bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morbus Menière – wie hilfreich ist die Magnetresonanztomografie?
Authors: Schaaf Helmut 
Published: May 2018

Patel VA et al. Magnetic resonance imaging findings in Ménière‘s disease. J Laryngol Otol 2017; 131: 602–607
Ein amerikanisches Wissenschaftlerteam veranschaulichte MRT-Befunde, die im Zusammenhang mit der Menière-Krankheit stehen. Diese umfassten kongenitale
Malformationen, Schädigung der weißen Substanz, Veränderungen der hinteren Zirkulation und temporäre Abweichungen der Knochenstruktur.
Sorting cancer karyotypes using double-cut-and-joins, duplications and deletions
Authors: Zeira Ron , Shamir Ron 
Published: May 2018

Abstract

Motivation
Problems of genome rearrangement are central in both evolution and cancer research. Most genome rearrangement models assume that the genome contains a single copy of each gene and the only changes in the genome are structural, i.e. reordering of segments. In contrast, tumor genomes also undergo numerical changes such as deletions and duplications, and thus the number of copies of genes varies. Dealing with unequal gene content is a very challenging task, addressed by few algorithms to date. More realistic models are needed to help trace genome evolution during tumorigenesis.

Results
Here, we present a model for the evolution of genomes with multiple gene copies using the operation types double-cut-and-joins, duplications and deletions. The events supported by the model are reversals, translocations, tandem duplications, segmental deletions and chromosomal amplifications and deletions, covering most types of structural and numerical changes observed in tumor samples. Our goal is to find a series of operations of minimum length that transform one karyotype into the other. We show that the problem is NP-hard and give an integer linear programming formulation that solves the problem exactly under some mild assumptions. We test our method on simulated genomes and on ovarian cancer genomes. Our study advances the state of the art in two ways: It allows a broader set of operations than extant models, thus being more realistic and it is the first study attempting to re-construct the full sequence of structural and numerical events during cancer evolution.

Availability and implementation
Code and data are available in https://github.com/Shamir-Lab/Sorting-Cancer-Karyotypes.

Supplementary information
Supplementary data are available at Bioinformatics online.
Necklace: combining reference and assembled transcriptomes for more comprehensive RNA-Seq analysis
Authors: Davidson Nadia M , Oshlack Alicia 
Published: May 2018

Abstract

Background
RNA sequencing (RNA-seq) analyses can benefit from performing a genome-guided and de novo assembly, in particular for species where the reference genome or the annotation is incomplete. However, tools for integrating an assembled transcriptome with reference annotation are lacking.

Findings
Necklace is a software pipeline that runs genome-guided and de novo assembly and combines the resulting transcriptomes with reference genome annotations. Necklace constructs a compact but comprehensive superTranscriptome out of the assembled and reference data. Reads are subsequently aligned and counted in preparation for differential expression testing.

Conclusions
Necklace allows a comprehensive transcriptome to be built from a combination of assembled and annotated transcripts, which results in a more comprehensive transcriptome for the majority of organisms. In addition RNA-seq data are mapped back to this newly created superTranscript reference to enable differential expression testing with standard methods.
Outpatient Infection Prevention: A Practical Primer
Authors: Steinkuller Fozia , Harris Kristofer , Vigil Karen J , Ostrosky-Zeichner Luis 
Published: May 2018

AbstractAs more patients seek care in the outpatient setting, the opportunities for health care–acquired infections and associated outbreaks will increase. Without uptake of core infection prevention and control strategies through formal initiation of infection prevention programs, outbreaks and patient safety issues will surface. This review provides a step-wise approach for implementing an outpatient infection control program, highlighting some of the common pitfalls and high-priority areas.
Identification of the interaction of 2-aminosteroids with G-quadruplex in BCR/ABL gene promoter: An emerging potential target for treatment of human chronic myelogenous leukemia
Authors: He Qun , Yang Huihui 
Published: May 2018

AbstractOur preliminary studies have verified that the small molecules aminosteroid could inhibit the mRNA expression of bcr/abl fusion gene in CML (Chronic Myelogenous Leukemia) cells, which may be effective in treating CML and that may have dramatically different mechanism underlying the effects by tyrosine kinase inhibitors (TKI) binding to the BCR/ABL protein. Therefore, the exact mechanism of how the aminosteroid inhibited the CML growth should be clarified and we pay our attention to the promoter domain of BCR/ABL gene to see if any interaction between aminosteroid and the promoter. First, it should be verified if G-quadruplex could be formed in BCR/ABL promoter region. Secondly, it is highly desirable to verify if aminoteroid could be interacted with the G-quadruplex structure. Here, we reported a novel therapeutic strategy based on the targeting of the G-quadruplex which formed in the promoter regions of BCR/ABL gene by aminosteroid compounds KH and BH, verified by using bioinformatics and computer simulation, UV-Vis absorption spectra, circular dichrosism(CD), fluorescence absorption spectra, fluorescence emission lifetime expenditure experiments and polymerase chain stop assays. It showed that G-quadruplex structures can be folded in BCR/ABL promoter regions and aminosteroid inhibits the mRNA expression of BCR/ABL fusion gene by stabilizing the structure of G-quadruplex, and then inhibiting the DNA replication and transcription. This demonstrates the theory that is the so-called “chemical gene therapy” by aminosteroid in the interaction with G-quadruplex is an emerging therapeutic protocol in treatment of chronic myeloid leukemia.
Basidiobolus haptosporus-likefungus as a causal agent of gastrointestinal basidiobolomycosis and its link to the common house gecko (Hemidactylus frenatus) as a potential risk factor
Authors: Al Bshabshe Ali , Joseph Martin R.P. , Al Hakami Ahmed M. , Al Azraqi Tarig , Al Humayed Sulieman , Hamid Mohamed E. 
Published: May 2018

ABSTRACTBasidiobolusspp. are a significant causal agent of infections in man and animals including gastrointestinal basidiobolomycosis (GIB). Little information is available on how these infections are acquired or transmitted, apart from the postulation that environmental sources are implicated. This study aimed to identifyBasidiobolusspp. from GIB patients and from the house gecko as a possible source of infection in Aseer, Saudi Arabia.Basidiobolusspp. were isolated from patient specimens (colonic mass biopsy) and from house gecko (gut contents) from Muhayil Aseer areas, in southern Saudi Arabia, using Sabouraud dextrose agar (SDA) which was incubated aerobically for up to three weeks at 30°C. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Cultured specimens from humans and geckos revealed phenotypically similar zygomycete-like fungi which conform to those ofBasidiobolusspecies. The strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity withB. haptosporusand 99.97% withB. haptosporusvar.minorbut have a relatively remote similarity toB. ranarum(99.925%). One isolates from a gecko (L3) fall within the sub-clade encompassingB. haptosporusstrain NRRL28635. The study strongly suggests a new and a serious causal agent of GIB related toBasidiobolus haptosporus. The isolation of identicalBasidiobolus haptosporus-likestrains from humans and lizards from one area is an important step towards identifying risk factors for GIB. Research is underway to screen more environmental niches and fully describe theBasidiobolusstrains.
Negative Cooperativity between Gemin2 and RNA provides Insights into RNA Selection and the SMN Complex’s Release in snRNP Assembly
Authors: Yi Hongfei , Mu Li , Shen Congcong , Kong Xi , Wang Yingzhi , Hou Yan , Zhang Rundong 
Published: May 2018

ABSTRACTThe assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex’s release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.
h-channels contribute to divergent electrophysiological properties of supragranular pyramidal neurons in human versus mouse cerebral cortex
Authors: Kalmbach Brian E , Buchin Anatoly , Miller Jeremy A , Bakken Trygve E , Hodge Rebecca D , Chong Peter , de Frates Rebecca , Dai Kael , Gwinn Ryder P. , Cobbs Charles , Ko Andrew L , Ojemann Jeffrey G , Silbergeld Daniel L , Koch Christof , Anastassiou Costas A. , Lein Ed , Ting Jonathan T 
Published: May 2018

SummaryGene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provided evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.
Super-Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore
Authors: Chen Qixin , Jin Chengzhi , Shao Xintian , Guan Ruilin , Tian Zhiqi , Wang Chenran , Liu Fei , Ling Peixue , Guan Jun-Lin , Ji Liangnian , Wang Fengshan , Chao Hui , Diao Jiajie 
Published: May 2018

AbstractCombining luminescent transition metal complex (LTMC) with super-resolution microscopy is an excellent strategy for the long-term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super-resolution technique, structured illumination microscopy (SIM), to image subcellular structures.As described herein, we developed an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM. The dye demonstrated excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, we achieved an approximately 80-nm resolution that allowed the clear observation of the structure of mitochondrial cristae. We used the dye to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria-lysosome contact (MLC) under different conditions. MLC remained intact and fusion vanished when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, were knocked out, suggesting that these two processes are independence.
Internal Tensile Force and A2 Domain Unfolding of von Willebrand Factor Multimers in Shear Flow
Authors: Morabito Michael , Dong Chuqiao , Wei Wei , Cheng Xuanhong , Zhang Xiaohui F. , Oztekin Alparslan , Webb Edmund 
Published: May 2018

ABSTRACTUsing Brownian molecular dynamics simulations, we examine the internal dynamics and biomechanical response of von Willebrand Factor (vWF) multimers subject to shear flow. The coarse grain multimer description employed here is based on a monomer model in which the A2 domain of vWF is explicitly represented by a non-linear elastic spring whose mechanical response was fit to experimental force/extension data from vWF monomers. This permits examination of the dynamic behavior of hydrodynamic forces acting on A2 domains as a function of shear rate and multimer length, as well as position of an A2 domain along the multimer contour. Force/position data reveal that collapsed multimers exhibit a force distribution with two peaks, one near each end of the chain; unraveled multimers, however, show a single peak in A2 domain force near the center of multimers. Guided further by experimental data, significant excursions of force acting on a domain are associated with an increasing probability for A2 domain unfolding. Our results suggest that the threshold shear rate required to induce A2 domain unfolding is inversely proportional to multimer length. By examining data for the duration and location of significant force excursions, convincing evidence is advanced that unfolding of A2 domains, and therefore scission of vWF multimers by the size-regulating blood enzyme ADAMTS13, happen preferentially near the center of unraveled multimers.
One-step assembly of large CRISPR arrays enables multi-functional targeting and reveals constraints on array design
Authors: Liao Chunyu , Ttofali Fani , Slotkowski Rebecca A. , Denny Steven R. , Cecil Taylor D. , Leenay Ryan T. , Keung Albert J. , Beisel Chase L. 
Published: May 2018

SUMMARYCRISPR-Cas systems inherently multiplex through their CRISPR arrays--whether to confer immunity against multiple invaders or by mediating multi-target editing, regulation, imaging, and sensing. However, arrays remain difficult to generate due to their reoccurring repeat sequences. Here, we report an efficient, one-step scheme called CRATES to construct large CRISPR arrays through defined assembly junctions within the trimmed portion of array spacers. We show that the constructed arrays function with the single-effector nucleases Cas9, Cas12a, and Cas13a for multiplexed DNA/RNA cleavage and gene regulation in cell-free systems, bacteria, and yeast. We also applied CRATES to assemble composite arrays utilized by multiple Cas nucleases, where these arrays enhanced DNA targeting specificity by blocking off-target sites. Finally, array characterization revealed context-dependent loss of spacer activity and processing of unintended guide RNAs derived from Cas12a terminal repeats. CRATES thus can facilitate diverse applications requiring CRISPR multiplexing and help elucidate critical factors influencing array function.
Adaptive Partitioning of the tRNA Interaction Interface by Aminoacyl-tRNA-Synthetases
Authors: Collins-Hed Andy , Ardell David H. 
Published: May 2018

AbstractWe introduce rugged fitness landscapes called match landscapes for the coevolution of feature-based assortative interactions betweenP≥ 2 cognate pairs of tRNAs and aminoacyl-tRNA synthetases (aaRSs) in aaRS-tRNA interaction networks. Our genotype-phenotype-fitness maps assume additive feature-matching energies, a macroscopic theory of aminoacylation kinetics including proofreading, and selection for translational accuracy in multiple, perfectly encoded site-types. We compute the stationary genotype distributions of finite panmictic, asexual populations of haploid aaRs-tRNA interaction networks evolving under mutation, genetic drift, and selection for cognate matching and non-cognate mismatching of aaRS-tRNA pairs. We compared expected genotype frequencies under different matching rules and fitness functions, both with and without linked site-specific modifiers of interaction. Under selection for translational accuracy alone, our model predicts no selection on modifiers to eliminate non-cognate interactions, so long as they are compensated by tighter cognate interactions. Only under combined selection for both translational accuracy and rate do modifiers adaptively eliminate cross-matching in non-cognate aaRS/tRNA pairs. We theorize that the encoding of macromolecular interaction networks is a genetic language that symbolically maps identifying structural and dynamic features of genes and gene-products to functions within cells. Our theory helps explain 1) the remarkable divergence in how aaRSs bind tRNAs, 2) why interaction-informative features are phylogenetically informative, 3) why the Statistical Tree of Life became more tree-like after the Darwinian Transition, and 4) an approach towards computing the probability of the random origin of an interaction network.
An Assessment of Skin Lesion Measurement Techniques for Use in Clinical Trials of Acute Bacterial Skin and Skin Structure Infections
Authors: Dunne Michael W. , Das Anita , Talbot George H. 
Published: May 2018

AbstractBackgroundLimited data are available to support a reproducible measurement technique that could be used to assess the response of a skin lesion associated with a bacterial infection to antibacterial therapy.MethodsThis multicenter, observational study enrolled patients with a major cutaneous abscess, a traumatic wound or surgical site infection, or a cellulitis. The primary objective was to characterize the intra- and inter-observer variability inherent in measuring the size of the erythema associated with the presenting skin infection. At least two observers made ruler measurements of the infection site with the length of the infection measured as the longest dimension of the erythematous area and width measured as the largest dimension perpendicular to the longest length. Intra- and inter-observer variability was determined by the intraclass correlation coefficient (ICC). Photographs, tracings, and thermal imaging were also performed.ResultsThe intra-observer ICC (95% CI) for lesion area as measured by ruler was 0.999 (0.998, 0.999), suggesting only a very small amount of the variability was due to measurement error. The difference in mean lesion area measurements by the same observer was <1%. The inter-observer ICC (95% CI) for lesion area as measured by ruler was 0.990 (0.981, 0.995) suggesting that the results between observers were also highly reliable.ConclusionsMeasurement of infection area as defined by erythema and measured by ruler shows excellent intra- and inter-observer reliability and can be used in future clinical trials of acute bacterial skin infections.
Population Pharmacokinetics Study of Morinidazole in Patients with Moderate Hepatic Impairment
Authors: Kang Yue , Xu Fengyan , Wang Kun , Zhang Jing , Wu Xiaojie , Wu Jufang , Cao Guoying , Yu Jicheng , Guo Beining , Chen Yuancheng , Zhang Yingyuan 
Published: May 2018

AbstractObjectiveMorinidazole is a novel third generation 5-nitroimidazole antimicrobial drug which has demonstrated substantial antibacterial activity against clinical isolates of anaerobe. The aim of this study was to build population pharmacokinetic (PPK) model of morinidazole among patients with hepatic impairment and to provide dosage adjustment strategy for morinidazole in patients with hepatic impairment and/or renal dysfunction.MethodsThe nonlinear mixed effects modeling tool NONMEM (version7.3, ICON Development Solutions) was used to develop the PPK model of morinidazole.ResultsOne-compartment model was conducted to establish the morinidazole PPK model. Disease condition was the significant covariate for CL and weight was the significant covariate for V. The AUC0-∞ was 120.44±37.05 (79.25-207.20) μg×h/mL in hepatic impairment group and was 79.46±23.71 (42.94-116.75) μg×h/mL in control group. The AUC0-∞ was 164.9±44.8 μg×h/mL and 77.2±23.1 μg×h/mLin in the 3 subjects with both hepatic impairment and mild renal impairment and in the 3 matched healthy subjects, respectively.ConclusionIt is not necessary to adjust morinidazole dosage for patients with moderate hepatic impairment without confirmed renal dysfunction. For patient with moderate hepatic and mild renal impairment, morinidazole regimen should be considered as 500mg every 24 hours. When used in patients with moderate/severe hepatic impairment combined with renal dysfunction, both dosage and interval adjustment of morinidazole should be considered.
Modulation of TOR kinase activity inChlamydomonas reinhardtii: Effect of N-starvation and changing carbon pool
Authors: Upadhyaya Shivani , Agrawal Shreya , Gorakshakar Anmol , Jagadeeshwar Rao Basuthkar 
Published: May 2018

ABSTRACTTargetOfRapamycin (TOR) kinase is a sensor as well as a central integrator of internal and external metabolic cues. The upstream and downstream signals of this kinase are very well characterized in animals. However, in algae, higher plants and other photosynthetic organisms, the components of the TOR kinase-signaling are yet to be characterized. Here, we establish an assay system to study TOR kinase activity inC.reinhardtiiusing the phosphorylation status of its downstream target, CrS6K. We further use this assay to monitor TOR kinase activity under various physiological states such as photoautotrophy, heterotrophy, mixotrophy and nitrogen starvation. We observe that autotrophy in light (and not in dark) leads to TOR kinase attenuation during N starvation while the same is not observed in mixotrophy. Importantly, we show that the external carbon source glucose is sensed and uptaken byC.reinhardtiicells only in the presence of light and not in the dark. And such exogenously added glucose, as the photoassimilate carbon mimic, results in enhanced production of ROS, induction of autophagy and concomitant drop in TOR kinase activity, creating N-starvation-like cellular state even in N+ conditions. Interestingly, dose dependent addition of glucose revealed TOR kinase activation in low glucose regime (ROS independent) followed by attenuation of TOR kinase (ROS dependent) at high glucose levels.SummaryTOR kinase activity inC.reinhardtiiis modulated by available carbon source especially glucose, where low levels of glucose cause an increase whereas high levels cause a reduction in TOR kinase activity.