Exploring Vitamin B1 Cycling and Its Connections to the Microbial Community in the North Atlantic Ocean

Vitamin B1 (thiamin) is an essential coenzyme for all cells. Recent findings from experimental cell biology and genome surveys have shown that thiamin cycling by plankton is far more complex than was previously understood. Many plankton cells cannot produce thiamin (are auxotrophic) and obligately require an exogenous source of thiamin or one or more of 5 different thiamin-related compounds (TRCs). Despite this emerging evidence for the evolution among plankton of complex interactions related to thiamin, the influence of TRCs on plankton community structure and productivity are not understood. We report measurements of three dissolved TRCs 4-amino-5-aminomethyl-2-methylpyrimidine (AmMP), 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylic acid (cHET), and 4-methyl-5-thiazoleethanol (HET) that have never before been assayed in seawater. Here we characterize them alongside other TRCs that were measured previously [thiamin and 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP)], in depth profiles from a latitudinal transect in the north Atlantic in March 2018. TRC concentrations ranged from femptomolar to picomolar. Surface depletion relative to a maximum near the bottom of the euphotic zone and low concentrations at deeper depths were consistent features. Our observations suggest that when bacterial abundance and production are low, TRC concentrations approach a steady state where TRC production and consumption terms are balanced. Standing stocks of TRCs also appear to be positively correlated with bacterial production. However, near the period of peak biomass in the accumulation phase of a bloom we observed an inverse relationship between TRCs and bacterial production, coincident with an increased abundance of Flavobacteria that comparative genomics indicates could be vitamin B1 auxotrophs. While these observations suggest that the dissolved pool of TRCs is often at steady state, with TRC production and consumption balanced, our data suggests that bloom induced shifts in microbial community structure and activity may cause a decoupling between TRC production and consumption, leading to increased abundances of some populations of bacteria that are putatively vitamin B1 auxotrophs

Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Constraining Non-Standard Interactions of the Neutrino with Borexino

We use the Borexino 153.6 ton.year data to place constraints on non-standard neutrino-electron interactions, taking into account the uncertainty in the 7Be solar neutrino flux, and backgrounds due to 85Kr and 210Bi beta-decay. We find that the bounds are comparable to existing bounds from all other experiments. Further improvement can be expected in Phase II of Borexino due to the reduction in the 85Kr background.Comment: 21 pages, 16 pdf figures, 2 tables. Analysis updated including the uncertainty in sin^2\theta_{23}. Accepted in JHE

Primary Extra-gastrointestinal Stromal Tumor of Retroperitoneum

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. More rarely neoplasms with histology and immunohistochemistry similar to GISTs may occur outside the gastrointestinal tract (omentum, mesentery and retroperitoneum) and are so-called Extra-gastrointestinal Stromal Tumors (EGISTs). EGISTs arising in the retroperitoneum are extremely rare: to date, only 58 cases have been reported in the literature. Case Report We herein report a case of a primary EGIST of the retroperitoneum surgically treated. The pre-operative radiological evaluation showed a retroperitoneal mass, placed in left paravertebral region. Results Morphological and immunohistochemical features led to a diagnosis of extra-gastrointestinal stromal tumor (intermediate-low risk form). Conclusions As a result of the rarity of reports of primary EGISTs of retroperitoneum we need to analyze the data of reported cases in order to gain a better understanding about the pathogenesis, prognosis and optimal treatment of this disease

Laboratory evidence for proton energization by collisionless shock surfing

Charged particles can be accelerated to high energies by collisionless shock waves in astrophysical environments, such as supernova remnants. By interacting with the magnetized ambient medium, these shocks can transfer energy to particles. Despite increasing efforts in the characterization of these shocks from satellite measurements at Earth’s bow shock as well as powerful numerical simulations, the underlying acceleration mechanism or a combination thereof is still widely debated. Here we show that astrophysically relevant super-critical quasi-perpendicular magnetized collisionless shocks can be produced and characterized in the laboratory. We observe the characteristics of super-criticality in the shock profile as well as the energization of protons picked up from the ambient gas to hundreds of kiloelectronvolts. Kinetic simulations modelling the laboratory experiment identified shock surfing as the proton acceleration mechanism. Our observations not only provide direct evidence of early-stage ion energization by collisionless shocks but also highlight the role played by this particular mechanism in energizing ambient ions to feed further stages of acceleration. Furthermore, our results open the door to future laboratory experiments investigating the possible transition to other mechanisms, when increasing the magnetic field strength, or the effect that induced shock front ripples could have on acceleration processes

Detailed characterization of a laboratory magnetized supercritical collisionless shock and of the associated proton energization

Collisionless shocks are ubiquitous in the Universe and are held responsible for the production of nonthermal particles and high-energy radiation. In the absence of particle collisions in the system, theory shows that the interaction of an expanding plasma with a pre-existing electromagnetic structure (as in our case) is able to induce energy dissipation and allow shock formation. Shock formation can alternatively take place when two plasmas interact, through microscopic instabilities inducing electromagnetic fields that are able in turn to mediate energy dissipation and shock formation. Using our platform in which we couple a rapidly expanding plasma induced by high-power lasers (JLF/Titan at LLNL and LULI2000) with high-strength magnetic fields, we have investigated the generation of a magnetized collisionless shock and the associated particle energization. We have characterized the shock as being collisionless and supercritical. We report here on measurements of the plasma density and temperature, the electromagnetic field structures, and the particle energization in the experiments, under various conditions of ambient plasma and magnetic field. We have also modeled the formation of the shocks using macroscopic hydrodynamic simulations and the associated particle acceleration using kinetic particle-in-cell simulations. As a companion paper to Yao et al. [Nat. Phys. 17, 1177-1182 (2021)], here we show additional results of the experiments and simulations, providing more information to allow their reproduction and to demonstrate the robustness of our interpretation of the proton energization mechanism as being shock surfing acceleration