Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs

We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants

Playing Games with Tito:Designing Hybrid Museum Experiences for Critical Play

This article brings together two distinct, but related perspectives on playful museum experiences: Critical play and hybrid design. The article explores the challenges involved in combining these two perspectives, through the design of two hybrid museum experiences that aimed to facilitate critical play with/in the collections of the Museum of Yugoslavia and the highly contested heritage they represent. Based on reflections from the design process as well as feedback from test users, we describe a series of challenges: Challenging the norms of visitor behaviour, challenging the role of the artefact, and challenging the curatorial authority. In conclusion, we outline some possible design strategies to address these challenges

Genotype Prevalence and Risk Factors for Severe Clinical Adenovirus Infection, United States 2004-2006

Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus

The US Program in Ground-Based Gravitational Wave Science: Contribution from the LIGO Laboratory

Recent gravitational-wave observations from the LIGO and Virgo observatories have brought a sense of great excitement to scientists and citizens the world over. Since September 2015,10 binary black hole coalescences and one binary neutron star coalescence have been observed. They have provided remarkable, revolutionary insight into the "gravitational Universe" and have greatly extended the field of multi-messenger astronomy. At present, Advanced LIGO can see binary black hole coalescences out to redshift 0.6 and binary neutron star coalescences to redshift 0.05. This probes only a very small fraction of the volume of the observable Universe. However, current technologies can be extended to construct "3rd Generation" (3G) gravitational-wave observatories that would extend our reach to the very edge of the observable Universe. The event rates over such a large volume would be in the hundreds of thousands per year (i.e. tens per hour). Such 3G detectors would have a 10-fold improvement in strain sensitivity over the current generation of instruments, yielding signal-to-noise ratios of 1000 for events like those already seen. Several concepts are being studied for which engineering studies and reliable cost estimates will be developed in the next 5 years

More than making ends meat: Ridge Ruin faunal exploitation and social organization

Archaeological faunal remains reflect daily subsistence, social organization, and ceremonial behaviors among humans. In the prehistoric American Southwest, social organization was intimately tied to ceremonial power and ritual knowledge. By examining ritually important taxa and evaluating the nature of differential access to faunal resources, faunal remains offer insight into Sinagua culture and social organization. Ridge Ruin is a Sinagua site occupied from A.D. 1070 to 1175 in the San Francisco Peaks area of Northern Arizona. The site features include a 20-25 room pueblo, a plaza, and two ballcourts as well as the famous burial of the Magician, the richest burial ever found in the Southwest. These communal structures and the Magician’s burial indicate that Ridge Ruin was a ceremonial central place. Faunal remains from the site suggest that, unlike other sites in the San Francisco Peaks area, Ridge Ruin hosted communal feasts. The presence of ceremonially important taxa further suggests that Sinagua leaders relied on ritual knowledge to maintain status. Other taxa show that Ridge Ruin’s occupants maintained daily subsistence regimens. The Sinagua used faunal resources for daily subsistence, to supplement ceremonial practices, and to conduct feasts which served to simultaneously unite local communities and establish social hierarchy. Faunal data from this thesis are provided in a supplemental document

Mechanisms of Non-Enzymatic Peptide Bond Formation: Thioester and Transamidation Routes

The reaction mechanisms employed during non-ribosomal peptide (amide) synthesis in the non-ribosomal modular enzyme complex and in the enzyme glutaminyl cyclase were also used for spontaneous peptide (amide) synthesis in a buffered, abiotic solution. Analytical analyses revealed that spontaneous peptide (amide) bond formation occurred under mild prebiotic conditions during both the thioester-based production of phenylalanine peptides and peptidyl thioesters, and the spontaneous cyclization of glutamine t-butyl ester (Gln-tbe) into pyroglutamic acid t-butyl ester. Internal standard-based quantitative MS determined that 4.9 x 10-5 sec-1 was the rate constant for spontaneous Gln-tbe cyclization in imidazole buffer, pH 7, at 50°C, and that the enzyme glutaminyl cyclase exhibited a rate enhancement of 1.0 x 106 over the non-enzymatic rate. Interestingly, the rate of Gln-tbe loss at neutral pH was significantly affected by t-butyl ester hydrolysis. The rate of amino acid t-butyl hydrolysis has not been reported; however, in this study the experimental rate of Asn-tbe was determined to be 1.5 x 10-5 sec-1 . Hydrolysis of a t-butyl ester group readily occurs under acidic conditions and the amino acid t-butyl ester hydrolysis at neutral pH could be a result of intramolecular hydrogen bonding. Arrhenius and Eyring plots determined the energy of activation, activation enthalpy, and activation entropy to be 9.5 x 10-4 J mor1, 9.5 x 10-4 J mor1, and -1.5 x 10-5 J K-1 mor1, respectively. Both cellular and prebiotic environments undergo constant changes in reaction conditions, and a detailed kinetic investigation revealed that the rate constant for Gln-tbe degradation was not affected by buffer type (imidazole, citrate), buffer concentration (0 to20 mM), or pH level (4 to 7). In addition, the reaction rate increased linearly as temperature was increased (30 to 60°C). The correlation between enzymatic and non-enzymatic peptide (amide) bond formation under mild prebiotic conditions presented the transamidation and thioester routes as possible methods for ancestral peptide (amide) bond formation