bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competence-associated peptide BriC alters fatty acid biosynthesis inStreptococcus pneumoniae
Authors: Aggarwal Surya D. , Gullett Jessica M. , Fedder Tara , Safi J. Pedro F. , Rock Charles O. , Hiller N. Luisa 
Published: February 2021

ABSTRACTMembrane lipid homeostasis is required for bacteria to survive in a spectrum of host environments. This homeostasis is achieved by regulation of fatty acid chain length and of the ratio of saturated to unsaturated fatty acids. In the pathogenStreptococcus pneumoniae, fatty acid biosynthesis is encoded by a cluster of fatty acid biosynthesis (fab) genes (FASII locus) whose expression is controlled by the FabT repressor. Encoded immediately downstream of the FASII locus is BriC, a competence-induced, cell-cell communication peptide that promotes biofilm development as well as nasopharyngeal colonization in a murine model of pneumococcal carriage. Here, we demonstrate thatbriCis co-transcribed with genes of thefabgene cluster and that a reduction ofbriClevels, caused by decoupling its transcription fromfabgene cluster, negatively impacts biofilm development. BriC elevatesfabTtranscription, which is predicted to alter the balance of saturated and unsaturated fatty acids produced by the pathway. We find thatbriCinactivation results in a decreased production of unsaturated fatty acids that impact the membrane properties by decreasing the abundance of di-unsaturated phosphatidylglycerol molecular species. We propose that the link between BriC, FabT and phospholipid composition contributes to the ability ofS. pneumoniaeto alter membrane homeostasis in response to the production of a quorum-sensing peptide.IMPORTANCEAdaptation of bacteria to their host environment is a key component of colonization and pathogenesis. As an essential component of bacterial membranes, fatty acid composition contributes to host adaptation. Similarly, so does cell-cell communication, which serves as a mechanism for population levels responses. While much is known about the pathways that control the biosynthesis of fatty acids, many questions remain regarding regulation of these pathways and consequently the factors that impacts the balance between saturated and unsaturated fatty acids. We find that BriC, a cell-cell communication peptide implicated in biofilm regulation and colonization, is both influenced by a fatty acid biosynthesis pathway and impacts this same pathway. This study identified a link between cell-cell communication, fatty acid composition, and biofilms and, in doing so, suggests that these pathways are integrated into the networks that control pneumococcal colonization and host adaptation.
Accelerated vaccine induction of IgM neutralising antibody enables vaccine protection against same day lethal influenza virus challenge
Authors: Honda-Okubo Yoshikazu , Li Lei , Baldwin Jeremy , Petrovsky Nikolai 
Published: February 2021

ABSTRACTNovel influenza strains to which humans have no pre-existing immunity can trigger global pandemics without warning. Current pandemic vaccines typically require two doses and up to 6 weeks to induce protective immunity. In addition, to their role in increasing vaccine-induced immune response, adjuvants may also play a part in reducing the time between immunization and vaccine protection, although this role has seldom been previously explored in literature. This study assessed the speed of protection achievable with a standard inactivated influenza vaccine when formulated with or without a novel delta-inulin adjuvant (Advax). When formulated with Advax adjuvant mice were protected even when the vaccine was administered intramuscularly contemporaneously with a lethal intranasal virus challenge. The protection was found to be B-cell dependent and transfer of day 6 immune serum from mice immunised with Advax-adjuvanted influenza vaccine conferred protection to naïve animals. This protection was shown to be mediated by vaccine induced IgM rather than IgG neutralising antibodies. The results show that influenza vaccine can be formulated to provide immediate protection following immunization with this novel concept warranting testing in human trials.IMPORTANCEIn the past 100 years there have been several major influenza pandemics that resulted in significant loss of life. The time taken for individuals to develop vaccine protection is an important factor in curbing the spread of infection and reducing pandemic mortality rates. Current influenza vaccines can take up to 5-6 weeks to generate full protection leaving front-line heath care workers and others, at risk for an extended period of time. Our novel accelerated vaccine protection approach provides effectively immediate vaccine protection against lethal virus challenge. This would assist front-line workers to continue to provide essential services and maintain critical infrastructure during pandemic. The study also highlights the often-overlooked role that antigen-specific IgM plays in virus protection and provides a novel adjuvanted strategy for enlisting IgM to provide accelerated vaccine protection.
Aspergillus fumigatusIn-Host HOG pathway mutation for Cystic Fibrosis Lung Microenvironment Persistence
Authors: Ross Brandon S. , Lofgren Lotus A. , Ashare Alix , Stajich Jason E. , Cramer Robert A. 
Published: February 2021

AbstractThe prevalence ofAspergillus fumigatuscolonization in individuals with Cystic Fibrosis (CF) and subsequent fungal persistence in the lung is increasingly recognized. However, there is no consensus for clinical management ofA. fumigatusin CF individuals, due largely to uncertainty surroundingA. fumigatusCF pathogenesis and virulence mechanisms. To address this gap in knowledge, a longitudinal series ofA. fumigatusisolates from an individual with CF were collected over 4.5 years. Isolate genotypes were defined with whole genome sequencing that revealed both transitory and persistentA. fumigatusin the lung. Persistent lineage isolates grew most readily in a low oxygen culture environment and conidia were more sensitive to oxidative stress inducing conditions compared to non-persistent isolates. Closely related persistent isolates harbor a unique allele of the high osmolarity glycerol (HOG) pathway mitogen activated protein kinase kinase, Pbs2 (pbs2C2). Data suggest this novelpbs2C2allele arosein vivoand is necessary for the fungal response to osmotic stress in a low oxygen environment through hyperactivation of the HOG (SakA) signaling pathway. Hyperactivation of the HOG pathway throughpbs2C2comes at the cost of decreased conidia stress resistance in the presence of atmospheric oxygen levels. These novel findings shed light on pathoadaptive mechanisms ofA. fumigatusin CF, lay the foundation for identifying persistentA. fumigatusisolates that may require antifungal therapy, and highlight considerations for successful culture of persistent fungal CF isolates.ImportanceAspergillus fumigatusinfection causes a spectrum of clinical manifestations. For individuals with Cystic Fibrosis (CF), Allergic Bronchopulmonary Aspergillosis (ABPA) is an established complication, but there is a growing appreciation forA. fumigatusairway persistence in CF disease progression. There currently is little consensus for clinical management ofA. fumigatuslong-term culture positivity in CF. A better understanding ofA. fumigatuspathogenesis mechanisms in CF is expected to yield insights into when antifungal therapies are warranted. Here, a 4.5-year longitudinal collection ofA. fumigatusisolates identified a persistent lineage that harbors a unique allele of the Pbs2 MAPKK necessary for unique CF-relevant stress phenotypes. Importantly forA. fumigatusCF patient diagnostics, this allele provides increased CF lung fitness at a cost of reducedin vitrogrowth in standard laboratory conditions. These data illustrate a molecular mechanism forA. fumigatusCF lung persistence with implications for diagnostics and antifungal therapy.
Indoleamine 2,3-dioxygenase upregulates PD-1 expression on ovarian tumor infiltrating CD8+ T cells via kynurenine activation of the aryl hydrocarbon receptor
Authors: Amobi-McCloud Adaobi , Muthuswamy Ravikumar , Battaglia Sebastiano , Yu Han , Liu Tao , Wang Jianmin , Putluri Vasanta , Singh Prashant K , Qian Feng , Huang Ruea-Yea , Putluri Nagireddy , Tsuji Takemasa , Lugade Amit A , Liu Song , Odunsi Kunle 
Published: February 2021

AbstractThe immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO1) and the PD-1/PD-L1 axis are potent mechanisms that impede effective anti-tumor immunity in ovarian cancer. However, whether the IDO pathway regulates PD-1 expression in T cells is currently unknown. Here we show that tumoral IDO1 expression led to profound changes in tryptophan, nicotinate/nicotinamide, and purine metabolic pathways in the ovarian tumor microenvironment, and to an increased frequency of PD-1+CD8+ tumor infiltrating T cells. We determined that activation of the aryl hydrocarbon receptor (AHR) by kynurenine induced PD-1 expression, and this effect was significantly abrogated by the AHR antagonist CH223191. Mechanistically, kynurenine alters chromatin accessibility in regulatory regions of T cell inhibitory receptors, allowing AHR to bind to consensus XRE motifs in the promoter region of PD-1. These results enable the design of strategies to target the IDO1 and AHR pathways for enhancing anti-tumor immunity in ovarian cancer.
Genome-wide insights into population structure and host specificity ofCampylobacter jejuni
Authors: Epping Lennard , Walther Birgit , Piro Rosario M. , Knüver Marie-Theres , Huber Charlotte , Thürmer Andrea , Flieger Antje , Fruth Angelika , Janecko Nicol , Wieler Lothar H. , Stingl Kerstin , Semmler Torsten 
Published: February 2021

AbstractThe zoonotic pathogenCampylobacter jejuniis among the leading causes of foodborne diseases worldwide. WhileC. jejunicolonises many wild animals and livestock, persistence mechanisms enabling the bacterium to adapt to host species’ guts are not fully understood. In order to identify putative determinants influencing host preferences of distinct lineages, bootstrapping based on stratified random sampling combined with ak-mer-based genome-wide association was conducted on 490 genomes from diverse origins in Germany and Canada.We show a strong association of both the core and the accessory genome characteristics with distinct host animal species, indicating multiple adaptive trajectories defining the evolution ofC. jejunilifestyle preferences in different ecosystems. Here, we demonstrate that adaptation towards a specific host niche ecology is most likely a long evolutionary and multifactorial process, expressed by gene absence or presence and allele variations of core genes. Several host-specific allelic variants from different phylogenetic backgrounds, includingdnaE,rpoB,ftsX or pycB play important roles for genome maintenance and metabolic pathways. Thus, variants of genes important forC. jejunito cope with specific ecological niches or hosts may be useful markers for both surveillance and future pathogen intervention strategies.
Replication-related control over cell division inEscherichia coliis growth-rate dependent
Authors: Tiruvadi-Krishnan Sriram , Männik Jaana , Kar Prathitha , Lin Jie , Amir Ariel , Männik Jaan 
Published: February 2021

SummaryHow replication and division processes are coordinated in the cell cycle is a fundamental yet poorly understood question in cell biology. InEscherichia colidifferent data sets and models have supported a range of conclusions from one extreme where these two processes are tightly linked to another extreme where these processes are completely independent of each other. Using high throughput optical microscopy and cell cycle modeling, we show that in slow growth conditions replication and division processes are strongly correlated, indicating a significant coupling between replication and division. This coupling weakens as the growth rate of cells increases. Our data suggest that the underlying control mechanism in slow growth conditions is related to unreplicated chromosome blocking the onset of constriction at the midcell. We show that the nucleoid occlusion protein SlmA does not play a role in this process and neither do other known factors involved in positioning bacterial Z-ring relative to the chromosome. Altogether this work reconciles different ideas from the past and brings out a more nuanced role of replication in controlling the division process in a growth-rate dependent manner.
Revisiting the early evolution of Cyanobacteria with a new thylakoid-less and deeply diverged isolate from a hornwort
Authors: Rahmatpour Nasim , Hauser Duncan A. , Nelson Jessica M. , Chen Pa Yu , Villarreal A. Juan Carlos , Ho Ming-Yang , Li Fay-Wei 
Published: February 2021

SummaryCyanobacteria have played pivotal roles in Earth’s geological history especially during the rise of atmospheric oxygen. However, our ability to infer the early transitions in Cyanobacteria evolution has been limited by their extremely lopsided tree of life—the vast majority of extant diversity belongs to Phycobacteria (or “crown Cyanobacteria”), while its sister lineage, Gloeobacteria, is depauperate and contains only two closely related species ofGloeobacterand a metagenome-assembled genome. Here we describe a new culturable member of Gloeobacteria,Anthocerobacter panamensis, isolated from a tropical hornwort.Anthocerobacterdiverged fromGloeobacterover 1.4 billion years ago and has low 16S identities with environmental samples. Our ultrastructural, physiological, and genomic analyses revealed that this species possesses a unique combination of traits that are exclusively shared with either Gloeobacteria or Phycobacteria. For example, similar toGloeobacter, it lacks thylakoids and circadian clock genes, but the carotenoid biosynthesis pathway is typical of Phycobacteria. Furthermore,Anthocerobacterhas one of the most reduced gene sets for photosystems and phycobilisomes among Cyanobacteria. Despite this,Anthocerobacteris capable of oxygenic photosynthesis under a wide range of light intensities, albeit with much less efficiency. Given its key phylogenetic position, distinct trait combination, and availability as a culture,Anthocerobacteropens a new window to further illuminate the dawn of oxygenic photosynthesis.
Dynamics and nanoscale organization of the postsynaptic endocytic zone at excitatory synapses
Authors: Catsburg Lisa A.E. , Westra Manon , van Schaik Annemarie M. L. , MacGillavry Harold D. 
Published: February 2021

ABSTRACTAt postsynaptic sites of neurons, a prominent clathrin-coated structure, the endocytic zone (EZ), controls the trafficking of glutamate receptors and is essential for synaptic plasticity. Despite its importance, little is known about how this clathrin structure is organized to mediate endocytosis. We used live-cell and super-resolution microscopy techniques to reveal the dynamic organization of this poorly understood clathrin structure. We found that a subset of endocytic proteins only transiently appeared at postsynaptic sites. In contrast, other proteins, including Eps15, intersectin1L, and β2-adaptin, were persistently enriched and partitioned at the edge of the EZ. We found that uncoupling the EZ from the synapse led to the loss of most of these components, while disrupting the actin cytoskeleton or AP2-membrane interactions did not alter EZ positioning. We conclude that the EZ is a stable, highly organized molecular platform where components are differentially recruited and positioned to orchestrate the endocytosis of synaptic receptors.
MITOCHONDRIAL GENOME REVEALS CONTRASTING PATTERN OF ADAPTIVE SELECTION IN TURTLES AND TORTOISES
Authors: Sahoo Subhashree , Kumar Ajit , Rai Jagdish , Gupta Sandeep Kumar 
Published: February 2021

AbstractTestudinoidea represents an evolutionarily unique taxon comprising both turtles and tortoises. The contrasting habitats that turtles and tortoises inhabit are associated with unique physio-ecological challenges hence enable distinct adaptive evolutionary strategies. To comparatively understand the pattern and strength of Darwinian selection and physicochemical evolution in turtle and tortoise mitogenomes, we employed adaptive divergence and selection analyses. We evaluated changes in structural and biochemical properties, and codon models on the mitochondrial protein-coding genes (PCGs) among three turtles and a tortoise lineage. We used mitochondrial PCGs that constitute the crucial oxidative phosphorylation (OXPHOS) respiratory system, a critical metabolic regulator which assumes key significance in energy regulation of ectotherms.We detected strong evidence of positive selection along the turtle lineages: Geoemydidae, Emydidae, and Platysternidae, but relatively weak signals in tortoises. The Platysternidae turtles revealed the highest gene and site-wise positive selection. In turtles, positively selected sites were prevalent in NAD2 and NAD4 genes in OXPHOS Complex I, and COB gene of Complex III, indicating convergent adaptive evolution. Besides, NAD3 was the only subunit that showed adaptive selection in both turtles and tortoises, expressing its relevance for all Testudinoidea. Structural and functional analysis revealed many sites and physiochemical changes in important conserved as well as biomedically significant regions, suggesting the influence of adaptive pressure on mitogenome functions. Hence, our study furnished novel evidence of contrasting evolutionary selective pressure acting on closely related groups such as turtles and tortoises with unique habitat preferences and associated eco-physiological challenges.
Substrate dynamics contribute to enzymatic specificity in human and bacterial methionine adenosyltransferases
Authors: Gade Madhuri , Tan Li Lynn , Damry Adam M. , Sandhu Mahakaran , Brock Jospeh S. , Delaney Andie , Villar-Briones Alejandro , Jackson Colin J. , Laurino Paola 
Published: February 2021

AbstractProtein conformational change can facilitate the binding of non-cognate substrates and underlie promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here we analyse human (hMAT2A) andEscherichia coli(eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, non-cognate substrates bind in a stable conformation to allow catalysis. In contrast, non-cognate substrates rarely sample stable productive binding modes in eMAT owing to altered mobility in the enzyme active site. Different cellular concentrations of substrate likely drove the evolutionary divergence of substrate specificity in these orthologs. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated level in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the effects of substrate and enzyme dynamics.
Disrupting short-term memory in premotor cortex affects serial dependence in visuomotor integration
Authors: de Azevedo Neto Raymundo Machado , Bartels Andreas 
Published: February 2021

AbstractHuman behavior is biased by past experience. For example, when intercepting a moving target, the speed of previous targets will bias responses in future trials. Neural mechanisms underlying this so-called serial dependence are still under debate. Here, we tested the hypothesis that the previous trial leaves a neural trace in brain regions associated with encoding task-relevant information in visual and/or motor regions. We reasoned that injecting noise by means of transcranial magnetic stimulation (TMS) over premotor and visual areas would degrade such memory traces and hence reduce serial dependence. To test this hypothesis, we applied bursts of TMS pulses to right visual motion processing region hV5/MT+ and to left dorsal premotor cortex during inter-trial intervals of a coincident timing task performed by twenty healthy human participants (15 female). Without TMS, participants presented a bias towards the speed of the previous trial when intercepting moving targets. TMS over dorsal premotor cortex decreased serial dependence in comparison to the control Vertex stimulation, whereas TMS applied over hV5/MT+ did not. In addition, TMS seems to have specifically affected the memory trace that leads to serial dependence, as we found no evidence that participants’ behavior worsened after applying TMS. These results provide causal evidence that an implicit short-term memory mechanism in premotor cortex keeps information from one trial to the next, and that this information is blended with current trial information so that it biases behavior in a visuomotor integration task with moving objects.Significance StatementHuman perception and action are biased by the recent past. The origin of such serial bias is still not fully understood, but a few components seem to be fundamental for its emergence: the brain needs to keep previous trial information in short-term memory and blend it with incoming information. Here, we present evidence that a premotor area has a potential role in storing previous trial information in short-term memory in a visuomotor task, and that this information is responsible for biasing ongoing behavior. These results corroborate the perspective that areas associated with processing information of a stimulus or task also participate in maintaining that information in short-term memory even when this information is no longer relevant for current behavior.
Perceptual history acts in world-centred coordinates
Authors: Mikellidou Kyriaki , Cicchini Guido Marco , Burr David C. 
Published: February 2021

AbstractSerial dependence effects have been observed using a variety of stimuli and tasks, revealing that the recent past can bias current percepts, leading to increased similarity between two. The aim of this study is to determine whether this temporal integration occurs in egocentric or allocentric coordinates. We ask participants to perform an orientation reproduction task using grating stimuli while the head is kept at a fixed position throughout the whole session or while alternating position from one trial to the next, from left (−20°) to right (+20°), putting the egocentric and allocentric cues in conflict. Under these conditions, allocentric cues prevail.
Carotenoid and tocopherol fortification of zucchini fruits using a viral RNA vector
Authors: Houhou Fakhreddine , Cordero Teresa , Aragonés Verónica , Martí Maricarmen , Cebolla-Cornejo Jaime , de Castro Ana Pérez , Rodríguez-Concepción Manuel , Picó Belén , Daròs José-Antonio 
Published: February 2021

AbstractCarotenoids and tocopherols are health-promoting metabolites in livestock and human diets. Some important crops have been genetically modified to increase their content. Although the usefulness of transgenic plants to alleviate nutritional deficiencies is obvious, their social acceptance has been controversial. Here, we demonstrate an alternative biotechnological strategy for carotenoid and tocopherol fortification of edible fruits in which no transgenic DNA is involved. A viral RNA vector derived fromZucchini yellow mosaic virus(ZYMV) was modified to express a bacterial phytoene synthase (crtB), and inoculated in zucchini (Cucurbita pepoL.) leaves nurturing pollinated flowers. After the viral vector moved to the developing fruit and expressedcrtB, the rind and flesh of the fruits developed yellow-orange rather than green color. Metabolite analyses showed a substantial enrichment in health-promoting carotenoids, such as α- and β-carotene (pro-vitamin A), lutein and phytoene, in both rind and flesh. Considerably higher accumulation of α- and γ-tocopherol was also detected, particularly in fruit rind. Although this strategy is perhaps not free from controversy due to the use of genetically modified viral RNA, our work does demonstrate the possibility of metabolically fortifying edible fruits using an approach in which no transgenes are involved.