bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Reduced Prolonged-release Tacrolimus Exposure in De Novo Kidney Transplantation: A Randomized, Open-label, Pilot Study in Asia—OPTIMIZE Study
Authors: Kim Young Hoon , Chiang Yang-Jen , Kim Sung-Joo , Kim Myoung Soo , Park Sung Bae , Wu Sheng-Tang , Horita Kazuhiro , Nakashima Yoshihiro , Jiang Hongsi , Han Duck-Jong 
Published: March 2019

Background
A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs).

Methods
Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded.

Results
Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively.

Conclusions
Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.
Conformational resolution of nucleotide cycling and effector interactions for multiple small GTPases in parallel
Authors: Killoran Ryan C. , Smith Matthew J. 
Published: March 2019

AbstractSmall GTPase proteins alternatively bind GDP/GTP guanine nucleotides to gate signaling pathways that direct most cellular processes. Numerous GTPases are implicated in oncogenesis, particularly three RAS isoforms HRAS, KRAS and NRAS, and the RHO family GTPase RAC1. Signaling networks comprising small GTPases are highly connected, and there is evidence of direct biochemical crosstalk between the functional G-domains of these proteins. The activation potential of a given GTPase is contingent on a co-dependent interaction with nucleotide and a Mg2+ion, which bind to individual variants via distinct affinities coordinated by residues in the nucleotide binding pocket. Here, we utilize a selective-labelling strategy coupled with real-time nuclear magnetic resonance (NMR) spectroscopy to monitor nucleotide exchange, GTP hydrolysis and effector interactions of multiple small GTPases in a single complex system. We provide new insight on nucleotide preference and the role of Mg2+in activating both wild-type and oncogenic mutant enzymes. Multiplexing reveals GEF, GAP and effector binding specificity in mixtures of GTPases and establishes the complete biochemical equivalence of the three related RAS isoforms. This work establishes that direct quantitation of the nucleotide-bound conformation is required to accurately resolve GTPase activation potential, as GTPases such as RALA or the G12C mutant of KRAS demonstrate fast exchange kinetics but have a high affinity for GDP. Further, we propose that the G-domains of small GTPases behave autonomously in solution and nucleotide cycling proceeds independent of protein concentration but is highly impacted by Mg2+abundance.
Laminar Specific fMRI Reveals Directed Interactions in Distributed Networks During Language Processing
Authors: Sharoh Daniel , van Mourik Tim , Bains Lauren J. , Segaert Katrien , Weber Kirsten , Hagoort Peter , Norris David G. 
Published: March 2019

AbstractLaminar resolution, functional magnetic resonance imaging (lfMRI) is a noninvasive technique with the potential to distinguish top-down and bottom-up signal contributions on the basis of laminar specific interactions between distal regions. Hitherto, lfMRI could not be demonstrated for either whole-brain distributed networks or for complex cognitive tasks. We show that lfMRI can reveal whole-brain directed networks during word reading. We identify distinct, language critical regions based on their association with the top-down signal stream and establish lfMRI for the noninvasive assessment of directed connectivity during task performance.
Moving microbes: the dynamics of transient microbial residence on human skin
Authors: Vandegrift Roo , Fahimipour Ashkaan K. , Muscarella Mario , Bateman Ashley C. , Van Den Wymelenberg Kevin , Bohannan Brendan J.M. 
Published: March 2019

AbstractThe human skin microbiome interacts intimately with human health, yet the drivers of skin microbiome composition and diversity are not well-understood. The composition of the skin microbiome has been characterized as both highly variable and relatively stable, depending on the time scale under consideration, and it is not clear what role contact with environmental sources of microbes plays in this variability. We experimentally mimicked human skin contact with two common environmental sources of microorganisms — soils and plant leaves — and characterized the dynamics of microbial acquisition and persistence on skin on very short time scales. Repeatable changes in skin community composition following encounters with environmental sources were observed, and these trajectories largely depend on donor community biomass distributions. Changes in composition persisted for at least 24 hours and through a soap and water wash following exposures to relatively high biomass soil communities. In contrast, exposures to lower biomass leaf communities were undetectable after a 24 hour period. Absolute abundances of bacterial taxa in source communities predicted transmission probabilities and residence times, independent of phylogenetic considerations. Our results suggest that variability in the composition of the skin microbiome can be driven by transient encounters with common environmental sources, and that these relatively transient effects can persist when the source is of sufficient biomass.ImportanceHumans come into contact with environmental sources of microbes, such as soil or plants, constantly. Those microbial exposures have been linked to health through training and modulation of the immune system. While much is known about the human skin microbiome, the short term dynamics after a contact event, such as touching soil, have not been well characterized. In this study, we examine what happens after such a contact event, describing trends in microbial transmission to and persistence on the skin. Additionally, we use computational sampling model simulations to interrogate null expectations for these kinds of experiments. This work has broad implications for infection control strategies and therapeutic techniques that rely on modification of the microbiome, such as probiotics and faecal transplantation.
Structural determinants of microtubule minus end preference in CAMSAP CKK domains
Authors: Atherton Joseph , Luo Yanzhang , Xiang Shengqi , Yang Chao , Jiang Kai , Stangier Marcel , Vemu Annapurna , Cook Alexander D. , Wang Su , Roll-Mecak Antonina , Steinmetz Michel O. , Akhmanova Anna , Baldus Marc , Moores Carolyn A. 
Published: March 2019

AbstractCAMSAP/Patronins regulate microtubule minus-end dynamics. Their end specificity is mediated by their CKK domains, which we proposed recognise specific tubulin conformations found at minus ends. To critically test this idea, we compared the human CAMSAP1 CKK domain (HsCKK) with a CKK domain fromNaegleria gruberi(NgCKK), which has lost minus-end specificity. Near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit subtly different footprints on microtubules. Whereas NgCKK binding does not alter the microtubule architecture, HsCKK remodels its microtubule interaction site and changes the underlying polymer structure because the tubulin lattice conformation is not optimal for its binding. NMR experiments show that HsCKK is remarkably rigid, supporting this remodelling ability. Thus, in contrast to many MAPs, CKK domains can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.
MCT4 is a high affinity transporter capable of exporting lactate in high-lactate environments
Authors: Contreras-Baeza Y , Sandoval PY , Alarcón R , Galaz A , Cortés-Molina F , Alegría K , Baeza-Lehnert F , Arce-Molina R , Guequén A , Flores CA , San Martín A , Barros LF 
Published: March 2019

AbstractMCT4 is an H+-coupled transporter expressed in metastatic cancer cells, macrophages, and other highly glycolytic cells, where it extrudes excess lactate generated by the Warburg phenomenon or by hypoxia. Intriguingly, its reported Kmfor lactate, obtained with pH-sensitive probes, is more than an order of magnitude higher than physiological lactate. Here we examined MCT4-rich MDA-MB-231 cells using the FRET sensor Laconic and found a median Kmfor lactate uptake of only 1.7 mM, while parallel estimation in the same cells with a pH probe gave a Kmof 27 mM. The median Kmof MCT4 for lactate was 0.7 mM in MCT4-expressing HEK293 cells and 1.2 mM in human macrophages, suggesting that high substrate affinity is a robust property of the transporter. Probed with the FRET sensor Pyronic, MCT4 showed a Kmfor pyruvate of only 4.2 mM in MDA-MB-231 cells, as opposed to > 150 mM reported previously. We conclude that prior estimates of MCT4 affinity based on pH probes were severely biased by the confounding action of pH regulatory mechanisms. Numerical simulation showed that MCT4, but not MCT1 or MCT2, endows cells with the capability of lactate extrusion in high lactate environments. The revised kinetic properties and novel transport assays may help in developing small-molecule MCT4 blockers for research and therapy.
The complete chloroplast genome of Chinese medicine (Psoralea corylifolia Linn): Molecular Structures, barcoding analysis, and phylogenetic Analysis
Authors: Tan Wei , Gao Han , Zhang Huanyu , Yu Xiaolei , Tian Xiaoxuan , Jiang Weiling , Zhou Kun 
Published: March 2019

AbstractPsoralea corylifoliais one kind of traditional Chinese medicine used in China widely. In this study, we sequence the complete chloroplast genome ofP. corylifolia, which is 153,114 bp in size and includes a pair of inverted repeats regions of 25,557 bp interspersed by a small single copy of 17,885 bp and a large single copy of 84,115 bp region. Approximately 98 simple sequence repeats, 14 forward, 2 reverse, 2 complement, 32 palindromic and 49 tandem repeats are identified in theP. corylifoliachloroplast genome. The chloroplast genomes ofP. corylifoliaand threeGlycinespecies are conserved in gene order and content, but show high diversity within intergenic spacers.P. corylifoliawith threeGlycinespecies in Papilionoideae fall into the same clade based on 75 conserved coding-protein genes phylogenomic analysis. Moreover, four chloroplast DNA regions (ycf1, matK, accD, ndhF) can serve as the barcodes. In general, our findings will dedicate to better comprehension of the genome aspect as well as evolutionary status ofP. corylifolia.
Bioremediation of soils contaminated with petroleum solid wastes and drill cuttings byPleurotussp. strains under different treatment scales
Authors: Romero-Silva Roberto , Sánchez-Reyes Ayixon , Díaz-Rodríguez Yuletsis , Batista-García Ramón Alberto , Hernández-Hernández Danai , de Robles Judith Tabullo 
Published: March 2019

AbstractWastes from the oil industry represent one of the sources of soil pollution with the greatest environmental impact. Both drill cuttings and crude residues are delivered to the soil and produce severe toxic effects, mainly due to the presence of polycyclic aromatic hydrocarbons. Various bioremediation technologies have been implemented in order to restore the soil quality and the natural auto depuration capabilities, amongst them: composting, bioaugmentation and biostimulation. All of these bioremediation techniques promise to be eco-friendlier and cheaper alternatives than other approaches. In this work we have evaluated several strains ofPleurotussp. for their effect on the bioremediation of oil-contaminated wastes and drill cuttings disposed in storage tanks or in open-air soil lots for many years. Our results suggest that combined natural attenuation mechanism and directed fungal biodegradation activities, could be promising strategies to remediate heavily petroleum polluted soils and drilling wastes both at the laboratory and in field conditions. Furthermore, we present new data that supportingPleurotusgenera as able to degrade asphaltenes, the most recalcitrant fraction of petroleum. This study proposes an approach that at the same time can treat soils contaminated with waste from drill cuttings and bottoms of crude storage tanks.
Divergent mitochondrial and nuclear OXPHOS genes are candidates for genetic incompatibilities inFicedulaFlycatchers
Authors: van der heijden Eva , McFarlane S. Eryn , van der Valk Tom , Qvarnström Anna 
Published: March 2019

AbstractHybrid dysfunction is an important source of reproductive isolation between emerging species. Bateson-Dobzhansky-Muller incompatibilities are theoretically well-recognized as the underlying cause of low hybrid dysfunction. However, especially in wild populations, little empirical evidence exists for which genes are involved in such incompatibilities. The relative role of ecological divergence in causing the build-up of genetic incompatibilities in relation to other processes such as genomic conflict therefore remains largely unknown. Genes involved in energy metabolism are potential candidates for genetic incompatibilities, since energy metabolism depends on co-expression of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) leading to mitonuclear coadaptation. When mitochondrial and nuclear genes lacking a co-evolutionary history appear together in hybrids, incompatibilities could arise.Ficedulaflycatcher F1 hybrids have a higher resting metabolic rate (RMR) compared to the parental species, which could be a sign of genetic incompatibilities between energy metabolism genes that diverged in response to environmental differences while the species were in allopatry. Based on sequences of 15 mitochondrial genes of 264 individuals, we show that the two species have divergent mtDNA caused by the build-up of mainly synonymous mutations and a few non-synonymous mutations. Pied flycatcher mitogenomes show evidence of non-neutrality, indicating a selective sweep or population expansion. There is little variation in the nuclear OXPHOS-related proteins and no significant deviation from neutrality, however, specific codon identified sites might be under positive selection in both mitochondrial and nuclear genes encoding OXPHOS proteins for complex I and III. Taken together, these diverged mitonuclear genes therefore constitute possible candidates underlying, at least part of the genetic incompatibilities that cause hybrid dysfunction in crosses between collared and pied flycatchers.
Visually evoked responses are enhanced when engaging in a video game
Authors: Ki Jason J. , Parra Lucas C. , Dmochowski Jacek P. 
Published: March 2019

AbstractWhile it is well known that vision guides movement, less appreciated is that the motor cortex also provides input to the visual system. Here we asked whether neural processing of visual stimuli is acutely modulated during motor activity, hypothesizing that visual evoked responses are enhanced when engaged in a motor task that depends on the visual stimulus. To test this, we told participants that their brain activity was controlling a video game that was in fact the playback of a prerecorded game. The deception, which was effective in half of participants, aimed to engage the motor system while avoiding evoked responses related to actual movement or somatosensation. In other trials, subjects actively played the game with keyboard control or passively watched a playback. The strength of visually evoked responses was measured as the temporal correlation between the continuous stimulus and the evoked potentials on the scalp. We found reduced correlation during passive viewing, but no difference between active and sham play. Alpha band (8-12 Hz) activity was reduced over central electrodes during sham play, indicating recruitment of motor cortex despite the absence of overt movement. To account for the potential increase of attention during game play, we conducted a second study with subjects counting screen items during viewing. We again found increased correlation during sham play, but no difference between counting and passive viewing. While we cannot fully rule out the involvement of attention, our findings do demonstrate an enhancement of visual evoked responses during active vision.
A logical model of homology for comparative biology
Authors: Mabee Paula M. , Balhoff James P. , Dahdul Wasila M. , Lapp Hilmar , Mungall Christopher J. , Vision Todd J. 
Published: March 2019

AbstractThere is a growing body of research on the evolution of anatomy in a wide variety of organisms. Discoveries in this field could be greatly accelerated by computational methods and resources that enable these findings to be compared across different studies and different organisms and linked with the genes responsible for anatomical modifications. Homology is a key concept in comparative anatomy; two important types are historical homology (the similarity of organisms due to common ancestry) and serial homology (the similarity of repeated structures within an organism). We explored how to most effectively represent historical and serial homology across anatomical structures to facilitate computational reasoning. We assembled a collection of homology assertions from the literature with a set of taxon phenotypes for vertebrate fins and limbs from the Phenoscape Knowledgebase (KB). Using six competency questions, we evaluated the reasoning ramifications of two logical models: the Reciprocal Existential Axioms Homology Model (REA) and the Ancestral Value Axioms Homology Model (AVA). Both models returned the user-expected results for all but one historical homology query and all serial homology queries. Additionally, for each competency question, the AVA model returns the search term and any subtypes. We identify some challenges of implementing complete homology queries due to limitations of OWL reasoning. This work lays the foundation for homology reasoning to be incorporated into other ontology-based tools, such as those that enable synthetic supermatrix construction and candidate gene discovery.
Functional relevance of dual olfactory bulb in olfactory coding
Authors: Kuruppath Praveen , Bai Li , Belluscio Leonardo 
Published: March 2019

AbstractBilateral convergence of external stimuli is a common feature of vertebrate sensory systems. This convergence of inputs from the bilateral receptive fields allows higher order sensory perception, such as depth perception in the vertebrate visual system and stimulus localization in the auditory system. The functional role of such bilateral convergence in the olfactory system is mostly unknown. To test whether each olfactory bulb contributes a separate piece of olfactory information, and whether information from the bilateral olfactory bulb is integrated, we synchronized the activation of olfactory bulbs with blue light in mice expressing channelrhodopsin in the olfactory sensory neurons and behaviorally assessed the relevance of dual olfactory bulb in olfactory perception. Our findings suggest that each olfactory bulb contributes separate components of olfactory information and mice integrate the olfactory information from each olfactory bulb to identify an olfactory stimulus.Significance statementIdentifying an odor is the first step in olfactory coding, as it is critical for the survival of most animals. Previous studies have shown that bilateral olfactory bulbs help rodents to localize the odor source and navigate accordingly. But It is still unclear whether the bilateral olfactory information plays any role in determining odor identity. Here for the first time, using optogenetics and behavioral experiments, we demonstrate that each olfactory bulb provides distinct olfactory information, and rodents integrate information from the two bulbs to identify an odor.
From acoustic to linguistic analysis of temporal speech structure: acousto-linguistic transformation during speech perception using speech quilts
Authors: Overath Tobias , Paik Joon H. 
Published: March 2019

AbstractSpeech perception entails the mapping of the acoustic waveform to linguistic representations. For this mapping to succeed, the speech signal needs to be tracked over various temporal windows at high temporal precision in order to decode linguistic units ranging from phonemes (tens of milliseconds) to sentences (seconds). Here, we tested the hypothesis that cortical processing of speech-specific temporal structure is modulated by higher-level linguistic analysis. Using fMRI, we measured BOLD signal changes to 4-s long speech quilts with variable temporal structure (30, 120, 480, 960 ms segment lengths), as well as natural speech, created from a familiar (English) or foreign (Korean) language. We found evidence for the acoustic analysis of temporal speech properties in superior temporal sulcus (STS): the BOLD signal increased as a function of temporal speech structure in both familiar and foreign languages. However, activity in left inferior gyrus (IFG) revealed evidence for linguistic processing of temporal speech properties: the BOLD signal increased as a function of temporal speech structure only in familiar, but not in foreign speech. Network analyses suggested that left IFG modulates processing of speech-specific temporal structure in primary auditory cortex, which in turn sensitizes processing of speech-specific temporal structure in STS. The results thus reveal a network for acousto-linguistic transformation consisting of primary and non-primary auditory cortex, STS, and left IFG.Significance StatementWhere and how the acoustic information contained in complex speech signals is mapped to linguistic information is still not fully explained by current speech/language models. We dissociate acoustic from linguistic analyses of speech by comparing the same acoustic manipulation (varying the extent of temporal speech structure) in two languages (native, foreign). We show that acoustic temporal speech structure is analyzed in superior temporal sulcus (STS), while linguistic information is extracted in left inferior frontal gyrus (IFG). Furthermore, modulation from left IFG enhances sensitivity to temporal speech structure in STS. We propose a model for acousto-linguistic transformation of speech-specific temporal structure in the human brain that can account for these results.