bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexually Transmitted Infection Prevalence in Women With HIV: Is There a Role for Targeted Screening?
Authors: Dionne-Odom Jodie , Westfall Andrew O. , Van Der Pol Barbara , Fry Karen , Marrazzo Jeanne
Published: April 2018

Background

Rates of sexually transmitted infections (STIs) and HIV are highest in the southern United States but vary widely by sex, age, and risk behavior. Current guidelines recommend annual screening for chlamydia, gonorrhea, syphilis, and trichomoniasis in all sexually active women with HIV.

Methods

Screening rates and test positivity for chlamydia, gonorrhea, syphilis, and trichomoniasis were determined per calendar year in this retrospective cohort study of women in care at an urban HIV clinic in Birmingham, Alabama, from 2013 to 2015. Chlamydia, gonorrhea, and trichomonas infections were detected by molecular diagnostics and syphilis by serology. A combined end point for chlamydia/gonorrhea/syphilis (STI-3) was created based on similar test positivity and predictors. Predictors of STI-3 were identified using logistic regression and generalized estimating equations.

Results

Among 745 women with HIV, median age was 46.8 years, 78.8% were black, and 61% were sexually active. In 2015, 83.7% of women were tested for STI. Test positivity was 1.0% for chlamydia, 0.5% for gonorrhea, 1.6% for syphilis, and 13.3% for trichomoniasis. Independent predictors of STI-3 were recent chlamydia or gonorrhea (odds ratio [OR], 3.7; 95% confidence interval [CI], 1–13.4; P = 0.047), public insurance compared with private (OR, 3.5; CI, 1–11.8; P = 0.048), and sex after drugs/alcohol (OR, 3.0; CI, 1.2–8.0; P = 0.025). Women 50 years or older were less likely to have STI (OR, 0.3; CI, 0.1–1; P = 0.040).

Conclusions

In a cohort of women engaged in HIV care in the southern United States, detection of chlamydia, gonorrhea, and syphilis was infrequent but trichomoniasis was common. Many women screened for STI were low risk and universal testing strategies warrant evaluation.
Soluble Suppression Of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study
Authors: Ruiz-Castilla Mireia , Bosacoma Pau , Dos Santos Bruce , Baena Jacinto , Guilabert Patricia , Marin-Corral Judith , Masclans Joan R. , Roca Oriol , Barret Juan P.
Published: April 2018

Background:

The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients.

Methods:

Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d’Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages.

Results:

Sixty-nine patients (58 [84.1%] male, mean age 52 [35–63] years, total body surface area burned 21% [13%–30%], Abbreviated Burn Severity Index 6 [4–8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the receiver-operating curve 0.85 [0.71–0.99]; P < 0.001). The best cutoff point for the area under the receiver-operating curve index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level ≥2,561 measured at day 3 was significantly associated with mortality (hazard ratio 6.94 [1.73–27.74]; P = 0.006).

Conclusions:

Plasma sST2 at day 3 predicts hospital mortality in burn patients.
MiRNA-Mediated Mechanisms of Cardiac Protection in Ischemic and Remote Ischemic Preconditioning—A Qualitative Systematic Review
Authors: Kohns Malte , Huhn Ragnar , Bauer Inge , Brandenburger Timo
Published: April 2018

Background:

Ischemic preconditioning (IPC) and remote ischemic preconditioning (RIPC) protect myocardial tissue against subsequent ischemia and reperfusion injury (IRI) and have a high potential to improve patient outcome. The mediators and mechanisms of protection through IPC and RIPC remain largely unknown, but micro-RNAs (miRNAs) are promising candidates.

Methods:

Systematic review of Medline and Embase databases for biomedical scientific literature.

Results:

A total of 26 relevant publications (21 full-text original articles and 5 conference abstracts) were identified, 8 describing cell culture experiments, 14 animal experiments, and 4 randomized clinical trials in humans. Most commonly reported miRNAs with differential expression between preconditioned and control groups include miR-1, miR-21, and miR-144. Experimental designs and procedures differ widely, thereby limiting the potential to compare results between studies. Two of the four RCTs did not find any differentially expressed miRNAs.

Conclusions:

Results from RCTs should feed back into basic research and focused studies confirming or rejecting hypotheses generated by these RCTs are needed.
Nerve regeneration in the cephalopod molluscOctopus vulgaris:label-free multiphoton microscopy as a tool for investigation
Authors: Imperadore Pamela , Uckermann Ortrud , Galli Roberta , Steiner Gerald , Kirsch Matthias , Fiorito Graziano
Published: April 2018

Octopus and cephalopods are able to regenerate injured tissues. Recent advancements in the study of regeneration in cephalopods appear promising encompassing different approaches helping to decipher cellular and molecular machinery involved in the process. However, lack of specific markers to investigate degenerative/regenerative phenomena and inflammatory events occurring after damage is limiting these studies. Label-free multiphoton microscopy is applied for the first time to the transected pallial nerve ofOctopus vulgaris. Various optical contrast methods including coherent anti-Stokes Raman scattering (CARS), endogenous two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) have been used. We detected cells and structures often not revealed with classical staining methods. CARS highlighted the involvement of haemocytes in building up scar tissue; CARS and TPEF facilitated the identification of degenerating fibres; SHG allowed visualization of fibrillary collagen, revealing the formation of a connective tissue bridge between the nerve stumps, likely involved in axon guidance. Using label-free multiphoton microscopy, we studied the regenerative events in octopus without using any other labelling techniques. These imaging methods provided extremely helpful morpho-chemical information to describe regeneration events. The techniques applied here are species-specific independent and should facilitate the comparison among various animal species.
Long-range proton-coupled electron transfer in biological energy conversion: towards mechanistic understanding of respiratory complex I
Authors: Kaila Ville R. I.
Published: April 2018

Biological energy conversion is driven by efficient enzymes that capture, store and transfer protons and electrons across large distances. Recent advances in structural biology have provided atomic-scale blueprints of these types of remarkable molecular machinery, which together with biochemical, biophysical and computational experiments allow us to derive detailed energy transduction mechanisms for the first time. Here, I present one of the most intricate and least understood types of biological energy conversion machinery, the respiratory complex I, and how its redox-driven proton-pump catalyses charge transfer across approximately 300 Å distances. After discussing the functional elements of complex I, a putative mechanistic model for its
action-at-a-distance
effect is presented, and functional parallels are drawn to other redox- and light-driven ion pumps.
Understanding/unravelling carotenoid excited singlet states
Authors: Hashimoto Hideki , Uragami Chiasa , Yukihira Nao , Gardiner Alastair T. , Cogdell Richard J.
Published: April 2018

Carotenoids are essential light-harvesting pigments in natural photosynthesis. They absorb in the blue–green region of the solar spectrum and transfer the absorbed energy to (bacterio-)chlorophylls, and thus expand the wavelength range of light that is able to drive photosynthesis. This process is an example of singlet–singlet excitation energy transfer, and carotenoids serve to enhance the overall efficiency of photosynthetic light reactions. The photochemistry and photophysics of carotenoids have often been interpreted by referring to those of simple polyene molecules that do not possess any functional groups. However, this may not always be wise because carotenoids usually have a number of functional groups that induce the variety of photochemical behaviours in them. These differences can also make the interpretation of the singlet excited states of carotenoids very complicated. In this article, we review the properties of the singlet excited states of carotenoids with the aim of producing as coherent a picture as possible of what is currently known and what needs to be learned.
Identification of a bet-hedging network motif generating noise in hormone concentrations and germination propensity in
Arabidopsis
Authors: Johnston Iain G. , Bassel George W.
Published: April 2018

Plants have evolved to exploit stochasticity to hedge bets and ensure robustness to varying environments between generations. In agriculture, environments are more controlled, and this evolved variability decreases potential yields, posing agronomic and food security challenges. Understanding how plant cells generate and harness noise thus presents options for engineering more uniform crop performance. Here, we use stochastic chemical kinetic modelling to analyse a hormone feedback signalling motif in
Arabidopsis thaliana
seeds that can generate tunable levels of noise in the hormone ABA, governing germination propensity. The key feature of the motif is simultaneous positive feedback regulation of both ABA production and degradation pathways, allowing tunable noise while retaining a constant mean level. We uncover surprisingly rich behaviour underlying the control of levels of, and noise in, ABA abundance. We obtain approximate analytic solutions for steady-state hormone level means and variances under general conditions, showing that antagonistic self-promoting and self-repressing interactions can together be tuned to induce noise while preserving mean hormone levels. We compare different potential architectures for this ‘random output generator’ with the motif found in
Arabidopsis
, and report the requirements for tunable control of noise in each case. We identify interventions that may facilitate large decreases in variability in germination propensity, in particular, the turnover of signalling intermediates and the sensitivity of synthesis and degradation machinery, as potentially valuable crop engineering targets.
The hydrostatical works of George Sinclair (
c
.1630–1696): their neglect and criticism
Authors: Craik Alex D. D.
Published: April 2018

The Scottish natural philosopher George Sinclair (or Sinclar) (
c
.1630–1696) was one of the earliest British writers on hydrostatics. He visited London in 1662, when he met Sir Robert Moray and Robert Boyle and left a manuscript treatise at the Royal Society. Receipt of this work was never recorded by the Society, and Sinclair felt that he had been dealt with unfairly. A Latin version,
Ars nova et magna gravitatis et levitatis
, was published in 1669, followed by his
Hydrostaticks
in 1672. All Sinclair's works were vituperatively and pseudonymously criticized by James Gregory and William Sanders in
The Great and New Art of Weighing Vanity
of 1672. Here, Sinclair's life is summarized, and his disputes with the Royal Society and with Gregory and Sanders are examined. It is argued that, despite his other limitations, Sinclair's knowledge of hydrostatics was considerable, and that the criticisms made against him were exaggerated. Yet his work was subsequently neglected. Sinclair's treatment sheds light both on academic rivalries and on the procedures of the early Royal Society.
Characterisation of the UK honey bee (Apis mellifera) metagenome
Authors: Regan Tim , Barnett Mark W. , Laetsch Dominik R. , Bush Stephen J. , Wragg David , Budge Giles E. , Highet Fiona , Dainat Benjamin , de Miranda Joachim R. , Blaxter Mark , Freeman Tom C
Published: April 2018

The European honey bee (Apis mellifera) plays a major role in pollination and food production, but is under threat from emerging pathogens and agro-environmental insults. As with other organisms, honey bee health is a complex product of environment, host genetics and associated microbes (commensal, opportunistic and pathogenic). Improved understanding of bee genetics and their molecular ecology can help manage modern challenges to bee health and production. Sampling bee and cobiont genomes, we characterised the metagenome of 19 honey bee colonies across Britain. Low heterozygosity was observed in bees from many Scottish colonies, sharing high similarity to the native dark bee, A. mellifera mellifera. Apiaries exhibited high diversity in the composition and relative abundance of individual microbiome taxa. Most non-bee sequences derived from known honey bee commensal bacteria or known pathogens, e.g. Lotmaria passim (Trypanosomatidae), and Nosema spp. (Microsporidia). However, DNA was also detected from numerous additional bacterial, plant (food source), protozoan and metazoan organisms. To classify sequences from cobionts lacking genomic information, we developed a novel network analysis approach clustering orphan contigs, allowing the identification of a pathogenic gregarine. Our analyses demonstrate the power of high-throughput, directed metagenomics in agroecosystems identifying potential threats to honey bees present in their microbiota.
Lactobacillus acidophilusdisrupts collaborative multispecies bile acid metabolism
Authors: Dautel Sydney , Khan Nymul , Brandvold Kristoffer R. , Brislawn Colin J. , Hutchison Janine , Weitz Karl K. , Heyman Heino M. , Song Hyun-Seob , Ilhan Zehra Esra , Hill Eric A. , Hansen Joshua R. , Zheng Xueyun , Baker Erin S. , Cort John R. , Kim Young-Mo , Isern Nancy G. , DiBaise John K. , Krajmalnik-Brown Rosa , Jansson Janet K. , Wright Aaron T. , Metz Thomas O. , Bernstein Hans C.
Published: April 2018

Bile acids are metabolic links between hosts and their gut microbiomes, yet little is known about the roles they play in microbe-to-microbe interactions. Here we present a study designed to investigate the effect that a common probiotic,Lactobacillus acidophilus, has on microbial interactions that lead to formation of secondary bile acids. A model microbial consortium was built from three human gut isolates,Clostridium scindens, Collinsella aerofaciens,andBlautia obeum, and cultured under different bile acid and probiotic treatments. A multi-omics platform that included mass spectrometry-based metabolomics and activity-based proteomic probes was used to produce two major results. The first, was that an uncommon secondary bile acid – ursocholate – was produced by a multi-species chemical synthesis pathway. This result highlights a new microbe-to-microbe interaction mediated by bile acids. The second finding was that the probiotic strain,L. acidophilus,quenched the observed interactions and effectively halted consortial synthesis of ursocholate. Little is known about the role that ursocholate plays in human health and development. However, we did discover that a decrease in ursocholate abundance corresponded with successful weight loss in patients after gastric bypass surgery versus those who did not lose weight after surgery. Hence, this study uncovered basic knowledge that may aid future designs of custom probiotic therapies to combat obesity.
Word selectivity in high-level visual cortex and reading skill
Authors: Kubota Emily C. , Joo Sung Jun , Huber Elizabeth , Yeatman Jason D.
Published: April 2018

Word-selective neural responses in human ventral occipito-temporal cortex (VOTC) emerge as children learn to read, creating a visual word form area (VWFA) in the literate brain. It has been suggested that the VWFA arises through competition between pre-existing selectivity for other stimulus categories, changing the topography of VOTC to support rapid word recognition. Here, we hypothesized that competition between words and objects would be resolved as children acquire reading skill. Using functional magnetic resonance imaging (fMRI), we examined the relationship between responses to words and objects in VOTC in two ways. First, we defined the VWFA using a words > objects contrast and found that only skilled readers had a region that responded more to words than objects. Second, we defined the VWFA using a words > faces contrast and examined selectivity for words over objects in this region. We found that word selectivity strongly correlated with reading skill, suggesting reading skill-dependent tuning for words. Furthermore, we found that low word selectivity in struggling readers was not due to a lack of response to words, but to a high response to objects. Our results suggest that the fine-tuning of word-selective responses in VOTC is a critical component of skilled reading.
Levetiracetam and Rufinamide are effective at supressing spike and wave seizure activity in an in vitro model of absence epilepsy
Authors: Todorova Virdziniha , Ford Georgina , Traub Roger D. , Whittington Miles. A. , Hall Stephen. P.
Published: April 2018

Spike-and-wave discharges (SpW) are seen in absence-type epilepsies. They are heterogeneous in terms of their clinical burden and their electrographic signature, which is used to classify different types of absence seizures; typical absence, in which SpW frequency is 3-4Hz and atypical absence, which shows a slower 1-2Hz frequency. Treatment of SpW varies dependent upon the syndrome, but both Valproic Acid (VPA) and Ethosuximide (ESM) are shown to be effective in controlling typical absence seizures. Other anti-epileptic’s (AED’s), Levetiracetam (LEV) and Rufinamide (RUF), have shown promise in treating absence epilepsies and their associated syndromes. Here we examine the efficacy of these AED’s on an in vitro model of SpW.

Both LEV and RUF show an effective reduction in both the number of SpW events and the spike component amplitude; VPA shows no effect, whilst ESM enhances the spike amplitude. Phenytoin exacerbates the SpW activity, increasing both the number of SpW, amplitude of the SpW and the number of spikes within each event. These data suggest that both LEV and RUF could be effective in the treatment of absence-type epilepsies. They also suggest this model could be an effective tool to test other AED’s aimed at treating atypical absence syndromes.
Estimation of the cancer risk induced by rejuvenation therapy with young blood and treatment recommendations
Authors: Meyer-Hermann Michael
Published: April 2018

In recent years the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. While this process might increase life expectancy by prolonging functionality of organs, higher cell replication rates bear also the risk of cancer. The extent of this risk is not known.

While it is difficult to evaluate this cancer risk in experiments, this is possible with a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model suggests that young blood treatments can induce a substantial delay of organ failure with only minor increase in cancer risk. The benefit of rejuvenation therapy as well as the impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of the systemic treatment. In particular, the model predicts that the treatment schedules successfully applied in mice are not directly transferable to humans and guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of treatment protocols.

Additional information

There is NO competing interests.
Opposing pupil responses to offered and anticipated reward values
Authors: Cash-Padgett Tyler , Azab Habiba , Michael Yoo Seng Bum , Hayden Benjamin Y.
Published: April 2018

Previous studies have shown that the pupils dilate more in anticipation of larger rewards. This finding raises the possibility of a more general association between reward amount and pupil size. We tested this idea by characterizing macaque pupil responses to offered rewards during evaluation and comparison in a binary choice task. To control attention, we made use of a design in which offers occurred in sequence. By looking at pupil responses after choice but before reward, we confirmed the previously observed positive association between pupil size and anticipated reward values. Surprisingly, however, we find that pupil size is negatively correlated with the value of offered gambles before choice, during both evaluation and comparison stages of the task. These results demonstrate a functional distinction between offered and anticipated rewards, and present evidence against a narrow version of the simulation hypothesis, the idea that we represent offers by reactivating states associated with anticipating them. They also suggest that pupil size is correlated with relative, not absolute, values of offers, suggestive of an accept-reject model of comparison.
MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network
Authors: Shivram Haridha , Le Steven V. , Iyer Vishwanath R.
Published: April 2018

Gene expression can be regulated at multiple levels, but it is not known if and how there is broad coordination between regulation at the transcriptional and post-transcriptional levels. Transcription factors and chromatin regulate gene expression transcriptionally, while microRNAs (miRNAs) are small regulatory RNAs that function post-transcriptionally. Systematically identifying the post-transcriptional targets of miRNAs and the mechanism of transcriptional regulation of the same targets can shed light on regulatory networks connecting transcriptional and post-transcriptional control. We used iCLIP (individual crosslinking and immunoprecipitation) for the RISC (RNA-induced silencing complex) component AGO2 and global miRNA depletion to identify genes directly targeted by miRNAs. We found that PRC2 (Polycomb repressive complex 2) and its associated histone mark, H3K27me3, is enriched at hundreds of miRNA-repressed genes. We show that these genes are directly repressed by PRC2 and constitute a significant proportion of direct PRC2 targets. For just over half of the genes co-repressed by PRC2 and miRNAs, PRC2 promotes their miRNA-mediated repression by increasing expression of the miRNAs that are likely to target them. miRNAs also repress the remainder of the PRC2 target genes, but independently of PRC2. Thus, miRNAs post-transcriptionally reinforce silencing of PRC2-repressed genes that are inefficiently repressed at the level of chromatin, by either forming a feed-forward regulatory network with PRC2 or repressing them independently of PRC2.
Neuropathology and cognitive performance in centenarians
Authors: Ganz Andrea B. , Beker Nina , Hulsman Marc , Sikkes Sietske ,   NBB, Scheltens Philip , Smit August B. , Rozemuller Annemieke J. M. , Hoozemans Jeroen J.M. , Holstege Henne
Published: April 2018

With aging, the incidence of neuropathological hallmarks of neurodegenerative diseases increases in the brains of cognitively healthy individuals. It is currently unclear to what extent these hallmarks associate with symptoms of disease at extreme ages. Forty centenarians from the 100-plus Study cohort agreed to post-mortem brain donation. Centenarians self-reported to be cognitive healthy at baseline, which was confirmed by a proxy. Objective ante-mortem measurements of cognitive performance were associated with the prevalence, distribution and quantity of age- and AD-related neuropathological hallmarks. Despite self-reported cognitive health, objective neuropsychological testing suggested varying levels of ante-mortem cognitive functioning. Post-mortem, we found that most neuropathological hallmarks related to age and neurodegenerative diseases such as Aβ and Tau pathology, as well as atherosclerosis, were abundantly present in most or all centenarians, whereas Lewy body and pTDP-43 pathology were scarce. We observed that increased pathology loads correlated across pathology subtypes, and an overall trend of higher pathology loads to associate with a lower cognitive test performance. This trend was carried especially by the presence of neurofibrillary tangles (NFTs) and granulovacuolar degeneration (GVD) and to a lesser extent by Aβ-associated pathologies. Cerebral Amyloid Angiopathy (CAA) specifically associated with lower executive functioning in the centenarians. In conclusion, we find that while the centenarians in this cohort escaped or delayed cognitive impairment until extreme ages, their brains reveal varying levels of disease-associated neuropathological hallmarks, some of which associate with cognitive performance.
A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Authors: Kuhlwilm Martin , Boeckx Cedric
Published: April 2018

Throughout the past decade, studying ancient genomes provided unique insights into human prehistory, and differences between modern humans and other branches like Neanderthals can enrich our understanding of the molecular basis of unique modern human traits. Modern human variation and the interactions between different hominin lineages are now well studied, making it reasonable to go beyond fixed changes and explore changes that are observed at high frequency in present-day humans. Here, we identify 571 genes with non-synonymous changes at high frequency. We suggest that molecular mechanisms in cell division and networks affecting cellular features of neurons were prominently modified by these changes. Complex phenotypes in brain growth trajectory and cognitive traits are likely influenced by these networks and other changes presented here. We propose that at least some of these changes contributed to uniquely human traits, and should be prioritized for experimental validation.
Biofilm formation on agricultural waste pretreated with cold low-pressure nitrogen plasma and corona plasma discharges
Authors: Farber Ravit , Dabush-Busheri Inbal , Chaniel Gilad , Rozenfeld Shmuel , Bormashenko Edward , Multanen Victor , Cahan Rivka
Published: April 2018

Agricultural waste (AW) was pretreated with cold low-pressure nitrogen plasma (LPD) and corona atmospheric plasma discharges (CAPD), in an attempt to increase the bacterial attachment and biofilm formation. Biofilm formation was examined in the presence of exogenously addedP. putidaandB. cereusas well as in a sterile medium where only the indigenous bacteria which grow naturally on the wood surface could form biofilm. The exposure of AW to (LPD) led to a 3.5-fold increase in biofilm formation of the exogenously addP. putidaF1 in MMT (minimal medium supplied with toluene) and a 1.6-fold increase in MMG (minimal medium supplied with glucose) compared to the untreated AW. The increase in biofilm formation was also observed with the exogenously addedB. cereusor with indigenous bacteria that grow naturally on the AW. The effect of the CAPD on biofilm formation was weak. SEM analysis of the LPD-treated AW showed an increase in surface roughness, which we assume is one of the reasons for the enhancement of the biofilm formation. The apparent contact angle of a sessile drop on the surface of LPD-treated AW as well as on the bacterial layer showed their hydrophilic nature. In conclusion, the increase in biofilm formation of the exogenously addedP. putidaorB. cereuswas due to the LPD treatment.

Importance

To the best of our knowledge, this is the first study to describe the effect of wood plasma treatment on biofilm formation. This technology can be further implemented for bioremediation of contaminated soils.
Single-Cell Amplicon Sequencing Reveals Community Structures and Transmission Trends of Protist-Associated Bacteria in a Termite Host
Authors: Stephens Michael E. , Gage Daniel J.
Published: April 2018

The hindgut protists of wood-feeding termites are usually colonized by prokaryotic symbionts. Many of the hurdles that have prevented a better understanding of these symbionts arise from variation among protist and termite host species and the inability to maintain prominent community members in culture. These issues have made it difficult to study the fidelity, acquisition, and differences in colonization of protists by bacterial symbionts. In this study, we use high throughput amplicon sequencing of the V4 region of 16S rRNA genes to determine the composition of bacterial communities associated with single protist cells of six protist species, from the genera Pyrsonympha, Dinenympha, and Trichonympha that are present in the hindgut of the termite Reticulitermes flavipes. By analyzing amplicon sequence variants (ASVs), the diversity and distribution of protist-associated bacteria was compared within and across these six different protist species. ASV analysis showed that, in general, each protist genus associated with a distinct community of bacterial symbionts which were conserved across different termite colonies. However, some ASVs corresponding to ectosymbionts (Spirochaetes) were shared between different Dinenympha species and to a lesser extent with Pyrsonympha and Trichonympha hosts. This suggested that certain bacterial symbionts may be cosmopolitan to some degree and perhaps acquired by horizontal transmission. Using a fluorescence-based cell assay, we could observe the horizontal acquisition of surface-bound bacteria. This acquisition was shown to be time-dependent, involve active processes, and was non-random with respect to binding locations on some protists.
Molecular determinants of enterotoxigenicEscherichia coliheat-stable toxin secretion and delivery
Authors: Zhu Yuehui , Luo Qingwei , Davis Sierra M. , Westra Chase , Vickers Tim J. , Fleckenstein James M.
Published: April 2018

EnterotoxigenicEscherichia coli(ETEC), a heterogeneous diarrheal pathovar defined by production of heat-labile (LT) and/or heat-stable (ST) toxins, remain major causes of mortality among children in developing regions, and cause substantial morbidity in individuals living in or traveling to endemic areas. Studies demonstrating a major burden of ST-producing ETEC have focused interest on ST toxoids for ETEC vaccines. We therefore examined fundamental aspects of ETEC ST biology using ETEC H10407, which carriesestHandestPgenes encoding ST-H and ST-P, respectively, in addition toeltABgenes responsible for LT. In this background, we found that deletion ofestHsignificantly diminished cGMP activation in target epithelia, while deletion ofestPhad a surprisingly modest impact, and a dualestH/estPmutant was not appreciably different than theestHmutant. Nevertheless, either ST-H or ST-P recombinant peptides stimulated cGMP production. We also found that the TolC efflux protein was essential for both toxin secretion and delivery, providing a potential avenue for efflux inhibitors in treatment of acute diarrheal illness. In addition, we demonstrated that the EtpA adhesin is required for optimal delivery of ST and that antibodies against either the adhesin or ST-H significantly impaired toxin delivery and cGMP activation in target T84 cells. Finally, we used FLAG epitope fusions to demonstrate that the ST-H pro-peptide sequence is secreted by the bacteria, potentially providing additional targets for antibody neutralization. These studies collectively extend our understanding of ETEC pathogenesis and potentially inform additional avenues to mitigate disease by these common diarrheal pathogens.
ampvis2: an R package to analyse and visualise 16S rRNA amplicon data
Authors: Andersen Kasper S. , Kirkegaard Rasmus H. , Karst Søren M. , Albertsen Mads
Published: April 2018

Microbial community analysis using 16S rRNA gene amplicon sequencing is the backbone of many microbial ecology studies. Several approaches and pipelines exist for processing the raw data generated through DNA sequencing and convert the data into OTU-tables. Here we present ampvis2, an R package designed for analysis of microbial community data in OTU-table format with focus on simplicity, reproducibility, and sample metadata integration, with a minimal set of intuitive commands. Unique features include flexible heatmaps and simplified ordination. By generating plots using the ggplot2 package, ampvis2 produces publication-ready figures that can be easily customised. Furthermore, ampvis2 includes features for interactive visualisation, which can be convenient for larger, more complex data.

Availability

ampvis2 is implemented in the R statistical language and is released under the GNU A-GPL license. Documentation website and source code is maintained at:https://github.com/MadsAlbertsen/ampvis2

Contact

Mads Albertsen (ma@bio.aau.dk)
FBXL19 recruits CDK-Mediator to the CpG islands of developmental genes to prime them for activation during lineage commitment
Authors: Dimitrova Emilia , Kondo Takashi , Feldmann Angelika , Nakayama Manabu , Koseki Yoko , Konietzny Rebecca , Kessler Benedikt M , Koseki Haruhiko , Klose Robert J
Published: April 2018

CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.
Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes
Authors: Meer Dennis van der , Rokicki Jaroslav , Kaufmann Tobias , Córdova-Palomera Aldo , Moberget Torgeir , Alnæs Dag , Bettella Francesco , Frei Oleksandr , Doan Nhat Trung , Agartz Ingrid , Bertolino Alessandro , Bralten Janita , Brandt Christine L. , Buitelaar Jan K. , Djurovic Srdjan , Donkelaar Marjolein van , Dørum Erlend S. , Espeseth Thomas , Faraone Stephen V. , Fernández Guillén , D.Phil. Simon E. Fisher , Franke Barbara , Haatveit Beathe , Hartman Catharina A. , Hoekstra Pieter J. , Håberg Asta K. , Jönsson Erik G. , Kolskår Knut K. ,   Cand. Psychol., Hellard Stephanie Le , Lund Martina J. , Lundervold Astri J. , Lundervold Arvid , Melle Ingrid , Sánchez Jennifer Monereo , Norbom Linn C. , Nordvik Jan E. , Nyberg Lars , Oosterlaan Jaap , Papalino Marco , Papassotiropoulos Andreas , Pergola Giulio , de Quervain Dominique J.F. , Richard Geneviève , Sanders Anne-Marthe , Selvaggi Pierluigi , Shumskaya Elena , Steen Vidar M. , Tønnesen Siren , Cand.Psychol. Kristine M. Ulrichsen , Zwiers Marcel P. , Lars Ole A. Andreassen , Westlye Lars T.
Published: April 2018

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer’s disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields’ genetic architecture. T1-weighted brain scans (n=21297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, covarying for total hippocampal volume. We further calculated the single nucleotide polymorphism (SNP)-based heritability of twelve subfields, as well as their genetic correlation with each other, with other structural brain features, and with AD and schizophrenia. All outcome measures were corrected for age, sex, and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from .14 to .27, all p< 1×10-16) and clustered together based on their genetic correlations compared to other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Acute effects of drugs onC.elegansmovement reveal complex responses and plasticity
Authors: Spensley Mark , Del Borrello Samantha , Pajkic Djina , Fraser Andrew G
Published: April 2018

Many drugs act very rapidly — they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs onC.elegansmovement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hours. We find that many treatments show complex acute responses — a phase of rapid paralysis is followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g. recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive and complex natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways.

Author Summary

Drugs are powerful tools that let us switch on or off key pathways in whole animals and watch the effects. Here we set up a simple assay to measure how drugs affect the movement of the simple nematodeC.elegans— crucially, we look how those responses change over time. We find that worms have complex responses to many different drugs — they go through clear phases of paralysis and recovery. The recovery from the initial effect of any drug is not due to a generic stress response but is specific to the way each drug acts. We find for example that worms can recover from paralysis driven by one neurotransmitter pathway by activating a different neurotransmitter pathway or from paralysis caused by loss of one metabolic pathway by turning on a second one. These complex responses show how the basic genetic networks that are needed for normal behaviour and function can rewire and respond to the effect of many drugs. Importantly, the responses can vary in many ways — different aged worms or different individuals can have different responses and capturing how drug responses change over time is critical to dissect this complexity.
Confidence Analysis of DEER Data and its Structural Interpretation with Ensemble-Biased Metadynamics
Authors: Hustedt Eric J. , Marinelli Fabrizio , Stein Richard A. , Faraldo-Gómez José D. , Mchaourab Hassane S.
Published: April 2018

Given its ability to measure multicomponent distance distributions between electron-spin probes, Double Electron-Electron Resonance spectroscopy (DEER) has become a leading technique to assess the structural dynamics of biomolecules. However, methodologies to evaluate the statistical error of these distributions are not standard, often hampering a rigorous interpretation of the experimental results. Distance distributions are often determined from the experimental DEER data through a mathematical method known as Tikhonov regularization, but this approach makes rigorous error estimates difficult. Here, we build upon an alternative model-based approach in which the distance probability distribution is represented as a sum of Gaussian components and use propagation of errors to calculate an associated confidence band. Our approach considers all sources of uncertainty, including the experimental noise, the uncertainty in the fitted background signal, and the limited time-span of the data collection. The resulting confidence band reveals the most and least reliable features of the probability distribution, thereby informing the structural interpretation of DEER experiments. To facilitate this interpretation, we also generalize the molecular-simulation method known as Ensemble-Biased Metadynamics. This method, originally designed to generate maximum-entropy structural ensembles consistent with one or more probability distributions, now also accounts for the uncertainty in those target distributions, exactly as dictated by their confidence bands. After careful benchmarks, we demonstrate the proposed techniques using DEER results from spin-labeled T4 lysozyme.
L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis
Authors: Schauer Stephanie N. , Carreira Patricia E. , Shukla Ruchi , Gerhardt Daniel J. , Gerdes Patricia , Sanchez-Luque Francisco J. , Nicoli Paola , Kindlova Michaela , Ghisletti Serena , Santos Alexandre Dos , Rapoud Delphine , Samuel Didier , Faivre Jamila , Ewing Adam D. , Richardson Sandra R. , Faulkner Geoffrey J.
Published: April 2018

The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2)−/− mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including TF subfamily elements, and one GF subfamily example. One of the TF insertions carried a 3′ transduction, allowing us to identify its donor L1 and to demonstrate that this full-length TF element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors.
Phenoxide and alkoxide complexes of Mg, Al and Zn, and their use for the ring-opening polymerization of ɛ-caprolactone with initiators of different natures
Authors: Minyaev Mikhail E. , Nifant'ev Ilya E. , Shlyakhtin Andrey V. , Ivchenko Pavel V. , Lyssenko Konstantin A.
Published: April 2018

A new packing polymorph of bis(2,6-di-tert-butyl-4-methylphenolato-κO)bis(tetrahydrofuran-κO)magnesium, [Mg(C15H23O)2(C4H8O)2] or Mg(BHT)2(THF)2, (BHT is the 2,6-di-tert-butyl-4-methylphenoxide anion and THF is tetrahydrofuran), (1), has the same space group (P21) as the previously reported modification [Nifant'ev et al. (2017d). Dalton Trans.
46, 12132–12146], but contains three crystallographically independent molecules instead of one. The structure of (1) exhibits rotational disorder of the tert-butyl groups and positional disorder of a THF ligand. The complex of bis(2,6-di-tert-butyl-4-methylphenolato-κO)bis(μ2-ethyl glycolato-κ2
O,O′:κO)dimethyldialuminium, [Al2(CH3)2(C4H7O3)2(C15H23O)2] or [(BHT)AlMe(OCH2COOEt)]2, (2), is a dimer located on an inversion centre and has an Al2O2 rhomboid core. The 2-ethoxy-2-oxoethanolate ligand (OCH2COOEt) displays a μ2-κ2
O,O′:κO semi-bridging coordination mode, forming a five-membered heteronuclear Al–O–C–C–O ring. The same ligand exhibits positional disorder of the terminal methyl group. The redetermined structure of the heptanuclear complex octakis(μ3-benzyloxo-κO:κO:κO)hexaethylheptazinc, [Zn7(C2H5)6(C7H7O)8] or [Zn7(OCH2Ph)8Et6], (3), possesses a bicubic Zn7O8 core located at an inversion centre and demonstrates positional disorder of one crystallographically independent phenyl group. Cambridge Structural Database surveys are given for complexes structurally analogous to (2) and (3). Complexes (2) and (3), as well as derivatives of (1), are of interest as catalysts for the ring-opening polymerization of ɛ-caprolactone, and polymerization results are reported.