bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic and phenotypic diversity ofEnterococcus faecalisisolated from endophthalmitis
Authors: Chilambi Gayatri Shankar , Nordstrom Hayley R. , Evans Daniel R. , Kowalski Regis P. , Dhaliwal Deepinder K. , Jhanji Vishal , Shanks Robert MQ , Van Tyne Daria
Published: August 2020

Enterococcus faecalisare hospital-associated opportunistic pathogens and also causative agents of post-operative endophthalmitis. Patients with enterococcal endophthalmitis often have poor visual outcomes, despite appropriate antibiotic therapy. Here we investigated the genomic and phenotypic characteristics ofE. faecalisisolates collected from 13 patients treated at the University of Pittsburgh Medical Center Eye Center over 19 years. Comparative genomic analysis indicated that patients were infected withE. faecalisof diverse multi-locus sequence types (STs) previously associated with clinical, commensal, and environmental sources. We identified knownE. faecalisvirulence factors and antibiotic resistance genes in each genome, including genes conferring resistance to aminoglycosides, erythromycin, and tetracyclines. We assessed all isolates for their cytolysin production, biofilm formation, and antibiotic susceptibility, and observed phenotypic differences between isolates. Fluoroquinolone and cephalosporin susceptibilities were particularly variable, as were biofilm formation and cytolysin production. In addition, we found evidence ofE. faecalisadaptation during recurrent endophthalmitis by identifying genetic variants that arose in sequential isolates sampled over eight-months from the same patient. We identified a mutation in the DNA mismatch repair genemutSthat was associated with a hypermutator phenotype in the final isolate from the patient, which was also more resistant to ceftazidime. Overall this study documents the genomic and phenotypic variability amongE. faecaliscausing endophthalmitis, as well as possible adaptive mechanisms underlying bacterial persistence during recurrent ocular infection.

IMPORTANCE

Bacterial endophthalmitis is a sight-threatening infection of the inside of the eye.Enterococcus faecaliscause endophthalmitis occasionally, but when they do the infections are often severe. Here we investigated the genomes, antibiotic susceptibilities, and virulence-associated traits amongE. faecaliscollected from 13 patients with post-operative endophthalmitis. We wondered whether there were common bacterial factors that might explain why enterococcal endophthalmitis is so destructive to ocular tissues. Instead we found thatE. feacalisisolated from endophthalmitis were genetically and phenotypically diverse; isolates belonged to a variety of genetic lineages and showed varying levels of antibiotic resistance and biofilm formation. We also undertook further characterization of three closely relatedE. faecalisisolates from a patient with recurrent endophthalmitis, and found that a hypermutator strain emerged during persistent infection. Hypermutators have been found in a variety of other infection contexts; here we describe what we believe is the first case of a hypermutator arising during ocular infection.
Age disaggregation of crude excess deaths during the 2020 spring COVID–19 outbreak in Spain and Netherlands
Authors: Martín-Olalla José María
Published: August 2020

Spanish and Dutch official records of mortality and population during the 21st century are analyzed to determine the age specific crude death rate in the 2020 spring COVID–19 outbreak.

Excess death rate increases exponentially with age showing a doubling time [5.0, 5.6]a (Spain) and [3.9, 6.7]a (Netherlands), roughing doubling every five years of increase in age.The effective infection fatality rate in Spain also shows this doubling time.

Statistically significant mortality increase is noted above 45 a (Spain) and 60 a (Netherlands).

A statistically significant increase of mortality is also noted in Spain for the youngest age group.
CoMix: comparing mixing patterns in the Belgian population during and after lockdown
Authors: Coletti Pietro , Wambua James , Gimma Amy , Willem Lander , Vercruysse Sarah , Vanhoutte Bieke , Jarvis Christofer I , Van Zandvoort Kevin , Edmunds John , Beutels Philippe , Hens Niel
Published: August 2020

Background

The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening.

Methods

A representative sample of Belgian adults was asked about their contact behaviour from mid-April to mid-July, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of R0 with respect to pre-pandemic data.

Findings

During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. Since the end of May, the estimated reproduction number has a median value larger than one, although with a wide dispersion.

Conclusions

We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19.
The DNA mimic protein BCAS0292 is involved in the regulation of virulence ofBurkholderia cenocepacia
Authors: Dennehy Ruth , Dignam Simon , McCormack Sarah , Romano Maria , Hou Yueran , Ardill Laura , Whelan Matthew X. , Drulis-Kawa Zuzanna , Ó Cróinín Tadhg , Valvano Miguel A. , Berisio Rita , McClean Siobhán
Published: August 2020

Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host.Burkholderia cenocepacia, a Gram-negative bacterium that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages.B. cenocepaciapossesses a large genome encoding multiple virulence systems, stress response proteins and a large locus that responds to low oxygen. We previously identified BCAS0292, an acidic protein encoded on replicon 3. Deletion of the BCAS0292 gene resulted in altered abundance of >1000 proteins; 46 proteins became undetectable while 556 proteins showed ≥1.5-fold reduced abundance, suggesting BCAS0292 is a global regulator. Moreover, the ΔBCAS0292 mutant showed a range of pleiotropic effects: virulence, host-cell attachment and motility were reduced, antibiotic susceptibility was altered and biofilm formation enhanced. Its growth and survival were impaired in 6% oxygen. Structural analysis revealed BCAS0292 presents a dimeric β-structure with a negative electrostatic surface. Further, the ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. We propose that BCAS0292 acts as a DNA-mimic, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation ofB. cenocepaciato highly diverse environments.
The longitudinal stability of fMRI activation during reward processing in adolescents and young adults
Authors: Baranger David AA , Lindenmuth Morgan , Nance Melissa , Guyer Amanda E. , Keenan Kate , Hipwell Alison E , Shaw Daniel S , Forbes Erika E
Published: August 2020

Background

The use of functional neuroimaging has been an extremely fruitful avenue for investigating the neural basis of human reward function. This approach has included identification of potential neurobiological mechanisms of psychiatric disease and examination of environmental, experiential, and biological factors that may contribute to disease risk via effects on the reward system. However, a central and largely unexamined assumption of much of this research is that neural reward function is an individual difference characteristic that is relatively stable over time.

Methods

In two independent samples of adolescents and young adults studied longitudinally (Ns= 145 & 153, 100% female & 100% male, ages 15-21 & 20-22, 2-4 scans & 2 scans respectively), we tested within-person stability of reward-task BOLD activation, with a median of 1 and 2 years between scans. We examined multiple commonly used contrasts of active states and baseline in both the anticipation and feedback phases of a card-guessing reward task. We examined the effects of cortical parcellation resolution, contrast, network (reward regions and resting-state networks), region-size, and activation strength and variability on the stability of reward-related activation.

Results

Overall, stability (ICC; intra-class correlation) across 1-2 years was modest. In both samples, contrasts of an active state relative to a baseline were more stable (e.g., Win>Baseline; mean ICC = 0.13 – 0.33) than contrasts of two active states (e.g., Win>Loss; mean ICC = 0.048 – 0.05). Additionally, activation in reward regions was less stable than in many non-task networks (e.g., dorsal attention), and activation in regions with greater between-subject variability showed higher stability in both samples.

Conclusions

These results show that functional neuroimaging activation to reward has modest stability over 1-2 years. Notably, results suggest that contrasts intended to map cognitive function and show robust group-level effects (i.e. Win > Loss) may be less effective in studies of individual differences and disease risk. The robustness of group-level activation should be weighed against other factors when selecting regions of interest in individual difference fMRI studies.
FlyORF-TaDa allows rapid generation of new lines forin vivocell-type specific profiling of protein-DNA interactions inDrosophila melanogaster
Authors: Aughey Gabriel N , Delandre Caroline , Southall Tony D , Marshall Owen J
Published: August 2020

Targeted DamID (TaDa) is an increasingly popular method of generating cell-type specific DNA binding profilesin vivo. Although sensitive and versatile, TaDa requires the generation of new transgenic fly lines for every protein that is profiled, which is both time-consuming and costly. Here, we describe the FlyORF-TaDa system for converting an existing FlyORF library of inducible open reading frames (ORFs) to TaDa lines via a genetic cross, with recombinant progeny easily identifiable by eye colour. Profiling the binding of the H3K36me3-associated chromatin protein MRG15 in larval neural stem cells using both FlyORF-TaDa and conventional TaDa demonstrates that new lines generated using this system provide accurate and highly-reproducible DamID binding profiles. Our data further show that MRG15 binds to a subset of active chromatin domainsin vivo. Courtesy of the large coverage of the FlyORF library, the FlyORF-TaDa system enables the easy creation of TaDa lines for 74% of all transcription factors and chromatin modifying proteins within theDrosophilagenome.
The human PDZome 2.0: characterization of a new resource to test for PDZ interactions by Yeast Two-Hybrid
Authors: Castro-Cruz Monica , Lembo Frédérique , Borg Jean-Paul , Trave Gilles , Vincentelli Renaud , Zimmermann Pascale
Published: August 2020

PSD95-disc large-zonula occludens (PDZ) domains are globular modules of 80-90 amino acids that co-evolved with multicellularity. They commonly bind to carboxy-terminal sequences of a plethora of membrane-associated proteins and influence their trafficking and signaling. We previously built a PDZ resource (PDZome) allowing to unveil human PDZ interactions by Yeast two-hybrid. Yet, this resource is partial according to the current knowledge on the human PDZ proteome. Here we built the PDZome 2.0 library for Yeast two-hybrid, based in a PDZ library manually curated from online resources. The PDZome2.0 contains 305 individual clones (266 PDZ domains in isolation and 39 tandems), for which all boundaries have been designed based on available PDZ structures. Using as bait the E6 oncoprotein from HPV16, a known promiscuous PDZ interactor, we show that PDZome 2.0 outperforms the previous resource.
DDX50 is a viral restriction factor that enhances TRIF-dependent IRF3 activation
Authors: Pallett Mitchell A. , Lu Yongxu , Smith Geoffrey L.
Published: August 2020

The transcription factors IRF3 and NF-κB are crucial in innate immune signalling in response to many viral and bacterial pathogens. However, mechanisms leading to their activation remain incompletely understood. Canonical RLR signalling and detection of viral RNA is dependent upon the receptors RIG-I, MDA5 and TLR3. Alternatively, the DExD-Box RNA helicases DDX1-DDX21-DHX36 activate IRF3/NF-κB in a TRIF-dependent manner independent of RIG-I, MDA5 or TLR3. Here we describe DDX50, which shares 55.6% amino acid identity with DDX21, as a component of the dsRNA sensing machinery and signalling pathway. Deletion of DDX50 in mouse and human cells impaired activation of the IFNβ promoter, IRF3-dependent endogenous gene expression and cytokine/chemokine production in response to cytoplasmic dsRNA (polyIC transfection), and infection by RNA and DNA viruses. Mechanistically, DDX50 co-immunoprecipitated with TRIF and DDX1, promoting complex formation upon stimulation. Furthermore, whilst MAVs/TBK1 induced signalling is intact inDdx50KO cells, TRIF-dependent signalling was impaired suggesting DDX50 drives TRIF-dependentIfnβtranscription. Importantly, loss of DDX50 resulted in increased replication and dissemination of vaccinia virus, herpes simplex virus and Zika virus highlighting its important role as a viral restriction factor.

Author summary

The detection of viral RNA or DNA by host RNA or DNA sensors and the subsequent antiviral immune response are crucial for the outcome of infection and host survival in response to a multitude of viral pathogens. Detection of viral RNA or DNA culminates in the upregulation of inflammatory cytokines, chemokines and pathogen restriction factors that augment the host innate immune response, restrict viral replication and clear infection. The canonical RNA sensor RIG-I is a member of the large family of DExD/H-box helicases, however the biological role of many DExD/H-box helicases remain unknown. In this report, we describe the DExD-Box helicase DDX50 as a new component of the RNA sensing machinery. In response to DNA and RNA virus infection, DDX50 functions to enhance activation of the transcription factor IRF3, which enhances antiviral signalling. The biological importance of DDX50 is illustrated by its ability to restrict the establishment of viral infection and to diminish the yields of vaccinia virus, herpes simplex virus and Zika virus. These findings increase knowledge of the poorly characterised host protein DDX50 and add another factor to the intricate network of proteins involved in regulating antiviral signalling in response to infection.
The axonal sorting activity of pseudorabies virus Us9 protein depends on the state of neuronal maturation
Authors: Tanneti Nikhila S , Federspiel Joel D , Cristea Ileana M , Enquist Lynn W
Published: August 2020

Alpha-herpesviruses establish a life-long infection in the nervous system of the affected host; while this infection is restricted to peripheral neurons in a healthy host, the reactivated virus can spread within the neuronal circuitry, such as to the brain, in compromised individuals and lead to adverse health outcomes. Pseudorabies virus (PRV), an alpha-herpesvirus, requires the viral protein Us9 to sort virus particles into axons and facilitate neuronal spread. Us9 sorts virus particles by mediating the interaction of virus particles with neuronal transport machinery. Here, we report that Us9-mediated regulation of axonal sorting also depends on the state of neuronal maturation. Specifically, the development of dendrites and axons is accompanied with proteomic changes that influence neuronal processes. Immature superior cervical ganglionic neurons (SCGs) have rudimentary neurites that lack markers of mature axons. Immature SCGs can be infected by PRV, but they show markedly reduced Us9-dependent regulation of sorting, and increased Us9-independent transport of particles into neurites. Mature SCGs have relatively higher abundances of proteins characteristic of vesicle-transport machinery. We also identify Us9-associated neuronal proteins that can contribute to axonal sorting and subsequent anterograde spread of virus particles in axons. We show that SMPD4/nsMase3, a sphingomyelinase abundant in lipid-rafts, associates with Us9 and is a negative regulator of PRV sorting into axons and neuronal spread, a potential antiviral function.

Author Summary

Viral pathogenesis often is age-dependent, with more severe outcomes for infected fetuses and neonates compared to adults. As neurons age and mature, dendrites and axons polarize with distinct functions that affect neurotropic virus replication and neuronal spread of infection. This study investigates how neuronal maturation of peripheral nervous system neurons, the site of alpha-herpesvirus life-long latency and reactivation, affects replication and neuronal spread of pseudorabies virus. Characterization of infected immature and mature primary cultures of superior cervical ganglionic neurons revealed significant differences in protein composition and cellular processes that affected the activity of Us9, a viral protein required for sorting virus particles into axons. We identified neuronal and viral proteins that interact with Us9 in immature and mature neurons. Among these, we demonstrate that SMPD4/nsMase3, a sphingomyelinase critical for membrane organization and neuronal function, regulates PRV neuronal spread by preventing capsid association with Us9-containing membranes, presenting a possible antiviral function.
Chromosomal instability by mutations in a novel specificity factor of the minor spliceosome
Authors: de Wolf Bas , Oghabian Ali , Akinyi Maureen V. , Hanks Sandra , Tromer Eelco C. , van Hooff Jolien , van Voorthuijsen Lisa , van Rooijen Laura E. , Verbeeren Jens , Uijttewaal Esther C.H. , Baltissen Marijke P.A. , Yost Shawn , Piloquet Philippe , Vermeulen Michiel , Snel Berend , Isidor Bertrand , Rahman Nazneen , Frilander Mikko J. , Kops Geert J.P.L.
Published: August 2020

Aneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations inCENATAC(CCDC84). We show that CENATAC is a novel component of the minor (U12-dependent) spliceosome that promotes splicing of a specific, rare minor intron subtype. This subtype is characterized by AT-AN splice sites and relatively high basal levels of intron retention. CENATAC depletion or expression of disease mutants resulted in excessive retention of AT-AN minor introns in ~100 genes enriched for nucleocytoplasmic transport and cell cycle regulators, and caused chromosome segregation errors. Our findings reveal selectivity in minor intron splicing with a specific impact on the chromosome segregation process, and show how defects herein can cause constitutional aneuploidy.
Enhanced inflammatory response mediated by parenchymal cells associates with resistance towards mTOR inhibition
Authors: Jiao Long , Eickhoff Roman , Jumpertz Sandra , Roth Johanna , Erdem Merve , Kroh Andreas , Duimel Hans , López-Iglesias Carmen , Schmeding Maximilian , Heij Lara R. , Meierhofer David , Neumann Ulf P. , Cramer Thorsten
Published: August 2020

Activation of the mTOR pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established aliverepithelialcell (LEC)-specific knock-out (KO) of mTOR (mTORLECmice). We used these mice to characterize the growth of colorectal liver metastases with and without partial hepatectomy to model different clinical settings. While the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLECmice compared to wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-κB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-κB in mTORLECmice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in liver epithelial cells. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage to test if anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitor for cancer therapy.
A genome compendium reveals diverse metabolic adaptations of Antarctic soil microorganisms
Authors: Ortiz Maximiliano , Leung Pok Man , Shelley Guy , Van Goethem Marc W. , Bay Sean K. , Jordaan Karen , Vikram Surendra , Hogg Ian D. , Makhalanyane Thulani P. , Chown Steven L. , Grinter Rhys , Cowan Don A. , Greening Chris
Published: August 2020

A surprising diversity and abundance of microorganisms resides in the cold desert soils of Antarctica. The metabolic processes that sustain them, however, are poorly understood. In this study, we used metagenomic and biogeochemical approaches to study the microbial communities in 16 physicochemically diverse mountainous and glacial soils from remote sites in South Victoria Land, north of the Mackay Glacier. We assembled 451 metagenome-assembled genomes from 18 bacterial and archaeal phyla, constituting the largest resource of Antarctic soil microbial genomes to date. The most abundant and prevalent microorganisms are metabolically versatile aerobes that use atmospheric hydrogen and carbon monoxide to meet energy, carbon, and, through metabolic water production, hydration needs. Phylogenetic analysis and structural modelling infer that bacteria from nine phyla can scavenge atmospheric hydrogen using a previously unreported enzyme family, the group 1l [NiFe]-hydrogenases. Consistently, gas chromatography measurements confirmed most soils rapidly consume atmospheric hydrogen and carbon monoxide, and provide the first experimental evidence of methane oxidation in non-maritime Antarctica. We also recovered genomes of microorganisms capable of oxidizing other inorganic compounds, including nitrogen, sulfur, and iron compounds, as well as harvesting solar energy via photosystems and novel microbial rhodopsins. Bacterial lineages defined by symbiotic lifestyles, including Patescibacteria, Chlamydiae, and predatory Bdellovibrionota, were also surprisingly abundant. We conclude that the dominant microorganisms in Antarctic soils adopt mixotrophic strategies for energy and sometimes carbon acquisition, though they co-exist with diverse bacteria and archaea that adopt more specialist lifestyles. These unprecedented insights and associated genome compendium will inform efforts to protect biodiversity in this continent.
Decoding Multivoxel Representations of Affective Scenes in Retinotopic Visual Cortex
Authors: Bo Ke , Yin Siyang , Liu Yuelu , Hu Zhenhong , Meyyapan Sreenivasan , Kim Sungkean , Keil Andreas , Ding Mingzhou
Published: August 2020

The perception of opportunities and threats in complex scenes represents one of the main functions of the human visual system. In the laboratory, its neurophysiological basis is often studied by having observers view pictures varying in affective content. This body of work has consistently shown that viewing emotionally engaging, compared to neutral, pictures (1) heightens blood flow in limbic structures and frontoparietal cortex, as well as in anterior ventral and dorsal visual cortex, and (2) prompts an increase in the late positive event-related potential (LPP), a scalp-recorded and time-sensitive index of engagement within the network of aforementioned neural structures. The role of retinotopic visual cortex in this process has, however, been contentious, with competing theoretical notions predicting the presence versus absence of emotion-specific signals in retinotopic visual areas. The present study used multimodal neuroimaging and machine learning to address this question by examining the large-scale neural representations of affective pictures. Recording EEG and fMRI simultaneously while observers viewed pleasant, unpleasant, and neutral affective pictures, and applying multivariate pattern analysis to single-trial BOLD activities in retinotopic visual cortex, we identified three robust findings: First, unpleasant-versus-neutral decoding accuracy, as well as pleasant-versus-neutral decoding accuracy, were well above chance level in all retinotopic visual areas, including primary visual cortex. Second, the decoding accuracy in ventral visual cortex, but not in early visual cortex or dorsal visual cortex, was significantly correlated with LPP amplitude. Third, effective connectivity from amygdala to ventral visual cortex predicted unpleasant-versus-neutral decoding accuracy, and effective connectivity from ventral frontal cortex to ventral visual cortex predicted pleasant-versus-neutral decoding accuracy. These results suggest that affective pictures evoked valence-specific multivoxel neural representations in retinotopic visual cortex and that these multivoxel representations were influenced by reentry signals from limbic and frontal brain regions.
PARIETAL CONTRIBUTIONS TO ABSTRACT NUMEROSITY MEASURED WITH STEADY STATE VISUAL EVOKED POTENTIALS
Authors: Kohler Peter J. , Barzegaran Elham , Norcia Anthony M. , McCandliss Bruce D.
Published: August 2020

Non-symbolic number changes produce transient Event Related Potentials over parietal electrodes, while numerosity effects measured with Steady-State Visual Evoked Potentials (SSVEPs) appear to originate in occipital cortex. We hypothesized that the stimulation rates used in previous SSVEP studies may be too rapid to drive parietal numerosity mechanisms. Here we recorded SSVEPs and behavioral reports over a slower range of temporal frequencies than previously used. Isoluminant dot stimuli updated at a consistent “carrier” frequency (3-6 Hz) while periodic changes in numerosity (e.g. 8→5) formed an even slower “oddball” frequency (0.5-1 Hz). Each numerosity oddball condition had a matched control condition where the number of dots did not change. Carrier frequencies induced SSVEPs with midline occipital topographies that did not differentiate the presence or absence of numerosity oddballs. By contrast, SSVEPs at oddball frequencies had parietal topographies and responded more strongly when oddballs were present. Consistent with our hypothesis, numerosity effects were stronger at slower stimulation rates. In a second study, the numerosity change was either supra-threshold (e.g. 8→5 dots) or near the threshold required for detecting numerosity changes (e.g. 8→9 dots). We found robust parietal responses for the supra-threshold case only, indicating anumerical distance effect. A third study replicated the parietal oddball SSVEP effect across four distinct suprathreshold numerosity-change conditions and showed that number change direction does not influence the effect. These findings show that SSVEP oddball paradigms can probe parietal computations of abstract numerosity, and may provide a rapid, portable approach to quantifying number sense within educational settings.
Newly discovered cichlid fish biodiversity threatened by hybridization with non-native species
Authors: Blackwell Tabitha , Ford Antonia G.P. , Ciezarek Adam G. , Bradbeer Stephanie J. , Juarez Carlos A. Gracida , Ngatunga Benjamin P. , Shechonge Asilatu H. , Tamatamah Rashid , Etherington Graham , Haerty Wilfried , Di Palma Federica , Turner George F. , Genner Martin J.
Published: August 2020

Invasive freshwater fish systems are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show thatO. korogwefrom southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically-disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence ofO. korogwexniloticushybrids in three lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southernO. korogwepopulations most plausibly diverged approximately 140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly-discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.
Radiolabelled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesiclesin vivo
Authors: Siddiqui Nabil A. , Houson Hailey A. , Thomas Shindu C. , Blanco Jose R. , O’Donnell Robert E. , Hassett Daniel J. , Lapi Suzanne E. , Kotagiri Nalinikanth
Published: August 2020

Modern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial productsin vivo. We show that these novel contrast agents are able to identifyE. coliwith strain level specificity and other bacteria, such asK. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms.
Eocene origin, Miocene diversification and intercontinental dispersal of the genusDrosera(Droseraceae)
Authors: Sen Sandeep , Tiwari Neha , Ganesan R
Published: August 2020

Resolving the evolutionary history of plant carnivory is of great interest to biologists throughout the world. Among the carnivorous plants, GenusDrosera(Droseraceae) is highly diverse with a wide pantropical distribution. Despite being a group of interest for evolutionary biology studies since the time of Charles Darwin, the historical biogeography of this group remains poorly understood. In this study, with an improved species sampling from Genbank, we present a reanalyzed phylogenetic hypothesis of the genusDrosera. We developed a dated molecular phylogeny ofDroserafrom DNA sequences of nuclear ITS and chloroplast rbcL genes. Divergence times were estimated on the combined dataset using an uncorrelated lognormal relaxed clock model and a known fossil calibration implemented in BEAST. The maximum clade credibility tree was then used for ancestral range estimations using DEC+J model implemented in BioGeoBEARS. Our analysis suggests thatDroseraevolved during the Mid Eocene 36 Ma [95% HPD: 49.5-26] and have diversified and dispersed from the late Miocene onwards. Ancestral areas estimated using the DEC+J models suggest an African origin followed major radiation within Australia. Diversification inDroserais temporally congruent with the prevailing drier conditions during the Miocene. From Miocene, grasslands and open habitats dominated across continents and might have provided ecological opportunities for their dispersal and diversification. Several long-distance dispersals and range extensions and in situ radiations coinciding with the evolution of drier conditions can explain their extant distribution across continents. Overall our data set provides fresh insights into the biogeographic factors that shaped the origin and evolution of the genusDrosera.
CorRelator: An interactive and flexible toolkit for high-precision cryo-correlative light and electron microscopy
Authors: Yang Jie E. , Larson Matthew R. , Sibert Bryan S. , Shrum Samantha , Wright Elizabeth R.
Published: August 2020

Cryo-correlative light and electron microscopy (CLEM) is a technique that uses the spatiotemporal cues from fluorescence light microscopy (FLM) to investigate the high-resolution ultrastructure of biological samples by cryo-electron microscopy (cryo-EM). Cryo-CLEM provides advantages for identifying and distinguishing fluorescently labeled proteins, macromolecular complexes, and organelles from the cellular environment. Challenges remain on how correlation workflows and software tools are implemented on different microscope platforms to support microscopy-driven structural studies. Here, we present an open-source desktop application tool, CorRelator, to bridge between cryo-FLM and cryo-EM/ET data collection instruments. CorRelator was designed to be flexible for both on-the-fly and post-acquisition correlation schemes. The CorRelator workflow is easily adapted to any fluorescence and transmission electron microscope (TEM) system configuration. CorRelator was benchmarked under cryogenic and ambient temperature conditions using several FLM and TEM instruments, demonstrating that CorRelator is a rapid and efficient application for image and position registration in CLEM studies. CorRelator is a cross-platform software featuring an intuitive Graphical User Interface (GUI) that guides the user through the correlation process. CorRelator source code is available at:https://github.com/wright-cemrc-projects/corr.
Dissociation of Medial Frontal β-Bursts and Executive Control
Authors: Errington Steven P. , Woodman Geoffrey F. , Schall Jeffrey D.
Published: August 2020

The neural mechanisms of executive and motor control concern both basic researchers and clinicians. In human studies, preparation and cancellation of movements are accompanied by changes in the β-frequency band (15–29 Hz) of EEG. Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient β-bursts over sensorimotor cortical areas before movement initiation and increased β-bursting over medial frontal areas with movement cancellation. This modulation has been interpreted as contributing to the trial-by-trial control of behavior. We performed identical analyses of EEG recorded over the frontal lobe of macaque monkeys performing a saccade countermanding task. Whilst, we replicate the occurrence and modulation of β-bursts associated with initiation and cancellation of saccades, we found that β-bursts occur too infrequently to account for the observed stopping behavior. We also found β-bursts were more common after errors, but their incidence was unrelated to response time adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of β-band functional significance.

SIGNIFICANCE STATEMENT

The finding of increased β-bursting over medial frontal cortex with movement cancellation in humans is difficult to reconcile with the finding of modulation too late to contribute to movement cancellation in medial frontal cortex of macaque monkeys. To obtain comparable measurement scales, we recorded EEG over medial frontal cortex of macaques performing a stop signal (countermanding) task. We replicated the occurrence and modulation of β-bursts associated with the cancellation of movements, but we found that β-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether β-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.
A unified view of neighbour cell engagement during apoptotic cell extrusion
Authors: Duszyc Kinga , Gomez Guillermo A. , Lagendijk Anne K. , Yau Mei-Kwan , Gliddon Briony L. , Hall Thomas E. , Verma Suzie , Hogan Benjamin M. , Pitson Stuart M. , Fairlie David P. , Parton Robert G. , Yap Alpha S.
Published: August 2020

Epithelia must eliminate apoptotic cells to preserve tissue barriers and prevent inflammation [1]. Several different mechanisms exist for apoptotic clearance, including efferocytosis [2, 3] and apical extrusion [4, 5]. We found that extrusion was the first-line response to apoptosis in cultured monolayers and in zebrafish epidermis. During extrusion, the apoptotic cell elicited active lamellipodial protrusions and assembly of a contractile extrusion ring in its neighbours. Depleting E-cadherin compromised both the contractile ring and extrusion, implying that a cadherin-dependent pathway allows apoptotic cells to engage their neighbours for extrusion. We identify RhoA as the cadherin-dependent signal in the neighbour cells and show that it is activated in response to contractile tension from the apoptotic cell. This mechanical stimulus is conveyed by a Myosin VI-dependent mechanotransduction pathway that is necessary both for extrusion and to preserve the epithelial barrier when apoptosis was stimulated. Earlier studies suggested that release of sphingosine-1-phosphate (S1P) from apoptotic cells might define where RhoA was activated. However, we found that although S1P is necessary for extrusion, its contribution does not require a localized source of S1P in the epithelium. We therefore propose a unified view of how RhoA is stimulated to engage neighbour cells for apoptotic extrusion. Here, tension-sensitive mechanotransduction is the proximate mechanism that activates RhoA specifically in the immediate neighbours of apoptotic cells, but this also must be primed by S1P in the tissue environment. Together, these elements provide a coincidence detection system that confers robustness on the extrusion response.
High feature overlap reveals the importance of anterior and medial temporal lobe structures for learning by means of fast mapping
Authors: Zaiser Ann-Kathrin , Bader Regine , Meyer Patric
Published: August 2020

Contrary to traditional theories of declarative memory, it has recently been shown that novel, arbitrary associations can be rapidly and directly integrated into cortical memory networks by means of a learning procedure called fast mapping (FM), possibly bypassing time-consuming hippocampal-neocortical consolidation processes. In the typical FM paradigm, a picture of a previously unknown item is presented next to a picture of a previously known item and participants answer a question referring to an unfamiliar label. It is assumed that they thereby incidentally create associations between the unknown item and the label. However, contradictory findings have been reported and factors moderating rapid cortical integration through FM yet need to be identified. In the context of previous behavioral results showing rapid semantic integration through FM especially if the unknown and the known item shared many features, we propose that due to its computational mechanisms during the processing of complex and particularly highly similar objects, the perirhinal cortex might be especially qualified to support the rapid incorporation of these associations into cortical memory networks within the FM paradigm. We therefore expected that a high degree of feature overlap between the unknown and the known item would trigger strong engagement of the perirhinal cortex at encoding, which in turn might enhance rapid cortical integration of the novel picture-label associations. Within an fMRI experiment, we observed stronger activation for subsequent hits than misses during encoding in the perirhinal cortex and an associated anterior temporal network if the items shared many features than if they shared few features, indicating that the perirhinal cortex indeed contributes to the acquisition of novel associations by means of FM if feature overlap is high.
Sex, fitness decline and recombination – Muller’s ratchet vs. Ohta’s ratchet
Authors: Ruan Yongsen , Wang Haiyu , Zhang Lingjie , Wen Haijun , Wu Chung-I
Published: August 2020

It is generally accepted that the absence of recombination reduces the efficacy of natural selection for, or against, mutations. A special case is Muller’s Ratchet (MR) whereby non-recombining genomes experience irreversible fitness decline due to the accumulation of deleterious mutations. MR has been a main hypothesis for sexual reproduction as well as many other biological phenomena. We now ask whether the fitness decline can indeed be stopped if an asexual population turns sexual to become recombining. The possible fitness decline under recombination is referred to as Ohta’s Ratchet (OR). In comparison, MR is more effective in driving fitness reduction than OR, but only in a restricted parameter space of mutation rate, population size and selection. Outside of this space, the two ratchets are equally effective or, alternatively, neither is sufficiently powerful. Furthermore, beneficial mutations can affect the population fitness, which may diverge between the two ratchets, but only in a small parameter space. Since recombination plays a limited role in driving fitness decline, the operation of MR could be far less common in nature than believed. A companion report (see Supplement) surveying the biological phenomena attributed to MR indeed suggests the alternative explanations to be generally more compelling.
HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform
Authors: Bhaskaran K , Rentsch CT , MacKenna B , Schultz A , Mehrkar A , Bates C , Eggo RM , Morton CE , Bacon S , Inglesby P , Douglas IJ , Walker AJ , McDonald HI , Cockburn J , Williamson EJ , Evans D , Forbes HJ , Curtis HJ , Hulme W , Parry J , Hester F , Harper S , Evans SJW , Smeeth L , Goldacre B
Published: August 2020

Background

It is unclear whether HIV infection is associated with risk of COVID-19 death. We aimed to investigate this in a large-scale population-based study in England.

Methods

Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. People with a primary care record for HIV infection were compared to people without HIV. COVID-19 death was defined by ICD-10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death, initially adjusted for age and sex, then adding adjustment for index of multiple deprivation and ethnicity, and finally for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities and calendar time.

Results

17.3 million adults were included, of whom 27,480 (0.16%) had HIV recorded. People living with HIV were more likely to be male, of black ethnicity, and from a more deprived geographical area than the general population. There were 14,882 COVID-19 deaths during the study period, with 25 among people with HIV. People living with HIV had nearly three-fold higher risk of COVID-19 death than those without HIV after adjusting for age and sex (HR=2.90, 95% CI 1.96-4.30). The association was attenuated but risk remained substantially raised, after adjustment for deprivation and ethnicity (adjusted HR=2.52, 1.70-3.73) and further adjustment for comorbidities (HR=2.30, 1.55-3.41). There was some evidence that the association was larger among people of black ethnicity (HR = 3.80, 2.15-6.74, compared to 1.64, 0.92-2.90 in non-black individuals, p-interaction=0.045)

Interpretation

HIV infection was associated with a markedly raised risk of COVID-19 death in a country with high levels of antiretroviral therapy coverage and viral suppression; the association was larger in people of black ethnicity.
Detecting coronavirus contact using internet of things
Authors: M. Thangamani , M. Ganthimathi , S.R. Sridhar , M. Akila , R. Keerthana , P.S. Ramesh
Published: August 2020

Purpose

The purpose of this paper is to identify coronavirus contact using internet of things. The disease is said to be highly contagious with the contact of infected persons. Feared to be air-borne, droplets of body fluids can transmit the disease in a matter of hours. The predominant symptoms of the COVID-19 are high fever, cough, breathing problem, etc. Recent studies have demonstrated the evolution of the disease to hide its symptoms. As it is highly transmissible, this disease might spread at an exponential rate costing the lives of thousands of people. The chain of transmission has to be detected with utmost priority through early detection and isolation of infected people. Automated internet of things (IoT) devices can be used in design and implementation of a prediction scheme for reporting the health-care risks of the patients with various parameters such as temperature, humidity and blood pressure.

Design/methodology/approach

IoT is a configuration of multiple autonomous and embedded wireless devices for serving a purpose. Every object possesses an individual identity and will serve to register critical events as entries for future learning and decisions. IoT plays an inevitable role in medical industries, detection of vital signs of diseases and monitoring. Among other life-threatening diseases, a new pandemic is on rise among world nations. COVID-19, a novel severe acute respiratory syndrome virus originated from animals in December 2019 and is becoming a serious menace to Governments, despite serious measures of lockdowns.

Findings

In this paper, the authors defined an architecture of an IoT system to predict the Covid-19 disease by getting the data from the human through sensors and send the data to the doctor using mobile, computer, etc. The main goal is early health surveillance by predicting COVID-19. Accordingly, the authors are able to identify both symptomatic and asymptomatic patients, which will help in the early prediction of disease.

Originality/value

Using the proposed method, the authors can save the time of both patient and doctor by ensuring timely medical treatment and contribute toward breaking the transmission chain. In so doing, the method also contributes toward avoiding unnecessary expenses and saving human lives.