Entropic contributions to the splicing process

It has been recently argued that the depletion attraction may play an important role in different aspects of the cellular organization, ranging from the organization of transcriptional activity in transcription factories to the formation of the nuclear bodies. In this paper we suggest a new application of these ideas in the context of the splicing process, a crucial step of messanger RNA maturation in Eukaryotes. We shall show that entropy effects and the resulting depletion attraction may explain the relevance of the aspecific intron length variable in the choice of the splice-site recognition modality. On top of that, some qualitative features of the genome architecture of higher Eukaryotes can find an evolutionary realistic motivation in the light of our model.Comment: 15 pages, 6 figures. Extended version, accepted for publication in Physical Biolog

Cosmic acceleration from asymmetric branes

We consider a single 3-brane sitting in between two different five dimensional spacetimes. On each side of the brane, the bulk is a solution to Gauss-Bonnet gravity, although the bare cosmological constant, funda mental Planck scale, and Gauss-Bonnet coupling can differ. This asymmetry leads to weighted junction conditions across the brane and interesting brane cosmology. We focus on two special cases: a generalized Randall-Sundrum model without any Gauss-Bonnet terms, and a stringy model, without any bare cosmological constants, and positive Gauss-Bonnet coupling. Even though we assume there is no vacuum energy on the brane, we find late time de Sitter cosmologies can occur. Remarkably, in certain parameter regions, this acceleration is preceded by a period of matter/radiation domination, with $H^2 \propto \rho$, all the way back to nucleosynthesis.Comment: Version appearing in CQ

Ex-vivo changes in amino acid concentrations from blood stored at room temperature or on ice: implications for arginine and taurine measurements

Background: Determination of the plasma concentrations of arginine and other amino acids is important for understanding pathophysiology, immunopathology and nutritional supplementation in human disease. Delays in processing of blood samples cause a change in amino acid concentrations, but this has not been precisely quantified. We aimed to describe the concentration time profile of twenty-two amino acids in blood from healthy volunteers, stored at room temperature or on ice.Methods: Venous blood was taken from six healthy volunteers and stored at room temperature or in an ice slurry. Plasma was separated at six time points over 24 hours and amino acid levels were determined by high-performance liquid chromatography.Results: Median plasma arginine concentrations decreased rapidly at room temperature, with a 6% decrease at 30 minutes, 25% decrease at 2 hours and 43% decrease at 24 hours. Plasma ornithine increased exponentially over the same period. Plasma arginine was stable in blood stored on ice, with a < 10% change over 24 hours. Plasma taurine increased by 100% over 24 hours, and this change was not prevented by ice. Most other amino acids increased over time at room temperature but not on ice.Conclusion: Plasma arginine concentrations in stored blood fall rapidly at room temperature, but remain stable on ice for at least 24 hours. Blood samples taken for the determination of plasma amino acid concentrations either should be placed immediately on ice or processed within 30 minutes of collection

Alert classification for the ALeRCE broker system: The real-time stamp classifier

We present a real-time stamp classifier of astronomical events for the Automatic Learning for the Rapid Classification of Events broker, ALeRCE. The classifier is based on a convolutional neural network, trained on alerts ingested from the Zwicky Transient Facility (ZTF). Using only the science, reference, and difference images of the first detection as inputs, along with the metadata of the alert as features, the classifier is able to correctly classify alerts from active galactic nuclei, supernovae (SNe), variable stars, asteroids, and bogus classes, with high accuracy (~94%) in a balanced test set. In order to find and analyze SN candidates selected by our classifier from the ZTF alert stream, we designed and deployed a visualization tool called SN Hunter, where relevant information about each possible SN is displayed for the experts to choose among candidates to report to the Transient Name Server database. From 2019 June 26 to 2021 February 28, we have reported 6846 SN candidates to date (11.8 candidates per day on average), of which 971 have been confirmed spectroscopically. Our ability to report objects using only a single detection means that 70% of the reported SNe occurred within one day after the first detection. ALeRCE has only reported candidates not otherwise detected or selected by other groups, therefore adding new early transients to the bulk of objects available for early follow-up. Our work represents an important milestone toward rapid alert classifications with the next generation of large etendue telescopes, such as the Vera C. Rubin Observatory.The authors acknowledge support from the National Agency of Research and Development’s Millennium Science Initiative through grant IC12009, awarded to the Millennium Institute of Astrophysics (RC, ER, CV, FF, PE, GP, FEB, IR, PSS, GC, SE, Ja, EC, DR, DRM, MC) and from the National Agency for Research and Development (ANID) grants: BASAL Center of Mathematical Modelling AFB-170001 (CV, FF, IR, ECN, CS, ECI) and Centro de Astrofísica y Tecnologías Afines AFB170002 (FEB, PSS, MC); FONDECYT Regular #1171678 (PE), #1200710 (FF), #1190818(FEB), #1200495 (FEB), #1171273 (MC), #1201793(GP); FONDECYT Postdoctorado #3200250 (PSS); FONDECYT Iniciación #11191130 (CV); Magíster Nacional 2019 #22190947 (ER). This work was funded in part by project CORFO 10CEII-9157 Inria Chile (PS). The authors acknowledge financial support from the Spanish Ministry of Science, Innovation, and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019- 027683 (LG)

Mutational Biases and Selective Forces Shaping the Structure of Arabidopsis Genes

Recently features of gene expression profiles have been associated with structural parameters of gene sequences in organisms representing a diverse set of taxa. The emerging picture indicates that natural selection, mediated by gene expression profiles, has a significant role in determining genic structures. However the current situation is less clear in plants as the available data indicates that the effect of natural selection mediated by gene expression is very weak. Moreover, the direction of the patterns in plants appears to contradict those observed in animal genomes. In the present work we analized expression data for >18000 Arabidopsis genes retrieved from public datasets obtained with different technologies (MPSS and high density chip arrays) and compared them with gene parameters. Our results show that the impact of natural selection mediated by expression on genes sequences is significant and distinguishable from the effects of regional mutational biases. In addition, we provide evidence that the level and the breadth of gene expression are related in opposite ways to many structural parameters of gene sequences. Higher levels of expression abundance are associated with smaller transcripts, consistent with the need to reduce costs of both transcription and translation. Expression breadth, however, shows a contrasting pattern, i.e. longer genes have higher breadth of expression, possibly to ensure those structural features associated with gene plasticity. Based on these results, we propose that the specific balance between these two selective forces play a significant role in shaping the structure of Arabidopsis genes

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

Endostatin expression in a pancreatic cell line is modulated by a TNFα-dependent elastase

Endostatin, an inhibitor of angiogenesis, is a 20 kDa fragment of the basement membrane protein, collagen XVIII. The formation of endostatin relies upon the action of proteases on collagen XVIII. TNFα, produced by activated macrophages, is a multifunctional proinflammatory cytokine with known effects on endothelial function. We postulated that TNFα may modulate the activities of proteases and thus regulate endostatin formation in pancreatic cells. Collagen XVIII/endostatin mRNA was expressed in one pancreatic cell line, SUIT-2, but not in BxPc-3. The 20 kDa endostatin was found in the cell-conditioned medium of SUIT-2 cells. Precursor forms only were found in the cells. Exogenous endostatin was degraded by cellular lysates of SUIT-2 cells. Elastase activity was found in cell extracts but not the cell-conditioned media of SUIT-2 cells. Incubation of SUIT-2 cells with TNFα increased intracellular elastase activity and also increased secretion of endostatin into the medium. We conclude that endostatin is released by SUIT-2 cells and that increases in intracellular elastase, induced by TNFα, are correlated with increased secretion. Endostatin is however susceptible to degradation by intracellular proteases and if tissue injury accompanies inflammation, endostatin may be degraded, allowing angiogenesis to occur