Expand+Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors

Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code

Molecular Electroporation and the Transduction of Oligoarginines

Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.Comment: 15 pages, 5 figure

Primary productivity evolution during the latest Holocene (2,000 yr) off Oporto (Portuguese Margin)

European Geosciences Union General Assembly 2008 (EGU 2008), Vienna, Austria, April 13-18, 200

Millennial-scale deep ocean ventilation and sea-surface variability during the last four glacial cycles : a new assessment for the Northern Hemisphere ice-sheet growth

AGU Fall Meeting, S. Francisco (USA), 19-14 December 2007, Suppl., Abstract PP44B-0

Precipitation Maxima and upwelling trends at the NAO Southern Pole during the last millenium

European Geosciences Union General Assembly 2009 (EGU 2009), Vienna, Austria, April 19-24, 200

Theory of d-density wave viewed from a vertex model and its implications

The thermal disordering of the $d$-density wave, proposed to be the origin of the pseudogap state of high temperature superconductors, is suggested to be the same as that of the statistical mechanical model known as the 6-vertex model. The low temperature phase consists of a staggered order parameter of circulating currents, while the disordered high temperature phase is a power-law phase with no order. A special feature of this transition is the complete lack of an observable specific heat anomaly at the transition. There is also a transition at a even higher temperature at which the magnitude of the order parameter collapses. These results are due to classical thermal fluctuations and are entirely unrelated to a quantum critical point in the ground state. The quantum mechanical ground state can be explored by incorporating processes that causes transitions between the vertices, allowing us to discuss quantum phase transition in the ground state as well as the effect of quantum criticality at a finite temperature as distinct from the power-law fluctuations in the classical regime. A generalization of the model on a triangular lattice that leads to a 20-vertex model may shed light on the Wigner glass picture of the metal-insulator transition in two-dimensional electron gas. The power-law ordered high temperature phase may be generic to a class of constrained systems and its relation to recent advances in the quantum dimer models is noted.Comment: RevTex4, 10 pages, 11 figure

Surfactant protein D increases fusion of Mycobacterium tuberculosis- containing phagosomes with lysosomes in human macrophages

Lung surfactant protein D (SP-D) binds to Mycobacterium tuberculosis surface lipoarabinomannan and results in bacterial agglutination, reduced uptake, and inhibition of growth in human macrophages. Here we show that SP-D limits the intracellular growth of bacilli in macrophages by increasing phagosome-lysosome fusion but not by generating a respiratory burst

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Data report: early Pleistocene calcareous nannofossils, IODP Expedition 339, Site U1387

We present a revision and refinement of semiquantitative analyses of calcareous nannofossil assemblages in early Pleistocene samples from Holes U1387A and U1387C recovered toward the eastern end of the Faro Drift (36°48.3210N, 7°43.1321W) during Integrated Ocean Drilling Program Expedition 339, Mediterranean Outflow (November 2011–January 2012). The record is characterized by intervals very rich in calcareous nannofossils that are in general moderately to well preserved. On the other hand, the record contains an interval directly above the youngest dolomite layer in Section 339-U1387C-19R-4 (~0.7 m) where no coccoliths were preserved. The new stratigraphic constraints of events such as the lowest occurrence (LO) of large Gephyrocapsa, the highest occurrence (HO) of Calcidiscus macintyrei (1.66 Ma), the LO of medium-sized Gephyrocapsa group, and the HO of Discoaster brouweri (1.95 Ma) allow better interpretation of the isotope stratigraphy applied to this interval.FCT Portugal projects CCMAR:UID/Multi/04326/2019info:eu-repo/semantics/publishedVersio

Silage Additives

SummaryThrough the years a number of materials have been suggested for incorporation into silage to improve the preservation of nutrients, nutritive value or palatability of the silage. In addition to being called additives, some of these materials are referred to as preservatives or conditioners. Especially during recent years, many commercial preparations have been made available to the farmer, who naturally wonders whether their use will be economically sound. Thorough testing of these materials would require that each be used at several levels, with forages at various moisture contents, under different storage conditions and with many kinds of silage. Therefore, it is highly impractical, if not impossible, to attempt thorough testing of each. However, there is sufficient understanding of the process of silage formation, the requirements for preservation of its nutrients, and the principle of action of the ingredients used in the various additives to make sound decisions as to whether they might be economically worth-while. There is, in addition to this understanding, a rather large amount of research which has been done and reported, and this in its summation justifies the use of what is already known to make judgments. In order to make an appropriate judgment, one should be able to answer certain questions, as follows:1.What happens during the process of silage formation? 2. What does the additive being considered contain and what do its ingredients do?3. What is the value of the silage and what is the cost of the additive?4. How much preservation beyond that afforded by good ensiling procedures can one logically expect from the additive?5.Can one expect to improve the feeding value of a silage by using a particular additive?The discussion that follows deals with these questions