bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity and prevalence of colibactin- and yersiniabactin encoding mobile genetic elements in enterobacterial populations: insights into evolution and co-existence of two bacterial secondary metabolite determinants
Authors: Wami Haleluya , Wallenstein Alexander , Sauer Daniel , Stoll Monika , von Bünau Rudolf , Oswald Eric , Müller Rolf , Dobrindt Ulrich 
Published: January 2021

1 AbstractThe bacterial genotoxin colibactin interferes with the eukaryotic cell cycle by causing double-stranded DNA breaks. It has been linked to bacterially induced colorectal cancer in humans. Colibactin is encoded by a 54-kb genomic region inEnterobacteriaceae. The colibactin genes commonly co-occur with the yersiniabactin biosynthetic determinant. Investigating the prevalence and sequence diversity of the colibactin determinant and its linkage to the yersiniabactin operon in prokaryotic genomes, we discovered mainly species-specific lineages of the colibactin determinant and classified three main structural settings of the colibactin-yersiniabactin genomic region inEnterobacteriaceae. The colibactin gene cluster has a similar but not identical evolutionary track to that of the yersiniabactin operon. Both determinants could have been acquired on several occasions and/or exchanged independently between enterobacteria by horizontal gene transfer. Integrative and conjugative elements play(ed) a central role in the evolution and structural diversity of the colibactin-yersiniabactin genomic region. Addition of an activating and regulating module (clbAR) to the biosynthesis and transport module (clbB-S) represents the most recent step in the evolution of the colibactin determinant. In a first attempt to correlate colibactin expression with individual lineages of colibactin determinants and different bacterial genetic backgrounds, we compared colibactin expression of selected enterobacterial isolatesin vitro. Colibactin production in the testedKlebsiellaspp. andCitrobacter koseristrains was more homogeneous and generally higher than that in most of theE. coliisolates studied. Our results improve the understanding of the diversity of colibactin determinants and its expression level, and may contribute to risk assessment of colibactin-producing enterobacteria.
Moderately pathogenic maternal influenza A virus infection disrupts placental integrity but spares the fetal brain
Authors: Antonson Adrienne M. , Kenney Adam D. , Chen Helen J. , Corps Kara N. , Yount Jacob S. , Gur Tamar L. 
Published: January 2021

AbstractMaternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed lung inflammatory cytokine production and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of IL-17A signaling and fetal neuroinflammation, which are hallmarks of mimetic-induced MIA, were not detected. Our results suggest that mild or moderately pathogenic IAV infection during pregnancy does not inflame the developing fetal brain, and highlight the importance of live pathogen infection models for the study of MIA.HighlightsA mouse model of influenza A virus (IAV) infection during pregnancy was establishedModerate IAV infection induced lung inflammation and blunted weight gain in damsMaternal IAV infection caused mild pathology in the placenta without pup lossModerate gestational IAV infection did not induce fetal brain inflammationAn IAV infection severity threshold may exist for inducing fetal neuroinflammation
Analysis of Spleen Histopathology, Splenocyte composition and Hematological Parameters in Mice Infected withPlasmodium bergheiK173
Authors: Wang Huajing , Li Shuo , Cui Zhao , Qin Tingting , Shi Hang , Ma Ji , Li Lanfang , Yu Guihua , Jiang Tingliang , Li Canghai 
Published: January 2021

ABSTRACTMalaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of infection is believed to be accomplished by the spleen and mononuclear phagocytic system (MPS), both in the presence and absence of artemisinin treatment. The spleen filters infected RBCs from circulation through immune-mediated recognition of the infected RBCs followed by phagocytosis. Using different strains of mice infected withP. bergheiK173 (PbK173), the mechanisms leading to splenomegaly, histopathology, splenocyte activation and proliferation, and their relationship to control of parasitemia and host mortality were examined. Survival time of mice infected with PbK173 varied, although the infection was uniformly lethal. Mice of the C57BL/6 strain were the most resistant, while mice of the strain ICR were the most susceptible. BALB/c and KM mice were intermediate. In the course of PbK173 infection, both strains of mice experienced significant splenomegaly. Parasites were observed in the red pulp at 3 days post infection in all animals. All spleens retained late trophozoite stages as well as a fraction of earlier ring-stage parasites. The percentages of macrophages in infected C57BL/6 and KM mice were higher than uninfected mice on 8 dpi. Spleens of infected ICR and KM mice exhibited structural disorganization and remodeling. Furthermore, parasitemia was significantly higher in KM versus C57BL/6 mice at 8 dpi. The percentages of macrophages in ICR infected mice were lower than uninfected mice, and the parasitemia was higher than other strains. The results presented here demonstrate the rate of splenic mechanical filtration and the splenic macrophages likely contribute to an individual’s total parasite burden. This in turn can influence the pathogenesis of malaria. Finally, different genetic backgrounds of mice have different splenic mechanisms for controlling malaria infection.
Oral epithelial cells distinguish betweenCandidaspecies with high or low pathogenic potential through miRNA regulation
Authors: Horváth Márton , Nagy Gábor , Zsindely Nóra , Bodai László , Horváth Péter , Vágvölgyi Csaba , Nosanchuk Joshua D. , Tóth Renáta , Gácser Attila 
Published: January 2021

AbstractOral epithelial cells monitor microbiome composition and initiate immune response upon dysbiosis, as in case ofCandidaimbalances. Comparison of healthy oral epithelial cell responses revealed that the inability ofC. parapsilosisto induce a robust antifungal response was due to activation of various inflammation-independent pathways, whileC. albicansrobustly activated inflammation cascades. Regarding posttranscriptional regulation, several miRNAs were altered by both species. ForC. parapsilosis,the applied dose directly correlated with changes in transcriptomic responses. Carbohydrate metabolism, hypoxia- and cardiovascular development-related responses dominate afterC. parapsilosisstimulus, whereasC. albicansaltered inflammatory responses. Subsequent analyses of HIF1-α and HSC-activation pathways predicted target genes through which miRNA-dependent regulation of yeast-specific functions may occur, supporting the observed responses. Thus,C. parapsilosisis recognized as a commensal at low doses by the oral epithelium; however, increased fungal burden activates different pathways, some of which overlap with inflammatory processes induced byC. albicans.Impact statementAltered miRNA regulation discriminates betweenC. albicansandC. parapsilosisin human oral epithelial cells
ENHANCED GRAVITROPISM 2encodes a STERILE ALPHA MOTIVE containing protein that controls root growth angle in barley and wheat
Authors: Kirschner Gwendolyn K. , Rosignoli Serena , Vardanega Isaia , Guo Li , Imani Jafargholi , Altmüller Janine , Milner Sara G. , Balzano Raffaella , Nagel Kerstin A. , Pflugfelder Daniel , Forestan Cristian , Bovina Riccardo , Koller Robert , Stöcker Tyll G. , Mascher Martin , Simmonds James , Uauy Cristobal , Schoof Heiko , Tuberosa Roberto , Salvi Silvio , Hochholdinger Frank 
Published: January 2021

AbstractThe root growth angle defines how roots grow towards the gravity vector and is among the most important determinants of root system architecture. It controls water uptake capacity, nutrient use efficiency, stress resilience and as a consequence yield of crop plants. We demonstrated that theegt2(enhanced gravitropism 2) mutant of barley exhibits steeper root growth of seminal and lateral roots and an auxin independent higher responsiveness to gravity compared to wild type plants. We cloned theEGT2gene by a combination of bulked segregant analysis and whole genome sequencing. Subsequent validation experiments by an independent CRISPR/Cas9 mutant allele demonstrated thategt2encodes a STERILE ALPHA MOTIF domain containing protein.In situhybridization experiments illustrated thatEGT2is expressed from the root cap to the elongation zone. Subcellular localization experiments revealed thatEGT2localizes to the nucleus and cytoplasm. We demonstrated the evolutionary conserved role ofEGT2in root growth angle control between barley and wheat by knocking out theEGT2orthologs in the A and B genomes of tetraploid durum wheat. By combining laser capture microdissection with RNA-seq, we observed that seven expansin genes were transcriptionally downregulated in the elongation zone. This is consistent with a role ofEGT2in this region of the root where the effect of gravity sensing is executed by differential cell elongation. Our findings suggest thatEGT2is an evolutionary conserved regulator of root growth angle in barley and wheat that could be a valuable target for root-based crop improvement strategies in cereals.Significance StatementTo date the potential of utilizing root traits in plant breeding remains largely untapped. In this study we cloned and characterized theENHANCED GRAVITROPISM2(EGT2) gene of barley that encodes a STERILE ALPHA MOTIF domain containing protein. We demonstrated thatEGT2is a key gene of root growth angle regulation in response to gravity which is conserved in barley and wheat and could be a promising target for crop improvement in cereals.
Variation analysis of SARS-CoV-2 complete sequences from Iran
Authors: Moradi Jale , Moghoofei Mohsen , Alvandi Amir Houshang , Abiri Ramin 
Published: January 2021

AbstractThe SARS-CoV-2 is a new emerging coronavirus initially reported in China at the late December 2019 and rapidly spread to the whole of the world. To date, 1261903 total case and 55830 deaths are reported from Iran as 8 January. In this study, we investigated all the complete sequences of SARS-CoV-2 that publicly reported from Iran. Twenty-four sequences between March to September 2020 were analyzed to identify genome variations and phylogenetic relationships. Furthermore, we assessed the amino acid changes related to the spike glycoprotein as an important viral factor associated with the entry to the host cells and as a vaccine target. Most of the variations are occurred in the ORF1ab, S, N, intergenic and ORF7 regions. The analysis of spike protein mutations demonstrated that D614G mutation could be detected from the May and beyond. Phylogenetic analysis showed that most of the circulated viruses in Iran are belong to the B.4 lineage. Although, we found a limited number of variants associated to the B.1 lineage carrying D614G mutation. Furthermore, we detected a variant characterize as the B.1.36 lineage with sixteen mutations in the spike protein region. This study showed the frequency of the viral populations in Iran as September, therefore, there is an emergent need to genomic surveillance to track viral lineage shift in the country beyond the September. These data would help to predict future situation and apply better strategy to control of the pandemic.
A targeted and tuneable DNA damage tool using CRISPR/Cas9
Authors: Emmanouilidis Ioannis , Fili Natalia , Cook Alexander W. , Hari-Gupta Yukti , dos Santos Ália , Wang Lin , Martin-Fernandez Marisa , Ellis Peter J.I. , Toseland Christopher P. 
Published: January 2021

ABSTRACTMammalian cells are constantly subjected to a variety of DNA damaging events that lead to the activation of DNA repair pathways. Understanding the molecular mechanisms of the DNA damage response allows the development of therapeutics which target elements of these pathways.Double-Strand Breaks (DSB) are particularly deleterious to cell viability and genome stability. Typically, DSB repair is studied using DNA damaging agents such as ionising irradiation or genotoxic drugs. These induce random lesions at non-predictive genome sites, where damage dosage is difficult to control. Such interventions are unsuitable for studying how different DNA damage recognition and repair pathways are invoked at specific DSB sites in relation to the local chromatin state.The RNA-guided Cas9 (CRISPR associated protein 9) endonuclease enzyme, is a powerful tool to mediate targeted genome alterations. Cas9-based genomic intervention is attained through DSB formation in the genomic area of interest. Here, we have harnessed the power to induce DSBs at defined quantities and locations across the human genome, using custom-designed promiscuous guide RNAs, based onin silicopredictions. This was achieved using electroporation of recombinant Cas9-guide complex which provides a generic, low-cost and rapid methodology for inducing controlled DNA damage in cell culture models.
Long range, high-gamma phase coherence in the human brain during overt and covert speech
Authors: Valiante Taufik A. , Garic Bojan 
Published: January 2021

AbstractUsing intracranial electroencephalography (iEEG) in patients undergoing diagnostic workup for epilepsy, we show that during reading, phase coherent high-gamma activity emerges between spatially distant regions of proven involvement in vocalization. Using the novel metric of “phase-dependent power-causal correlations”, causal interactions were shown to be maximal at high-gamma frequencies, and displayed stronger correlations to power fluctuations near the optimal time delay, with this delay potentially accounted for by axonal conduction. We conclude that high-gamma activity may represents propagated, directed, large-scale integration between task related regions of the human brain.
De novogenome assembly of the land snailCandidula unifasciata(Mollusca: Gastropoda)
Authors: Chueca Luis J. , Schell Tilman , Pfenninger Markus 
Published: January 2021

AbstractAmong all molluscs, land snails are an economically and scientifically interesting group comprising edible species, alien species and agricultural pests. Yet, despite its high diversity, the number of whole genomes publicly available is still scarce. Here, we present the draft genome assembly of the land snailCandidula unifasciata, a widely distributed species along central Europe, which belongs to Geomitridae family, a group highly diversified in the Western-Palearctic region. We performed a whole genome sequencing, assembly and annotation of an adult specimen based on PacBio and Oxford Nanopore long read sequences as well as Illumina data. A genome of about 1.29 Gb was generated with a N50 length of 246 kb. More than 60% of the assembled genome was identified as repetitive elements, and 22,464 protein-coding genes were identified in the genome, where the 62.27% were functionally annotated. This is the first assembled and annotated genome for a geometrid snail and will serve as reference for further evolutionary, genomic and population genetic studies of this important and interesting group.
In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-Spike RBD interface
Authors: Villoutreix Bruno O. , Calvez Vincent , Marcelin Anne-Genevieve , Khatib Abdel-Majid 
Published: January 2021

AbstractSARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor and several in silico methods to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both UK and South African strains) should be favorable for the interaction with ACE2 while the K417N and E484K substitutions (South African) would seem unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the predicted less favorable (regarding binding) K417N and E484K Spike replacements. Our finding suggests that, if indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions outside the direct Spike-ACE2 interface.HihglightsTransmission of the UK and possibly South African SARS-CoV-2 strains appears substantially increased compared to other variantsThis could be due, in part, to increased affinity between the variant Spike proteins and ACE2We investigated in silico the 3D structure of the Spike-ACE2 complex with a focus on Spike K417N, E484K and N501YThe N501Y substitution is predicted to increase the affinity toward ACE2 (UK strain) with subsequent enhanced transmissibility and possibly pathogenicityAdditional substitutions at positions 417 and 484 (South African strain) may pertub the interaction with ACE2 raising questions about transmissibility and pathogenicity
Shedding light on the contribution of amygdalar excitatory projections to prepulse inhibition of the auditory startle reflex
Authors: Cano Jose Carlos , Huang Wanyun , Fénelon Karine 
Published: January 2021

AbstractBackgroundSensorimotor gating is a fundamental neural filtering process that allows attention to be focused on a given stimulus. Sensory gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders, including schizophrenia. Because PPI deficits are often associated with attention and cognitive impairments, they are widely used as biomarkers in pre-clinical research for anti-psychotic drug screening. Yet, the neurotransmitter systems and synaptic mechanisms underlying PPI are still not resolved, even under physiological conditions. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since amygdalar dysfunctions affect PPI and are common to pathologies displaying sensorimotor gating deficits, the present study was designed to test that direct projections to the PnC originating from the amygdala, contribute to PPI.ResultsUsing Wild Type and transgenic mice expressing eGFP under the control of the glycine transporter type 2 promoter (GlyT2-eGFP mice), we first employed tract-tracing, morphological reconstructions and immunohistochemical analyses to demonstrate that the central nucleus of the amygdala (CeA) sends glutamatergic inputs latero-ventrally to PnC neurons, including GlyT2+cells. Then, we showed the contribution of the CeA-PnC excitatory synapses to PPIin vivoby demonstrating that optogenetic inhibition of this connection decreases PPI, and optogenetic activation induces partial PPI. Finally, in GlyT2-Cre mice, whole-cell recordings of GlyT2+PnC neuronsin vitropaired with optogenetic stimulation of CeA fibers, as well as photo-inhibition of GlyT2+PnC neuronsin vivo, allowed us to implicate GlyT2+neurons in the PPI pathway.ConclusionsOur results uncover a feed-forward inhibitory mechanism within the brainstem startle circuit by which amygdalar glutamatergic inputs and GlyT2+PnC neurons play a key role in meditating PPI. We are providing new insights to the clinically-relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurodevelopmental diseases.
Emergence and fast spread of B.1.1.7 lineage in Lebanon
Authors: Younes Mahmoud , Hamze Kassem , Nassar Hassan , Makki Mohamad , Ghadar Maysaa , Nguewa Paul , Sater Fadi Abdel 
Published: January 2021

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a rapid spread emerging disease. Recently, a new variant of this virus called SARS-CoV-2 VOC 202012/01 (or B.1.1.7 lineage), described in the United Kingdom (UK), has become highly prevalent in several countries. Its rate of transmission has been estimated to be greatly higher. B.1.1.7 lineage harbors 23 mutations co-existed for the first time in the same variant. Herein, we are interested only by the deletion mutation ΔH69/ΔV70 in the spike protein.In the UK they were able to identify the increase of this new variant through the increase in the false negative result for the spike target of a three-target RT-PCR assay from Thermo Fisher Scientific (TaqPath kit). Later, the manufacturer announced that this false negative result is because of the deletion ΔH69/ΔV70 in the area targeted by the TaqPath Kit. Furthermore, The European CDC recommended that the use of this kit help to track the new variant.Genome sequencing is the gold method to confirm the new variant, but observational studies provide also stronger evidence if similar models are observed in multiple countries, especially when randomized studies are not possible. In Lebanon, the highest number of confirmed cases were reported in first week of 2021. In the present study, we show the emergence and the fast spreading of the new variant in Lebanon and a relationship between SARS-CoV-2 transmission intensity and the frequency of the new variant during the first twelve days of January.
Active packaging films and edible coatings based on polyphenol‐rich propolis extract: A review
Authors: Yong Huimin , Liu Jun 
Published: January 2021

AbstractThe development of active packaging films and edible coatings based on biopolymers and natural bioactive substances has received increasing attention in recent years. Propolis, also called bee glue, is a natural resin substance collected by worker‐bees from the mucilage, gum, and resin of several plants. In food industry, propolis is commonly extracted in solvents to afford polyphenol‐rich extract with potent antimicrobial and antioxidant activities. The prepared propolis extract can be mixed with biopolymers, plasticizers, emulsifiers, and reinforcing agents to develop active packaging films and edible coatings. The functionality of active packaging films and edible coatings is closely related to the type, harvesting method, geographic origin, extraction method and extraction conditions of propolis, the content and composition of polyphenolic compounds in the extract, and the presence of other bioactive substances. Active packaging films and edible coatings based on propolis extract can impact the physical, biochemical, and sensory properties of food (e.g., fruits, vegetables, meat, and fish) during storage. This review focuses on the recent advances of active packaging films and edible coatings based on polyphenol‐rich propolis extract. The impact of polyphenol‐rich propolis extract on the structural characterization, functionality, and potential food applications of the films and edible coatings is summarized.