bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific co-expression networks and sex-biased gene expression in the salmonid Brook Charr Salvelinus fontinalis
Authors: Sutherland Ben J. G. , Prokkola Jenni M. , Audet Céline , Bernatchez Louis
Published: April 2018

Networks of co-expressed genes produce complex phenotypes associated with functional novelty. Sex differences in gene expression levels or in the structure of gene co-expression networks can cause sexual dimorphism and may resolve sexually antagonistic selection. Here we used RNA-sequencing in the paleopolyploid salmonid Brook Charr Salvelinus fontinalis to characterize sex-specific co-expression networks in the liver of 47 female and 53 male offspring. In both networks, modules were characterized for functional enrichment, hub gene identification, and associations with 15 growth, reproduction, and stress-related phenotypes. Modules were then evaluated for preservation in the opposite sex, and in the congener Arctic Charr Salvelinus alpinus. Overall, more transcripts were assigned to a module in the female network than in the male network, which coincided with higher inter-individual gene expression and phenotype variation in the females. Most modules were preserved between sexes and species, including those involved in conserved cellular processes (e.g. translation, immune pathways). However, two sex-specific male modules were identified, and these may contribute to sexual dimorphism. To compare with the network analysis, differentially expressed transcripts were identified between the sexes, finding a total of 16% of expressed transcripts as sex-biased. For both sexes, there was no overrepresentation of sex-biased genes or sex-specific modules on the putative sex chromosome. Sex-biased transcripts were also not overrepresented in sex-specific modules, and in fact highly male-biased transcripts were enriched in preserved modules. Comparative network analysis and differential expression analyses identified different aspects of sex differences in gene expression, and both provided new insights on the genes underlying sexual dimorphism in the salmonid Brook Charr.
Circuit mechanisms for the maintenance and manipulation of information in working memory
Authors: Masse Nicolas Y. , Yang Guangyu R. , Song H. Francis , Wang Xiao-Jing , Freedman David J.
Published: April 2018

Recently it has been proposed that information in short-term memory may not always be stored in persistent neuronal activity, but can be maintained in “activity-silent” hidden states such as synaptic efficacies endowed with short-term plasticity (STP). However, working memory involves manipulation as well as maintenance of information in the absence of external stimuli. In this work, we investigated working memory representation using recurrent neural network (RNN) models trained to perform several working memory dependent tasks. We found that STP can support the short-term maintenance of information provided that the memory delay period is sufficiently short. However, in tasks that require actively manipulating information, persistent neuronal activity naturally emerges from learning, and the amount of persistent neuronal activity scales with the degree of manipulation required. These results shed insight into the current debate on working memory encoding, and suggest that persistent neural activity can vary markedly between tasks used in different experiments.
Multi-model inference of non-random mating from an information theoretic approach
Authors: Carvajal-Rodriguez Antonio
Published: April 2018

Non-random mating has a significant impact on the evolution of organisms. Here, I developed a modelling framework for discrete traits (with any number of phenotypes) to explore different models connecting the non-random mating causes (intra sexual competition and/or mate choice) and their consequences (sexual selection and/or assortative mating).

I derived the formulas for the maximum likelihood estimates of each model and used information criteria for performing multimodel inference. Simulation results showed a good performance of both model selection and parameter estimation. The methodology was applied to data from GalicianLittorina saxatilisecotypes, to show that the mating pattern is better described by models with two parameters that involve both mate choice and intrasexual competition, generating positive assortative mating plus female sexual selection.

As far as I know, this is the first standardized methodology for model selection and multimodel inference of mating parameters for discrete traits. The advantages of this framework include the ability of setting up models from which the parameters connect causes, as intrasexual competition and mate choice, with their outcome in the form of data patterns of sexual selection and assortative mating. For some models, the parameters may have a double effect i.e. they cause both kind of patterns, while for others models there are separated parameters for one kind of pattern or another.

The full methodology was implemented in a software called InfoMating (available athttp://acraaj.webs6.uvigo.es/InfoMating/Infomating.htm).
Geminivirus Replication Protein impairs SUMO conjugation of PCNA at two acceptor sites
Authors: Arroyo-Mateos Manuel , Sabarit Blanca , Maio Francesca , Sánchez-Durán Miguel A. , Rosas-Díaz Tabata , Prins Marcel , Ruiz-Albert Javier , Luna Ana P , van den Burg Harrold A. , Bejarano Eduardo R.
Published: April 2018

Geminiviruses are DNA viruses that replicate in nuclei of infected plant cells using the plant DNA replication machinery, including PCNA (Proliferating cellular nuclear antigen), a cofactor that orchestrates genome duplication and maintenance by recruiting crucial players to replication forks. These viruses encode a multifunctional protein, Rep, which is essential for viral replication, induces the accumulation of the host replication machinery and interacts with several host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Post-translational modification of PCNA by ubiquitin or SUMO plays an essential role in the switching of PCNA between interacting partners during DNA metabolism processes (e.g. replication, recombination, repair, etc.). In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that ectopic Rep expression results in very specific changes in the sumoylation pattern of plant cells. In this work, we show, using a reconstituted sumoylation system inEscherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we confirm that PCNA is sumoylatedin plantaand that Rep also interferes with PCNA sumoylation in plant cells.

Importance

SUMO adducts have a key role in regulating the activity of animal and yeast PCNA on DNA repair and replication. Our work demonstrates for the first time that sumoylation of plant PCNA occurs in plant cells and that a plant virus interferes with this modification. This work marks the importance of sumoylation in allowing viral infection and replication in plants. Moreover, it constitutes a prime example of viral proteins interfering with post-translational modifications of selected host factors to create a proper environment for infection.
Proteins in the periplasmic space and outer membrane vesicles ofRhizobium etliCE3 grown in minimal medium are largely distinct and change with growth phase
Authors: Taboada Hermenegildo , Meneses Niurka , Dunn Michael F. , Vargas-Lagunas Carmen , Buchs Natasha , Castro-Mondragon Jaime A. , Heller Manfred , Encarnación Sergio
Published: April 2018

Rhizobium etliCE3 grown in succinate-ammonium minimal medium (MM) excreted outer membrane vesicles (OMVs) with diameters of 40 to 100 nm. Proteins from the OMVs and the periplasmic space were isolated from 6 and 24 h cultures and identified by proteome analysis. A total 770 proteins were identified: 73.8 and 21.3 % of these proteins occurred only in the periplasm and OMVs, respectively, and only 4.9 % were found in both locations. The majority of proteins found in either location were present only at 6 or 24 h: in the periplasm and OMVs, only 24 and 9 % of proteins, respectively, were present at both sampling times, indicating a time-dependent differential sorting of proteins into the two compartments. The OMVs contained proteins with physiologically varied roles, includingRhizobiumadhering proteins (Rap), polysaccharidases, polysaccharide export proteins, autoaggregation and adherence proteins, glycosyl transferases, peptidoglycan binding and cross-linking enzymes, potential cell wall modifying enzymes, porins, multidrug efflux RND family proteins, ABC transporter proteins, and heat shock proteins. As expected, proteins with known periplasmic localizations (phosphatases, phosphodiesterases, pyrophosphatases) were found only in the periplasm, along with numerous proteins involved in amino acid and carbohydrate metabolism and transport. Nearly one-quarter of the proteins present in the OMVs were also found in our previous analysis of theR. etlitotal exproteome of MM-grown cells, indicating that these nanoparticles are an important mechanism for protein excretion in this species.

IMPORTANCE

The reduction of atmospheric nitrogen to ammonia by rhizobia symbiotically associated with legumes is of major importance in sustainable agricultural. Rhizobia excrete a variety of symbiotically important proteins using canonical secretion systems. In this work, we show thatRhizobium etligrown in culture also excretes proteins in membrane-enclosed structures called outer membrane vesicles (OMVs). This study reports OMV production by rhizobia. Proteins identified in the OMVs included Rhizobium adhering (Rap) and autoaggregation proteins, polysaccharidases, RTX toxins, porins and multidrug efflux proteins. Some of these proteins have important roles in theR. etli-common bean symbiosis, and their packaging into OMVs could deliver them to the environment in a concentrated yet diffusible form protected from degradation. The work described here provides a basis for future studies on the function of rhizobial OMVs in free life and symbiosis.
T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses
Authors: Herrera Bobby Brooke , Tsai Wen-Yang , Brites Carlos , Luz Estela , Pedroso Celia , Drexler Jan Felix , Wang Wei-Kung , Kanki Phyllis J.
Published: April 2018

The 2015-16 Zika virus (ZIKV) epidemic in the Americas and the Caribbean demonstrates that clinical assays to detect, distinguish, and characterize immune responses to flaviviral infections are needed. ZIKV and dengue virus (DENV) are mosquito-transmitted flaviviruses sharing overlapping geographical distribution and have significant sequence similarity that can increase the potential for antibody and T cell cross-reaction. Using nonstructural protein 1-based enzyme-linked immunosorbent assays (ELISAs), we determine the serostatus of individuals living in a DENV- and ZIKV-endemic region in Brazil, identifying individuals with primary DENV (pDENV) and ZIKV (pZIKV), ZIKV with primary DENV (ZIKVwpDENV), and secondary DENV (sDENV) infections; pDENV and pZIKV were further confirmed by neutralization tests. Development of an enzyme-linked immunospot (ELISPOT) assay for DENV and ZIKV structural and nonstructural (NS) protein antigens enables us to distinguish infections by these viruses based on T cells and to characterize those responses. We find that IFN-γ and TNF-α T cell responses to NS3 differentiates DENV and ZIKV infections with 94% sensitivity and 92% specificity. In general, we also show that pDENV and sDENV cases and pZIKV and ZIKVwpDENV cases elicit similar T cell response patterns, and that HIV-infected individuals have T cell responses that are lower in magnitude compared to HIV-negative individuals. These results have important implications for DENV and ZIKV diagnostic and vaccine development and provide critical insights into the T cell response in individuals with multiple flaviviral infections.
Large-scale organization of the hand action observation network in individuals born without hands
Authors: Vannuscorps Gilles , Wurm Moritz , Striem-Amit Ella , Caramazza Alfonso
Published: April 2018

The human high-level visual cortex comprises regions specialized for the processing of distinct types of stimuli, such as objects, animals, and human actions. How does this specialization emerge? Here, we investigated the role of sensorimotor experience in shaping the organization of the action observation network as a window on this question. Observed body movements are frequently coupled with corresponding motor codes, e.g. during monitoring one’s own movements and imitation, resulting in bidirectionally connected circuits between areas involved in body movements observation (e.g., of the hand) and the motor codes involved in their execution. If the organization of the action observation network is shaped by this sensorimotor coupling, then, it should not form for body movements that do not belong to individuals’ motor repertoire. To test this prediction, we used fMRI to investigate the spatial arrangement and functional properties of the hand and foot action observation circuits in individuals born without upper limbs. Multivoxel pattern decoding, pattern similarity, and univariate analyses revealed an intact hand action observation network in the individuals born without upper limbs. This suggests that the organization of the action observation network does not require effector-specific visuomotor coupling.
Parkinsons disease and bacteriophages as its overlooked contributors
Authors: Tetz George , Brown Stuart , Hao Yuhan , Tetz Victor
Published: April 2018

Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinsons disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.
Modelling the emergence of an egalitarian society in the n-player game framework
Authors: Tamura Kohei , Takikawa Hiroki
Published: April 2018

Unlike other primates, human foragers have an egalitarian society. Therefore, the evolution of egalitarian behaviour has been the subject of long-standing debate in a wide variety of disciplines. A recent hypothesis states that a social control against potentially dominant individuals played an important role in the emergence of an egalitarian society, although this has not been modelled directly. In the present study, we modelled this hypothesis based on the n-player game framework, in which the owner, who may attempt to monopolise resources, could be punished by a coalition of other group members. Our results suggest that a potentially despotic payoff structure can promote the evolution of egalitarian behaviour. Besides, large group size, small cost of competition, and variation in the strengths of individuals can promote the evolution of egalitarian behaviour. Our results suggest the importance of both social control against dominant individuals and benefits of a coalition for the evolution of egalitarian behaviour.
Differential valuation and learning from social and non-social cues in Borderline Personality Disorder
Authors: Fineberg Sarah K , Leavitt Jacob , Stahl Dylan S , Kronemer Sharif , Landry Christopher D. , Alexander-Bloch Aaron , Hunt Laurence T , Corlett Philip R
Published: April 2018

Background

Volatile interpersonal relationships are a core feature of Borderline Personality Disorder (BPD), and lead to devastating disruption of patients’ personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus non-social information, and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models.

Methods

Subjects (n=20 BPD, n=23 control) played an extended reward learning task with a partner (confederate) that requires learning about non-social and social cue reward probability (The Social Valuation Task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects’ weighting of social and non-social cues was tested in mixed-effects regression models. Subjects’ learning rates under stable and volatile conditions were modelled (Rescorla-Wagner approach) and group x condition interactions tested.

Results

Compared to controls, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily, but had blunted learning responses to (non-social and social) volatility.

Conclusions

This is the first report of patient behavior in the Social Valuation Task. The results suggest that BPD subjects expect higher volatility than do controls. These findings lay the groundwork for a neuro-computational dissection of social and non-social belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.
Immunomodulatory Role of Keratin 76 in Oral and Gastric Cancer
Authors: Sequeira Inês , Neves Joana F. , Carrero Dido , Peng Qi , Palasz Natalia , Liakath-Ali Kifayathullah , Lord Graham M. , Morgan Peter R. , Lombardi Giovanna , Watt Fiona M.
Published: April 2018

Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas (OSCC) correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76−/−Tregs have increased suppressive ability correlated with increased CD39 and CD73 expression, while their effector T cells are less proliferative than controls. Loss of Krt76 increases carcinogen-induced tumours in tongue and squamous stomach. Carcinogenesis is further increased when Treg levels are elevated experimentally. The carcinogenesis response includes upregulation of pro-inflammatory cytokines and enhanced accumulation of Tregs in the tumour microenvironment. Tregs also accumulate in human OSCC exhibiting Krt76 loss. Our study highlights the role of epithelial cells in modulating carcinogenesis via communication with cells of the immune system.
Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation
Authors: Serajpour Niloofar , Karimi Behnaz , Hooman Nakisa , Hosseini Rozita , Khosravi Pedram , Rasouly Hila Milo , Shojaei Azadeh
Published: April 2018

Background: Nephrotic syndrome is one of the most common kidney diseases in childhood. About 20% of children are steroid-resistant NS (SRNS) which progress to end-stage renal disease (ESRD). More than 53 genes are associated with SRNS which represent the genetic heterogeneity of SRNS. This study was aimed to screen disease causing mutations within NPHS1 and NPHS2 and evaluate new potential variants in other genes.

Method: In first phase of study, 25 patients with SRNS were analyzed for NPHS1 (exon 2, 26) and all exons of NPHS2 genes by Sanger sequencing. In the second phase, whole exome sequencing was performed on 10 patients with no mutations in NPHS1 and NPHS2.

Result: WES analysis revealed a novel mutation in FAT1 (c.10570C>A; Q3524K). We identified 4 pathogenic mutations, located in exon 4 and 5 of NPHS2 gene in 20% of patients (V180M, P118L, R168C and Leu156Phe). Also our study has contributed to the descriptions of previously known pathogenic mutations across WT1 (R205C) and SMARCAL1 (R764Q) and a novel polymorphism in CRB2.

Conclusion: Our study concludes that mutations of exon 4 and 5 NPHS2 gene are common in Iranian and some other ethnic groups. We suggest conducting WES after NPHS2 screening and further comprehensive studies to identify the most common genes in the development of SRNS, which might help in Clinical impact on management in patients with SRNS.

Detection of a novel mutation in SRNS
Probing brain developmental patterns of myelination and associations with psychopathology in youth using gray/white matter contrast
Authors: Norbom Linn B. , Doan Nhat Trung , Alnæs Dag , Kaufmann Tobias , Moberget Torgeir , Rokicki Jaroslav , Andreassen Ole A. , Westlye Lars T. , Tamnes Christian K.
Published: April 2018

Background

Cerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted magnetic resonance images (MRI).

Methods

To test the sensitivity of gray/white matter contrast (GWC) to age and individual differences in psychopathology and general cognitive ability in youth (8-23 years), we formed data-driven psychopathology and cognitive components using a large population-based sample, the Philadelphia Neurodevelopmental Cohort (PNC) (n=6487, 52% females). We then tested for associations with regional GWC defined by an independent component analysis (ICA) in a subsample with available MRI data (n=1467, 53% females).

Results

The analyses revealed a global GWC component, which showed an age-related decrease from late childhood and across adolescence. In addition, we found regional anatomically meaningful components with differential age associations explaining variance beyond the global component. When accounting for age and sex, both higher symptom levels of anxiety or prodromal psychosis and lower cognitive ability were associated with higher GWC in insula and cingulate cortices and with lower GWC in pre- and postcentral cortices. We also found several additional regional associations with anxiety, prodromal psychosis and cognitive ability.

Conclusion

Independent modes of GWC variation are sensitive to global and regional brain developmental processes, possibly related to differences between intracortical and subjacent white matter myelination, and individual differences in regional GWC are associated with both mental health and general cognitive functioning.
Spontaneous behaviors drive multidimensional, brain-wide activity
Authors: Stringer Carsen , Pachitariu Marius , Steinmetz Nicholas , Reddy Charu Bai , Carandini Matteo , Harris Kenneth D.
Published: April 2018

Cortical responses to sensory stimuli are highly variable, and sensory cortex exhibits intricate spontaneous activity even without external sensory input. Cortical variability and spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Here, by recording over 10,000 neurons in mouse visual cortex, we show that spontaneous activity reliably encodes a high-dimensional latent state, which is partially related to the mouse’s ongoing behavior and is represented not just in visual cortex but across the forebrain. Sensory inputs do not interrupt this ongoing signal, but add onto it a representation of visual stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information.
A multidisciplinary approach towards identification of novel antibiotic scaffolds forAcinetobacter baumannii
Authors: Bhamidimarri Satya Prathyusha , Zahn Michael , Prajapati Jigneshkumar Dahyabhai , Schleberger Christian , Söderholm Sandra , Hoover Jennifer , West Josh , Kleinekathöfer Ulrich , Bumann Dirk , Winterhalter Mathias , van den Berg Bert
Published: April 2018

Research efforts to discover potential new antibiotics for Gram-negative bacteria suffer from high attrition rates due to the synergistic action of efflux systems and the limited permeability of the outer membrane (OM). One potential strategy to overcome the OM permeability barrier is to identify small molecules that are natural substrates for abundant OM channels, and to use such compounds as scaffolds for the design of efficiently-permeating antibacterials. Here we present a multidisciplinary approach to identify such potential small-molecule scaffolds. Focusing on the pathogenic bacteriumAcinetobacter baumannii, we use OM proteomics to identify DcaP as the most abundant channel under various conditions that are relevant for infection. High-resolution X-ray structure determination of DcaP surprisingly reveals a trimeric, porin-like structure and suggests that dicarboxylic acids are potential transport substrates. Electrophysiological experiments and allatom molecular dynamics simulations confirm this notion and provide atomistic information on likely permeation pathways and energy barriers for several small molecules, including a clinically-relevant β-lactamase inhibitor. Our study provides a general blueprint for the identification of molecular scaffolds that will inform the rational design of future antibacterials.
gmxapi: a high-level interface for advanced control and extension of molecular dynamics simulations
Authors: Irrgang M. Eric , Hays Jennifer M. , Kasson Peter M.
Published: April 2018

Molecular dynamics simulations have found use in a wide variety of biomolecular applications, from protein folding kinetics to computational drug design to refinement of molecular structures. Two areas where users and developers frequently need to extend the built-in capabilities of most software packages are implementing custom interactions, for instance biases derived from experimental data, and running ensembles of simulations. We present a Python high-level interface for the popular simulation package GROMACS that 1) allows custom potential functions without modifying the simulation package code, 2) maintains the optimized performance of GROMACS, and 3) presents an abstract interface to building and executing computational graphs that allows transparent low-level optimization of data flow and task placement. Minimal dependencies make this integrated API for the GROMACS simulation engine simple, portable, and maintainable. We demonstrate this API for experimentally-driven refinement of protein conformational ensembles.

Availability

Source and installation instructions are available at https://github.com/kassonlab/gmxapi.
Early candidate biomarkers in urine of Walker-256 lung metastasis rat model
Authors: Wei Jing , Ni Na , Zhang Linpei , Gao Youhe
Published: April 2018

Cancer metastasis accounts for the majority of deaths by cancer. Detection of cancer metastasis at its early stage is important for the management and prediction of cancer progression. Urine, which is not regulated by homeostatic mechanisms, reflects systemic changes in the whole body and can potentially be used for the early detection of cancer metastasis. In this study, a lung metastasis of a Walker-256 rat model was established by tail-vein injection of Walker-256 cells. Urine samples were collected at days 2, 4, 6 and 9 after injection, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The urinary protein patterns changed significantly with the development of Walker-256 lung metastasis. On the fourth day, lung metastasis nodules appeared. On the sixth day, clinical symptoms started. On days 2, 4, 6 and 9, 11, 25, 34 and 44 differential proteins were identified in 7 lung metastatic rats by LC-MS/MS. Seventeen of these 62 differential proteins were identified on the second day, and 18 of them were identified on the fourth day. The differential urinary proteins changed significantly two days before lung metastasis nodules appeared. Differential urinary proteins differed in Walker-256 lung metastasis rat models and Walker-256 subcutaneous rat models. A total of 9 differential proteins (NHRF1, CLIC1, EZRI, AMPN, ACY1A, HSP7C, BTD, NID2, and CFAD) were identified in 7 lung metastatic rats at one or more common time points, and these 9 differential proteins were not identified in the subcutaneous rat model. Seven of these 9 differential proteins were associated with both breast cancer and lung cancer, eight of the nine were identified on the second day, and 8 of the nine can be identified on the fourth day; these early changes in urine were also identified with differential abundances at late stages of lung metastasis. Our results indicate that (1) the urine proteome changed significantly, even on the second day after tail-vein injection of Walker-256 cells and that (2) the urinary differential proteins were different in Walker-256 lung metastatic tumors and Walker-256 subcutaneous tumors. Our results provide the potential to detect early breast cancer lung metastasis, monitor its progression and differentiate it from the same cancer cells grown at other locations.
Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction
Authors: Garza-Villarreal Eduardo A , Alcalá-Lozano Ruth , Balducci Thania , Ángeles-Valdéz Diego , Chakravarty M. Mallar , Devenyi Gabriel A. , Gonzalez-Olvera Jorge J
Published: April 2018

Substance addiction is regarded as an important public health problem, perpetuated by fronto-striatal circuit pathology. A usual finding in neuroimaging human and murine studies is cortical thinning and lower volume when compared to healthy controls. In this study we wished to replicate cortical thinning findings and find if striatum morphology may explain the cortical pathology. For this we analyzed T1w neuroimaging data from an ongoing addiction Mexican dataset. This dataset includes cocaine addicts diagnosed by expert psychiatrists and healthy controls. For the analysis we used voxel-based morphometry, cortical thickness and volumetric analysis of the basal ganglia, and we correlated striatum volume with cortical thickness to find pathological patterns. Our group contrast showed cortical thinning and striatum volume differences in cocaine addicts correlated to their years of substance use, craving and age. Our correlation between striatum-cortex morphology showed higher significant correlations in healthy controls, not observed in cocaine addicts. The correlation between striatum volume and cortical thickness in healthy controls involved similar areas as those shown with less cortical thickness in cocaine addicts. We suggest that striatum morphological changes in addiction may explain the pattern of cortical thinning observed across several substances addiction studies.

Research Data Related to this Submission

Data sethttps://zenodo.org/record/1409808#.W5E3oCOZPIF Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction

This dataset includes all the data and scripts needed to reproduce the analysis and results on the manuscript “Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction” (link). The brain data is not raw, as T1w were not defaced. We will do so in the near future for version 2.0. Instead we include only the “output/thickness” files used in the final analysis. For the use of raw T1w images, please contact the main author EAGV.
DNA polymerase β fingers movement revealed by single-molecule FRET suggests a partially closed conformation as a fidelity checkpoint
Authors: Fijen Carel , Mahmoud Mariam , Kaup Rebecca , Towle-Weicksel Jamie , Sweasy Joann , Hohlbein Johannes
Published: April 2018

The eukaryotic DNA polymerase β plays an important role in cellular DNA repair as it fills gaps in single nucleotide gapped DNA that result from removal of damaged bases. Since defects in DNA repair may lead to cancer and genetic instabilities, Pol β has been extensively studied, especially substrate binding and a fidelity-related conformational change called fingers closing. Here, we applied single-molecule Förster resonance energy transfer to study the conformational dynamics of Pol β. Using an acceptor labelled polymerase and a donor labelled DNA substrate, we measured distance changes associated with DNA binding and fingers movement. Our findings suggest that Pol β does not bend its gapped DNA substrate to the extent related crystal structures indicate: instead, bending seems to be significantly less profound. Furthermore, we visualized dynamic fingers closing in single Pol β-DNA complexes upon addition of complementary nucleotides and derived rates of conformational changes. Additionally, we provide evidence that the fingers close only partially when an incorrect nucleotide is bound. This ajar conformation found in Pol β, a polymerase of the X-family, suggests the existence of an additional fidelity checkpoint similar to what has been previously proposed for a member of the A-family, the bacterial DNA polymerase I.
FMRIPrep: a robust preprocessing pipeline for functional MRI
Authors: Esteban Oscar , Markiewicz Christopher J. , Blair Ross W. , Moodie Craig A. , Isik A. Ilkay , Erramuzpe Asier , Kent James D. , Goncalves Mathias , DuPre Elizabeth , Snyder Madeleine , Oya Hiroyuki , Ghosh Satrajit S. , Wright Jessey , Durnez Joke , Poldrack Russell A. , Gorgolewski Krzysztof J.
Published: April 2018

Preprocessing of functional MRI (fMRI) involves numerous steps to clean and standardize data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each new dataset, building upon a large inventory of tools available for each step. The complexity of these workflows has snowballed with rapid advances in MR data acquisition and image processing techniques. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for task-based and resting fMRI data. FMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing with no manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software-testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection comprising participants from 54 different studies in the OpenfMRI repository. We review the distinctive features of fMRIPrep in a qualitative comparison to other preprocessing workflows. We demonstrate that fMRIPrep achieves higher spatial accuracy as it introduces less uncontrolled spatial smoothness than commonly used preprocessing tools. FMRIPrep has the potential to transform fMRI research by equipping neuroscientists with a high-quality, robust, easy-to-use and transparent preprocessing workflow which can help ensure the validity of inference and the interpretability of their results.
HaploJuice: Accurate haplotype assembly from a pool of sequences with known relative concentrations
Authors: Wong Thomas K. F. , Ranjard Louis , Lin Yu , Rodrigo Allen G.
Published: April 2018

Pooling techniques, where multiple sub-samples are mixed in a single sample, are widely used to take full advantage of high-throughput DNA sequencing. Recently, Ranjard et al. [1] proposed a pooling strategy without the use of barcodes. Three sub-samples were mixed in different known proportions (i.e. 62.5%, 25% and 12.5%), and a method was developed to use these proportions to reconstruct the three haplotypes effectively. HaploJuice provides an alternative haplotype reconstruction algorithm for Ranjard et al.’s pooling strategy. HaploJuice significantly increases the accuracy by first identifying the empirical proportions of the three mixed sub-samples and then assembling the haplotypes using a dynamic programming approach. HaploJuice was evaluated against five different assembly algorithms, Hmmfreq [1], ShoRAH [2], SAVAGE [3], PredictHaplo [4] and QuRe [5]. Using simulated and real data sets, HaploJuice reconstructed the true sequences with the highest coverage and the lowest error rate. HaploJuice achieves high accuracy in haplotype reconstruction, making Ranjard et al.’s pooling strategy more efficient, feasible, and applicable, with the benefit of reducing the sequencing cost.
Direct evidence of an increasing mutational load in humans
Authors: Aris-Brosou Stéphane
Published: April 2018

The extent to which selection has shaped present-day human populations has attracted intense scrutiny, and examples of local adaptations abound. However, the evolutionary trajectory of alleles that, today, are deleterious has received much less attention. To address this question, the genomes of 2,062 individuals, including 1,179 ancient humans, were reanalyzed to assess how frequencies of risk alleles and their homozygosity changed through space and time in Europe over the past 45,000 years. While the overall deleterious homozygosity has consistently decreased, risk alleles have steadily increased in frequency over that period of time. Those that increased most are associated with diseases such as asthma, Crohn disease, diabetes and obesity, which are highly prevalent in present-day populations. These findings may not run against the existence of local adaptations, but highlight the limitations imposed by drift and population dynamics on the strength of selection in purging deleterious mutations from human populations.
Pressure sensitivity of ANME-3 predominant anaerobic methane oxidizing community from coastal marine Lake Grevelingen sediment
Authors: Cassarini C. , Zhang Y. , Lens P. N.
Published: April 2018

Anaerobic oxidation of methane (AOM) coupled to sulfate reduction is mediated by, respectively, anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria (SRB). When a microbial community from coastal marine Lake Grevelingen sediment, containing ANME-3 as the most abundant type of ANME, was incubated under a pressure gradient (0.1-40 MPa) for 77 days, ANME-3 was more pressure sensitive than the SRB. ANME-3 activity was higher at lower (0.1, 0.45 MPa) over higher (10, 20 and 40 MPa) CH4total pressures. Moreover, the sulfur metabolism was shifted upon changing the incubation pressure: only at 0.1 MPa elemental sulfur was detected in a considerable amount and SRB of theDesulfobacteralesorder were more enriched at elevated pressures than theDesulfubulbaceae. This study provides evidence that ANME-3 can be constrained at shallow environments, despite the scarce bioavailable energy, because of its pressure sensitivity. Besides, the association between ANME-3 and SRB can be steered by changing solely the incubation pressure.

Importance

Anaerobic oxidation of methane (AOM) coupled to sulfate reduction is a biological process largely occurring in marine sediments, which contributes to the removal of almost 90% of sedimentary methane, thereby controlling methane emission to the atmosphere. AOM is mediated by slow growing archaea, anaerobic methanotrophs (ANME) and sulfate reducing bacteria. The enrichment of these microorganisms has been challenging, especially considering the low solubility of methane at ambient temperature and pressure. Previous studies showed strong positive correlations between the growth of ANME and the methane pressure, since the higher the pressure the more methane is dissolved. In this research, a shallow marine sediment was incubated under methane pressure gradients. The investigated effect of pressure on the AOM-SR activity, the formation sulfur intermediates and the microbial community structure is important to understand the pressure influence on the processes and the activity of the microorganisms involved to further understand their metabolism and physiology.
Colistin heteroresistance and the involvement of the PmrAB regulatory system in Acinetobacter baumannii
Authors: Charretier Yannick , Diene Seydina M. , Baud Damien , Chatellier Sonia , Santiago-Allexant Emmanuelle , van Belkum Alex , Guigon Ghislaine , Schrenzel Jacques
Published: April 2018

Multidrug-resistant Acinetobacter baumannii infection has recently emerged as a worldwide clinical problem and colistin is increasingly being used as last resort therapy. Despite its favorable bacterial killing, resistance and heteroresistance to colistin have been described. Mutations in the PmrAB regulatory pathway have been already associated with colistin resistance whereas the mechanisms for heteroresistance remain largely unknown. The purpose of the present study is to investigate the role of PmrAB in laboratory-selected mutants representative of global epidemic strains. During brief colistin exposure, colistin resistant and colistin heteroresistant mutants were selected in a one-step strategy. Population Analysis Profiling (PAP) was performed to confirm the suspected phenotype. Upon withdrawal of selective pressure, compensatory mutations were evaluated in another one-step strategy. A trans-complementation assay was designed to delineate the involvement of the PmrAB regulatory system using qPCR and PAP. Mutations in the PmrAB regulatory pathway were associated with colistin resistance and colistin heteroresistance as well. The transcomplementation assay provides a proof for the role played by changes in the PmrAB regulatory pathway. The level of colistin resistance is correlated to the level of expression of pmrC. The resistance phenotype was partially restored since the complemented strain became heteroresistant. This report shows the role of different mutations in the PmrAB regulatory pathway and warns on the development of colistin heteroresistance that could be present but not easily detected with routine testing.
When higher carrying capacities lead to faster propagation
Authors: Haond Marjorie , Morel-Journel Thibaut , Lombaert Eric , Vercken Elodie , Mailleret Ludovic , Roques Lionel
Published: April 2018

This preprint has been reviewed and recommended by Peer Community In Ecology (https://dx.doi.org/10.24072/pci.ecology.100004). Finding general patterns in the expansion of natural populations is a major challenge in ecology and invasion biology. Classical spatio-temporal models predict that the carrying capacity (K) of the environment should have no influence on the speed (v) of an expanding population. We tested the generality of this statement with reaction-diffusion equations, stochastic individual-based models, and microcosms experiments withTrichogramma chiloniswasps. We investigated the dependence betweenKandvunder different assumptions: null model (Fisher-KPP-like assumptions), strong Allee effects, and positive density-dependent dispersal. These approaches led to similar and complementary results. Strong Allee effects, positive density-dependent dispersal and demographic stochasticity in small populations lead to a positive dependence betweenKandv. A positive correlation between carrying capacity and propagation speed might be more frequent than previously expected, and be the rule when individuals at the edge of a population range are not able to fully drive the expansion.
EnTAP: Bringing Faster and Smarter Functional Annotation to Non-Model Eukaryotic Transcriptomes
Authors: Hart Alexander J. , Ginzburg Samuel , Xu Muyang (Sam) , Fisher Cera R. , Rahmatpour Nasim , Mitton Jeffry B. , Paul Robin , Wegrzyn Jill L.
Published: April 2018

EnTAP (Eukaryotic Non-Model Transcriptome Annotation Pipeline) was designed to improve the accuracy, speed, and flexibility of functional gene annotation for de novo assembled transcriptomes in non-model eukaryotes. This software package addresses the fragmentation and related assembly issues that result in inflated transcript estimates and poor annotation rates, while focusing primarily on protein-coding transcripts. Following filters applied through assessment of true expression and frame selection, open-source tools are leveraged to functionally annotate the translated proteins. Downstream features include fast similarity search across three repositories, protein domain assignment, orthologous gene family assessment, and Gene Ontology term assignment. The final annotation integrates across multiple databases and selects an optimal assignment from a combination of weighted metrics describing similarity search score, taxonomic relationship, and informativeness. Researchers have the option to include additional filters to identify and remove contaminants, identify associated pathways, and prepare the transcripts for enrichment analysis. This fully featured pipeline is easy to install, configure, and runs significantly faster than comparable annotation packages. EnTAP is optimized to generate extensive functional information for the gene space of organisms with limited or poorly characterized genomic resources.
The Genome of BAM-degrading Aminobacter sp. MSH1 with Several Low Copy Plasmids
Authors: Nielsen Tue Kjærgaard , Hylling Ole , Ellegaard-Jensen Lea , Aamand Jens , Hansen Lars Hestbjerg
Published: April 2018

As one of the only described degraders of the recalcitrant metabolite 2,6-dichlorobenzamide (BAM) of the pesticide dichlobenil, Aminobacter sp. MSH1 has been intensively studied for its characteristics with regards to physiology and its use in bioremediation. Two plasmid sequences from strain MSH1 have previously been published, while the remaining genome sequence has been left uninvestigated. We here present the complete genome sequence of this important strain, which consists of a chromosome, two megaplasmids and five smaller plasmids. Intriguingly, the plasmid copy numbers are mostly below one per bacterial chromosome, indicating that plasmids in strain MSH1 are under very unstable conservation. The results of this report improve our understanding of the genomic dynamics of Aminobacter sp. MSH1.