bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
Authors: Stark Victoria A. , Facey Caroline O. B. , Opdenaker Lynn , Fields Jeremy Z. , Boman Bruce M. 
Published: February 2023

ABSTRACTOne reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple cancer stem cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if:i) multiple CSC subpopulations exist in a human CRC cell population, andii) miRNAs are differentially expressed in the different CSC subpopulations. We discovered that at least four different CSC populations (ALDH1, CD166, LGR5, LRIG1) exist in the HT29 cell line. CSC subpopulations were quantified using co-staining for multiple stem cell markers, isolated using FACS, and analyzed by NanoString miRNA profiling. The miRNA expression pattern in each CSC subpopulation was analyzed relative to miRNA expression patterns in other CSC subpopulations. Messenger RNAs predicted to be targeted by the upregulated miRNAs in each CSC subpopulation were: 1) identified using bioinformatics analyses, and 2) classified according to their predicted functions using David functional annotation analyses. We found multiple CSC subpopulations with a unique miRNA signature in each CSC subpopulation. Notably, the miRNAs expressed within one CSC subpopulation are predicted to target and downregulate the CSC genes and pathways that establish the other CSC subpopulations. Moreover, mRNAs predicted to be targeted by miRNAs in the different CSC subpopulations have different cellular functional classifications. That different CSC subpopulations express miRNAs that are predicted to target CSC genes expressed in other CSC subpopulations provides a mechanism that might explain the co-existence of multiple CSC subpopulations, tumor heterogeneity, and cancer therapy resistance.
Accelerated nanopore basecalling with SLOW5 data format
Authors: Samarakoon Hiruna , Ferguson James M. , Gamaarachchi Hasindu , Deveson Ira W. 
Published: February 2023

ABSTRACTNanopore sequencing is emerging as a key pillar in the genomic technology landscape but computational constraints limiting its scalability remain to be overcome. The translation of raw current signal data into DNA or RNA sequence reads, known as ‘basecalling’, is a major friction in any nanopore sequencing workflow. Here, we exploit the advantages of the recently developed signal data format ‘SLOW5’ to streamline and accelerate nanopore basecalling on high-performance computer (HPC) and cloud environments. SLOW5 permits highly efficient sequential data access, eliminating a significant analysis bottleneck. To take advantage of this, we introduceButtery-eel, an open-source wrapper for Oxford Nanopore’sGuppybasecaller that enables SLOW5 data access, resulting in performance improvements that are essential for scalable, affordable basecalling.
No evidence for HPAI H5N1 2.3.4.4b incursion into Australia in 2022
Authors: Wille Michelle , Klaassen Marcel 
Published: February 2023

AbstractThere is an ongoing and profound burden of lineage 2.3.4.4b high pathogenicity avian influenza (HPAI) H5 on wild birds and poultry, globally. Herein we report the continued absence of HPAI in Australia from September – December 2022, in inbound migratory birds. Given the ever changing phenotype of this virus, worldwide studies on the occurence, or here absence of the virus, are of critical importance to understand the virus’ dispersal and incursion risk and development of response strategies.
Changes in physicochemical properties and microbial community succession during leaf stacking fermentation
Authors: Zhang Guanghai , Zhao Lu , Li Wei , Yao Heng , Lu Canhua , Zhao Gaokun , Liu Ziyi , Wu Yuping , Yang Wanlong , Li Yongping , Kong Guanghui 
Published: February 2023

ABSTRACTLeaf stacking fermentation involves enzymatic actions of many microorganisms and is an efficient and environmentally benign process for degrading macromolecular organic compounds. We investigated the dynamics of metabolite profiles, bacterial and fungal communities and their interactions during fermentation using cigar leaves from three geographic regions. The results showed that the contents of total sugar, reducing sugar, starch, cellulose, lignin, pectin, polyphenol and protein in cigar tobacco leaves was significantly decreased during fermentation. Notably, the furfural, neophytadiene, pyridine, benzyl alcohol, geranyl acetone, 2-butanone, 3-hydroxy-, N-hexanal, isoamylalcohol and 2,3-pentanedione were important features volatile aroma compounds during fermentation. The α-diversity of fungi and bacteria initially increased and then decreased during fermentation. The microbial diversity was influenced by fermentation stages and growing locations, in which the fermentation stages had greater impacts on the microbial diversity than locations. Microbiome profiling had identified several core bacteria includingSphingomonas, Bacillus, Staphylococcus, Pseudomonas, Ralstonia, MassiliaandFibrobacter. Fungal biomarkers includedAspergillus, Penicillium, Fusarium, CladosporiumandTrichomonascus. Interestingly, the molecular ecological networks showed that the core taxa had significant correlations with metabolic enzymes and physicochemical properties; bacteria and fungi jointly participated in the carbohydrate and nitrogen compound degrading and volatile aroma compound chemosynthesis processes during fermentation. These studies provide insights into the coupling of material conversion and microbial community succession during leaf fermentation.IMPORTANCECigar tobacco leaves are still crude after air curing. Fermentation can eliminate the pungent and bitter taste of the leaves and promote the accumulations of aromatic compounds. Hitherto, there has been no systematic study on the material conversion, metabolic enzymes and microbial community changes and their interactions in fermented leaves. The significance of our research is in identifying the potential metabolic cooperation related to microbial community, which will greatly enhance our understanding of microorganism to convert macromolecular organic to small molecules during the leaf stacking fermentation process.
Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens
Authors: James Joe , Billington Elizabeth , Warren Caroline J , De Sliva Dilhani , Genova Cecilia Di , Airey Maisie , Meyer Stephanie M. , Lewis Thomas , Peers-Dent Jacob , Thomas Saumya S. , Lofts Abigail , Furman Natalia , Slomka Marek J. , Brown Ian H. , Banyard Ashley C. 
Published: February 2023

AbstractThe 2021/2022 epizootic of high pathogenicity avian influenza (HPAIV) remains one of the largest ever in the UK, being caused by a clade 2.3.4.4b H5N1 HPAIV. This epizootic affected more than 145 poultry premises, most likely through independent incursion from infected wild birds, supported by more than 1700 individual detections of H5N1 from wild bird mortalities. Here an H5N1 HPAIV, representative of this epizootic (H5N1-21), was used to investigate its virulence, pathogenesis and transmission in layer chickens and pekin ducks, two species of epidemiological importance. We inoculated both avian species with decreasing H5N1-21 doses. The virus was highly infectious in ducks, with high infection levels and accompanying shedding of viral RNA, even in ducks inoculated with the lowest dose, reflecting the strong waterfowl adaptation of the clade 2.3.4.4 HPAIVs. Duck-to-duck transmission was very efficient, coupled with high environmental contamination. H5N1-21 was frequently detected in water sources, serving as likely sources of infection for ducks, but inhalable dust and aerosols represented low transmission risks. In contrast, chickens inoculated with the highest dose exhibited lower rates of infection compared to ducks. There was no evidence for experimental H5N1-21 transmission to any naive chickens, in two stocking density scenarios, coupled with minimal and infrequent contamination being detected in the chicken environment. Systemic viral dissemination to multiple organs reflected the pathogenesis and high mortalities in both species. In summary, the H5N1-21 virus is highly infectious and transmissible in anseriformes, yet comparatively poorly adapted to galliformes, supporting strong host preferences for wild waterfowl. Key environmental matrices were also identified as being important in the epidemiological spread of this virus during the continuing epizootic.
The hydrophobic nature of dengue 2 M residue 36 influences E protein and ApoptoM peptide
Authors: Decotter Jason , Desprès Philippe , Gadea Gilles 
Published: February 2023

ABSTRACTThe recent epidemics of dengue in South West Indian Ocean coincided with the emergence of Cosmopolitan dengue virus type 2, including viral strains DES-14 in Tanzania and then RUN-18 in La Reunion. The initial step of dengue virus assembly is the formation of heterodimers between prM and E proteins where prM acts as a chaperone for E. During dengue virus maturation, prM is cleaved into membrane protein M which embeds a pro-apoptotic peptide consisting of residues 31/41 and referred as ApoptoM. An infrequent valine at position M-36 was found in DES-14 whereas RUN-18 bears a common isoleucine. Here, we investigated whether Ile-to-Val substitution at position M-36 may have an impact on RUN-18 E expression and cell-death promoting capability of RUN-18 ApoptoM. Using recombinant RUN-18 envelope proteins expressed in human epithelial A549 cells, we showed that Ile-to-Val but not Ile-to-Ala substitution affects the behavior E protein reducing the cytotoxicity of prM and E proteins. The substitution of isoleucine by valine at position M-36 leads to increase the apoptosis-inducing activity of ApoptoM. Our data highlight that hydrophobic nature of amino-acid residue in position 36 of dengue virus M protein influences E protein expression and death-promoting activity of ApoptoM opens up important perspectives in the development of effective live-attenuated DENV vaccines.
Ecological and evolutionary dynamics of cell-virus-virophage systems
Authors: Nino Barreat Jose Gabriel , Katzourakis Aris 
Published: February 2023

AbstractMicrobial eukaryotes can be infected by giant viruses, which can be infected by virophages. Virophages are parasites of the virus transcription machinery and can interfere with virus replication, resulting in a benefit to the eukaryotic host population. Surprisingly, virophages can integrate into the genomes of their cell or virus hosts, and have been shown to reactivate during coinfection. This raises interesting questions about the role of integration in the dynamics of cell-virus-virophage systems. Here, we use mathematical models and computational simulations to understand the effect of virophage integration on populations of cells and viruses. We also investigate programmed-cell death (PCD) and multicellularity as potential antiviral defence strategies used by cells. We found that virophages which enter the cell independently of the host virus, such as Mavirus, are expected to integrate commonly into the genomes of their cell hosts. In contrast, we show that virophages like Sputnik which form a complex with the giant virus, should rarely be found integrated in cell genomes. Alternatively, we found that Sputnik virophages can stably persist integrated in the virus population, as long as they do not completely inhibit virus replication. We also show that increasing virophage inhibition can stabilise oscillatory dynamics, which may explain the long-term persistence of viruses and virophages in the environment. Our results demonstrate that inhibition by virophages, PCD and multicellularity are effective antiviral strategies that may act in synergy against viral infection in microbial species.
callsync: an R package for alignment and analysis of multi-microphone animal recordings
Authors: Smeele Simeon Q. , Tyndel Stephen A. , Klump Barbara C. , Alarcón-Nieto Gustavo , Aplin Lucy M. 
Published: February 2023

SummaryTo better understand how vocalisations are used during interactions of multiple individuals, studies are increasingly deploying on-board devices with a microphone on each animal. The resulting recordings are extremely challenging to analyse, since microphone clocks drift non-linearly and record the vocalisations of non-focal individuals as well as noise.Here we address this issue withcallsync, an R package designed to align recordings, detect and assign vocalisations to the caller, trace the fundamental frequency, filter out noise and perform basic analysis on the resulting clips.We present a case study where the pipeline is used on a dataset of six captive cockatiels (Nymphicus hollandicus) wearing backpack microphones. Recordings initially had drift of ∼2 minutes, but were aligned to within ∼2 seconds with our package. Usingcallsync, we detected and assigned 2101 calls across three multi-hour recording sessions. Two had loud beep markers in the background designed to help the manual alignment process. One contained no obvious markers, in order to demonstrate that markers were not necessary to obtain optimal alignment. We then used a function that traces the fundamental frequency and applied spectrographic cross correlation to show a possible analytical pipeline where vocal similarity is visually assessed.Thecallsyncpackage can be used to go from raw recordings to a clean dataset of features. The package is designed to be modular and allows users to replace functions as they wish. We also discuss the challenges that might be faced in each step and how the available literature can provide alternatives for each step.
Evolutionary conservation of mechanical strain distributions in functional transitions of protein structures
Authors: Sartori Pablo , Leibler Stanislas 
Published: February 2023

AbstractOne of the tenets of molecular biology is that dynamic transitions between three-dimensional structures determine the function of proteins. Therefore, it seems only natural that evolutionary analysis of proteins, presently based mainly on their primary sequence, needs to shift its focus towards their function as assessed by corresponding structural transitions. This can be facilitated by recent progress in cryogenic electron microscopy that provides atomic structures of multiple conformational states for proteins and protein assemblies isolated from evolutionarily related species. In this work, we study evolutionary conservation of multi-protein assembly function by using mechanical strain as a quantitative footprint of structural transitions. We adopt the formalism of finite strain analysis, developed in condensed matter physics, and apply it, as a case study, to a classical multi-protein assembly, the ATP synthase. Our Protein Strain Analysis (PSA) provides a precise characterization of rotation domains that agrees with the present biophysical knowledge. In addition, we obtain a strain distribution on the protein structure associated with functional transitions. By analyzing in detail, the strain patterns of the chains responsible for ATP synthesis across distinct species, we show that they are evolutionarily conserved for the same functional transition. Such conservation is not revealed by displacement or rotation patterns. Furthermore, within each functional transition, we can identify conserved strain patterns for ATP synthases isolated from different organisms. The observed strain conservation across evolutionary distant species indicates that strain should be essential in future structure-based evolutionary studies of protein function.
A cingulate-hippocampal circuit mediates early depressive symptoms in Alzheimer’s disease
Authors: Chen Yanbing , Peng Huimin , Zhuang Kai , Xie Wenting , Li Chenli , Xue Jin , Chen Meiqin , Huang Xiaoting , Zou Tingting , Wang Ya , Can Dan , Li Huifang , Yuan Tifei , Zhang Jie 
Published: February 2023

AbstractDepressive symptoms are prevalent and precedes cognitive decline in Alzheimer’s disease (AD), which worsen the clinical outcome and severely challenge the life quality of the patients. However, the neural circuitry mediating mood disturbance in AD remains elusive. Here we report that the glutamatergic projection from the anterior cingulate cortex (ACC) to the ventral hippocampal CA1 (vCA1) acts as the neural substrate of depressive symptoms in AD. We systemically mapped axonal projection in early stage of 5xFAD mice (3 months), which accompanies depressive- like behavior in these animals and identified reduced axonal projection from ACC to vCA1. This is in accordance with reduced axonal calcium signals detected with in vivo fiber photometry. Chemogenetic or optogenetic reversal of ACC-vCA1 circuitry activity efficiently ameliorated the depressive-like behaviors as well as cognitive impairment in 5xFAD mice. We further identified the synaptic molecules neuregulin-1 (Nrg1) as one vital signal regulating the synaptic glutamate transmission from the ACC to the vCA1. Collectively, these results indicated ACC-vCA1 as a critical pathway that regulates emotional states in Alzheimer’ disease. Targeting cingulate cortices with brain stimulation may treat depression in AD.
A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and alleviates experimental atherosclerosis
Authors: Castro R , Kalecký K , Huang NK , Petersen K , Singh V , Ross AC , Neuberger T , Bottiglieri T 
Published: February 2023

AbstractKetogenic diets (KD) are very low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. In this study, we used apolipoprotein E deficient (ApoE-/-)mice to investigate the vascular impact and plasma metabolic signature of a very high-fat KD compared to a non-ketogenic high-fat diet (HFD). Plasma samples were collected after 4, 8, and 12 weeks on the experimental diets and used to quantify the major ketone body β-hydroxybutyrate (BHB), inflammatory cytokines (interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1; and tumor necrosis factor α, TNF-α), and targeted metabolomic profiling by mass spectrometry. Moreover, aortic atherosclerotic lesions were quantified ex vivo by magnetic resonance imaging (MRI) on a 14-tesla system. The results showed that, relative to HFD mice, the KD mice had markedly higher levels of BHB and lower levels of cytokines, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation. Moreover, mice under nutritional ketosis displayed a distinct plasma amino acid profile evidencing a KD-induced alteration in protein metabolism. Significant changes in the plasma metabolome in KD mice included a decrease in lipophilic and increase in hydrophilic metabolites. Despite the higher fat content of the KD versus the HFD, KD mice presented significantly lower levels of several lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides. Consistent with the shift in energy metabolism toward fatty acid oxidation caused by the KD, the ratio of acylcarnitines to free carnitine was significantly higher in KD than in HFD mice., the aortic plaque burden was significantly lower in the KD versus the HFD group. In conclusion, nutritional ketosis induced by the KD was associated with specific metabolic changes and an atheroprotective phenotype versus the HFD.
Co-worker incivility and employee engagement among Ghanaian bank workers: does emotional intelligence matter?
Authors: Amponsah-Tawiah Kwesi , Baafi Nana Kojo Ayimadu , Mensah Jusice 
Published: February 2023

PurposeThe purpose of this study is to ascertain the mechanism through which an employee engages at the workplace when faced with an uncivil act.Design/methodology/approachThe study adopted a cross-sectional survey design to sample 482 participants drawn from commercial banks operating in Ghana. The population of the study (employees working in banks in Ghana) was selected owing to the recent reforms in the sector coupled with the emerging fear of loss of jobs as a result of the corona virus pandemic and the potential impact on employee work attitudes. Participants were however selected conveniently and employees who were available and willing to participate given questionnaires to complete.FindingsCo-worker incivility significantly and negatively predicted employee engagement, while emotional intelligence (EI) predicted employee engagement positively. Furthermore, EI served as a mediator between co-worker incivility and engagement.Research limitations/implicationsDespite these encouraging findings, the mechanism underlying these effects could not be identified. Therefore, future studies can establish the underlying mechanisms of these effects by using qualitative studies or the mixed-method. Future studies can also explore other personal resources such as psychological capital or personality traits in mitigating the negative effects of workplace incivility.Practical implicationsGiven the fact that incivility has a significant negative influence on employees within the organisation, there is the need for government and policy makers to enact an inclusive policy that deals with employee mistreatments and most especially low key mistreatment. This could be done through the promulgation of a national policy on psychosocial risk management (PRIMA) as most of the uncivil acts in organisations present as psychosocial risk factors. Secondly, at the organisational level there is the need to consider EI of employees most especially when recruiting employees so as to avoid squared pegs being placed in round holes.Originality/valueThis research found out that for an employee to engage or not when faced with an uncivil act, one’s EI has to play a role. The appraisal theory was used to provide a sufficient grounds in exploring the role of EI in the evaluations and determination of occurrences in organisations as intentional or unintentional, positive or negative and hence the resultant work outcomes.