bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable preparations of tyrosine hydroxylase provide the solution structure of the full-length enzyme
Authors: Bezem Maria T. , Baumann Anne , Skjærven Lars , Meyer Romain , Kursula Petri , Martinez Aurora , Flydal Marte I. 
Published: July 2016

AbstractTyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of catecholamine neurotransmitters. TH is a highly complex enzyme at mechanistic, structural and regulatory levels and the preparation of kinetically and conformationally stable enzyme for structural characterization has been challenging. Here, we report on improved protocols for purification of recombinant human TH isoform 1 (TH1), which provide large amounts of pure, stable, active TH1 with an intact N-terminus. TH1 purified through fusion with a His-tagged maltose-binding protein on amylose resin was representative of the iron-bound functional enzyme, showing high activity and stabilization by the natural feedback inhibitor dopamine. TH1 purified through fusion with a His-tagged ZZ domain on TALON is remarkably stable, as it was partially inhibited by resin-derived cobalt. This more stable enzyme preparation provided high-quality small-angle X-ray scattering (SAXS) data and reliable structural models of full-length tetrameric TH1. The SAXS-derived model reveals an elongated conformation (Dmax = 20 nm) for TH1, different arrangement of the catalytic domains compared with the crystal structure of truncated forms and an N-terminal region with an unstructured tail that hosts the phosphorylation sites and a separated Ala-rich helical motif that may have a role in regulation of TH by interacting with binding partners.
Rapid identification of intact bacterial resistance plasmids via optical mapping of single DNA molecules
Authors: Nyberg Lena K. , Quaderi Saair , Emilsson Gustav , Karami Nahid , Lagerstedt Erik , Müller Vilhelm , Noble Charleston , Hammarberg Susanna , Nilsson Adam N. , Sjöberg Fei , Fritzsche Joachim , Kristiansson Erik , Sandegren Linus , Ambjörnsson Tobias , Westerlund Fredrik 
Published: July 2016

AbstractThe rapid spread of antibiotic resistance – currently one of the greatest threats to human health according to WHO – is to a large extent enabled by plasmid-mediated horizontal transfer of resistance genes. Rapid identification and characterization of plasmids is thus important both for individual clinical outcomes and for epidemiological monitoring of antibiotic resistance. Toward this aim, we have developed an optical DNA mapping procedure where individual intact plasmids are elongated within nanofluidic channels and visualized through fluorescence microscopy, yielding barcodes that reflect the underlying sequence. The assay rapidly identifies plasmids through statistical comparisons with barcodes based on publicly available sequence repositories and also enables detection of structural variations. Since the assay yields holistic sequence information for individual intact plasmids, it is an ideal complement to next generation sequencing efforts which involve reassembly of sequence reads from fragmented DNA molecules. The assay should be applicable in microbiology labs around the world in applications ranging from fundamental plasmid biology to clinical epidemiology and diagnostics.
Temporal asynchrony and spatial perception
Authors: Lev Maria , Polat Uri 
Published: July 2016

AbstractCollinear facilitation is an enhancement in the visibility of a target by laterally placed iso-oriented flankers in a collinear (COL) configuration. Iso-oriented flankers placed in a non-collinear configuration (side-by-side, SBS) produce less facilitation. Surprisingly, presentation of both configurations simultaneously (ISO-CROSS) abolishes the facilitation rather than increases it - a phenomenon that can’t be fully explained by the spatial properties of the target and flankers. Based on our preliminary data and recent studies, we hypothesized that there might be a novel explanation based on the temporal properties of the excitation and inhibition, resulting in asynchrony between the lateral inputs received from COL and SBS, leading to cancelation of the facilitatory component in ISO-CROSS. We explored this effect using a detection task in humans. The results replicated the previous results showing that the preferred facilitation for COL and SBS was abolished for the ISO-CROSS configuration. However, presenting the SBS flankers, but not the COL flankers 20 msec before ISO-CROSS restored the facilitatory effect. We propose a novel explanation that the perceptual advantage of collinear facilitation may be cancelled by the delayed input from the sides; thus, the final perception is determined by the overall spatial-temporal integration of the lateral interactions.
Screening for Gram-negative bacteria: Impact of preanalytical parameters
Authors: Warnke Philipp , Johanna Pohl Friederike Pola , Kundt Guenther , Podbielski Andreas 
Published: July 2016

AbstractScreening recommendations for multidrug-resistant Gram-negative bacteria comprise microbiological analyses from rectal swabs. However, essential specifications of the preanalytic steps of such screenings, i.e. the sampling technique, sampling devices and sampling site, are lacking. For standardized and optimum screening conditions these parameters are indispensable. Here, the optimum parameters were examined irrespective of the antibiotic resistance patterns of the target bacteria in order to establish a general basis for this type of screening. Swabs with rayon, polyurethane-cellular-foam and nylon-flocked tips were tested. Different sampling locations were evaluated, i.e. perianal, intraanal and deep intraanal. Subjects were swabbed and quantities of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii were assessed. Overall prevalences of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii were 94%, 16%, 12% and 2%, respectively. Bacterial recovery rates were independent from the sampling-timepoint during hospital stay. Polyurethane-cellular-foam or nylon-flocked swabs recovered significantly more bacteria as compared to rayon swabs. Intraanal swabbing resulted in significantly higher bacterial quantities as compared to perianal swabbing. In contrast, for the detection of A. baumannii, perianal swabbing seems more suitable than intraanal swabbing. Gender-related differences in bacterial recovery could be detected from perianal but not from intraanal swabs.
Electrochemical deposition of conductive and adhesive polypyrrole-dopamine films
Authors: Kim Semin , Jang Lindy K. , Park Hyun S. , Lee Jae Young 
Published: July 2016

AbstractElectrode surfaces have been widely modified with electrically conductive polymers, including polypyrrole (PPY), to improve the performance of electrodes. To utilize conductive polymers for electrode modification, strong adhesion between the polymer films and electrode substrates should be ensured with high electrical/electrochemical activities. In this study, PPY films were electrochemically polymerized on electrodes (e.g., indium tin oxide (ITO)) with dopamine as a bio-inspired adhesive molecule. Efficient and fast PPY electrodeposition with dopamine (PDA/PPY) was found; the resultant PDA/PPY films exhibited greatly increased adhesion strengths of up to 3.7 ± 0.8 MPa and the modified electrodes had electrochemical impedances two to three orders of magnitude lower than that of an unmodified electrode. This electrochemical deposition of adhesive and conductive PDA/PPY offers a facile and versatile electrode modification for various applications, such as biosensors and batteries.
Three Distinct Glutamate Decarboxylase Genes in Vertebrates
Authors: Grone Brian P. , Maruska Karen P. 
Published: July 2016

AbstractGamma-aminobutyric acid (GABA) is a widely conserved signaling molecule that in animals has been adapted as a neurotransmitter. GABA is synthesized from the amino acid glutamate by the action of glutamate decarboxylases (GADs). Two vertebrate genes, GAD1 and GAD2, encode distinct GAD proteins: GAD67 and GAD65, respectively. We have identified a third vertebrate GAD gene, GAD3. This gene is conserved in fishes as well as tetrapods. We analyzed protein sequence, gene structure, synteny and phylogenetics to identify GAD3 as a homolog of GAD1 and GAD2. Interestingly, we found that GAD3 was lost in the hominid lineage. Because of the importance of GABA as a neurotransmitter, GAD3 may play important roles in vertebrate nervous systems.
Combined Detoxification and In-situ Product Removal by a Single Resin During Lignocellulosic Butanol Production
Authors: Gao Kai , Rehmann Lars 
Published: July 2016

AbstractPhragmites australis (an invasive plant in North America) was used as feedstock for ABE (acetone-butanol-ethanol) fermentation by Clostridium saccharobutylicum. Sulphuric acid pretreated phragmites hydrolysate (SAEH) without detoxification inhibited butanol production (0.73 g/L butanol from 30 g/L sugars). The treatment of SAEH with resin L-493 prior the fermentation resulted in no inhibitory effects and an ABE titer of 14.44 g/L, including 5.49 g/L butanol was obtained, corresponding to an ABE yield and productivity of 0.49 g/g and 0.60 g/L/h, respectively. Dual functionality of the resin was realized by also using it as an in-situ product removal agent. Integrating in-situ product removal allowed for the use of high substrate concentrations without the typical product inhibition. Resin-detoxified SAEH was supplemented with neat glucose and an effective ABE titer of 33 g/L (including 13.7 g/L acetone, 16.4 g/L butanol and 1.9 g/L ethanol) was achieved with resin-based in-situ product removal, corresponding to an ABE yield and productivity of 0.41 g/g and 0.69 g/L/h, respectively. Both detoxification of the substrate and the products was achieved by the same resin, which was added prior the fermentation. Integrating hydrolysate detoxification and in-situ butanol removal in a batch process through single resin can potentially simplify cellulosic butanol production.
Ediacaran discs from South America: probable soft-bodied macrofossils unlock the paleogeography of the Clymene Ocean
Authors: Arrouy María Julia , Warren Lucas V. , Quaglio Fernanda , Poiré Daniel G. , Simões Marcello Guimarães , Rosa Milena Boselli , Peral Lucía E. Gómez 
Published: July 2016

AbstractThe origin, affinity and paleoecology of macrofossils of soft-bodied organisms of the terminal Ediacaran Period have been highly debated. Previous discoveries in South America are restricted to small shelly metazoans of the Nama Assemblage. Here we report for the first time the occurrence of discoidal structures from the Upper Ediacaran Cerro Negro Formation, La Providencia Group, Argentina. Specimens are preserved in tabular sandstones with microbially-induced sedimentary structures. Flute marks and linear scours at the base of the sandstone layers indicate deposition under high energy, episodic flows. Stratigraphic, sedimentologic, petrographic and taphonomic analyses indicate that the origin of these structures is not related to abiotic process. Preservational and morphological features, as invagination and the presence of radial grooves, indicate that they resemble typical morphs of the Aspidella plexus. The large number of small-sized individuals and the wide range of size classes with skewed distribution suggest that they lived in high-density communities. The presence of Aspidella in the Cerro Negro Formation would represent the first reliable record of Ediacaran soft-bodied organisms in South America. It also supports the paleogeographic scenario of the Clymene Ocean, in which a shallow sea covered part of the southwest Gondwana at the end of the Ediacaran.
Comparison and Interpretation of Taxonomical Structure of Bacterial Communities in Two Types of Lakes on Yun-Gui plateau of China
Authors: Han Maozhen , Gong Yanhai , Zhou Chunyu , Zhang Junqian , Wang Zhi , Ning Kang 
Published: July 2016

AbstractBacterial communities from freshwater lakes are shaped by various factors such as nutrients, pH value, temperature, etc. Their compositions and relative abundances would undergo changes to adapt the changing environments and in turn could affect the environments of freshwater lakes. Analyses of the freshwater lake’s bacterial communities under different environments would be of pivotal importance to monitor the condition of waterbody. In this study, we have collected freshwater samples from two lakes on Yun-Gui plateau of China, Lake Dianchi and Lake Haixihai and analyzed the bacterial community structures from these samples based on 16S rRNA sequencing. Results have shown that: Firstly, the bacterial community of these samples have very different taxonomical structures, not only between two lakes but also among the intra-groups for samples collected from Dianchi. Secondly, the differences between samples from two lakes are highly associated with the chemical-geographical properties of the two lakes. Thirdly, for samples of Dianchi and Haixihai, analytical results of physicochemical, taxonomical structure and relative abundance of community revealed that extreme physicochemical factors caused by human activities have strongly affected the bacterial ecosystem in Dianchi. These results have clearly indicated the importance of combining biological profiling and chemical-geographical properties for monitoring Chinese plateau freshwater bacterial ecosystem, which could provide clues for Chinese freshwater ecosystem remediation on plateau.
Clinical Application of Evoked Response Audiometry
Authors: McCandless Geary A. 
Published: July 2016

Summed evoked cortical responses to auditory stimuli were recorded on 128 clinical patients who were unable or unwilling to respond accurately to conventional audiometric techniques. Definable responses were recorded on 90 of 102 children, age 10 and younger. Subjective audiometric thresholds on children old enough to respond tended to be slightly lower than evoked response thresholds. Technically less satisfactory results were obtained in the very young child, but responses were more reliable on children age 2 and older. Evoked response audiometry in older children and adults with nonorganic hearing loss were easily measured and appeared to give an accurate measure of auditory sensitivity.
There is considerable difficulty in the interpretation of ERA measures in younger children due to influences on the response waveform of rapid changes in the alerting level. Interpretations of response should be made only after considerable experience in the use of the ERA technique.
AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity
Authors: Di Micco Antonia , Frera Gianluca , Lugrin Jérôme , Jamilloux Yvan , Hsu Erh-Ting , Tardivel Aubry , De Gassart Aude , Zaffalon Léa , Bujisic Bojan , Siegert Stefanie , Quadroni Manfredo , Broz Petr , Henry Thomas , Hrycyna Christine A. , Martinon Fabio 
Published: July 2016

SignificanceInflammasomes are cellular sensors of harmful situations such as the presence of microbes or alterations in cellular homeostasis. Upon activation, inflammasomes trigger the proteolytic maturation and release of inflammatory cytokines to initiate immune and repair responses. The assembly of inflammasome relies on a diverse repertoire of sensor proteins that can detect specific stimuli. For example, the AIM2 inflammasome is activated by the presence of microbial DNA within the cytosol. In this paper, alterations of the nuclear envelope integrity are found to cause the exposure of nuclear DNA in the cytosol to promote the activation of the AIM2 inflammasome. Nuclear envelope stress can therefore directly engage innate immune sensors to elicit inflammation.
Chemical shift imprint of intersubunit communication in a symmetric homodimer
Authors: Falk Bradley T. , Sapienza Paul J. , Lee Andrew L. 
Published: July 2016

SignificanceRegulatory signals between protein subunits depend on communication between sequential binding events. How such long-range communication, or allostery, operates at the subdomain level has been elusive, especially for homooligomeric proteins. To address this problem, homodimers of thymidylate synthase were generated for optimized study of individual protomers of the singly bound dimer. Mixed15N-labeled dimers were created with a single functional active site, allowing site-specific, protomer-specific chemical shifts to report on step-wise binding effects. Long-range intersubunit communication was observed although this communication was apparent only in the second ligand-binding step, in which changes were in the first ligand-bound region. Visualization of up to four peaks for each residue amide provides a unique way to assess the allosteric mechanism.
Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β
Authors: Yim Kendrick H. , Prince Thomas L. , Qu Shiwei , Bai Fang , Jennings Patricia A. , Onuchic José N. , Theodorakis Emmanuel A. , Neckers Leonard 
Published: July 2016

SignificanceThe molecular chaperone heat-shock protein 90 (Hsp90) is a key member of the cellular proteostasis network, and as such helps to protect cells against proteotoxic stress. Cancer cells have up-regulated members of this network, including Hsp90, to promote their survival and growth. Several Hsp90 inhibitors have undergone clinical trials, but these drugs, which bind to a shared nucleotide pocket in the N-terminal domain, do not differentiate between the four Hsp90 family members [Hsp90α, Hsp90β, GRP94 (glucose-regulated protein 94 kDa), and TRAP1 (tumor necrosis receptor-associated protein 1)]. In this report, we identify a pharmacophore contained within the natural product gambogic acid that binds uniquely to a site in Hsp90β, thus identifying this compound as a prototype of a new class of isoform-specific Hsp90 inhibitors.
Joan Tower, Silver Ladders (1986)
Authors: Bernard Jonathan W. 
Published: July 2016

Abstract
Although at first glance Joan Tower’s orchestral work Silver Ladders (1986) might seem to follow a well-established twentieth-century tradition of “octatonicism,” closer analytical examination reveals compositional uses of the octatonic collection that are quite original. A typology is developed that makes distinctions between employment of the octatonic in just one of its transpositions and the projection of two or even all three transpositions at once, and that identifies mechanisms by which one transposition can be gradually transformed into another or into non-octatonic collections such as the total chromatic. This typology is applied to analysis of passages of varying length, permitting provisional conclusions to be reached concerning form. The final section of the essay offers some musings on the significance of these analytical findings in light of Tower’s comments on her attitudes toward composition in general and on her working methods in particular.
A Reduced Duty Hours Model for Senior Internal Medicine Residents: A Qualitative Analysis of Residents’ Experiences and Perceptions
Authors: Mathew Rebecca , Gundy Serena , Ulic Diana , Haider Shariq , Wasi Parveen 
Published: July 2016

Purpose
To assess senior internal medicine residents’ experience of the implementation of a reduced duty hours model with night float, the transition from the prior 26-hour call system, and the new model’s effects on resident quality of life and perceived patient safety in the emergency department and clinical teaching unit at McMaster University.

Method
Qualitative data were collected during May 2013–July 2014, through resident focus groups held prior to implementation of a reduced duty hours model and 10 to 12 months postimplementation. Data analysis was guided by a constructivist grounded theory based in a relativist paradigm. Transcripts were coded; codes were collapsed into themes.

Results
Thematic analysis revealed five themes. Residents described reduced fatigue in the early morning, counterbalanced with worsened long-term fatigue on night float blocks; anticipation of negative impacts of the loss of distributed on-call experience and on-call shift volume; an urgency to sleep postcall in anticipation of consecutive night float shifts accompanied by conflicting role demands to stay postcall for care continuity; increased handover frequency accompanied by inaccurate/incomplete communication of patients’ issues; and improvement in the senior resident experience on the clinical teaching unit, with increased ownership over patient care and improved relationships with junior housestaff.

Conclusions
A reduced duty hours model with night float has potential to improve residents’ perceived fatigue on call and care continuity on the clinical teaching unit. This must be weighed against increased handover frequency and loss of the postcall day, which may negatively affect patient care and resident quality of life.
Co-occurring Disordered Gambling Among Treatment-Seekers at a Community Outpatient Addiction Clinic
Authors: Elman Igor , Borodovsky Jacob , Howard Margaret , Scoglio Arielle , Steinkamp Jackson , Sobieszczyk Amy , Mysels David , Albanese Mark 
Published: July 2016

Background:Parallel to the ongoing expansion of legalized gambling activities is a growing concern about rising occurrence of uncontrollable gambling. People with preexisting gambling and/or chemical addictions may be particularly vulnerable, but the extent of such co-occurring conditions and their demographic and clinical characteristics have not been sufficiently elucidated. To that end, the present study attempted to both, quantify the presence and to characterize co-occurring pathological or problem gambling (ie, respectively, at least 1- or at least 5 pathological gambling criteria from theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) among treatment-seeking patients at a community outpatient addiction program.Methods:The patients were assessed with the South Oaks Gambling Screen and their charts were reviewed for the extraction of demographic and clinical information according to a predetermined template. Data from 183 subjects withstood quality control procedures and were included.Results:The prevalence rates of co-occurring problem- (18.6%) and pathological (10.9%) gambling were strikingly higher than those found in the general population (2% and 0.5%, respectively). No increase in the clinical severity indices was observed across the gambling groups.Conclusions:Our data replicate those of prior studies reporting heightened prevalence of problematic gambling in patients with substance use disorders and extend the prior findings by including a subject population of treatment-seekers. In the era of the gambling industry growth, these results call for creation and/or adjustment of clinical addiction services to meet emerging preventive and therapeutic needs.