MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Low vitamin D status is associated with systemic and gastrointestinal inflammation in dogs with a chronic enteropathy

Vitamin D is traditionally known for its role in calcium homeostasis and bone metabolism. However, it has been demonstrated that numerous types of cells express the vitamin D receptor and it is now clear that the physiological roles of vitamin D extend beyond the maintenance of skeletal health. Vitamin D insufficiency, which is typically assessed by measuring the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with a number of disorders in people including hypertension, diabetes, cardiovascular diseases, cancer, autoimmune conditions and infectious diseases. Meta-analyses have demonstrated that serum 25(OH)D concentrations are an important predictor of survival in people with a wide variety of illnesses and have been linked to all-cause mortality in the general human population. The role of vitamin D in non-skeletal disorders in cats and dogs is poorly understood. This is surprising since cats and dogs could act as excellent models for probing the biology of vitamin D. Vitamin D status in people is largely dependent on cutaneous production of vitamin D. This is influenced by many factors such as season, latitude and exposure to ultraviolet (UV) radiation. The interpretation of human studies investigating the effects vitamin D status on disease outcomes are therefore influenced by a number of confounding variables. Unlike humans, domesticated cats and dogs do not produce vitamin D cutaneously and obtain vitamin D only from their diet. The physiological functions and regulation of vitamin D are otherwise similar to humans. Most pets are fed commercial diets containing a relatively standard amount of vitamin D. Consequently, companion animals are attractive model systems in which to examine the relationship vitamin D status and health outcomes. Furthermore, spontaneously occurring model systems which did not require disease to be induced in healthy animals would allow the numbers of animals used in scientist research to be reduced. This thesis aimed to define vitamin D homeostasis in companion animals in three disease settings; in cats with feline immunodeficiency virus (FIV) infection, dogs with chronic enteropathies (CE) and in hospitalised ill cats. Additional aims were to assess the prognostic significance of serum 25(OH)D concentrations in companion animals and the relationship between serum 25(OH)D concentrations and markers of inflammation. The hypothesis of this thesis was that vitamin status D would negatively correlate with presence of disease, markers of inflammation and disease outcomes. As similar findings have been demonstrated in human medicine, the hypothesis was that cats and dogs would be suitable models to investigate the role of vitamin D in human disease. This thesis demonstrates that in dogs with a CE serum 25(OH)D concentrations are negatively correlated with inflammation and are predictive of clinical outcomes. Vitamin D status was also lower in cats with FIV and importantly vitamin D status was predictive of short term mortality in hospitalised ill cats. This research will be of interest to veterinary surgeons and opens the possibility for clinical trials which examine if low vitamin D status is causally associated with ill health and whether vitamin D supplementation results in superior treatment outcomes in companion animals. This thesis also demonstrates the potential of cats and dogs as model systems in which to examine the role of vitamin D in human health

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar, and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys

Effectiveness of an Ayurveda treatment approach in knee osteoarthritis - a randomized controlled trial

OBJECTIVE Ayurveda is commonly used in South Asia to treat knee osteoarthritis (OA). We aimed to evaluate the effectiveness of Ayurvedic treatment compared to conventional conservative care in patients with knee OA. METHOD According to American College of Rheumatology (ACR) criteria knee OA patients were included in a multicenter randomized, controlled, open-label trial and treated in 2 hospital clinics and 2 private outpatient clinics in Germany. Participants received either a multi-modal Ayurvedic treatment or multi-modal conventional care with 15 treatments over 12 weeks respectively. Primary outcome was the change on the Western Ontario and McMaster University Osteoarthritis (WOMAC) Index after 12 weeks. Secondary outcomes included WOMAC subscales; the pain disability index and a pain experience scale, numeric rating scales for pain and sleep quality, quality-of-life and mood, rescue medication use, and safety issues. RESULTS One hundred fifty-one participants (Ayurveda n = 77, conventional care n = 74) were included. Changes of the WOMAC Index from baseline to 12 weeks were more pronounced in the Ayurveda group (mean difference 61.0 [95%CI: 52.4;69.6]) than in the conventional group (32.0 [95%CI: 21.4;42.6]) resulting in a significant between-group difference (p < 0.001) and a clinically relevant effect size (Cohen's d 0.68 [95% CI:0.35;1.01]). Similar trends were observed for all secondary outcomes at week 12. Effects were sustained at follow-ups after 6 and 12 months. CONCLUSION Results suggest that Ayurvedic treatment is beneficial in reducing knee OA symptoms. Further studies should be conducted to confirm the magnitude of the effect and to clarify the role of different treatment components and non-specific effects. REGISTRATION: at clinicaltrials.gov (NCT01225133; initial release 10/06/2010)