Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody to MyoD or Myogenin Decreases Acetylcholine Receptor Clustering in C2C12 Myotube Culture

Skeletal muscle development is influenced by myogenic regulatory factors, including the expression of MyoD and myogenin. Our objective was to use the C2C12 cell culture model to test the hypothesis that both MyoD and myogenin were required for agrin-induced acetylcholine receptor (AChR) clustering and the fusion of myoblasts into myotubes. We induced fusion of myoblasts into myotubes by switching from growth medium (GM) to differentiation medium (DM). During myotube formation AChRs cluster spontaneously, but treatment with motor neuron derived agrin increases clustering of AChRs and other postsynaptic components of the neuromuscular synapse. We examined the normal expression pattern of MyoD and myogenin in C2C12 cell culture using immunofluorescence. MyoD was highly expressed while myoblasts were in GM, but expression declined within 72 hours after cell cultures were switched to DM. Myogenin expression was low in GM, but increased when cell cultures were switched to DM. Next we used antibodies to decrease MyoD and/or myogenin function. Fluorescence microscopy images were captured and then analyzed to assess agrin-induced AChR clustering with or without antibody treatment. Finally we calculated the proportion of nuclei in myotubes and myoblasts by creating digital overlays of phase contrast and DAPI stained microscopy images. This allowed the comparison of myotube formation with or without antibody treatment. We report that antibody to either MyoD or myogenin decreases the frequency of agrin-induced AChR clustering without affecting myotube formation. We conclude that agrin-induced AChR clustering requires both MyoD and myogenin.
Endogenous neural progenitor cells in the repair of the injured spinal cord

Stem cell treatments, and in particular, stem cell transplants have been identified as potential therapeutic strategies for a range of neurodegenerative and acquired conditions of the central nervous system (CNS). Stem cell transplants are seen as a way of replacing lost neurons, or providing a cellular environment that is more permissible for axon and cell regeneration. An alternate strategy to transplantation of exogenous stem cells is the recruitment and manipulation of endogenous neural progenitor cells (NPC). NPCs exist in the spinal cord and have been shown to proliferate, migrate and differentiate in response to injury (Mothe and Tator, 2005; Meletis et al., 2008; Hamilton et al., 2009). NPCs may have a wider role than previously thought and it has been reported that NPCs also engage in ‘cross talk’ with immune cells and may be able to modulate the inflammatory response following injury. Our research has focussed on determining the exact timing and location of NPC activation after injury. It is clear that there will be a critical window of opportunity to implement a treatment that harnesses the NPC response to spinal cord injury (SCI), and that this must occur before the full cascade of inflammation has been initiated.
Cannabis and progression to other substance use in young adults: findings from a 13-year prospective population-based study

Background Adolescent cannabis use predicts the onset of later illicit drug use. In contrast, little is known about whether cannabis in young adulthood also predicts subsequent progression or cessation of licit or illicit drug use. Methods 13-year longitudinal cohort study with recruitment in secondary school students in Victoria, Australia. There were six waves of adolescent data collection (mean age 14.9–17.4 years) followed by three in young adulthood (mean age 20.7, 24.1 and 29.0 years). Discrete-time proportional hazards models were used to assess predictive associations between cannabis use frequency (occasional (<weekly), weekly to less than daily and daily) in 1756 participants in earlier young adult waves and subsequent cigarette smoking, high-risk alcohol use and amphetamine, ecstasy and cocaine use, including incident use (uptake) and cessation in later young adult waves. Results Compared with continuing occasional cannabis use: (1) never use provided the strongest protection from uptake of all drugs; (2) quitting cannabis lowered rates of illicit drug use uptake; (3) weekly+cannabis users had two to three times the rates of illicit drug use uptake, while daily users had six times the rate of uptake of cigarette smoking; and (4) never use of cannabis was associated with higher rates of cessation from licit drug use, while daily cannabis predicted lower cessation rates for all drugs except cocaine. Conclusions This study provides compelling evidence of the continuing association between cannabis, licit and other illicit drug use well into young adulthood. Preventing cannabis use uptake and use escalation remain crucial health aims given the burden associated with cigarette, alcohol and illicit drug use.
Disease‐specific growth charts for Korean infants with Prader–Willi syndrome

Patients with Prader–Willi syndrome (PWS) present with short stature and obesity. The growth pattern of children with PWS is different from that of the healthy population. Therefore, it is not appropriate to use normal growth charts to evaluate the growth status of children with PWS. We aimed to develop disease‐specific growth charts for height and weight for nongrowth hormone‐treated Korean infants with PWS aged between 0 and 36 months and to use these growth charts for the evaluation and management of infants with PWS. We conducted a retrospective review of the medical records of 122 infants with genetically confirmed PWS. Data on the patients’ height and weight measurements before they underwent growth hormone treatment were recorded. Disease‐specific growth charts were generated and the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th centiles were calculated using the LMS (refers to λ, μ, and σ, respectively) smoothing procedure for height and weight. The disease‐specific growth charts for Korean infants with PWS can be used when examining infants with PWS and when evaluating their growth at later stages for comparison purposes. They are also useful for monitoring growth patterns, nutritional assessments, and recording responses to growth hormone treatment. © 2014 Wiley Periodicals, Inc.
Effects of local administration of ibuprofen on sciatic nerve regeneration and reinnervation after egg shell membrane conduit repair in rat.

AIM The objective was to assess the effect of locally administered ibuprofen (IBU) on transected peripheral nerve regeneration and functional recovery. MATERIALS AND METHODS Seventy--five male Wistar rats were divided into five experimental groups (n = 15), randomly: In authograft group (AUTO) a segment of sciatic nerve was transected and reimplanted reversely. In transected group (TC), left sciatic nerve was transected and stumps were fixed in the adjacent muscle. In treatment group defect was bridged using an egg shell membrane conduit (ESM/IBU) filled with 10 μL ibuprofen (100 ng/mL). In ESM conduit group (ESM), the conduit was filled with phosphate--buffered saline alone. In sham--operated group (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into three subgroups of five animals each and regenerated nerve fibers were studied 4, 8 and 12 weeks after surgery. RESULTS Behavioral testing, biomechanical studies, sciatic nerve functional study, electrophysiological, gastrocnemius muscle mass and morphometric indices confirmed faster recovery of regenerated axons in ESM/IBU than ESM group (p < 0.05). In immunohistochemistry, location of reactions to S--100 in ESM/IBU was clearly more positive than that in ESM group. CONCLUSION Ibuprofen accelerated and improved functional recovery and morphometric indices of sciatic nerve. This study is expected to set a stage for testing the ibuprofen in the human patients.
The Mid-Range of the Adjusted Level of Ferritin Can Predict the Chronic Course in Patients with Adult Onset Still’s Disease

Objective. To find a measure that can predict the disease course in patients with adult onset Still’s disease (AOSD). Methods. We retrospectively investigated the medical records of 71 hospitalized patients with AOSD. Patients were divided according to chronic and nonchronic disease course. The initial laboratory results were defined as those at the time of admission, the extremely deviated laboratory results as the highest or the lowest results, and the adjusted laboratory results as area under the curve divided by the days of hospitalization. All measures were compared and the odds ratio (OR) for the chronic disease pattern was assessed. Results. The mean age was 39.7 ± 13.5 years and women accounted for 63 of the total 71 (88.7%). Thirty patients (42.3%) had self-limited disease, 9 (12.7%) intermittent disease, and 23 (32.4%) the chronic disease pattern (32.4%). Nine patients (12.7%) died. The initial levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ferritin, the highest levels of lactate dehydrogenase (LDH) and ferritin, and the adjusted level of ferritin in patients with chronic disease were significantly higher than those with nonchronic disease. Among them, only the middle range of the adjusted ferritin level (784.1~4120.0 ng/ml) was found to have a significant predictive value for the chronic disease pattern (OR 81.7, p = 0.007). Conclusion. A novel measure, the adjusted level of ferritin during the first hospitalization, might be useful to predict progression to chronic disease in patients with AOSD.
Assessment of accuracy for soft classification: SCAASFER as a tool

Accuracy assessment is an important issue for validation of image classification. There are several tools that provide accuracy analysis using confusion matrix, Kappa coefficients and others incorporated in ERDAS_IMAGINE, ArcGIS, ENVI, Geomatica etc. There are some of tools available for soft or sub-pixel classification which gives fraction images as output like, FUZCEN, SMIC. Each fraction image is associated to single class from classification schema and represents membership to that class in gray scale for all pixels of input multispectral image. This paper introduces SCAASFER: Soft Classification Accuracy Assessment using SCM, FERM, Entropy and RMSE as a tool for accuracy assessment for soft classified data. This tool automated the accuracy assessment process with several popular accuracy measures available for soft classification, like FERM (Fuzzy Error Matrix), SCM (Sub-pixel Confusion uncertainty Matrix), MIN-PROD Error matrix, RMSE (Root Mean Square Error) and Entropy. SCAASFER provide an interactive way to acquire samples data for accuracy from fraction images with different options, like Random points, stratified random points, manual selection of points and area from fraction image or take compete image census for accuracy analysis. This tool also provides facility to view and save accuracy assessment results as well as sample points on hard disk. This tool is developed in JAVA programming language. JAVA is a platform independent language and allows running this tool on different operating Systems and machines.
Multiple Memory Systems: What and Why

Evidence from a variety of domains converges on the view that there are multiple learning/memory systems, but there is no clear understanding of what these systems are, and why they should exist. I review an hypothesis about multiple memory systems postulated by O'Keefe and Nadel (The hippocampus ac a Cognitive map, Oxford: Clarendon Press, 1978), in particular our assertions about the nature of two kinds of systems (the locale and taxon systems), and what differentiates them from each other. I concentrate on our assumption that systems differ in terms of the type of information they process, rather than in terms of the temporal duration over which they function. Our content-driven dichotomy is contrasted with several other current views, none of which appears to explain extant data, or provides clear predictions about when one or the other kind of system would be engaged. Finally, 1 briefly consider why such distinct systems might have evolved.
Who Knows More About Condoms? A Comparison Between Nursing Students, Education Students, and at-Risk Adolescents

Purpose To examine knowledge regarding appropriate use of condoms and lubricants among three groups: female at-risk adolescents, nursing students, and education students. Methods Study participants were 236 adolescents: 65 recruited through community agencies, 79 female nursing students, and 92 female education students. These participants completed anonymous questionnaires concerning lubricants, general condom knowledge, and sexual experience. Results Neither nursing students nor education students were more knowledgeable than adolescents not enrolled in college. All participants were about as likely to think unsafe lubricants were safe as they were to think that safe lubricants were unsafe. Personal experience with vaginal intercourse and condom use was associated with increased knowledge (p < 0.05). However, 27% to 66% of participants who had used condoms answered the lubricant questions incorrectly. Implications Nursing students need more education about condoms and condom lubricants if they intend to teach patients effectively. Moreover, nurses should not assume that youth are knowledgeable about appropriate condom use based on their level of education or sexual experience.
The effect of plant sterol-enriched turkey meat on cholesterol bio-accessibility during in vitro digestion and Caco-2 cell uptake

Abstract This study evaluated the effect of a plant sterol-enriched turkey product on cholesterol bio-accessibility during in vitro digestion and cholesterol uptake by Caco-2 monolayers. Turkey products, one plant sterol-enriched (PS) and one plant sterol-free (C), were produced in an industrial pilot plant. Before simulated digestion, matrices were spiked with cholesterol (1:5 weight ratio of cholesterol to plant sterol). Plant sterols were included at a concentration equivalent to the minimum daily intake recommended by the European Food Safety Authority (EFSA) for cholesterol lowering. After simulated digestion, the percentage of cholesterol micellarization and uptake by Caco-2 cells in the presence of PS meat were measured. Compared to C meat, PS meat significantly inhibited cholesterol micellarization on average by 24% and Caco-2 cell accumulation by 10%. This study suggests that plant sterols in meat can reduce cholesterol uptake by intestinal epithelia and it encourages efforts to make new PS-based functional foods.
PET Imaging Analysis with 64Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Menkes disease (MD), an X-linked recessive disorder of copper metabolism caused by mutations in the copper-transporting ATP7A gene, results in growth failure and severe neurodegeneration in early childhood. Subcutaneous copper-histidine injection is the standard treatment for MD, but it has limited clinical efficacy. Furthermore, long-term copper injection causes excess copper accumulation in the kidneys, resulting in renal dysfunction. To attempt to resolve this issue, we used PET imaging with 64Cu to investigate the effects of disulfiram on copper biodistribution in living mice serving as an animal model for MD (MD model mice). Methods: Macular mice were used as MD model mice, and C3H/He mice were used as wild-type mice. Mice were pretreated with 2 types of chelators (disulfiram, a lipophilic chelator, and d-penicillamine, a hydrophilic chelator) 30 min before 64CuCl2 injection. After 64CuCl2 injection, emission scans covering the whole body were performed for 4 h. After the PET scans, the brain and kidneys were analyzed for radioactivity with γ counting and autoradiography. Results: After copper injection alone, marked accumulation of radioactivity (64Cu) in the liver was demonstrated in wild-type mice, whereas in MD model mice, copper was preferentially accumulated in the kidneys (25.56 ± 3.01 percentage injected dose per gram [%ID/g]) and was detected to a lesser extent in the liver (13.83 ± 0.26 %ID/g) and brain (0.96 ± 0.08 %ID/g). Copper injection with disulfiram reduced excess copper accumulation in the kidneys (14.54 ± 2.68 %ID/g) and increased copper transport into the liver (29.42 ± 0.98 %ID/g) and brain (5.12 ± 0.95 %ID/g) of MD model mice. Copper injection with d-penicillamine enhanced urinary copper excretion and reduced copper accumulation in most organs in both mouse groups. Autoradiography demonstrated that disulfiram pretreatment induced copper transport into the brain parenchyma and reduced copper accumulation in the renal medulla. Conclusion: PET studies with 64Cu revealed that disulfiram had significant effects on the copper biodistribution of MD. Disulfiram increased copper transport into the brain and reduced copper uptake in the kidneys of MD model mice. The application of 64Cu PET for the treatment of MD and other copper-related disorders may be useful in clinical settings.
The Use of Yeast Two‐Hybrid Screens in Studies of Protein:Protein Interactions Involved in Trafficking

The yeast two‐hybrid system has provided a convenient means to both screen for proteins that interact with a protein of interest and to characterise the known interaction between two proteins. Several groups with an interest in the molecular mechanisms that underlie discrete steps along trafficking pathways have exploited the yeast two‐hybrid system. Here, we provide a brief background to the technology, attempt to point out some of the pitfalls and benefits of the different systems that can be employed, and mention some of the areas (within the trafficking field) where yeast two‐hybrid interaction assays have been particularly informative.
Developing and Using a Partnership Covenant to Guide a Study of Late HIV Diagnosis

Background: Late diagnosis of HIV is an important problem in the United States, particularly in ethnically and socially diverse communities. Objectives: We created and used a partnership covenant to ensure our adherence to community-based participatory research (CBPR) principles as we began studying and addressing individual and structural barriers to timely HIV testing. Methods: Sample CBPR principles were used to help develop a partnership covenant that in turn was used in steering committee (SC) meetings to gauge our adherence to CBPR in our work together and in the field. Results: Continuing dialogue around our fidelity to the covenant resulted in concrete changes including a “crash course” on sampling for community partners and development of a community advisory board (CAB). Our ability to meet the project’s specific aims was enhanced by using the covenant. Conclusions: Although time consuming, development and use of a CBPR covenant can improve high-level engagement and help to accomplish a study’s specific aims.
Identification of a novel functional androgen response element within hPar1 promoter: implications to prostate cancer progression

Human protease‐activated receptor‐1 (hPar1) plays a role in malignant and physiological invasion processes. We have identified a functional androgen response element (ARE) located in the hPar1 promoter upstream of the transcription start site at ‐1791 to ‐1777. Dihydrotestosterone treatment of the prostate cancer cell line LNCaP increased endogenous hPar1 mRNA levels, consistent with the threefold increase in promoter activity of hPar1‐luciferase reporter con‐ struct. Specific binding of the hPar1‐derived ARE to LNCaP nuclear extracts was demonstrated by electro‐ phoretic mobility shift assay. This binding was abro‐ gated by antiandrogen receptor (anti‐AR) antibodies or excess cold oligonucleotide but not by a mutated oligonucleotide. Moreover, using chromatin immuno‐ precipitation assays, we confirm the in vivo interaction between the AR and ARE domain of the hPar1 pro‐ moter. In parallel, we show that hormone ablation therapy markedly reduces the otherwise high hPar1 expression levels in prostate cancer biopsy specimens. We suggest that the hPar1 gene is regulated transcrip‐ tionally by androgens, representing one of several target genes effectively reduced during hormone abla‐ tion therapy. A major limitation of hormonal depriva‐ tion is that it causes only a temporary remission, and the cancer eventually reappears in a more malignant, androgen‐independent form. hPar1 is also overex‐ pressed in CL1 cells, an aggressively metastasizing, hormone‐independent subclone of LNCaP, and in PC3 prostate adenocarcinoma lacking AR in a mechanism yet to be fully elucidated. These data may imply that hPar1 expression correlates with prostate cancer pro‐ gression in androgen‐dependent and ‐independent phases and therefore, provides an instrumental, thera‐ peutic target for treatment in prostate cancer. FASEBJ. 19, 62‐72 (2005)
Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3

The regulation of microtubule dynamics is critical to ensure essential cell functions. End binding protein 1 (EB1) is a master regulator of microtubule dynamics that autonomously binds an extended GTP/GDP-Pi structure at growing microtubule ends and recruits regulatory proteins at this location. However, negative regulation of EB1 association with growing microtubule ends remains poorly understood. We show here that microtubule-associated tumor suppressor ATIP3 interacts with EB1 through direct binding of a non-canonical proline-rich motif. Results indicate that ATIP3 does not localize at growing microtubule ends and that in situ ATIP3-EB1 molecular complexes are mostly detected in the cytosol. We present evidence that a minimal EB1-interacting sequence of ATIP3 is both necessary and sufficient to prevent EB1 accumulation at growing microtubule ends in living cells and that EB1-interaction is involved in reducing cell polarity. By fluorescence recovery of EB1-GFP after photobleaching, we show that ATIP3 silencing accelerates EB1 turnover at microtubule ends with no modification of EB1 diffusion in the cytosol. We propose a novel mechanism by which ATIP3-EB1 interaction indirectly reduces the kinetics of EB1 exchange on its recognition site, thereby accounting for negative regulation of microtubule dynamic instability. Our findings provide a unique example of decreased EB1 turnover at growing microtubule ends by cytosolic interaction with a tumor suppressor.
Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis.

RATIONALE Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor cells (MDSCs), has been described in cancer, which suppresses T-cell responses and fosters disease progression. The role of MDSCs in infection is insufficiently addressed. OBJECTIVES To examine the presence and function of MDSCs during experimental pulmonary tuberculosis (TB) and further understand the immunologic consequences of direct interactions between MDSCs and lung bacterial pathogens. METHODS Using cell-based approaches and experimental mouse models for pulmonary TB we characterized MDSCs as novel myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb). MEASUREMENTS AND MAIN RESULTS MDSCs readily phagocytosed Mtb, and released proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in the lung in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4Rα and heightened TB lethality, whereas targeted depletion of MDSCs ameliorated disease. CONCLUSIONS Our data reveal that MDSCs provide a niche for pathogen survival and tailor immunity in TB. These findings suggest MDSCs as amenable targets for host-directed therapies and emphasize them as cellular-immune regulators during chronic inflammatory conditions, including chronic infections and microbial complications of neoplastic disorders.