bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection from epidemics is a driving force for evolution of lifespan setpoints
Authors: Lidsky Peter V. , Andino Raul
Published: November 2017

Most living organisms age, as determined by species-specific limits to lifespan1–6. The biological driving force for a genetically-defined limit on the lifespan of a given species (herein called “lifespan setpoint”) remains poorly understood. Here we present mathematical models suggesting that an upper limit of individual lifespans protects their cohort population from infection-associated penalties. A shorter lifespan setpoint helps control pathogen spread within a population, prevents the establishment and progression of infections, and accelerates pathogen clearance from the population when compared to populations with long-lived individuals. Strikingly, shorter-living variants efficiently displace longer-living individuals in populations that are exposed to pathogens and exist in spatially structured niches. The beneficial effects of shorter lifespan setpoints are even more evident in the context of zoonotic transmissions, where pathogens undergo adaptation to a new host. We submit that the selective pressure of infectious disease provides an evolutionary driving force to limit individual lifespan setpoints after reproductive maturity to secure its kin’s fitness. Our findings have important public health implications for efforts to extend human’s lifespan.
High genomic diversity of multi-drug resistant wastewater Escherichia coli
Authors: Mahfouz Norhan , Caucci Serena , Achatz Eric , Semmler Torsten , Guenther Sebastian , Berendonk Thomas U. , Schroeder Michael
Published: November 2017

Wastewater treatment plants play an important role in the release of antibiotic resistance into the environment. It has been shown that wastewater contains multi-drug resistant Escherichia coli, but information on strain diversity is surprisingly scarce. Here we present an exceptionally large dataset on multidrug resistant Escherichia coli, originating from wastewater, over a thousand isolates were phenotypically characterized for twenty antibiotics and for 103 isolates whole genomes were sequenced. To our knowledge this is the first study documenting such a comprehensive diversity of multi-drug resistant Escherichia coli in wastewater. The genomic diversity of the isolates was unexpectedly high and contained a high number of resistance and virulence genes. To illustrate the genomic diversity of the isolates we calculated the pan genome of the wastewater Escherichia coli and found it to contain over sixteen thousand genes. To analyse this diverse dataset, we devised a computational approach correlating genotypic variation and resistance phenotype, this way we were able to identify not only known, but also candidate resistance genes. Finally, we could verify that the effluent of a wastewater treatment plant will contain multi-drug resistant Escherichia coli belonging to clinically important clonal groups.
A Pilot Randomized Trial of Oral Magnesium Supplementation on Supraventricular Arrhythmias
Authors: Lutsey Pamela L. , Chen Lin Y. , Eaton Anne , Jaeb Melanie , Rudser Kyle D. , Neaton James D. , Alonso Alvaro
Published: November 2017

Background

Magnesium is believed to have a physiologic role in cardiac contractility, and evidence from epidemiologic and clinical studies has suggested that low serum concentrations of magnesium may be associated with increased risk of atrial fibrillation (AF).

Objective

As part of the planning effort for a large randomized trial to prevent AF with magnesium supplementation, we conducted a 12-week pilot study to assess adherence to oral magnesium supplementation and matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory monitoring device (ZioPatch) for assessing premature atrial contractions (PACs), a predictor of AF.

Design

Double-blind randomized pilot clinical trial comparing supplementation with 400 mg magnesium oxide daily (versus placebo) over 12 weeks of follow-up. The ZioPatch was applied for 14 days at baseline and the end of follow-up. Adherence to the assigned treatment, and changes in PACs, serum magnesium concentration, glucose and blood pressure were assessed.

Results

A total of 59 participants, 73% women and average age 62 years, were randomized. 98% of participants completed follow-up. Those assigned to the magnesium supplement took 75% of tablets as compared to 83% for those in the placebo group. Change in magnesium concentrations was significantly greater for those given magnesium supplement compared to placebo (0.07; 95% confidence interval (CI): 0.03, 0.12 mEq/L; p = 0.002). ZioPatch was worn for an average of 13.0 of the requested 14 days at baseline; at the end of follow-up, the average number of days of monitoring was 13.0 days for the magnesium supplement group and 12.7 days for the placebo group. For log PAC burden (episodes per hour), the average change from baseline was −0.05 (95% CI: −0.31, 0.20) for those randomized to magnesium supplement and 0.04 (95% CI: −0.24, 0.31) for those randomized to placebo (p=0.79 for difference). Gastrointestinal problems were reported by 50% of participants in the magnesium supplement group and 7% in the placebo group. Only one person in the magnesium supplement group and none in the placebo group experienced adverse events which led to treatment discontinuation.

Conclusions

In this pilot randomized clinic trial, although gastrointestinal side effects to the magnesium supplement were common, adherence, measured by pill counts, was very good and, as a consequence, magnesium concentrations were greater for those randomly assigned to the magnesium supplement compared to placebo. Participant acceptance of the planned monitoring with ZioPatch was also very good. While the difference in the change in PACs was not significant, this pilot study was small, short-term, and did not include participants at high risk of AF. Thus, we could not reliably evaluate the effect of magnesium supplementation on PACs.

Clinicaltrials.gov registration

NCT02837328
Split personality of Aluminum Activated Malate Transporter family proteins: facilitation of both GABA and malate transport
Authors: Ramesh Sunita A. , Kamran Muhammad , Sullivan Wendy , Chirkova Larissa , Okamoto Mamoru , Degryse Fien , McLaughlin Michael , Gilliham Matthew , Tyerman Stephen D.
Published: November 2017

Plant aluminum activated malate transporters (ALMTs) are currently classified as anion channels; they are also known to be regulated by diverse signals leading to a range of physiological responses. Gamma-aminobutyric acid (GABA) regulation of anion flux through ALMT proteins requires the presence of a specific amino acid motif in ALMTs that shares similarity with a GABA-binding site in mammalian GABAAreceptors. Here, we explore why TaALMT1-activation leads to a negative correlation between malate efflux and endogenous GABA concentrations ([GABA]i) in both wheat root tips and in heterologous expression systems. We show that TaALMT1 activation reduces [GABA]ibecause TaALMT1 facilitates GABA efflux. TaALMT1-expression also leads to GABA transport into cells, demonstrated by a yeast complementation assay and via14CGABA uptake into TaALMT1-expressingXenopus laevisoocytes; this was found to be a general feature of all ALMTs we examined. Mutation of the GABA motif (TaALMT1F213C) prevented both GABA influx and efflux, and uncoupled the relationship between malate efflux and [GABA]i. We conclude that ALMTs are likely to act as both GABA and anion transportersin planta. GABA and malate appear to interact with ALMTs in a complex manner regulating each other’s transport, suggestive of a role for ALMTs in communicating metabolic status.
Coupling MALDI-TOF mass spectrometry protein and specialized metabolite analyses to rapidly discriminate bacterial function
Authors: Clark Chase M. , Costa Maria S. , Sanchez Laura M. , Murphy Brian T.
Published: November 2017

For decades, researchers have lacked the ability torapidlycorrelate microbial identity with bacterial metabolism. Since specialized metabolites are critical to bacterial function and survival in the environment, we designed a data acquisition and bioinformatics technique (IDBac) that utilizesin situmatrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze protein and specialized metabolite spectra of single bacterial colonies from agar plates. We demonstrated the power of our approach by discriminating between twoBacillus subtiliscolonies in under 30 minutes, which differ by a single genomic mutation, solely on the basis of their differential ability to produce cyclic peptide antibiotics surfactin and plipastatin. Next, we employed our IDBac technique to detect subtle intra-species differences in the production of metal scavenging acyl-desferrioxamines in a group of eight freshwaterMicromonosporaisolates that share >99% sequence similarity in the 16S rRNA gene. Finally, we employed our method to simultaneously extract protein and specialized metabolite MS profiles from unidentified species of Lake Michigan sponge-associated bacteria cultivated on an agar plate. In just 3 hours, we created hierarchical protein MS groupings of 11 environmental isolates (10 MS replicates each, for a total of 110 samples) that accurately mirrored phylogenetic groupings. We further distinguished isolates within these groupings, which share nearly identical 16S rRNA gene sequence identity, based on inter- and intra-species differences in specialized metabolite production. To our knowledge, IDBac is the first attempt to couplein situMS analyses of protein contentandspecialized metabolite production to allow the distinction of closely related bacterial colonies.

Significance

Mass spectrometry is a powerful technique that has been used to identify bacteria via protein content, and to assess bacterial function in an environment via analysis of specialized metabolites. However, until now these analyses have operated independently, and this has resulted in the inability to rapidly connect bacterial phylogenetic identity with patterns of specialized metabolism. To bridge this gap, we designed a MALDI-TOF mass spectrometry data acquisition and bioinformatics pipeline (IDBac) to discriminate both intact protein and specialized metabolite spectra directly from bacterial cells grown on agar. To our knowledge, this is the first technique that organizes bacteria into highly similar phylogenetic groups and allows for comparison of metabolic differences of hundreds of isolates in just a few hours.
Chunking sequence information by mutually predicting recurrent neural networks
Authors: Asabuki Toshitake , Hiratani Naoki , Fukai Tomoki
Published: November 2017

Interpretation and execution of complex sequences is crucial for various cognitive tasks such as language processing and motor control. The brain solves this problem arguably by dividing a sequence into discrete chunks of contiguous items. While chunking has been accounted for by predictive uncertainty, alternative mechanisms have also been suggested, and the mechanism underlying chunking is poorly understood. Here, we propose a class of unsupervised neural networks for learning and identifying repeated patterns in sequence input with various degrees of complexity. In this model, a pair of reservoir computing modules, each of which comprises a recurrent neural network and readout units, supervise each other to consistently predict others’ responses to frequently recurring segments. Interestingly, this system generates neural responses similar to those formed in the basal ganglia during habit formation. Our model extends reservoir computing to higher cognitive function and demonstrates its resemblance to sequence processing by cortico-basal ganglia loops.
Paternal grandparental exposure to crop failure or surfeit during a childhood slow growth period: Epigenetic marks on grandchildren’s growth, glucoregulatory and stress genes
Authors: Olov Bygren Lars , Müller Patrick , Brodin David , Kaati Gunnar , Gustafsson Jan-Åke , Kral John G.
Published: November 2017

This latest in our series of papers describes transgenerational methylation related to midchildhood food availability in 19th century Överkalix, Sweden. Failed vs. bountiful crops differentially influenced methylation in grandchildren of paternal grandparents exposed to feast or famine during their Slow Growth Period (SGP), a sensitive period preceding the pre-pubertal growth spurt. In this case-study of 8 tracked 75-year old progeny with differential ancestral exposure, we found, in 40 posited gene ontology pathways, 39 differentially methylated CpG regions (DMRs) related to famine, excess food and food-insecurity stress, 9 of which with DMRs above 5%. Three gene ontology terms (GOs) “insulin processing”, “adipose development” and “hypothalamus development” were key, with DMRs >14%. An unbiased test of known pathways revealed four nuclear transcription factors upstream of promotors repressing the pathway following paternal grandparental famine experience, as well as 4 upregulated GOs with average DMRs >20%. We conclude that this is the first demonstration of human transgenerational inheritance of epigenetic marks following ancestral childhood exposure to variable food availability inducing early developmental origins of adult disease.
Weak spatiotemporal response of prey to predation risk in a freely interacting system
Authors: Cusack Jeremy J. , Kohl Michel T. , Metz Matthew C. , Coulson Tim , Stahler Daniel R. , Smith Douglas W. , MacNulty Daniel R.
Published: November 2017

The extent to which prey space use actively minimises predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured, and lack of robust null expectations.

We addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by grey wolves (Canis lupus) during winter in northern Yellowstone, USA.

We quantified spatial overlap between the winter home ranges of GPS-collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf-killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterised by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach.

Although a small proportion of elk did show a tendency to minimise use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone.

Our results suggest that predator-prey interactions may not always result in strong spatiotemporal patterns of avoidance.
Accurate detection of HIV transmission clusters from phylogenetic trees using a multi-state birth-death model
Authors: Barido-Sottani Joëlle , Stadler Tanja
Published: November 2017

HIV transmission networks are highly clustered, and accurate identification of these clusters is essential for effective targeting of public health interventions. This clustering affects the transmission dynamics of the HIV epidemic, which affects the pathogen phylogenies reconstructed from patient samples. We present a new method for identifying transmission clusters by detecting the changes in transmission rate provoked by the introduction of the epidemic into a new cluster. The method employs a multi-state birth-death (MSBD) model where each state represents a cluster. Transmission rates in each cluster decrease exponentially over time, simulating susceptible depletion in the cluster. This model is fitted to the pathogen phylogeny using a Maximum Likelihood approach. Using simulated datasets we show that the MSBD method is able to reliably infer both the cluster repartition and the transmission parameters from a pathogen phylogeny. In contrast to existing cutpoint-based methods for cluster identification, which are dependent on a parameter set by the user, the MSBD method is consistently reliable. It also performs better on phylogenies containing nested clusters. We present an application of our method to the inference of transmission clusters using sequences obtained from the Swiss HIV Cohort Study. The MSBD method is available as an R package.
Acute memory deficits in chemotherapy-treated adults
Authors: Lindner Oana C. , Mayes Andrew , McCabe Martin G. , Talmi Deborah
Published: November 2017

Data from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory-Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients’ first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically-relevant implications.
PKD2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium
Authors: Liu Xiaowen , Vien Thuy , Duan Jingjing , Sheu Shu-Hsien , DeCaen Paul G. , Clapham David E.
Published: November 2017

Mutations in eitherPkd1orPkd2result in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although PKD2 is proposed to be an ion channel subunit, recordings of PKD2 ion channels conflict in their properties. Using a new ADPKD mouse model, we observe primary cilia are abnormally long in cells associated with cysts. Using primary cultures of collecting duct epithelial cells, we show that PKD2, but not PKD1, is a required subunit for primary cilia ion channel. The ciliary PKD2 channel conducts potassium and sodium ions, but little calcium. We also demonstrate that PKD2 is not constitutively active in the plasma membrane, but PKD2 channels are functional in primary cilia and are sensitized by high cilioplasmic [Ca2+]. We introduce a novel method for measuring PKD2 channels heterologously expressed in primary cilia of HEK-293 cells, which will have utility characterizingPkd2variants that cause ADPKD in their native ciliary membrane.
Lack of insurance is associated with lower probability of diagnostic imaging use among US trauma patients: An instrumental variable analysis and simulation
Authors: Renson Audrey , Schubert Finn D. , Bjurlin Marc A.
Published: November 2017

Background

Uninsured trauma patients have higher mortality than their insured counterparts. One possible reason is disparities in utilization of appropriate diagnostic imaging, including computed tomography (CT), X-ray, ultrasound (US), and magnetic resonance imaging (MRI). We examined the association between lack of insurance and use of diagnostic imaging.

Methods

Data come from the National Trauma Databank 2010-2015. Patients were determined uninsured if payment mode was self-pay or missing. The primary outcome was any diagnostic imaging procedure, and secondary outcomes included CT, X-ray, US, or MRI. Risk ratios (RRs) were adjusted for demographics, comorbidities, injury characteristics, facility characteristics. We also used the 2010 Patient Protection and Affordable Care Act as an instrumental variable (IV), with linear terms for year to account for annual trends in imaging use. Monte carlo simulations to test effect of hypothetical violations to IV assumptions of relevance, no direct effect, and no confounding.

Results

Of 4,373,554 patients, 953,281 (21.8%) were uninsured. After adjusting, uninsured patients had lower chance of any imaging (RR 0.98, 95% CI 0.98 to 0.98), x-ray (RR 0.99, 95% CI 0.99 to 1.00), and MRI (RR 0.82, 95% CI 0.81 to 0.83), and higher chance of ultrasound (RR 1.01, 95% CI 1.01 to 1.02). In IV analysis, uninsured status was associated with reduction in any imaging (RR 0.60, 95% CI 0.52 to 0.70), tomography (RR 0.52, 95% CI 0.44 to 0.62) ultrasound (RR 0.46, 95% CI 0.32 to 0.65), and MRI (RR 0.19, 95% CI 0.10 to 0.37) and increased likelihood of x-ray use (RR 1.74, 95% CI 1.31 to 2.32). Simulations indicated that a direct effect RD of −0.02 would be necessary to produce observed results under the null hypothesis.

Discussion

Our study suggests an association between insurance status and use of imaging that is unlikely to be driven by confounding or violations of IV assumptions. Mechanisms for this remain unclear, but could include unconscious provider bias or institutional financial constraints. Further research is warranted to elucidate mechanisms and assess whether differences in diagnostic imaging use mediate the association between insurance and mortality.
Needle in a haystack? A comparison of eDNA metabarcoding and targeted qPCR for detection of the great crested newt (Triturus cristatus)
Authors: Harper Lynsey R. , Handley Lori Lawson , Hahn Christoph , Boonham Neil , Rees Helen C. , Gough Kevin C. , Lewis Erin , Adams Ian P. , Brotherton Peter , Phillips Susanna , Hänfling Bernd
Published: November 2017

Environmental DNA (eDNA) analysis is a rapid, cost-effective, non-invasive biodiversity monitoring tool which utilises DNA left behind in the environment by organisms for species detection. The method is used as a species specific survey tool for rare or invasive species across a broad range of ecosystems. Recently, eDNA and ‘metabarcoding’ have been combined to describe whole communities rather than focusing on single target species. However, whether metabarcoding is as sensitive as targeted approaches for rare species detection remains to be evaluated. The great crested newt Triturus cristatus is a flagship pond species of international conservation concern and the first UK species to be routinely monitored using eDNA. We evaluate whether eDNA metabarcoding has comparable sensitivity to targeted real-time quantitative PCR (qPCR) for T. cristatus detection. Extracted eDNA samples (N = 532) were screened for T. cristatus by qPCR and analysed for all vertebrate species using High-Throughput Sequencing technology. With qPCR and a detection threshold of 1/12 positive qPCR replicates, newts were detected in 50% of ponds. Detection decreased to 32% when the threshold was increased to 4/12 positive qPCR replicates. With metabarcoding, newts were detected in 34% of ponds without a detection threshold, and in 28% of ponds when a threshold (0.028%) was applied. Therefore, qPCR provided greater detection than metabarcoding but metabarcoding detection with no threshold was equivalent to qPCR with a stringent detection threshold. The proportion of T. cristatus sequences in each sample was positively associated with the number of positive qPCR replicates (qPCR score) suggesting eDNA metabarcoding may be indicative of eDNA concentration. eDNA metabarcoding holds enormous potential for holistic biodiversity assessment and routine freshwater monitoring. We advocate this community approach to freshwater monitoring to guide management and conservation, whereby entire communities can be initially surveyed to best inform use of funding and time for species-specific surveys.
Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer’s disease
Authors: Liu Hongde , Luo Kun
Published: November 2017

Alzheimer’s disease (AD) is a severe neurodegenerative disorder. Identification of differentially expressed genes in AD would help to find biomarker and therapeutic target. Here, we carried out an analysis to identify the age-independent and AD-specific genes. We found that genes MET, WIF1 and NPTX2 are down regulated in AD. WIF1 and MET are in signaling of WNT and MET, regulating the activity of GSK3β, thus in AD. Importantly, we found gene GMPR shows a gradual increase in AD progress. A logistic model based on GMPR exhibits a good capacity in classifying AD cases. GMPR’s product GMPR1 links with AMPK and adenosine receptor pathways, thus associating phosphorylation of Tau in AD. This allows GMPR1 to be a therapeutic target. Therefore, we screened five possible inhibitors to GMPR1 by docking GMPR1 with 1174 approved drugs. Among them, lumacaftor is ideal due to its high affinity and light molecular weight. We then tested the effect of lumacaftor on AD model mice. After twenty days of oral administration, β-Amyloid accumulation is slowed down and phosphorylation of Tau is almost eliminated in the treated mice, showing a satisfying effect. In conclusion, the elevated expression level of GMPR tightly associates with AD progress and leads to AD phenotype probably through AMPK and adenosine receptor pathways; and one of therapeutic strategies is to inhibit GMPR’s product with lumacaftor.

Significance Statement

We found the elevated expression level of GMPR tightly associates with AD progress and leads to AD phenotype probably through AMPK and adenosine receptor pathways; and the therapeutic strategy targeting GMPR1 with lumacaftor shows a satisfying result.
Genome scan identifies flowering-independent effects of barley HsDry2.2 locus on yield traits under water deficit
Authors: Merchuk-Ovnat Lianne , Silberman Roi , Laiba Efrat , Maurer Andreas , Pillen Klaus , Faigenboim Adi , Fridman Eyal
Published: November 2017

Increasing crop productivity under climate change requires the identification, selection and utilization of novel alleles for breeding. We analyzed the genotype and field phenotype of the barley HEB-25 multi-parent mapping population under well-watered and water-limited (WW and WL) environments for two years. A genome-wide association study (GWAS) for genotype by-environment interactions was performed for ten traits including flowering time (HEA), plant grain yield (PGY). Comparison of the GWAS for traits per-se to that for QTL-by-environment interactions (QxE), indicates the prevalence of QxE mostly for reproductive traits. One QxE locus on chromosome 2, Hordeum spontaneum Dry2.2 (HsDry2.2), showed a positive and conditional effect on PGY and grain number (GN). The wild allele significantly reduced HEA, however this earliness was not conditioned by water deficit. Furthermore, BC2F1 lines segregating for the HsDry2.2 showed the wild allele confers an advantage over the cultivated in PGY, GN and harvest index as well as modified shoot morphology, longer grain filling period and reduced senescence (only under drought), therefore suggesting adaptation mechanism against water deficit other than escape. This study highlights the value of evaluating wild relatives in search of novel alleles and clues to resilience mechanism underlying crop adaptation to abiotic stress.

Highlight

A flowering-time independent reproductive advantage of wild over cultivated allele under drought identified in a barley GWAS for genotype-by-environment interactions, with modified shoot morphology, reduced senescence and longer grain filling
TraRECo: A Greedy Approach based de novo Transcriptome Assembler with Read Error Correction using Consensus Matrix
Authors: Yoon Seokhyun , Kim Daeseung , Kang Keunsoo , Park Woong June
Published: November 2017

Background

Challenges in developing a good de novo transcriptome assembler include how to deal with read errors and sequence repeats. Almost all de novo assemblers utilize de Bruijn graph, which has a complexity linearly growing with data size while suffers from errors and repeat. Although one can correct errors by inspecting topological structure of the graph, it is an uneasy task when there are too many branches. There are two research directions: improving either graph reliability or path search precision. We focused on improving the reliability.

Results

We present TraRECo, a greedy approach to de novo assembly employing error-aware graph construction. The idea is similar to overlap-layout-consensus approach used for genome assembly, but is different in that consensus is made through the entire graph construction step. Basically, we built contigs by direct read alignment within a distance margin and performed junction search to construct splicing graphs. While doing so, however, a contig of length l was represented by 4×1 matrix (called consensus matrix), of which each element was the base count of aligned reads so far. A representative sequence is obtained, by taking majority in each column of the consensus matrix, to be used for further read alignment. Once splicing graphs were obtained, we used IsoLasso to find paths with noticeable read depth. The experiments using real and simulated reads showed that the method provides considerable improvements in sensitivity and reasonably better performances when comparing both sensitivity and precision. This could be achieved by making more erroneous reads to be participated in graph construction, which, in turn, improved the depth information quality used for the subsequent path search step. The results for simulated reads showed also challenges are still remaining since non-negligible percentage of transcripts with high abundance were not recovered by the assemblers we considered.

Conclusion

de novo assembly is mainly to explore not-yet-discovered isoforms and must be able to represent as much reads as possible in an efficient way. In this sense, TraRECo provides us a potential alternative to improve graph reliability, even though the computational burden can be much higher than single k-mer de Bruijn graph approach.
Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription
Authors: Sharma Priyanka , Lioutas Antonios , Fernandez-Fuentes Narcis , Quilez Javier , Carbonell-Caballero José , Wright Roni H.G. , Di Vona Chiara , Le Dily François , Schüller Roland , Eick Dirk , Oliva Baldomero , Beato Miguel
Published: November 2017

Highlights

Peptidyl arginine deiminase 2 (PADI2) citrullinates arginine1810 (cit1810) present at carboxy-terminal domain of RNA polymerase II (RNAP2-CTD).

PADI2 and R1810 of RNAP2-CTD regulate transcription and proliferation of breast cancer cells.

Absence of cit1810 at RNAP2-CTD leads to RNAP2 accumulation at proximal promoter regions.

Cit1810 at RNAP2-CTD facilitate interaction with P-TFEb complex.

The post-translational modification of key residues at the carboxy-terminal domain of RNA polymerase II (RNAP2-CTD), coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases including cancer. We show that among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 result in accumulation of RNAP2 at transcription start sites, reduced gene expression and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells.
A biophysical dynamic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN)
Authors: Hernández-Hernández Valeria , Barrio Rafael A. , Benítez Mariana , Nakayama Naomi , Romero-Arias José Roberto , Villarreal Carlos
Published: November 2017

Intracellular polarisation of auxin efflux carriers is crucial for understanding how auxin gradients form in plants. The polarisation dynamics of auxin efflux carriers PIN-FORMED (PIN) depends on both biomechanical forces as well as chemical, molecular and genetic factors. Biomechanical forces have shown to affect the localisation of PIN transporters to the plasma membrane. We proposed a biophysical module of PIN polarisation that integrates biomechanical, molecular, and cellular processes as well as their non-linear interactions. The module was implemented as a discrete Boolean model and then approximated to a continuous dynamic system, in order to explore the relative contribution of the factors mediating PIN polarisation at the scale of single cell. Our models recovered qualitative behaviours that have been experimentally observed and enabled us to postulate that, in the context of PIN polarisation, the effects of the mechanical forces can predominate over the activity of molecular factors such as the GTPase ROP6 and the CRIB-motif CRIB-motif RIC1.
Reactivating vocabularies in the elderly
Authors: Cordi M.J. , Schreiner T. , Rasch B.
Published: November 2017

Quality of memory and sleep decline with age, but the mechanistic interactions underlying the memory function of sleep in older adults are still unknown. It is widely assumed that the beneficial effect of sleep on memory relies on reactivation during Non-rapid eye movement (NREM) sleep, and targeting these reactivations by cue re-exposure reliably improves memory in younger participants. Here we tested whether the reactivation mechanism during sleep is still functional in old age by applying targeted memory reactivation (TMR) during NREM sleep in healthy adults over 60 years. In contrast to previous studies in young participants, older adults’ memories do not generally benefit from TMR during NREM sleep. On an individual level, a subgroup of older adults still profited from cueing during sleep. These improvers tended to have a better sleep efficiency than non-improvers. In addition, the oscillatory results resembled those obtained in younger participants, involving increases in theta (~6Hz) and spindle (~13 Hz) power for remembered and gained words in a later time windows. In contrast, non-improvers showed no increases in theta activity and even strongly reduced spindle power for later gained vs. lost words. Our results suggest that reactivations during sleep might lose their functionality for memory in some older adults, while this mechanism is still intact in a subgroup of participants. Further studies need to examine more closely the determinants of preserving the memory function of sleep during healthy aging.

Grant information

The study was supported by grant of the Swiss National Science Foundation (SNSF) No. 100014_162388. T.S. is supported by a grant of the Swiss National Science Foundation (SNSF) No. P2ZHP1_164994.

Abbreviations

N1 and N2

Stage 1 and 2 sleep

SWS

Slow-wave sleep

SWA

slow-wave activity

REM

Rapid eye movement sleep

TST

Total sleep time

TMR

targeted memory reactivation
Mouse lemurs’ and degraded habitat
Authors: Knoop Simon , Chikhi Lounès , Salmona Jordi
Published: November 2017

Madagascar is known for its unique biodiversity including its endemic primates, the lemurs. This biodiversity is threatened by deforestation, forest degradation and anthropogenic disturbances. Several mouse lemurs (genus Microcebus) have been shown to cope with habitat disturbances and degradation. However, there are 24 recognized mouse lemur species living in very different habitats, and it is not clear whether all these species respond similarly to forest degradation. Here, we review the literature on mouse lemur use of degraded habitat. We further question whether mouse lemurs show variation in degraded habitat use, with respect to forest type, conservation status and distribution range. We show that data on degraded forest (DF) use is available for 14 species and geographically aggregated in a few locations. However, data are scarce for most species, and lacking for almost half of the currently recognized species. Our results however confirm that most mouse lemur species are able to cope with, but do not necessarily respond positively to habitat degradation. We found no variation in degraded habitat use, with respect to forest type, conservation status and distribution range. However, we identified food resources availability, understory structure, predation, and tree hole availability to be the most frequently invoked factors potentially influencing DF use. The relative frequency of these four factors vary among forest types suggesting that differences may exist but still require research efforts for ecological and environmental differences among regions to be fully understood.

RESEARCH HIGHLIGHTS

Little differences in the use of degraded forest (DF) between forest types, distribution ranges or conservation status.

Varying factors potentially affecting DF use, such as food resources, forest structure, tree hole availability and predation.
Influence ofOenococcus oeniandBrettanomyces bruxellensison Aged Wine Microbial Taxonomic and Functional Profiles
Authors: Zepeda-Mendoza Marie Lisandra , Edwards Nathalia Kruse , Madsen Mikkel Gulmann , Abel-Kistrup Martin , Puetz Lara , Sicheritz-Ponten Thomas , Swiegers Jan H.
Published: November 2017

In the wine making process, the interactions between lactic acid bacteria (LAB), yeast and other wine microflora have an impact on the wine quality. In this study, we investigate the influence of the LABOenococcus oeniand the spoilage yeastBrettanomyces bruxellensison the microbial community of a Cabernet Sauvignon wine. We generated metagenomic datasets from inoculations of three strains ofB. bruxellensis, in combination with twoO. oenistrains, one with and one without cinnamoyl esterase activity. This esterase activity releases hydroxycinnamic acids (HCAs) that can subsequently be processed by someB. bruxellensisstrains able to generate off-flavor compounds. We evaluated the influence of theO. oeniandB. bruxellensison the microbial taxonomic and functional potential profile, particularly regarding off-flavor formation due to HCAs. We found that the effect on the microbial profiles depends oni) theO. oeniandB. bruxellensisstrains being combined andii) the abundance they reach in the final wine, which depends on certain unidentified conditions. We confirmed that the potential ofB. bruxellensisto produce off-flavor compounds from HCAs depends on the strain. Interestingly, the samples without microbial inoculants also had this potential, suggesting that native grape microbiota could also influence the levels of HCA. We also found that the presence ofB. bruxellensisdoes not interfere with the malolactic fermentation of the evaluatedO. oenistrains, which leads to a less acidic taste. We show that metagenomic approaches can help uncover the complex wine microbial community traits, such as flavor, impacted by the simultaneous presence ofO. oeniandB. bruxellensis.
Could cyanobacteria have made the salinity transition during the late Archean?
Authors: Herrmann A. , Gehringer M.M.
Published: November 2017

Modern molecular evolutionary studies suggest the freshwater origin of cyanobacteria during the late Archean, about 2.7 Ga ago, with an even earlier evolution of oxidative photosynthesis. The large amount of oxygen required to oxygenate the Earth’s atmosphere during the Great Oxygenation Event (GOE) ~2.4 Ga is thought to have been produced by large cyanobacterial blooms in the open ocean. This then poses the question as to whether ancient lineages of cyanobacteria would have survived the salinity transition. This study investigates the effect of increasing salinity on the photosynthetic efficiency of two modern day descendants of ancient cyanobacteria, Chroococidiopsis thermalis PCC7203 and the root species, Gloeobacter violaceus PCC7421. Organisms were cultured in fresh, brackish or sea water analogous media under a present atmospheric level (PAL) atmosphere or an atmosphere with reduced O2 and elevated CO2 (rO2eCO2). The net photosynthesis (NP) rates were determined in liquid cultures, while the O2 and redox profiles were determined in pseudomats. While C. thermalis PCC7203 was able to grow under increasing salinities under both atmospheres tested, G. violaceus PCC7421 could not make the salinity change to sea water. NP rates were reduced for C. thermalis under increasing salinities, as were the levels of dissolved O2 in the media. A gene screen indicated that C. thermalis genome carries genes for both sucrose and trehalose synthesis, whereas G. violaceus has only the later genetic component, suggesting a mechanism for their differing salt tolerances. This study supports the hypothesis of Cyanobacterial evolution in freshwater environments and their transition into increasingly salty environments during the late Archaean, prior to the GOE.
Chemotaxis allows bacteria to overcome host-generated reactive oxygen species that constrain gland colonization
Authors: Collins Kieran D. , Hu Shuai , Grasberger Helmut , Kao John Y. , Ottemann Karen M.
Published: November 2017

The epithelial layer of the gastrointestinal tract contains invaginations, called glands or crypts, which are colonized by symbiotic and pathogenic microorganisms and may function as designated niches for certain species. Factors that control gland colonization are poorly understood, but bacterial chemotaxis aids occupation of these sites. We report here that a Helicobacter pylori cytoplasmic chemoreceptor, TlpD, is required for gland colonization in the stomach. tlpD mutants demonstrate gland colonization defects characterized by a reduction in the percent of glands colonized, but not in number of bacteria per gland. Consistent with TlpD’s reported role in reactive oxygen species (ROS) avoidance, tlpD mutants showed hallmarks of exposure to large amounts of ROS. To assess the role of host-generated ROS in TlpD-dependent gland colonization, we utilized mice that lack either the ability to generate epithelial hydrogen peroxide or immune cell superoxide. tlpD gland colonization defects were rescued to wild-type H. pylori levels in both of these mutants. These results suggest that multiple types of innate immune generated ROS production limit gland colonization and that bacteria have evolved specific mechanisms to migrate through this gauntlet to establish in the glands.

Classification: Biological sciences; microbiology

Significance statement

Microbial colonization of the gastrointestinal tract occurs at distinct sites within the tissue including glandular structures found in the stomach and intestine. Multiple lines of evidence suggest that glands supply niches that promote chronic microbial colonization, a process that is critical for symbiotic and pathogenic bacteria to maintain themselves. In this report, we show that host-produced reactive oxygen species (ROS) constrain gland colonization by the gastric pathogen Helicobacter pylori. A bacterial cytoplasmic chemoreceptor, TlpD, allows H. pylori to avoid ROS and enhances H. pylori’s ability to colonize a broad swath of glands. We propose that hosts limit gland access and spread by producing ROS, and bacteria counter with chemotactic responses that allow navigation through this gauntlet.
Three dimensional cross-modal image inference: label-free methods for subcellular structure prediction
Authors: Ounkomol Chek , Fernandes Daniel A. , Seshamani Sharmishtaa , Maleckar Mary M. , Collman Forrest , Johnson Gregory R.
Published: November 2017

Fluorescence microscopy has enabled imaging of key subcellular structures in living cells; however, the use of fluorescent dyes and proteins is often expensive, time-consuming, and damaging to cells. Here, we present a tool for the prediction of fluorescently labeled structures in live cells solely from 3D brightfield microscopy images. We show the utility of this approach in predicting several structures of interest from the same static 3D brightfield image, and show that the same tool can prospectively be used to predict the spatiotemporal position of these structures from a bright-field time series. This approach could also be useful in a variety of application areas, such as cross-modal image registration, quantification of live cell imaging, and determination of cell state changes.
Pyk2 suppresses contextual fear memory in a kinase-independent manner
Authors: Suo Lun , Zheng Jin , Zhou Yuxiao , Jia Liling , Kuang Yanping , Wu Qiang
Published: November 2017

Post-traumatic stress disorder (PTSD) is a psychological illness characterized by recalling a feeling of distress when re-experiencing the original trauma-related cues. This associative fear response plays an important role in some psychiatric disorders and elucidation of the underlying mechanisms is of great importance. Here, we constructed Pyk2 null mice and found that these mutant mice showed enhancement in contextual-fear memory, but no changes in auditory-cued and spatial-referenced learning and memory. Moreover, using kinase mutant mice, we observed that Pyk2 suppressed contextual fear memory in a kinase-independent pathway. Using high-throughput RNA sequencing, we found that immediate early genes (IEGs), such as Npas4, cFos, Zif268/Egr1, Arc, and Nr4a1, were enhanced in Pyk2 null mice. We further demonstrated that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics. Thus, we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provides a model for understanding fear-related disorders.
Dynamics and interactions of highly resolved marine plankton via automated high frequency sampling
Authors: Needham David M. , Fichot Erin B. , Wang Ellice , Berdjeb Lyria , Cram Jacob A. , Fichot Cedric G. , Fuhrman Jed A.
Published: November 2017

Short time-scale observations are valuable for understanding microbial ecological processes. We assessed dynamics in relative abundance and potential activities by sequencing the small sub-unit ribosomal RNA gene (rRNA gene) and rRNA molecules (rRNA) ofBacteria,Archaea, andEukaryotaonce to twice-daily between March 2014 and May 2014 from the surface ocean off Catalina Island, California. TypicallyOstreococcus, Braarudosphaera, Teleaulax, and Synechococcusdominated phytoplankton sequences (including chloroplasts) while SAR11,Sulfitobacter, andFluviicoladominated non-phytoplanktonBacteriaandArchaea. We observed short-lived increases of diatoms, mostlyPseudo-nitzschiaandChaetoceros, with quickly respondingBacteriaandArchaeaincludingFlavobacteriaceae(Polaribacter&Formosa),Roseovarius, andEuryarchaeota(MGII), notably the exact amplicon sequence variants we observed responding similarly to another diatom bloom nearby, three years prior. We observed correlations representing known interactions among abundant phytoplankton rRNA sequences, demonstrating the biogeochemical and ecological relevance of such interactions: 1) The kleptochloroplastidic ciliateMesodinium18S rRNA gene sequences and a singleTeleaulaxtaxon (via 16S rRNA gene sequences) were correlated (Spearmanr=0.83) yet uncorrelated to aTeleaulax18S rRNA gene OTU, or any other taxon (consistent with a kleptochloroplastidic or karyoklepty relationship) and 2) the photosynthetic prymnesiophyteBraarudosphaera bigelowiiand two strains of diazotrophic cyanobacterium UCYN-A were correlated and each taxon was also correlated to other taxa, includingB. bigelowiito a verrucomicrobium and a dictyochophyte phytoplankter (allr> 0.8). We also report strong correlations (r> 0.7) between various ciliates, bacteria, and phytoplankton, suggesting interactions via currently unknown mechanisms. These data reiterate the utility of high-frequency time-series to show rapid microbial reactions to stimuli, and provide new information aboutin-situdynamics of previously recognized and hypothesized interactions.