On the extent and role of the small proteome in the parasitic eukaryote Trypanosoma brucei

Background: Although technical advances in genomics and proteomics research have yielded a better understanding of the coding capacity of a genome, one major challenge remaining is the identification of all expressed proteins, especially those less than 100 amino acids in length. Such information can be particularly relevant to human pathogens, such as Trypanosoma brucei, the causative agent of African trypanosomiasis, since it will provide further insight into the parasite biology and life cycle. Results: Starting with 993 T. brucei transcripts, previously shown by RNA-Sequencing not to coincide with annotated coding sequences (CDS), homology searches revealed that 173 predicted short open reading frames in these transcripts are conserved across kinetoplastids with 13 also conserved in representative eukaryotes. Mining mass spectrometry data sets revealed 42 transcripts encoding at least one matching peptide. RNAi-induced down-regulation of these 42 transcripts revealed seven to be essential in insect-form trypanosomes with two also required for the bloodstream life cycle stage. To validate the specificity of the RNAi results, each lethal phenotype was rescued by co-expressing an RNAi-resistant construct of each corresponding CDS. These previously non-annotated essential small proteins localized to a variety of cell compartments, including the cell surface, mitochondria, nucleus and cytoplasm, inferring the diverse biological roles they are likely to play in T. brucei. We also provide evidence that one of these small proteins is required for replicating the kinetoplast (mitochondrial) DNA. Conclusions: Our studies highlight the presence and significance of small proteins in a protist and expose potential new targets to block the survival of trypanosomes in the insect vector and/or the mammalian host

Cell type-specific expression and localization of cytochrome P450 isoforms in tridimensional aggregating rat brain cell cultures.

Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content. Double-immunolabeling revealed their presence in astrocytes, in neurons, and to a minor extent in oligodendrocytes, confirming the cell-specific localization of CYPs in the brain. These results together with the recently reported formation of an amiodarone metabolite following repeated exposure suggest that this cell culture system possesses some metabolic potential, most likely contributing to its high performance in neurotoxicological studies and support the use of this model in studying brain neurotoxicity involving mechanisms of toxication/detoxication

Land and cryosphere products from Suomi NPP VIIRS: overview and status

[1] The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument was launched in October 2011 as part of the Suomi National Polar-Orbiting Partnership (S-NPP). The VIIRS instrument was designed to improve upon the capabilities of the operational Advanced Very High Resolution Radiometer and provide observation continuity with NASA's Earth Observing System's Moderate Resolution Imaging Spectroradiometer (MODIS). Since the VIIRS first-light images were received in November 2011, NASA- and NOAA-funded scientists have been working to evaluate the instrument performance and generate land and cryosphere products to meet the needs of the NOAA operational users and the NASA science community. NOAA's focus has been on refining a suite of operational products known as Environmental Data Records (EDRs), which were developed according to project specifications under the National Polar-Orbiting Environmental Satellite System. The NASA S-NPP Science Team has focused on evaluating the EDRs for science use, developing and testing additional products to meet science data needs, and providing MODIS data product continuity. This paper presents to-date findings of the NASA Science Team's evaluation of the VIIRS land and cryosphere EDRs, specifically Surface Reflectance, Land Surface Temperature, Surface Albedo, Vegetation Indices, Surface Type, Active Fires, Snow Cover, Ice Surface Temperature, and Sea Ice Characterization. The study concludes that, for MODIS data product continuity and earth system science, an enhanced suite of land and cryosphere products and associated data system capabilities are needed beyond the EDRs currently available from the VIIRS

Tollip, an early regulator of the acute inflammatory response in the substantia nigra.

Tollip is a ubiquitously expressed protein, originally described as a modulator of the IL-1R/TLR-NF-κB signaling pathways. Although this property has been well characterized in peripheral cells, and despite some evidence of its expression in the central nervous system, the role of Tollip in neuroinflammation remains poorly understood. The present study sought to explore the implication of Tollip in inflammation in the substantia nigra pars compacta, the structure affected in Parkinson's disease. We first investigated Tollip distribution in the midbrain by immunohistochemistry. Then, we addressed TLR4-mediated response by intra-nigral injections of lipopolysaccharide (LPS), a TLR4 agonist, on inflammatory markers in Tollip knockout (KO) and wild-type (WT) mice. We report an unexpectedly high Tollip immunostaining in dopaminergic neurons of the mice brain. Second, intra-nigral injection of LPS led to increased susceptibility to neuroinflammation in Tollip KO compared to Tollip WT mice. This was demonstrated by a significant increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and interferon gamma (IFN-γ) messenger RNA (mRNA) in the midbrain of Tollip KO mice upon LPS injection. Consistently, brain rAAV viral vector transduction with a nuclear factor kappa B (NF-κB)-inducible reporter gene confirmed increased NF-κB activation in Tollip KO mice. Lastly, Tollip KO mice displayed higher inducible NO synthase (iNOS) production, both at the messenger and protein level when compared to LPS-injected WT mice. Tollip deletion also aggravated LPS-induced oxidative and nitrosative damages, as indicated by an increase of 8-oxo-2'-deoxyguanosine and nitrotyrosine immunostaining, respectively. Altogether, these findings highlight a critical role of Tollip in the early phase of TLR4-mediated neuroinflammation. As brain inflammation is known to contribute to Parkinson's disease, Tollip may be a potential target for neuroprotection

Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work

Air Corrosivity in U.S. Outdoor-Air-Cooled Data Centers is Similar to That in Conventional Data Centers

There is a concern that environmental-contamination caused corrosion may negatively affect Information Technology (IT) equipment reliability. Nineteen data centers in the United States and two in India were evaluated using Corrosion Classification Coupons (CCC) to assess environmental air quality as it may relate IT equipment reliability. The data centers were of two basic types: closed and outside-air cooled. A closed data center provides cool air to the IT equipment using air conditioning in which only a small percent age of the recirculation air is make-up air continuously supplied from outside to meet human health requirements. An outside-air cooled data center uses outside air directly as the primary source for IT equipment cooling. Corrosion measuring coupons containing copper and silver metal strips were placed in both closed and outside-air cooled data centers. The coupons were placed at each data center (closed and outside-air cooled types) with the location categorized into three groups: (1) Outside - coupons sheltered, located near or at the supply air inlet, but located before any filtering, (2) Supply - starting just after initial air filtering continuing inside the plenums and ducts feeding the data center rooms, and (3) Inside located inside the data center rooms near the IT equipment. Each coupon was exposed for thirty days and then sent to a laboratory for a corrosion rate measurement analysis. The goal of this research was to investigate whether gaseous contamination is a concern for U.S. data center operators as it relates to the reliability of IT equipment. More specifically, should there be an increased concern if outside air for IT equipment cooling is used To begin to answer this question limited exploratory measurements of corrosion rates in operating data centers in various locations were undertaken. This study sought to answer the following questions: (1) What is the precision of the measurements (2) What are the approximate statistical distributions of copper and silver corrosion rates in the sampled data centers(3) To what extent are copper and silver corrosion measurements related (4) What is the relationship of corrosion rate measurements between outside-air cooled data centers compared to closed data centers (5) How do corrosivity measurements relate to IT equipment failure rates The data from our limited sample size suggests that most United States data center operators should not be concerned with environmental gaseous contamination causing high IT equipment failure rates even when using outside-air cooling. The research team recommends additional basic research on how environmental conditions, specifically gaseous contamination, affect electronic equipment reliability

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

Managing Performance Throughout Periods of Travel

Understanding the impact of travel on physical performance is an increasing area of interest for the strength and conditioning practitioner. Previous research surrounding the effect of travel on the physiology of an athlete has focused on sleep. Of concern to coaches and athletes are strategies to help attenuate any detrimental impact of travel on subsequent performance. The aim of this article is to provide informative practical guidelines for before, during, and after travel that can be implemented by coaches and athletes. The key coping strategies addressed include timed light exposure; managing sleep deprivation and nutritional recommendations

Utilization of duckweed as fish meal replacement in common carp (Cyprinus carpio)

Duckweed, the family Lemnaceae, comprises a group of around 40 different aquatic flowering plant species. They can grow very fast, producing higher biomasses compared to terrestrial plants (up to 79 t DM ha-1 a-1, Leng et al. 1995). Furthermore, they are very efficient in uptake of nitrogen and phosphorous and are producing protein of high quality (Stadtlander et al. 2019). Protein contents usually range between 25 to 35% of DM (dry matter) but have been reported to be as high as 45% of DM. Duckweed (Spirodela polyrhiza) has been successfully grown on diluted cow slurry and been fed to rainbow trout fry (Stadtlander et al. 2019). Common carp (Cyprinus carpio) is among the most important cultured fish species in the world, with a production of 4.13 mio t in 2017, and cyprinids (carp-like fish) in general contribute around 50% of global aquaculture fish production. In this study, we tested two different duckweed (S. polyrhiza) meals, one dried (DWD) and one fermented (DWF), in three different concentrations in the diet of carp fry and compared results to a duckweed free control (C)

Characterization of the K2-38 planetary system: Unraveling one of the densest planets known to date

.-- Toledo-Padrón, B. et al.Context. An accurate characterization of the known exoplanet population is key to understanding the origin and evolution of planetary systems. Determining true planetary masses through the radial velocity (RV) method is expected to experience a great improvement thanks to the availability of ultra-stable echelle spectrographs. Aims. We took advantage of the extreme precision of the new-generation echelle spectrograph ESPRESSO to characterize the transiting planetary system orbiting the G2V star K2-38 located at 194 pc from the Sun with V 11.4. This system is particularly interesting because it could contain the densest planet detected to date. Methods. We carried out a photometric analysis of the available K2 photometric light curve of this star to measure the radius of its two known planets, K2-38b and K2-38c, with Pb = 4.01593 ± 0.00050 d and Pc = 10.56103 ± 0.00090 d, respectively. Using 43 ESPRESSO high-precision RV measurements taken over the course of 8 months along with the 14 previously published HIRES RV measurements, we modeled the orbits of the two planets through a Markov chain Monte Carlo analysis, significantly improving their mass measurements. Results. Using ESPRESSO spectra, we derived the stellar parameters, Teff = 5731 ± 66, log g = 4.38 ± 0.11 dex, and [Fe/H] = 0.26 ± 0.05 dex, and thus the mass and radius of K2-38, Ma = 1.03-0.02+0.04 MaS and Ra = 1.06-0.06+0.09 RaS. We determine new values for the planetary properties of both planets. We characterize K2-38b as a super-Earth with RP = 1.54 ± 0.14 RaS and Mp = 7.3-1.0+1.1 MaS, and K2-38c as a sub-Neptune with RP = 2.29 ± 0.26 RaS and Mp = 8.3-1.3+1.3 MaS. Combining the radius and mass measurements, we derived a mean density of ρp = 11.0-2.8+4.1 g cm-3 for K2-38b and ρp = 3.8-1.1+1.8 g cm-3 for K2-38c, confirming K2-38b as one of the densest planets known to date. Conclusions. The best description for the composition of K2-38b comes from an iron-rich Mercury-like model, while K2-38c is better described by a rocky-model with H2 envelope. The maximum collision stripping boundary shows how giant impacts could be the cause for the high density of K2-38b. The irradiation received by each planet places them on opposite sides of the radius valley. We find evidence of a long-period signal in the RV time-series whose origin could be linked to a 0.25-3 MJ planet or stellar activity.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737