Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis.

A small RNA encoded within the nucleus is an essential subunit of a RNA processing endonuclease (RNase MRP) hypothesized to generate primers for mitochondrial DNA replication from the heavy strand origin of replication. Controversy has arisen, however, concerning the authenticity of an intramitochondrial pool of MRP RNA, and has called into question the existence of pathways for nucleo-mitochondrial transport of nucleic acids in animal cells. In an effort to resolve this controversy, we combined ultrastructural in situ hybridization and biochemical techniques to assess the subcellular partitioning of MRP RNA. Cryosections of mouse cardiomyocytes were hybridized with biotin-labeled RNA probes complementary to different regions of MRP RNA and varying in length from 115 to 230 nucleotides, followed by immunogold labeling. In addition, we transfected mouse C2C12 myogenic cells with constructs bearing mutated forms of the mouse MRP RNA gene and compared the relative abundance of the resulting transcripts to that of control RNAs within whole cell and mitochondrial fractions. In the former analysis we observed preferential localization of MRP RNA to nucleoli and mitochondria in comparison to the nucleoplasm and cytoplasm. In the latter series of studies we observed that wild-type MRP RNA partitions to the mitochondrial fraction by comparison to other RNA transcripts that are localized to the extramitochondrial cytoplasmic space (28S rRNA) or to the nucleoplasm (U1 snRNA). Deletions within 5' or 3' regions of the MRP RNA gene produced transcripts that remain competent for mitochondrial targeting. In contrast, deletion of the midportion of the coding region (nt 118 to 175) of the MRP RNA gene resulted in transcripts that fail to partition to the mitochondrial fraction. We conclude that an authentic intramitochondrial pool of MRP RNA is present in these actively respiring cells, and that specific structural determinants within the MRP RNA molecule permit it to be partitioned to mitochondria

A review of the current use of commercial wearable technology and smartphone apps with application in monitoring individuals following total hip replacement surgery

The advent of commercially available wearable activity monitors and smartphone apps allows objective digital monitoring of daily activities of patients before and after THR surgery. A wide variety of wearable activity monitors and smartphone apps are being marketed to assist with enhancing physical activity following surgery. A systematic review of commercial wearable tech- nology and smartphone apps was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation and patient monitoring following THR. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES and PubMed of studies from January 2000 to January 2019. Five studies met the eligibility criteria. A review of the studies found very little evidence to support long term efficacy of the technology in enhancing rehabilitation and patient monitoring post THR. Future work is required to establish which commercially available monitoring technology is most valuable to patients, which ones improve clinical outcomes post THR, and what are the best economical models for their deployment

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

[EN] Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostatespecific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4¿5 mm). Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organdedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.The work presented in this article has been partially funded by a research grant from the regional government of the Comunitat Valenciana (Spain), co-funded by the European Union ERDF funds (European Regional Development Fund) of the Comunitat Valenciana 2014-2020, with reference IDIFEDER/2018/032 (High-Performance Algorithms for the Modelling, Simulation and early Detection of diseases in Personalized Medicine). This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU Grant 603002 under the FP7 program and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant e and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad.Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Freire, M.; Lamprou, E.; Barrio, J.; Sánchez Martínez, F.; Benlloch Baviera, JM.... (2020). Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance. EJNMMI Physics. 7(1):1-17. https://doi.org/10.1186/s40658-020-00305-yS11771GLOBOCAN 2018. http://www.gco.iarc.fr/today/ datasources-methods. Accessed 26 Dec 2019.Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;2015:136–E359.Rawla P. Epidemiology of prostate cancer. 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MR-guided focused ultrasound: enhancement of intratumoral uptake of [H]-docetaxel in vivo. Phys Med Biol. 2010;55(24):–7399.Osborne JR, et al. Prostate-specific membrane antigen-based imaging. Seminars and Original Investigations: Urologic Oncology; 2012.Gonzalez AJ, et al. Organ-dedicated molecular imaging systems. IEEE Trans. Rad. Plasma Med. Scie. 2018;2:388.Majewski S, Proffitt J. Dedicated mobile high resolution prostate PET imager with an insertable transrectal probe. US Patent. 2010;7:858–944.Weinberg IN, et al. Flexible geometries for hand-held PET and SPECT cameras. IEEE NSS-MIC Conference Record. 2002.Weinberg I. Dedicated apparatus and method for positron emission tomography of the prostate. US Patent. 2006;7:102–34.Gonzalez-Montoro A, et al. Performance study of a large monolithic LYSO PET detector with accurate photon DOI using retroreflector layers. IEEE Trans. Rad. Plasma Med. Scie. 2017;1:229.Gonzalez-Montoro A, et al. Detector block performance based on a monolithic LYSO crystal using a novel signal multiplexing method. Nucl Instrum Meth. 2018;912:372-77.Gonzalez-Montoro A, et al. Performance comparison of large-area SiPM arrays suitable for gamma ray detectors. Biomed Phys Eng Express. 2019;5:045013.Seimetz M, et al. Correction algorithms for signal reduction in insensitive areas of a small gamma camera. J Instrum. 2014;9(05):C05042.Freire M, et al. Calibration of gamma ray impacts in monolithic-based detectors using Voronoi diagrams. In IEEE Transactions on Radiation and Plasma Medical Sciences. 2019. https://doi.org/10.1109/TRPMS.2019.2947716 .Jan S, et al. GATE: a simulation toolkit for PET and SPECT. Phys Med Biol. 2004;49:4543–61.Merlin T, et al. CASToR: a generic data organization and processing code framework for multi-modal and multi-dimensional tomographic reconstruction. Phys Med Biol. 2018;63(18):5505.Jacobs F, et al. A fast algorithm to calculate the exact radiological path through a pixel or voxel space. J Comput Inf Technol. 1998;6(1).Gonzalez-Montoro A, et al. Novel method to measure the intrinsic spatial resolution in PET detectors based on monolithic crystals. Nucl. Instrum. Meth. A. 2019;920:39(9).Vicente E, et al. Normalization in 3D PET: dependence on the activity distribution of the source. IEEE Nuclear Science Symposium Conference Record. 2006:M06–379.Soriano A, et al. Attenuation correction without transmission scan for the MAMMI breast PET. Nucl Instrum Meth A. 2011;648:S75.Yushkevich PA, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;34(3):1116-28.Gonzalez AJ, et al. Initial results of the MINDView PET insert inside the 3T mMR. IEEE Trans Rad Plasma Med Scie. 2019;3:343.Suti S, et al. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med. 2007;48(3):471–80.Watson C, et al. NEMA NU 2 performance tests for scanners with intrinsic radioactivity. J Nucl Med. 2004;45:822.National Electrical Manufacturers Association. NEMA NU 4-2008. Performance measurements of small animal positron emission tomographs. 2008.Gonzalez AJ, et al. A PET design based on SiPM and monolithic LYSO crystals: performance evaluation. IEEE Trans Nucl Scie. 2016;63:2471.Barbosa FG. Clinical perspectives of PSMA PET/MRI for prostate cancer. Clinics. 2018;73(Suppl 1):e586s.Uprimny C, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44(6):941-49.Koerber SA, et al. 68Ga-PSMA-11 PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med. 2017;58(12):1943–8

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins

Indexación: Web of ScienceThe evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative effect of local and global environmental selective pressures, genetic drift, and gene flow. We hypothesize that high gene flow among populations of Humboldt and Magellanic penguins limits local adaptation in MHC I and MHC II, and signatures of selection differ between markers, locations, and species. We evaluated the MHC I and II diversity using 454 next-generation sequencing of 100 Humboldt and 75 Magellanic penguins from seven different breeding colonies. Higher genetic diversity was observed in MHC I than MHC II for both species, explained by more than one MHC I loci identified. Large population sizes, high gene flow, and/or similar selection pressures maintain diversity but limit local adaptation in MHC I. A pattern of isolation by distance was observed for MHC II for Humboldt penguin suggesting local adaptation, mainly on the northernmost studied locality. Furthermore, trans species alleles were found due to a recent speciation for the genus or convergent evolution. High MHC I and MHC II gene diversity described is extremely advantageous for the long term survival of the species.http://onlinelibrary.wiley.com/doi/10.1002/ece3.2502/epd

Influence of Wheat Straw Pelletizing and Inclusion Rate in Dry Rolled or Steam-flaked Corn-based Finishing Diets on Characteristics of Digestion for Feedlot Cattle.

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p&lt;0.01) and total tract (p = 0.03) organic matter (OM) digestion. As expected, increasing wheat straw level from 7% to 14% decreased (p&lt;0.05) ruminal and total tract digestion of OM. Digestion of neutral detergent fiber (NDF) and starch, per se, were not affected (p&gt;0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p&gt;0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p&lt;0.01), and total-tract starch (p = 0.05) digestion were greater for ground than for pelleted wheat straw diets, resulting in a tendency for increased post-ruminal (p = 0.06) and total tract (p = 0.07) OM digestion. Pelleting wheat straw decreased (p&lt;0.01) ruminal pH, although ruminal volatile fatty acids (VFA) concentration and estimated methane were not affected (p≥0.27). Ruminal digestion of OM and starch, and post-ruminal and total tract digestion of OM, starch and N were greater (p&lt;0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal NDF digestion was greater (p = 0.02) for dry rolled than for steam-flaked corn, although total tract NDF digestion was unaffected (p = 0.94). Ruminal microbial efficiency and ruminal degradation of feed N were not affected (p&gt;0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p&lt;0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal pH and total VFA concentration were not affected (p≥ 0.16) by corn processing method. Compared with dry rolled corn, steam-flaked corn-based diets resulted in decreased acetate:propionate molar ratio (p = 0.02). It is concluded that at 7% or 14% straw inclusion rate, changes in physical characteristics of wheat straw brought about by pelleting negatively impact OM digestion of both steam-flaked and dry-rolled corn-based finishing diets. This effect is due to decreased post-ruminal starch digestion. Replacement of ground straw with pelleted straw also may decrease ruminal pH

Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production

Emergence of structure in mouse embryos: Structural Entropy morphometry applied to digital models of embryonic anatomy

We apply an information-theoretic measure to anatomical models of the Edinburgh Mouse Atlas Project. Our goal is to quantify the anatomical complexity of the embryo and to understand how this quantity changes as the organism develops through time. Our measure, Structural Entropy, takes into account the geometrical character of the intermingling of tissue types in the embryo. It does this by a mathematical process that effectively imagines a point-like explorer that starts at an arbitrary place in the 3D structure of the embryo and takes a random path through the embryo, recording the sequence of tissues through which it passes. Consideration of a large number of such paths yields a probability distribution of paths making connections between specific tissue types, and Structural Entropy is calculated from this (mathematical details are given in the main text). We find that Structural Entropy generally decreases (order increases) almost linearly throughout developmental time (4–18 days). There is one `blip’ of increased Structural Entropy across days 7–8: this corresponds to gastrulation. Our results highlight the potential for mathematical techniques to provide insight into the development of anatomical structure, and also the need for further sources of accurate 3D anatomical data to support analyses of this kind

Galactose Ingested with a High-Fat Beverage Increases Postprandial Lipemia Compared with Glucose but Not Fructose Ingestion in Healthy Men.

BACKGROUND: Fructose ingestion with a high-fat beverage increases postprandial lipemia when compared with glucose. It is unknown whether other sugars, such as galactose, also increase postprandial lipemia. OBJECTIVES: The objective was to assess whether galactose ingestion within a high-fat beverage increases postprandial lipemia relative to glucose or fructose. METHODS: Two experiments were conducted, which contrasted different test drinks under otherwise standardized conditions. In Experiment 1, 10 nonobese men (age: 22 ± 1 y; BMI, 23.5 ± 2.2 kg/2) ingested either galactose or glucose (0.75 g supplemented carbohydrate per⋅kilogram body mass) within a high-fat test drink (0.94 g fat per kilogram body mass). In Experiment 2, a separate group of 9 nonobese men (age: 26 ± 6 y; BMI: 23.5 ± 2.6 kg/m2) ingested either galactose or fructose (identical doses as those in Experiment 1) within the same high-fat test drink. Capillary blood was sampled before and at frequent intervals after ingestion of the test drinks for a 300-min period to determine plasma triacylglycerol, glucose, lactate, nonesterified fatty acid, and insulin concentrations. Paired t tests and 2-way, repeated-measures ANOVA were used to compare conditions within each experiment. RESULTS: The incremental AUC for triacylglycerol was greater following galactose ingestion compared with glucose (127 ± 59 compared with 80 ± 48 mmol⋅L-1 × 300 min, respectively; P = 0.04) but not compared with fructose (136 ± 74 compared with 133 ± 63 mmol⋅L-1 ×300 min, respectively; P = 0.91). Plasma lactate concentrations also increased to a greater extent with galactose compared with glucose ingestion (time-condition interaction: P < 0.001) but not fructose ingestion (time-condition interaction: P = 0.17). CONCLUSIONS: Galactose ingestion within a high-fat beverage exacerbates postprandial lipemia and plasma lactate concentrations compared with glucose but not fructose in nonobese men. These data suggest that galactose metabolism may be more similar to fructose than to glucose, providing a rationale to reassess the metabolic fate of galactose ingestion in humans. This trial was registered at clinicaltrials.gov as NCT03439878

Black shale deposition and early diagenetic dolomite cementation during Oceanic Anoxic Event 1: The mid-Cretaceous Maracaibo Platform, northwestern South America

Thin laterally continuous organic-rich dolomitic marlstones were deposited in the extended Late Aptian - Early Albian epicontinental sea of northwestern South America. These intervals are the proximal equivalents of thick hemipelagic black shale-ammonitic floatstone couplets, deposited in the distally stepped, differentially subsiding part of the Maracaibo Platform. The marlstones reflect the dynamic conditions resulting from orbital forcing mechanisms and can be genetically related to (1) minor sea-level changes, (2) proximal turnovers in marine productivity, and (3) sudden climate shifts affecting mid-Cretaceous shoaling upward, shallow marine, carbonate cyclicity. Therefore, the marlstones may well be linked to the multiple environmental perturbations collectively referred to as Oceanic Anoxic Event 1. The interstitial euhedral dolomite has a medium crystallinity, and exhibits unusual textural relations with framboidal pyrite and gypsum. The authigenic mineral assemblage also includes quartz, Ca-F apatite, and barite, which together with the chemical signals of dolomite, point to an unsteady climate regime. Bulk-rock biomarker parameters, rare earth element geochemistry, and iron speciation data point to widespread photic zone anoxia and transient shallow marine euxinia by the time of deposition, with climatic instability driving the delivery of oxidized detritus from the hinterlands. These conditions led to a schizohaline redox stratified environment favorable to dolomite precipitation. In such a depositional setting, the bio-utilization of Fe, Mn, and sulfur for organic matter respiration sustained elevated pore-water alkalinity and pH, and allowed for the pre-compactional growth of interstitial dolomite