bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducible Plasmid Self-Destruction (IPSD) assisted genome engineering in lactobacilli and bifidobacteria
Authors: Zuo Fanglei , Zeng Zhu , Hammarström Lennart , Marcotte Harold 
Published: May 2019

ABSTRACTGenome engineering is essential for application of synthetic biology in probiotics including lactobacilli and bifidobacteria. Several homologous recombination system-based mutagenesis tools have been developed for these bacteria but still, have many limitations in different species or strains. Here we developed a genome engineering method based on an inducible self-destruction plasmid delivering homologous DNA into bacteria. Excision of the replicon by induced recombinase facilitates selection of homologous recombination events. This new genome editing tool called Inducible Plasmid Self-Destruction (IPSD) was successfully used to perform gene knock-out and knock-in in lactobacilli and bifidobacteria. Due to its simplicity and universality, the IPSD strategy may provide a general approach for genetic engineering of various bacterial species.
Rats can learn a temporal task in a single session
Authors: Reyes Marcelo Bussotti , Miranda Diego Henrique de , Tunes Gabriela Chiuffa , Caetano Marcelo Salvador 
Published: May 2019

AbstractFixed interval, peak interval, and temporal bisection procedures have been used to assess cognitive functions and address questions such as how animals perceive, represent, and reproduce time intervals. They have also been extensively used to test the effects of drugs on behavior, and to describe the neural correlates of interval timing. However, those procedures usually require several weeks of training for behavior to stabilize. Here, we compared three types of training protocols and reported a procedure in which performance by the end of the very first session nearly matches the performance of long-term training. We also discuss this fast-learning protocol in terms of an information-theory approach. This one-day training protocol can be used to investigate temporal learning and may be especially useful to electrophysiological and neuropharmacological studies.
Neural trajectories in the supplementary motor area and primary motor cortex exhibit distinct geometries, compatible with different classes of computation
Authors: Russo Abigail A. , Khajeh Ramin , Bittner Sean R. , Perkins Sean M. , Cunningham John P. , Abbott Laurence F. , Churchland Mark M. 
Published: May 2019

AbstractThe supplementary motor area (SMA) is believed to contribute to higher-order aspects of motor control. To examine this contribution, we employed a novel cycling task and leveraged an emerging strategy: testing whether population trajectories possess properties necessary for a hypothesized class of computations. We found that, at the single-neuron level, SMA exhibited multiple response features absent in M1. We hypothesized that these diverse features might contribute, at the population level, to avoidance of ‘population trajectory divergence’ – ensuring that two trajectories never followed the same path before separating. Trajectory divergence was indeed avoided in SMA but not in M1. Network simulations confirmed that low trajectory divergence is necessary when guidance of future action depends upon internally tracking contextual factors. Furthermore, the empirical trajectory geometry – helical in SMA versus elliptical in M1 – was naturally reproduced by networks that did, versus did not, internally track context.
Biochemical Reduction of the Topology of the Diverse WDR76 Protein Interactome
Authors: Dayebgadoh Gerald , Sardiu Mihaela E. , Florens Laurence , Washburn Michael P. 
Published: May 2019

AbstractA hub protein in protein interaction networks will typically have a large number of diverse interactions. Determining the core interactions and the function of such a hub protein remains a significant challenge in the study of networks. Proteins with WD40 repeats represent a large class of proteins that can be hub proteins. WDR76 is a poorly characterized WD40 repeat protein with possible involvement in DNA damage repair, cell cycle progression, apoptosis, gene expression regulation, and protein quality control. WDR76 has a large and diverse interaction network that has made its study challenging. Here, we rigorously carry out a series of affinity-purification coupled to mass spectrometry (AP-MS) to map out the WDR76 interactome through different biochemical conditions. We apply AP-MS analysis coupled to size exclusion chromatography to resolve WDR76-based protein complexes. Furthermore, we also show that WDR76 interacts with the CCT complex via its WD40 repeat domain and with DNA-PK-KU, PARP1, GAN, SIRT1, and histones outside of the WD40 domain. An evaluation of the stability of WDR76 interactions led to focused and streamlined reciprocal analyses that validate the interactions with GAN and SIRT1. Overall, the approaches used to study WDR76 would be valuable to study other proteins containing WD40 repeat domains, which are conserved in a large number of proteins in many organisms
Autumn shifts in cold tolerance metabolites in overwintering adult mountain pine beetles
Authors: Thompson Kirsten M. , Huber Dezene P. W. , Murray Brent W. 
Published: May 2019

AbstractThe mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae) is a major forest pest of pines in western North America. Beetles typically undergo a one-year life cycle with larval cold hardening in preparation for overwintering. Two-year life cycle beetles have been observed but not closely studied. This study tracks cold-hardening and preparation for overwintering by adult MPB in their natal galleries. Adults were collected in situ between September and December (2016) for a total of nine time points during 91 days. Concentrations of 41 metabolites in these pooled samples were assessed using quantitative NMR. Levels of glycerol and proline increased significantly with lowering temperature during the autumn. Newly eclosed mountain pine beetles prepare for winter by generating the same cold-tolerance compounds found in larvae, but high on-site mortality suggested that two-year life cycle adults have a less efficacious acclimation process. This is the first documentation of cold acclimation metabolite production in overwintering new adult beetles and is evidence of physiological plasticity that would allow evolution by natural selection of alternate life cycles (shortened or lengthened) under a changing climate or during expansion into new geoclimatic areas.
Inference of Synaptic Connectivity and External Variability in Neural Microcircuits
Authors: Baker Cody , Froudarakis Emmanouil , Yatsenko Dimitri , Tolias Andreas S. , Rosenbaum Robert 
Published: May 2019

AbstractA major goal in neuroscience is to estimate neural connectivity from large scale extracellular recordings of neural activity in vivo. This is challenging in part because any such activity is modulated by the unmeasured external synaptic input to the network, known as the common input problem. Many different measures of functional connectivity have been proposed in the literature, but their direct relationship to synaptic connectivity is often assumed or ignored. For in vivo data, measurements of this relationship would require a knowledge of ground truth connectivity, which is nearly always unavailable. Instead, many studies use in silico simulations as benchmarks for investigation, but such approaches necessarily rely upon a variety of simplifying assumptions about the simulated network and can depend on numerous simulation parameters. We combine neuronal network simulations, mathematical analysis, and calcium imaging data to address the question of when and how functional connectivity, synaptic connectivity, and latent external input variability can be untangled. We show numerically and analytically that, even though the precision matrix of recorded spiking activity does not uniquely determine synaptic connectivity, it is often closely related to synaptic connectivity in practice under various network models. This relation becomes more pronounced when the spatial structure of neuronal variability is considered jointly with precision.
Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging
Authors: Lu Kun-Han , Cao Jiayue , Phillips Robert , Powley Terry L , Liu Zhongming 
Published: May 2019

AbstractBackgroundVagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the functional impact of different VNS parameters on postprandial gastric motility remains incompletely characterized. Moreover, while most studies focused on stimulating the motor limb (i.e. efferent VNS) of the vagovagal circuitry, the contribution of electrically activating the reflex arc of the circuitry (i.e. afferent VNS) to downstream control of gastric function has seldom been investigated.MethodsHere, we used dynamic gastric magnetic resonance imaging (MRI) to assess antropyloric motility in anesthetized rats during which VNS was applied to the left cervical vagus. The configuration of VNS was varied in terms of directionality (i.e. afferent, efferent or combined afferent and efferent VNS) as well as parameter settings (i.e. pulse amplitude, pulse width, and frequency). The motility measurements were computed using a previously developed computer-assisted image processing pipeline.Key ResultsWe found that electrical activation that favored the afferent pathway could promote gastric motility and coordination more effectively than direct activation of the efferent pathway. A reduction in antral contraction amplitude and pyloric tone under high-dose efferent VNS highlighted the inhibitory role of the efferent vagovagal circuitry.Conclusions & InferencesThis study demonstrated the direct and reflex gastric responses to cervical VNS measured with MRI. Our findings suggest that selective stimulation of vagal afferents is potentially more favorable than stimulation of vagal efferents in facilitating coordinated antropyloric motility.Key PointsVagus nerve stimulation is emerging as a new bioelectronic therapy for remedying gastric symptoms. However, the effects of graded VNS settings and directionality preferences of VNS on gastric functions remain incompletely characterized.Dynamic gastric MRI revealed that electrical activation of the afferent pathway could promote antropyloric motility more effectively than direct activation of the efferent pathway.MRI can noninvasively characterize post-prandial gastric motility with high spatial and temporal resolution that could be used to guide the selection of VNS settings.
Deep spectral learning for label-free optical imaging oximetry with uncertainty quantification
Authors: Liu Rongrong , Cheng Shiyi , Tian Lei , Yi Ji 
Published: May 2019

AbstractMeasurement of blood oxygen saturation (sO2) by optical imaging oximetry provides invaluable insight into local tissue functions and metabolism. Despite different embodiments and modalities, all label-free optical imaging oximetry utilize the same principle of sO2-dependent spectral contrast from hemoglobin. Traditional approaches for quantifying sO2 often rely on analytical models that are fitted by the spectral measurements. These approaches in practice suffer from uncertainties due to biological variability, tissue geometry, light scattering, systemic spectral bias, and variations in experimental conditions. Here, we propose a new data-driven approach, termed deep spectral learning (DSL) for oximetry to be highly robust to experimental variations, and more importantly to provide uncertainty quantification for each sO2 prediction. To demonstrate the robustness and generalizability of DSL, we analyze data from two visible light optical coherence tomography (vis-OCT) setups across two separate in vivo experiments in rat retina. Predictions made by DSL are highly adaptive to experimental variabilities as well as the depth-dependent backscattering spectra. Two neural-network-based models are tested and compared with the traditional least-squares fitting (LSF) method. The DSL-predicted sO2 shows significantly lower mean-square errors than the LSF. For the first time, we have demonstrated en face maps of retinal oximetry along with pixel-wise confidence assessment. Our DSL overcomes several limitations in the traditional approaches and provides a more flexible, robust, and reliable deep learning approach for in vivo non-invasive label-free optical oximetry.
Measuring quality of antenatal care: a secondary analysis of national survey data from India
Authors: Singh L , Dubey R , Singh S , Goel R , Nair S , Singh PK 
Published: May 2019

ObjectiveTo assess the coverage and adequacy of antenatal care services (ANC) available to women and examine the socio‐economic determinants affecting service utilisation.DesignSecondary data analysis of a population‐based national survey.SettingIndia, 2015/16.SampleIn all, 190 898 women between 15 and 49 years of age who had a live birth during the 5 years preceding the survey.MethodsOrdinal logistic regression.Main outcome variableAdequacy of ANC services received was measured under four categories – delivery of services by skilled personnel, timely provision of services, sufficiency and appropriateness of content. Quality of care was categorised as adequate ANC, inadequate ANC and no ANC.ResultsOnly 23.5% (95% CI 23.1–23.9%) of all women received adequate ANC, while 58.8% (95% CI 58.4–59.2%) received inadequate and 17.7% (95% CI 17.4–18.0%) received no ANC services. Regression analysis revealed that women belonging to the adolescent age group, illiterate women, and those in the poorest wealth quintile and in rural areas were less likely to receive any ANC.ConclusionThere is a need to improve the quality of ANC services. Currently, <25% of women of all ages receive adequate ANC. Socio‐economic conditions play a vital part in determining the quality of care that women receive.Tweetable abstractNearly one out of four women in India received adequate ANC, nearly three in every five women received inadequate ANC and 18% lacked ANC for their recent live birth.
Occult mediastinal lymph node metastasis in FDG‐PET/CT node‐negative lung adenocarcinoma patients: Risk factors and histopathological study
Authors: Miao Huang , Shaolei Li , Nan Li , Yumei Lai , Shanyuan Zhang , Fangliang Lu , Yue Yang 
Published: May 2019

BackgroundThe aim of this study was to investigate predictive factors of occult mediastinal lymph node metastasis (MLNM) in preoperative 18F‐fluorodeoxy‐glucose PET/CT node‐negative lung adenocarcinoma patients.MethodsWe reviewed the clinical data and PET/CT parameters of 360 consecutive pulmonary adenocarcinoma patients who were scheduled to undergo anatomical pulmonary resection and systemic mediastinal node dissection. The nodal metastasis was pathologically defined and all resected tumors were classified according to the 2011 IASLC/ATS/ERS classification. Univariate and multivariate analysis were conducted to evaluate the associations between clinicopathological variables and MLNM.ResultsOf all 360 patients, 54 (15.0%) had pathological N2 diseases. The serum CEA level, nodule type, hilar nodal SUVmax, tumor SUVmax, size, location and histologic subtype were associated with MLNM significantly on univariate analysis. On multivariate analysis, CEA ≥ 5.0 ng/mL (P < 0.001), solid nodule (P = 0.012), tumor SUVmax ≥ 3.7 (P < 0.027), hilar nodal SUVmax ≥ 2.0 (P < 0.001) and centrally located tumor (P = 0.035) were independent risk factors for MLNM. The area under the ROC curve (AUC) for tumor SUVmax and hilar nodal SUVmax in predicting MLNM was 0.764 and 0.730, respectively, and the combined use of five factors yielded a higher AUC of 0.885.ConclusionIncreased primary tumor and hilar lymph node SUVmax, solid nodule, centrally located tumor and increased CEA level predicted the increased risk of mediastinal lymph node metastasis. Combined use of these factors improved the diagnostic capacity for predicting N2 disease preoperatively. Invasive mediastinal staging should be considered for patients with these risk factors, even those with a negative mediastinum on PET/CT.
Effects of folic acid on oligozoospermia withMTHFRpolymorphisms in term of seminal parameters,DNAfragmentation, and live birth rate: a double‐blind, randomized, placebo‐controlled trial
Authors: Huang Wen‐Jie , Lu Xi‐Lan , Li Jun‐Tao , Zhang Jian‐Min 
Published: May 2019

AbstractBackgroundIt has been reported that paternal folic acid deficiency is correlated with male infertility and increased birth defects in the offspring. However, there are few data concerning the influence of folic acid supplementation on male‐factor infertility withMTHFRgene polymorphisms.ObjectivesTo evaluate whether folic acid supplementation has a beneficial effect on oligozoospermia withMTHFRgene polymorphisms in Chinese infertility population.Materials and methodsThe infertile men suffering oligozoospermia withMTHFRgene polymorphisms were randomly divided into the folic acid treatment groups receiving folic acid 0.8 mg daily for 3 months and the placebo groups receiving placebo for 3 months. Semen parameters, seminalMDA, andDNAfragmentation were measured. Furthermore, spontaneous pregnancy rate and live birth rate were evaluated.ResultsAdministration of folic acid for 3 months could significantly improve the seminal parameters in patients withMTHFR677TTgenotype in comparison with that receiving placebo. Moreover, seminalMDAand spermDNAfragmentation index in patients withMTHFR677TTgenotype significantly declined at the end of treatment. Spontaneous pregnancy rate and live birth rate tended to be significantly higher in couples in which the men withMTHFR677TTgenotype receiving folic acid than that receiving placebo. However, folic acid treatment did not exhibit any advantage inMTHFR677CT, 1298AC, 1298CC, 1793GA, or combined 677CT/1298ACgenotype.DiscussionThe anti‐oxidation function of folic acid is one of possible mechanisms invovled in improving seminal parameters and pregnancy outcome.ConclusionsFolic acid supplementation has a beneficial effect on oligozoospermia withMTHFR677TTgenotype in term of seminal parameters, seminalMDA, spermDNAfragmentation, and pregnancy outcome.
Do female age and body weight modify the effect of individualized FSH dosing in IVF/ICSI treatment? A secondary analysis of the OPTIMIST trial
Authors: Leijdekkers Jori A. , van Tilborg Theodora C. , Torrance Helen L. , Oudshoorn Simone C. , Brinkhuis Egbert A. , Koks Carolien A. M. , Lambalk Cornelis B. , de Bruin Jan Peter , Fleischer Kathrin , Mochtar Monique H. , Kuchenbecker Walter K. H. , Laven Joop S. E. , Mol Ben Willem J. , Broekmans Frank J. M. , Eijkemans Marinus J. C. ,   the OPTIMIST study group
Published: May 2019

AbstractIntroductionThe OPTIMIST trial revealed that for women starting in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment, no substantial differences exist in first cycle and cumulative live birth rates between an antral follicle count (AFC)‐based individualized follicle‐stimulating hormone (FSH) dose and a standard dose. Female age and body weight have been suggested to cause heterogeneity in the effect of FSH dose individualization. The objective of the current study is to evaluate whether these patient characteristics modify the effect of AFC‐based individualized FSH dosing in IVF/ICSI treatment.Material and methodsA secondary data‐analysis of the OPTIMIST trial. Women initiating IVF/ICSI treatment were classified as predicted poor (AFC 0‐7), suboptimal (AFC 8‐10) or hyper responders (AFC >15), and randomly allocated to a standard FSH dose (150 IU/d) or an individualized FSH dose (450, 225 or 100 IU/d for predicted poor, suboptimal and hyper responders, respectively). In each predicted response category, logistic regression models with interaction terms were used to evaluate the presence of effect modification. The first cycle was analyzed, and the primary outcomes were first complete cycle live birth rate (including fresh plus frozen‐thawed embryo transfers) and ovarian hyperstimulation syndrome (OHSS) risks.ResultsNo effect modification was revealed in the predicted poor (n = 234) and suboptimal (n = 277) responders. In the predicted hyper responders (n = 521), the effect of the individualized FSH dose on the first cycle live birth rate was modified by female age (P = 0.02) and the effect on OHSS risks was modified by body weight (P = 0.02). A dose reduction from 150 to 100 IU/d generally decreased the OHSS risks in predicted hyper responders, but also reduced the chance of a live birth in young women, and had no beneficial impact on OHSS risks in women with a relatively low body weight.ConclusionsIn women with a predicted hyper response undergoing IVF/ICSI treatment, female age and body weight seem to modify the effect of FSH dose individualization. Although a reduced FSH starting dose generally decreases the OHSS risks, it may also reduce the chance of a live birth, specifically for young women. Future studies could consider these findings when investigating the optimal approach to reduce OHSS risks while maintaining the probability of a live birth for predicted hyper responders in IVF/ICSI treatment.
Quantitative evaluation of visual function in patients with cornea verticillata associated with Fabry disease
Authors: Koh Shizuka , Haruna Mai , Asonuma Sanae , Maeda Naoyuki , Hamano Takayuki , Sakai Norio , Hara Chikako , Maruyama Kazuichi , Nishida Kohji 
Published: May 2019

AbstractPurposeTo evaluate the visual function of patients with cornea verticillata associated with Fabry disease through quantitative evaluations of contrast sensitivity function and straylight.MethodsWe enrolled 28 eyes of 14 patients with Fabry disease (mean age, 37.1 ± 17.2 years) and 20 eyes of 20 age‐matched healthy controls. Comprehensive ophthalmological examinations were performed and contrast sensitivity and letter contrast sensitivity were measured for all patients, following which the area under the log contrast sensitivity function (AULCSF) was calculated. Straylight was quantified using a straylight metre. Furthermore, subgroup analysis was performed according to the whorl‐like pattern of cornea verticillata (mild and typical groups).ResultsAll 28 eyes showed cornea verticillata. Visual acuity and letter contrast sensitivity values were the same for normal eyes and those with Fabry disease. AULCSF differed by 0.15 log[s] between the eyes with Fabry disease and the control eyes (p < 0.001), while straylight differed by 0.45 log[s] between the two groups (p < 0.001). Subgroup analysis based on the whorl‐like pattern of cornea verticillata showed that AULCSF and straylight differed by 0.11 log[s] and 0.08 log[s], respectively, between the typical and mild groups (p = 0.036 and p = 0.147, respectively).ConclusionAlthough cornea verticillata associated with Fabry disease does not affect the visual acuity and letter contrast sensitivity, more comprehensive testing of visual function by the inclusion of straylight and grating contrast sensitivity measurements shows clear functional deficits in these patients.