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

Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

Equal fitness paradigm explained by a trade-off between generation time and energy production rate

Most plant, animal and microbial species of widely varying body size and lifestyle are nearly equally fit as evidenced by their coexistence and persistence through millions of years. All organisms compete for a limited supply of organic chemical energy, derived mostly from photosynthesis, to invest in the two components of fitness: survival and production. All organisms are mortal because molecular and cellular damage accumulates over the lifetime; life persists only because parents produce offspring. We call this the equal fitness paradigm. The equal fitness paradigm occurs because: (1) there is a trade-off between generation time and productive power, which have equal-but-opposite scalings with body size and temperature; smaller and warmer organisms have shorter lifespans but produce biomass at higher rates than larger and colder organisms; (2) the energy content of biomass is essentially constant, ~22.4 kJ g−1 dry body weight; and (3) the fraction of biomass production incorporated into surviving offspring is also roughly constant, ~10–50%. As organisms transmit approximately the same quantity of energy per gram to offspring in the next generation, no species has an inherent lasting advantage in the struggle for existence. The equal fitness paradigm emphasizes the central importance of energy, biological scaling relations and power–time trade-offs in life history, ecology and evolution

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Alcohol devaluation has dissociable effects on distinct components of alcohol behaviour

Rationale Substance-related behaviour is often viewed as an appetitive behaviour, motivated by the reinforcing effects of the drug. However, there are various indices of substance motivation (e.g. attentional bias, behavioural economic demand, craving) and it is unclear how these are related or whether they play an important role in all types of substance-related behaviour. Objectives (1) To determine the effect of alcohol devaluation on several indices of alcohol motivation and goal-directed and cue-elicited alcohol behaviour. (2) To investigate which components of motivation mediate any effect of devaluation on behaviour. Methods Sixty-two social drinkers gave baseline measures of alcohol craving, behavioural economic demand and choice for alcohol vs. soft drink. Participants tasted alcohol which was either unadulterated (control) or adulterated with a bitter solution (devaluation) before craving and demand were measured again. Alcohol choice was assessed in several phases: extinction (evaluating goal-directed behaviour), in the presence of drink cues (Pavlovian-to-instrumental transfer (PIT, cue-elicited behaviour)), and reacquisition. Attentional bias (AB) was measured by tracking eye movements towards the drink cues during novel PIT trials where both cues were presented. Finally, consumption was evaluated in a taste test. Results Alcohol devaluation reduced alcohol-related demand, AB, alcohol choice in all phases, and consumption. Alcohol cues presented during PIT increased alcohol choice above baseline irrespective of devaluation. AB and demand for alcohol fully mediated the effect of devaluation on alcohol choice during extinction, AB fully mediated the effect on cue-elicited (specific PIT) alcohol choice and alcohol consumption. Conclusions Alcohol behaviour in social drinkers is largely sensitive to devaluation, i.e. governed by current motivational value of the drug (suggesting goal-directed behaviour). However, a dissociable form of stimulus control can also drive alcohol-seeking independently of drug value (specific PIT). Mediation analyses suggests that AB may play a paradoxical role in both forms of alcohol seeking and consumption

CMS Data Processing Workflows during an Extended Cosmic Ray Run

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Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run

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Commissioning of the CMS high-level trigger with cosmic rays

This is the Pre-print version of the Article. The official published version of the paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS High-Level Trigger (HLT) is responsible for ensuring that data samples with potentially interesting events are recorded with high efficiency and good quality. This paper gives an overview of the HLT and focuses on its commissioning using cosmic rays. The selection of triggers that were deployed is presented and the online grouping of triggered events into streams and primary datasets is discussed. Tools for online and offline data quality monitoring for the HLT are described, and the operational performance of the muon HLT algorithms is reviewed. The average time taken for the HLT selection and its dependence on detector and operating conditions are presented. The HLT performed reliably and helped provide a large dataset. This dataset has proven to be invaluable for understanding the performance of the trigger and the CMS experiment as a whole.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Identification and Filtering of Uncharacteristic Noise in the CMS Hadron Calorimeter

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