bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferred walking speed on rough terrain; is it all about energetics?
Authors: Gast Koren , Kram Rodger , Riemer Raziel
Published: May 2018

Humans have evolved the ability to walk very efficiently. Further, humans prefer to walk at speeds that approximately minimize their metabolic energy expenditure per unit distance (i.e. gross cost of transport, COT). This has been found in a variety of population groups and other species. However, these studies were performed on smooth, level ground or on treadmills. We hypothesized that the objective function for walking is more complex than only minimizing the COT. To test this idea, we compared the preferred speeds and the relationships between COT and speed for people walking on both a smooth, level floor and a rough, natural terrain trail. Rough terrain presumably introduces other factors, such as stability, to the objective function. 10 healthy men walked on both a straight, flat, smooth floor and on an outdoor trail strewn with rocks and boulders. In both locations, subjects performed 6-8 trials at different speeds relative to their preferred speed. The COT-speed relationships were similarly U-shaped for both surfaces, but the COT values on rough terrain were approximately 215% greater. On the smooth surface, the preferred speed (1.24+/-0.14 m/sec) was 5.1% faster (p>0.05) than the speed that minimized COT (1.18 m/sec) but on rough terrain, the preferred speed (1.06+/-0.07 m/sec) was 6.2% slower (p>0.05) than the COT minimum speed (1.13 m/sec). This suggests that the objective function when walking on rough terrain includes additional factors such as stability.

Summary statement: On rough terrain, humans do not choose their walking speed based on metabolic energy minimization alone.
Polygenic adaptation fuels genetic redundancy inDrosophila
Authors: Barghi Neda , Tobler Raymond , Nolte Viola , Jaksic Ana Marija , Mallard Francois , Otte Kathrin Anna , Dolezal Marlies , Taus Thomas , Kofler Robert , Schlöetterer Christian
Published: May 2018

The genetic architecture of adaptive traits is of key importance to predict evolutionary responses. Most adaptive traits are polygenic – i.e. result from selection on a large number of genetic loci – but most molecularly characterized traits have a simple genetic basis. This discrepancy is best explained by the difficulty in detecting small allele frequency changes across many contributing loci. To resolve this, we use laboratory natural selection, a framework that is powerful enough to detect signatures for selective sweeps and polygenic adaptation. We exposed 10 replicates of aDrosophila simulanspopulation to a new temperature regime and uncovered a polygenic architecture of an adaptive trait with high genetic redundancy among adaptive alleles. We observed convergent phenotypic responses, e.g. fitness, metabolic rate and fat content, and a strong polygenic response (99 selected alleles; means=0.061). However, each of these selected alleles increased in frequency only in a subset of the evolving replicates. Our results show that naturalD. simulanspopulations harbor a vast reservoir of adaptive variation facilitating rapid evolutionary responses. The observed genetic redundancy potentiates this genotypic variation through multiple genetic pathways leading to phenotypic convergence. This key property of adaptive alleles requires the modification of testing strategies in natural populations beyond the search for convergence on the molecular level.
Asymmetrical interference between number and item size perception provide evidence for a domain specific impairment in dyscalculia
Authors: Castaldi Elisa , Mirassou Anne , Dehaene Stanislas , Piazza Manuela , Eger Evelyn
Published: May 2018

Dyscalculia, a specific learning disability that impacts arithmetical skills, has previously been associated to a deficit in the precision of the system that estimates the approximate number of objects in visual scenes (the so called ‘number sense’ system). However, because in tasks involving numerosity comparisons dyscalculics’ judgements appears disproportionally affected by continuous quantitative dimensions (such as the size of the items), an alternative view linked dyscalculia to a domain-general difficulty in inhibiting task-irrelevant responses.

To arbitrate between these views, we evaluated the degree of reciprocal interference between numerical and non-numerical quantitative dimensions in adult dyscalculics and matched controls. We used a novel stimulus set orthogonally varying in mean item size and numerosity, putting particular attention into matching both features’ perceptual discriminability. Participants compared those stimuli based on each of the two dimensions. While control subjects showed no significant size interference when judging numerosity, dyscalculics’ numerosity judgments were strongly biased by the unattended size dimension. Importantly however, both groups showed the same degree of interference from number when judging mean size. Moreover, only the ability to discard the irrelevant size information when comparing numerosity (but not the reverse) significantly predicted calculation ability across subjects.

Overall, our results show that numerosity discrimination is less prone to interference than discrimination of another quantitative feature (mean item size) when the perceptual discriminability of these features is matched, as here in control subjects. By quantifying, for the first time, dyscalculic subjects’ degree of interference on another orthogonal dimension of the same stimuli, we are able to exclude a domain-general inhibition deficit as explanation for their poor / biased numerical judgement. We suggest that enhanced reliance on non-numerical cues during numerosity discrimination can represent a strategy to cope with a less precise number sense.
Human vicarious trial and error is predictive of spatial navigation performance
Authors: Santos-Pata Diogo , Verschure Paul FMJ
Published: May 2018

When learning new environments, rats often pause at decision points and look back and forth over their possible trajectories as if they were imagining the future outcome of their actions, a behavior termed “Vicarious trial and error” (VTE). As the animal learns the environmental configuration, rats change from deliberative to habitual behavior, and VTE tends to disappear, suggesting a functional relevance in the early stages of learning. Despite the extensive research on spatial navigation, learning and VTE in the rat model, fewer studies have focused on humans. Here, we tested whether head-scanning behaviors that humans typically exhibit during spatial navigation are as predictive of spatial learning as in the rat. Subjects performed a goal-oriented virtual navigation task in a symmetric environment. Spatial learning was assessed through the analysis of trajectories, timings, and head orientations, under habitual and deliberative spatial navigation conditions. As expected, we found that trajectory length and duration decreased with the trial number, implying that subjects learned the spatial configuration of the environment over trials. Interestingly, IdPhi (a standard metric of VTE) also decreased with the trial number, suggesting that humans benefit from the same head-orientation scanning behavior as rats at spatial decision-points. Moreover, IdPhi captured exclusively at the first decision-point of each trial, was correlated with trial trajectory duration and length. Our findings demonstrate that in VTE is a signature of the stage of spatial learning in humans, and can be used to predict performance in navigation tasks with high accuracy.
Overt social interaction and resting state in young adult males with autism: core and contextual neural features
Authors: Jasmin Kyle , Gotts Stephen J. , Xu Y. , Liu S. , Riddell Cameron , Ingeholm John , Kenworthy Lauren , Wallace Gregory L. , Braun Allen R. , Martin Alex
Published: May 2018

Conversation is an important and ubiquitous social behavior. Individuals with Autism Spectrum Disorder (autism) without intellectual disability often have normal structural language abilities but deficits in social aspects of communication like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic connections among neural circuits involved with social processing are disrupted in autism, but to date no neuroimaging study has examined neural activity during the most commonplace yet challenging social task: spontaneous conversation. Here we used functional MRI to scan autistic males (N=19) without intellectual disability and age- and IQ-matched typically developing controls (N=20) while they engaged in a total of 193 face-to-face interactions. Participants completed two kinds of tasks: Conversation, which had high social demand, and Repetition, which had low social demand. Autistic individuals showed abnormally increased task-driven inter-regional temporal correlation relative to controls, especially among social processing regions and during high social demand. Furthermore, these increased correlations were associated with parent ratings of participants’ social impairments. These results were then compared with previously-acquired resting-state data (56 Autism, 62 Control participants). While some inter-regional correlation levels varied by task or rest context, others were strikingly similar across both task and rest, namely increased correlation among the thalamus, dorsal and ventral striatum, somatomotor, temporal and prefrontal cortex in the autistic individuals, relative to the control groups. These results suggest a basic distinction. Autistic cortico-cortical interactions vary by context, tending to increase relative to controls during Task and decrease during Rest. In contrast, striato- and thalamocortical relationships with socially engaged brain regions are increased in both Task and Rest, and may be core to the condition of autism.
A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals
Authors: Carlson Jenna C. , Anand Deepti , Butali Azeez , Buxo Carmen J. , Christensen Kaare , Deleyiannis Frederic , Hecht Jacqueline T. , Moreno Lina M. , Orioli Ieda M. , Padilla Carmencita , Shaffer John R. , Vieira Alexandre R. , Wehby George L. , Weinberg Seth M. , Murray Jeffrey C. , Beaty Terri H. , Saadi Irfan , Lachke Salil A. , Marazita Mary L. , Feingold Eleanor , Leslie Elizabeth J.
Published: May 2018

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes – cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a “cleft map” of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 (CP), WNT5A (CLP)), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.
Genetic tools weed out misconceptions of strain reliability inCannabis sativa: Implications for a budding industry
Authors: Schwabe Anna L. , McGlaughlin Mitchell E.
Published: May 2018

Cannabis sativais listed as a Schedule I substance by the United States Drug Enforcement Agency and has been federally illegal in the United States since 1937. However, the majority of states in the United States, as well as several countries, now have various levels of legalCannabis. Products are labeled with identifying strain names but there is no official mechanism to registerCannabisstrains, therefore the potential exists for incorrect identification or labeling. This study uses genetic analyses to investigate strain reliability from the consumer point of view. Ten microsatellite regions were used to examine samples from strains obtained from dispensaries in three states. Samples were examined for genetic similarity within strains, and also a possible genetic distinction between Sativa, Indica, or Hybrid types. The analyses revealed genetic inconsistencies within strains. Additionally, although there was strong statistical support dividing the samples into two genetic groups, the groups did not correspond to commonly reported Sativa/Hybrid/Indica types. Genetic differences have the potential to lead to phenotypic differences and unexpected effects, which could be surprising for the recreational user, but have more serious implications for patients relying on strains that alleviate specific medical symptoms.
Absence of surface IgD does not impair naive B cell homeostasis and memory B cell formation in humans
Authors: Nechvatalova J. , Bartol S.J.W. , Chovancova Z. , Boon L. , Vlkova M. , van Zelm M.C.
Published: May 2018

One Sentence Summary

Human B cells with a genetic defect inIGHDdevelop normallyin vivo, and do not have a competitive disadvantage to IgD-expressing B cells for developing into memory B cells.

Surface immunoglobulin D (IgD) is co-expressed with IgM on naive mature B cells. Still, the role of surface IgD remains enigmatic even 50 years after its initial discovery. We here examined thein vivorole of surface IgD in human B-cell homeostasis and antibody responses in four individuals with heterozygous nonsense mutations inIGHD. AllIGHDheterozygous individuals had normal numbers of B cells and serum immunoglobulins, and did not show signs of immunodeficiency or immune dysregulation. IgD+and IgD– naive mature B cells were present in equal numbers and showed similar immunophenotypes, except for decreased expression of CD79b in the IgD– subset. Furthermore, both IgD+ and IgD– naive mature B cells had normal replication histories, similar capacities to differentiate into plasma cells uponin vitrostimulation, and Ig switched memory B cells showed similar levels of somatic hypermutations. Thus human B cells lacking IgD expression develop normally and generate immunological memoryin vivo, suggesting that surface IgD might function more restricted in regulating of B-cell activation to specific antigenic structures.
Cytokine profile in human olfactory cleft mucus and associated changes in olfactory function
Authors: Wang Hong , Jaen Cristina , Yoshikawa Keiichi , Haneoka Mai , Saito Naoko , Nakamura Junji , Adappa Nithin D. , Cohen Noam A. , Dalton Pamela
Published: May 2018

Multiple factors, including physical changes of the nasal mucosa and epithelium and exposure to air-borne environmental agents, appear to contribute to age-related olfactory loss. However, the molecular aspects of aging-associated olfactory loss in humans are not well understood. Although inflammation can be a significant underlying cause for olfactory impairment, whether aging increases the levels of inflammatory cytokines in the human olfactory mucosa and whether any inflammatory markers are associated with age-related olfactory loss remain unclear. Using a noninvasive method for collecting human olfactory mucus, we characterized and compared inflammatory cytokines, chemokines, and some growth factors, in the mucus collected from the olfactory cleft or the anterior nasal cavity from 12 healthy, young (18-40 years old) and 12 elderly (60-85 years old) individuals. We also hoped to identify candidate molecular biomarkers associated with age-associated olfactory loss in humans. Olfactory thresholds were obtained for two odorants and individual mucus samples were analyzed using multiplex assays for the levels of 30 cytokines. Results indicated elevated levels of certain inflammatory cytokines (IL-12, MCP-1) in olfactory mucus of the elderly, and high levels of some inflammatory factors (MCP-1, IL-8, IL-13 and VEGF) were associated with reduced olfactory sensitivity, suggesting that inflammation may play a role in olfactory decline associated with aging.
NAT/NCS2-hound: A Webserver for the detection and evolutionary classification of prokaryotic and eukaryotic nucleobase–cation symporters of the NAT/NCS2 family
Authors: Chaliotis A , Vlastaridis P , Ntountoumi C , Botou M , Yalelis V , Lazou P , Tatsaki E , Mossialos D , Frillingos S , Amoutzias GD
Published: May 2018

Nucleobase transporters are important for supplying the cell with purines and/or pyrimidines, for controlling the intracellular pool of nucleotides and for obtaining exogenous nitrogen/carbon sources for the metabolism. Nucleobase transporters are also evaluated as potential targets for antimicrobial therapies, since several pathogenic microorganisms rely on purine/pyrimidine salvage from their hosts. The majority of known nucleobase transporters belong to the evolutionarily conserved and ubiquitous NAT/NCS2 protein family. Based on a large-scale phylogenetic analysis that we performed on thousands of prokaryotic proteomes, we have developed a webserver that can detect and distinguish this family of transporters from other homologous families that recognize different substrates. We can further categorize these transporters to certain evolutionary groups with distinct substrate preferences. The webserver scans whole proteomes and graphically displays which proteins are identified as NAT/NCS2, to which evolutionary groups and subgroups they belong to and which conserved motifs they have. For key subgroups and motifs, the server displays annotated information from published crystal-structures and mutational studies pointing to key functional amino acids that may help experts assess the transport capability of the target sequences. The server is 100% accurate in detecting NAT/NCS2 family members. We also used the server to analyze 9109 prokaryotic proteomes and identified Clostridia, Bacilli, β- and γ-Proteobacteria, Actinobacteria and Fusobacteria as the taxa with the largest number of NAT/NCS2 transporters per proteome. An analysis of 120 representative eukaryotic proteomes also demonstrates the server’s capability of correctly analyzing this major lineage, with plants emerging as the group with the highest number of NAT/NCS2 members per proteome.
The structure of the genetic code as an optimal graph clustering problem
Authors: Błażej Paweł , Kowalski Dariusz R. , Mackiewicz Dorota , Wnetrzak Małgorzata , Aloqalaa Daniyah A. , Mackiewicz Paweł
Published: May 2018

The standard genetic code (SGC) is the set of rules by which genetic information is translated into proteins, from codons, i.e. triplets of nucleotides, to amino acids. The questions about the origin and the main factor responsible for the present structure of the code are still under a hot debate. Various methodologies have been used to study the features of the code and assess the level of its potential optimality. Here, we introduced a new general approach to evaluate the quality of the genetic code structure. This methodology comes from graph theory and allows us to describe new properties of the genetic code in terms of conductance. This parameter measures the robustness of codon groups against the potential changes in translation of the protein-coding sequences generated by single nucleotide substitutions. We described the genetic code as a partition of an undirected and unweighted graph, which makes the model general and universal. Using this approach, we showed that the structure of the genetic code is a solution to the graph clustering problem. We presented and discussed the structure of the codes that are optimal according to the conductance. Despite the fact that the standard genetic code is far from being optimal according to the conductance, its structure is characterised by many codon groups reaching the minimum conductance for their size. The SGC represents most likely a local minimum in terms of errors occurring in protein-coding sequences and their translation.
UDP-glucose:anthocyanidin 3-O-glucoside-2”-O-glucosyltransferase catalyzes further glycosylation of anthocyanins in purple Ipomoea batatas
Authors: Wang Hongxia , Wang Chengyuan , Fan Weijuan , Yang Jun , Appelhagen Ingo , Wu Yinliang , Zhang Peng
Published: May 2018

Glycosylation contributes to the diversity and stability of anthocyanins in plants. The process is catalyzed by various glucosyltransferases using different anthocyanidin aglycones and glycosyl donors. An anthocyanidin 3-O-glucoside-2”-O-glucosyltransferase (3GGT) from purple sweetpotato (cv. Ayamurasaki) served for the catalytic conversion of anthocyanidin 3-O-glucoside into anthocyanidin 3-O-sophoroside, which is functionally different from the 3GGT ortholog of Arabidopsis. The phylogenetic analysis indicates regioselectivity of 3GGT using UDP-xylose or UDP-glucose as the glycosyl is divergent between Convolvulaceae and Arabidopsis. Homology-based protein modeling and site-directed mutagenesis of Ib3GGT and At3GGT suggested that the Thr-138 of Ib3GGT is a key amino acid residue for UDP-glucose recognition and plays a major role in sugar donor selectivity. The wild type and ugt79b1 mutants of Arabidopsis plants overexpressing Ib3GGT produced the new component cyanidin 3-O-sophoroside. Moreover, Ib3GGT expression was associated with anthocyanin accumulation in different tissues during Ayamurasaki plant development and was regulated by the transcription factor IbMYB1. The localization assay of Ib3GGT showed that further glycosylation occurs in the cytosol and not endoplasmic reticulum. The present study revealed the function of Ib3GGT in further glycosylation of anthocyanins and its Thr-138 is the key amino acid residue for UDP-glucose recognition.
ProfPPIdb: pairs of physical protein-protein interactions predicted for entire proteomes
Authors: Tran Linh , Hamp Tobias , Rost Burkhard
Published: May 2018

Motivation

Protein-protein interactions (PPIs) play a key role in many cellular processes. Most annotations of PPIs mix experimental and computational data. The mix optimizes coverage, but obfuscates the annotation origin. Some resources excel at focusing on reliable experimental data. Here, we focused on new pairs of interacting proteins for several model organisms based solely on sequence-based prediction methods.

Results

We extracted reliable experimental data about which proteins interact (binary) for eight diverse model organisms from public databases, namely from Escherichia coli, Schizosaccharomyces pombe, Plasmodium falciparum, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, Rattus norvegicus, Arabidopsis thaliana, and for the previously used Homo sapiens and Saccharomyces cerevisiae. Those data were the base to develop a PPI prediction method for each model organism. The method used evolutionary information through a profile-kernel Support Vector Machine (SVM). With the resulting eight models, we predicted all possible protein pairs in each organism and made the top predictions available through a web application. Almost all of the PPIs made available were predicted between proteins that have not been observed in any interaction, in particular for less well-studied organisms. Thus, our work complements existing resources and is particularly helpful for designing experiments because of its uniqueness. Experimental annotations and computational predictions are strongly influenced by the fact that some proteins have many partners and others few. To optimize machine learning, recent methods explicitly ignored such a network-structure and rely either on domain knowledge or sequence-only methods. Our approach is independent of domain-knowledge and leverages evolutionary information. The database interface representing our results is accessible from https://rostlab.org/services/ppipair/. The data can also be downloaded from https://figshare.com/collections/ProfPPI-DB/4141784.
R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts
Authors: Barnea Maayan , Stein Merle , Winograd-Katz Sabina , Shalev Moran , Arman Esther , Brenner Ori , Thalji Fadi , Kanaan Moien , Elinav Hila , Stepensky Polina , Geiger Benjamin , Tuckermann Jan , Elson Ari
Published: May 2018

The molecular mechanisms that regulate fusion of monocytes into functional osteoclasts are virtually unknown. We describe a knock-in mouse model for the R51Q mutation in sorting nexin 10 (SNX10) that exhibits osteopetrosis and related symptoms of patients of autosomal recessive osteopetrosis linked to this mutation. Osteopetrosis arises in homozygous R51Q SNX10 mice due to a unique combination of reduced numbers of osteoclasts that are non-functional. Fusion of mutant monocytes is deregulated and occurs rapidly and continuously to form giant, non-functional osteoclasts. Mutant osteoclasts mature quickly and survive poorlyin vitro, possibly accounting for their scarcityin vivo. These cells also exhibit impaired ruffled borders, which are required for bone resorption, providing an additional basis for the osteopetrotic phenotype. More broadly, we propose that the maximal size of osteoclasts is actively determined by a genetically-regulated, cell-autonomous mechanism that limits precursor cell fusion, and for which SNX10 is required.
Histological, transcriptomic andin vitroanalysis reveal an intrinsic activated state of myogenic precursors in hyperplasic muscle of trout
Authors: Jagot Sabrina , Sabin Nathalie , Le Cam Aurélie , Bugeon Jérôme , Rescan Pierre-Yves , Gabillard Jean-Charles
Published: May 2018

Background

The dramatic increase in myotomal muscle mass in post-hatching fish is related to their ability to lastingly produce new muscle fibres, a process termed hyperplasia. The molecular and cellular mechanisms underlying fish muscle hyperplasia largely remain unknown. In this study, we aimed to characterize intrinsic properties of myogenic cells originating from fish hyperplasic muscle. For this purpose, we comparedin situproliferation,in vitrocell behavior and transcriptomic profile of myogenic precursors originating from hyperplasic muscle of juvenile trout (JT) and from non-hyperplasic muscle of fasted juvenile trout (FJT) and adult trout (AT).

Results

For the first time, we showed that myogenic precursors proliferate in hyperplasic muscle from JT as shown byin vivoBrdU labeling. This proliferative rate was very low in AT and FJT muscle. Transcriptiomic analysis revealed that myogenic cells from FJT and AT displayed close expression profiles with only 64 differentially expressed genes (BH corrected p-val < 0.001). In contrast, 2623 differentially expressed genes were found between myogenic cells from JT and from both FJT and AT. Functional categories related to translation, mitochondrial activity, cell cycle, and myogenic differentiation were inferred from genes up regulated in JT compared to AT and FJT myogenic cells. Conversely, Notch signaling pathway, that signs cell quiescence, was inferred from genes down regulated in JT compared to FJT and AT. In line with our transcriptomic data,in vitroJT myogenic precursors displayed higher proliferation and differentiation capacities than FJT and AT myogenic precursors.

Conclusions

The transcriptomic analysis and examination of cell behavior converge to support the view that myogenic cells extracted from hyperplastic muscle of juvenile trout are intrinsically more potent to form myofibres than myogenic cells extracted from non-hyperplasic muscle. The generation of gene expression profiles in myogenic cell extracted from muscle of juvenile trout may yield insights into the molecular and cellular mechanisms controlling hyperplasia and provides a useful list of potential molecular markers of hyperplasia.
Limits for resolving tandem mass tag reporter ions with identical integer mass using phase constrained spectrum deconvolution
Authors: Kelstrup Christian D. , Aizikov Konstantin , Batth Tanveer S. , Kreutzman Arne , Grinfeld Dmitry , Lange Oliver , Mourad Daniel , Makarov Alexander , Olsen Jesper V.
Published: May 2018

A popular method for peptide quantification relies on isobaric labeling such as tandem mass tags (TMT) which enables multiplexed proteome analyses. Quantification is achieved by reporter ions generated by fragmentation in a tandem mass spectrometer. However, with higher degrees of multiplexing, the smaller mass differences between the reporter ions increase the mass resolving power requirements. This contrasts with faster peptide sequencing capabilities enabled by lowered mass resolution on Orbitrap instruments. It is therefore important to determine the mass resolution limits for highly multiplexed quantification when maximizing proteome depth. Here we defined the lower boundaries for resolving TMT reporter ions with 0.0063 Da mass differences using an ultra-high-field Orbitrap mass spectrometer. We found the optimal method depends on the relative ratio between closely spaced reporter ions and that 64 ms transient acquisition time provided sufficient resolving power for separating TMT reporter ions with absolute ratio changes up to 16-fold. Furthermore, a 32 ms transient processed with phase-constrained spectrum deconvolution provides >50% more identifications with >99% quantified, but with a slight loss in quantification precision and accuracy. These findings should guide decisions on what Orbitrap resolution settings to use in future proteomics experiments relying on TMT reporter ion quantification with identical integer masses.
Modeling meiotic chromosome pairing: increased fidelity from a tug of war between telomere forces and a pairing-based Brownian ratchet
Authors: Marshall Wallace F. , Fung Jennifer C.
Published: May 2018

Meiotic homolog pairing involves associations between homologous DNA regions scattered along the length of a chromosome. When homologs associate, they tend to do so by a processive zippering processive, which apparently results from avidity effects. Using a computational model, we show that this avidity-driven processive zippering reduces the selectivity of pairing. When active random forces are applied to telomeres, this drop in selectivity is eliminated in a force-dependent manner. Further simulations suggest that active telomere forces are engaged in a tug-of-war against zippering, which can be interpreted as a Brownian ratchet with a stall force that depends on the dissociation constant of pairing. When perfectly homologous regions of high affinity compete with homeologous regions of lower affinity, the affinity difference can be amplified through this tug of war effect provided the telomere force acts in a range that is strong enough to oppose zippering of homeologs while still permitting zippering of correct homologs. The degree of unzippering depends on the radius of the nucleus, such that complete unzippering of homeologous regions can only take place if the nucleus is large enough to pull the two chromosomes completely apart. A picture of meiotic pairing thus emerges that is fundamentally mechanical in nature, possibly explaining the purpose of active telomere forces, increased nuclear diameter, and the presence of “Maverick” chromosomes in meiosis.
The Portal Project: a long-term study of a Chihuahuan desert ecosystem
Authors: Ernest S. K. Morgan , Yenni Glenda M. , Allington Ginger , Bledsoe Ellen K. , Christensen Erica M. , Diaz Renata M. , Geluso Keith , Goheen Jacob R. , Guo Qinfeng , Heske Edward , Kelt Douglas , Meiners Joan M. , Munger Jim , Restrepo Carla , Samson Douglas A. , Schutzenhofer Michele R. , Skupski Marian , Supp Sarah R. , Thibault Kate , Taylor Shawn , White Ethan , Ye Hao , Davidson Diane W. , Brown James H. , Valone Thomas J.
Published: May 2018

This is a data paper for the Portal Project, a long-term ecological study of rodents, plants, and ants located in southeastern Arizona, U.S.A. This paper contains an overview of methods and information about the structure of the data files and the relational structure among the files. This is a living data paper and will be updated with new information as major changes or additions are made to the data. All data - along with more detailed data collection protocols and site information - is archived at:https://doi.org/10.5281/zenodo.1215988.
ERVcaller: Identify polymorphic endogenous retrovirus (ERV) and other transposable element (TE) insertions using whole-genome sequencing data
Authors: Chen Xun , Li Dawei
Published: May 2018

Motivation

Approximately 8% of the human genome is derived from endogenous retroviruses (ERVs). In recent years, an increasing number of human diseases have been found to be associated with ERVs. However, it remains challenging to accurately detect the full spectrum of polymorphic (unfixed) ERVs using next-generation sequencing (NGS) data.

Results

We designed a new tool, ERVcaller, to detect and genotype transposable element (TE) insertions, including ERVs, in the human genome. We evaluated ERVcaller using both simulated and real benchmark whole-genome sequencing (WGS) datasets. By comparing with existing tools, ERVcaller consistently obtained both the highest sensitivity and precision for detecting simulated ERV and other TE insertions derived from real polymorphic TE sequences. For the WGS data from the 1000 Genomes Project, ERVcaller detected the largest number of TE insertions per sample based on consensus TE loci. By analyzing the experimentally verified TE insertions, ERVcaller had 94.0% TE detection sensitivity and 96.6% genotyping accuracy. PCR and Sanger sequencing in a small sample set verified 86.7% of examined insertion statuses and 100% of examined genotypes. In conclusion, ERVcaller is capable of detecting and genotyping TE insertions using WGS data with both high sensitivity and precision. This tool can be applied broadly to other species.

Availability

www.uvm.edu/genomics/software/ERVcaller.html

Contact

dawei.li@uvm.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Culture‐independent characterization of a novel magnetotactic member affiliated to the Beta class of the Proteobacteria phylum from an acidic lagoon
Authors: Abreu Fernanda , Leão Pedro , Vargas Gabriele , Cypriano Jefferson , Figueiredo Viviane , Enrich‐Prast Alex , Bazylinski Dennis A. , Lins Ulysses
Published: May 2018

Magnetotactic bacteria (MTB) comprise a group of motile microorganisms common in most mesothermal aquatic habitats with pH values around neutrality. However, during the last two decades, a number of MTB from extreme environments have been characterized including: cultured alkaliphilic strains belonging to the Deltaproteobacteria class of the Proteobacteria phylum; uncultured moderately thermophilic strains belonging to the Nitrospirae phylum; cultured and uncultured moderately halophilic or strongly halotolerant bacteria affiliated with the Deltaproteobacteria and Gammaproteobacteria classes and an uncultured psychrophilic species belonging to the Alphaproteobacteria class. Here, we used culture‐independent techniques to characterize MTB from an acidic freshwater lagoon in Brazil (pH ∼ 4.4). MTB morphotypes found in this acidic lagoon included cocci, rods, spirilla and vibrioid cells. Magnetite (Fe3O4) was the only mineral identified in magnetosomes of these MTB while magnetite magnetosome crystal morphologies within the different MTB cells included cuboctahedral (present in spirilla), elongated prismatic (present in cocci and vibrios) and bullet‐shaped (present in rod‐shaped cells). Intracellular pH measurements using fluorescent dyes showed that the cytoplasmic pH was close to neutral in most MTB cells and acidic in some intracellular granules. Based on 16S rRNA gene phylogenetic analyses, some of the retrieved gene sequences belonged to the genus Herbaspirillum within the Betaproteobacteria class of the Proteobacteria phylum. Fluorescent in situ hybridization using a Herbaspirillum‐specific probe hybridized with vibrioid MTB in magnetically‐enriched samples. Transmission electron microscopy of the Herbaspirillum‐like MTB revealed the presence of many intracellular granules and a single chain of elongated prismatic magnetite magnetosomes. Diverse populations of MTB have not seemed to have been described in detail in an acid environment. In addition, this is the first report of an MTB phylogenetically affiliated with Betaproteobacteria class.
Buchanania obovata: An Australian Indigenous food for diet diversification
Authors: Fyfe Selina A. , Netzel Michael E. , Tinggi Ujang , Biehl Eva M. , Sultanbawa Yasmina
Published: May 2018

Aim

Buchanania obovata Engl., the Green Plum, is a small green fruit eaten by Australian Indigenous peoples of the Northern Territory and Western Australia that has had limited study and has potential as a source of food for diet diversification. The flesh and seed of the fruit are eaten and the plant is used as bush medicine.

Methods

Physical characteristics of the fruit were measured. The flesh and seed freeze dried powders were measured separately for proximates, mineral/trace elements and heavy metals, and folate analysis. Vitamin C was analysed in the flesh.

Results

The flesh is high in protein (12.8 g/100 g dry weight (DW)) and both flesh and seed are high in dietary fibre (55.1 and 87.7 g/100 g DW, respectively). The flesh is high in potassium (2274.7 mg/100 g DW), and is a good source of magnesium (570.5 mg/100 g DW), calcium (426.0 mg/100 g DW) and phosphorous (216.8 mg/100 g DW), whereas the seed is high in iron (8.15 mg/100 g DW). The flesh contains folate at 752.4 μg/100 g DW and the seed contains 109.5 μg/100 g DW as pteroylmonoglutamic acid equivalents.

Conclusions

The flesh and seed have good nutritional properties and the results support the use of the Green Plum for diet diversification and nutrition in Indigenous and non‐Indigenous populations in Australia.
Harnessing the power of microbial nanowires
Authors: Reguera Gemma
Published: May 2018

The reduction of iron oxide minerals and uranium in model metal reducers in the genus Geobacter is mediated by conductive pili composed primarily of a structurally divergent pilin peptide that is otherwise recognized, processed and assembled in the inner membrane by a conserved Type IVa pilus apparatus. Electronic coupling among the peptides is promoted upon assembly, allowing the discharge of respiratory electrons at rates that greatly exceed the rates of cellular respiration. Harnessing the unique properties of these conductive appendages and their peptide building blocks in metal bioremediation will require understanding of how the pilins assemble to form a protein nanowire with specialized sites for metal immobilization. Also important are insights into how cells assemble the pili to make an electroactive matrix and grow on electrodes as biofilms that harvest electrical currents from the oxidation of waste organic substrates. Genetic engineering shows promise to modulate the properties of the peptide building blocks, protein nanowires and current‐harvesting biofilms for various applications. This minireview discusses what is known about the pilus material properties and reactions they catalyse and how this information can be harnessed in nanotechnology, bioremediation and bioenergy applications.
No wisdom in the crowd: genome annotation in the era of big data – current status and future prospects
Authors: Danchin Antoine , Ouzounis Christos , Tokuyasu Taku , Zucker Jean‐Daniel
Published: May 2018

Science and engineering rely on the accumulation and dissemination of knowledge to make discoveries and create new designs. Discovery‐driven genome research rests on knowledge passed on via gene annotations. In response to the deluge of sequencing big data, standard annotation practice employs automated procedures that rely on majority rules. We argue this hinders progress through the generation and propagation of errors, leading investigators into blind alleys. More subtly, this inductive process discourages the discovery of novelty, which remains essential in biological research and reflects the nature of biology itself. Annotation systems, rather than being repositories of facts, should be tools that support multiple modes of inference. By combining deduction, induction and abduction, investigators can generate hypotheses when accurate knowledge is extracted from model databases. A key stance is to depart from ‘the sequence tells the structure tells the function’ fallacy, placing function first. We illustrate our approach with examples of critical or unexpected pathways, using MicroScope to demonstrate how tools can be implemented following the principles we advocate. We end with a challenge to the reader.
Is there gender convergence in risky drinking when taking birth cohorts into account? Evidence from an Australian national survey 2001–13
Authors: Livingston Michael , Callinan Sarah , Dietze Paul , Stanesby Oliver , Kuntsche Emmanuel
Published: May 2018

Background and aims

Recent studies have argued that there has been substantial gender convergence in alcohol consumption. However, many of these rely on comparisons of different cohorts and do not adjust for age differences in male and female drinking patterns. We aimed to examine (1) whether the gender gap in risky drinking in Australia narrowed between 2001 and 2013, (2) if the evidence for gender convergence (or divergence) was consistent across age groups and (3) how a cohort‐focused analysis of gender convergence compared with an age‐focused approach.

Design

Repeated cross‐sectional data from five waves of the National Drug Strategy Household Survey (2001, 2004, 2007, 2010, 2013). Interaction terms in logistic and linear regression models were used to test for significantly different trends between men and women.

Setting

Australia.

Participants

Australians aged 14 years and older (n = 125 215) who provided data on alcohol consumption in the National Drug Strategy Household Survey.

Measurements

Prevalence of long‐term risky drinking (average of 20 g or more per day) and prevalence of risky single occasion drinking (12 or more sessions of 50 g or more).

Findings

Gender differences were large for all age groups except adolescents (14–17‐year‐olds), with men typically reporting levels of drinking at least twice as high as women across the study period. Overall, there was statistically significant gender convergence in alcohol use measures showing a slight decrease in men's drinking and a slight increase in women's drinking. However, when age‐specific analyses were conducted gender convergence was only observed for 50–69‐year‐olds.

Conclusions

In Australia, gender convergence in risky drinking since 2001 has been evident only in people aged 50–69 years.
The effect of parental drinking on alcohol use in young adults: the mediating role of parental monitoring and peer deviance
Authors: Mahedy Liam , MacArthur Georgina J. , Hammerton Gemma , Edwards Alexis C. , Kendler Kenneth S. , Macleod John , Hickman Matthew , Moore Simon C. , Heron Jon
Published: May 2018

Background and Aims

Evidence demonstrating an association between parental alcohol use and offspring alcohol use from robust prospective studies is lacking. We tested the direct and indirect associations between parental and young adult alcohol use via early alcohol initiation, parental monitoring and associating with deviant peers.

Design

Prospective birth cohort study. Path analysis was used to assess the possible association between parental alcohol use (assessed at 12 years) and alcohol use in young adults (assessed at 18 years) via potential mediators (assessed at 14 and 15.5 years, respectively).

Setting

South West England.

Participants

Data were available on 3785 adolescents and their parents from the Avon Longitudinal Study of Parents and Children.

Measurements

The continuous Alcohol Use Disorders Identification Test (AUDIT) score was used as the primary outcome measure. Maternal alcohol use was defined as light (< 4 units on any day), moderate (≥ 4 units on 1–3 days) and high‐risk (≥ 4 units on ≥ 4 days in 1 week). Partner alcohol use was also defined as light, moderate and high risk. Socio‐economic variables were included as covariates.

Findings

There was strong evidence of a total effect from maternal alcohol use to young adult alcohol use [moderate: b = 1.07, 95% confidence interval (CI) = 0.64, 1.49, P < 0.001; high risk: b = 1.71, 95% CI = 1.07, 2.35, P < 0.001]. The majority of this association was explained through early alcohol initiation (moderate: b = 0.14, 95% CI = 0.04, 0.25, P = 0.01; high risk: b = 0.24, 95% CI = 0.07, 0.40, P < 0.01) and early alcohol initiation/associating with deviant peers (moderate: b = 0.06, 95% CI = 0.02, 0.10, P < 0.01; high risk: b = 0.10, 95% CI = 0.03, 0.16, P < 0.01). There was strong evidence of a remaining direct effect (moderate: b = 0.81, 95% CI = 0.39, 1.22, P < 0.001; high risk: b = 1.28, 95% CI = 0.65, 1.91, P < 0.001). A similar pattern of results was evident for partner alcohol use.

Conclusions

Young adults whose parents have moderate or high‐risk alcohol consumption are more likely to consume alcohol than those with parents with lower alcohol consumption. This association appears to be partly accounted for by earlier alcohol use initiation and higher prevalence of association with deviant peers.
Evolution of clinical characteristics and outcomes of synthetic cannabinoid receptor agonist exposure in the United States: analysis of National Poison Data System data from 2010 to 2015
Authors: Cordeiro Samuel K. , Daro Ryan C. , Seung Hyunuk , Klein‐Schwartz Wendy , Kim Hong K.
Published: May 2018

Background and aims

New synthetic cannabinoid receptor agonists (SCRAs) are synthesized each year to evade US governmental regulation and sold for recreational use. Our aim was to estimate the changes in the clinical effects and patient disposition associated with SCRA exposure from 2010 to 2015.

Design

A retrospective observational cohort study.

Setting

National Poison Data System that collects data on reports of poisonings from US poison centers.

Participants

A total of 19 388 isolated SCRA cases between 1 January 2010 and 31 December 2015 were identified. The mean age was 24.6 years and 77.8% were male.

Measurements

Primary outcome was the change in the trend of patient disposition, i.e. treated and released versus hospitalization (e.g. non‐critical care, critical care unit or psychiatry) between 2010 and 2015. Secondary outcomes included the trends in the clinical effects and their duration, and therapeutic interventions nationally and regionally.

Findings

Reports of SCRA exposure peaked in 2011 (n = 5305) and 2015 (n = 5475). The majority of patients required supportive care and were treated and released from an emergency department. Hospitalization increased by annual percentage change in the log odds (APCO) of 21.0% (P < 0.0001) during the 6 years, with significant increases in admissions to critical care units and non‐critical care units. Overall, tachycardia (32.1%), agitation/irritation (25.6%) and drowsiness/lethargy (20.4%) were the most frequently reported clinical effects from SCRA exposure. Clinical effects resolved within 2–8 hours in 52.8% of cases, but their duration increased markedly by 2015. Regionally, the largest number of SCRA cases was reported in the South (n = 9374, 48.6%). SCRA cases in the Northeast were hospitalized more frequently (27.4%), with cases in the Midwest being admitted more frequently to critical care units (15.3%). However, there were no significant differences in clinical toxicity or disposition among the regions.

Conclusion

Hospitalization resulting from toxicity from synthetic cannabinoid receptor agonists exposure in the United States increased significantly between 2010 and 2015.