bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of satellite observations in understanding the impact of El Niño on the carbon cycle: current capabilities and future opportunities
Authors: Palmer Paul I.
Published: October 2018

The 2015/2016 El Niño was the first major climate variation when there were a range of satellite observations that simultaneously observed land, ocean and atmospheric properties associated with the carbon cycle. These data are beginning to provide new insights into the varied responses of land ecosystems to El Niño, but we are far from fully exploiting the information embodied by these data. Here, we briefly review the atmospheric and terrestrial satellite data that are available to study the carbon cycle. We also outline recommendations for future research, particularly the closer integration of satellite data with forest biometric datasets that provide detailed information about carbon dynamics on a range of timescales.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Widespread reduction in sun-induced fluorescence from the Amazon during the 2015/2016 El Niño
Authors: Koren Gerbrand , van Schaik Erik , Araújo Alessandro C. , Boersma K. Folkert , Gärtner Antje , Killaars Lars , Kooreman Maurits L. , Kruijt Bart , van der Laan-Luijkx Ingrid T. , von Randow Celso , Smith Naomi E. , Peters Wouter
Published: October 2018

The tropical carbon balance dominates year-to-year variations in the CO
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exchange with the atmosphere through photosynthesis, respiration and fires. Because of its high correlation with gross primary productivity (GPP), observations of sun-induced fluorescence (SIF) are of great interest. We developed a new remotely sensed SIF product with improved signal-to-noise in the tropics, and use it here to quantify the impact of the 2015/2016 El Niño Amazon drought. We find that SIF was strongly suppressed over areas with anomalously high temperatures and decreased levels of water in the soil. SIF went below its climatological range starting from the end of the 2015 dry season (October) and returned to normal levels by February 2016 when atmospheric conditions returned to normal, but well before the end of anomalously low precipitation that persisted through June 2016. Impacts were not uniform across the Amazon basin, with the eastern part experiencing much larger (10–15%) SIF reductions than the western part of the basin (2–5%). We estimate the integrated loss of GPP relative to eight previous years to be 0.34–0.48 PgC in the three-month period October–November–December 2015.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
ENSO Drives interannual variation of forest woody growth across the tropics
Authors: Rifai Sami W. , Girardin Cécile A. J. , Berenguer Erika , del Aguila-Pasquel Jhon , Dahlsjö Cecilia A. L. , Doughty Christopher E. , Jeffery Kathryn J. , Moore Sam , Oliveras Imma , Riutta Terhi , Rowland Lucy M. , Murakami Alejandro Araujo , Addo-Danso Shalom D. , Brando Paulo , Burton Chad , Ondo Fidèle Evouna , Duah-Gyamfi Akwasi , Amézquita Filio Farfán , Freitag Renata , Pacha Fernando Hancco , Huasco Walter Huaraca , Ibrahim Forzia , Mbou Armel T. , Mihindou Vianet Mihindou , Peixoto Karine S. , Rocha Wanderley , Rossi Liana C. , Seixas Marina , Silva-Espejo Javier E. , Abernethy Katharine A. , Adu-Bredu Stephen , Barlow Jos , da Costa Antonio C. L. , Marimon Beatriz S. , Marimon-Junior Ben H. , Meir Patrick , Metcalfe Daniel B. , Phillips Oliver L. , White Lee J. T. , Malhi Yadvinder
Published: October 2018

Meteorological extreme events such as El Niño events are expected to affect tropical forest net primary production (NPP) and woody growth, but there has been no large-scale empirical validation of this expectation. We collected a large high–temporal resolution dataset (for 1–13 years depending upon location) of more than 172 000 stem growth measurements using dendrometer bands from across 14 regions spanning Amazonia, Africa and Borneo in order to test how much month-to-month variation in stand-level woody growth of adult tree stems (NPPstem) can be explained by seasonal variation and interannual meteorological anomalies. A key finding is that woody growth responds differently to meteorological variation between tropical forests with a dry season (where monthly rainfall is less than 100 mm), and aseasonal wet forests lacking a consistent dry season. In seasonal tropical forests, a high degree of variation in woody growth can be predicted from seasonal variation in temperature, vapour pressure deficit, in addition to anomalies of soil water deficit and shortwave radiation. The variation of aseasonal wet forest woody growth is best predicted by the anomalies of vapour pressure deficit, water deficit and shortwave radiation. In total, we predict the total live woody production of the global tropical forest biome to be 2.16 Pg C yr−1, with an interannual range 1.96–2.26 Pg C yr−1between 1996–2016, and with the sharpest declines during the strong El Niño events of 1997/8 and 2015/6. There is high geographical variation in hotspots of El Niño–associated impacts, with weak impacts in Africa, and strongly negative impacts in parts of Southeast Asia and extensive regions across central and eastern Amazonia. Overall, there is high correlation (r= −0.75) between the annual anomaly of tropical forest woody growth and the annual mean of the El Niño 3.4 index, driven mainly by strong correlations with anomalies of soil water deficit, vapour pressure deficit and shortwave radiation.

This article is part of the discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Vulnerability of Amazonian forests to repeated droughts
Authors: Anderson Liana Oighenstein , Ribeiro Neto Germano , Cunha Ana Paula , Fonseca Marisa Gesteira , Mendes de Moura Yhasmin , Dalagnol Ricardo , Wagner Fabien Hubert , de Aragão Luiz Eduardo Oliveira e Cruz
Published: October 2018

Extreme droughts have been recurrent in the Amazon over the past decades, causing socio-economic and environmental impacts. Here, we investigate the vulnerability of Amazonian forests, both undisturbed and human-modified, to repeated droughts. We defined vulnerability as a measure of (i) exposure, which is the degree to which these ecosystems were exposed to droughts, and (ii) its sensitivity, measured as the degree to which the drought has affected remote sensing-derived forest greenness. The exposure was calculated by assessing the meteorological drought, using the standardized precipitation index (SPI) and the maximum cumulative water deficit (MCWD), which is related to vegetation water stress, from 1981 to 2016. The sensitivity was assessed based on the enhanced vegetation index anomalies (AEVI), derived from the newly available Moderate Resolution Imaging Spectroradiometer (MODIS)/Multi-Angle Implementation of Atmospheric Correction algorithm (MAIAC) product, from 2003 to 2016, which is indicative of forest's photosynthetic capacity. We estimated that 46% of the Brazilian Amazon biome was under severe to extreme drought in 2015/2016 as measured by the SPI, compared with 16% and 8% for the 2009/2010 and 2004/2005 droughts, respectively. The most recent drought (2015/2016) affected the largest area since the drought of 1981. Droughts tend to increase the variance of the photosynthetic capacity of Amazonian forests as based on the minimum and maximum AEVI analysis. However, the area showing a reduction in photosynthetic capacity prevails in the signal, reaching more than 400 000 km
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of forests, four orders of magnitude larger than areas with AEVI enhancement. Moreover, the intensity of the negative AEVI steadily increased from 2005 to 2016. These results indicate that during the analysed period drought impacts were being exacerbated through time. Forests in the twenty-first century are becoming more vulnerable to droughts, with larger areas intensively and negatively responding to water shortage in the region.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Aquaporin-4 facilitator TGN-073 demonstrates novel analgesic activity
Authors: Huber Vincent J. , Kwee Ingrid L. , Nakada Tsutomu
Published: October 2018

During pre-clinical development, we tested the novel, internally developed AQP-4 facilitator TGN-073 for its effect in a rodent pain model. Therein, TGN-073 was found to exert a strong analgesic effect. Following a single 200 mg/kg (i.p.) administration of TGN-073, a virtually complete block in the acetic acid writhing test was observed. Subsequent in vitro tests demonstrated that TGN-073 had no binding affinity for the μ-opioid or NK-1 receptors. Accordingly, we suspect TGN-073 or other AQP-4 facilitators may be developed into potent non-opioid analgesic agents. Given the potential significance of this discovery, we feel it should be openly shared with the scientific community.
The perils of interaction prediction
Authors: Mao Weiguang , Kostka Dennis , Chikina Maria
Published: October 2018

The availability of genome-wide maps of enhancer-promoter interactions (EPIs) has made it possible to use machine learning approaches to extract and interpret features that determine these interactions in different biological contexts. Multiple methods have claimed to accomplish the task of predicting enhancer-promoter interactions based on corresponding genomic features, but this problem is actually still far from being solved. In our analysis, we show that individual enhancer and promoter regions have widely different marginal interaction probabilities, e.g. propensities, which can lead to overfitting and memorization when random cross-validation is employed. Further even when a proper cross-validation scheme is adopted, a simple propensity-based model can still achieve a competitive performance without capturing any information about the EPI mechanism.
Neural markers of category-based selective working memory in aging
Authors: Mok Robert M , O'Donoghue M. Clare , Myers Nicholas E , Drazich Erin H.S. , Nobre Anna Christina
Published: October 2018

Working memory (WM) is essential for normal cognitive function, but shows marked decline in aging. Studies have shown that the ability to attend selectively to relevant information amongst competing distractors is related to WM capacity. The extent to which WM deficits in aging are related to impairments in selective attention is unclear. To investigate the neural mechanisms supporting selective attention in WM in aging, we tested a large group of older adults using functional magnetic resonance imaging whilst they performed a category-based (faces/houses) selective-WM task. Older adults were able to use attention to encode targets and suppress distractors to reach high levels of task performance. A subsequent, surprise recognition-memory task showed strong consequences of selective attention. Attended items in the relevant category were recognised significantly better than items in the ignored category. Neural measures also showed reliable markers of selective attention during WM. Purported control regions including the dorsolateral and inferior prefrontal and anterior cingulate cortex were reliably recruited for attention to both categories. Activation levels in category-sensitive visual cortex showed reliable modulation according to attentional demands, and positively correlated with subsequent memory measures of attention and WM span. Psychophysiological interaction analyses showed that activity in category-sensitive areas were coupled with non-sensory cortex known to be involved in cognitive control and memory processing, including regions in the PFC and hippocampus. In summary, we found that brain mechanisms of attention for selective WM are relatively preserved in aging, and individual differences in these abilities corresponded to the degree of attention-related modulation in the brain.
G-quadruplex formation on specific surface-exposed regions of the human ribosomal RNA
Authors: Mestre-Fos Santi , Penev Petar I. , Suttapitugsakul Suttipong , Ito Chieri , Petrov Anton S. , Wartell Roger M. , Wu Ronghu , Williams Loren Dean
Published: October 2018

Profound similarities and critical differences mark ribosomes across phylogeny. The ribosomal core, approximated by the prokaryotic ribosome, is universal, yet mammalian ribosomes are nearly twice as large as those of prokaryotes. Differences in size are due in part to rRNA expansion segments. Here we show rRNA tentacles of Expansion Segment 7 (ES7) of Homo sapiens can form G-quadruplexes in vitro. G-quadruplex-forming regions are located on the most surface-exposed regions of the ribosome, near the termini of rRNA tentacles. We characterized rRNA of the large ribosomal subunit by computation, circular dichroism, gel mobility, fluorescent probes, nuclease accessibility, electrophoretic mobility shifts and blotting. We investigated ES7 and oligomers derived from ES7, intact 28S rRNA, and 80S ribosomes and polysomes. We used mass spectrometry to identify proteins that bind to rRNA G-quadruplexes in cell lysates. Proteins that associate with rRNA G-quadruplexes include helicases (DDX3, CNBP, DDX21, DDX17) and heterogeneous nuclear ribonucleoproteins (hnRNPs). And finally, by multiple sequence alignments, we observed that G-quadruplex-forming sequences appear to be a general feature LSU rRNA of the phylum Chordata but not in other phyla. It is known that G-quadruplexes form in telomeres, promoters, and untranslated regions of mRNA but, to our knowledge, they have not been reported previously in ribosomes.
EMBL2checklists: A Python package to facilitate the user-friendly submission of plant DNA barcoding sequences to ENA
Authors: Gruenstaeudl Michael , Hartmaring Yannick
Published: October 2018

Background

The submission of DNA sequences to public sequence databases is an essential, but insufficiently automated step in the process of generating and disseminating novel DNA sequence data. Despite the centrality of database submissions to biological research, the range of available software tools that facilitate the preparation of sequence data for database submissions is low, especially for sequences generated via plant DNA barcoding. Current submission procedures can be complex and prohibitively time expensive for any but a small number of input sequences. A user-friendly software tool is needed that streamlines the file preparation for database submissions of DNA sequences that are commonly generated in plant DNA barcoding.

Methods

A Python package was developed that converts DNA sequences from the common EMBL and GenBank flat file formats to submission-ready, tab-delimited spreadsheets (so-called “checklists”) for a subsequent upload to the public sequence database of the European Nucleotide Archive (ENA). The software tool, titled “EMBL2checklists”, automatically converts DNA sequences, their annotation features, and associated metadata into the idiosyncratic format of marker-specific ENA checklists and, thus, generates output that can be uploaded via the interactive Webin submission system of ENA.

Results

EMBL2checklists provides a simple, platform-independent tool that automates the conversion of common plant DNA barcoding sequences into easily editable spreadsheets that require no further processing but their upload to ENA via the interactive Webin submission system. The software is equipped with an intuitive graphical as well as an efficient command-line interface for its operation. The utility of the software is illustrated by its application in the submission of DNA sequences of two recent plant phylogenetic investigations and one fungal metagenomic study.

Discussion

EMBL2checklists bridges the gap between common software suites for DNA sequence assembly and annotation and the interactive data submission process of ENA. It represents an easy-to-use solution for plant biologists without bioinformatics expertise to generate submission-ready checklists from common plant DNA sequence data. It allows the post-processing of checklists as well as work-sharing during the submission process and solves a critical bottleneck in the effort to increase participation in public data sharing.
Emergence of enteroaggregativeEscherichia coliwithin the ST131 lineage as a cause of extraintestinal infections
Authors: Boll Erik J. , Stegger Marc , Hasman Henrik , Roer Louise , Overballe-Petersen Søren , Ng Kim , Scheutz Flemming , Hammerum Anette M. , Dungu Arnold , Hansen Frank , Lilje Berit , Schrøder Hansen Dennis , Krogfelt Karen A. , Price Lance B. , Johnson James R. , Struve Carsten , Olesen Bente
Published: October 2018

Escherichia colisequence type 131 (ST131) is a major cause of urinary and bloodstream infections and its association with extended-spectrum β-lactamases (ESBL) significantly complicates treatment. Most notorious is its rapidly expandingH30-Rx clade (named for containing allele 30 of the type-1 fimbrial adhesin genefimHand extensive antimicrobial resistance), which appears to have emerged in the United States due in part due to the acquisition of the ESBL-encodingblaCTX-M-15gene and resistance to fluoroquinolones. However, non-H30 ST131 lineages with acquired CTX-M-type resistance genes also are emerging. Based on whole-genome analyses, we describe here the presence of an (fimH)H27E. coliST131 lineage that currently is causing an outbreak of community-acquired bacteremia and recurrent urinary tract infections (UTIs) in Denmark. This lineage has acquired both a virulence plasmid (pAA) that defines the enteroaggregativeE. coli(EAEC) diarrheagenic pathotype and multiple genes associated with extraintestinalE. coli(ExPEC) that combined has made this particular ST131 lineage highly successful at colonizing its human host and cause recurrent UTI. Moreover, using a historic World Health OrganizationE. colicollection and publically available genome sequences, we identify a globalH27 EAEC ST131 lineage dating back as far as 1998. MostH27 EAEC ST131 isolates harbor pAA or pAA-like plasmids, which analysis strongly imply was caused by a single ancestral acquisition. These findings illustrate the profound plasticity of this important pathogenicE. coli H27 lineage in general, and the genetic acquisitions of EAEC-specific virulence traits that likely confer an enhanced ability to cause intestinal colonization.

Importance

TheE. coliST131 lineage is a notorious extraintestinal pathogen. A signature characteristic of ST131 is its ability to asymptomatically colonize the gastrointestinal tract and then opportunistically cause extraintestinal infections, such as cystitis, pyelonephritis and urosepsis. In this study, we report a novel ST131 sublineage that has acquired the enteroaggregative diarrheagenic phenotype, spread across multiple continents and has been associated with multiple outbreaks of community-acquired bloodstream infections in Denmark. The strain’s ability to both cause diarrhea and colonize the human gastrointestinal tract may facilitate its dissemination and establishment in the community, whereas the strain’s clonal nature may facilitate targeted control strategies, such as vaccination.
Inner-membrane GspF of the bacterial type II secretion system is a dimeric adaptor mediating pseudopilus biogenesis
Authors: Van Putte Wouter , De Vos Tatjana , Van Den Broeck Wim , Stahlberg Henning , Kudryashev Misha , Savvides Savvas N.
Published: October 2018

The type II secretion system (T2SS), a protein complex spanning the bacterial envelope, is pivotal to bacterial pathogenicity. Central to T2SS function is the extrusion of protein cargos from the periplasm into the extracellular environment mediated by a pseudopilus and motorized by a cytosolic ATPase. GspF, an inner-membrane component of T2SS has long been considered to be a key player in this process, yet the structural basis of its role had remained elusive. Here, we employed single-particle electron microscopy based on XcpS (GspF) from the T2SS of pathogenicP. aeruginosastabilized by a nanobody, to show that XcpS adopts a dimeric structure mediated by its transmembrane helices. This assembly matches in terms of overall organization and dimensions the basal inner-membrane cassette of a T2SS machinery. Thus, GspF is poised to serve as an adaptor involved in the mediation of propeller-like torque generated by the motor ATPase to the secretion pseudopilus.

Non-technical author summary

Antibiotic resistance by bacteria imposes a worldwide threat that can only be overcome through a multi-front approach: preventive actions and the parallel development of novel molecular strategies to combat antibiotic resistance mechanisms. One such strategy might focus on antivirulence drugs that prevent host invasion and spreading by pathogenic bacteria, without shutting down essential functions related to bacterial survival. The rationale behind such an approach is that it might limit selective pressure leading to slower evolutionary rates of resistant bacterial strains. Bacterial secretion systems are an appropriate target for such therapeutic approaches as their impairment will inhibit the secretion of a multitude of virulence factors. This study focuses on the structural characterization of one of the proteins residing in the inner-membrane cassette of the type II secretion system (T2SS), a multi-protein complex in multiple opportunistic pathogens that secretes virulence factors. The targeted protein is essential for the assembly of the pseudopilus, a rod-like supramolecular structure that propels the secretion of virulence factors by pathogenic Gram-negative bacteria. Our study crucially complements growing evidence supporting a rotational assembly model of the pseudopilus and contributes to a better understanding of the functioning of the T2SS and the related secretion systems. We envisage that such knowledge will facilitate targeting of these systems for therapeutic purposes.
Sleep restriction caused impaired emotional regulation without detectable brain activation changes – a functional magnetic resonance imaging study
Authors: Tamm Sandra , Nilsonne Gustav , Schwarz Johanna , Golkar Armita , Kecklund Göran , Petrovic Predrag , Fischer Håkan , Åkerstedt Torbjörn , Lekander Mats
Published: October 2018

Sleep restriction has been proposed to cause impaired emotional processing and emotional regulation by inhibiting top-down control from prefrontal cortex to amygdala. Intentional emotional regulation after sleep restriction has however never been studied using brain imaging. We here aimed to investigate the effect of sleep restriction on emotional regulation through cognitive reappraisal. Forty-seven young (age 20-30) and 33 older (age 65-75) participants (38/23 with complete data and successful sleep intervention) performed a cognitive reappraisal task during fMRI after a night of normal sleep and after restricted sleep (3h). Emotional downregulation was associated with significantly increased activity in dorsolateral prefrontal cortex (pFWE < 0.05) and lateral orbital cortex (pFWE < 0.05) in young, but not in older subjects. Sleep restriction was associated with a decrease in self-reported regulation success to negative stimuli (p < 0.01) and a trend towards perceiving all stimuli as less negative (p = 0.07), in young participants. No effects of sleep restriction on brain activity nor connectivity were found in either age group. In conclusion, our data do not support the idea of a prefrontal-amygdala disconnect after sleep restriction, and neural mechanisms underlying behavioural effects on emotional regulation after insufficient sleep require further investigation.
Molecular basis for high affinity agonist binding in GPCRs
Authors: Warne Tony , Edwards Patricia C. , Doré Andrew S. , Leslie Andrew G. W. , Tate Christopher G.
Published: October 2018

A characteristic of GPCRs in the G protein-coupled state is that the affinity of the agonist often increases significantly, but the molecular basis for this is unclear. We have determined six active-state structures of the β1-adrenoceptor (β1AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. A direct comparison with structures of β1AR in inactive states bound to the identical ligands showed a 24-42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. GPCRs are highly conserved, so these factors will likely be essential in increasing the affinity of a wide range of structurally distinct agonists.

One Sentence Summary

High affinity agonist binding to G protein-coupled GPCRs results from an increase in the number and strength of protein-ligand interactions.
Locations in the Neocortex: A Theory of Sensorimotor Object Recognition Using Cortical Grid Cells
Authors: Lewis Marcus , Purdy Scott , Ahmad Subutai , Hawkins Jeff
Published: October 2018

The neocortex is capable of anticipating the sensory results of movement but the neural mechanisms are poorly understood. In the entorhinal cortex, grid cells represent the location of an animal in its environment, and this location is updated through movement and path integration. In this paper, we propose that sensory neocortex incorporates movement using grid cell-like neurons that represent the location of sensors on an object. We describe a two-layer neural network model that uses cortical grid cells and path integration to robustly learn and recognize objects through movement and predict sensory stimuli after movement. A layer of cells consisting of several grid cell-like modules represents a location in the reference frame of a specific object. Another layer of cells which processes sensory input receives this location input as context and uses it to encode the sensory input in the object’s reference frame. Sensory input causes the network to invoke previously learned locations that are consistent with the input, and motor input causes the network to update those locations. Simulations show that the model can learn hundreds of objects even when object features alone are insufficient for disambiguation. We discuss the relationship of the model to cortical circuitry and suggest that the reciprocal connections between layers 4 and 6 fit the requirements of the model. We propose that the subgranular layers of cortical columns employ grid cell-like mechanisms to represent object specific locations that are updated through movement.
KPNA2 promotes cellular proliferation and inhibits apoptosis in the Saos-2 osteosarcoma cell line
Authors: Wei Dinglu , Ge Qiaofeng , Sun Xiaojuan , Zhang Long , Li Jia , Chen Chenglong , Lv Zhi
Published: October 2018

Karyopherin α2 plays a critical role in tumorigenesis and tumor progression. However, nothing is currently known about the effects of KPNA2 on osteosarcomas. This study aimed to investigate differential KPNA2 protein and mRNA expression in human osteosarcoma tumor cells and normal bone tissue. We also sought to determine whether KPNA2 can influence the proliferation and apoptosis of the Saos-2 osteosarcoma cell line. Immunohistochemistry (IHC) was used to investigate KPNA2 protein expression. Real-time quantitative PCR (qPCR) was used to detect levels of KPNA2 mRNA expression, and lentivirus-mediated short-hairpin RNAs (shRNAs) were used to knock down KPNA2 expression in Saos-2 cells. The MTT assay and multiparametric high-content screening (HCS) were used to measure cell proliferation and growth, respectively. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. The results revealed significantly higher KPNA2 expression levels in osteosarcoma tissues than in normal bone tissues; furthermore, KPNA2 mRNA was also highly expressed in three osteosarcoma cell lines. After transducing Saos-2 cells with KPNA2-shRNA lentivirus, the proliferative rate was notably decreased compared to that of the negative control (NC) lentivirus group (P<0.05). Flow cytometry results indicated that KPNA2 may arrest cell cycle progression and regulate the growth of these cells. The results for apoptosis indicated an apoptotic rate of 13.38±0.48% in KPNA2-shRNA cells, which was significantly higher than the rate for cells in the control group (5.13 ±0.33%). Therefore, this study showed that KPNA2 is highly expressed in osteosarcoma tissues and that reduced KPNA2mRNA levels inhibited proliferation and promoted apoptosis in an osteosarcoma cell line.
Molecular detection of virulence and resistance genes in Salmonella enterica serovar Typhi and Paratyphi A, B and C isolated from human diarrhea samples and lettuce in Burkina Faso
Authors: Somda Namwin Siourimè , Savadogo Aly , Bonkoungou Juste Isidore Ouindgueta , Traoré Oumar , Sambe-Ba Bissoume , Wane Abdoul Aziz , Traoré Yves , Gassama-Sow Amy
Published: October 2018

Objectives

In Burkina Faso (BF), dirty water, in particular those of the stoppings and the gutter are used for irrigation of vegetables. The aim of this study is to contribute to the knowledge on the molecular level of Salmonella Typhi and Paratyphi circulating in the hospitals and environment next to hospitals in BF.

Methods

Salmonella Typhi and Paratyphi strains isolated from patients between 2009 to 2015 and lettuce samples isolated in 2014 in BF were characterized by simple PCR using specific primers.

Results

Out of 100 Salmonella isolated, 53% were from human and 47% from lettuce samples. Globally, the highest prevalence was observed with invA, misL, pipD, orfL and spvR genes in 97%, 96%; 74%; and 21%. Forty of these isolates carried class 1 integron, 31 from clinical samples and 9 from lettuce samples. Sequencing showed seven different gene cassette arrangements, with aadA1 in 13/15 strains, aadA7 and aac(3)-Id in 2/15 strains. Eight percent (8/100) of Salmonella harbored gyrB and parE genes with 6 from clinical and 2 from lettuce isolates. Sequencing showed no mutation in these genes. Three distinct PFGE types were observed from clinical samples with 90-95% similarity in each case. All Salmonella from lettuce had similar pulsotypes.

Conclusion

This study showed the diversity virulence and resistance genes harbored of S. Typhi and Paratyphi from both clinical and lettuce samples in BF. Lettuce is a potential source of transmission of Salmonella causing diarrhea among human in BF.
Synthetic pluripotent bacterial stem cells
Authors: Molinari Sara , Shis David L. , Chappell James , Igoshin Oleg A. , Bennett Matthew R.
Published: October 2018

A defining property of stem cells is their ability to differentiate via asymmetric cell division, in which a stem cell creates a differentiated daughter cell but retains its own phenotype. Here, we describe a synthetic genetic circuit for controlling asymmetrical cell division in Escherichia coli. Specifically, we engineered an inducible system that can bind and segregate plasmid DNA to a single position in the cell. Upon division, the co-localized plasmids are kept by one and only one of the daughter cells. The other daughter cell receives no plasmid DNA and is hence irreversibly differentiated from its sibling. In this way, we achieved asymmetric cell division though asymmetric plasmid partitioning. We also characterized an orthogonal inducible circuit that enables the simultaneous asymmetric partitioning of two plasmid species – resulting in pluripotent cells that have four distinct differentiated states. These results point the way towards engineering multicellular systems from prokaryotic hosts.
Metabolites associated with early cognitive changes implicated in Alzheimer’s disease
Authors: Darst Burcu F. , Jonaitis Erin M. , Koscik Rebecca L. , Clark Lindsay R. , Lu Qiongshi , Hogan Kirk J. , Johnson Sterling C. , Engelman Corinne D.
Published: October 2018

We investigated the metabolomics of early cognitive changes related to Alzheimer’s disease (AD) in order to better understand mechanisms that could contribute to early stages and progression of this disease. This investigation used longitudinal plasma samples from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a cohort of participants who were dementia free at enrollment and enriched with a parental history of AD. Metabolomic profiles were quantified for 2,338 fasting plasma samples among 1,206 participants, each with up to three study visits. Of 1,097 metabolites tested, levels of seven were associated with executive function trajectories, including an amino acid and three fatty acids, but none were associated with delayed recall trajectories. Our time-varying metabolomic results suggest potential mechanisms that could contribute to the earliest signs of cognitive decline. In particular, fatty acids may be associated with cognition in a manner that is more complex than previously suspected.
Tomato fruit ripening factor NOR controls leaf senescence
Authors: Ma Xuemin , Balazadeh Salma , Mueller-Roeber Bernd
Published: October 2018

NAC transcription factors (TFs) are important regulators of expressional reprogramming during plant development, stress responses and leaf senescence. NAC TFs also play important roles in fruit ripening. In tomato (Solanum lycopersicum), one of the best characterized NAC involved in fruit ripening is NON-RIPENING (NOR) and the non-ripening (nor) mutation has been widely used to extend fruit shelf life in elite varieties. Here, we show that NOR additionally controls leaf senescence. Expression of NOR increases with leaf age, and developmental as well as dark-induced senescence are delayed in the nor mutant, while overexpression of NOR promotes leaf senescence. Genes associated with chlorophyll degradation as well as senescence-associated genes (SAGs) show reduced and elevated expression, respectively, in nor mutants and NOR overexpressors. Overexpression of NOR also stimulates leaf senescence in Arabidopsis thaliana. In tomato, NOR supports senescence by directly and positively regulating the expression of several senescence-associated genes including, besides others, SlSAG15 and SlSAG113, SlSGR1 and SlYLS4. Finally, we find that another senescence control NAC TF, namely SlNAP2, acts upstream of NOR to regulate its expression. Our data support a model whereby NAC TFs have often been recruited by higher plants for both, the control of leaf senescence and fruit ripening.
An open microscopy framework suited for tracking dCas9 in live bacteria
Authors: Martens Koen J. A. , van Beljouw Sam P. B. , van der Els Simon , Baas Sander , Vink Jochem N. A. , Brouns Stan J. J. , van Baarlen Peter , Kleerebezem Michiel , Hohlbein Johannes
Published: October 2018

Super-resolution microscopy is frequently employed in the life sciences, but the number of freely accessible and affordable microscopy frameworks, especially for single particle tracking photo-activation localization microscopy (sptPALM), remains limited. To this end, we designed the miCube: a versatile super-resolution capable fluorescence microscope, which combines high spatiotemporal resolution, good adaptability, low price, and easy installation. By providing all details, we hope to enable interested researchers to build an identical or derivative instrument. The capabilities of the miCube are assessed with a novel sptPALM assay relying on the heterogeneous expression of target genes. Here, we elucidate mechanistic details of catalytically inactive Cas9 (dead Cas9) in live Lactococcus lactis. We show that, lacking specific DNA target sites, the binding and unbinding of dCas9 to DNA can be described using simplified rate constants of kbound→free = 30−80 s−1 and kfree→bound = 15−40 s−1. Moreover, after providing specific DNA target sites via DNA plasmids, the plasmid-bound dCas9 population size decreases with increasing dCas9 copy number via a mono-exponential decay, indicative of simple disassociation kinetics.
Functional Connectivity of Corticostriatal Circuitry and Psychosis-Like Experiences in the General Community
Authors: Sabaroedin Kristina , Tiego Jeggan , Parkes Linden , Sforazzini Francesco , Finlay Amy , Johnson Beth , Pinar Ari , Cropley Vanessa , Harrison Ben J , Zalesky Andrew , Pantelis Christos , Bellgrove Mark , Fornito Alex
Published: October 2018

Background

Psychotic symptoms are proposed lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in non-clinical populations to frank disorder. Here, we investigate neurobiological correlates of this symptomatologic continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in patients and high-risk individuals, is associated with the severity of subclinical PLEs.

Methods

A community sample of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis (PCA) estimated major dimensions of PLEs from the questionnaires. PCA dimension scores were then correlated with whole-brain voxelwise functional connectivity (FC) maps of the striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol.

Results

PCA identified two dimensions of PLEs accounting for 62.57% of variance in the measures, corresponding to positive and negative PLEs. Reduced FC between the dorsal striatum and prefrontal cortex correlated with higher positive PLEs. Negative PLEs correlated with increased FC between the dorsal striatum and visual and sensorimotor areas. In the ventral corticostriatal system, positive and negative PLEs were both associated with FC between the ventro-rostral putamen and sensorimotor cortices.

Conclusions

Consistent with past findings in patients and high-risk individuals, subthreshold positive symptomatology is associated with reduced FC of the dorsal circuit. These findings suggest that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.
Sequence Imputation from Low Density Single Nucleotide Polymorphism Panel in a Black Poplar Breeding population
Authors: Pégard Marie , Rogier Odile , Bérard Aurélie , Faivre-Rampant Patricia , Le Paslier Marie-Christine , Bastien Catherine , Jorge Véronique , Sánchez Leopoldo
Published: October 2018

Background

Genomic selection accuracy increases with the use of high SNP (single nucleotide polymorphism) coverage. However, such gains in coverage come at high costs, preventing their operational implementation by breeders. Low density panels imputed to higher densities offer a cheaper alternative. Our study is one of the first to explore the imputation in a tree species: black poplar. About 1000 pure-breed Populus nigra trees corresponding to a subsample of the French breeding population were selected and genotyped with a 12K custom Infinium Bead-Chip. Forty-three of those individuals corresponding mostly to nodal trees in the pedigree were fully sequenced (reference), while the remaining majority (target) was imputed from 8K to 1.4 million SNPs using FImpute. Each SNP and individual was evaluated for imputation errors by leave-one-out cross validation in the training sample of 43 sequenced trees. Some summary statistics such as Hardy Weinberg Equilibrium exact test p-value, quality of sequencing, depth of sequencing per site and per individual, minor allele frequency, marker density ratio or SNP information redundancy were calculated. Principal component and Boruta analyses were used on all these parameters to rank the factors affecting the quality of imputation. Additionally, we characterize the impact of the relatedness between reference population and target population.

Results

During the imputation process, we used 7,540 SNPs from the chip to impute 1,438,827 SNPs from sequences along the 19 Chromosomes. At the individual level, imputation accuracy was very high with a proportion of SNPs correctly imputed between 0.84 and 0.99. The variation in accuracies was mostly due to differences in relatedness between individuals. At a SNP level, the imputation quality strongly depended on genotyped SNP density and to a lesser extent on the original minor allele frequency. The imputation did not appear to result in an increase of linkage disequilibrium. The genotype densification not only brought a better distribution of markers all along the genome, but also we did not detect any substantial bias in annotation categories.

Conclusions

This study shows that it is possible to impute low-density marker panels to whole genome sequence with good accuracy under certain conditions that could be common to many breeding populations.
Comprehensive Benchmarking and Integration of Tumour Microenvironment Cell Estimation Methods
Authors: Jiménez-Sánchez Alejandro , Cast Oliver , Miller Martin
Published: October 2018

The tumour microenvironment comprises complex cellular compositions and interactions between cancer, immune, and stromal components which all play crucial roles in cancer. Various computational approaches have been developed during the last decade that estimate the relative abundance of different cell types in an unbiased manner using bulk tumour RNA data. However, a comparison that objectively evaluates the performance of these approaches against one another has not been conducted. Here we benchmarked six widely used tools and gene sets: Bindea et al. gene sets, Davoli et al. gene sets, CIBERSORT, MCP-counter, TIMER, and xCell. We also introduce ConsensusTME, a consensus approach that uses the union of genes that the six tools used for cell estimation, and corrects for tumour-type specificity. We benchmarked the seven tools using TCGA DNA-derived purity scores (33 tumour-types), methylation-derived leukocyte scores (30 tumour-types), and H&E deep learning derived lymphocyte counts (13 tumour types), and individual benchmark data sets (PBMCs and 2 tumour types). Although none of the seven tools outperformed others in every benchmark, ConsensusTME ranked consistently well in all cancer-related benchmarks making it the top performing method overall. Computational methods that provide robust and accurate estimates of non-cancerous cell populations in the tumour microenvironment from tumour bulk expression data are important tools that can advance our understanding of tumour, immune, and stroma interactions, with potential clinical application if high accuracy estimates are achieved.
Ontology based mining of pathogen-disease associations from literature
Authors: Kafkas Șenay , Hoehndorf Robert
Published: October 2018

Background

Infectious diseases claim millions of lives especially in the developing countries each year, and resistance to drugs is an emerging threat worldwide. Identification of causative pathogens accurately and rapidly plays a key role in the success of treatment. To support infectious disease research and mechanisms of infection, there is a need for an open resource on pathogen-disease associations that can be utilized in computational studies. A large number of pathogen-disease associations is available from the literature in unstructured form and we need automated methods to extract the data.

Results

We developed a text mining system designed for extracting pathogen-disease relations from literature. Our approach utilizes background knowledge from an ontology and statistical methods for extracting associations between pathogens and diseases. In total, we extracted a total of 3,420 pathogen-disease associations from literature. We integrated our literature-derived associations into a database which links pathogens to their phenotypes for supporting infectious disease research.

Conclusions

To the best of our knowledge, we present the first study focusing on extracting pathogen-disease associations from publications. We believe the text mined data can be utilized as a valuable resource for infectious disease research. All the data is publicly available from https://github.com/bio-ontology-research-group/padimi and through a public SPARQL endpoint from http://patho.phenomebrowser.net/.
Automated lesion segmentation with BIANCA: impact of population-level features, classification algorithm and locally adaptive thresholding
Authors: Sundaresan Vaanathi , Zamboni Giovanna , Le Heron Campbell , Rothwell Peter M. , Husain Masud , Battaglini Marco , De Stefano Nicola , Jenkinson Mark , Griffanti Ludovica
Published: October 2018

White matter hyperintensities (WMH) or white matter lesions exhibit high variability in their characteristics both at population- and subject-level, making their detection a challenging task. Population-level factors such as age, vascular risk factors and neurode-generative diseases affect lesion load and spatial distribution. At the individual level, WMH vary in contrast, amount and distribution in different white matter regions.

In this work, we aimed to improve BIANCA, the FSL tool for WMH segmentation, in order to better deal with these sources of variability. We worked on two stages of BIANCA by improving the lesion probability map estimation (classification stage) and making the lesion probability map thresholding stage automated and adaptive to local lesion probabilities. Firstly, in order to take into account the effect of population-level factors, we included population-level lesion probabilities, modelled with respect to a parametric factor (e.g. age), in the classification stage. Secondly, we tested BIANCA performance when using four alternative classifiers commonly used in the literature, with respect to K-nearest neighbour algorithm currently used for lesion probability map estimation in BIANCA. Finally, we propose LOCally Adaptive Threshold Estimation (LOCATE), a supervised method for determining optimal local thresholds to apply to the estimated lesion probability map, as an alternative option to global thresholding (i.e. applying the same threshold to the entire lesion probability map). For these experiments we used data from a neurodegenerative cohort and a vascular cohort.

We observed that including population-level parametric lesion probabilities with re-spect to age and using alternative machine learning techniques provided negligible im-provement. However, LOCATE provided a substantial improvement in the lesion segmentation performance when compared to the global thresholding currently used in BIANCA. We further validated LOCATE on a cohort of CADASIL (Cerebral autoso-mal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) patients, a genetic form of cerebral small vessel disease characterised by extensive WMH burden, and healthy controls showing that LOCATE adapts well to wide variations in lesion load and spatial distribution.