β-AG) microplatelets exposing (100) plane. We find α form anhydrous guanine (α-AG) and single-crystal β-AG nanoplatelets in the very early stage of the eyes of the juvenile scallops, while the α-AG was supposed to be formed via amorphous guanine during the sample preparation process. Besides β-AG and α-AG, amorphous guanine was found in the eyes of juvenile scallops with size of 2.5 mm according to the Raman spectra. A formation mechanism was proposed for the biogenic twinning guanine platelets. Firstly, amorphous guanine is formed as an intermediate phase, which transforms into single crystalline β-AG nanoplatelets, or, dissolve and recrystallize to single crystalline β-AG nanoplatelets. Then, a second layer of β-AG forms on the top of the original single crystalline β-AG nanoplatelets, forming twinning β-AG nanoplatelets with twocaxes with a certain angle, 83° or 14°. Each layer of the β-AG nanoplatelets is calculated to be about 14 ± 2 nm. This is the first time to report the formation mechanism of biogenic twinning β-AG microplatelets. Uncovering the formation mechanism of twinning platelets of organic crystals may shed light on the formation of functional synthetic twinning organic crystals in the laboratories.
Deletion ofTRPC6, an autism risk gene, induces hyperexcitability in cortical neurons derived from human pluripotent stem cells
Authors: Shin Kyung Chul , Ali Gowher , Ali Moussa Houda Yasmine , Gupta Vijay , de la Fuente Alberto , Kim Hyung-Goo , Stanton Lawrence W , Park Yongsoo
Published: November 2022

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder linked to numerous rare, inherited and arisingde novogenetic variants. ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons. However, the physiological and molecular mechanisms underlying hyperexcitability in ASD remain poorly understood. Transient receptor potential canonical-6 (TRPC6) is a Ca2+-permeable cation channel that regulates store-operated calcium entry (SOCE) and is a candidate risk gene for ASD. Using human pluripotent stem cell (hPSC)-derived cortical neurons, single cell calcium imaging, and electrophysiological recording, we show that TRPC6 knockout (KO) reduces SOCE signaling and leads to hyperexcitability of neurons by increasing action potential frequency and network burst frequency. Our data provide evidence that reduction of SOCE by TRPC6 KO results in neuronal hyperexcitability, which we hypothesize is an important contributor to the cellular pathophysiology underlying hyperactivity in some ASD.
Deciphering divergent trypanosomatid nuclear complexes by analyzing interactomic datasets with AlphaFold2 and genetic approaches
Authors: Araya Elvio Rodriguez , Merli Marcelo L. , Cribb Pamela , de Souza Vinicius C. , Serra Esteban
Published: November 2022

Acetylation signaling pathways in trypanosomatids, a group of early branching organisms, are poorly understood due to highly divergent protein sequences. To overcome this challenge, we used interactomic datasets and AlphaFold2-multimer to predict direct interactions and validated them using yeast two and three-hybrid assays. We focused on MRG domain-containing proteins and their interactions, typically found in histone acetyltransferase/deacetylase complexes. The results identified a structurally conserved complex,TcTINTIN, which is orthologous to human and yeast TINTIN complexes; and another trimeric complex involving an MRG domain, only seen in trypanosomatids. The identification of a key component ofTcTINTIN,TcMRGBP, would not have been possible through traditional homology-based methods. We also conducted molecular dynamics simulations, revealing a conformational change that potentially affects its affinity forTcBDF6. The study also revealed a novel way in which an MRG domain participates in simultaneous interactions with two MRG binding proteins binding two different surfaces, a phenomenon not previously reported. Overall, this study demonstrates the potential of using AlphaFold2-processed interactomic datasets to identify protein complexes in deeply branched eukaryotes, which can be challenging to study based on sequence similarity. The findings provide new insights into the acetylation signaling pathways in trypanosomatids, specifically highlighting the importance of MRG domain-containing proteins in forming complexes, which may have important implications for understanding the biology of these organisms and developing new therapeutics. On the other hand, our validation of AlphaFold2 models for the determination of multiprotein complexes illuminates the power of using such artificial intelligence-derived tools in the future development of biology.

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BIM-based analysis of construction safety tracking using behavior-based safety in Bangladeshi construction industry
Authors: Meem Tamanna Islam , Hossain Md. Mehrab , Akter Jhumana
Published: November 2022

Purpose

In comparison to other industries, the construction industry is one of the most dangerous industries. Behavior-based safety (BBS) is a common and useful technique for risk indicator processing. Almost all studies are based on the BBS checklist, but very few of them focus on the increasing dangers faced by construction workers and the important factors that lead to accidents. This research represents a risk spatiotemporal analysis and visual tracking approach based on BBS and Building Information Modeling (BIM).

Design/methodology/approach

After the literature review, a BBS checklist was developed. Then a survey was conducted based on the BBS checklist and the temporal evolution of risks has been completed. After that, managing the risk with the automatic rule checking (ARC) system using BIM was conducted simultaneously to develop a framework by conducting a case study.

Findings

Based on the grey clustering analysis, this work provides a temporal evolution analysis approach for dynamic analyzing BBS risk. According to the grey relational analysis (GRA) data, the main key factor of risk was the missing guardrail/handrail system. After that, a case study was performed and the system automatically warn in the preconstruction phase that the barrier is missing as the system benefits.

Originality/value

A systematic framework has been provided for risk analysis through which high health and safety performance outcomes can be achieved on construction projects. This study will assist design engineers in addressing the potential danger to employees during the preconstruction stage and monitoring dynamic changes in risk on any construction site.
Transport infrastructure and manufacturing sector: an energy perspective from India
Authors: Shameem P. Mohammed , Chittedi Krishna Reddy , Villanthenkodath Muhammed Ashiq
Published: November 2022

Purpose

The purpose of this study is to dissect the transport infrastructure performance, public spending in transport infrastructure development and the manufacturing sector in determining the transport sector energy consumption.

Design/methodology/approach

An analysis of transport energy consumption with the transport infrastructure performance, public spending in transport infrastructure and manufacturing sector output in India using annual data for the period 1987–2019. The study used the autoregressive distributed lag (ARDL) bounds test approach along with FMOLS, DOLS and canonical cointegration regression (CCR) methods.

Findings

The results of the ARDL bounds test provide evidence for the long- and short-run relationships among study variables. It evidenced that transport infrastructure performance reduces transport energy consumption by using FMOLS, DOLS and CCR methods. Furthermore, the inference of the positive impact of value added in the manufacturing sector on transport energy consumption validates the higher energy demand of the manufacturing sector from a mobility perspective.

Practical implications

The estimated finding of this study is expected to be contributing to policy-making discussions on transport infrastructure and manufacturing sector development in an emerging economy like India with insights on energy consumption.

Originality/value

To the best of the authors’ knowledge, this is the first study that integrates the impact of manufacturing sector output on transport sector energy consumption along with transport infrastructure performance and public investment in the transport infrastructure.
Service quality scale development for fully automatic operation metro system
Authors: He Zhen , Hu Hao , Zhang Min , Qin Fang
Published: November 2022

Purpose

Fully automatic operation (FAO) metro system is the trend of urban rail in modern cities. This study aims to develop a service quality scale for measuring passenger service perception in the context of FAO metro system.

Design/methodology/approach

Based on the interviews and the dimensions proposed in the previous service quality scales of the public transport sector, this study develops a multidimension service quality scale. Face-to-face interviews and surveys are conducted to obtain the riding experience and satisfaction of passengers in the metro stations of Beijing Subway Yanfang Line and Beijing Daxing International Airport Express that are FAO metro lines. Reliability, validity and nomological validity of our scale are demonstrated.

Findings

Six dimensions (i.e. tangibles, information, safety, efficiency, empathy and innovation) and 22 items are included in the scale through quantitative analysis. It is found that all of the six dimensions have a significant relationship with passenger satisfaction. Especially information and innovation are the more important dimensions of FAO metro system service quality.

Originality/value

This study contributes to the service quality literature in the public transport sector taking the FAO metro system as the object. The findings may provide a guide for the FAO metro operators to evaluate and improve their service quality.
Consumer satisfaction with local rice attributes and willingness to pay for improvement by internal migrants and natives in urban Ghana
Authors: Amfo Bismark , Abankwah Vincent , Tanko Mohammed
Published: November 2022

Purpose

This study investigated consumers' satisfaction with local rice attributes and willingness to pay (WTP) for improvement by internal migrants and natives in urban Ghana.

Design/methodology/approach

Primary data was sourced from 304 urban consumers and ordered probit regression was employed.

Findings

Urban consumers had higher satisfaction with imported rice attributes than local rice. Consumers were unsatisfied with aroma, availability/accessibility, cleanliness, packaging, grain appearance, measurement standard, and taste of local rice. Moreover, 90% were willing to pay higher prices for local rice with improved attributes and WTP was higher among natives than migrants. Averagely, urban consumers are willing to pay 51% increase in market price of local rice if attributes were improved. Natives, males, educated, high-income, local rice consumption, shopping from supermarkets, trust in certification bodies, and dissatisfaction with local rice attributes boost WTP for improved local rice attributes.

Research limitations/implications

There is a great market potential for local rice with improved attributes. Thus, there should be an improvement in local rice attributes and sold at moderate price and in supermarkets.

Originality/value

We compared consumers' satisfaction and WTP for improved local rice attributes among internal migrants and natives in urban Ghana.