Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Compartmentalized Axonal Mitochondrial Biogenesis: Mitochondrial DNA Replication Increases in Distal Axons As an Early Response to Parkinson's Disease-Relevant Stress

Dysregulation of mitochondrial biogenesis is implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). However, it is not clear how mitochondrial biogenesis is regulated in neurons, with their unique compartmentalized anatomy and energetic demands. This is particularly relevant in PD because selectively vulnerable neurons feature long, highly arborized axons where degeneration initiates. We previously found that exposure of neurons to chronic, sublethal doses of rotenone, a complex I inhibitor linked to PD, causes early increases in mitochondrial density specifically in distal axons, suggesting possible upregulation of mitochondrial biogenesis within axons. Here, we directly evaluated for evidence of mitochondrial biogenesis in distal axons and examined whether PD-relevant stress causes compartmentalized alterations. Using BrdU labeling and imaging to quantify replicating mitochondrial DNA (mtDNA) in primary rat neurons (pooled from both sexes), we provide evidence of mtDNA replication in axons along with cell bodies and proximal dendrites. We found that exposure to chronic, sublethal rotenone increases mtDNA replication first in neurites and later extending to cell bodies, complementing our mitochondrial density data. Further, isolating axons from cell bodies and dendrites, we discovered that rotenone exposure upregulates mtDNA replication in distal axons. Utilizing superresolution stimulated emission depletion (STED) imaging, we identified mtDNA replication at sites of mitochondrial–endoplasmic reticulum contacts in axons. Our evidence suggests that mitochondrial biogenesis occurs not only in cell bodies, but also in distal axons, and is altered under PD-relevant stress conditions in an anatomically compartmentalized manner. We hypothesize that this contributes to vulnerability in neurodegenerative diseases. SIGNIFICANCE STATEMENT Mitochondrial biogenesis is crucial for maintaining mitochondrial and cellular health and has been linked to neurodegenerative disease pathogenesis. However, regulation of this process is poorly understood in CNS neurons, which rely on mitochondrial function for survival. Our findings offer fundamental insight into these regulatory mechanisms by demonstrating that replication of mitochondrial DNA, an essential precursor for biogenesis, can occur in distal regions of CNS neuron axons independent of the soma. Further, this process is upregulated specifically in axons as an early response to neurodegeneration-relevant stress. This is the first demonstration of the compartmentalized regulation of CNS neuronal mitochondrial biogenesis in response to stress and may prove a useful target in development of therapeutic strategies for neurodegenerative disease.
Towards an Efficient Identification Process for Large-Scale RFID Systems †

Radio Frequency Identification (RFID) is one of the most widely used wireless communications technologies nowadays. Among the numerous processes executed within an RFID system, the identification processis the most important one. There have been several proposals to efficiently execute such a mechanism, which are based on the use of an RFID identification method. Besides, one of the most studied scenarios comprises one reader and a set of RFID tags, which we call the centralized approach. Recent work shows that executing the identification process in a distributed or parallel way may be of great benefit for applications with high requirements on time and resources usage, i.e., applications where the time required to execute the identification process needs to be low. In this paper, we focus is on large RFID systems and compare two identification mechanisms, one based on the centralized approach and the other based on the distributed approach. Our aim is to find the advantages and disadvantages of each approach for general RFID scenarios. We observe that the distributed approach is very promising compared to the traditional approach since considerable improvements are found in identification delay, and also the implementation costs would be highly reduced.
Reducing Ex Vivo Culture Improves the Antileukemic Activity of Chimeric Antigen Receptor (CAR) T Cells

The efficacy of CAR T-cell therapy depends on the engraftment and persistence of T cells following adoptive transfer. Limiting ex vivo culture time of CD19-specific CAR T cells during manufacturing yielded improved persistence and effector function in vivo. The success of chimeric antigen receptor (CAR)–mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential of T-cell therapies with directed cytotoxicity against specific tumor antigens. The efficacy of CAR T-cell therapy depends on the engraftment and persistence of T cells following adoptive transfer. Most protocols for T-cell engineering routinely expand T cells ex vivo for 9 to 14 days. Because the potential for engraftment and persistence is related to the state of T-cell differentiation, we hypothesized that reducing the duration of ex vivo culture would limit differentiation and enhance the efficacy of CAR T-cell therapy. We demonstrated that T cells with a CAR-targeting CD19 (CART19) exhibited less differentiation and enhanced effector function in vitro when harvested from cultures at earlier (day 3 or 5) compared with later (day 9) timepoints. We then compared the therapeutic potential of early versus late harvested CART19 in a murine xenograft model of ALL and showed that the antileukemic activity inversely correlated with ex vivo culture time: day 3 harvested cells showed robust tumor control despite using a 6-fold lower dose of CART19, whereas day 9 cells failed to control leukemia at limited cell doses. We also demonstrated the feasibility of an abbreviated culture in a large-scale current good manufacturing practice–compliant process. Limiting the interval between T-cell isolation and CAR treatment is critical for patients with rapidly progressing disease. Generating CAR T cells in less time also improves potency, which is central to the effectiveness of these therapies. Cancer Immunol Res; 6(9); 1100–9. ©2018 AACR.
A Novel Synchronous Micro Motor for Intravascular Ultrasound Imaging

<italic>Objective:</italic> Intravascular ultrasound (IVUS) is an important method for evaluating lumen dimensions and guiding intervention. However, the current IVUS catheter using a proximal motor and flexible drive shaft is easily rotated at an unstable speed when it passes through along bending vessel. One approach to solve this problem is to develop a catheter driven by a distal motor. <italic>Methods:</italic> This paper presents a rotation device incorporating a high-frequency transducer as an attempt to facilitate this approach. A novel micro distal synchronous micro motor with 3.7 mm length and 1.2 mm outer diameter was proposed as an actuator for the IVUS catheter. A 0.5 mm × 0.5 mm Pb(Mg<sub>1/3</sub>Nb<sub>2/3</sub>)O<sub>3</sub>–PbTiO<sub>3</sub> single crystal 1–3 composite single-element transducer was designed and manufactured. The probe is fixed to the front end of the catheter. The 45° reflector, which is opposite to the probe, was used to steer ultrasound to the tissue. <italic>Results:</italic> The results showed that the maximum torque and rotation speed of the motor were 2.79 <italic>μ</italic>Nm and 275 revolutions per second, respectively, at a driving current of 0.34 A. The maximum angular error was 7° at 0.13 A and 30 Hz. The center frequency and −6 dB fractional bandwidth of single element were 34 MHz and 72%, respectively. At the center frequency, the two-way insertion loss was 14 dB. <italic>Conclusion:</italic> The integrated distal motor IVUS catheter, with small dimensions, a good torque, speed stability, and good ultrasound imaging performance, has tremendous potential in blood vessel imaging. <italic>Significance:</italic> The novel structure of the catheter could facilitate endoluminal sonography, reducing risks of the clinical diagnosis.
Automated scoring of dicentric chromosomes differentiates increased radiation sensitivity of young children after low dose CT exposure in vitro

Abstract Purpose: Automated detection of dicentric chromosomes from a large number of cells was applied to study age-dependent radiosensitivity after in vitro CT exposure of blood from healthy donors. Materials and methods: Blood samples from newborns, children (2–5 years) and adults (20–50 years) were exposed in vitro to 0 mGy, 41 mGy and 978 mGy using a CT equipment. In this study, automated scoring based on 13,000–31,000 cells/dose point/age group was performed. Results for control and low dose points were validated by manually counting about 26,000 cells/dose point/age group. Results: For all age groups, the high number of analyzed cells enabled the detection of a significant increase in the frequency of radiation induced dicentric chromosomes in cells exposed to 41 mGy as compared to control cells. Moreover, differences between the age groups could be resolved for the low dose: young donors showed significantly increased risk for induced dicentrics at 41 mGy compared to adults. Conclusions: The results very clearly demonstrate that the automated dicentric scoring method is capable of discerning radiation induced biomarkers in the low dose range (<100 mGy) and thus may open possibilities for large-scale molecular epidemiology studies in radiation protection.
Calibration and Noise Identification of a Rolling Shutter Camera and a Low-Cost Inertial Measurement Unit

A low-cost inertial measurement unit (IMU) and a rolling shutter camera form a conventional device configuration for localization of a mobile platform due to their complementary properties and low costs. This paper proposes a new calibration method that jointly estimates calibration and noise parameters of the low-cost IMU and the rolling shutter camera for effective sensor fusion in which accurate sensor calibration is very critical. Based on the graybox system identification, the proposed method estimates unknown noise density so that we can minimize calibration error and its covariance by using the unscented Kalman filter. Then, we refine the estimated calibration parameters with the estimated noise density in batch manner. Experimental results on synthetic and real data demonstrate the accuracy and stability of the proposed method and show that the proposed method provides consistent results even with unknown noise density of the IMU. Furthermore, a real experiment using a commercial smartphone validates the performance of the proposed calibration method in off-the-shelf devices.
Genetic Contribution to Variation in Risk Taking: A Functional MRI Twin Study of the Balloon Analogue Risk Task

Excessive risk-taking behaviors have been implicated as a potential endophenotype for substance use disorders and psychopathological gambling. However, the genetic and environmental influences on risk taking and the risk-related brain activations remain unclear. This study investigated the heritability of risk taking and the genetic influence on individual variation in risk-related brain activation. The Balloon Analogue Risk Task was used to assess individuals’ risk-taking behavior. In a sample of 244 pairs of young adult twins, we found that there was a moderate heritability (41%) of risk taking. Using voxel-level analysis, we found a moderate genetic influence on risk-related brain activation. We also found a moderate genetic correlation between risk-taking behavior and risk-related brain activation in the left insula, right striatum, and right superior parietal lobule in the active-choice condition. The present study provides important evidence for the genetic correlation between risk-taking behavior and risk-related brain activation.
The Role of the RhoA/ROCK Signaling Pathway in Mechanical Strain-Induced Scleral Myofibroblast Differentiation.

Purpose Biomechanical properties changes and α-smooth muscle actin (α-SMA) overexpression are involved in myopia scleral remodeling. However, interactions between altered tissue biomechanics and cellular signaling that sustain scleral remodeling have not been well defined. We determine the mechanisms of mechanotransduction in the regulation of α-SMA expression during myopia scleral remodeling. Methods Guinea pigs were used to establish a form-deprivation myopia (FDM) model. Protein profiles in myopic sclera were examined using tandem mass spectrometry. Ras homolog gene family member A (RhoA) and α-SMA expressions were confirmed using quantitative (q) RT-PCR and Western blotting. Scleral fibroblasts were cultured and subjected to 4% cyclic strain. Levels of RhoA, rho-associated protein kinase-2 (ROCK2), myocardin-related transcription factor-A (MRTF-A), serum response factor (SRF), and α-SMA were determined by qRT-PCR and Western blotting in groups with or without the RhoA siRNA or ROCK inhibitor Y27632. MRTF-A and α-SMA were evaluated by confocal immunofluorescent microscopy and myofibroblasts were enumerated using flow cytometry. Results mRNA and protein levels of RhoA and α-SMA were significantly increased in the FDM eyes after 4 weeks of form-deprivation treatment. The 4% static strain increased expressions of RhoA, ROCK2, MRTF-A, SRF, and α-SMA as well as nuclear translocalization of MRTF-A in scleral fibroblasts compared to those without strain stimulation. Additionally, the percentage of myofibroblasts increased after strain stimulation. Conversely, inhibition of RhoA or ROCK2 reversed the strain-induced α-SMA expression and myofibroblast ratio. Conclusions Mechanical strain activated RhoA signaling and scleral myofibroblast differentiation. Strain also mediated myofibroblast differentiation via the RhoA/ROCK2-MRTF-A/SRF pathway. These findings provided evidence for a mechanical strain-induced RhoA/ROCK2 pathway that may contribute to myopia scleral remodeling.
Increased Proportion of Fusion Surgery for Degenerative Lumbar Spondylolisthesis and Changes in Reoperation Rate: A Nationwide Cohort Study With a Minimum 5-Year Follow-up

Study Design. A retrospective cohort study. Objective. The objectives of the present study were to examine the changes in the number of surgeries, surgical methods selected, and reoperation rates between the years 2003 and 2008. Summary of Background Data. The selection of the appropriate surgical method between decompression-only (D) and decompression plus fusion (DF) represents a challenging clinical dilemma in patients with degenerative lumbar spinal spondylolisthesis. DF is selected in greater than 90% of patients, mostly due to the associated low reoperation rate. However, the outcomes of D have been improved with minimally invasive decompression surgery techniques. Methods. The Health Insurance Review and Assessment Service database was used to create cohorts of all Korean patients who underwent surgery for degenerative lumbar spinal spondylolisthesis in 2003 (2003 cohort, n = 5624) and 2008 (2008 cohort, n = 11,706). All patients were followed up for at least 5 years. Reoperation was defined as the occurrence of any type of second lumbar surgery during the follow-up period. The probabilities of reoperation were calculated using the Kaplan-Meier method. Results. The number of surgeries increased 2.08-fold in 2008. Patients older than 60 years comprised 38.6% of the 2003 cohort and 52.4% of the 2008 cohort. The proportion of DF surgery was 31.13% in the 2003 cohort but 91.54% in the 2008 cohort. However, the high proportion of fusion surgery failed to reduce the reoperation probability in the 2008 cohort (8.1%) compared with that in the 2003 cohort (6.2%). The cost of DF was US$5264 and that of D was $2719 in 2008. DF decreased the reoperation probability by 1% at the cost of $421/patient in the 2008 cohort. Conclusion. The increased proportion of fusion surgery without improvement in reoperation probability in an aging society may be cautiously addressed in deciding future health policies. Level of Evidence: 4
Characterization of UDP-Activated Purinergic Receptor P2Y6 Involved in Japanese Flounder Paralichthys olivaceus Innate Immunity

Uridine 5’-diphosphate (UDP)-activated purinergic receptor P2Y6 is a member of a G-protein-coupled purinergic receptor family that plays an important role in mammalian innate immunity. However, the role of the P2Y6 receptor (P2Y6R) in fish immunity has not been investigated. In this report, we characterized a P2Y6R gene from Japanese flounder (Paralichthys olivaceus) and examined its role in fish innate immunity. Sequence analysis reveals that the Japanese flounder P2Y6R protein is conserved and possesses four potential glycosylation sites. Quantitative real-time RT-PCR analysis shows that P2Y6R is broadly distributed in all examined Japanese flounder tissues with dominant expression in the liver. In addition, P2Y6R gene expression was up-regulated in head kidney macrophages (HKMs) upon lipopolysaccharides (LPS) and poly(I:C) stimulations but down-regulated by LPS challenge in peripheral blood leukocytes (PBLs). Furthermore, pharmacological inhibition of the endogenous P2Y6 receptor activity by the potently selective P2Y6R antagonist, MRS 2578, greatly up-regulated pro-inflammatory cytokine interleukin (IL)-1β, IL-6 and TNF-α gene expression in PBL cells treated with UDP. Moreover, LPS- and poly(I:C)-induced gene expression of IL-1β and TNF-α in Japanese flounder PBL cells was attenuated significantly by inhibition of P2Y6R activity with antagonist MRS 2578. Collectively, we, for the first time, showed the involvement of functional purinergic P2Y6R in fish innate immunity.
Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction

The dermatophyte Trichophyton rubrum is the major fungal pathogen of skin, hair, and nails that uses keratinized substrates as the primary nutrients during infection. Few strategies are available that permit a better understanding of the molecular mechanisms involved in the interaction of T. rubrum with the host because of the limitations of models mimicking this interaction. Dual RNA-seq is a powerful tool to unravel this complex interaction since it enables simultaneous evaluation of the transcriptome of two organisms. Using this technology in an in vitro model of co-culture, this study evaluated the transcriptional profile of genes involved in fungus-host interactions in 24 h. Our data demonstrated the induction of glyoxylate cycle genes, ERG6 and TERG_00916, which encodes a carboxylic acid transporter that may improve the assimilation of nutrients and fungal survival in the host. Furthermore, genes encoding keratinolytic proteases were also induced. In human keratinocytes (HaCat) cells, the SLC11A1, RNASE7, and CSF2 genes were induced and the products of these genes are known to have antimicrobial activity. In addition, the FLG and KRT1 genes involved in the epithelial barrier integrity were inhibited. This analysis showed the modulation of important genes involved in T. rubrum–host interaction, which could represent potential antifungal targets for the treatment of dermatophytoses.
Pigment cell differentiation in the fire‐bellied toad, Bombina orientalis. I. Structural, chemical, and physical aspects of the adult pigment pattern

Wild‐collected adults of Bombina orientalis are bright green dorsally and red to red‐orange ventrally. As a prelude to an analysis of the differentiation of pigment cells in developing B. orientalis, we describe structural and chemical aspects of the fully differentiated pigment pattern of the “normal” adult.
Predicting Mood Disturbance Severity with Mobile Phone Keystroke Metadata: A BiAffect Digital Phenotyping Study

Background Mood disorders are common and associated with significant morbidity and mortality. Better tools are needed for their diagnosis and treatment. Deeper phenotypic understanding of these disorders is integral to the development of such tools. This study is the first effort to use passively collected mobile phone keyboard activity to build deep digital phenotypes of depression and mania. Objective The objective of our study was to investigate the relationship between mobile phone keyboard activity and mood disturbance in subjects with bipolar disorders and to demonstrate the feasibility of using passively collected mobile phone keyboard metadata features to predict manic and depressive signs and symptoms as measured via clinician-administered rating scales. Methods Using a within-subject design of 8 weeks, subjects were provided a mobile phone loaded with a customized keyboard that passively collected keystroke metadata. Subjects were administered the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) weekly. Linear mixed-effects models were created to predict HDRS and YMRS scores. The total number of keystrokes was 626,641, with a weekly average of 9791 (7861), and that of accelerometer readings was 6,660,890, with a weekly average 104,076 (68,912). Results A statistically significant mixed-effects regression model for the prediction of HDRS-17 item scores was created: conditional R2=. 63, P=. 01. A mixed-effects regression model for YMRS scores showed the variance accounted for by random effect was zero, and so an ordinary least squares linear regression model was created: R2=. 34, P=. 001. Multiple significant variables were demonstrated for each measure. Conclusions Mood states in bipolar disorder appear to correlate with specific changes in mobile phone usage. The creation of these models provides evidence for the feasibility of using passively collected keyboard metadata to detect and monitor mood disturbances.
Ethical Decision Making Levels of Nursing Students

Objective: The present study was conducted to determine nursing students’ levels of ethical decision-making. Methods: The sample of the descriptive study consisted of 240 nursing students. The data were collected using the Student Information Form and “Nursing Dilemma Test”. Results: It was found that Principled Thinking (PT) mean score (48.38±7.97) of nursing students was above average while their Practical Consideration (PC) mean score (17.87±4.13) was close to average. It was also determined that the nursing students participated in the study were not familiar (17.75±2.77) with the dilemmas included in the Nursing Ethical Dilemma Test. Conclusion: The students paid attention to consider ethical principles when making decisions about ethical dilemmas; however, they are also affected by environmental factors as well. Sex and class level were found to be influential in the process of ethical decision making.