bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence-dependent model of genes with dual σ factor preference
Authors: Baptista Ines S. C. , Kandavalli Vinodh , Chauhan Vatsala , Bahrudeen Mohammed N. M. , Almeida Bilena L. B. , Palma Cristina , Dash Suchintak , Ribeiro Andre S. 
Published: November 2021

AbstractEscherichia coli uses σ factors to quickly control large gene cohorts during stress conditions. While most of its genes respond to a single σ factor, approximately 5% of them have dual σ factor preference. The most common are those responsive to both σ70, which controls housekeeping genes, and σ38, which activates genes during stationary growth and stresses. Using RNA-seq and flow-cytometry measurements, we show that ‘σ70+38 genes’ are nearly as upregulated in stationary growth as ‘σ38 genes’. Moreover, we find a clear quantitative relationship between their promoter sequence and their response strength to changes in σ38 levels. We then propose and validate a sequence dependent model of σ70+38 genes, with dual sensitivity to σ38 and σ70, that is applicable in the exponential and stationary growth phases, as well in the transient period in between. We further propose a general model, applicable to other stresses and σ factor combinations. Given this, promoters controlling σ70+38 genes (and variants) could become important building blocks of synthetic circuits with predictable, sequence-dependent sensitivity to transitions between the exponential and stationary growth phases.
Ribosome profiling of porcine reproductive and respiratory syndrome virus reveals novel features of viral gene expression
Authors: Cook Georgia M. , Brown Katherine , Shang Pengcheng , Li Yanhua , Soday Lior , Dinan Adam M. , Tumescheit Charlotte , Adrian Mockett A. P. , Fang Ying , Firth Andrew E. , Brierley Ian 
Published: November 2021

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus which causes significant economic losses to the swine industry worldwide. Here, we use ribosome profiling (RiboSeq) and parallel RNA sequencing (RNASeq) to characterise the transcriptome and translatome of both species of PRRSV and analyse the host response to infection. We quantified viral gene expression over a timecourse of infection, and calculated the efficiency of programmed ribosomal frameshifting (PRF) at both sites on the viral genome. At the nsp2 frameshift site (a rare example of protein-stimulated frameshifting), −2 PRF efficiency increases over time, likely facilitated by accumulation of the PRF- stimulatory viral protein (nsp1β) during infection. This marks arteriviruses as the second example of temporally regulated PRF. Surprisingly, we also found PRF efficiency at the canonical ORF1ab frameshift site increases over time, in apparent contradiction of the common assumption that RNA structure-directed frameshift sites operate at a fixed efficiency. This has potential implications for the numerous other viruses with canonical PRF sites. Furthermore, we discovered several highly translated additional viral ORFs, the translation of which may be facilitated by multiple novel viral transcripts. For example, we found a 125-codon ORF overlapping nsp12, which is expressed as highly as nsp12 itself at late stages of replication, and is likely translated from novel subgenomic (sg) RNA transcripts that overlap the 3′ end of ORF1b. Similar transcripts were discovered for both PRRSV-1 and PRRSV- 2, suggesting a potential conserved mechanism for temporal regulation of expression of the 3′-proximal region of ORF1b. In addition, we identified a highly translated, short upstream ORF (uORF) in the 5′ UTR, the presence of which is highly conserved amongst PRRSV-2 isolates. This is the first application of RiboSeq to arterivirus-infected cells, and reveals new features which add to the complexity of gene expression programmes in this important family of nidoviruses.
Body shape as a visual feature: evidence from spatially-global attentional modulation in human visual cortex
Authors: Thorat Sushrut , Peelen Marius V. 
Published: November 2021

AbstractFeature-based attention modulates visual processing beyond the focus of spatial attention. Previous work has reported such spatially-global effects for low-level features such as color and orientation, as well as for faces. Here, using fMRI, we provide evidence for spatially-global attentional modulation for human bodies. Participants were cued to search for one of six object categories in two vertically-aligned images. Two additional, horizontally-aligned, images were simultaneously presented but were never task-relevant across three experimental sessions. Analyses time-locked to the objects presented in these task-irrelevant images revealed that responses evoked by body silhouettes were modulated by the participants’ top-down attentional set, becoming more body-selective when participants searched for bodies in the task-relevant images. These effects were observed both in univariate analyses of the body-selective cortex and in multivariate analyses of the object-selective visual cortex. Additional analyses showed that this modulation reflected response gain rather than a bias induced by the cues, and that it reflected enhancement of body responses rather than suppression of non-body responses. These findings provide evidence for a spatially-global attention mechanism for body shapes, supporting the rapid and parallel detection of conspecifics in our environment.
Micro-state-based neural decoding of speech categorization using Bayesian non-parametrics
Authors: Al-Fahad Rakib , Yeasin Mohammed , Moinuddin Kazi Ashraf , Bidelman Gavin M 
Published: November 2021

ABSTRACTUnderstanding the many-to-many mapping between patterns of functional brain connectivity and discrete behavioral responses is critical for speech-language processing. We present a microstate-based analysis of EEG recordings to characterize spatio-temporal dynamics of neural activities that underly rapid speech categorization decisions. We implemented a data driven approach using Bayesian non-parametrics to capture the mapping between EEG and the speed of listeners’ phoneme identification [i.e., response time (RT)] during speech labeling tasks. Based on our empirical analyses, we show task-relevant events such as resting-state, stimulus coding, auditory-perceptual object (category) formation, and response selection can be explained using patterns of micro-state dwell-time and are decodable as unique time segments during speech perception. State-dependent activities localize to a fronto-temporo-parietal circuit (superior temporal, supramarginal, inferior frontal gyri) exposing a core decision brain network (DN) underlying rapid speech categorization. Furthermore, RTs were inversely proportional to the frequency of state transitions, such that the rate of change between brain microstates was higher for trials with slower compared to faster RTs. Our findings imply that during rapid speech perception, higher uncertainty producing prolonged RTs (slower decision-making) is associated with staying in the DN longer compared lower RTs (faster decisions). We also show that listeners’ perceptual RTs are highly sensitive to individual differences. Our computational method opens a new avenue in segmentation and dynamic brain connectivity for modeling neuroimaging data and understanding task-related cognitive events.
Effects of crude oil on juvenile threespine stickleback somatic and immune development
Authors: Ireland Kelly S. , Milligan-Myhre Kathryn 
Published: November 2021

AbstractAquatic oil spills have resounding effects on surrounding ecosystems, and thus significant resources are committed to oil spill responses to remove the oil from the environment as quickly as possible. Oil has immunotoxic effects and may be particularly harmful to larval and juvenile fish as it can cause a number of developmental defects and stunt growth. In spite of significant efforts to clean oil, it is unclear whether larval and juvenile fish can recover from the effects of oil and no work has been done on the effect crude oil has on developing threespine stickleback (Gasterosteus aculeatus) fish. Threespine stickleback are a ubiquitous sentinel species in the northern hemisphere and are an important food source for many larger, economically valuable fish. As fish with fully marine, anadromous, and freshwater populations, stickleback are exposed to oil in a variety of aquatic environments. We hypothesized that oil exposure would suppress both growth and immunity of developing stickleback, but that fish health could be recovered by removal of the crude oil. Fish were exposed to Alaska North Slope crude oil and then were moved to water without crude oil for two weeks (depuration). Measurements of growth and immunity were taken before and after the depuration. We found that crude oil effected different developmental pathways independently, significantly impacting some but not others. This is the first study to examine the effect crude oil has on early stages of stickleback development, and that stickleback fish are unable to recover from exposure after being transferred to clean water for two-weeks, suggesting larval/juvenile stickleback exposed to crude oil need longer than two-weeks to recover if they are able to recover at all.
A novel growth and isolation medium for exoelectrogenic bacteria
Authors: Nazeer Zumaira , Fernando Eustace Y. 
Published: November 2021

AbstractA microbiological isolation and growth medium that can effectively discriminate electrochemically active exoelectrogenic bacteria from other non-exoelectrogenic bacteria, is currently unavailable. In this study, we developed a novel chromogenic growth and isolation solid medium based on MnO2 that can selectively allow the growth of exoelectrogenic bacteria and change the medium colour in the process. Known exoelectrogenic bacteria such as Shewanella oneidensis MR1 and other such bacteria from functional microbial fuel cell (MFC) anodes were capable of growing and changing colour in the novel growth medium. On the contrary, non-exoelectrogenic bacteria such as Escherichia coli ATCC 25922 were incapable of growing and inducing a colour change in the novel medium. Further biochemical characterisation of these isolated exoelectrogenic bacteria by Raman micro-spectroscopy demonstrated that these bacteria over express cytochrome proteins that are vital in extracellular electron transfer events. This medium is a convenient method to isolate exoelectrogenic bacteria from complex environmental samples.
53BP1 mediated recruitment of RASSF1A at ribosomal DNA breaks facilitates local ATM signal amplification
Authors: Tsaridou Stavroula , Velimezi Georgia , Willenbrock Frances , Chatzifrangkeskou Maria , Panagopoulos Andreas , Karamitros Dimitris , Gorgoulis Vassilis , Lygerou Zoi , O’Neill Eric , Pefani Dafni Eleftheria 
Published: November 2021

AbstractDNA lesions occur across the genome and constitute a threat to cell viability; however, damage at specific genomic loci has a disproportionally greater impact on the overall genome stability. The ribosomal RNA gene repeats (rDNA) are emerging fragile sites due to repetitive nature, clustering and high transcriptional activity. Notably, recent progress in understanding how the rDNA damage response is organized has highlighted the key role of adaptor proteins in the response.Here we identify that the scaffold and tumor suppressor, RASSF1A is recruited at sites of damage and particularly enriched at rDNA breaks. Employing targeted nucleolar DNA damage, we find that RASSF1A recruitment requires ATM activity and depends on the 53BP1. At sites of damage RASSF1A facilitates local ATM signal establishment and rDNA break repair. RASSF1A silencing, a common epigenetic event during malignant transformation, results in persistent breaks, rDNA copy number alterations and decreased cell viability. Moreover, meta-analysis of a lung adenocarcinoma cohort showed that epigenetic silencing of the scaffold leads in rDNA copy number discrepancies. Overall, we present evidence that RASSF1A acts as a DNA repair factor and offer mechanistic insight in how the nucleolar DNA damage response is organized.
Aspergillus fumigatus ffmA encodes a C2H2-containing transcriptional regulator that modulates azole resistance and is required for normal growth
Authors: Paul Sanjoy , Bowyer Paul , Bromley Michael , Moye-Rowley W. Scott 
Published: November 2021

AbstractThe production of a collection of disruption mutant strains corresponding to a large number of transcription factors from the filamentous fungal pathogen Aspergillus fumigatus has permitted rapid identification of transcriptional regulators involved in a range of different processes. Here we characterize a gene designated ffmA (favors fermentative metabolism) as an C2H2-containing transcription factor that is required for azole drug resistance and normal growth. Loss of ffmA caused cells to exhibit significant defects in growth, either under untreated or azole-challenged conditions. Loss of FfmA caused a reduction in expression of the AbcG1 ATP-binding cassette transporter, previousy shown to contribute to azole resistance. Strikingly, overproduction of the AtrR transcription factor gene restored a wild-type growth phenotype to a ffmAΔ strain. Overexpression of AtrR also suppressed the defect in AbcG1 expression caused by loss of FfmA. Replacement of the ffmA promoter with a doxycycline-repressible promoter restored near normal growth in the absence of doxycycline. Finally, chromatin immunoprecipitation experiments indicated that FfmA bound to its own promoter as well as to the abcG1 promoter. These data imply that FfmA and AtrR interact both with respect to abcG1 expression and also more broadly to regulate hyphal growth.ImportanceInfections associated with azole-resistant forms of the primary human pathogen, Aspergillus fumigatus, are associated with poor outcomes in patient populations. This makes analysis of the mechanisms underlying azole resistance of A. fumigatus a high priority. In this work, we describe characterization of a gene designated ffmA that encodes a sequence-specific transcriptional regulator. We identified ffmA in a screen of a collection of gene disruption mutant strains made in A. fumigatus. Loss of ffmA caused sensitivity to azole drugs and also a large reduction in normal growth. We found that overproduction of the AtrR transcription factor was able to restore growth to ffmA null cells. We provide evidence that FfmA can recognize promoters of genes involved in azole resistance as well as the ffmA promoter itself. Our data indicate that FfmA and AtrR interact to support azole resistance and normal growth.
Polygenic Risk Scores for Prediction of Breast Cancer in Korean women
Authors: Jee Yon Ho , Ho Weang-Kee , Park Sohee , Easton Douglas F. , Teo Soo-Hwang , Jung Keum Ji , Kraft Peter 
Published: November 2021

ABSTRACTBackgroundPolygenic risk scores (PRSs) developed using European and Asian GWAS have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models based on a PRS or PRS combined with lifestyle clinical and environmental factors in Asian women is limited. We evaluate the discrimination and calibration of several breast cancer PRSs among Korean women; these PRSs were developed using Asian and/or European training samples and include between 11 and 947,621 variants.MethodsFor each PRS, we compared discrimination (area under the curve [AUC]) and calibration (expected-to-observed ratio [E/O]) of three absolute risk models among 41,031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality, and risk factor distributions (reference inputs) among U.S. women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.ResultsAll Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women; a PRS trained using both European and Asian GWAS results led to the greatest improvement (Qx: AUC=0.65, Qx+PRS: AUC=0.72). U.S.- based absolute risk models overestimated the risks for women age ≥50 years, and this overestimation was larger for models that only included PRS (E/O=1.2 for women <50, E/O=2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.ConclusionsIncorporation of Asian and European PRS can improve discrimination in Korean women and may be useful for the risk-stratified interventions.Key Messages⍰Prospective validation of absolute risk prediction models combining lifestyle and polygenic risk scores in Asian women is limited.⍰We evaluated the calibration and discrimination of five PRSs developed using Asian and/or European training samples; two PRS were restricted to genome-wide significant SNPs, two included sub-genome-wide significant SNPs, and a multi-ancestry PRS using both European and Asian GWAS results.⍰Incorporation of PRS previously developed in Asian and European-ancestry populations can improve discrimination in Korean women.⍰Calibration improved for risk models that incorporate age-specific incidence rates from the target population relative to models that use external incidence rates⍰Our finding suggests that PRS may be useful for prioritizing individuals for targeted intervention on their lifestyle such as alcohol intake and obesity.⍰Further studies are needed to evaluate the value of incorporating PRS into risk models in ancestrally diverse populations.
Activating silent glycolysis bypasses inEscherichia coli
Authors: Iacometti Camillo , Marx Katharina , Hönick Maria , Biletskaia Viktoria , Schulz-Mirbach Helena , Satanowski Ari , Dronsella Beau , Delmas Valérie A. , Berger Anne , Dubois Ivan , Bouzon Madeleine , Döring Volker , Noor Elad , Bar-Even Arren , Lindner Steffen N. 
Published: November 2021

AbstractAll living organisms share similar reactions within their central metabolism to provide precursors for all essential building blocks and reducing power. To identify whether alternative metabolic routes of glycolysis can operate inE. coli, we complementarily employedin silicodesign, rational engineering, and adaptive laboratory evolution. First, we used a genome-scale model and identified two potential pathways within the metabolic network of this organism replacing canonical Embden-Meyerhof-Parnas (EMP) glycolysis to convert phosphosugars into organic acids. One of these glycolytic routes proceeds via methylglyoxal, the other via serine biosynthesis and degradation. Then, we implemented both pathways inE. colistrains harboring defective EMP glycolysis. Surprisingly, the pathway via methylglyoxal immediately operated in a triosephosphate isomerase deletion strain cultivated on glycerol. By contrast, in a phosphoglycerate kinase deletion strain, the overexpression of methylglyoxal synthase was necessary for implementing a functional methylglyoxal pathway. Furthermore, we engineered the ‘serine shunt’ which converts 3-phosphoglycerate via serine biosynthesis and degradation to pyruvate, bypassing an enolase deletion. Finally, to explore which of these alternatives would emerge by natural selection we performed an adaptive laboratory evolution study using an enolase deletion strain. The evolved mutants were shown to use the serine shunt. Our study reveals the flexible repurposing of metabolic pathways to create new metabolite links and rewire central metabolism.
Antagonism of the azoles to olorofim and cross-resistance are governed by linked transcriptional networks in Aspergillus fumigatus
Authors: van Rhijn Norman , Hemmings Sam , Storer Isabelle S. R. , Valero Clara , Alshammri Hajer , Goldman Gustavo H. , Gsaller Fabio , Amich Jorge , Bromley Michael J 
Published: November 2021

AbstractAspergillosis, in its various manifestations, is a major cause of morbidity and mortality. Very few classes of antifungal drugs have been approved for clinical use to treat these diseases and resistance to the first line therapeutic class, the triazoles, is increasing. A new class of antifungals that target pyrimidine biosynthesis, the orotomides, are currently in development with the first compound in this class, olorofim in late-stage clinical trials. In this study, we identify an antagonistic action of the triazoles on the action of olorofim. We show that this antagonism is the result of an azole induced upregulation of the pyrimidine biosynthesis pathway and regulation. Intriguingly, we show that loss of function in the higher order transcription factor, HapB a member of the heterotrimeric HapB/C/E (CBC) complex or the regulator of nitrogen metabolic genes AreA, leads to cross resistance to both the azoles and olorofim indicating that factors that govern resistance are under common regulatory control. However loss of azole induced antagonism requires decoupling of the pyrimidine biosynthetic pathway in a manner independent of the action of a single transcription factor. Our study provides a first insight into antagonism between the azoles and olorofim through dysregulation of the pyrimidine and ergosterol pathway, showing complex crosstalk between these two pathways.
Essential role for an isoform ofEscherichia colitranslation initiation factor IF2 in repair of two-ended DNA double-strand breaks
Authors: Mallikarjun Jillella , Gowrishankar J 
Published: November 2021

AbstractInEscherichia coli, three isoforms of the essential translation initiation factor IF2 (IF2-1, IF2-2, and IF2-3) are generated from separate in-frame initiation codons ininfB. The isoforms have earlier been suggested to additionally participate in DNA damage repair and replication restart. It is also known that the proteins RecA and RecBCD are needed for repair of DNA double-strand breaks (DSBs) in E.coli. Here we show that strains lacking IF2-1 are profoundly sensitive to two-ended DSBs in DNA generated by radiomimetic agents phleomycin or bleomycin, or by endonuclease I-SceI. However, these strains remained tolerant to other DSB-generating genotoxic agents or perturbations to whichrecAandrecBCmutants remained sensitive, such as to mitomycin C, type-2 DNA topoisomerase inhibitors, or DSB caused by palindrome cleavage behind a replication fork. Data from genome-wide copy number analyses following I-SceI cleavage at a single chromosomal locus suggested that, in a strain lacking IF2-1, the magnitude of break induced replication through replication restart mechanisms is largely preserved but the extent of DNA resection around the DSB site is reduced. We propose that in absence of IF2-1 it is the annealing of a RecA nucleoprotein filament to its homologous target that is weakened, which in turn leads to a specific failure in assembly ofTer-to-oriCdirected replisomes needed for consummation of two-ended DSB repair.ImportanceDouble-strand breaks (DSBs) in DNA are major threats to genome integrity. InEscherichia coli, DSBs are repaired by Rec- and RecBCD-mediated homologous recombination (HR). This study demonstrates a critical role for an isoform (IF2-1) of the translation initiation factor IF2 in the repair of two-ended DSBs inE. coli(that can be generated by ionizing radiation, certain DNA-damaging chemicals, or endonuclease action). It is proposed that IF2-1 acts to facilitate the function of RecA in the annealing between a pair of DNA molecules during HR.