bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization and sequence analysis of plasmid-mediated quinolone resistance genes in extended-spectrum beta-lactamases producing uropathogenic Escherichia coli in Babylon Province, Iraq
Authors: Al-Hasnawy Huda H. , Jodi Mohammed R. , Hamza Hiba J. 
Published: June 2018

The current study was aimed to detect qnrA, qnrB, qnrC, qnrD and qnrS genes in quinolone-resistance extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli isolates that recovered from patients with urinary tract infection in Babylon Province, Iraq. Uropathogenic E. coli (UPEC) was regarded as the most important causative agent of urinary tract infections. Fluoroquinolones are regularly used in the management of these infections; on the other hand, in recent years, an increasing rate of quinolone resistance has been stated globally. Clinical isolates of UPEC were collected from patients with infection of urinary tract and identified by standard laboratory protocols. PCR was used for detection of quinolone resistance genes (qnrA, qnrB, qnrC, qnrD and qnrS) in ESBL-producing isolates, and sequencing of some qnr genes confirmed the results. Out of 208 urine specimens, 42 UPEC isolates of ESBL producing were detected; of them, 27 (64.28%) isolates were found to be resistant to quinolones. PCR results revealed that out of 27 UPEC, five (18.51%) isolates were found to carry both genes qnrS and qnrB, whereas four (14.81%) isolates were harbored qnrD and qnrA, and no isolate was found to have qnrC. Sequencing of qnrB and qnrS genes revealed that mutational changes were observed in qnrB gene; however, no mutational variation was observed in qnrS gene.
The results of the current study revealed the dissemination of ESBL genes in all UPEC isolates that carry the plasmid-mediated qnr genes with low frequency among the clinical isolates and UPEC isolates; these results confirmed that the quinolone resistance in Babylon Province, Iraq might be because of chromosomal genes for this resistance.
The effects of hemorrhage on the pharmacokinetics of tranexamic acid in a swine model
Authors: Derickson Michael J. , McClellan John M. , Marko Shannon T. , Kuckelman John P. , Phillips Cody J. , Barron Morgan R. , Martin Matthew J. , Loughren Michael J. 
Published: June 2018

BACKGROUNDThe early use of tranexamic acid (TXA) is strongly advocated in patients who are likely to require massive transfusion to decrease mortality. This study determines the influence of hemorrhage on the pharmacokinetics of TXA in a porcine model.METHODSThe investigation was a prospective experimental study in Yucatan minipigs. First, in vitro plasma-cell partitioning of TXA was evaluated by inoculating whole blood with known aliquots, centrifuging, and measuring the supernatant with high-performance liquid chromatography with mass spectrometry (HPLC-MS). Then, using in vivo modeling, normovolemic and hypovolemic (35% reduction in blood volume) swine (n = 4 per group) received 1 g of intravenous TXA and had blood sampled at 14 time points over 4 hours to determine baseline clearance via HPLC-MS. Additional swine (n = 4) were hemorrhaged 35% of their blood volume, and TXA was administered as a 15 mg/kg infusion over 10 minutes followed by infusion of 1.875 mg/kg per hour to simulate massive hemorrhage scenario. During the first hour of TXA administration, one total blood volume was hemorrhaged and simultaneously replaced with TXA free blood. Serial blood samples and the hemorrhaged blood were analyzed by HPLC-MS to determine the percentage of dose lost via hemorrhage.RESULTSClearance of TXA was diminished in the hypovolemic group compared with the normovolemic group (115 ± 4 vs 70 ± 7 mL/min). Percentage of dose lost via hemorrhage averaged 25%. The lowest measured plasma level during the exchange transfusion was 34 μg/mL.CONCLUSIONMean 25% of the present 2017 Joint Trauma System Clinical Practice Guideline dosing of TXA can be lost to hemorrhage if a blood volume is transfused within an hour of initiating therapy. In the case of TXA, which has limited distribution and is administered during active hemorrhage and massive blood transfusions, replacement strategies should be developed and tested to find simple methods of adjusting the current dosing guidelines to maintain therapeutic plasma concentrations.LEVEL OF EVIDENCETherapeutic, level II.
Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation
Authors: Kabagambe Sandra K. , Palma Ivonne P. , Smolin Yulia , Boyer Tristan , Palma Ivania , Sageshima Junichiro , Troppmann Christoph , Santhanakrishnan Chandrasekar , McVicar John P. , Jen Kuang-Yu , Nuño Miriam , Perez Richard V. 
Published: June 2018

Background
Despite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation.

Methods
From June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed.

Results
After a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance.

Conclusions
Favorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.
T cell and peripheral blood parameters define progression of autoimmune disease in the IL-2Rα KO model
Authors: Mullins Genevieve N. , Valentine Kristen M. , Al-Kuhlani Mufadhal , Davini Dan , Jensen Kirk D.C. , Hoyer Katrina K. 
Published: June 2018

AbstractIL-2Rα is required to generate the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. Mice deficient in IL-2Rα (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18-80 days of age. These mice develop kinetically differing autoimmune disease, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters that distinguish cohorts of mice that develop early- and late-stage autoimmune disease in the IL-2Rα-KO genetic background. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, and hematopoietic progenitor changes, to assess the extent of peripheral autoimmune hemolytic anemia and bone marrow failure. Early onset disease correlated with anti-RBC antibodies and lower hematocrit on day 19. We also found that predicted late stage-disease IL-2Rα-KO mice have higher numbers of developing memory CD4 and CD8 T cells and reduced AIHA at early ages. The expansion of CD8 T cells seen in IL-2R -KO mice is driven by unimpaired IL-2 signaling which correlated with increased IL-2RP expression. Using a simple CBC we were able to predict disease kinetics to explore mechanisms underlying early and late disease.
A histone H4K20 methylation-mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing
Authors: Shoaib Muhammad , Walter David , Gillespie Peter J. , Izard Fanny , Fahrenkrog Birthe , Lleres David , Lerdrup Mads , Johansen Jens Vilstrup , Hansen Klaus , Julien Eric , Blow J. Julian , Sørensen Claus S. 
Published: June 2018

ABSTRACTThe decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. The mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here, we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, appropriate chromatin relaxation is safeguarded by SET8-dependent methylation of histone H4 on lysine 20. Thus, in the absence of either SET8 or the H4K20 residue, substantial genome-wide chromatin decompaction occurs which allows excessive loading of the Origin Recognition Complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and the loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase.
Quantification and discovery of sequence determinants of protein per mRNA amount in 29 human tissues
Authors: Eraslan Basak , Wang Dongxue , Gusic Mirjana , Prokisch Holger , Hallström Björn , Uhlen Mathias , Asplund Anna , Ponten Frederik , Wieland Thomas , Hopf Thomas , Hahne Hannes , Kuster Bernhard , Gagneur Julien 
Published: June 2018

AbstractDespite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein-to-mRNA (PTR) ratios and a quantification of their effects is still lacking. Here we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We analyzed the contribution of known sequence determinants of protein synthesis and degradation and 15 novel mRNA and protein sequence motifs that we found by association testing. While the dynamic range of PTR ratios spans more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2-fold. A reporter assay provided significant functional support for two novel UTR motifs and a proteome-wide competition-binding assay identified motif-specific bound proteins for one motif. Moreover, our direct comparison of protein to RNA levels led to a new metrics of codon optimality. Altogether, this study shows that a large fraction of PTR ratio variance across genes can be predicted from sequence and identified many new candidate post-transcriptional regulatory elements in the human genome.
Identification of evolutionarily conserved virulence factor by selective pressure analysis ofStreptococcus pneumoniae
Authors: Yamaguchi Masaya , Goto Kana , Hirose Yujiro , Yamaguchi Yuka , Sumitomo Tomoko , Nakata Masanobu , Nakano Kazuhiko , Kawabata Shigetada 
Published: June 2018

AbstractEvolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins sinceStreptococcus pneumoniaeis one of the pathogen posing the greatest threats to human health. Phylogenetic and molecular analyses revealed thatcbpJhad the highest codon rates to total numbers of codons under significant negative selection among those examined. Ourin vitroandin vivoassays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency ofcbpLunder relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.
Similarity and strength of glomerular odor representations define neural metric of sniff-invariant discrimination time
Authors: Bhattacharjee Anindya S. , Konakamchi Sasank , Turaev Dmitrij , Vincis Roberto , Nunes Daniel , Dingankar Atharva A. , Spors Hartwig , Carleton Alan , Kuner Thomas , Abraham Nixon M. 
Published: June 2018

AbstractThe olfactory environment is first represented by glomerular activity patterns in the olfactory bulb. It remained unclear, how these activity patterns intersect with sampling behavior to account for the time required to discriminate odors. Using different classes of volatile stimuli, we investigated glomerular activity patterns and sniffing behavior during olfactory decision-making. Mice discriminated monomolecular odorants and binary mixtures on a fast time scale and learned to increase their breathing frequency at a fixed latency after trial initiation, independent of odor identity. Relative to the increase in breathing frequency, monomolecular odorants were discriminated within 10-40 ms while binary mixtures required an additional 60-70 ms. Intrinsic imaging of odor-evoked glomerular activity maps in anesthetized and awake mice revealed that the Euclidean distance between glomerular patterns elicited by different odors, a measure of similarity and activation strength, was anti-correlated with discrimination time. Therefore, the similarity of glomerular patterns and their activation strengths, rather than sampling behavior, define the extent of neuronal processing required for odor discrimination, establishing a neural metric to predict olfactory discrimination time.
Overwhelming presence of non-food vegetation undermines the reliability of NDVI as a surrogate of forage abundance for a large herbivore in a tropical forest habitat
Authors: Gautam Hansraj , Arulmalar Evangeline , Kulkami Mihir R , Vidya TNC 
Published: June 2018

AbstractThe use of remotely-sensed vegetation indices has increased in wildlife studies but field-based support for their utility as a measure of forage availability largely comes from open-canopy habitats. In this paper, we assessed whether the popular vegetation index, NDVI, actually represents forage availability for Asian elephants in a southern Indian tropical forest. We found that the number of food species was a small percentage of all plant species, and the abundance of food species compared to total species abundance varied across different vegetation categories. NDVI was not a good measure of food abundance in any vegetation category partly because of a) small to moderate proportional abundances of food species relative to the total abundance of all species in that category (herb and shrub categories), b) abundant overstorey vegetation resulting in low correlations between NDVI and food abundance despite a high proportional abundance of food species and a concordance between total abundance and food species abundance (graminoid category), and c) the relevant variables measured and important as food at the ground level (count and GBH) not being related to primary productivity (trees and recruits). NDVI had a negative relationship with the total abundance of graminoids, which represent a bulk of elephant and other herbivore diet, because of the presence of other vegetation types and canopy cover that positively explained NDVI. We also found that spatially interpolated total graminoid abundance modelled from field data outperformed NDVI in predicting total graminoid abundance, although interpolation models of food graminoid species abundance were not satisfactory. Our results reject the utility of NDVI as a surrogate of elephant forage abundance in tropical forests with multistorey vegetation, a finding that has implications for studies of other herbivores in such habitats.
Combined quantification of intracellular (phospho-)proteins and transcriptomics from fixed single cells
Authors: Gerlach Jan. P. , van Buggenum Jessie A. G. , Tanis Sabine E.J. , Hogeweg Mark , Heuts Branco M. H. , Muraro Mauro J. , Elze Lisa , Rivello Francesca , Rakszewska Agata , van Oudenaarden Alexander , Huck Wilhelm T. S. , Stunnenberg Hendrik G. , Mulder Klaas W. 
Published: June 2018

AbstractEnvironmental stimuli often lead to heterogeneous cellular responses and transcriptional output. We developed single-cell RNA and Immunodetection (RAID) to allow combined analysis the transcriptome and intracellular (phospho-)proteins from fixed single cells. RAID successfully recapitulated differentiation-state changes at the protein and mRNA level in human keratinocytes. Furthermore, we show that differentiated keratinocytes that retain high phosphorylated FAK levels, a feature associated with stem cells, also express a selection of stem cell associated transcripts. Our data demonstrates that RAID allows investigation of heterogenenous cellular responses to environmental signals at the mRNA and phospho-proteome level.
Disentangling the process of speciation using machine learning
Authors: Smith Megan L. , Carstens Bryan C. 
Published: June 2018

AbstractHistorically, investigations into the processes driving speciation have largely been isolated from systematic investigations into species limits. Recent advances in sequencing technology have led to a rapid increase in the availability of genomic data, and this, in turn, has led to the introduction of many novel methods for species delimitation. However, these methods have been limited to divergence-only scenarios and have not attempted to evaluate complex modes of speciation, such as those that include gene flow during early stages of divergence (sympatric speciation) or population size changes (founder effect speciation). To address this shortcoming, we introducedelimitR, an approach that enables biologists to infer species boundaries and evaluate the demographic processes that may have led to speciation.delimitRuses the binned multidimensional Site Frequency Spectrum and a machine-learning algorithm (Random Forests) to compare speciation models. We use simulations to evaluate the accuracy ofdelimitR. When comparing models that include lineage divergence and gene flow for three populations, error rates are near zero with recent divergence times (<100,000 generations) and a modest number of Single Nucleotide Polymorphisms (SNPs; 1,500). When applied to a more complex model set (including divergence, gene flow, and population size changes), error rates are moderate (~0.15 with 10,000 SNPs), and misclassifications are generally between highly similar models. We also evaluate the utility ofdelimitRusing three previously published datasets and find results that corroborate previous findings. Our analyses indicate thatdelimitRcan serve as an important conceptual bridge uniting various investigations into the process of speciation.
The ‘filtering’ metaphor revisited: competition and environment jointly structure invasibility and coexistence
Authors: Germain Rachel M. , Mayfield Margaret M. , Gilbert Benjamin 
Published: June 2018

Abstract‘Filtering’, or the reduction in species diversity that occurs because not all species can persist in all locations, is thought to unfold hierarchically, at large scales due to the environment and at small scales due to competition. However, the ecological effects of competition and the environment are not independent, and observational approaches preclude investigation into their interplay. We use a demographic approach with 30 plant species to experimentally test (i) the effect of competition on species persistence in two soil moisture environments, and (ii) the effect of environmental conditions on the mechanisms underlying competitive coexistence. We find that competitors cause differential persistence of species across environments even when these effects are lacking in the absence of competition, and that the traits that determine persistence depend on the competitive environment. Changing environmental conditions generated idiosyncratic effects on coexistence outcomes, increasing competitive exclusion of some species while promoting coexistence of others. Our results highlight the importance of considering environmental filtering in light of, rather than in isolation from, competition, and challenge community assembly models and approaches to projecting future species distributions.
Solution and gas-phase modifiers effect on heme proteins environment and conformational space
Authors: Butcher D. , Miksovska J. , Ridgeway M. E. , Park M. A. , Fernandez-Lima F. 
Published: June 2018

AbstractThe molecular environment is known to impact the secondary and tertiary structure of biomolecules, shifting the equilibrium between different conformational and oligomerization states. In the present study, the effect of solution additives and gas-phase modifiers on the molecular environment of two common heme proteins, bovine cytochrome c and equine myoglobin, is investigated as a function of the time after desolvation (e.g., 100 - 500 ms) using trapped ion mobility spectrometry – mass spectrometry. Changes in the mobility profiles are observed depending on the starting solution composition (i.e., in aqueous solution at neutral pH or in the presence of organic content: methanol, acetone, or acetonitrile) depending on the protein. In the presence of gas-phase modifiers (i.e., N2containing methanol, acetone, or acetonitrile), a shift in the mobility profiles driven by the gas-modifier mass and size and changes in the relative abundances and number of IMS bands are observed. We attribute these changes in the mobility profiles in the presence of gas-phase modifiers to a clustering/declustering mechanism by which organic molecules adsorb to the protein ion surface and lower energetic barriers for interconversion between conformational states, thus redefining the free energy landscape and equilibria between conformers. These structural biology experiments open new avenues for manipulation and interrogation of biomolecules in the gas-phase with the potential to emulate a large suite of solution conditions, ultimately including conditions that more accurately reflect a variety of intracellular environments.