Miracle-dz/UniFAR-FTUs huggingface dataset:
A Trigger for Opioid Misuse: Chronic Pain and Stress Dysregulate the Mesolimbic Pathway and Kappa Opioid System

Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.
Adult murine CNS stem cells express aquaporin channels

Background information. Fluid homoeostasis is of critical importance in many functions of the CNS (central nervous system) as indicated by the fact that dysregulation of cell volume underlies clinical conditions such as brain oedema and hypoxia. Water balance is also important during neurogenesis as neural stem cells move considerable amounts of water into or out of the cell to rapidly change their volume during differentiation. Consistent with the relevance of water transport in CNS, multiple AQP (aquaporin) water channels have been recognized and partially characterized in brain cell function. However, the presence and distribution of AQPs in CNS stem cells has not yet been assessed.
Neurological and Behavioral Outcomes of Focal Cerebral Ischemia in Rats

The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats. Methods We induced permanent occlusion of the left middle cerebral artery in 14 Sprague- Dawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage. Results Ischemia induced large infarcts in the cortex (138.6±8.5 mm3) and caudate-putamen (48.8±2.6 mm3) and, compared with sham-operated rats, produced a dramatic neurological deficit (p<0.001) characterized by sensorimotor dysfunctions and hemiplegia. Memory retention was significantly (p<0.05) impaired in the passive avoidance task, but neither vigilance and exploratory behavior measured in the modified open-field test nor working memory evaluated in the Y maze test were disturbed. Infarct size was not correlated with the neurological or behavioral deficits. Conclusions This lack of correlation indicates the necessity of carrying out parallel histological, neurological, and behavioral studies in any assays of new drugs using this model of focal ischemia.
The Pattern of Retinal Ganglion Cell Loss in OPA 1-Related Autosomal Dominant Optic Atrophy Inferred From Temporal , Spatial , and Chromatic Sensitivity Losses

University College London, Institute of Ophthalmology, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom Department of Ophthalmology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland School of Optometry and Vision Sciences, Cardiff University Cardiff, and Cardiff Eye Unit, University Hospital Wales, Cardiff, United Kingdom Ophthalmology Department, University of California-San Francisco School of Medicine, San Francisco, California, United States Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University and Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom
Circulating MiR-133a as a Biomarker Predicts Cardiac Hypertrophy in Chronic Hemodialysis Patients

Background MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy. Methods We profiled miRNAs using RNA isolated from the plasma of participants. The results were validated in 64 MHD patients and 18 healthy controls. Results Levels of plasma miR-133a decreased in MHD patients with LVH compared with those in healthy controls. Plasma miR-133a concentrations were negatively correlated with LVMI and IVS. After single hemodialytic treatment, plasma miR-133a levels remained unchanged. Cardiac Troponin I and T were not associated with LVMI and IVS. Conclusions Our observations supplied the possibility that circulating miR-133a could be a surrogate biomarker of cardiac hypertrophy in MHD patients.
Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs

The notochord has major roles in vertebral column formation: indirectly by inducing sclerotome cell differentiation; and directly by forming the nucleus pulposus of intervertebral discs. Sox5 and Sox6 encode Sry-related HMG box transcription factors that act redundantly to promote chondroblast differentiation in all cartilages of the mouse embryo. We show that Sox5 and Sox6 are expressed in the notochord cell lineage and required for notochord late development. In Sox5–/–/Sox6–/– embryos, the notochord formed a typical rod-like structure. It fulfilled its inductive functions, as indicated by expression of sonic hedgehog and sclerotome specification. However, the notochord failed to become surrounded with an extracellular matrix sheath. This phenotype was associated with a downregulation of extracellular matrix genes, including the genes for collagen 2, aggrecan and perlecan in both notochord cells and surrounding chondrocytic cells of presumptive inner annuli and vertebral bodies. The mutant notochord then underwent an aberrant, fatal dismantling after sclerotome cell migration. Its cells became removed first from intervertebral spaces and then from vertebral bodies, and it progressively underwent apoptosis. Meanwhile, the development of inner annuli and vertebral bodies was dramatically impaired. Consequently, the vertebral column of Sox5–/–/Sox6–/– fetuses consisted of a very deficient cartilage and was devoid of nuclei pulposi. In Sox5–/–/Sox6+/– and more severely in Sox5+/–/Sox6–/– embryos, the notochord sheath was thinner, but cells survived. By birth, nuclei pulposi were rudimentary, and its cells poorly swelled and still expressing sonic hedgehog. Hence, Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and formation of nuclei pulposi. Through these roles and essential roles in cartilage formation, they are central transcriptional regulators of vertebral column development.
Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study

Background and aims: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. Methods: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. Results: The presence of Escherichia coli was associated with a higher risk of developing eczema (ORadj = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (pfor trend = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (ORadj = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (ORadj = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (ORadj = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (ORadj = 1.73; 95% CI 1.08 to 2.78). Conclusion: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.
Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition

Background and Objectives Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals. Experimental Design The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated. Principal Observations Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250–360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity. Conclusions Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition.
GreenScaler: Automatically training software energy models with big data

Software energy consumption is a performance related non-functional requirement that complicates building software on mobile devices today. Energy hogging applications are a liability to both the end-user and software developer. Measuring software energy consumption is non-trivial, requiring both equipment and expertise, yet many researchers have found that software energy consumption can be modelled. Prior works have hinted that with more energy measurement data one can make more accurate energy models but this data was expensive to extract because it required energy measurement of running test cases (rare) or time consuming manually written tests. We address these concerns by automatically generating test cases to drive applications undergoing energy measurement. Automatic test generation allows a model to be continuously improved in a model building process whereby applications are extracted, tests are generated, energy is measured and combined with instrumentation to train a grander big-data model of software energy consumption. This continuous process has allowed the authors to generate and extract measurements from hundreds of applications in order to build accurate energy models capable of predicting the energy consumption of applications without end-user energy measurement. We clearly show that models built from more applications reduce energy modelling error.
A Reliable Transmission Protocol for ZigBee-Based Wireless Patient Monitoring

Patient monitoring systems are gaining their importance as the fast-growing global elderly population increases demands for caretaking. These systems use wireless technologies to transmit vital signs for medical evaluation. In a multihop ZigBee network, the existing systems usually use broadcast or multicast schemes to increase the reliability of signals transmission; however, both the schemes lead to significantly higher network traffic and end-to-end transmission delay. In this paper, we present a reliable transmission protocol based on anycast routing for wireless patient monitoring. Our scheme automatically selects the closest data receiver in an anycast group as a destination to reduce the transmission latency as well as the control overhead. The new protocol also shortens the latency of path recovery by initiating route recovery from the intermediate routers of the original path. On the basis of a reliable transmission scheme, we implement a ZigBee device for fall monitoring, which integrates fall detection, indoor positioning, and ECG monitoring. When the triaxial accelerometer of the device detects a fall, the current position of the patient is transmitted to an emergency center through a ZigBee network. In order to clarify the situation of the fallen patient, 4-s ECG signals are also transmitted. Our transmission scheme ensures the successful transmission of these critical messages. The experimental results show that our scheme is fast and reliable. We also demonstrate that our devices can seamlessly integrate with the next generation technology of wireless wide area network, worldwide interoperability for microwave access, to achieve real-time patient monitoring.
Out of Dedication or Constraint? A Dual Model of Post-Adoption Phenomena and its Empirical Test in the Context of Online Services

Sustained website traffic through consumers' patronage at the post-adoption stages is known as a key to the survival of an online service provider. Although a firm's survival depends much on repeated use, whether or not a firm survives is also influenced by a variety of other behavioral outcomes that include, but are not limited to, word-of-mouth, willingness to pay, and inattentiveness to alternatives. Whereas post-adoption research has recently paid attention to repeated use, the information systems field still lacks a systematic investiation into other behavioral outcomes that transcend mere usage. In an attempt to extend the horizons of post-adoption research, we develop and test a model that explains post-adoption behaviors in the context of online services. First, drawing on a dual model of relationship maintenance in consumer behavior research, we propose a conceptual framework to study and explain online consumer behavior. In particular, our model predicts that two contrasting mechanisms, that is, dedication and constraint, are the main drivers of post-adoption phenomena (i.e., consumers' post-adoption reactions to online services-beliefs, attitudes, intentions, and behaviors). We empirically test the proposed dual model through the use of data collected from 510 users of online portals. The results of structural equation modeling analysis indicate that, as expected, the dedication- and constraint-based mechanisms simultaneously, yet differentially, determine online consumer behavior. In general, our findings suggest that it is essential in examining the complex nature of post-adoption phenomena to take into account the interplay of the dedication- and constraint-based mechanisms.
Evaluation of Groundwater Simulations in Benin from the ALMIP2 Project

A comprehensive estimation of water budget components, particularly groundwater storage (GWS) and fluxes, is crucial. In this study, we evaluate the terrestrial water budget of the Donga basin (Benin, West Africa), as simulated by three land surface models (LSMs) used in the African Monsoon Multidisciplinary Analysis Land Surface Model Intercomparison Project, phase 2 (ALMIP2): CLM4, Catchment LSM (CLSM), and Minimal Advanced Treatments of Surface Interaction and Runoff (MATSIRO). All three models include an unconfined groundwater component and are driven by the same ALMIP2 atmospheric forcing from 2005 to 2008. Results show that all three models simulate substantially shallower water table depth (WTD) with smaller seasonal variations, approximately 1–1.5 m compared to the observed values that range between 4 and 9.6 m, while the seasonal variations of GWS are overestimated by all the models. These seemingly contradictory simulation results can be explained by the overly high specific yield prescribed in all models. All models achieve similar GWS simulations but with different fractions of precipitation partitioning into surface runoff, base flow, and evapotranspiration (ET), suggesting high uncertainty and errors in the terrestrial and groundwater budgets among models. The poor performances of models can be attributed to bias in the hydrological partitioning (base flow vs surface runoff) and sparse subsurface data. This analysis confirms the importance of subsurface hydrological processes in the current generation of LSMs and calls for substantial improvement in both surface water budget (which controls groundwater recharge) and the groundwater system (hydrodynamic parameters, vertical geometry).
Dysfunctional Crohn’s Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association

Polymorphisms in NOD2 represent the single greatest genetic risk factor for the development of Crohn’s disease. Three different non-synonomous NOD2 polymorphisms – R702W, G908R, and L1007fsincC – account for roughly 80% of all NOD2-associated cases of Crohn’s disease and are reported to result in a loss of receptor function in response to muramyl dipeptide (MDP) stimulation. Loss of NOD2 signaling can result from a failure to detect ligand; alterations in cellular localization; and changes in protein interactions, such as an inability to interact with the downstream adaptor protein RIPK2. Using an overexpression system, we analyzed ~50 NOD2 polymorphisms reportedly connected to Crohn’s disease to determine if they also displayed loss of function and if this could be related to alterations in protein localization and/or association with RIPK2. Just under half the polymorphisms displayed a significant reduction in signaling capacity following ligand stimulation, with nine of them showing near complete ablation. Only two polymorphisms, R38M and R138Q, lost the ability to interact with RIPK2. However, both these polymorphisms still associated with cellular membranes. In contrast, L248R, W355stop, L550V, N825K, L1007fsinC, L1007P, and R1019stop still bound RIPK2, but showed impaired membrane association and were unable to signal in response to MDP. This highlights the complex contributions of NOD2 polymorphisms to Crohn’s disease and reiterates the importance of both RIPK2 binding and membrane association in NOD2 signaling. Simply ascertaining whether or not NOD2 polymorphisms bind RIPK2 or associate with cellular membranes is not sufficient for determining their signaling competency.
CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets

UNLABELLED MicroRNAs (miRNAs) are approximately 20- to 22-nt long endogenous RNA sequences that play a critical role in the regulation of gene expression in eukaryotic genomes. Confident identification of miRNA targets is vital to understand their functions. Currently available computational algorithms for miRNA target prediction have diverse degrees of sensitivity and specificity and as a consequence each predicted target generally requires experimental confirmation. miRNAs and other small RNAs that direct endonucleolytic cleavage of target mRNAs produce diagnostic uncapped, polyadenylated mRNA fragments. Degradome sequencing [also known as PARE (parallel analysis of RNA ends) and GMUCT (genome-wide mapping of uncapped transcripts)] samples the 5'-ends of uncapped mRNAs and can be used to discover in vivo miRNA targets independent of computational predictions. Here, we describe a generalizable computational pipeline, CleaveLand, for the detection of cleaved miRNA targets from degradome data. CleaveLand takes as input degradome sequences, small RNAs and an mRNA database and outputs small RNA targets. CleaveLand can thus be applied to degradome data from any species provided a set of mRNA transcripts and a set of query miRNAs or other small RNAs are available. AVAILABILITY The code and documentation for CleaveLand is freely available under a GNU license at http://www.bio. psu.edu/people/faculty/Axtell/AxtellLab/Software.html
Streptococcus pyogenes Infection Induces Septic Arthritis with Increased Production of the Receptor Activator of the NF-κB Ligand

ABSTRACT Bacterial arthritis is a rapidly progressive and highly destructive joint disease in humans, with Staphylococcus aureus and Neisseria gonorrhoeae the major causative agents, although beta-hemolytic streptococci as well often induce the disease. We demonstrate here that intravenous inoculation of CD-1 mice with the group A streptococcus (GAS) species Streptococcus pyogenes resulted in a high incidence of septic arthritis. Signs of arthritis emerged within the first few days after injection, and bacterial examinations revealed that colonization of the inoculated GAS in the arthritic joints persisted for 21 days. Induction of persistent septic arthritis was dependent on the number of microorganisms inoculated. Immunohistochemical staining of GAS with anti-GAS antibodies revealed colonization in the joints of infected mice. Cytokine levels were quantified in the joints and sera of infected mice by using an enzyme-linked immunosorbent assay. High levels of interleukin-1β (IL-1β) and IL-6 were detected in the joints from 3 to 20 days after infection. We noted that an increase in the amount of receptor activator of NF-κB ligand (RANKL), which is a key cytokine in osteoclastogenesis, was also evident in the joints of the infected mice. RANKL was not detected in sera, indicating local production of RANKL in the infected joints. Blocking of RANKL by osteoprotegerin, a decoy receptor of RANKL, prevented bone destruction in the infected joints. These results suggest that GAS can colonize in the joints and induce bacterial arthritis. Local RANKL production in the infected joints may be involved in bone destruction.