Miracle-dz/UniFAR-FTUs huggingface dataset:
Norovirus RNA Synthesis Is Modulated by an Interaction between the Viral RNA-Dependent RNA Polymerase and the Major Capsid Protein, VP1

ABSTRACT Using a cell-based assay for RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of noroviruses, we previously observed that VP1, the major structural protein of the human GII.4 norovirus, enhanced the GII.4 RdRp activity but not that of the related murine norovirus (MNV) or other unrelated RNA viruses (C. V. Subba-Reddy, I. Goodfellow, and C. C. Kao, J. Virol. 85:13027–13037, 2011). Here, we examine the mechanism of VP1 enhancement of RdRp activity and the mechanism of mouse norovirus replication. We determined that the GII.4 and MNV VP1 proteins can enhance cognate RdRp activities in a concentration-dependent manner. The VP1 proteins coimmunoprecipitated with their cognate RdRps. Coexpression of individual domains of VP1 with the viral RdRps showed that the VP1 shell domain (SD) was sufficient to enhance polymerase activity. Using SD chimeras from GII.4 and MNV, three loops connecting the central β-barrel structure were found to be responsible for the species-specific enhancement of RdRp activity. A differential scanning fluorimetry assay showed that recombinant SDs can bind to the purified RdRps in vitro. An MNV replicon with a frameshift mutation in open reading frame 2 (ORF2) that disrupts VP1 expression was defective for RNA replication, as quantified by luciferase reporter assay and real-time quantitative reverse transcription-PCR (qRT-PCR). Trans-complementation of VP1 or its SD significantly recovered the VP1 knockout MNV replicon replication, and the presence or absence of VP1 affected the kinetics of viral RNA synthesis. The results document a regulatory role for VP1 in the norovirus replication cycle, further highlighting the paradigm of viral structural proteins playing additional functional roles in the virus life cycle.
Phase Transformations in a Human Tooth Tissue at the Initial Stage of Caries

The aim of the paper is to study phase transformations in solid tissues of the human teeth during the development of fissure caries by Raman and fluorescence microspectroscopy. The study of the areas with fissure caries confirmed the assumption of the formation of a weak interaction between phosphate apatite enamel and organic acids (products of microorganisms). The experimental results obtained with by Raman microspectroscopy showed the formation of dicalcium phosphate dihydrate - CaHPO4-2H2O in the area of mural demineralization of carious fissure. A comparative analysis of structural and spectroscopic data for the intact and carious enamel shows that emergence of a more soluble phase - carbonate-substituted hydroxyapatite - is typical for the initial stage of caries. It is shown that microareas of dental hard tissues in the carious fissure due to an emerging misorientation of apatite crystals have a higher fluorescence yield than the area of the intact enamel. These areas can be easily detected even prior to a deep demineralization (white spot stage) for the case of irreversibly changed organomineral complex and intensive removal of the mineral component.
Comparative Analysis of Total Phenolic Content in Sea Buckthorn Wine and Other Selected Fruit Wines

This is the first report from India on a beverage resulting from alcoholic fermentation of the juice of sea buckthorn (Hippophae rhamnoides L) using lab isolated yeast strain. The health promoting potential of the product was evaluated based on its total phenolic content. The most important finding was that under the present fermentation condition, the total phenolic content of the wine product was 689 mg GAE/L. Investigation of influence of bottle ageing on the sea buckthorn wine showed a slight decrease in the phenolic content (534 m mg GAE/L). This study also includes the comparative analysis of the phenolic content of wines from other selected fruit juices like grape, apple and black currant. Keywords—Alcoholic fermentation, Hippophae, Total phenolic content, Wine
The Spectrum of Autonomic Dysfunction in Myasthenic Crisis

Background: Autoimmune autonomic dysfunction is described in Myasthenia Gravis. In myasthenic crisis, the spectrum of autonomic dysfunction is hitherto uncharacterized. Objective: The objective of this study is to describe the spectrum of autonomic dysfunction in myasthenic crises using the composite autonomic symptom scale 31 (COMPASS 31) autonomic symptom questionnaire and power spectral analysis of heart rate variability (HRV), which is a simple way of estimating general autonomic dysfunction. Methods: Adult patients with myasthenic crisis from January 1, 2014 to March 15, 2015, were prospectively included in this study. The COMPASS 31 questionnaire for symptoms of autonomic dysfunction and power spectral analysis of HRV were assessed. These were compared with the patient's demographic and clinical parameters and with previous literature. IRB approval was obtained. Results: Sixteen patients were included (M:F 3:1). 15/16 patents (93%) had autonomic dysfunction on COMPASS 31 questionnaire. The domains of involvement were gastrointestinal (80%), orthostatic (67.7%), pupillomotor (67.7%); sudomotor (33.3%), and vasomotor (13.3%). Parasympathetic dysfunction predominance was suggested by the symptom profile. HRV analysis showed a low frequency (LF) spectral shift suggesting slowed parasympathetic responsiveness (LF normalized unit (nu): high frequency [HF] nu mean 8.35, standard deviation ± 5.4, 95% confidence interval 2.2–12.5), which significantly exceeded the mean LF nu: HF nu ratios of the majority of previously reported noncrises myasthenic populations. Conclusions: Myasthenic crisis has autonomic dysfunction involving multiple organ systems. Increased latency of parasympathetic reflexes is suggested. A comprehensive management protocol addressing different autonomic domains is required for holistic patient care.
Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis

Background Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. Principal Findings Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. Conclusions Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.
Long-term Memories Bias Sensitivity and Target Selection in Complex Scenes

In everyday situations, we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location [Summerfield, J. J., Rao, A. , Garside, N. , & Nobre, A. C. Biasing perception by spatial long-term memory. The Journal of Neuroscience, 31, 14952–14960, 2011; Summerfield, J. J., Lepsien, J., Gitelman, D. R. , Mesulam, M. M. , & Nobre, A. C. Orienting attention based on long-term memory experience. Neuron, 49, 905–916, 2006]. This study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc ERP to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top–down sources of information.
Punishment promotes response control deficits in obsessive-compulsive disorder: evidence from a motivational go/no-go task

Background Obsessive-compulsive disorder (OCD) has been associated with response inhibition deficits under motivationally neutral contingencies. We examined response inhibition performance in the presence of reward and punishment. We further investigated whether the hypothesized difficulties in flexibly updating behaviour based on external feedback in OCD would also lead to a reduced ability to adjust to changes in the reward and punishment contingencies. Method Participants completed a go/no-go task that used punishments or rewards to promote response activation or suppression. The task was administered to OCD patients free of current Axis-I co-morbidities including major depression (n = 20) and a group of healthy controls (n = 32). Results Compared with controls, patients with OCD had increased commission errors in punishment conditions, and failed to slow down immediately after receiving punishment. The punishment-induced increase in commission errors correlated with self-report measures of OCD symptom severity. Additionally, patients did not differ from controls in adapting their overall response style to the changes in task contingencies. Conclusions Individuals with OCD showed reduced response control selectively under punishment conditions, manifesting in an impulsive response style that was related to their current symptom severity. This stresses failures of cognitive control in OCD, particularly under negative motivational contingencies.
Motor Practice Promotes Increased Activity in Brain Regions Structurally Disconnected After Subcortical Stroke

Background. Motor practice is an important component of neurorehabilitation. Imaging studies in healthy individuals show that dynamic brain activation changes with practice. Defining patterns of functional brain plasticity associated with motor practice following stroke could guide rehabilitation. Objective. The authors aimed to test whether practice-related changes in brain activity differ after stroke and to explore spatial relationships between activity changes and patterns of structural degeneration. Methods. They studied 10 patients at least 6 months after left-hemisphere subcortical strokes and 18 healthy controls. Diffusion-weighted magnetic resonance imaging (MRI) was acquired at baseline, and functional MRI (fMRI) was acquired during performance of a visuomotor tracking task before and after a 15-day period of practice of the same task. Results. Smaller short-term practice effects at baseline correlated with lower fractional anisotropy in the posterior limbs of the internal capsule (PLIC) bilaterally in patients (t > 3; cluster P < .05). After 15 days of motor practice a Group × Time interaction (z > 2.3; cluster P < .05) was found in the basal ganglia, thalamus, inferior frontal gyrus, superior temporal gyrus, and insula. In these regions, healthy controls showed decreases and patients showed increases in activity with practice. Some regions of interest had a loss of white matter connectivity at baseline. Conclusions. Performance gains with motor practice can be associated with increased activity in regions that have been either directly or indirectly impaired by loss of connectivity. These results suggest that neurorehabilitation interventions may be associated with compensatory adaptation of intact brain regions as well as enhanced activity in regions with impaired structural connectivity.
What Enables a Machine to Understand?

The 'Strong AI' claim that suitably programmed computers can manipulate symbols that THEY understand is defended, and conditions for understanding discussed. Even computers without AI programs exhibit a significant subset of characteristics of human understanding. To argue about whether machines can REALLY understand is to argue about mere definitional matters. But there is a residual ethical question.
Neural Greedy Constituent Parsing with Dynamic Oracles

Dynamic oracle training has shown substantial improvements for dependency parsing in various settings, but has not been explored for constituent parsing. The present article introduces a dynamic oracle for transition-based constituent parsing. Experiments on the 9 languages of the SPMRL dataset show that a neural greedy parser with morphological features , trained with a dynamic oracle, leads to accuracies comparable with the best non-reranking and non-ensemble parsers.
How Does Dog-Walking Influence Perceptions of Health and Wellbeing in Healthy Adults? A Qualitative Dog-Walk-Along Study

ABSTRACT The aim of this study was to explore perceptions of health and wellbeing related to dog-walking in healthy adults. Ten self-reported healthy adult dog-walkers took part in one dog-walk-along interview, and nine of the 10 participants also attended one follow-up participatory analysis session. All interviews took place within the metropolitan area of Dunedin, Aotearoa/New Zealand. Dog-walk-along interviews were participant-led, audio and video recorded, and transcribed. Participants’ input into the inductive generation of themes was sought during the follow-up participatory analysis session. Three themes were identified: participants had an “Emotional Connection” with their dog(s); dog-walking led to “Healthy Interactions” (social and environmental interactions); and participants had come to value dog-walking for its aggregate benefits for Psychological Wellbeing. Our dog-walk-along interviews have revealed novel insights about how the emotional connection between human and dog strengthens intrinsic motivation to exercise (through dog-walking) whilst concurrently enhancing human psychological wellbeing through the act of giving something that gives pleasure to the dog. Through the combined methods of dog-walk-along interviews and participatory analysis sessions, we were able to identify negative influences on human psychological well-being that included anxiety about both dog behaviors and social encounters with other humans. Positive and negative aspects of dog-walking that we identified can be used by health promotion advocates to refine dog-walking related advice, programs, and initiatives.
Molecular Subtype-Specific Expression of MicroRNA-29c in Breast Cancer Is Associated with CpG Dinucleotide Methylation of the Promoter

Basal-like breast cancer is a molecularly distinct subtype of breast cancer that is highly aggressive and has a poor prognosis. MicroRNA-29c (miR-29c) has been shown to be significantly down-regulated in basal-like breast tumors and to be involved in cell invasion and sensitivity to chemotherapy. However, little is known about the genetic and regulatory factors contributing to the altered expression of miR-29c in basal-like breast cancer. We here report that epigenetic modifications at the miR-29c promoter, rather than copy number variation of the gene, may drive the lower expression of miR-29c in basal-like breast cancer. Bisulfite sequencing of CpG sites in the miR-29c promoter region showed higher methylation in basal-like breast cancer cell lines compared to luminal subtype cells with a significant inverse correlation between expression and methylation of miR-29c. Analysis of primary breast tumors using The Cancer Genome Atlas (TCGA) dataset confirmed significantly higher levels of methylation of the promoter in basal-like breast tumors compared to all other subtypes. Furthermore, inhibition of CpG methylation with 5-aza-CdR increases miR-29c expression in basal-like breast cancer cells. Flourescent In Situ Hybridization (FISH) revealed chromosomal abnormalities at miR-29c loci in breast cancer cell lines, but with no correlation between copy number variation and expression of miR-29c. Our data demonstrated that dysregulation of miR-29c in basal-like breast cancer cells may be in part driven by methylation at CpG sites. Epigenetic control of the miR-29c promoter by epigenetic modifiers may provide a potential therapeutic target to overcome the aggressive behavior of these cancers.
Effect of IL12A and IL12B polymorphisms on the risk of Chlamydia trachomatis-induced tubal factor infertility and disease severity.

BACKGROUND Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease. METHODS The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52). CONCLUSIONS The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.
Development of the Hippocampal Cognitive Map in Preweanling Rats

The Space in Your Head Space, and events associated with places and spaces, are represented in the brain by a circuitry made of place cells, head direction cells, grid cells, and border cells. These cell types form a collective dynamic representation of our position as we move through the environment. How this representation is formed has remained a mystery. Is it acquired, or are we born with the ability to represent external space (see the Perspective by Palmer and Lynch)? Langston et al. (p. 1576) and Wills et al. (p. 1573) investigated the early development of spatial activity in the hippocampal formation and the entorhinal cortex of rat pups when they first began to explore their environment. Rudiments of place cells, head direction cells, and grid cells already existed when the pups made their first movements out of the nest. A neural representation of external space at this early time points to strong innate components for perception of space. These findings provide experimental support for Kant's 200-year-old concept of space as an a priori faculty of the mind. Some aspects of spatial cognition develop very early and may be determined innately. Orienting in large-scale space depends on the interaction of environmental experience and preconfigured, possibly innate, constructs. Place, head-direction, and grid cells in the hippocampal formation provide allocentric representations of space. Here we show how these cognitive representations emerge and develop as rat pups first begin to explore their environment. Directional, locational, and rhythmic organization of firing are present during initial exploration, including adultlike directional firing. The stability and precision of place cell firing continue to develop throughout juvenility. Stable grid cell firing appears later but matures rapidly to adult levels. Our results demonstrate the presence of three neuronal representations of space before extensive experience and show how they develop with age.
The role of microRNAs in cell fate determination of mesenchymal stem cells : balancing adipogenesis and osteogenesis

Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into adipocytes, osteoblasts, or chondrocytes. A mutually inhibitory relationship exists between osteogenic and adipogenic lineage commitment and differentiation. Such cell fate decision is regulated by several signaling pathways, including Wnt and bone morphogenetic protein (BMP). Accumulating evidence indicates that microRNAs (miRNAs) act as switches for MSCs to differentiate into either osteogenic or adipogenic lineage. Different miRNAs have been reported to regulate a master transcription factor for osteogenesis, such as Runx2, as well as molecules in the Wnt or BMP signaling pathway, and control the balance between osteoblast and adipocyte differentiation. Here, we discuss recent advancement of the cell fate decision of MSCs by miRNAs and their targets. [BMB Reports 2015; 48(6): 319-323]
Free water elimination and mapping from diffusion MRI

Relating brain tissue properties to diffusion tensor imaging (DTI) is limited when an image voxel contains partial volume of brain tissue with free water, such as cerebrospinal fluid or edema, rendering the DTI indices no longer useful for describing the underlying tissue properties. We propose here a method for separating diffusion properties of brain tissue from surrounding free water while mapping the free water volume. This is achieved by fitting a bi‐tensor model for which a mathematical framework is introduced to stabilize the fitting. Applying the method on datasets from a healthy subject and a patient with edema yielded corrected DTI indices and a more complete tract reconstruction that passed next to the ventricles and through the edema. We were able to segment the edema into areas according to the condition of the underlying tissue. In addition, the volume of free water is suggested as a new quantitative contrast of diffusion MRI. The findings suggest that free water is not limited to the borders of the brain parenchyma; it therefore contributes to the architecture surrounding neuronal bundles and may indicate specific anatomical processes. The analysis requires a conventional DTI acquisition and can be easily merged with existing DTI pipelines. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.