The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma.

BACKGROUND: Despite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals. OBJECTIVE: We reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role. METHODS: There were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs). RESULTS: SPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs. CONCLUSION: FDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients

Overcoming the Challenges Associated with Image-based Mapping of Small Bodies in Preparation for the OSIRIS-REx Mission to (101955) Bennu

The OSIRIS-REx Asteroid Sample Return Mission is the third mission in NASA's New Frontiers Program and is the first U.S. mission to return samples from an asteroid to Earth. The most important decision ahead of the OSIRIS-REx team is the selection of a prime sample-site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission-critical decision, the surface of Bennu is mapped using the OSIRIS-REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample-sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS-REx team for image-based mapping of irregular small bodies. We emphasize the importance of using 3D shape models and the ability to work in body-fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body-fixed latitude and longitude.Comment: 31 pages, 10 figures, 2 table

A prospective antibiotic point prevalence survey in two primary referral hospitals during and after pilgrims stay in Madinah, Saudi Arabia

Purpose: To assess current patterns of antibiotic use by carrying out two point-prevalence surveys (PPS) in Madinah after the return of hajj pilgrims from Makkah and when Madinah is free from pilgrims. Methods: In September 2016 and November 2016, a prospective PPS was conducted on two separate dates (during the hajj pilgrims stay in Madinah and after they leave). Data on antibiotics use were generated during these two periods. This involved an audit from all the departments of two referral hospitals (King Fahad Hospital (KFH) - 425 beds, and Al Ansar Hospital - 100 beds) of inpatients records. Data were collected using standard forms adapted from the European Centre for Disease Control (ECDC). Results: A total of 675 inpatients were included in PPS; among them, 332 (49.18 %) patients were receiving antibiotic therapy. In September 2016, 168 patients were treated with antibiotics, with a prevalence rate of 50.60 %, whereas, in November 2016, the prevalence rate was 49.40 %. Overall, 198 patients were identified in surgical wards, of which 132 patients (66.6 %) were receiving antibiotic therapy; 121 patients in ICU of which 70 patients (57.8 %) received antibiotics; 13 patients in other wards of which 6 (46.1 %) received antibiotic treatment; and 343 patients in medical wards of which 126 patients (36.7 %) were treated with antibiotics. There was no significant difference in prevalence of antibiotic prescribing between the two surveys (Pearson Chi-square test, p = 0.56) and with regards to patient age between the two surveys (Mann-Whitney U-test, p = 0.32). Conclusion: The results demonstrate that antibiotic use with adherence to hospital guidelines and PPS helps in identifying targets for quality improvement. Moreover, to escalate the prudent use of antibiotics in hospitals, PPS provides a useful tool. Furthermore, this survey provides a background to evaluate antibiotic use by a standardized methodology. Keywords: Point prevalence survey, Antibiotic use, Prescribing practices, Antibiotic resistance, Quality improvement, Antibiotic stewardship, Hajj, Pilgrim

Cross calibration between Hayabusa2/ONC-T and OSIRIS-REx/MapCam for comparative analyses between asteroids Ryugu and Bennu

Proximity observations of (162173) Ryugu by the telescopic Optical Navigation Camera onboard Hayabusa2 and (101955) Bennu by MapCam onboard Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer found opposite spectral trends of space weathering on these carbonaceous asteroids. Whether the space weathering trends on these asteroids evolved from the same starting spectra would place an important constraint for understanding their relation. However, systematic error between data obtained by the two imagers needed to be reduced for accurate comparison. To resolve this problem, we cross calibrated albedo and color data using the Moon as the common standard. We show that the cross-calibrated reflectance can be obtained by upscaling the pre-cross-calibrated reflectance of Bennu by 12 +/- 2% at v-band, reducing the systematic errors down to 2%. The cross-calibrated data show that Bennu is brighter by 16 +/- 2% at v-band and bluer in spectral slope by 0.19 +/- 0.05 (/um) than Ryugu. The spectra of fresh craters on Ryugu and Bennu before cross calibration appeared to follow two parallel trend lines with offset, but they converged to a single trend after cross calibration. Such a post-cross-calibration perspective raise the possibility that Ryugu and Bennu evolved from materials with similar visible spectra but evolved in diverging directions by space weathering. The divergent evolution can be caused by the difference in space weathering dose/process and/or composition of the starting material. Thus, comparing the composition of samples returned from Ryugu and Bennu may change the way we interpret the spectral variation of C-complex asteroids

Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications

Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin’s multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered

Overcoming the Challenges Associated with Image-Based Mapping of Small Bodies in Preparation for the OSIRIS-REx Mission to (101955) Bennu

The OSIRIS‐REx Asteroid Sample Return Mission is the third mission in National Aeronautics and Space Administration (NASA)'s New Frontiers Program and is the first U.S. mission to return samples from an asteroid to Earth. The most important decision ahead of the OSIRIS‐REx team is the selection of a prime sample‐site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission‐critical decision, the surface of Bennu is mapped using the OSIRIS‐REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS‐REx team for image‐based mapping of irregular small bodies. We emphasize the importance of using 3‐D shape models and the ability to work in body‐fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body‐fixed latitude and longitude.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Ensemble Modeling for Aromatic Production in Escherichia coli

Ensemble Modeling (EM) is a recently developed method for metabolic modeling, particularly for utilizing the effect of enzyme tuning data on the production of a specific compound to refine the model. This approach is used here to investigate the production of aromatic products in Escherichia coli. Instead of using dynamic metabolite data to fit a model, the EM approach uses phenotypic data (effects of enzyme overexpression or knockouts on the steady state production rate) to screen possible models. These data are routinely generated during strain design. An ensemble of models is constructed that all reach the same steady state and are based on the same mechanistic framework at the elementary reaction level. The behavior of the models spans the kinetics allowable by thermodynamics. Then by using existing data from the literature for the overexpression of genes coding for transketolase (Tkt), transaldolase (Tal), and phosphoenolpyruvate synthase (Pps) to screen the ensemble, we arrive at a set of models that properly describes the known enzyme overexpression phenotypes. This subset of models becomes more predictive as additional data are used to refine the models. The final ensemble of models demonstrates the characteristic of the cell that Tkt is the first rate controlling step, and correctly predicts that only after Tkt is overexpressed does an increase in Pps increase the production rate of aromatics. This work demonstrates that EM is able to capture the result of enzyme overexpression on aromatic producing bacteria by successfully utilizing routinely generated enzyme tuning data to guide model learning

Robustness Analysis and Behavior Discrimination in Enzymatic Reaction Networks

Characterizing the behavior and robustness of enzymatic networks with numerous variables and unknown parameter values is a major challenge in biology, especially when some enzymes have counter-intuitive properties or switch-like behavior between activation and inhibition. In this paper, we propose new methodological and tool-supported contributions, based on the intuitive formalism of temporal logic, to express in a rigorous manner arbitrarily complex dynamical properties. Our multi-step analysis allows efficient sampling of the parameter space in order to define feasible regions in which the model exhibits imposed or experimentally observed behaviors. In a first step, an algorithmic methodology involving sensitivity analysis is conducted to determine bifurcation thresholds for a limited number of model parameters or initial conditions. In a second step, this boundary detection is supplemented by a global robustness analysis, based on quasi-Monte Carlo approach that takes into account all model parameters. We apply this method to a well-documented enzymatic reaction network describing collagen proteolysis by matrix metalloproteinase MMP2 and membrane type 1 metalloproteinase (MT1-MMP) in the presence of tissue inhibitor of metalloproteinase TIMP2. For this model, our method provides an extended analysis and quantification of network robustness toward paradoxical TIMP2 switching activity between activation or inhibition of MMP2 production. Further implication of our approach is illustrated by demonstrating and analyzing the possible existence of oscillatory behaviors when considering an extended open configuration of the enzymatic network. Notably, we construct bifurcation diagrams that specify key parameters values controlling the co-existence of stable steady and non-steady oscillatory proteolytic dynamics

Ground and In-Flight Calibration of the OSIRIS-REx Camera Suite

The OSIRIS-REx Camera Suite (OCAMS) onboard the OSIRIS-REx spacecraft is used to study the shape and surface of the mission’s target, asteroid (101955) Bennu, in support of the selection of a sampling site. We present calibration methods and results for the three OCAMS cameras—MapCam, PolyCam, and SamCam—using data from pre-flight and in-flight calibration campaigns. Pre-flight calibrations established a baseline for a variety of camera properties, including bias and dark behavior, flat fields, stray light, and radiometric calibration. In-flight activities updated these calibrations where possible, allowing us to confidently measure Bennu’s surface. Accurate calibration is critical not only for establishing a global understanding of Bennu, but also for enabling analyses of potential sampling locations and for providing scientific context for the returned sample