The Timurid Legacy: A Reaffirmation and a Reassessment

The Timurids have universally been acknowledged by medieval Islamic cultural historians as representing the pinnacle of patronage of the arts and letters, notably poetry, calligraphy, painting and manuscript illumination, as well as architecture. They also patronized entire areas that are just beginning to come to light with new research and that further underscore the important role that this dynasty of Turko-Mongolian origin played in the cultural history of the eastern Islamic world. The e..

Poly(A)-tail profiling reveals an embryonic switch in translational control

Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other ‘housekeeping’ proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.National Institutes of Health (U.S.) (Grant GM067031)National Institutes of Health (U.S.) (Medical Scientist Training Program Fellowship T32GM007753

Poly(A)-tail profiling reveals an embryonic switch in translational control

Poly(A) tails enhance the stability and translation of most eukaryotic mRNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here, we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other “housekeeping” proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiency in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization

Extensive alternative polyadenylation during zebrafish development

The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3′ untranslated regions (3′ UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-seq reads substantially increased and improved existing 3′ UTR annotations, resulting in confidently identified 3′ UTRs for >79% of the annotated protein-coding genes in zebrafish. mRNAs from most zebrafish genes undergo alternative CPA, with those from more than a thousand genes using different dominant 3′ UTRs at different stages. These included one of the poly(A) polymerase genes, for which alternative CPA reinforces its repression in the ovary. 3′ UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3′ UTRs are highly expressed in the ovary, yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3′ UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3′ UTRs provide a resource for studying gene regulation during vertebrate development.National Institutes of Health (U.S.) (Grant GM067031)

The Anatomy of a Regicide Attempt: Shāhrukh, the Ḥurūfīs, and the Timurid Intellectuals in 830/1426–27

This article provides a contextual analysis of the assassination attempt on the Timurid ruler Shahrukh’s life on 21 February 1427 in Herat. According to the contemporary Timurid chroniclers, Ahmad-i Lur, a Hurufi by profession, tried to kill Shahrukh

The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes

Background: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. Results: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. Conclusions: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length.National Institutes of Health (U.S.) (Grant K99GM102319)National Institutes of Health (U.S.) (Grant T32GM007753)National Institutes of Health (U.S.) (Grant R01GM067031)National Institutes of Health (U.S.) (Grant R35GM118135)Natural Sciences and Engineering Research Council of Canada (Discovery Grant

INTRAORAL AIR PRESSURE MEASURES IN ADULTS

The effect of age, gender, and repeated measures on intraoral air pressure (P0) was examined. Sixty adults comprised of ten males and ten females in each of three age groups (i.e., 20 to 39, 40 to 59, and 60 to 83 years) participated. P0 was assessed during voiceless stop plosive /p/ productions in repeated vowel/consonant syllables. The three medial plosives of a seven syllable train were averaged to comprise a token. Five tokens were obtained and averaged for each of three trials. Thus each participant contributed 105 syllables and a subsequent three P0s for analyses. There was no statistically significant difference in P0 as a function of age or gender (p>.05). These findings support the conception that P0 remains stable throughout adulthood and is not dependent on gender. Differences in repeated measures of P0 attained statistical significance (p = .03), however the mean differences between trials (.23 cm H20) were negligible and deemed to be clinically insignificant. Thus, across a short sampling session, P0 is a relatively stable measurement and does not change as a function of age or gender

Determinants of property rights in Poland and Ukraine: the polity or politicians?

North (1994) famously remarked that ‘it is the polity that defines and enforces property rights’. This paper traces the development of property rights in Poland and Ukraine and explores their divergence over the past three centuries using North's framework of economic calculation. In each country, the distribution of political power and political institutions had a profound impact on property rights. Indeed, while it was the Polish polity that defined the evolution of property rights from 1386 to 1795 and then from 1989 onward, due to diffusion of power, it was Ukrainian politicians that controlled the destiny of property rights for most of Ukraine's history. This situation has not changed despite the Maidan revolution in Ukraine, and recent moves in Poland show how tenuous property rights are in the face of political opposition

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell