bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Influence underlying Brain Connectivity Phenotype: A Study on Two Age-Specific Cohorts
Authors: Cong Shan , Yao Xiaohui , Xie Linhui , Yan Jingwen , Shen Li ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

Background

Human brain structural connectivity is an important imaging quantitative trait for brain development and aging. Mapping the network connectivity to the phenotypic variation provides fundamental insights in understanding the relationship between detailed brain topological architecture, function, and dysfunction. However, the underlying neurobiological mechanism from gene to brain connectome, and to phenotypic outcomes, and whether this mechanism changes over time, remain unclear.

Methods

This study analyzes diffusion weighted imaging data from two age-specific neuroimaging cohorts, extracts structural connectome topological network measures, performs genome-wide association studies (GWAS) of the measures, and examines the causality of genetic influences on phenotypic outcomes mediated via connectivity measures.

Results

Our empirical study has yielded several significant findings: 1) It identified genetic makeup underlying structural connectivity changes in the human brain connectome for both age groups. Specifically, it revealed a novel association between the minor allele (G) of rs7937515 and the decreased network segregation measures of the left middle temporal gyrus across young and elderly adults, indicating a consistent genetic effect on brain connectivity across the lifespan. 2) It revealed rs7937515 as a genetic marker for body mass index (BMI) in young adults but not in elderly adults. 3) It discovered brain network segregation alterations as a potential neuroimaging biomarker for obesity. 4) It demonstrated the hemispheric asymmetry of structural network organization in genetic association analyses and outcome-relevant studies.

Discussion

These imaging genetic findings underlying brain connectome warrant further investigation for exploring their potential influences on brain-related diseases, given the significant involvement of altered connectivity in neurological, psychiatric and physical disorders.

Impact Statement

The genetic architecture underlying brain connectivity, and whether this mechanism changes over time, remain largely unknown. To understand the inter-individual variability at different life stages, this study performed genome-wide association studies of brain network connectivity measures from two age-specific neuroimaging cohorts, and identified a common association between the minor allele (G) of rs7937515 and decreased network segregation measures of the left middle temporal gyrus. The mediation analysis further elucidated neurobiological pathway of brain connectivity mediators linking the genes FAM86C1/FOLR3 with body mass index. This study provided new insights into the genetic mechanism of inter-regional connectivity alteration in the brain.
FtsN activates septal cell wall synthesis by forming a processive complex with the septum-specific peptidoglycan synthase in E. coli
Authors: Lyu Zhixin , Yahashiri Atsushi , Yang Xinxing , McCausland Joshua W. , Kaus Gabriela M. , McQuillen Ryan , Weiss David S. , Xiao Jie
Published: August 2021

The FtsN protein of Escherichia coli and other proteobacteria is an essential and highly conserved bitopic membrane protein that triggers the inward synthesis of septal peptidoglycan (sPG) during cell division. Previous work has shown that the activation of sPG synthesis by FtsN involves a series of interactions of FtsN with other divisome proteins and the cell wall. Precisely how FtsN achieves this role is unclear, but a recent study has shown that FtsN promotes the relocation of the essential sPG synthase FtsWI from an FtsZ-associated track (where FtsWI is inactive) to an sPG-track (where FtsWI engages in sPG synthesis). Whether FtsN works by displacing FtsWI from the Z-track or capturing/retaining FtsWI on the sPG-track is not known. Here we use single-molecule imaging and genetic manipulation to investigate the organization and dynamics of FtsN at the septum and how they are coupled to sPG synthesis activity. We found that FtsN exhibits a spatial organization and dynamics distinct from those of the FtsZ-ring. Single FtsN molecules move processively as a single population with a speed of ∼ 9 nm s-1, similar to the speed of active FtsWI molecules on the sPG-track, but significantly different from the ∼ 30 nm s-1 speed of inactive FtsWI molecules on the FtsZ-track. Furthermore, the processive movement of FtsN is independent of FtsZ’s treadmilling dynamics but driven exclusively by active sPG synthesis. Importantly, only the essential domain of FtsN, a three-helix bundle in the periplasm, is required to maintain the processive complex containing both FtsWI and FtsN on the sPG-track. We conclude that FtsN activates sPG synthesis by forming a processive synthesis complex with FtsWI exclusively on the sPG-track. These findings favor a model in which FtsN captures or retains FtsWI on the sPG-track rather than one in which FtsN actively displaces FtsWI from the Z-track.
Species-scale genomic analysis of S. aureus genes influencing phage host range and their relationships to virulence and antibiotic resistance genes
Authors: Moller Abraham G. , Petit Robert A. , Read Timothy D.
Published: August 2021

Phage therapy has been proposed as a possible alternative treatment for infections caused by the ubiquitous bacterial pathogen Staphylococcus aureus. However, successful phage therapy requires knowing both host and phage genetic factors influencing host range for rational cocktail formulation. To further our understanding of host range, we searched 40,000+ public S. aureus genome sequences for previously identified phage resistance genes. We found that phage adsorption targets and genes that block phage assembly were significantly more conserved than genes targeting phage biosynthesis. Core phage resistance genes had similar nucleotide diversity, ratio of non-synonymous to synonymous substitutions, and functionality (measured by delta-bitscore) to other core genes in a set of 380 non-redundant S. aureus genomes (each from a different MLST sequence type). Non-core phage resistance genes were significantly less consistent with the core genome phylogeny than all non-core genes in this set. Only superinfection immunity genes correlated with empirically determined temperate phage resistance, accessory genome content, and numbers of accessory antibiotic resistance or virulence genes encoded per strain. Taken together, these results suggested that, while phage adsorption genes are heavily conserved in the S. aureus species, they are not undergoing positive selection, arms race dynamics. They also suggested genes classified as involved in assembly are least phylogenetically constrained and superinfection immunity genes best predict both empirical phage resistance and levels of phage-mediated HGT.

Importance

Staphylococcus aureus is a widespread, hospital- and community-acquired pathogen that is commonly antibiotic resistant. It causes diverse diseases affecting both the skin and internal organs. Its ubiquity, antibiotic resistance, and disease burden make new therapies urgent, such as phage therapy, in which viruses specific to infecting bacteria clear infection. S. aureus phage host range not only determines whether phage therapy will be successful by killing bacteria but also horizontal gene transfer through transduction of host genetic material by phages. In this work, we comprehensively reviewed existing literature to build a list of S. aureus phage resistance genes and searched our database of almost 43,000 S. aureus genomes for these genes to understand their patterns of evolution, finding that prophages’ superinfection immunity correlates best with phage resistance and HGT. These findings improved our understanding of the relationship between known phage resistance genes and phage host range in the species.
Survival of a threatened salmon is linked to spatial variability in river conditions
Authors: Hause Colby L. , Singer Gabriel P. , Buchanan Rebecca A. , Cocherell Dennis E. , Fangue Nann A. , Rypel Andrew L.
Published: August 2021

Extirpation of the Central Valley spring-run Chinook Salmon ESU (Oncorhynchus tshawytscha) from the San Joaquin River is emblematic of salmonid declines across the Pacific Northwest. Habitat restoration and fish reintroduction efforts are ongoing, but recent telemetry studies have revealed low outmigration survival of juveniles to the ocean. Previous investigations have focused on modeling survival relative to river discharge and geographic regions, but have largely overlooked the effects of habitat variability. To evaluate the link between environmental conditions and survival of juvenile spring-run Chinook Salmon, we combined high spatial resolution habitat mapping approaches with acoustic telemetry along a 150 km section of the San Joaquin River during the spring of 2019. While overall outmigration survival was low (5%), our habitat-based classification scheme described variation in survival of acoustic-tagged smolts better than other candidate models based on geography or distance. There were two regional mortality sinks evident along the longitudinal profile of the river, revealing poor survival in areas that shared warmer temperatures but that diverged in chlorophyll-α, fDOM, turbidity and dissolved oxygen levels. These findings demonstrate the value of integrating river habitat classification frameworks to improve our understanding of survival dynamics of imperiled fish populations. Importantly, our data generation and modeling methods can be applied to a wide variety of fish species that transit heterogeneous and diverse habitat types.
MyoView: Fully-automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers
Authors: Rahmati Masoud , Rashno Abdolreza
Published: August 2021

Skeletal muscle is an adaptive tissue with the ability to regenerate in response to exercise training. Cross-sectional area (CSA) quantification, as a main parameter to assess muscle regeneration capability, is highly tedious and time-consuming, necessitating an accurate and automated approach to analysis. Although several excellent programs are available to automate analysis of muscle histology, they fail to efficiently and accurately measure CSA in regenerating myofibers in response to exercise training. Here, we have developed a novel fully-automated image segmentation method based on neutrosophic set algorithms to analyse whole skeletal muscle cross sections in exercise-induced regenerating myofibers, referred as MyoView, designed to obtain accurate fiber size and distribution measurements. MyoView provides relatively efficient, accurate, and reliable measurements for detecting different myofibers and CSA quantification in response to the post-exercise regenerating process. We showed that MyoView is comparable with manual quantification. We also showed that MyoView is more accurate and efficient to measure CSA in post-exercise regenerating myofibers as compared with Open-CSAM, MuscleJ, SMASH and MyoVision. Furthermore, we demonstrated that to obtain an accurate CSA quantification of exercise-induced regenerating myofibers, whole muscle cross-section analysis is an essential part, especially for the measurement of different fiber-types. We present MyoView as a new tool for CSA quantification in skeletal muscle from any experimental condition including exercise-induced regenerating myofibers.
Direct RNA sequencing reveals SARS-CoV-2 m6A sites and possible differential DRACH motif methylation among variants
Authors: Campos João H. , Maricato Juliana T. , Braconi Carla T. , Antoneli Fernando , Janini Luiz Mario R. , Briones Marcelo R. S.
Published: August 2021

The causative agent of COVID-19 pandemic, the SARS-CoV-2 coronavirus, has a 29,903 bases positive-sense single-stranded RNA genome. RNAs exhibit about 100 modified bases that are essential for proper function. Among internal modified bases, the N6-methyladenosine, or m6A, is the most frequent, and is implicated in SARS-CoV-2 immune response evasion. Although the SARS-CoV-2 genome is RNA, almost all genomes sequenced so far are in fact, reverse transcribed complementary DNAs. This process reduces the true complexity of these viral genomes because incorporation of dNTPs hides RNA base modifications. Here, in this perspective paper, we present an initial exploration of the Nanopore direct RNA sequencing to assess the m6A residues in the SARS-CoV-2 sequences of ORF3a, E, M, ORF6, ORF7a, ORF7b, ORF8, N, ORF10 and the 3’-untranslated region. We identified 15 m6A methylated positions, of which, 6 are in ORF N. Also, because m6A is associated with the DRACH motif, we compared its distribution in major SARS-CoV-2 variants. Although DRACH is highly conserved among variants we show that variants Beta and Eta have a fourth position C>U change in DRACH at 28,884b that could affect methylation. The Nanopore technology offers a unique opportunity for the study of viral epitranscriptomics. This technique is PCR-free and is not sequencing-by-synthesis, therefore, no PCR bias and synthesis errors are introduced. The modified bases are preserved and assessed directly with no need for chemical treatments or antibodies. This is the first report of direct RNA sequencing of a Brazilian SARS-CoV-2 sample coupled with the identification of modified bases.
Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
Authors: Ren Wenlin , Lan Jun , Ju Xiaohui , Gong Mingli , Long Quanxin , Zhu Zihui , Yu Yanying , Wu Jianping , Zhong Jin , Zhang Rong , Fan Shilong , Zhong Guocai , Huang Ailong , Wang Xinquan , Ding Qiang
Published: August 2021

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.
bletl - A Python Package for Integrating Microbioreactors in the Design-Build-Test-Learn Cycle
Authors: Osthege Michael , Tenhaef Niklas , Zyla Rebecca , Müller Carolin , Hemmerich Johannes , Wiechert Wolfgang , Noack Stephan , Oldiges Marco
Published: August 2021

Microbioreactor (MBR) devices have emerged as powerful cultivation tools for tasks of microbial phenotyping and bioprocess characterization and provide a wealth of online process data in a highly parallelized manner. Such datasets are difficult to interpret in short time by manual workflows. In this study, we present the Python package bletl and show how it enables robust data analyses and the application of machine learning techniques without tedious data parsing and preprocessing.bletlreads raw result files from BioLector I, II and Pro devices to make all the contained information available to Python-based data analysis workflows. Together with standard tooling from the Python scientific computing ecosystem, interactive visualizations and spline-based derivative calculations can be performed. Additionally, we present a new method for unbiased quantification of time-variable specific growth ratebased on a novel method of unsupervised switchpoint detection with Student-t distributed random walks. With an adequate calibration model, this method enables practitioners to quantify time-variable growth rate with Bayesian uncertainty quantification and automatically detect switch-points that indicate relevant metabolic changes. Finally, we show how time series feature extraction enables the application of machine learning methods to MBR data, resulting in unsupervised phenotype characterization. As an example, t-distributed Stochastic Neighbor Embedding (t-SNE) is performed to visualize datasets comprising a variety of growth/DO/pH phenotypes.

Practical Application

Thebletlpackage can be used to analyze microbioreactor datasets in both data analysis and autonomous experimentation workflows. Using the example of BioLector datasets, we show that loading such datasets into commonly used data structures with one line of Python code is a significant improvement over spreadsheet or hand-crafted scripting approaches. On top of established standard data structures, practitioners may continue with their favorite data analysis routines, or make use of the additional analysis functions that we specifically tailored to the analysis of microbioreactor time series.

Particularly our function to fit cross-validated smoothing splines can be used foron-linesignals from any microbioreactor system and has the potential to improve robustness and objectivity of many data analyses. Likewise, our random walk basedmethod for inferring growth rates under uncertainty, but also the time-series feature extraction may be applied toon-linedata from other cultivation systems as well.
Force-induced changes of PilY1 drive surface sensing by Pseudomonas aeruginosa
Authors: Webster Shanice S. , Mathelié-Guinlet Marion , Verissimo Andreia F. , Schultz Daniel , Viljoen Albertus , Lee Calvin K. , Schmidt William C. , Wong Gerard C. L. , Dufrene Yves F. , O’Toole George A.
Published: August 2021

During biofilm formation, the opportunistic pathogen Pseudomonas aeruginosa uses its type IV pili (TFP) to sense a surface, eliciting increased second messenger production and regulating target pathways required to adapt to a surface lifestyle. The mechanisms whereby TFP detect surface contact is still poorly understood, although mechanosensing is often invoked with little data supporting this claim. Using a combination of molecular genetics and single cell analysis, with biophysical, biochemical and genomics techniques we show that force-induced changes mediated by the von Willebrand A (vWA) domain-containing, TFP tip-associated protein PilY1 are required for surface sensing. Atomic force microscopy shows that PilY1 can undergo force-induced, sustained conformational changes akin to those observed for mechanosensitive proteins like titin. We show that mutation of a single cysteine residue in the vWA domain results in modestly lower surface adhesion forces, increased nanospring-like properties, as well as reduced c-di-GMP signaling and biofilm formation. Mutating this cysteine has allowed us to genetically separate TFP function in twitching from surface sensing signaling. The conservation of this Cys residue in all P. aeruginosa PA14 strains, and its absence in the ~720 sequenced strains of P. aeruginosa PAO1, could contribute to explaining the observed differences in surface colonization strategies observed for PA14 versus PAO1.

Importance

Most bacteria live on abiotic and biotic surfaces in surface-attached communities known as biofilms. Surface sensing and increased levels of the second messenger molecule c-di-GMP are crucial to the transition from planktonic to biofilm growth. The mechanism(s) underlying TFP-mediated surface detection that triggers this c-di-GMP signaling cascade are unclear. Here, we provide a key insight into this question: we show that the eukaryotic-like, vWA domain of the TFP tip-associated protein PilY1 responds to mechanical force, which in turn drives production of a key second messenger needed to regulate surface behaviors. Our studies highlight a potential mechanism that could account for differing surface colonization strategies.
Inexpensive monitoring of flying insect activity and abundance using wildlife cameras
Authors: Wallace Jesse R A , Reber Therese , Beaton Brendan , Dreyer David , Warrant Eric J
Published: August 2021

The ability to measure flying insect activity and abundance is important for ecologists, conservationists and agronomists alike. However, existing methods are laborious and produce data with low temporal resolution (e.g. trapping and direct observation), or are expensive, technically complex, and require vehicle access to field sites (e.g. radar and lidar entomology).

We propose a method called “camfi” for long-term non-invasive monitoring of the activity and abundance of low-flying insects using images obtained from inexpensive wildlife cameras, which retail for under USD$100 and are simple to operate. We show that in certain circumstances, this method facilitates measurement of wingbeat frequency, a diagnostic parameter for species identification. To increase usefulness of our method for very large monitoring programs, we have developed and implemented a tool for automatic detection and annotation of flying insect targets based on the popular Mask R-CNN framework. This tool can be trained to detect and annotate insects in a few hours, taking advantage of transfer learning.

We demonstrate the utility of the method by measuring activity levels and wingbeat frequencies in Australian Bogong moths Agrotis infusa in the Snowy Mountains of New South Wales, and find that these moths have log-normally distributed wingbeat frequencies (mean = 49.4 Hz, std = 5.25 Hz), undertake dusk flights in large numbers, and that the intensity of their dusk flights is modulated by daily weather factors. Validation of our tool for automatic image annotation gives baseline performance metrics for comparisons with future annotation models. The tool performs well on our test set, and produces annotations which can be easily modified by hand if required. Training completed in less than 2 h on a single machine, and inference took on average 1.15 s per image on a laptop.

Our method will prove invaluable for ongoing efforts to understand the behaviour and ecology of the iconic Bogong moth, and can easily be adapted to other flying insects. The method is particularly suited to studies on low-flying insects in remote areas, and is suitable for very large-scale monitoring programs, or programs with relatively low budgets.
Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats
Authors: Silva Everidiene K. V. B. , Bomfim Camila G. , Barbosa Ana P. , Noda Paloma , Noronha Irene L. , Fernandes Bianca H V. , Machado Rafael R. G. , Durigon Edison L. , Catanozi Sergio , Rodrigues Letícia G. , Pieroni Fabiana , Lima Sérgio G. , Queiroz Zelita A. J. , Charlie-Silva Ives , Silveira Lizandre K. R. , Teodoro Walcy R. , Capelozzi Vera L. , Guzzo Cristiane R. , Fanelli Camilla
Published: August 2021

The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.
TopoRoot: A method for computing hierarchy and fine-grained traits of maize roots from X-ray CT images
Authors: Zeng Dan , Li Mao , Jiang Ni , Ju Yiwen , Schreiber Hannah , Chambers Erin , Letscher David , Ju Tao , Topp Christopher N.
Published: August 2021

Background

3D imaging, such as X-ray CT and MRI, has been widely deployed to study plant root structures. Many computational tools exist to extract coarse-grained features from 3D root images, such as total volume, root number and total root length. However, methods that can accurately and efficiently compute fine-grained root traits, such as root number and geometry at each hierarchy level, are still lacking. These traits would allow biologists to gain deeper insights into the root system architecture (RSA).

Results

We present TopoRoot, a high-throughput computational method that computes fine-grained architectural traits from 3D X-ray CT images of field-excavated maize root crowns. These traits include the number, length, thickness, angle, tortuosity, and number of children for the roots at each level of the hierarchy. TopoRoot combines state-of-the-art algorithms in computer graphics, such as topological simplification and geometric skeletonization, with customized heuristics for robustly obtaining the branching structure and hierarchical information. TopoRoot is validated on both real and simulated root images, and in both cases it was shown to improve the accuracy of traits over existing methods. We also demonstrate TopoRoot in differentiating a maize root mutant from its wild type segregant using fine-grained traits. TopoRoot runs within a few minutes on a desktop workstation for volumes at the resolution range of 400^3, without need for human intervention.

Conclusions

TopoRoot improves the state-of-the-art methods in obtaining more accurate and comprehensive fine-grained traits of maize roots from 3D CT images. The automation and efficiency makes TopoRoot suitable for batch processing on a large number of root images. Our method is thus useful for phenomic studies aimed at finding the genetic basis behind root system architecture and the subsequent development of more productive crops.
A gene-based capture assay for surveying patterns of genetic diversity and insecticide resistance in a worldwide group of invasive mosquitoes
Authors: Aardema Matthew L. , Campana Michael G. , Wagner Nicole E. , Ferreira Francisco C. , Fonseca Dina M.
Published: August 2021

Understanding patterns of diversification, genetic exchange, and pesticide resistance in insect species of human health concern is necessary for effective population reduction and management. With the broad availability of next-generation sequencing technologies, one of the best approaches for surveying such patterns involves the simultaneous genotyping of many samples for large numbers of genetic markers from across the known genome. To this end, the targeting of gene sequences of known function or inheritance can be a cost-effective strategy. One insect group of substantial health concern are the mosquito taxa that make up the Culex pipiens complex. Members of this complex transmit damaging arboviruses and filariae worms to humans, as well as other pathogens that are detrimental to endangered vertebrate species such as bird malaria. Here we describe our development of a targeted gene-based assay for surveying genetic diversity and population structure in this mosquito complex. To test the utility of this assay, we examined taxonomic divergence among samples from several members of the complex, as well as distinct populations of the relatively under-studied Culex quinquefasciatus, an urban pantropical species. We also examined the presence of known insecticide-resistance conferring alleles. Broadly, our developed gene-based assay proved effective for examining patterns of taxonomic and geographic clustering within the species complex, as well as for surveying genetic variants that have been associated with insecticide resistance. This assay will be useful for future studies that aim to understand the genetic mechanisms underlying the evolution of ubiquitous and increasingly damaging disease vectors.
Genomic screening of antimicrobial resistance markers in UK and US Campylobacter isolates highlights stability of resistance over an 18 year period
Authors: van Vliet Arnoud H.M. , Thakur Siddhartha , Prada Joaquin M. , Mehat Jai W. , La Ragione Roberto M.
Published: August 2021

Campylobacter jejuni and Campylobacter coli are important bacterial causes of human foodborne illness. Despite several years of reduced antibiotics usage in livestock production in the UK and US, high prevalence of antimicrobial resistance (AMR) persists in Campylobacter. Both countries have instigated genome sequencing-based surveillance programs for Campylobacter, and here we have identified AMR genes in 32,256 C. jejuni and 8,776 C. coli publicly available genome sequences to compare the prevalence and trends of AMR in Campylobacter isolated in the UK and US between 2001-2018. AMR markers were detected in 68% of C. coli and 53% of C. jejuni, with 15% of C. coli being multi-drug resistant (MDR) compared to only 2% of C. jejuni. The prevalence of aminoglycoside, macrolide, quinolone and tetracycline resistance remained fairly stable from 2001-2018 in both C. jejuni and C. coli, but statistically significant differences were observed between the UK and US. There was a statistically significant higher prevalence of aminoglycoside and tetracycline resistance for US C. coli and C. jejuni, and macrolide resistance for US C. coli. In contrast, UK C. coli and C. jejuni showed a significantly higher prevalence of quinolone resistance. Specific MLST clonal complexes (e.g. ST-353/464) showed >95% quinolone resistance. This large-scale comparison of AMR prevalence has shown that the prevalence of AMR remains stable for Campylobacter in the UK and the US. This suggests that antimicrobial stewardship and restricted antibiotic usage may help contain further expansion of AMR prevalence in Campylobacter, but are unlikely to reduce it in the short term.
The AIRE G228W mutation disturbs the interaction of AIRE with its partner molecule SIRT1
Authors: Santos Jadson C. , Dametto Mariangela , Masson Ana Paula , Faça Vitor M. , Bonacin Rodrigo , Donadi Eduardo A. , Passos Geraldo Aleixo
Published: August 2021

The autoimmune regulator (AIRE) protein functions as a tetramer, interacting with partner proteins to form the “AIRE complex,” which relieves RNA Pol II stalling in the chromatin of medullary thymic epithelial cells (mTECs). AIRE is the primary mTEC transcriptional controller, promoting the expression of a large set of peripheral tissue antigen genes implicated in the negative selection of self-reactive thymocytes. Under normal conditions, the SIRT1 protein temporarily interacts with AIRE and deacetylates K residues of the AIRE SAND domain. Once the AIRE SAND domain is deacetylated, the binding with SIRT1 is undone, allowing the AIRE complex to proceed downstream with the RNA Pol II to the elongation phase of transcription. Considering that the in silico and in vitro binding of the AIRE SAND domain with SIRT1 provides a powerful model system for studying the dominant SAND G228W mutation mechanism, which causes the autoimmune polyglandular syndrome-1, we integrated computational molecular modeling, docking, dynamics between the whole SAND domain with SIRT1, and surface plasmon resonance using a peptide harboring the 211 to 230 residues of the SAND domain, to compare the structure and energetics of binding/release between AIRE G228 (wild-type) and W228 (mutant) SAND domain to SIRT1. We observed that the G228W mutation in the SAND domain negatively influences the AIRE-SIRT1 interaction. The disturbed interaction might cause a disruption in the binding of the AIRE SAND domain with the SIRT1 catalytic site, impairing the AIRE complex to proceed downstream with RNA Pol II.
Plant Polymerase IV sensitizes chromatin through histone modifications to preclude spread of silencing into protein-coding domains
Authors: Sundar G Vivek Hari , Swetha Chenna , Basu Debjani , Pachamuthu Kannan , Raju Steffi , Chakraborty Tania , Mosher Rebecca A. , Shivaprasad P. V.
Published: August 2021

Across eukaryotes, gene regulation is manifested via chromatin states roughly distinguished as heterochromatin and euchromatin. The establishment, maintenance and modulation of the chromatin states is mediated using several factors including chromatin modifiers. However, factors that avoid the intrusion of silencing signals into protein coding genes are poorly understood. Here we show that a plant specific paralogue of RNA polymerase (pol) II, named pol IV, is involved in avoidance of facultative heterochromatic marks in protein coding genes, in addition to its well-established functions in silencing repeats and transposons. In its absence, H3K27 trimethylation (me3) mark intruded the protein coding genes, more profoundly in genes embedded with repeats. In a subset of genes, spurious transcriptional activity resulted in small(s) RNA production leading to post-transcriptional gene silencing. We show that such effects are significantly pronounced in rice, a plant with larger genome with distributed heterochromatin when compared to Arabidopsis. Our results indicate the surprising division of labour among plant-specific polymerases, not just in establishing effective silencing via sRNAs and DNA methylation, but also in influencing chromatin boundaries.
VTA-projecting cerebellar neurons mediate stress-dependent depression-like behavior
Authors: Baek Soo Ji , Park Jinsung , Kim Jinhyun , Yamamoto Yukio , Tanaka-Yamamoto Keiko
Published: August 2021

Although cerebellar alterations have been implicated in mental depression, the exact contribution of the cerebellum to depressive symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the chronic stress-induced development of depression-like behavior. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and depression-like behavior, which were triggered by chronic stress application. Furthermore, specific inhibition of neurons in the DN that project to the VTA prevented stressed mice from showing depression-like behavior, whereas specific activation of these neurons alone triggered depression-like behavior that was comparable with the one triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders.
Mechanochemical synthesis insights and solid-state characterization of quininium aspirinate, a glass-forming drug–drug salt
Authors: Harris Nehemiah , Benedict Jubilee , Dickie Diane A. , Pagola Silvina
Published: August 2021

Quinine (an antimalarial) and aspirin (a nonsteroidal anti-inflammatory drug) were combined into a new drug–drug salt, quininium aspirinate, C20H25N2O2
+·C9H7O4
−, by liquid-assisted grinding using stoichiometric amounts of the reactants in a 1:1 molar ratio, and water, EtOH, toluene, or heptane as additives. A tetrahydrofuran (THF) solution of the mechanochemical product prepared using EtOH as additive led to a single crystal of the same material obtained by mechanochemistry, which was used for crystal structure determination at 100 K. Powder X-ray diffraction ruled out crystallographic phase transitions in the 100–295 K interval. Neat mechanical treatment (in a mortar and pestle, or in a ball mill at 20 or 30 Hz milling frequencies) gave rise to an amorphous phase, as shown by powder X-ray diffraction; however, FT–IR spectroscopy unambiguously indicates that a mechanochemical reaction has occurred. Neat milling the reactants at 10 and 15 Hz led to incomplete reactions. Thermogravimetry and differential scanning calorimetry indicate that the amorphous and crystalline mechanochemical products form glasses/supercooled liquids before melting, and do not recrystallize upon cooling. However, the amorphous material obtained by neat grinding crystallizes upon storage into the salt reported. The mechanochemical synthesis, crystal structure analysis, Hirshfeld surfaces, powder X-ray diffraction, thermogravimetry, differential scanning calorimetry, FT–IR spectroscopy, and aqueous solubility of quininium aspirinate are herein reported.
Key elements of green supply chain management drivers and barriers empirical study of solar energy companies in South Egypt
Authors: Yassin Ahmed Mostafa Mahmoud , Hassan Mohamed Ahmed , Elmesmary Hebatallah Mohamed
Published: August 2021

Purpose

There are several important strategic projects in the field of renewable energy in Egypt. Benban project is considered as one of the largest solar generation facilities in the world, which aims to increase clean energy produced, provide electricity needs for citizens and help to increase the volume of Egypt's electricity exports. The purpose of this paper is to explore the most important drivers and barriers that affect the implementation of green supply chain management (GSCM) practices in the field of solar energy production.

Design/methodology/approach

It is an exploratory research that conducts a case study about solar energy companies operating in Benban, south Egypt. It adopts a mixed approach; qualitative and quantitative research strategy to test the relationship between dependent and independent variables through a survey.

Findings

This research concluded that normative drivers involving stakeholder pressure are of the greatest drivers of GSCM practice, while external barriers including lack of government regulations and government support, poor supplier commitment, customers’ unawareness of sustainable green products, lack of markets receiving and manufacturing recycled materials, lack of renewal or technological innovation in markets and lack of human resources or expertise in market are among the biggest barriers to GSCM implementation.

Research limitations/implications

The researchers collected 30 responses during the field survey, which is a nonrandom sample that does not allow generalization. In addition, samples are only from companies in the solar energy sector only.

Originality/value

As there is a need for research that addresses sustainability practices and solutions in developing countries, especially in Egypt, this paper theoretically contributes to literature by proposing a conceptual framework that identifies the drivers and barriers of GSCM from the existing literature, then investigates and measures their impact on the implementation of GSCM on an Egyptian case study. As regards the practical contribution, this research is a trial to experimentally test the importance of top management’s role in motivating and training employees to improve the brand image of their company and making them aware of the benefits of the successful GSCM implementation.
Limited liability companies in Jordan: another story for piercing the corporate veil
Authors: Alawamleh Kamal Jamal , Al-Qaisi Abeer Hassan , Alfaouri Fathi Tawfiq
Published: August 2021

Purpose

In different recent judgments, the Jordanian Court of Cassation, among many other Jordanian Courts, has found that a limited liability company's shareholder may be held liable in addition to the company itself as to claims related to the company's debits and different obligations. While the aforementioned approach does constitute a departure from the well-established former approach that the same Court has followed for a long period, the Court have unsurprisingly brought up different interpretations to the insufficient provisions that the Jordanian Companies' Law no. 22 of the year 1997 does contain pertaining this specific area of law. Accordingly, this paper aims to attempt to point out and critically examine the aforementioned Courts' decisions and law provisions to demonstrate the extent to which limited liability companies in Jordan are truly limited in liability and whether such Courts have pierced the corporate veil for adequate reasons.

Design/methodology/approach

To examine the extent to which limited liability companies in Jordan are truly limited in liability, this work uses the most relevant secondary data available in this relation as the main method to complete such examination and this shall include different interrelated law provisions, case law and jurisprudence. Through critically analyzing and comparing such data, this work will identify the problems connected to this specific area of law and accordingly proposes different recommendations and conclusions.

Findings

This work submits that the aforementioned Courts and Legislator have not dealt with such a matter in an adequate and comprehensive manner and that they should have addressed this area of law in a different and more specific way. Furthermore, this work argues that while the reasons behind the Courts' decisions shall be respected, the distinct characteristics that brought up limited liability companies into practice shall be also respected and left intact.

Originality/value

Taking into consideration the recent different approach followed by the Jordanian Courts to this specific area of law, and as far as the author is aware, it would not be surprising to say that there is no comprehensive and updated scholarly work which has either examined such an issue or addressed its implications from technical and legal standpoints. This paper receives its originality and value from being the first work that examines and addresses such important matter.
Familial occurrence of follicular keratosis of the chin
Authors: Egawa Kiyofumi
Published: August 2021

Follicular keratosis of the chin is a rare and poorly understood pediatric disorder with a characteristic presentation of multiple follicular papules on the chin. Although prolonged friction or pressure over the chin is considered an etiology, such history is not present in most cases. It sometimes occurs within families without any evidence of physical trauma, suggesting a genetic predisposition of the patients to develop the disease. In the present study, we report two brothers with the disease, in whom no definite physical trauma was identified but comedo formation was evident. The clinical presentation of follicular keratosis of the chin is unique, particularly owing to its specific location on the chin with an age predilection from late childhood to puberty. We assume that the hormone status is an etiology of the disease since the chin is an area where androgenic hormones target at puberty and comedogenesis is a well‐known biological function of the hormone. We also assumed that the susceptibility to the hormone may involve in the development of the familial follicular keratosis of the chin.
PrbP modulates biofilm formation in Liberibacter crescens
Authors: Pan Lei , Gardner Christopher L. , Beliakoff Reagan , da Silva Danilo , Zuo Ran , Pagliai Fernando A. , Padgett‐Pagliai Kaylie A. , Merli Marcelo L. , Bahadiroglu Erol , Gonzalez Claudio F. , Lorca Graciela L.
Published: August 2021

In Liberibacter asiaticus, PrbP is a transcriptional regulatory protein involved in survival and persistence during host infection. Tolfenamic acid was previously found to inhibit interactions between PrbP and the promotor region of rplK, resulting in reduced survival of L. asiaticus in the citrus host. In this study, we performed transcriptome analyses to elucidate the PrbP regulon in L. crescens, as it is phylogenetically the closest related species to L. asiaticus that can be grown in laboratory conditions. Chemical inhibition of PrbP with tolfenamic acid revealed that PrbP is involved in the regulation of diverse cellular processes, including stress response, cell motility, cell cycle and biofilm formation. In vitro DNA binding and bacterial two‐hybrid assays also suggested that PrbP is a global regulator of multiple transcription factors (RpoH, VisN, PleD, MucR, MocR and CtrA) at both transcriptional and/or post‐transcriptional levels. Sub‐lethal concentrations of tolfenamic acid significantly reduced the attachment of L. crescens during biofilm formation and decreased long‐term persistence in biofilm structures. Overall, our findings show the importance of PrbP in regulating diverse biological processes through direct and indirect interactions with other transcriptional regulators in L. crescens.
Applying Kolb's experiential learning framework to investigate the safety of energy drinks in a critical thinking general education course
Authors: Rath Danielle Robertson , Rock Cheryl Rosita
Published: August 2021

Through a collaboration between a professor in academia and an industry professional, entry‐level food science students were given the opportunity to critically evaluate the safety of energy drinks. This evaluation occurred through a General Education (Category A3) course designated “Critical Thinking” at California State University – Long Beach (CSULB), where students were introduced to a variety of controversial issues in food science. The goal of the course was for students to apply critical thinking skills to formulate conclusions that are factual, rather than judgmental and biased. Using Kolb's experiential learning framework, students completed exercises in an active‐learning classroom (ALC) environment, which encouraged exploration, reflection, and application. For the exploration phase, students were presented with six commercially available caffeinated beverages and were asked to categorize them as “energy drink” or “not energy drink.” For the reflection phase, students were presented with news articles, as well as peer‐reviewed scientific research articles. Students were tasked with reflecting on how the information in the research articles confirmed or disproved the information in the news articles. Finally, for the application phase, students were asked whether they believed energy drinks should be banned and why or why not. In conclusion, through Kolb's exploration‐reflection‐application framework and through the ALC environment, students learned how to use critical thinking to identify fallacies in news coverage of controversial products, such as energy drinks.