bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analysis and prediction of amino acid variations that influence protein posttranslational modifications
Authors: Shi Shaoping , Wang Lina , Cao Man , Chen Guodong , Yu Jialin
Published: April 2018

Accumulative studies have indicated that amino acid variations through changing the type of residues of the target sites or key flanking residues could directly or indirectly influence protein posttranslational modifications (PTMs) and bring about a detrimental effect on protein function. Computational mutation analysis can greatly narrow down the efforts on experimental work. To increase the utilization of current computational resources, we ﬁrst provide an overview of computational prediction of amino acid variations that influence protein PTMs and their functional analysis. We also discuss the challenges that are faced while developing novel in silico approaches in the future. The development of better methods for mutation analysis-related protein PTMs will help to facilitate the development of personalized precision medicine.
Random forest based similarity learning for single cell RNA sequencing data
Authors: Pouyan Maziyar Baran , Kostka Dennis
Published: April 2018

Motivation

Genome-wide transcriptome sequencing applied to single cells (scRNA-seq) is rapidly becoming an assay of choice across many fields of biological and biomedical research. Scientific objectives often revolve around discovery or characterization of types or sub-types of cells, and therefore, obtaining accurate cell–cell similarities from scRNA-seq data is a critical step in many studies. While rapid advances are being made in the development of tools for scRNA-seq data analysis, few approaches exist that explicitly address this task. Furthermore, abundance and type of noise present in scRNA-seq datasets suggest that application of generic methods, or of methods developed for bulk RNA-seq data, is likely suboptimal.

Results

Here, we present RAFSIL, a random forest based approach to learn cell–cell similarities from scRNA-seq data. RAFSIL implements a two-step procedure, where feature construction geared towards scRNA-seq data is followed by similarity learning. It is designed to be adaptable and expandable, and RAFSIL similarities can be used for typical exploratory data analysis tasks like dimension reduction, visualization and clustering. We show that our approach compares favorably with current methods across a diverse collection of datasets, and that it can be used to detect and highlight unwanted technical variation in scRNA-seq datasets in situations where other methods fail. Overall, RAFSIL implements a flexible approach yielding a useful tool that improves the analysis of scRNA-seq data.

Availability and implementation

The RAFSIL R package is available at www.kostkalab.net/software.html

Supplementary information

Supplementary data are available at Bioinformatics online.
GSEA-InContext: identifying novel and common patterns in expression experiments
Authors: Powers Rani K , Goodspeed Andrew , Pielke-Lombardo Harrison , Tan Aik-Choon , Costello James C
Published: April 2018

Motivation

Gene Set Enrichment Analysis (GSEA) is routinely used to analyze and interpret coordinate pathway-level changes in transcriptomics experiments. For an experiment where less than seven samples per condition are compared, GSEA employs a competitive null hypothesis to test significance. A gene set enrichment score is tested against a null distribution of enrichment scores generated from permuted gene sets, where genes are randomly selected from the input experiment. Looking across a variety of biological conditions, however, genes are not randomly distributed with many showing consistent patterns of up- or down-regulation. As a result, common patterns of positively and negatively enriched gene sets are observed across experiments. Placing a single experiment into the context of a relevant set of background experiments allows us to identify both the common and experiment-specific patterns of gene set enrichment.

Results

We compiled a compendium of 442 small molecule transcriptomic experiments and used GSEA to characterize common patterns of positively and negatively enriched gene sets. To identify experiment-specific gene set enrichment, we developed the GSEA-InContext method that accounts for gene expression patterns within a background set of experiments to identify statistically significantly enriched gene sets. We evaluated GSEA-InContext on experiments using small molecules with known targets to show that it successfully prioritizes gene sets that are specific to each experiment, thus providing valuable insights that complement standard GSEA analysis.

Availability and implementation

GSEA-InContext implemented in Python, Supplementary results and the background expression compendium are available at: https://github.com/CostelloLab/GSEA-InContext.
A note on algal population dynamics
Authors: Brennen C E , Keady G , Imberger J
Published: April 2018

This is a contribution to the special issue honoring the late John R. Blake of the University of Birmingham. All three authors had the pleasure of extensive technical interactions with John Blake during his career in the UK, USA and Australia and benefited both professionally and personally from his friendship. John’s work in developing fundamental mathematical solutions for Stokes’ flows and his application of those mathematical tools to analyses of microorganism locomotion led to special new insights into the world of small-scale swimming. This special issue devoted to John’s memory seems an appropriate occasion to present another fluid mechanical challenge associated with microorganisms, namely the dynamics of algal blooms. Though it is a special reduced-order model that is of limited practical value, John would have particularly enjoyed the analytical solution to the dynamics of algae that was presented by Rutherford Aris (1997, Reflections on Keats’ equation. Chem. Eng. Sci., 52, 2447–2455) in a somewhat eccentric paper. We revisit that solution in this paper and present an extension to Aris’ solution that includes sedimentation of the algae. We think that John would have enjoyed this solution and would, in all likelihood, have been able to expand upon it to include other features such as microorganism buoyancy variations (see, e.g. Kromkamp & Walsby 1990; Belov & Giles, 1997, Dynamical model of buoyant cyanobacteria. Hydrobiologia, 349, 87–97; Brookes & Ganf, 2001, Variations in the buoyancy response of Microcystis aeruginosa to nitrogen, phosphorus and light. J. Plankton Res., 23, 1399–1411), the death of algae (see, e.g. Serizawa et al., 2008a, Computer simulations of seasonal outbreak and diurnal vertical migration of cyanobacteria. Limnology, 9, 185–194; Reynolds, 1984, The Ecology of Freshwater Phytoplankton. Cambridge University Press), the swimming of algae (see, e.g. Pedley, 2016, Spherical squirmers: models for swimming micro-organisms. IMA J. Appl. Math., 81, 488–521) and other relevant hydrodynamic matters.
Almost automorphic synchronization of quaternion-valued high-order Hopfield neural networks with time-varying and distributed delays
Authors: Li Yongkun , Wang Huimei , Meng Xiaofang
Published: April 2018

In this paper, we consider the problem of the almost automorphic synchronization of quaternion-valued high-order Hopfield neural networks (QVHHNNs) with time-varying and distributed delays. Firstly, to avoid the non-commutativity of quaternion multiplication, we decompose QVHHNNs into an equivalent real-valued system. Secondly, we use the Banach fixed point theorem to obtain the existence of almost automorphic solutions of QVHHNNs. Thirdly, by designing a novel state-feedback controller and constructing suitable Lyapunov functions, we obtain that the drive-response structure of QVHHNNs with almost automorphic coefficients can realize the exponential synchronization. Our results are completely new. Finally, a numerical example is given to illustrate the feasibility of our results.
K-Theory of Locally Compact Modules over Rings of Integers
Authors: Braunling Oliver
Published: April 2018

We generalize a recent result of Clausen; for a number field with integers $\mathcal{O}$, we compute the K-theory of locally compact $\mathcal{O}$-modules. For the rational integers this recovers Clausen’s result as a special case. Our method of proof is quite different; instead of a homotopy coherent cone construction in $\infty$-categories, we rely on calculus of fraction type results in the style of Schlichting. This produces concrete exact category models for certain quotients, a fact that might be of independent interest. As in Clausen’s work, our computation works for all localizing invariants, not just K-theory.
Make the chemical industry clean with green chemistry: an interview with Buxing Han
Authors: Zhao Weijie
Published: April 2018

In the foreseeable future, human beings will continue to live on this blue planet named Earth. Our planet has limited space, resources and environmental carrying capacity, yet the human population and quality of life will continue to rise. Economic development and environmental protection are often conflicting goals, and it is a great challenge for us to achieve both at the same time: to develop sustainably. Green chemistry—the aim of making the whole industrial chain of chemistry and chemical industry environmentally friendly—has contributed, and will further contribute, to the sustainable development of the chemical industry. Recently, NSR talked with Buxing Han—an academician of the Chinese Academy of Sciences and one of the leading scientists in this field. Han introduced the major scientific issues of green chemistry and talked about the challenges and future developments of this field.
Tractography Verified by Intraoperative Magnetic Resonance Imaging and Subcortical Stimulation During Tumor Resection Near the Corticospinal Tract
Authors: Münnich Timo , Klein Jan , Hattingen Elke , Noack Anika , Herrmann Eva , Seifert Volker , Senft Christian , Forster Marie-Therese
Published: April 2018

BACKGROUND

Tractography is a popular tool for visualizing the corticospinal tract (CST). However, results may be influenced by numerous variables, eg, the selection of seeding regions of interests (ROIs) or the chosen tracking algorithm.

OBJECTIVE

To compare different variable sets by correlating tractography results with intraoperative subcortical stimulation of the CST, correcting intraoperative brain shift by the use of intraoperative MRI.

METHODS

Seeding ROIs were created by means of motor cortex segmentation, functional MRI (fMRI), and navigated transcranial magnetic stimulation (nTMS). Based on these ROIs, tractography was run for each patient using a deterministic and a probabilistic algorithm. Tractographies were processed on pre- and postoperatively acquired data.

RESULTS

Using a linear mixed effects statistical model, best correlation between subcortical stimulation intensity and the distance between tractography and stimulation sites was achieved by using the segmented motor cortex as seeding ROI and applying the probabilistic algorithm on preoperatively acquired imaging sequences. Tractographies based on fMRI or nTMS results differed very little, but with enlargement of positive nTMS sites the stimulation-distance correlation of nTMS-based tractography improved.

CONCLUSION

Our results underline that the use of tractography demands for careful interpretation of its virtual results by considering all influencing variables.
Microvascular Anastomosis: Proposition of a Learning Curve
Authors: Mokhtari Pooneh , Tayebi Meybodi Ali , Benet Arnau , Lawton Michael T
Published: April 2018

BACKGROUND

Learning to perform a microvascular anastomosis is one of the most difficult tasks in cerebrovascular surgery. Previous studies offer little regarding the optimal protocols to maximize learning efficiency. This failure stems mainly from lack of knowledge about the learning curve of this task.

OBJECTIVE

To delineate this learning curve and provide information about its various features including acquisition, improvement, consistency, stability, and recall.

METHODS

Five neurosurgeons with an average surgical experience history of 5 yr and without any experience in bypass surgery performed microscopic anastomosis on progressively smaller-caliber silastic tubes (Biomet, Palm Beach Gardens, Florida) during 24 consecutive sessions. After a 1-, 2-, and 8-wk retention interval, they performed recall test on 0.7-mm silastic tubes. The anastomoses were rated based on anastomosis patency and presence of any leaks.

RESULTS

Improvement rate was faster during initial sessions compared to the final practice sessions. Performance decline was observed in the first session of working on a smaller-caliber tube. However, this rapidly improved during the following sessions of practice. Temporary plateaus were seen in certain segments of the curve. The retention interval between the acquisition and recall phase did not cause a regression to the prepractice performance level.

CONCLUSION

Learning the fine motor task of microvascular anastomosis adapts to the basic rules of learning such as the “power law of practice.” Our results also support the improvement of performance during consecutive sessions of practice. The objective evidence provided may help in developing optimized learning protocols for microvascular anastomosis.
Infrared spectro-polarimeter on the Solar Flare Telescope at NAOJ/Mitaka
Authors: Sakurai Takashi , Hanaoka Yoichiro , Arai Takehiko , Hagino Masaoki , Kawate Tomoko , Kitagawa Naomasa , Kobiki Toshihiko , Miyashita Masakuni , Morita Satoshi , Otsuji Ken’ichi , Shinoda Kazuya , Suzuki Isao , Yaji Kentaro , Yamasaki Takayuki , Fukuda Takeo , Noguchi Motokazu , Takeyama Norihide , Kanai Yoshikazu , Yamamuro Tomoyasu
Published: April 2018

An infrared spectro-polarimeter installed on the Solar Flare Telescope at the Mitaka headquarters of the National Astronomical Observatory of Japan is described. The new spectro-polarimeter observes the full Sun via slit scans performed at two wavelength bands, one near 1565 nm for a Zeeman-sensitive spectral line of Fe i and the other near 1083 nm for He i and Si i lines. The full Stokes profiles are recorded; the Fe i and Si i lines give information on photospheric vector magnetic fields, and the helium line is suitable for deriving chromospheric magnetic fields. The infrared detector we are using is an InGaAs camera with 640 × 512 pixels and a read-out speed of 90 frames s−1. The solar disk is covered by two swaths (the northern and southern hemispheres) of 640 pixels each. The final magnetic maps are made of 1200 × 1200 pixels with a pixel size of $1{^{\prime\prime}_{.}}8$. We have been carrying out regular observations since 2010 April, and have provided full-disk, full-Stokes maps, at the rate of a few maps per day, on the internet.
Pediatric Patient With Cerebral Metastasis From Papillary Thyroid Cancer
Authors: Korhonen Katrina , Zhuang Hongming
Published: April 2018

Brain metastasis from papillary thyroid carcinoma is uncommon. Concurrent cerebral and pulmonary metastases from papillary thyroid carcinoma is rare, especially in pediatric patients. We report a case of a brain metastasis revealed on post-therapy 131I scan in a 12 year old girl with thyroid cancer who also had diffuse pulmonary metastases which were partially responsive to sequential 131I therapy.
Sequential Sentinel Node Scintigraphy With Planar and SPECT/CT Images Revealed Contralateral Drainage From Ipsilateral Breast Tumor Relapse in a Patient With Bilateral Breast Cancer
Authors: Koizumi Mitsuru , Koyama Masamichi , Morizono Hidetomo , Miyagi Yumi
Published: April 2018

Radio-guided sentinel node (SN) biopsy is routinely performed in patients with early breast cancer. However, repeated SN scintigraphy in ipsilateral breast tumor relapse (IBTR) often shows extra-axillary drainage, including contralateral axilla. A patient diagnosed with bilateral breast cancer, of which one was IBTR, was studied by sequential radio-guided SN mapping, radiocolloid injection to an IBTR breast and scanning, and then radiocolloid injection to the other breast and scanning. This revealed the lymphatic flow from the IBTR breast to the contralateral axilla. Sequential method may help to depict contralateral axillary lymphatic flow from an IBTR breast in patients with bilateral breast cancer.
Visualizing Wnt secretion from Endoplasmic Reticulum to Filopodia
Authors: Moti Naushad , Yu Jia , Boncompain Gaelle , Perez Franck , Virshup David M
Published: April 2018

Wnts are a family of secreted palmitoleated glycoproteins that play a key role in cell to cell communications during development and regulate stem cell compartments in adults. Wnt receptors, downstream signaling cascades and target pathways have been extensively studied while less is known about how Wnts are secreted and move from producing cells to receiving cells. We used the synchronization system called Retention Using Selective Hook (RUSH) to study Wnt trafficking from endoplasmic reticulum to Golgi and then to plasma membrane and filopodia in real time. Consistent with prior studies, inhibition of porcupine (PORCN) or knockout of Wntless (WLS) blocked Wnt exit from the ER. Indeed, WLS was rate-limiting for Wnt ER exit. Wnt-containing vesicles paused at sub-cortical regions of the plasma membrane before exiting the cell. Wnt-containing vesicles were transported to adjacent cells associated with filopodia. Increasing the number of filopodia by expression of LGR5 in the producing cell increased the ability of a cell to send a Wnt signal. The RUSH system is a powerful tool to provide new insights into the Wnt secretory pathway.
Parental neural responsivity to infants’ visual attention: how mature brains scaffold immature brains during social interaction
Authors: S.V. Wass , V. Noreika , S. Georgieva , K. Clackson , L. Brightman , R. Nutbrown , L. Santamaria , V. Leong
Published: April 2018

Almost all attention and learning - in particular, most early learning – takes place in social settings. But little is known of how our brains support dynamic social interactions. We recorded dual-EEG from infants and parents during solo play and joint play. During solo play, fluctuations in infants’ Theta power significantly forward-predicted their subsequent attentional behaviours. But this forwards-predictiveness was lower during joint play than solo play, suggesting that infants’ endogenous neural control over attention is greater during solo play. Overall, however, infants were more attentive to the objects during joint play. To understand why, we examined how adult brain activity related to infant attention. We found that parents’ Theta power closely tracked and responded to changes in their infants’ attention. Further, instances in which parents showed greater neural responsivity were associated with longer sustained attention by infants. Our results offer new insights into how one partner influences another during social interaction.
The diversity of antibiotic resistance and virulence genes are correlated in human gut and environmental microbiomes
Authors: Escudeiro Pedro , Pothier Joël , Dionisio Francisco , Nogueira Teresa
Published: April 2018

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of non-pathogenic bacterial species are affected as well. Therefore, both pathogenic and non-pathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still co-occurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes issuing from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (ARd) and virulence factors (VFd) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut there are less ARd and VFd than in more diversified environments, and yet correlations between the ARd and VFd are stronger. They can vary from very high in Malawi, where antibiotic consumption is unattended, to non-existent in the uncontacted Amerindians. We conclude that there is co-occurrence of resistance and virulence determinants, suggesting a possible co-selective mechanism. For example, by selecting for resistant bacteria, we may be selecting for more virulent strains as a side effect of antimicrobial therapy.
RAB-35 aids apoptotic cell clearance by regulating cell corpse recognition and phagosome maturation
Authors: Haley Ryan C. , Wang Ying , Zhou Zheng
Published: April 2018

In metazoans, apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Multiple small GTPases in the Rab family are known to function in phagosome maturation by regulating vesicle trafficking. We discoveredrab-35as a new gene important for apoptotic cell clearance using an RNAi screen targeting putative Rab GTPases inCaenorhabditis elegans. We further identified TBC-10 as a putative GTPase-activating protein (GAP), and FLCN-1 and RME-4 as two putative Guanine Nucleotide Exchange Factors (GEFs), for RAB-35. RAB-35 function was found to be required for the incorporation of early endosomes to phagosomes and for the timely degradation of apoptotic cell corpses. More specifically, RAB-35 facilitates the switch of phagosomal membrane phosphatidylinositol species from PtdIns(4,5)P2to PtdIns(3)P and promotes the recruitment of the small GTPase RAB-5 to phagosomal surfaces, processes that are essential for phagosome maturation. Interestingly, we observed that CED-1 performs these same functions, and to a much larger extent than RAB-35. Remarkably, in addition to cell corpse degradation, RAB-35 also facilitates the recognition of cell corpses independently of the CED-1 and CED-5 pathways. RAB-35 localizes to extending pseudopods and is further enriched on nascent phagosomes, consistent with its dual roles in regulating cell corpse-recognition and phagosome maturation. Epistasis analyses indicate thatrab-35represents a novel third genetic pathway that acts in parallel to both of the canonicalced-1/6/7andced-2/5/10/12engulfment pathways. We propose that RAB-35 acts as a robustness factor, leading a pathway that aids the canonical pathways for the engulfment and degradation of apoptotic cells.
Evaluation and optimization of the protocols for measuring cytochrome P450 activity in aphids
Authors: Cao He-He , Liu Tong-Xian
Published: April 2018

Cytochrome P450 enzymes play major roles in insect detoxification of plant toxins and insecticides. However, measuring P450 activity in aphids has variable success, and a reliable method is not available yet. In this study, we evaluated and optimized the method for measuring P450 activity in aphids using the 7-ethoxycoumarin as the substrate. First, we found that nicotinamide adenine dinucleotide phosphate and protective agents are not needed in the aphid P450 activity assay, and homogenizing the green peach aphid,Myzus persicae, in the microplate resulted in significantly higher P450 activities than those in Eppendorf tube. Homogenizing aphids in Eppendorf tube could grind tissues thoroughly and released uncharacterized compounds that could inhibit aphid and pig liver P450 activities, whereas aphids in the microplate likely could not be thoroughly ground and thus released fewer such inhibitors. Then, the microplate homogenization method was optimized to follows: one or two aphids were put into one well of the microplate and ground in phosphate buffer using pipette tips for 20 cycles, followed by addition of 7-ethoxycoumarin, and then incubated for 1 h at room temperature, after which glycine buffer-ethanol mixture was added to stop the reaction. This method is also suitable for the pea aphid,Acyrthosiphon pisum, and the bird cherry □oat aphid,Rhopalosiphum padi.These results emphasize the importance of considering inhibitory effect of endogenous compounds in insects on their P450 activity and provide one possible method to reduce this inhibitory effect.
Comment on ‘Multiple Origin but Single Domestication Led to Oryza sativa’
Authors: Civáň Peter , Brown Terence A.
Published: April 2018

In 2015, we published an analysis of rice genomic data and showed that the japonica, indica and aus groups of cultivated rice were independently domesticated. Our conclusions were controversial as they contradicted a previous, high-profile analysis of the same dataset, which had suggested that all of cultivated rice derives from a single origin. Although there have been attempts since 2015 to bolster the single-origin hypothesis, until recently there has been no direct rebuttal of the methodology that we used to infer multiple origins. Such a rebuttal has now been published (Choi J.Y., Purugganan M.D., 2018 Multiple origin but single domestication led to Oryza sativa. G3 8:797-803), but the reanalysis that is presented only supports the single origin hypothesis if phylogenetic trees that are clearly paraphyletic are interpreted as monophyletic, and furthermore addresses only one component of the evidence that we presented for multiple domestications. We caution against accepting these analyses uncritically.
Sensory domain of the cell cycle kinase CckA inCaulobacter crescentusregulates the differential DNA binding activity of the master regulator CtrA
Authors: Narayanan Sharath , Kumar Lokesh , Radhakrishnan Sunish Kumar
Published: April 2018

Sophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways facilitates the cells to overcome cellular damage and thereby warrant integrity. Here we demonstrate the pliability of the CckA-CtrA two component signaling system in the freshwater bacteriumCaulobacter crescentus. Our forward genetic screen to analyse suppressor mutations that can negate the chromosome segregation block induced by the topoisomerase IV inhibitor, NstA, yielded various point mutations in the cell cycle histidine kinase, CckA. Notably, we identified a point mutation in the PAS-B domain of CckA, which resulted in increased levels of phosphorylated CtrA (CtrA~P), the master cell cycle regulator. Surprisingly, this increase in CtrA~P levels did not translate into a genome-wide increase in the DNA occupancy of CtrA, but specifically enriched its affinity to the chromosomal origin of replication, Cori, and a very small sub-set of CtrA regulated promoters. We show that through this enhanced binding of CtrA to the Cori, cells are able to overcome the toxic defects rendered by stable NstA through a possible slow down in the chromosome cycle. Taken together, our work opens up an unexplored and intriguing aspect of the CckA-CtrA signal transduction pathway. The distinctive DNA binding nature of CtrA and its regulation by CckA might also be crucial for pathogenesis because of the highly conserved nature of CckA-CtrA pathway in alphaproteobacteria.
Identification of protein abundance changes in biopsy-level hepatocellular carcinoma tissues using PCT-SWATH
Authors: Zhu Yi , Zhu Jiang , Lu Cong , Sun Ping , Xie Wei , Zhang Qiushi , Yue Liang , Zhu Tiansheng , Ruan Guan , Aebersold Ruedi , Huang Shi’ang , Guo Tiannan
Published: April 2018

In this study, we optimized the pressure-cycling technology (PCT) and SWATH mass spectrometry workflow to analyze biopsy-level tissue samples (2 mg wet weight) from 19 hepatocellular carcinoma (HCC) patients. Using OpenSWATH and pan-human spectral library, we quantified 11,787 proteotypic peptides from 2,579 SwissProt proteins in 76 HCC tissue samples within about 9 working days (from receiving tissue to SWATH data). The coefficient of variation (CV) of peptide yield using PCT was 32.9%, and the R2 of peptide quantification was 0.9729. We identified protein changes in malignant tissues compared to matched control samples in HCC patients, and further stratified patient samples into groups with high α-fetoprotein (AFP) expression or HBV infection. In aggregate, the data identified 23 upregulated pathways and 13 ones. We observed enhanced biomolecule synthesis and suppressed small molecular metabolism in liver tumor tissues. 16 proteins of high documented relevance to HCC are highlighted in our data. We also identified changes of virus-infection-related proteins including PKM, CTPS1 and ALDOB in the HBV+ HCC subcohort. In conclusion, we demonstrate the practicality of performing proteomic analysis of biopsy-level tissue samples with PCT-SWATH methodology with moderate effort and within a relatively short timeframe.
Taxa-driven functional shifts associated with stormflow in an urban stream microbial community
Authors: Chaudhary Adit , Kauser Imrose , Ray Anirban , Poretsky Rachel
Published: April 2018

Urban streams are susceptible to stormwater and sewage inputs that can impact their ecological health and water quality. Microbial communities in streams play important functional roles and their composition and metabolic potential can help assess ecological state and water quality. Although these environments are highly heterogenous, little is known about the influence of isolated perturbations, such as those resulting from rain events on urban stream microbiota. Here, we examined the microbial community composition and diversity in an urban stream during dry and wet weather conditions with both 16S rRNA gene sequencing across multiple years and shotgun metagenomics to more deeply analyze a single stormflow event. Metagenomics was used to assess population-level dynamics as well as shifts in the microbial community taxonomic profile and functional potential before and after a substantial rainfall. Results demonstrated general trends present in the stream under stormflow vs. baseflow conditions across years and seasons and also highlighted the significant influence of increased effluent flow following rain in shifting the stream microbial community from abundant freshwater taxa to those more associated with urban/anthropogenic settings. Shifts in the taxonomic composition were also linked to changes in functional gene content, particularly for transmembrane transport and organic substance biosynthesis. We also observed an increase in relative abundance of genes encoding degradation of organic pollutants and antibiotic resistance after rain. Overall, this study provided evidence of stormflow impacts on an urban stream microbiome from an environmental and public health perspective.

Importance

Urban streams in various parts of the world are facing increased anthropogenic pressure on their water quality, and stormflow events represent one such source of complex physical, chemical and biological perturbations. Microorganisms are important components of these streams from both ecological and public-health perspectives, and analyzing the effect of such perturbations on the stream microbial community can help improve current knowledge on the impact such chronic disturbances can have on these water resources. This study examines microbial community dynamics during rain-induced stormflow conditions in an urban stream of the Chicago Area Waterway System. Additionally, using shotgun metagenomics we identified significant shifts in the microbial community composition and functional gene content following a high rainfall event, with potential environment and public health implications. Previous work in this area has been limited to specific genes/organisms or has not assessed immediate stormflow impact.
Feammox Acidimicrobiaceae bacterium A6, a lithoautotrophic electrode-colonizing bacterium
Authors: Ruiz-Urigüen Melany , Shuai Weitao , Jaffé Peter R.
Published: April 2018

An Acidimicrobiaceae bacterium A6 (A6), from the Acitnobacteria phylum was recently identified as a microorganism that can carry out anaerobic ammonium oxidation coupled to iron reduction, a process also known as Feammox. Being an iron-reducing bacterium, A6 was studied as a potential electrode-reducing bacterium that may transfer electrons extracellularly onto electrodes while gaining energy from ammonium oxidation. Actinobacteria species have been overlooked as electrogenic bacteria, and the importance of lithoautotrophic iron-reducers as electrode-reducing bacteria at anodes has not been addressed. By installing electrodes in soil of a forested riparian wetland where A6 thrives, as well as in A6 bioaugmented constructed wetland (CW) mesocosms, characteristics and performances of this organism as an electrode-reducing bacterium candidate were investigated. In this study, we show that Acidimicrobiaceae bacterium A6 is a lithoautotrophic bacterium, capable of colonizing electrodes in the field as well as in CW mesocosoms, and that it appears to be an electrode-reducing bacterium since there was a boost in current production shortly after the CWs were seeded with Acidimicrobiaceae bacterium A6.

IMPORTANCE

Most studies on electrogenic microorganisms have focused on the most abundant heterotrophs, while other microorganisms also commonly present in electrode microbial communities such as Actinobacteria have been overlooked. The novel Acidimicrobiaceae bacterium A6 (Actinobacteria) is an iron-reducing bacterium that can colonize the surface of anodes and is linked to electrical current production, making it an electrode-reducing candidate. Furthermore, A6 can carry out anaerobic ammonium oxidation coupled to iron reduction, therefore, findings from this study open up the possibility of using electrodes instead of iron as electron acceptors as a mean to promote A6 to treat ammonium containing wastewater more efficiently. Altogether, this study expands our knowledge on electrogenic bacteria and opens up the possibility to develop Feammox based technologies coupled to bioelectric systems for the treatment NH4+ and other contaminants in anoxic systems.
Fermentation characteristics of mead and wine generated by yeasts isolated from beehives of two Austrian regions
Authors: Gangl Helmut , Lopandic Ksenija , Tscheik Gabriele , Mandl Stefan , Leitner Gerhard , Wechselberger Katharina , Batusic Maria , Tiefenbrunner Wolfgang
Published: April 2018

Mead is a traditional alcoholic beverage that is produced by fermentation of diluted honey. The mead quality is primarily influenced by the honey variety, although the yeast microflora as the main catalyst of alcoholic fermentation also plays a significant role in the organoleptic and chemical quality of the final product. The impact of the indigenous honey associated-yeasts on the mead properties has scarcely been investigated. To fill this gap the main objective of this work was to assess the metabolic properties of the yeasts isolated from honey and pollen from beehives of northeast Austria.

The biodiversity was low and only two yeast species were identified,Zygosaccharomyces rouxiiandCandida apicola.The fermentation potentials of these yeasts were estimated in two media, grape juice (since yeasts isolated from honey may be useful for sweet wine production) and diluted honey of similar sugar concentration, and compared with those of the reference strainsSaccharomyces cerevisiae;S. uvarumandS. eubayanus.Depending on the fermentation substrate, yeasts differed with respect to their metabolic power, fermentation rate, sugar utilization and production of glycerol and organic acids. During mead fermentationSaccharomycesspecies showed the highest metabolic turnover, while the fermentation rate did not differ significantly. Addition of assimilable nitrogen to the diluted honey enhanced fermentation rate ofS. cerevisiae, but not of the other species. Fermentation of grape juice occurred much faster than that of diluted honey and differences between yeasts were more pronounced. TheS. cerevisiaecommercial wine strain, adapted to high alcohol concentrations, andS. eubayanusoutperformed the others,S. uvarumwas comparable withZ. rouxii, whileC. apicolahad the lowest fermentation rate. Fructophily ofZ. rouxiiand to a lesser degree ofC. apicolawas observed in both media. An increased production of glycerol was achieved byS. eubayanusin both media and byC. apicoladuring the fermentation of honey must. A commercialS. cerevisiaestrain,S. eubayanusandZ. rouxiiwere able to metabolize malic acid in wine. In mead, theS. eubayanusandS. uvarumyeasts showed the tendency of increasing the level of malic acid. Aroma profile depended profoundly on yeast species. This study demonstrates that the composition and complexity of the fermentation substrate determines the activity and the final metabolic outcomes of the studied yeasts.
The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes inNrxn2deletion mice
Authors: Pervolaraki Eleftheria , Tyson Adam L. , Pibiri Francesca , Poulter Steven L. , Reichelt Amy C. , Rodgers R. John , Clapcote Steven J. , Lever Colin , Andreae Laura C. , Dachtler James
Published: April 2018

Background

Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role forNRXN2in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to theNrxn2αknockout (KO) model.

Methods

Fixed brains ofNrxn2αKO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified.

Results

DTI revealed decreases in fractional anisotropy and increases in apparent diffusion coefficient in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Radial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased inNrxn2αKO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density.

Conclusions

Our findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.
Dynamic modeling ofStreptococcus pneumoniaecompetence provides regulatory mechanistic insights
Authors: Weyder Mathias , Prudhomme Marc , Bergé Mathieu , Polard Patrice , Fichant Gwennaele
Published: April 2018

In the human pathogenStreptococcus pneumoniae, the gene regulatory circuit leading to the transient state of competence for natural transformation is based on production of an auto-inducer that activates a positive feedback loop. About one hundred genes are activated in two successive waves linked by a central alternative sigma factor ComX. This mechanism appears to be fundamental to the biological fitness ofS. pneumoniae.We have developed a knowledge-based model of the competence cycle that describes average cell behavior. It reveals that the expression rates of the two competence operon,comABandcomCDE, involved in the positive feedback loop must be coordinated to elicit spontaneous competence. Simulations revealed the requirement for an unknown latecomgene product that shuts of competence by impairing ComX activity. Further simulations led to the predictions that the membrane protein ComD bound to CSP reacts directly to pH change of the medium and that blindness to CSP during the post-competence phase is controlled by late DprA protein. Both predictions were confirmed experimentally.
Investigating the neuroprotective effect of AAV-mediated β-synuclein overexpression in a transgenic model of synucleinopathy
Authors: Sargent Dorian , Bétemps Dominique , Drouyer Matthieu , Verchere Jérémy , Gaillard Damien , Arsac Jean-Noël , Lakhdar Latifa , Salvetti Anna , Baron Thierry
Published: April 2018

Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by inclusions mainly composed of α-synuclein (α-syn) aggregates. The objective of this study was to investigate if β-synuclein (β-syn) overexpression could have beneficial effects by inhibiting the aggregation of α-syn. The M83 transgenic mouse is a model of synucleinopathy, which develops severe motor symptoms associated with aggregation of α-syn. M83 neonate or adult mice were injected with adeno-associated virus vectors carrying the human β-syn gene (AAVβ-syn) or green fluorescent protein gene (AAVGFP) using different injection sites. One or two months later, M83 disease was accelerated or not using brain M83 extracts from mouse (M83) or human (MSA) origins. AAV mediated β-syn overexpression detected by ELISA did not delay the disease onset, regardless of the AAV injection route and of the inoculation of brain extracts. Accordingly, phosphorylated α-syn levels detected by ELISA in sick mice were similar after injecting AAVβ-syn or AAVGFP. Instead, immunohistochemistry analysis of β-syn indicated the presence of proteinase-K resistant β-syn staining specifically in sick M83 mice inoculated with AAVβ-syn. This study indicated for the first time that β-syn could form aggregates in a model of synucleinopathy when it is expressed by a viral vector.
Pervasive hybridizations in the history of wheat relatives
Authors: Glémin Sylvain , Scornavacca Celine , Dainat Jacques , Burgarella Concetta , Viader Véronique , Ardisson Morgane , Sarah Gautier , Santoni Sylvain , David Jacques , Ranwez Vincent
Published: April 2018

Bread wheat and durum wheat derive from an intricate evolutionary history of three genomes, namely A, B and D, present in both extent diploid and polyploid species. Despite its importance for wheat research, no consensus on the phylogeny of the wheat clade has emerged so far, possibly because of hybridizations and gene flows that make phylogeny reconstruction challenging. Recently, it has been proposed that the D genome originated from an ancient hybridization event between the A and B genomes1. However, the study only relied on four diploid wheat relatives when 13 species are accessible. Using transcriptome data from all diploid species and a new methodological approach, we provide the first comprehensive phylogenomic analysis of this group. Our analysis reveals that most species belong to the D-genome lineage and descend from the previously detected hybridization event, but with a more complex scenario and with a different parent than previously thought. If we confirmed that one parent was the A genome, we found that the second was not the B genome but the ancestor ofAegilops mutica(T genome), an overlooked wild species. We also unravel evidence of other massive gene flow events that could explain long-standing controversies in the classification of wheat relatives. We anticipate that these results will strongly affect future wheat research by providing a robust evolutionary framework and refocusing interest on understudied species. The new method we proposed should also be pivotal for further methodological developments to reconstruct species relationship with multiple hybridizations.
The influence of the supramolecular complex PRE -1 on permeability of membranes of mitochondria
Authors: Mardieva Kamila , Burkhanova Munira
Published: April 2018

The change in the state of the mitochondrial pore of nonspecific conductivity plays a key role in the processes of triggering and regulating apoptosis. Therefore, the study of mechanisms of opening and regulating the state of these pores can have a great importance to find the ways of correcting many mitochondrial dysfunctions, including those which are associated with age-related changes. In our work, we have done a comparative analysis for swelling of brain mitochondria of adult (9 months) and mature rats (12-15 months).
Robust representation of natural images by sparse and variable population of active neurons in visual cortex
Authors: Yoshida Takashi , Ohki Kenichi
Published: April 2018

Natural scenes sparsely activate neurons in the primary visual cortex (V1). However, how sparsely active neurons robustly represent natural images and how the information is optimally decoded from the representation have not been revealed. We reconstructed natural images from V1 activity in anaesthetized and awake mice. A single natural image was linearly decodable from a surprisingly small number of highly responsive neurons, and an additional use of remaining neurons even degraded the decoding. This representation was achieved by diverse receptive fields (RFs) of the small number of highly responsive neurons. Furthermore, these neurons reliably represented the image across trials, regardless of trial-to-trial response variability. The reliable representation was supported by multiple neurons with overlapping RFs. Based on our results, the diverse, partially overlapping RFs ensure sparse and reliable representation. We propose a new representation scheme in which information is reliably represented while the representing neuronal patterns change across trials and that collecting only the activity of highly responsive neurons is an optimal decoding strategy for the downstream neurons
Contribution of the endosomal-lysosomal and proteasomal systems in Amyloid-β Precursor Protein derived fragments processing
Authors: Evrard Caroline , Kienlen-Campard Pascal , Opsomer Rémi , Tasiaux Bernadette , Octave Jean-Noël , Buée Luc , Sergeant Nicolas , Vingtdeux Valérie
Published: April 2018

Aβ peptides, the major components of amyloid deposits of Alzheimer’s disease, are released following sequential cleavages by secretases of its precursor named the amyloid precursor protein (APP). In addition to secretases, degradation pathways, in particular the endosomal/lysosomal and proteasomal systems have also been reported to contribute to APP processing. However, the respective role of each of these pathways towards APP metabolism remains to be established. To address this, we used HEK 293 cells and primary neurons expressing full-length APPWTor the β-secretase-derived C99 fragments (β-CTFs) in which degradation pathways were selectively blocked using pharmacological drugs. APP metabolites, including carboxy-terminal fragments (CTFs), soluble APP (sAPP) and Aβ peptides were studied. In this report, we show that APP-CTFs produced from endogenous or overexpressed full-length APP are mainly processed by γ-secretase and the endosomal/lysosomal pathway, while in sharp contrast, overexpressed C99 alone is mainly degraded by the proteasome and to a lesser extent by γ-secretase.
B cell receptor crosslinking can augment T cell help-mediated germinal center B cell selection
Authors: Turner Jackson S. , Ke Fang , Grigorova Irina L.
Published: April 2018

Selection of germinal center (GC) B cells with B cell receptors (BCR) possessing high affinity to foreign antigen (Ag) and their differentiation into antibody-secreting long-lived plasma cells is critical for potent long-term humoral immunity. Ag-dependent engagement of GC B cell BCR triggers Ag internalization and loading of antigenic peptides on MHCII molecules for presentation to follicular helper T cells (Tfh) and acquisition of T cell help. However, whether it also provides signals that are critical or synergistic with T cell help for GC B cell selection and differentiationin vivois not known. Here we show that T cell help is sufficient to induce GC B cell expansion and plasmablast (PB) formation in the absence of recurrent BCR engagement with Ag. Ag-mediated BCR crosslinking on the other hand is not sufficient to promote GC B cell selection, but can synergize with T cell help to enhance the GC B cell and PB responses when T cell help is limiting.