Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

Calibration and first results of relative humidity sensor MEDA HS onboard M2020 rover

MEDA HS is the relative humidity sensor on the Mars 2020 Perseverance rover provided by theFinnish Meteorological Institute (FMI). The sensor is a part of Mars Environmental DynamicAnalyzer (MEDA), a suite of environmental sensors provided by Centro de Astrobiología in Madrid,Spain. MEDA HS, along with METEO-H in ExoMars 2022 surface platform, is a successor of REMS-Hon board Curiosity.Calibration of relative humidity (RH) instruments for Mars missions is challenging due to the rangeof RH (from 0 to close to 100%) and temperature conditions (from about -90 ºC to + 22 ºC) thatneed to be simulated in the lab. Thermal gradients in different parts of the system need to be wellknown and controlled to ensure reliable reference RH readings. For MEDA HS the calibration testshave been performed for different models of MEDA HS in three Martian humidity simulatorlaboratories: FMI laboratory, Michigan Mars Environmental Chamber (MMEC) and DLR PASLAB(Planetary Analog Simulation Laboratory). MEDA HS flight model was tested at FMI together with flight spare and ground reference models inlow pressure dry CO2 gas from +22ºC to -70ºC and in saturation conditions from -40ºC down to-70ºC. Further, the MEDA HS flight model final calibration is complemented by calibration datatransferred from an identical ground reference model which has gone through rigorous testingalso after the flight model delivery. During the test campaign at DLR PASLAB that started inAutumn 2020, MEDA HS has been calibrated over the full relative humidity scale between -70 to-40ºC in CO2 in the pressure ranges from 5.5 to 9.5 hPa, representative of Martian surfaceatmospheric pressure. The results can be extrapolated to higher and lower temperatures.In this presentation the final flight calibration and performance of the MEDA HS will be presentedtogether with first results expected from the surface of Mars by the Perseverance rover

The Mars Environmental Dynamics Analyzer, MEDA. A Suite of Environmental Sensors for the Mars 2020 Mission

86 pags., 49 figs., 24 tabs.NASA’s Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ∼1.5 m and ∼0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.This work has been funded by the Spanish Ministry of Economy and Competitiveness, through the projects No. ESP2014-54256-C4-1-R (also -2-R, -3-R and -4-R) and AYA2015-65041-P; Ministry of Science, Innovation and Universities, projects No. ESP2016-79612-C3-1-R (also -2-R and -3-R), ESP2016-80320-C2-1-R, RTI2018-098728-B-C31 (also -C32 and -C33) and RTI2018-099825-B-C31; Instituto Nacional de Técnica Aeroespacial; Ministry of Science and Innovation’s Centre for the Development of Industrial Technology; Grupos Gobierno Vasco IT1366-19; and European Research Council Consolidator Grant no 818602. The US co-authors performed their work under sponsorship from NASA’s Mars 2020 project, from the Game Changing Development program within the Space Technology Mission Directorate and from the Human Exploration and Operations Directorate

Gene Ontology annotations and resources.

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources

Dust Devil Frequency of Occurrence and Radiative Effects at Jezero Crater, Mars, as Measured by MEDA Radiation and Dust Sensor (RDS)

The Mars Environmental Dynamics Analyzer, onboard the Perseverance rover, is a meteorological station that is operating on Mars and includes, among other sensors, the radiometer Radiation and Dust Sensor (RDS). From RDS irradiance observations, a total of 374 dust devils (DDs) were detected for the first 365 sols of the mission (Ls = 6°–182°), which along with wind and pressure measurements, we estimated a DD frequency of formation at Jezero between 1.3 and 3.4 DD km −2 sol −1 (increasing as we move from spring into summer). This frequency is found to be smaller than that estimated at the Spirit or Pathfinder landing sites but much greater than that derived at InSight landing site. The maximum in DD frequency occurs between 12:00 and 13:00 local true solar time, which is when the convective heat flux and lower planetary boundary layer IR heating are both predicted to peak in Jezero crater. DD diameter, minimum height, and trajectory were studied showing (a) an average diameter of 29 m (or a median of 25 m) and a maximum and minimum diameter of 132 ± 63.4 and 5.6 ± 5.5 m; (b) an average minimum DD height of 231 m and a maximum minimum-height of 872 m; and (c) the DD migration direction is in agreement with wind measurements. For all the cases, DDs decreased the UV irradiance, while at visible or near-IR wavelengths both increases and decreases were observed. Contrary to the frequency of formation, these results indicate similar DD characteristics in average for the studied period

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

The diverse meteorology of Jezero crater over the first 250 sols of Perseverance on Mars

ASA’s Perseverance rover’s Mars Environmental Dynamics Analyzer is collecting data at Jezero crater, characterizing the physical processes in the lowest layer of the Martian atmosphere. Here we present measurements from the instrument’s first 250 sols of operation, revealing a spatially and temporally variable meteorology at Jezero. We find that temperature measurements at four heights capture the response of the atmospheric surface layer to multiple phenomena. We observe the transition from a stable night-time thermal inversion to a daytime, highly turbulent convective regime, with large vertical thermal gradients. Measurement of multiple daily optical depths suggests aerosol concentrations are higher in the morning than in the afternoon. Measured wind patterns are driven mainly by local topography, with a small contribution from regional winds. Daily and seasonal variability of relative humidity shows a complex hydrologic cycle. These observations suggest that changes in some local surface properties, such as surface albedo and thermal inertia, play an influential role. On a larger scale, surface pressure measurements show typical signatures of gravity waves and baroclinic eddies in a part of the seasonal cycle previously characterized as low wave activity. These observations, both combined and simultaneous, unveil the diversity of processes driving change on today’s Martian surface at Jezero crater