An RNA structure-mediated, posttranscriptional model of human α-1-antitrypsin expression

Protein and mRNA expression are in most cases poorly correlated, which suggests that the posttranscriptional regulatory program of a cell is an important component of gene expression. This regulatory network is still poorly understood, including how RNA structure quantitatively contributes to translational control. We present here a series of structural and functional experiments that together allow us to derive a quantitative, structure-dependent model of translation that accurately predicts translation efficiency in reporter assays and primary human tissue for a complex and medically important protein, α-1-antitrypsin. Our model demonstrates the importance of accurate, experimentally derived RNA structural models partnered with Kozak sequence information to explain protein expression and suggests a strategy by which α-1-antitrypsin expression may be increased in diseased individuals

Mechanisms underlying reduced weight gain in intestinal fatty acid-binding protein (IFABP) null mice

Intestinal- fatty acid binding protein (IFABP; FABP2) is a 15-kDa intracellular protein abundantly present in the cytosol of the small intestinal (SI) enterocyte. High-fat (HF) feeding of IFABP-/- mice resulted in reduced weight gain and fat mass relative to wild-type (WT) mice. Here, we examined intestinal properties that may underlie the observed lean phenotype of high fat-fed IFABP-/- mice. No alterations in fecal lipid content were found, suggesting that the IFABP-/- mice are not malabsorbing dietary fat. However, the total excreted fecal mass, normalized to food intake, was increased for the IFABP-/- mice relative to WT mice. Moreover, intestinal transit time was more rapid in the IFABP-/- mice. IFABP-/- mice displayed a shortened average villus length, a thinner muscularis layer, reduced goblet cell density, and reduced Paneth cell abundance. The number of proliferating cells in the crypts of IFABP-/- mice did not differ from that of WT mice, suggesting that the blunt villi phenotype is not due to alterations in proliferation. IFABP-/- mice were observed to have altered expression of genes and proteins related to intestinal structure, while immunohistochemical analyses revealed increased staining for markers of inflammation. Taken together, these studies indicate that the ablation of IFABP, coupled with high-fat feeding, leads to changes in gut motility and morphology, which likely contribute to the relatively leaner phenotype occurring at the whole-body level. Thus, IFABP is likely involved in dietary lipid sensing and signaling, influencing intestinal motility, intestinal structure, and nutrient absorption, thereby impacting systemic energy metabolism.Fil: Lackey, Atreju I.. Rutgers University; Estados Unidos. Rutgers Center for Lipid Research; Estados UnidosFil: Chen, Tina. Rutgers University; Estados UnidosFil: Zhou, Yin X.. Rutgers University; Estados UnidosFil: Bottasso Arias, Natalia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Doran, Justine M.. Rutgers University; Estados UnidosFil: Zacharisen, Sophia M.. Rutgers University; Estados UnidosFil: Gajda, Angela M.. Rutgers University; Estados Unidos. Rutgers Center for Lipid Research; Estados UnidosFil: Jonsson, William O.. Rutgers University; Estados Unidos. Rutgers Center for Lipid Research; Estados UnidosFil: Córsico, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Anthony, Tracy G.. Rutgers University; Estados Unidos. Rutgers Center for Lipid Research; Estados UnidosFil: Joseph, Laurie B.. Rutgers Center for Lipid Research; Estados Unidos. Rutgers University; Estados UnidosFil: Storch, Judith. Rutgers University; Estados Unidos. Rutgers Center for Lipid Research; Estados Unido

Quantitative prediction of variant effects on alternative splicing in MAPT using endogenous pre-messenger RNA structure probing

Splicing is highly regulated and is modulated by numerous factors. Quantitative predictions for how a mutation will affect precursor mRNA (pre-mRNA) structure and downstream function are particularly challenging. Here, we use a novel chemical probing strategy to visualize endogenous precursor and mature MAPT mRNA structures in cells. We used these data to estimate Boltzmann suboptimal structural ensembles, which were then analyzed to predict consequences of mutations on pre-mRNA structure. Further analysis of recent cryo-EM structures of the spliceosome at different stages of the splicing cycle revealed that the footprint of the Bact complex with pre-mRNA best predicted alternative splicing outcomes for exon 10 inclusion of the alternatively spliced MAPT gene, achieving 74% accuracy. We further developed a β-regression weighting framework that incorporates splice site strength, RNA structure, and exonic/intronic splicing regulatory elements capable of predicting, with 90% accuracy, the effects of 47 known and 6 newly discovered mutations on inclusion of exon 10 of MAPT. This combined experimental and computational framework represents a path forward for accurate prediction of splicing-related disease-causing variants

Evaluation of the genus Thiothrix Winogradsky 1888 (Approved Lists 1980) emend. Aruga et al. 2002: reclassification of Thiothrix disciformis to Thiolinea disciformis gen. nov., comb. nov., and of Thiothrix flexilis to Thiofilum flexile gen. nov., comb nov., with emended description of Thiothrix.

Thiothrix is the type genus of the Thiotrichaceae in the Thiotrichales of the 21 Gammaproteobacteria, comprising nine species of sulfur-oxidising filamentous Bacteria, 22 which are variously autotrophic, heterotrophic or have mixed metabolic modes. Within the 23 genus, 4 species show 16S rRNA gene identities lower the Yarza threshold for the rank of 24 genus (94.5 %) – Thiothrix disciformis, Thiothrix flexilis, Thiothrix defluvii and Thiothrix 25 eikelboomii – as they show no affiliation to extant genera, a polyphasic study was undertaken 26 including biochemical, physiological and genomic properties and phylogeny based on the 27 16S rRNA gene (rrs), recombination protein A (RecA), polynucleotide nucleotidyltransferase 28 (Pnp), translation initiation factor IF-2 (InfB), glyceraldehyde-3-phosphate dehydrogenase 29 (GapA), glutaminyl-tRNA synthetase (GlnS), elongation factor EF-G (FusA) and 30 concatamers of 53 ribosomal proteins encoded by rps, rpl and rpm operons, all of which 31 support the reclassification of these species. We thus propose Thiolinea gen. nov. and 32 Thiofilum gen. nov. for which the type species are Thiolinea disciformis gen. nov., comb. 33 nov. and Thiofilum flexile gen. nov., comb. nov. We also propose that these genera are each 34 circumscribed into novel families Thiolinaceae fam. nov. and Thiofilaceae fam. nov., and 35 that Leucothrix and Cocleimonas are circumscribed into Leucotrichaceae fam. nov. and 36 provide emended descriptions of Thiothrix and Thiotrichaceae

Toyo Ito

This project was designed to allow us as a group to research a famous architect and begin to understand what influenced his style of work and how he grew through his years. By looking at several of Toyo Ito\u27s works and his background, we began to develop a deeper connection and understanding to why and how he became the designer he currently is. The analysis of this architect allowed us to be influenced by his work and pushed us to develop our own styles of architectural design further with the exposure to new information and techniques

Method for forming microspheres for encapsulation of nuclear waste.

Microspheres for nuclear waste storage are formed by gelling droplets containing the waste in a gelation fluid, transferring the gelled droplets to a furnace without the washing step previously used, and heating the unwashed gelled droplets in the furnace under temperature or humidity conditions that result in a substantially linear rate of removal of volatile components therefrom. Fuel particles were also produced using this method

PHEV real world driving cycle energy and fuel and consumption reduction potential for connected and automated vehicles

This paper presents real-world driving energy and fuel consumption results for the second-generation Chevrolet Volt plug-in hybrid electric vehicle (PHEV). A drive cycle, local to Michigan Technological University, was designed to mimic urban and highway driving test cycles in terms of distance, transients and average velocity, but with significant elevation changes to establish an energy intensive real-world driving cycle for assessing potential energy savings for connected and automated vehicle (CAV) control. The investigation began by establishing baseline and repeatability of energy consumption at various battery states of charge. It was determined that drive cycle energy consumption under a randomized set of boundary conditions varied within 3.6% of mean energy consumption regardless of initial battery state of charge. After completing 30 baseline drive cycles, a design for six sigma (DFSS) L18 array was designed to look at sensi-tivity of a range of parameters to energy consumption as related to connected and automated vehicles to target highest return on engineering development effort. The parameters explored in the DFSS array that showed the most sensitivity, in order of importance, were battery state of charge, vehicle mass, propulsion system thermal conditioning, HVAC setting and driver behavior. Each of these areas are explored for energy savings and discussed briefly in the context of CAV control opportunity for energy savings potential