Distinct Biological Network Properties between the Targets of Natural Products and Disease Genes

We show that natural products target proteins with a high number of protein−protein functional interactions (high biological network connectivity) and that these protein targets have higher network connectivity than disease genes. This feature may facilitate disruption of essential biological pathways, resulting in competitor death. This result also suggests that additional sources of small molecules will be required to discover drugs targeting the root causes of human disease in the future.Chemistry and Chemical Biolog

Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Altres ajuts: Cancer Prevention and Research Institute of Texas (CPRIT), Core Facility Support Award (CPRIT-RP180672, R1313, 1R01GM138781-01); NIH (CA125123, RR024574); Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (P50HD103555); BCM start-up funds; Albert and Margaret Alkek Foundation; McNair Medical Institute; Robert and Janice McNair Foundation; BCM Seed Funding (1P20CA221731-01A1); National Institute of General Medical Sciences (R01 GM120033); Cynthia and Antony Petrello Endowment; Mark A. Wallace Endowment; McKnight Foundation; Dana Foundation; BCM Computational and Integrative Biomedical Research Center seed grant.Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis

The Development of the NNBAR Experiment

The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with a sensitivity improvement of three orders of magnitude compared to the last such search. This paper describes progress towards a conceptual design report for NNBAR. The design of a moderator, neutron reflector, beamline, shielding and annihilation detector is reported. The simulations used form part of a model which will be used for optimisation of the experiment design and quantification of its sensitivity.Comment: 30 pages, 26 figures, accepted for publication in Journal of Instrumentation (JINST

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Neutrino Target-of-Opportunity Observations with Space-based and Suborbital Optical Cherenkov Detectors

Cosmic-ray accelerators capable of reaching ultra-high energies are expected to also produce very-high energy neutrinos via hadronic interactions within the source or its surrounding environment. Many of the candidate astrophysical source classes are either transient in nature or exhibit flaring activity. Using the Earth as a neutrino converter, suborbital and space-based optical Cherenkov detectors, such as EUSO-SPB2 and POEMMA, will be able to detect upward-moving extensive air showers induced by decay tau-leptons generated from cosmic tau neutrinos with energies ∼10 PeV and above. Both EUSO-SPB2 and POEMMA will be able to quickly repoint, enabling rapid response to astrophysical transient events. we calculate the transient sensitivity and sky coverage for both EUSO-SPB2 and POEMMA, accounting for constraints imposed by the Sun and the Moon on the observation time. We also calculate both detectors\u27 neutrino horizons for a variety of modeled astrophysical neutrino fluences. We find that both EUSO-SPB2 and POEMMA will achieve transient sensitivities at the level of modeled neutrino fluences for nearby sources. We conclude with a discussion of the prospects of each mission detecting at least one transient event for various modeled astrophysical neutrino sources

Observation of ELVES with Mini-EUSO telescope on board the International Space Station

Mini-EUSO is a detector observing the Earth in the ultraviolet band from the International Space Station through a nadir-facing window, transparent to the UV radiation, in the Russian Zvezda module. Mini-EUSO main detector consists in an optical system with two Fresnel lenses and a focal surface composed of an array of 36 Hamamatsu Multi-Anode Photo-Multiplier tubes, for a total of 2304 pixels, with single photon counting sensitivity. The telescope also contains two ancillary cameras, in the near infrared and visible ranges, to complement measurements in these bandwidths. The instrument has a field of view of 44 degrees, a spatial resolution of about 6.3 km on the Earth surface and of about 4.7 km on the ionosphere. The telescope detects UV emissions of cosmic, atmospheric and terrestrial origin on different time scales, from a few s upwards. On the fastest timescale of 2.5 s, Mini EUSO is able to observe atmospheric phenomena as Transient Luminous Events and in particular the ELVES, which take place when an electromagnetic wave generated by intra-cloud lightning interacts with the ionosphere, ionizing it and producing apparently superluminal expanding rings of several 100 km and lasting about 100 s. These highly energetic fast events have been observed to be produced in conjunction also with Terrestrial Gamma-Ray Flashes and therefore a detailed study of their characteristics (speed, radius, energy ...) is of crucial importance for the understanding of these phenomena. In this paper we present the observational capabilities of ELVE detection by Mini-EUSO and specifically the reconstruction and study of ELVE characteristics

Neutrino Target-of-Opportunity Observations with Space-based and Suborbital Optical Cherenkov Detectors

Cosmic-ray accelerators capable of reaching ultra-high energies are expected to also produce very-high energy neutrinos via hadronic interactions within the source or its surrounding environment. Many of the candidate astrophysical source classes are either transient in nature or exhibit flaring activity. Using the Earth as a neutrino converter, suborbital and space-based optical Cherenkov detectors, such as POEMMA and EUSO-SPB2, will be able to detect upward-moving extensive air showers induced by decaying tau-leptons generated from cosmic tau neutrinos with energies ∼10 PeV and above. Both EUSO-SPB2 and POEMMA will be able to quickly repoint, enabling rapid response to astrophysical transient events. We calculate the transient sensitivity and sky coverage for both EUSO-SPB2 and POEMMA, accounting for constraints imposed by the Sun and the Moon on the observation time. We also calculate both detectors\u27 neutrino horizons for a variety of modeled astrophysical neutrino fluences. We find that both EUSO-SPB2 and POEMMA will achieve transient sensitivities at the level of modeled neutrino fluences for nearby sources. We conclude with a discussion of the prospects of each mission detecting at least one transient event for various modeled astrophysical neutrino sources

Simulation studies for the Mini-EUSO detector

Mini-EUSO is a mission of the JEM-EUSO program flying onboard the International Space Station since August 2019. Since the first data acquisition in October 2019, more than 35 sessions have been performed for a total of 52 hours of observations. The detector has been observing Earth at night-time in the UV range and detected a wide variety of transient sources all of which have been modeled through Monte Carlo simulations. Mini-EUSO is also capable of detecting meteors and potentially space debris and we performed simulations for such events to estimate their impact on future missions for cosmic ray science from space. We show here examples of the simulation work done in this framework to analyze the Mini-EUSO data. The expected response of Mini-EUSO with respect to ultra high energy cosmic ray showers has been studied. The efficiency curve of Mini-EUSO as a function of primary energy has been estimated and the energy threshold for Cosmic Rays has been placed to be above 10$^{21}$ eV. We compared the morphology of several transient events detected during the mission with cosmic ray simulations and excluded that they can be due to cosmic ray showers. To validate the energy threshold of the detector, a system of ground based flashers is being used for end-to-end calibration purposes. We therefore implemented a parameterization of such flashers into the JEM-EUSO simulation framework and studied the response of the detector with respect to such sources

Measurement of UV light emission of the nighttime Earth by Mini-EUSO for space-based UHECR observations

The JEM-EUSO (Joint Experiment Missions for Extreme Universe Space Observatory) program aims at the realization of the ultra-high energy cosmic ray (UHECR) observation using wide field of view fluorescence detectors in orbit. Ultra-violet (UV) light emission from the atmosphere such as airglow and anthropogenic light on the Earth\u27s surface are the main background for the space-based UHECR observations. The Mini-EUSO mission has been operated on the International Space Station (ISS) since 2019 which is the first space-based experiment for the program. The Mini-EUSO instrument consists of a 25 cm refractive optics and the photo-detector module with the 2304-pixel array of the multi-anode photomultiplier tubes. On the nadir-looking window of the ISS, the instrument is capable of continuously monitoring a ~300 km x 300 km area. In the present work, we report the preliminary result of the measurement of the UV light in the nighttime Earth using the Mini-EUSO data downlinked to the ground. We mapped UV light distribution both locally and globally below the ISS obit. Simulations were also made to characterize the instrument response to diffuse background light. We discuss the impact of such light on space-based UHECR observations and the Mini-EUSO science objectives