bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse dLGN receives input from a diverse population of retinal ganglion cells with limited convergence
Authors: Rosón Miroslav Román , Bauer Yannik , Berens Philipp , Euler Thomas , Busse Laura 
Published: May 2018

SUMMARYIn the mouse, the parallel output of more than 30 functional types of retinal ganglion cells (RGCs) serves as the basis for all further visual processing. Little is known about how the representation of visual information changes between the retina and the dorsolateral geniculate nucleus (dLGN) of the thalamus, the main relay station between the retina and cortex. Here, we functionally characterized responses of retrogradely labeled dLGN-projecting RGCs and dLGN neurons to the same set of visual stimuli. We found that many of the previously identified functional RGC types innervate the dLGN, which maintained a high degree of functional diversity. Using a linear model to assess functional connectivity between RGC types and dLGN neurons, we found that the responses of dLGN neurons could be predicted as a linear combination of inputs from on average five RGC types, but only two of those had the strongest functional impact. Thus, mouse dLGN receives input from a diverse population of RGCs with limited functional convergence.
A low-cost hyperspectral scanner for natural imaging above and under water
Authors: Nevala N. E. , Baden T. 
Published: May 2018

ABSTRACTHyperspectral imaging is a widely used technology for industrial and scientific purposes, but the high cost and large size of commercial setups have made them impractical for most basic research. Here, we designed and implemented a fully open source and low-cost hyperspectral scanner based on a commercial spectrometer coupled to custom optical, mechanical and electronic components. We demonstrate our scanner’s utility for natural imaging in both terrestrial and underwater environments. Our design provides sub-nm spectral resolution between 350–1000 nm, including the UV part of the light spectrum which has been mostly absent from commercial solutions and previous natural imaging studies. By comparing the full light spectra from natural scenes to the spectral sensitivity of animals, we show how our system can be used to identify subtle variations in chromatic details detectable by different species. In addition, we have created an open access database for hyperspectral datasets collected from natural scenes in the UK and India. Together with comprehensive online build- and use-instructions, our setup provides an inexpensive and customisable solution to gather and share hyperspectral imaging data.
Automatic Localization of the Subthalamic Nucleus on Patient-Specific Clinical MRI by Incorporating 7T MRI and Machine Learning: Application in Deep Brain Stimulation
Authors: Kim Jinyoung , Duchin Yuval , Shamir Reuben R. , Patriat Remi , Vitek Jerrold , Harel Noam , Sapiro Guillermo 
Published: May 2018

ABSTRACTDeep Brain Stimulation (DBS) of the subthalamic nucleus (STN) has shown clinical potential for relieving the motor symptoms of advanced Parkinson’s disease. While accurate localization of the STN is critical for consistent across-patients effective DBS, clear visualization of the STN under standard clinical MR protocols is still challenging. Therefore, intraoperative microelectrode recordings (MER) are incorporated to accurately localize the STN. However, MER require significant neurosurgical expertise and lengthen the surgery time. Recent advances in 7T MR technology facilitate the ability to clearly visualize the STN. The vast majority of centers, however, still do not have 7T MRI systems, and fewer have the ability to collect and analyze the data. This work introduces an automatic STN localization framework based on standard clinical MRIs without additional cost in the current DBS planning protocol. Our approach benefits from a large database of 7T MRI and its clinical MRI pairs. We first model in the 7T database, using efficient machine learning algorithms, the spatial and geometric dependency between the STN and its adjacent structures (predictors). Given a standard clinical MRI, our method automatically computes the predictors and uses the learned information to predict the patient-specific STN. We validate our proposed method on clinical T2W MRI of 80 subjects, comparing with experts-segmented STNs from the corresponding 7T MRI pairs. The experimental results show that our framework provides more accurate and robust patient-specific STN localization than using state-of-the-art atlases. We also demonstrate the clinical feasibility of the proposed technique assessing the post-operative electrode active contact locations.
Optimization of Golden Gate assembly through application of ligation sequence-dependent fidelity and bias profiling
Authors: Vladimir Potapov , Ong Jennifer L. , Kucera Rebecca B. , Langhorst Bradley W. , Bilotti Katharina , Pryor John M. , Cantor Eric J. , Canton Barry , Knight Thomas F. , Evans Thomas C. , Lohman Gregory J. S. 
Published: May 2018

ABSTRACTModern synthetic biology depends on the manufacture of large DNA constructs from libraries of genes, regulatory elements or other genetic parts. Type IIS restriction enzyme-dependent DNA assembly methods (e.g., Golden Gate) enable rapid one-pot, ordered, multi-fragment DNA assembly, facilitating the generation of high-complexity constructs. The order of assembly of genetic parts is determined by the ligation of flanking Watson-Crick base-paired overhangs. The ligation of mismatched overhangs leads to erroneous assembly, and the need to avoid such pairings has typically been accomplished by using small sets of empirically vetted junction pairs, limiting the number of parts that can be joined in a single reaction. Here, we report the use of a comprehensive method for profiling end-joining ligation fidelity and bias to predict highly accurate sets of connections for ligation-based DNA assembly methods. This data set allows quantification of sequence-dependent ligation efficiency and identification of mismatch-prone pairings. The ligation profile accurately predicted junction fidelity in ten-fragment Golden Gate assembly reactions, and enabled efficient assembly of a lac cassette from up to 24-fragments in a single reaction. Application of the ligation fidelity profile to inform choice of junctions thus enables highly flexible assembly design, with >20 fragments in a single reaction.
Physiomarkers in Real-Time Physiological Data Streams Predict Adult Sepsis Onset Earlier Than Clinical Practice
Authors: van Wyk Franco , Khojandi Anahita , Davis Robert L. , Kamaleswaran Rishikesan 
Published: May 2018

AbstractRationale:Sepsis is a life-threatening condition with high mortality rates and expensive treatment costs. To improve short- and long-term outcomes, it is critical to detect at-risk sepsis patients at an early stage.Objective:Our primary goal was to develop machine learning models capable of predicting sepsis using streaming physiological data in real-time.Methods:A dataset consisting of high-frequency physiological data from 1,161 critically ill patients admitted to the intensive care unit (ICU) was analyzed in this IRB-approved retrospective observational cohort study. Of that total, 634 patients were identified to have developed sepsis. In this paper, we define sepsis as meeting the Systemic Inflammatory Response Syndrome (SIRS) criteria in the presence of the suspicion of infection. In addition to the physiological data, we include white blood cell count (WBC) to develop a model that can signal the future occurrence of sepsis. A random forest classifier was trained to discriminate between sepsis and non-sepsis patients using a total of 108 features extracted from 2-hour moving time-windows. The models were trained on 80% of the patients and were tested on the remaining 20% of the patients, for two observational periods of lengths 3 and 6 hours.Results:The models, respectively, resulted in F1 scores of 75% and 69% half-hour before sepsis onset and 79% and 76% ten minutes before sepsis onset. On average, the models were able to predict sepsis 210 minutes (3.5 hours) before the onset.Conclusions:The use of robust machine learning algorithms, continuous streams of physiological data, and WBC, allows for early identification of at-risk patients in real-time with high accuracy.
Understanding the impact of crosslinked PCL/PEG/GelMA electrospun nanofibers on bactericidal activity
Authors: De-Paula Mirian Michelle Machado , Ghannadian Paria , Afewerki Samson , Marciano Fernanda Roberta , Viana Bartolomeu Cruz , Harb Samarah Vargas , Bassous Nicole Joy , Webster Thomas Jay , Lobo Anderson Oliveira 
Published: May 2018

AbstractHerein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential bactericidal activity against three different bacteriaStaphylococcus aureus, Pseudomonas aeruginosa, andMethicillin-resistant Staphylococcus aureus(MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds bactericidal activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient bactericidal activity without the association of any antibiotics.
Connectivity-Informed Adaptive Regularization for Generalized Outcomes
Authors: Brzyski Damian , Karas Marta , Ances Beau , Dzemidzic Mario , Goni Joaquin , Randolph Timothy W , Harezlak Jaroslaw 
Published: May 2018

AbstractOne of the challenging problems in the brain imaging research is a principled incorporation of information from different imaging modalities in association studies. Frequently, data from each modality is analyzed separately using, for instance, dimensionality reduction techniques, which result in a loss of mutual information. We propose a novel regularization method, griPEER (generalized ridgified Partially Empirical Eigenvectors for Regression) to estimate the association between the brain structure features and a scalar outcome within the generalized linear regression framework. griPEER provides a principled approach to use external information from the structural brain connectivity to improve the regression coefficient estimation. Our proposal incorporates a penalty term, derived from the structural connectivity Laplacian matrix, in the penalized generalized linear regression. We address both theoretical and computational issues and show that our method is robust to the incomplete information about the structural brain connectivity. We also provide a significance testing procedure for performing inference on the estimated coefficients in this model. griPEER is evaluated in extensive simulation studies and it is applied in classification of the HIV+ and HIV- individuals.
C. elegans germ cells divide and differentiate along a folded epithelium
Authors: Seidel Hannah S. , Smith Tilmira A. , Evans Jessica K. , Stamper Jarred Q. , Mast Thomas G. , Kimble Judith 
Published: May 2018

AbstractKnowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the ‘progenitor zone’. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described “steps” in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.
Viral Taxonomy Derived From Evolutionary Genome Relationships
Authors: Dougan Tyler J. , Quake Stephen R. 
Published: May 2018

AbstractWe describe a new genome alignment-based model for classification of viruses based on evolutionary genetic relationships. This approach uses information theory and a physical model to determine the information shared by the genes in two genomes. Pairwise comparisons of genes from the viruses are created from alignments using NCBI BLAST, and their match scores are combined to produce a metric between genomes, which is in turn used to determine a global classification using the 5,817 viruses on RefSeq. In cases where there is no measurable alignment between any genes, the method falls back to a coarser measure of genome relationship: the mutual information of k-mer frequency. This results in a principled model which depends only on the genome sequence, which captures many interesting relationships between viral families, and which creates clusters which correlate well with both the Baltimore and ICTV classifications. The incremental computational cost of classifying a novel virus is low and therefore newly discovered viruses can be quickly identified and classified.
The iron-dependent repressor YtgR regulates the tryptophan salvage pathway through a bipartite mechanism of transcriptional control inChlamydia trachomatis
Authors: Pokorzynski Nick D. , Brinkworth Amanda J. , Carabeo Rey A. 
Published: May 2018

AbstractDuring infection, pathogens are starved of essential nutrients such as iron and tryptophan by host immune effectors. Without conserved global stress response regulators, how the obligate intracellular bacteriumChlamydia trachomatisarrives at a physiologically similar “persistent” state in response to starvation of either nutrient remains unclear. Here, we report on the iron-dependent regulation of thetrpRBAtryptophan salvage pathway inC. trachomatis. Iron starvation specifically inducestrpBAexpression from a novel promoter element within an intergenic region flanked bytrpRandtrpB.YtgR, the only known iron-dependent regulator inChlamydia,can bind to thetrpRBAintergenic region upstream of the alternativetrpBApromoter to repress transcription. Simultaneously, YtgR binding promotes the termination of transcripts from the primary promoter upstream oftrpR.This is the first description of an iron-dependent mechanism regulating prokaryotic tryptophan biosynthesis that may indicate the existence of novel approaches to gene regulation and stress response inChlamydia.
Protein mismatches caused by reassortment influence functions of the reovirus capsid
Authors: Thete Deepti , Danthi Pranav 
Published: May 2018

ABSTRACTFollowing attachment to host receptors via σ1, reovirus particles are endocytosed and disassembled to generate infectious subvirion particles (ISVPs). ISVPs undergo conformational changes to form ISVP*, releasing σ1 and membrane-targeting peptides from the viral μ1 protein. ISVP* formation is required for delivery of the viral core into the cytoplasm for replication. We characterized the properties of T3DF/T3DCS1, a S1 gene monoreassortant between two laboratory isolates of prototype reovirus strain T3D: T3DFand T3DC. T3DF/T3DCS1 is poorly infectious. This deficiency is a consequence of inefficient encapsidation of S1-encoded σ1 on T3DF/T3DCS1 virions. Additionally, in comparison to T3DF, T3DF/T3DCS1 undergoes ISVP-to-ISVP* conversion more readily, revealing an unexpected role for σ1 in regulating ISVP* formation. The σ1 protein is held within turrets formed by the λ2 protein. To test if the altered properties of T3DF/T3DCS1 are due to a mismatch between σ1 and λ2 proteins from T3DFand T3DC, properties of T3DF/T3DCL2 and T3DF/T3DCS1L2, which express a T3DC-derived λ2, were compared. The presence of T3DCλ2 allowed more efficient σ1 incorporation, producing particles that exhibit T3DF-like infectivity. In comparison to T3DF, T3DF/T3DCL2 prematurely converts to ISVP* uncovering a role for λ2 in regulating ISVP* formation. Importantly, a virus with matching σ1 and λ2 displayed a more regulated conversion to ISVP* than either T3DF/T3DCS1 or T3DF/T3DCL2. In addition to identifying new regulators of ISVP* formation, our results highlight that protein mismatches produced by reassortment can alter virus assembly and thereby influence subsequent functions of the virus capsid.
Bacterial plasma membrane is the main cellular target of silver nanoparticles inEscherichia coliandPseudomonas aeruginosa
Authors: Bondarenko Olesja M , Sihtmäe Mariliis , Kuzmičiova Julia , Ragelienė Lina , Kahru Anne , Daugelavičius Rimantas 
Published: May 2018

ABSTRACTSilver nanoparticles (AgNP) are widely used in consumer products, mostly due to their excellent antimicrobial properties. One of the well-established antibacterial mechanisms of AgNP is their efficient contact with bacteria and dissolution on cell membranes. To our knowledge, the primary mechanism of cell wall damage and the event(s) initiating bactericidal action of AgNP are not yet elucidated.In this study we used a combination of different assays to reveal the effect of AgNP on i) bacterial envelope in general, ii) outer membrane (OM) and iii) on plasma membrane (PM). We showed that bacterial PM was the main target of AgNP in Gram-negative bacteriaEscherichia coliandPseudomonas aeruginosa. AgNP depolarized bacterial PM, induced the leakage of the intracellular K+, inhibited respiration and caused the depletion of the intracellular ATP. In contrast, AgNP had no significant effect on the bacterial OM. Most of the adverse effects on bacterial envelope and PM occurred within the seconds and in the concentration range of 7-160 μM AgNP, depending on the bacteria and assay used, while irreversible inhibition of bacterial growth (minimal bactericidal concentration after 1-h exposure of bacteria to AgNP) occurred at 40 μM AgNP forP. aeruginosaand at 320 μM AgNP forE. coli.Flow cytometry analysis showed that AgNP were binding toP. aeruginosabut not toE. colicells and were found inside theP. aeruginosacells. Taking into account that AgNP did not damage OM, we speculate that AgNP enteredP. aeruginosa viaspecific mechanism, e.g., transport through porins.
The multidrug resistance efflux pump MexCD-OprJ is a switcher of thePseudomonas aeruginosaquorum sensing response
Authors: Alcalde-Rico Manuel , Olivares-Pacheco Jorge , Alvarez-Ortega Carolina , Cámara Miguel , Martínez José Luis 
Published: May 2018

AbstractMost antibiotic resistance genes acquired by human pathogens originate from environmental microorganisms. Therefore, understanding the additional functions of these genes, other than conferring antibiotic resistance, is relevant from an ecological point of view. We examined the effect that overexpression of the MexCD-OprJ multidrug efflux pump has in the physiology of the environmental opportunistic pathogenPseudomonas aeruginosa. Overexpression of this intrinsic resistance determinant shuts down theP. aeruginosaquorum sensing (QS) response. Impaired QS response is due to the extrusion of 4-hydroxy-2-heptylquinoline (HHQ), the precursor of thePseudomonasQuinolone Signal (PQS), leading to low PQS intracellular levels and reduced production of QS signal molecules. TheP. aeruginosaQS response induces the expression of hundreds of genes, which can be costly unless such activation becomes beneficial for the bacterial population. While it is known that the QS response is modulated by population density, information on additional signals/cues that may alert the cells about the benefits of mounting the response is still scarce. It is possible that MexCD-OprJ plays a role in this particular aspect; our results indicate that, upon overexpression, MexCD-OprJ can act as a switcher in the QS population response. If MexCD-OprJ alleviate the cost associated to trigger the QS response when un-needed, it could be possible that MexCD-OprJ overproducer strains might be eventually selected even in the absence of antibiotic selective pressure, acting as antibiotic resistant cheaters in heterogeneousP. aeruginosapopulations. This possibility may have potential implications for the treatment ofP. aeruginosachronic infections.
Ascitic bacterial composition is associated with clinical outcomes in cirrhotic patients with culture-negative and nonneutrocytic ascites
Authors: Chen Yanfei , Guo Jing , Shi Ding , Fang Daiqiong , Chen Chunlei , Li Lanjuan 
Published: May 2018

AbstractBackground: Ascites bacterial burden is associated with poor clinical outcomes in patients with end-stage liver disease. However, the impact of ascitic microbial composition on clinical course was still not clear. In this study, the ascitic microbiota composition of 100 cirrhotic patients with culture-negative and nonneutrocytic ascites were researched. Results: By characterizing the ascitic microbial composition, two distinct microbial clusters were observed, Cluster 1 (86 patients) and Cluster 2 (14 patients). Cluster 1 showed lower microbial richness than Cluster 2. At the phylum level, Cluster 1 had greater abundance of Bacteroidetes and Firmicutes, but less abundance of Proteobacteria and Actinobacteria than Cluster 2. At the family level, family Bacteroidales S24-7 group, Prevotellaceae, Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Vibrionaceae were found over-represented in Cluster 1. And family Acetobacteraceae, Erysipelotrichaceae, Rickettsiaceae, and Streptococcaceae were found enriched in Cluster 2. The levels of plasma cytokine IL-17A, IL-7, and PDGF-BB were found significantly higher in Cluster 1 than in Cluster 2. There were four OTUs closely correlated with plasma cytokines, which were OTU 140 and OTU 271 (both from Bacteroidales S24-7 group), OTU 68 (Veillonellaceae), and OTU 53 (Helicobacteraceae). Patients from Cluster 1 showed significant higher short-term mortality than patients from Cluster 2. Conclusion: Our study demonstrated that the microbial composition of culture-negative and nonneutrocytic ascites in cirrhotic patients is associated with short-term clinical outcomes. The results here offer a rational for the identification of patients with high risk, and provide references for selective use of prophylactic methods.
The RZZ complex facilitates Mad1 binding to Bub1 ensuring efficient checkpoint signaling
Authors: Zhang Gang , Kruse Thomas , Nilsson Jakob 
Published: May 2018

Introductory paragraphThe recruitment of Mad1 to unattached kinetochores is essential for generating a “wait anaphase” signal during mitosis yet Mad1 localization is poorly understood in mammalian cells. In yeast the Bub1 checkpoint protein is the sole Mad1 receptor but in mammalian cells the Rod-ZW10-Zwilch (RZZ) complex is also required for Mad1 kinetochore localization. The exact function of the two mammalian Mad1 receptors and whether there is any interplay between them is unclear. Here we use CRISPR genome editing to generate RNAi sensitized human cell lines revealing a strong requirement for both Rod and Bub1 in checkpoint signaling. We show that the RZZ complex facilitates Mad1 binding to Bub1 and that a region of Bub1 overlapping the Mad1 binding site stimulates RZZ kinetochore recruitment. The requirement for RZZ in the checkpoint, but not Bub1, can be bypassed by tethering Mad1 to kinetochores or by increasing the strength of the Bub1-Mad1 interaction. Our data support a model in which the primary role of RZZ is to localize Mad1 at kinetochores allowing for the efficient checkpoint generating Mad1-Bub1 interaction. As such, the core checkpoint principle is conserved from yeast to man.