bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Postlabeling Delay Time in 3-Dimensional Pseudocontinuous Arterial Spin-Labeled Perfusion Imaging in Normal Children
Authors: Tang Shilong , Liu Xianfan , He Ling , Liu Bo , Qin Bin , Feng Chuan 
Published: September 2019

Objective
To explore the application value of postlabeling delay (PLD) in 3D pseudocontinuous arterial spin–labeled (3D-pcASL) perfusion imaging in normal children and to find the optimal PLD values for children at each age group.

Methods
Five groups of children, with 50 patients in each group, who underwent routine magnetic resonance imaging scans with normal results were included. The patients were stratified according to the following ages: younger than 1 month, more than 1 month to 6 months, more than 6 months to 12 months, more than 1 year to 3 years, more than 3 years to 6 years, and more than 6 years to 18 years. All patients received 3D-pcASL perfusion magnetic resonance scanning. The PLD values were set to 1025, 1525, or 2025 milliseconds. In subjective evaluations, the signal-to-noise ratio (SNR) and cerebral blood flow (CBF) of 3D-pcASL perfusion images under different PLD values were compared and analyzed.

Results
For patients in the <1-month group and >1-month to 6-month group, the images were mainly grade A when the PLD value was 1025 milliseconds, which equaled 43 and 46 cases, respectively. The brain CBF values and SNR values were higher than those of the images with PLD values of 1525 and 2025 milliseconds. For patients in the >6-month to 12-month group, >1-year to 3-year group, >3-year to 6-year group, and >6-year to 18-year group, the images were mainly grade A when the PLD value was 1525 milliseconds, which equaled 43, 45, 43, and 46 cases, respectively. The brain CBF values and SNR values were higher than those of the images with PLD values of 1025 and 2025 milliseconds.

Conclusions
The optimal PLD values for 3D-pcASL perfusion imaging are different in children of different ages. The optimal PLD value for infants who are 6 months younger is 1025 milliseconds. The optimal PLD value for children older than 6 months to 18 years is 1525 milliseconds.
Simulation-Based Training in Measurement of Blood Pressure
Authors: Basheer Aneesh , Das Subhasis , Iqbal Nayyar , Kandasamy Ravichandran 
Published: September 2019

Introduction
Simulators are used for training competencies including blood pressure (BP) measurement. Whether such training translates to competency in real life is unclear.

Methods
We randomized 145 first-year undergraduate medical students to train on a BP simulator or arms of colleagues. After training, all students were assessed for accuracy (within 4 mm Hg above or below assessor's simultaneous recording) and methodology of BP recordings by an objectively structured clinical examination on real patients.

Results
Overall, 67 (46.2%) and 92 (63.4%) students accurately measured systolic and diastolic BP, respectively. Forty-three (58.1%) of 74 students in the conventional training recorded systolic BP accurately compared with 24 (33.8%) of 71 students in simulator training (P = 0.005). Diastolic BP was accurately recorded by 56 (75.7%) of 74 students in conventional group as against 36 (50.7%) of 71 students trained on simulator (P = 0.002). Median (interquartile range) objectively structured clinical examination score in conventional group was 8 (7–9) compared with 6 (5–7) in simulator group (P < 0.001).

Conclusions
Simulator-based training did not translate to clinical competence in terms of accuracy and methodology of BP recordings in real-life settings. Notwithstanding its advantages, simulator-based BP training needs integration with human element to make it meaningful and relevant to clinical practice.
The Impact of Transport Modality on Efficiency of Simulated Neonatal Endotracheal Intubation
Authors: Geyer Emily D. , Walia Hina , Syed Faizaan , Hakim Mohammed , Tumin Dmitry , Tobias Joseph D. , Moharir Alok 
Published: September 2019

Introduction
Although the transport of neonates is generally safe, adverse events can occur where equipment is a contributing factor. The aims of the study were to explore how the types of neonatal intensive care unit bed in use could impact a simulated emergency endotracheal intubation and to identify future areas for training and education.

Methods
The efficiency of endotracheal intubation performed during simulated neonatal transport using 3 different transport modalities (closed incubator bed, open incubator bed, and open radiant warmer bed) was assessed. Twenty participants were enrolled. Outcomes included time to intubation, intubation success, and ease of mannequin access and were compared using Wilcoxon signed-rank tests and McNemar exact tests.

Result
Median times to intubation were 59, 44, and 37 seconds with the incubator top closed, with the top open, and with the open radiant warmer bed, respectively. Intubation was slowest and subjective ease of access was most difficult with the incubator top closed.

Conclusions
Experienced anesthesia providers had significantly greater difficulty with simulated emergency endotracheal intubation when performing neonatal transport with the incubator top closed compared with available alternative modes.
Diauxie and co-utilization are not exclusive during growth in nutritionally complex environments
Authors: Perrin Elena , Giovannini Michele , Di Patti Francesca , Cardazzo Barbara , Carraro Lisa , Fagorzi Camilla , Ghini Veronica , Turano Paola , Fani Renato , Fondi Marco 
Published: September 2019

AbstractThe classic view of microbial growth strategy when multiple carbon sources are available states that they either metabolize them sequentially (diauxic growth) or simultaneously (co-utilization). This perspective is biased by the fact that this process has been mainly analysed in over-simplified laboratory settings, i.e. using a few model microorganisms and growth media containing only two alternative compounds. Models concerning the mechanisms and the dynamics regulating nutrients assimilation strategies in conditions that are closer to the ones found in natural settings (i.e. with many alternative carbon/energy sources) are missing. Here, we show that bacterial co-utilization and sequential uptake of multiple substrates can coexist when multiple possible nutrients are provided in the same growth experiment, leading to an efficient exploitation of nutritionally complex settings. The order of nutrient uptake is determined by the actual biomass yield (and growth rate) that can be achieved when the same compounds are provided as single carbon sources. Finally, using two alternative theoretical models we show that this complex metabolic phenotype can be explained by a tight regulation process that allows microbes to actively modulate the different assimilatory pathways involved.
Implicit versus explicit control strategies in models for vector-borne disease epidemiology
Authors: Demers Jeffery , Robertson Suzanne L. , Bewick Sharon , Fagan William F. 
Published: September 2019

AbstractThroughout the vector-borne disease modeling literature, there exist two general frameworks for incorporating vector management strategies (e.g. area-wide adulticide spraying and larval source reduction campaigns) into vector population models, namely, the “implicit” and “explicit” control frameworks. The more simplistic “implicit” framework facilitates derivation of mathematically rigorous results on disease suppression and optimal control, but the biological connection of these results to realworld “explicit” control actions that could guide specific management actions is vague at best. Here, we formally define the biological and mathematical relationships between implicit and explicit control, and we provide detailed mathematical expressions relating the strength of implicit control to management-relevant properties of explicit control for four common intervention strategies. These expressions allow optimal control and sensitivity analysis results in existing implicit control studies to be interpreted in terms of real world actions. Our work reveals a previously unknown fact: implicit control is a meaningful approximation of explicit control only when resonance-like synergistic effects between multiple controls have a negligible effect on average population reduction. When non-negligible synergy exists, implicit control results, despite their mathematical tidiness, fail to provide accurate predictions regarding vector control and disease spread. The methodology we establish can be applied to study the interaction of phenological effects with control strategies, and we present a new technique for finding impulse control strategies that optimally reduce a vector population in the presence of seasonally oscillating model parameters. Collectively, these elements build an effective bridge between analytically interesting and mathematically tractable implicit control and the challenging, action-oriented explicit control.
The role of early acoustic experience in song discrimination
Authors: Hudson Emily J. , Creanza Nicole , Shizuka Daizaburo 
Published: September 2019

AbstractOscine songbirds are an ideal system for investigating how early experience affects behavior. Young songbirds face a challenging task: how to recognize and selectively learn only their own species’ song, often during a time-limited window. Because birds are capable of hearing birdsong very early in life, early exposure to song could plausibly affect recognition of appropriate models; however, this idea conflicts with the traditional view that song learning occurs only after a bird leaves the nest. Thus, it remains unknown whether natural variation in acoustic exposure prior to song learning affects the template for recognition. In a population where sister species, golden-crowned and white-crowned sparrows, breed syntopically, we found that nestlings discriminate between heterospecific and conspecific song playbacks prior to the onset of song memorization. We then asked whether natural exposure to more frequent or louder heterospecific song explained any variation in golden-crowned nestling response to heterospecific song playbacks. We characterized the amount of each species’ song audible in golden-crowned sparrow nests and showed that even in a relatively small area, the ratio of heterospecific to conspecific song exposure varies widely. However, although many songbirds hear and respond to acoustic signals before fledging, golden-crowned sparrow nestlings that heard different amounts of heterospecific song did not behave differently in response to heterospecific playbacks. This study provides the first evidence that song discrimination at the onset of song learning is robust to the presence of closely related heterospecifics in nature, which may be an important adaptation in sympatry between potentially interbreeding taxa.
Capturing the dynamics of peripersonal space by integrating sound propagation properties and expectancy effects
Authors: Hobeika Lise , Taffou Marine , Carpentier Thibaut , Warusfel Olivier , Viaud-Delmon Isabelle 
Published: September 2019

AbstractHighlightsLogarithmically distributed auditory distances provides an apt granularity of PPSMeasuring expectation helps to interpret behavioral impact of audiotactile integrationTactile RTs follows a logarithmic decrease due to audiotactile integrationPeripersonal space is better characterized and quantified with this refinementBackgroundHumans perceive near space and far space differently. Peripersonal space, i.e. the space directly surrounding the body, is often studied using paradigms based on auditory-tactile integration. In these paradigms, reaction time to a tactile stimulus is measured in the presence of a concurrent auditory looming stimulus.New MethodWe propose here to refine the experimental procedure considering sound propagation properties in order to improve granularity and relevance of auditory-tactile integration measures. We used a logarithmic distribution of distances for this purpose. We also want to disentangle behavioral contributions of the targeted audiotactile integration mechanisms from expectancy effects. To this aim, we added to the protocol a baseline with a fixed sound distance.ResultsExpectation contributed significantly to overall behavioral responses. Subtracting it isolated the audiotactile effect due to the stimulus proximity. This revealed that audiotactile integration effects have to be tested on a logarithmic scale of distances, and that they follow a linear variation on this scale.Comparison with Existing Method(s)The granularity of the current method is more relevant, providing higher spatial resolution in the vicinity of the body. Furthermore, most of the existing methods propose a sigmoid fitting, which rests on the intuitive framework that PPS is an in-or-out zone. Our results suggest that behavioral effects follow a logarithmic decrease, thus a response graduated in space.ConclusionsThe proposed protocol design and method of analysis contribute to refine the experimental investigation of the factors influencing and modifying multisensory integration phenomena in the space surrounding the body.
Single mutation at a highly conserved region of chloramphenicol acetyltransferase enables thermophilic isobutyl acetate production directly from cellulose by Clostridium thermocellum
Authors: Seo Hyeongmin , Lee Jong-Won , Garcia Sergio , Trinh Cong T. 
Published: September 2019

ABSTRACTBackgroundEsters are versatile chemicals and potential drop-in biofuels. To develop a sustainable production platform, microbial ester biosynthesis using alcohol acetyltransferases (AATs) has been studied for decades. Volatility of esters endows thermophilic production with advantageous downstream product separation. However, due to the limited thermal stability of AATs known, the ester biosynthesis has largely relied on use of mesophilic microbes. Therefore, developing thermostable AATs is important for thermophilic ester production directly from lignocellulosic biomass by the thermophilic consolidated bioprocessing (CBP) microbes, e.g., Clostridium thermocellum.ResultsIn this study, we engineered a thermostable chloramphenicol acetyltransferase from Staphylococcus aureus (CATSa) for enhanced isobutyl acetate production at elevated temperature. We first analyzed the broad alcohol substrate range of CATSa. Then, we targeted a highly conserved region in the binding pocket of CATSa for mutagenesis. The mutagenesis revealed that F97W significantly increased conversion of isobutanol to isobutyl acetate. Using CATSa F97W, we demonstrated the engineered C. thermocellum could produce isobutyl acetate directly from cellulose.ConclusionsThis study highlights that CAT is a potential thermostable AAT that can be harnessed to develop the thermophilic CBP microbial platform for biosynthesis of designer bioesters directly from lignocellulosic biomass.
The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation
Authors: Mealer Robert G. , Jenkins Bruce G. , Chen Chia-Yen , Daly Mark J. , Ge Tian , Lehoux Sylvain , Marquardt Thorsten , Palmer Christopher D. , Park Julien H. , Parsons Patrick J. , Sackstein Robert , Williams Sarah E. , Cummings Richard D. , Scolnick Edward M. , Smoller Jordan W. 
Published: September 2019

AbstractA common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations in SLC39A8 result in undetectable serum manganese (Mn) and a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity of glycosyltransferases to Mn concentration. Here, we identified several Mn-related changes in human carriers of the common SLC39A8 missense allele. Analysis of structural brain MRI scans showed a dose-dependent change in the ratio of T2w to T1w signal in several regions. Comprehensive trace element analysis confirmed a specific reduction of only serum Mn, and plasma protein N-glycome profiling revealed reduced complexity and branching. N-glycome profiling from two individuals with SLC39A8-CDG showed similar but more severe alterations in branching that improved with Mn supplementation, suggesting that the common variant exists on a spectrum of hypofunction with potential for reversibility. Characterizing the functional impact of this variant will enhance our understanding of schizophrenia pathogenesis and identify novel therapeutic targets and biomarkers of disease.SummaryA common variant in the manganese transporter SLC39A8 is associated with numerous phenotypes including schizophrenia. Mealer et. al. presents an in-depth analysis of brain MRI and plasma glycomics in human carriers of the common variant, identifying several manganese-related changes with potential for diagnostic and therapeutic biomarker development.
Low miRNA abundance disables microRNA pathway in mammalian oocytes
Authors: Kataruka Shubhangini , Modrak Martin , Kinterova Veronika , Zeitler Daniela M. , Malik Radek , Kanka Jiri , Meister Gunter , Svoboda Petr 
Published: September 2019

ABSTRACTMicroRNAs (miRNAs) are ubiquitous small RNAs, which guide post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and is dispensable for development. We report that miRNAs do not accumulate like maternal mRNAs during oocyte growth. The most abundant miRNAs total tens of thousands of molecules in fully-grown oocytes, a number similar to that observed in much smaller fibroblasts. The lack of miRNA accumulation acts like miRNA knock-down, where miRNAs can engage their targets but are not abundant enough to produce significant silencing effect. Injection of 100,000 miRNAs was sufficient to restore reporter repression in oocytes, confirming that miRNA inactivity primarily stems from low miRNA abundance and not from an active repression of the miRNA pathwayper se. Similar situation was observed in rat, hamster, porcine, and bovine oocytes arguing that miRNA inactivity is not a mouse-specific adaptation but a common mammalian oocyte feature.
Elevated exposure to prenatal thyroid hormones affects embryonic mortality but has no clear effects into adulthood
Authors: Sarraude Tom , Hsu Bin-Yan , Groothuis Ton G.G. , Ruuskanen Suvi 
Published: September 2019

AbstractMaternal thyroid hormones (THs) are known to be crucial in embryonic development in humans, but their influence on other, especially wild, animals remains poorly understood. So far, the studies that experimentally investigated the consequences of maternal THs focused on short-term effects, while early organisational effects with long-term consequences, as shown for other prenatal hormones, could also be expected. In this study, we aimed at investigating both the short- and long-term effects of prenatal THs in a bird species, the Japanese quailCoturnix japonica.We experimentally elevated yolk TH content (the prohormone T4, and its active metabolite T3, as well as a combination of both hormones). We analysed hatching success, embryonic development, offspring growth and oxidative stress as well as their potential organisational effects on reproduction, moult, and oxidative stress in adulthood. We found that eggs injected with both hormones had a higher hatching success compared with control eggs, suggesting conversion of T4into T3by the embryo. We detected no other clear short-term or long-term effects of yolk THs. These results suggest that yolk thyroid hormones are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal thyroid hormones will greatly benefit from studies investigating how embryos use and respond to this maternal signalling. Long-term studies on prenatal THs in other taxa in the wild are needed for a better understanding of this hormone-mediated maternal pathway.
OR1D2 receptor mediates bourgeonal-induced human CatSper activation in a G-protein dependent manner
Authors: Cheng Yi-min , Luo Tao , Peng Zhen , Chen Hou-yang , Zhang Jin , Zeng Xu-Hui 
Published: September 2019

AbstractDuring fertilization, sperm are guided towards eggs by physiological chemokines, a process named sperm chemotaxis. Human sperm chemotaxis is speculated to be mediated by olfactory receptor OR1D2 in a pathway requiring calcium influx. Bourgeonal, an artificial ligand of OR1D2, can activate CatSper, the primary calcium channel in human sperm. However, whether bourgeonal-induced CatSper activation requires OR1D2 and how CatSper is activated remain unclear. Herein, we show that OR1D2 antibody can inhibit bourgeonal-induced CatSper activation and sperm chemotaxis, proving that OR1D2 mediates bourgeonal-induced CatSper activation. Furthermore, bourgeonal-evoked CatSper currents can be greatly suppressed by either GDP-β-S or antibody of Gαs. Interestingly, bourgeonal can transiently increase sperm cAMP level, and this effect can be abolished by OR1D2 antibody. Consistently, bourgeonal-induced CatSper activation can be inhibited by membrane adenylate cyclases inhibitor. Overall, our results indicate that bourgeonal activates CatSper via OR1D2-G protein-cAMP pathway. Although CatSper can be activated by various physiological and environmental factors, this study represents the most recent progress proving that CatSper can be indirectly activated by extracellular regulators through a G-protein-dependent intracellular signaling pathway.
Functional coupling between NMDA receptors and SK channels in rat hypothalamic magnocellular neurons: altered mechanisms during heart failure
Authors: Ferreira-Neto HC , Stern JE 
Published: September 2019

ABSTRACTGlutamatergic NMDA receptors (NMDAR) and small conductance Ca2+-activated K+ channels (SK) are critical synaptic and intrinsic mechanisms that regulate the activity of hypothalamic magnocellular neurosecretory neurons (MNNs) under physiological and pathological states, including lactation and heart failure (HF). Still, whether NMDARs and SK channels in MNNs are functionally coupled, and whether changes in this coupling contribute to exacerbated neuronal activity during HF is at present unknown. In the present study, we addressed these questions using patch-clamp electrophysiology and confocal Ca2+ imaging in a rat model of ischaemic HF. We found that in MNNs of sham rats, blockade of SK channels with apamin (200 nM) significantly increased the magnitude of an NMDAR-evoked current (INMDA). We also observed that blockade of SK channels potentiated NMDAR-evoked firing, and abolished spike frequency adaptation in MNNs from sham, but not HF rats. Importantly, a larger INMDA-ΔCa2+response was observed under basal conditions in HF compared to sham rats. Finally, we found that dialyzing recorded cells with the Ca2+ chelator BAPTA (10 mM) increased the magnitude of INMDA in MNNs from both sham and HF rats, and occluded the effects of apamin in the former. Together, our studies demonstrate that in MNNs, NMDARs and SK channels are functionally coupled, forming a local negative feedback loop that restrains the excitatory effect evoked by NMDAR activation. Moreover, our studies also support a blunted NMDAR-SK channel coupling in MNNs of HF rats, standing thus as a pathophysiological mechanism contributing to exacerbated hypothalamic neuronal activity during this prevalent neurogenic cardiovascular disease.