bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinship ties across the lifespan in human communities
Authors: Koster Jeremy , Lukas Dieter , Nolin David , Power Eleanor , Alvergne Alexandra , Mace Ruth , Ross Cody T. , Kramer Karen , Greaves Russell , Caudell Mark , MacFarlan Shane , Schniter Eric , Quinlan Robert , Mattison Siobhan , Reynolds Adam , Yi-Sum Chun , Massengill Eric
Published: July 2019

A hypothesis for the evolution of long post-reproductive lifespans in the human lineage involves asymmetries in relatedness between young immigrant females and the older females in their new groups. In these circumstances, inter-generational reproductive conflicts between younger and older females are predicted to resolve in favour of the younger females, who realize fewer inclusive fitness benefits from ceding reproduction to others. This conceptual model anticipates that immigrants to a community initially have few kin ties to others in the group, gradually showing greater relatedness to group members as they have descendants who remain with them in the group. We examine this prediction in a cross-cultural sample of communities, which vary in their sex-biased dispersal patterns and other aspects of social organization. Drawing on genealogical and demographic data, the analysis provides general but not comprehensive support for the prediction that average relatedness of immigrants to other group members increases as they age. In rare cases, natal members of the community also exhibit age-related increases in relatedness. We also find large variation in the proportion of female group members who are immigrants, beyond simple traditional considerations of patrilocality or matrilocality, which raises questions about the circumstances under which this hypothesis of female competition are met. We consider possible explanations for these heterogenous results, and we address methodological considerations that merit increased attention for research on kinship and reproductive conflict in human societies.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
One piece of the matrilineal puzzle: the socioecology of maternal uncle investment
Authors: Starkweather Kathrine , Keith Monica
Published: July 2019

Maternal uncle relationships in which men invest resources (usually in the form of inheritance of material wealth) into their sisters' children are characteristic of matrilineal systems and hypothesized to arise under certain socioecological circumstances, but little research has systematically investigated conditions that are associated with this type of investment. We quantify relationships between household-level socioeconomic variables and different types of maternal uncle investment (direct care and indirect resource investment) within a bilateral, semi-nomadic population. Shodagor people of Bangladesh allow us to consider matrilineal behaviours in an evolutionary framework owing to their flexible social structure in which 39% of families receive some investment from a maternal uncle. Variables associated with direct maternal uncle care reflect the significance of maintaining consistent residence throughout the year and an increased need for childcare in families residing on boats versus those living on the land. Informative predictors of indirect investment indicate that a mother's birth history corresponds with more tangible contributions such as food and clothing. These results identify household-level variables specific to direct versus indirect maternal uncle investment, whereas having more older brothers or being firstborn increased the odds of a mother receiving any investment from brothers at all. Exploring these social and ecological associations in a bilateral, relatively flexible population unveils household circumstances that may lead to the development of female-biased kinship.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals'.
How can non-human primates inform evolutionary perspectives on female-biased kinship in humans?
Authors: Emery Thompson Melissa
Published: July 2019

The rarity of female-biased kinship organization in human societies raises questions about ancestral hominin family structures. Such questions require grounding in the form and function of kin relationships in our close phylogenetic relatives, the non-human primates. Common features of primate societies, such as low paternity certainty and lack of material wealth, are consistent with features that promote matriliny in humans. In this review, I examine the role of kinship in three primate study systems (socially monogamous species, female-bonded cercopithecines and great apes) that, each for different reasons, offer insights into the evolutionary roots of matriliny. Using these and other examples, I address potential analogues to features of female-biased kinship organization, including residence, descent and inheritance. Social relationships are biased towards matrilineal kin across primates, even where female dispersal limits access to them. In contrast to the strongly intergenerational nature of human kinship, most primate kin relationships function laterally as the basis for cooperative networks and require active reinforcement. There is little evidence that matrilineal kin relationships in primates are functionally equivalent to descent or true inheritance, but further research is needed to understand whether human cultural constructs of kinship produce fundamentally different biological outcomes from their antecedents in primates.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals'.
When does matriliny fail? The frequencies and causes of transitions to and from matriliny estimated from a de novo coding of a cross-cultural sample
Authors: Shenk Mary K. , Begley Ryan O. , Nolin David A. , Swiatek Andrew
Published: July 2019

The question of when and why societies have transitioned away from matriliny to other types of kinship systems—and when and why they transition towards matriliny—has a long history in anthropology, one that is heavily engaged with both evolutionary theory and cross-cultural research methods. This article presents tabulations from a new coding of ethnographic documents from the Standard Cross-Cultural Sample (SCCS), tallying claims of transitions in kinship systems both away from and to matriliny using various levels of stringency. We then use our counts as the outcome variables in a set of Bayesian analyses that simultaneously estimate the probability of a transition occurring given societal covariates alongside the conditional probability of detecting a transition given the volume of ethnographic data available to code. Our goal is to estimate the cross-cultural and comparative frequency of transitions away from and to matriliny, as well as to explore potential causes underlying these patterns. We find that transitions away from matriliny have been significantly more common than ‘reverse transitions' to matriliny. Our evidence suggests that both rates may be, in part, an artefact of the colonial and globalizing period during which the data comprising much of the current ethnographic record were recorded. Analyses of the correlates of transitions away from matriliny are consistent with several of the key causal arguments made by anthropologists over the past century, especially with respect to subsistence transition (to pastoralism, intensive agriculture and market economies), social complexity and colonialism, highlighting the importance of ecological factors in such transitions.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
Confounding adjustment performance of ordinal analysis methods in stroke studies
Authors: Zonneveld T.P. , Aigner A. , Groenwold R.H.H. , Algra A. , Nederkoorn P.J. , Grittner U. , Kruyt N.D. , Siegerink B.
Published: July 2019

Background

In acute stroke studies, ordinal logistic regression (OLR) is often used to analyze outcome on the modified Rankin Scale (mRS), whereas the non-parametric Mann-Whitney measure of superiority (MWS) has also been suggested. It is unclear how these perform comparatively when confounding adjustment is warranted. Our aim is to quantify the performance of OLR and MWS in different confounding variable settings.

Methods

We set up a simulation study with three different scenarios; (1) dichotomous confounding variables, (2) continuous confounding variables, and (3) confounding variable settings mimicking a study on functional outcome after stroke. We compared adjusted ordinal logistic regression (aOLR) and stratified Mann-Whitney measure of superiority (sMWS), and also used propensity scores to stratify the MWS (psMWS). For comparability, OLR estimates were transformed to a MWS. We report bias, the percentage of runs that produced a point estimate deviating by more than 0.05 points (point estimate variation), and the coverage probability.

Results

In scenario 1, there was no bias in both sMWS and aOLR, with similar point estimate variation and coverage probabilities. In scenario 2, sMWS resulted in more bias (0.04 versus 0.00), and higher point estimate variation (41.6% versus 3.3%), whereas coverage probabilities were similar. In scenario 3, there was no bias in both methods, point estimate variation was higher in the sMWS (6.7%) versus aOLR (1.1%), and coverage probabilities were 0.98 (sMWS) versus 0.95 (aOLR). With psMWS, bias remained 0.00, with less point estimate variation (1.5%) and a coverage probability of 0.95.

Conclusions

The bias of both adjustment methods was similar in our stroke simulation scenario, and the higher point estimate variation in the MWS improved with propensity score based stratification. The stratified MWS is a valid alternative for adjusted OLR only when the ratio of number of strata versus number of observations is relatively low, but propensity score based stratification extends the application range of the MWS.
Educational differentials in domain specific physical activity by ethnicity, age, and gender: findings from over 44,000 participants in The UK Household Longitudinal Study (2013-2015)
Authors: Fluharty Meg E , Pinto Perira Snehal M , Benzeval Michaela , Hamer Mark , Jefferis Barbara , Griffiths Lucy , Cooper Rachel , Bann David
Published: July 2019

Background

The prevalence of overall physical inactivity remains high, particularly amongst socioeconomically disadvantaged groups. It is unclear however if such inequalities vary systematically by age, sex, or ethnicity, and if there are differing effects across physical activity (PA) domains.

Methods

We used data from a nationally representative survey of the UK, Understanding Society, with information on educational attainment (our indicator of socioeconomic position), PA and demographics collected in 2013-2015 (N= 44,903). Logistic regression analyses were conducted to test associations of education with three different PA domains (active travel, occupational and leisure time). To examine modification of the associations between education and physical activity in each domain by sex, age and ethnicity, we tested two-way interaction terms (education x ethnicity; education x sex; education x age).

Results

Lower educational attainment was associated with higher active transportation and occupational physical activity, but lower weekly leisure-time activity. These associations were modified by sex, ethnicity, and age. For example, education-related differences in active travel were larger for females (difference in predicted probability of activity between highest and lowest educational groups: −10% in females, (95% CI: −11.9, 7.9) −3% in males (−4.8, −0.4). The education-related differences in occupational activity were larger among males −35% (−36.9, −32.4) than females −17% (−19.4, −15.0). Finally, education related differences in moderate to vigorous leisure time activity varied most substantially by ethnicity; for example, differences were 17% (16.2, 18.7) for White individuals compared with 6% (0.6, 11.6) for Black individuals.

Conclusions

Educational differences in PA vary by domain, and are modified by age, sex, and ethnicity. A better understanding of physically inactive sub-groups may aid development of tailored interventions to increase activity levels and reduce health inequalities.
Reliability and validity of the UK Biobank cognitive tests
Authors: Fawns-Ritchie Chloe , Deary Ian J
Published: July 2019

UK Biobank is a health resource with data from over 500,000 adults. The participants have been assessed on cognitive function since baseline. The cognitive tests in UK Biobank are brief and bespoke, and are administered without supervision on a touchscreen computer. Psychometric information on the tests is limited. The present study examined their concurrent validity and short-term test-retest reliability. A sample of 160 participants (mean age=62.59, SD=10.24) completed the UK Biobank cognitive assessment and a range of well-validated cognitive tests (‘reference tests’). Fifty-two participants returned 4 weeks later to repeat the UK Biobank tests. Correlations were calculated between UK Biobank tests and the reference tests. Four-week test-retest correlations were calculated for UK Biobank tests. UK Biobank cognitive tests showed a range of correlations with their respective reference tests, i.e. those tests that are thought to assess the same underlying cognitive ability (mean Pearson r=0.53, range=0.22 to 0.83, p≤.005). Four-week test-retest reliability of the UK Biobank tests were moderate-to-high (mean Pearson r=0.55, range=0.40 to 0.89, p≤.003). Despite the brief, non-standard nature of the UK Biobank cognitive tests, some showed substantial concurrent validity and test-retest reliability. These psychometric results provide currently-lacking information on the validity of the UK Biobank cognitive tests.
An Assessment of Transparency and Reproducibility-related Research Practices in Otolaryngology
Authors: Johnson Austin L. , Torgerson Trevor , Skinner Mason , Hamilton Tom , Tritz Daniel , Vassar Matt
Published: July 2019

Introduction

Clinical research serves as the foundation for evidence-based patient care, and reproducibility of results is consequently critical. We sought to assess the transparency and reproducibility of research studies in otolaryngology by evaluating a random sample of publications in otolaryngology journals between 2014 and 2018.

Methods

We used the National Library of Medicine catalog to identify otolaryngology journals that met the inclusion criteria (available in the English language and indexed in MEDLINE). From these journals, we extracted a random sample of 300 publications using a PubMed search for records published between January 1, 2014, and December 31, 2018. Specific indicators of reproducible and transparent research practices were evaluated in a blinded, independent, and duplicate manner using a pilot-tested Google form.

Results

Our initial search returned 26,498 records, from which 300 were randomly selected for analysis. Of these 300 records, 286 met inclusion criteria and 14 did not. Among the empirical studies, 2% (95% CI, 0.4%-3.5%) of publications indicated that raw data were available, 0.6% (95% CI, 0.3%-1.6%) reported an analysis script, 5.3% (95% CI, 2.7%-7.8%) were linked to an accessible research protocol, and 3.9% (95% CI, 1.7%-6.1%) were preregistered. None of the publications had a clear statement claiming to replicate, or to be a replication of, another study.

Conclusions

Inadequate reproducibility practices exist in otolaryngology. Nearly all studies in our analysis lacked a data or material availability statement, did not link to an accessible protocol, and were not preregistered. Most studies were not available as open access. Taking steps to improve reproducibility would likely also improve patient care.
Collaborative Cross Mouse Populations as a Resource for the Study of Epilepsy
Authors: Gu Bin , Shorter John R. , Williams Lucy H. , Bell Timothy A. , Hock Pablo , Dalton Katherine A. , Pan Yiyun , Miller Darla R. , Shaw Ginger D. , Cooley Brian C. , Philpot Benjamin D. , de Villena Fernando Pardo-Manuel
Published: July 2019

Epilepsy is a neurological disorder with complex etiologies and genetic architecture. Animal models have a critical role in understanding the pathophysiology of epilepsy. Here we studied epilepsy utilizing a genetic reference population of Collaborative Cross (CC) mice with publicly available whole genome sequences. We measured multiple epilepsy traits in 35 CC strains, and we identified novel animal models that exhibit extreme outcomes in seizure susceptibility, seizure propagation, epileptogenesis, and sudden unexpected death in epilepsy. We performed QTL mapping in an F2 population and identified seven novel and one previously identified loci associated with seizure sensitivity. We combined whole genome sequence and hippocampal gene expression to pinpoint biologically plausible candidate genes and candidate variants associated with seizure sensitivity. These resources provide a powerful toolbox for studying complex features of seizures and for identifying genes associated with particular seizure outcomes, and hence will facilitate the development of new therapeutic targets for epilepsy.
CD4+Thimmunogenicity of theAscaris spp. secreted products
Authors: Ebner Friederike , Morrison Eliot , Bertazzon Miriam , Midha Ankur , Hartmann Susanne , Freund Christian , Álvaro-Benito Miguel
Published: July 2019

Ascaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet highly complex (>250 proteins) antigens ofAscaris spp.as defining the pathogen-host interplay. We applied anin vitroantigen processing system coupled to quantitative proteomics to identify potential CD4+Thcell epitopes inAscaris suum-secreted products. This approach restricts the theoretical list of epitopes, based on affinity prediction, by a factor of ∼1200. More importantly, selection of 2 candidate peptides based on experimental evidence demonstrated the presence of epitope-reactive T cells inAscaris-specific T cell lines generated from healthy human individuals. Thus, this stringent work pipeline identifies a human haplotype-specific T cell epitope of a major human pathogen. The methodology described represents an easily adaptable platform for characterization of highly complex pathogenic antigens and their MHCII-restriction.
Discovering venom-derived drug candidates using differential gene expression
Authors: Romano Joseph D. , Li Hai , Napolitano Tanya , Realubit Ronald , Karan Charles , Holford Mandë , Tatonetti Nicholas P.
Published: July 2019

Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform—named VenomSeq—to systematically identify putative associations between venoms and drugs/diseases via high-throughput transcriptomics and perturbational differential gene expression analysis. In this study, we describe the architecture of VenomSeq and its evaluation using the crude venoms from 25 diverse animal species and 9 purified teretoxin peptides. By integrating comparisons to public repositories of differential expression, associations between regulatory networks and disease, and existing knowledge of venom activity, we provide a number of new therapeutic hypotheses linking venoms to human diseases supported by multiple layers of preliminary evidence.
Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η
Authors: Sassa Akira , Tada Haruto , Takeishi Ayuna , Harada Kaho , Suzuki Megumi , Tsuda Masataka , Sasanuma Hiroyuki , Takeda Shunichi , Sugasawa Kaoru , Yasui Manabu , Honma Masamitsu , Ura Kiyoe
Published: July 2019

DNA polymerases often incorporate non-canonical nucleotide, i.e., ribonucleoside triphosphates into the genomic DNA. Aberrant accumulation of ribonucleotides in the genome causes various cellular abnormalities. Here, we show the possible role of human nucleotide excision repair (NER) and DNA polymerase η (Pol η) in processing of a single ribonucleotide embedded into DNA. We found that the reconstituted NER system can excise the oxidized ribonucleotide on the plasmid DNA. Taken together with the evidence that Pol η accurately bypasses a ribonucleotide, i.e., riboguanosine (rG) or its oxidized derivative (8-oxo-rG) in vitro, we further assessed the mutagenic potential of the embedded ribonucleotide in human cells lacking NER or Pol η. A single rG on the supF reporter gene predominantly induced large deletion mutations. An embedded 8-oxo-rG caused base substitution mutations at the 3’-neighboring base rather than large deletions in wild-type cells. The disruption of XPA, an essential factor for NER, or Pol η leads to the increased mutant frequency of 8-oxo-rG. Furthermore, the frequency of 8-oxo-rG-mediated large deletions was increased by the loss of Pol η, but not XPA. Collectively, our results suggest that base oxidation of the embedded ribonucleotide enables processing of the ribonucleotide via alternative DNA repair and damage tolerance pathways.
EEG spectral power, but not theta/beta ratio, is a neuromarker for adult ADHD
Authors: Kiiski Hanni , Bennett Marc , Rueda-Delgado Laura M. , Farina Francesca , Knight Rachel , Boyle Rory , Roddy Darren , Grogan Katie , Bramham Jessica , Kelly Clare , Whelan Robert
Published: July 2019

Background

Adults with attention-deficit/hyperactivity disorder (ADHD) have been described as having altered resting-state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behavior (mediational endophenotypes).

Methods

Resting-state eyes-open and eyes-closed EEG were measured from 38 adults with ADHD, 45 first-degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1-45 Hz) and TBR could classify participants into ADHD, first-degree relatives and/or control groups. Random-label permutation was used to quantify any bias in the analysis.

Results

Eyes-open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = .71-.77). The best predictors of ADHD status were increased power in delta, theta and low-alpha over centro-parietal regions, and in frontal low-beta and parietal mid-beta. TBR did not classify ADHD status. Elevated eyes-open power in delta, theta, low-alpha and low-beta distinguished first-degree relatives from controls (area under receiver operating characteristic = .68-.72), suggesting that these features may be a mediational endophenotype for adult ADHD.

Conclusions

Resting-state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.
Temporal cascade of frontal, motor and muscle processes underlying human action-stopping
Authors: Jana Sumitash , Hannah Ricci , Muralidharan Vignesh , Aron Adam R.
Published: July 2019

Action-stopping is a canonical executive function thought to involve top-down control over the motor system. Here we aimed to validate this stopping system using high temporal resolution methods in humans. We show that, following the requirement to stop, there was an increase of right frontal beta (∼13 to 30 Hz) at ∼120 ms, likely a proxy of right inferior frontal gyrus; then, at 140 ms, there was a broad skeletomotor suppression, likely reflecting the impact of the subthalamic nucleus on basal ganglia output; then, at ∼160 ms, suppression was detected in the muscle, and, finally, the behavioral time of stopping was ∼220 ms. This temporal cascade confirms a detailed model of action-stopping, and partitions it into subprocesses that are isolable to different nodes and are more precise than the behavioral speed of stopping. Variation in these subprocesses, including at the single-trial level, could better explain individual differences in impulse control.
Ralstonia solanacearumdepends on catabolism of myo-inositol, sucrose, and trehalose for virulence in an infection stage-dependent manner
Authors: Hamilton Corri D. , Steidl Olivia , MacIntyre April M. , Allen Caitilyn
Published: July 2019

The soilborne pathogenRalstonia solanacearum (Rs)causes lethal bacterial wilt disease of tomato and many other crops by infecting host roots and then colonizing the xylem vessels. Tomato xylem sap is nutritionally limiting but it does contain sucrose and trehalose. Transcriptomic analyses revealed thatRsexpresses distinct sets of catabolic pathways at low cell density (LCD) and high cell density (HCD). To investigate the links between bacterial catabolism, infection stage, and virulence, we measured thein plantafitness of bacterial mutants lacking carbon catabolic pathways expressed at either LCD or HCD. We hypothesized that the bacterium needs LCD carbon sources early in disease (root infection) while HCD carbon sources are required during late disease (stem colonization). AnRs ΔiolGmutant unable to use the LCD nutrient myo-inositol was defective in root colonization but once it reached the stem, this strain colonized and caused symptoms as well as wild type. In contrast,Rsmutants unable to use sucrose (ΔscrA), trehalose (ΔtreA), or both(ΔscrA/treA), infected roots as well as wild type but were defective in colonization and competitive fitness in tomato mid-stems and were reduced in bacterial wilt virulence. Additionally, xylem sap from tomato plants colonized byΔscrA, ΔtreA, or ΔscrA/treAcontained more sucrose than sap from plants colonized by wild-typeRs. Together, these findings suggestRsmetabolism is specifically adapted for success in the different nutritional environments of plant roots and xylem sap.
Viral rebound kinetics following single and combination immunotherapy for HIV/SIV
Authors: Prague Mélanie , Gerold Jeffrey M , Balelli Irene , Pasin Chloé , Li Jonathan Z , Barouch Dan H , Whitney James B , Hill Alison L
Published: July 2019

HIV infection can be treated but not cured with antiretroviral therapy, motivating the development of new therapies that instead target host immune responses. Three such immunotherapies were recently tested in non-human primates – a TLR7-agonist, therapeutic vaccine, and broadly-neutralizing antibody – and cured a subset of animals by preventing or controlling viral rebound after antiretrovirals were stopped. However, their mechanism of action remains unknown; for example, whether they reduced the pool of latently-infected cells versus boosted antiviral immunity, and whether they acted independently or synergistically. Here we conduct a detailed analysis of the kinetics of viral rebound after immunotherapy, and use mathematical models combined with rigorous statistical fitting to quantify the impact of these interventions on viral dynamics. We find that the vaccine reduced reactivation of latent virus by 4-fold, and boosted the avidity of antiviral immune responses by 17-fold when alone and 210-fold when combined with the TLR7-agonist. In the context of later initiation of antiretroviral therapy only, the TLR7-agonist reduced latent reservoir reactivation by 8-fold, but also slightly increased target cell availability (1.5-fold). The antibody boosted immune response avidity (8-fold) and displayed no detectable synergy with the TLR7-agonist. To predict the impact of these immunotherapies in clinical trials, we calibrated a model of HIV rebound to human treatment interruption trials and simulated the effect of adding each therapy. Overall, our results provide a framework for understanding the relative contributions of different mechanisms of preventing viral rebound and highlight the multifaceted roles of TLR7-agonists for HIV/SIV cure.
Host defense responses of CO441 and CL30 maize lines toFusarium graminearumanalyzed by comparative label-free quantitative proteomics
Authors: Reid Lana M. , Altosaar Illimar
Published: July 2019

Gibberella ear rot is a disease of maize associated with low yields and the production of harmful mycotoxins therein. The disease is caused by the infection of hostZea mayswith fungal pathogenFusarium graminearum. Resistant (CO441) and susceptible (CL30) inbred maize line kernels were inoculated with conidial suspensions ofF. graminearumor water (controls). Ears of maize (cobs) from each line were harvested upon maturation and proteins were extracted from the embryo tissue of the kernels to study tissue-specific response of the host. Embryo proteins from both CO441 and CL30 lines were sequenced using mass spectrometry (LC-MS/MS) and quantified using Label Free Quantification (LFQ). Following filtering, 509 proteins were identified. These proteins were grouped into nine functional categories:Fusarium-derived, late embryogenesis abundant, oil-body, metabolism, stress, cellular, protein storage, metabolism, and defense. Defense proteins were up-regulated in response to infection in both CO441 and CL30 lines. Furthermore,F. graminearumderived proteins were only found in CL30 infected kernels suggesting that resistance may be attributed in part to the inability ofFusariumto establish itself in the embryo. To our knowledge this is the first successful application of LFQ mass spectrometry to the study of host-pathogen response toF. graminearum.

Biological significance

Fungal pathogenFusarium graminearumis responsible for billion dollar losses in crops and contamination of global grains with harmful mycotoxins. By studying host-pathogen interactions ofFusariumand maize on a proteomic level with resistant and susceptible genotypes, the biological interactions occurring during infection of the maturing seed were characterized. Mature kernels of theF. graminearumsusceptible maize line CL30 and resistant CO441 line were dissected to permit a proteomic survey of the new sporophytic generation, the embryo. Detailed knowledge of this Host-pathogen interactome will assist development of new cereal lines resistant to the rot diseases caused byFusarium graminearum.

Highlights

Susceptible (CL30) and Resistant (CO441) lines were injected with water mock or F. graminearum LC-MS/MS of maize embryo protein extracts followed by Label Free Quantification (LFQ) permitted identification, quantification and comparison of proteomes between maize genotypes and treatments Fusarium-derived proteins were abundant only in the susceptible infected embryo Defense proteomes were up-regulated in both lines following infection nsLTP and Protease Inhibitor were significantly over-expressed in the Susceptible line after infection; chitinase and WIP1 were significantly over-expressed in the Resistant line after infection
Sugar-phosphate metabolism regulates stationary phase entry and stalk elongation inCaulobacter crescentus
Authors: de Young Kevin D. , Stankeviciute Gabriele , Klein Eric A.
Published: July 2019

Bacteria have a variety of mechanisms for adapting to environmental perturbations. Changes in oxygen availability result in a switch between aerobic and anaerobic respiration, whereas iron limitation may lead to siderophore secretion. In addition to metabolic adaptations, many organisms respond by altering their cell shape.Caulobacter crescentus, when grown under phosphate limiting conditions, dramatically elongates its polar stalk appendage. The stalk is hypothesized to facilitate phosphate uptake; however, the mechanistic details of stalk synthesis are not well characterized. We used a chemical mutagenesis approach to isolate and characterize stalk-deficient mutants, one of which had two mutations in the phosphomannose isomerase gene (manA) that were necessary and sufficient to inhibit stalk elongation. Transcription of thephoregulon was unaffected in themanAmutant; therefore, ManA plays a unique regulatory role in stalk synthesis. The mutant ManA had reduced enzymatic activity resulting in a 5-fold increase in the intracellular fructose 6-phosphate: mannose 6-phosphate ratio. This metabolic imbalance impaired the synthesis of cellular envelope components derived from mannose 6-phosphate, namely lipopolysaccharide O-antigen and exopolysaccharide. Furthermore, themanAmutations preventedC. crescentuscells from efficiently entering stationary phase. Deletion of the stationary-phase response regulatorspdRinhibited stalk elongation in wild-type cells while overproduction of the alarmone ppGpp, which triggers growth arrest and stationary phase entry, increased stalk length in themanAmutant strain. These results demonstrate that sugar-phosphate metabolism regulates stalk elongation independently of phosphate starvation.

Importance

Bacteria have various mechanisms for adapting to environmental perturbations including morphological alterations. During phosphate limitation,Caulobacter crescentusdramatically elongates its polar stalk appendage. The stalk is hypothesized to facilitate phosphate uptake; however, the mechanism of stalk synthesis is not well characterized. We isolated stalk-deficient mutants, one of which had mutations in the phosphomannose isomerase gene (manA) that blocked stalk elongation, despite normal activation of the phosphate-starvation response. The mutant ManA produced an imbalance in sugar-phosphate concentrations that impaired the synthesis of cellular envelope components and prevented entry into stationary phase. Overproduction of the alarmone ppGpp, which promotes stationary phase entry, increased stalk length in themanAmutant demonstrating that sugar-phosphate metabolism regulates stalk elongation independently of phosphate starvation.
Direct Metatranscriptome RNA-seq and Multiplex RT-PCR Amplicon Sequencing on Nanopore MinION – Promising Strategies for Multiplex Identification of Viable Pathogens in Food
Authors: Yang Manyun , Cousineau Alyssa , Liu Xiaobo , Sun Daniel , Li Shaohua , Gu Tingting , Sun Luo , Luo Yaguang , Xu Mingqun , Zhang Boce
Published: July 2019

Viable pathogenic bacteria are major biohazards that pose a significant threat to food safety. Despite the recent developments in detection platforms, multiplex identification of viable pathogens in food remains a major challenge. A novel strategy is developed through direct metatranscriptome RNA-seq and multiplex RT-PCR amplicon sequencing on Nanopore MinION to achieve real-time multiplex identification of viable pathogen in food. Specifically, this study reports an optimized universal Nanopore sample extraction and library preparation protocol applicable to both Gram-positive and Gram-negative pathogenic bacteria, demonstrated using a cocktail culture ofE. coliO157:H7,Salmonella enteritidis, andListeria monocytogenes, which were selected based on their impact on economic loss or prevalence in recent outbreaks. Further evaluation and validation confirmed the accuracy of direct metatranscriptome RNA-seq and multiplex RT-PCR amplicon sequencing using Sanger sequencing and selective media. The study also included a comparison of different bioinformatic pipelines for metatranscriptomic and amplicon genomic analysis. MEGAN without rRNA mapping showed the highest accuracy of multiplex identification using the metatranscriptomic data. EPI2ME also demonstrated high accuracy using multiplex RT-PCR amplicon sequencing. In addition, a systemic comparison was drawn between Nanopore sequencing of the direct metatranscriptome RNA-seq and RT-PCR amplicons. Both methods are comparable in accuracy and time. Nanopore sequencing of RT-PCR amplicon has higher sensitivity, but Nanopore metatranscriptome sequencing excels in read length and dealing with complex microbiome and non-bacterial transcriptome backgrounds. To the best of our knowledge, this is the first report of metatranscriptome sequencing of cocktail microbial RNAs on the emerging Nanopore platform. Direct RNA-seq and RT-PCR amplicons sequencing of metatranscriptome enable the direct identification of nucleotide analogs in RNAs, which is highly informative for determining microbial identities while detecting ecologically relevant processes. The information pertained in this study could be important for future revelatory research, including predicting antibiotic resistance, elucidating host-pathogen interaction, prognosing disease progression, and investigating microbial ecology, etc.
Extent and context dependence of pleiotropy revealed by high-throughput single-cell phenotyping
Authors: Geiler-Samerotte Kerry A , Li Shuang , Lazaris Charalampos , Taylor Austin , Ziv Naomi , Ramjeawan Chelsea , Paaby Annalise B , Siegal Mark L
Published: July 2019

Pleiotropy – when a single mutation affects multiple traits – is a controversial topic with far-reaching implications. Pleiotropy plays a central role in debates about how complex traits evolve and whether biological systems are modular or are organized such that every gene has the potential to affect many traits. Pleiotropy is also critical to initiatives in evolutionary medicine that seek to trap infectious microbes or tumors by selecting for mutations that encourage growth in some conditions at the expense of others. Research in these fields, and others, would benefit from understanding the extent to which pleiotropy reflects inherent relationships among phenotypes that correlate no matter the perturbation (vertical pleiotropy). Alternatively, pleiotropy may result from genetic changes that impose correlations between otherwise independent traits (horizontal pleiotropy). We distinguish these possibilities by using clonal populations of yeast cells to quantify the inherent relationships between single-cell morphological features. Then, we demonstrate how often these relationships underlie vertical pleiotropy and how often these relationships are modified by genetic variants (QTL) acting via horizontal pleiotropy. Our comprehensive screen measures thousands of pairwise trait correlations across hundreds of thousands of yeast cells and reveals ample evidence of both vertical and horizontal pleiotropy. Additionally, we observe that the correlations between traits can change with the environment, genetic background and cell-cycle position. These changing dependencies suggest a nuanced view of pleiotropy: biological systems demonstrate limited pleiotropy in any given context, but across contexts (e.g., across diverse environments and genetic backgrounds) each genetic change has the potential to influence a larger number of traits. Our method suggests that exploiting pleiotropy for applications in evolutionary medicine would benefit from focusing on traits with correlations that are less dependent on context.
Biocontrol of PGPR strain Bacillus amyloliquefaciens Ba168 against Phytophthora nicotianae on tobacco
Authors: Guo Dongsheng , Yuan Chenhong , Luo Yunyan , Chen YaHan , Lu Meihuan , Chen Guochan , Ren Guangwei , Cui Chuanbin , Zhang Jiatao , An Derong
Published: July 2019

Tobacco black shank (TBS) caused by Phytophthora nicotianae is destructive to almost all kinds of tobacco cultivars and is widespread in many tobacco-planted countries. Here, an isolated plant growth-promoting rhizobacteria (PGPR) strain Ba168 is promise in biocontrol of TBS. In vitro assays disclosed a strong P. nicotianae suppression activity and the field utilization potential (FUP) by characterized the crude extract of culture filtrates of Ba168. P. nicotianae’s growth was inhibited by the crude extract at minimum inhibitory concentration (MIC) of 5μl/mL. Extracellular conductivity, pH and the wet, dry weight of P. nicotianae’s mycelia, were significantly different after treated with different concentrations of the crude extract and the deformity and perforation of treated P. nicotianae’s hyphae can be observed in scanning electron microscope (SEM) analysis. Proteome characterizations of the crude extract were used as supplementary proofs that further evaluated FUP of Ba168. We then identified strain Ba168 as B. amyloliquefaciens by its genetic and phenotypic characteristics. Field assays comparatively evaluated TBS control efficacy of these PGPRs and agrochemicals. Pooling analysis of the results showed that the biocontrol efficacy of Ba168 preparation is only lower than Mixture of Propamocarb hydrochloride and Azoxystrobin (MPA) but better than other tested subjects. Although the existence of differences in biocontrol efficacy, PGPR preparations effectively reduced the disease index of tobacco.

Importance

This work demonstrates the promising biocontrol potential of B. amyloliquefaciens Ba168 and highlights the positive roles of PGPR in suppression of this soil-borne disease.
Malassezia interaction with a reconstructed human epidermis: imaging studies
Authors: Pedrosa Ana Filipa , Lisboa Carmen , Branco Joana , Almeida Ana Coelho , Mendes Claudia , Pellevoisin Christian , Leite-Moreira Adelino , Miranda Isabel Marcos , Rodrigues Acácio Gonçalves
Published: July 2019

Background

Biofilm formation represents a major microbial virulence attribute especially at epithelial surfaces such as the skin. Malassezia biofilm formation at the skin surface has not yet been addressed.

Objective

The present study aimed to evaluate Malassezia interaction with a reconstructed human epidermis (RhE) model.

Methods

Malassezia clinical isolates were previously isolated from volunteers with pityriasis versicolor and seborrheic dermatitis. Yeasts of two strains of M. furfur and M. sympodialis were inoculated onto the SkinEthic™ RHE. The tissues were processed for light microscopy, wide-field fluorescence microscopy and scanning-electron microscopy.

Results

Colonization of the RhE surface with aggregates of Malassezia yeasts entrapped in a multilayer sheet with variable amount of extracellular matrix was unveiled by imaging techniques following 24, 48, 72 and 96 hours of incubation. Whenever yeasts were suspended in RPMI medium supplemented with lipids, the biofilm substantially increased with a dense extracellular matrix in which the yeast cells were embedded (not seen in control samples). Slight differences were found in the biofilm architectural structure between the two tested species.

Conclusion

Skin isolates of M. furfur and M. sympodialis were capable of forming biofilm in vitro at the epidermal surface simulating in vivo conditions. Following 24 hours of incubation, without added lipids, rudimental matrix was barely visible, conversely to the reported at plastic surfaces. The amount of biofilm apparently increased progressively from 48 to 96 hours. A structural heterogeneity of biofilm between species was found with higher entrapment by a denser and more gelatinous extracellular matrix in M. furfur biofilm.
Optimized visual stimuli for BCI with hessenberg decomposition based extreme learning machine
Authors: Yayık Apdullah , Kutlu Yakup , Altan Gökhan
Published: July 2019

Background and Objectives

Brain-computer interfaces (BCIs) aim to provide neuroscientific communication platform for human-beings, in particular locked-in patients. In most cases event-related potentials (ERPs), averaged voltage responses to a specific target stimuli over time, have key roles in designing BCIs. With this reason, for the last several decades BCI researchers heavily have focused on signal processing methods to improve quality of ERPs. However, designing visual stimulus with considering their physical properties with regard to rapid and also reliable machine learning algorithms for BCIs remain relatively unexplored. Addressing the issues explained above, in summary the main contributions of this study are as follows: (1) optimizing visual stimulus in terms of size, color and background and, (2) to enhance learning capacity of conventional extreme learning machine (ELM) using advanced linear algebra techniques.

Methods

Two different sized (small and big), three different colored (blue, red and colorful) images with four different backgrounds (white, black and concentric) for each of them were designed and utilized as single object paradigm. Hessenberg decomposition method was proposed for learning process and compared with conventional ELM and multi-layer perceptron in terms of training duration and performance measures.

Results

Performance measures of small colorful images with orange-concentric background were statistically higher than those of others. Visual stimulus with white background led to relatively higher performance measures than those with black background. Blue colored images had much more impact on improvement of P300 waves than red colored ones had. Hessenberg decomposition method provided 1.5 times shortened training duration than conventional ELM, in addition with comparable performance measures.

Conclusions

Herein, a visual stimuli model based on improving quality of ERP responses and machine learning algorithm relies on hessenberg decomposition method are introduced with demonstration of their advantages in the context of BCI. Methods and findings described in this study may pave the way for widespread applications, particularly in clinical health-informatics.
Mechanistic Elucidation of the Antitumor Properties of a Novel Death Receptor 5 Activator
Authors: Wang Mengxiong , Law Mary E. , Davis Bradley J. , Yaaghubi Elham , Ghilardi Amanda F. , Ferreira Renan B. , Chiang Chi-Wu , Guryanova Olga A. , Kopinke Daniel , Heldermon Coy D. , Castellano Ronald K. , Law Brian K.
Published: July 2019

Disulfide bond Disrupting Agents (DDAs) are a new chemical class of agents recently shown to have activity against breast tumors in animal models. However, it is unknown how DDAs trigger cancer cell death without affecting nontransformed cells. As demonstrated here, DDAs are the first compounds identified that upregulate the TRAIL receptor DR5 through both transcriptional and posttranscriptional mechanisms. At the protein level, DDAs alter DR5 disulfide bonding to increase steady-state DR5 levels and oligomerization, leading to downstream Caspase 8 and 3 activation. DDAs and TRAIL synergize to kill cancer cells and are cytotoxic to HER2+ cancer cells with acquired resistance to the EGFR/HER2 tyrosine kinase inhibitor. Investigation of the mechanisms responsible for DDA selectivity for cancer cells reveals that DDA-induced upregulation of DR5 is enhanced in the context of EGFR overexpression, and DDA-induced cytotoxicity is strongly amplified by MYC overexpression. Together, the results demonstrate selective DDA lethality against oncogene-transformed cells, DDA-mediated DR5 upregulation and protein stabilization, and DDAs against drug-resistant and metastatic cancer cells. DDAs thus represent a new therapeutic approach to cancer therapy.
Zymobacter palmaepyruvate decarboxylase is less efficient than that ofZymomonas mobilisfor ethanol production in metabolically engineeredSynechocystissp PCC6803
Authors: Quinn Lorraine , Armshaw Patricia , Soulimane Tewfik , Sheehan Con , Ryan Michael P , Pembroke J Tony
Published: July 2019

Pyruvate decarboxylase (PDC) fromZymobacter palmae(ZpPDC) has been reported to have a lower Km theZymomonas mobilisPDC (ZmPDC). ZpPDC was combined with nativeslr1192alcohol dehydrogenase (adh) in an attempt to increase ethanol production in the photoautotrophic cyanobacteriumSynechocystissp. PCC 6803 over constructs created with Zmpdc. Native (Zppdc) and codon optimised (ZpOpdc) versions of the ZpPDC were cloned into a construct where thepdcexpression was controlled via thepsbA2light inducible promoter fromSynechocystisPCC 6803. These constructs were transformed into wildtypeSynechocystisPCC 6803. Ethanol levels were then compared with identical constructs containing the Zmpdc. While strains with the Zppdc(UL071) and ZpOpdc(UL072) constructs did produce ethanol, levels were lower compared to a control strain (UL004) expressing thepdcfromZymomonas mobilis. The utilisation of a PDC with a lower Km fromZymobacter palmaedid not result in enhanced ethanol production inSynechocystisPCC 6803.