Star-PAP RNA Binding Landscape Reveals Novel Role of Star-PAP in mRNA Metabolism That Requires RBM10-RNA Association

Star-PAP is a non-canonical poly(A) polymerase that selects mRNA targets for polyadenylation. Yet, genome-wide direct Star-PAP targets or the mechanism of specific mRNA recognition is still vague. Here, we employ HITS-CLIP to map the cellular Star-PAP binding landscape and the mechanism of global Star-PAP mRNA association. We show a transcriptome-wide association of Star-PAP that is diminished on Star-PAP depletion. Consistent with its role in the 3′-UTR processing, we observed a high association of Star-PAP at the 3′-UTR region. Strikingly, there is an enrichment of Star-PAP at the coding region exons (CDS) in 42% of target mRNAs. We demonstrate that Star-PAP binding de-stabilises these mRNAs indicating a new role of Star-PAP in mRNA metabolism. Comparison with earlier microarray data reveals that while UTR-associated transcripts are down-regulated, CDS-associated mRNAs are largely up-regulated on Star-PAP depletion. Strikingly, the knockdown of a Star-PAP coregulator RBM10 resulted in a global loss of Star-PAP association on target mRNAs. Consistently, RBM10 depletion compromises 3′-end processing of a set of Star-PAP target mRNAs, while regulating stability/turnover of a different set of mRNAs. Our results establish a global profile of Star-PAP mRNA association and a novel role of Star-PAP in the mRNA metabolism that requires RBM10-mRNA association in the cell.

United Arab Emirates will push global ambitions

Significance This will be Abu Dhabi’s first time on the Security Council since the 1980s, and it is promoting it as a marker of global leadership status, together with its ventures into space and hosting of key international events. Impacts The UAE will also intensify efforts to raise its global profile by hosting more cultural, sporting and related events. Abu Dhabi’s first UNSC presidency, which it takes up in March 2022, will allow it to set the agenda on key topics of interest. The UAE may take the opportunity to draw attention to its longstanding ‘Three-Island Dispute’ with Iran.

A “Hindu Mystic” or a “Harrovian Realist”? U.S., Australian, and Canadian Representations of Jawaharlal Nehru, 1947–1964

This article analyzes how officials from the U.S., Australia, and Canada represented Indian Prime Minister Jawaharlal Nehru’s psychology in diplomatic contexts between 1947 and 1964. Nehru was the representative of a newly sovereign state, whose people were often stereotyped as mystical, spiritual, and irrational. In this article, we show how Nehru was constructed as “irrational,” “primitive,” “effeminate,” and racially resentful by Western diplomats. He was, conversely, also seen as a “Harrovian realist” or “transplanted Englishman” with an attendant air of “superiority.” Cold War imperatives gave these ambivalent cultural and psychological projections a special salience, particularly as each confronted the implications of Nehru’s non-alignment and his global profile as a proponent of Third World nationalism. The ambivalent representations of Nehru that we trace within U.S., Australian, and Canadian foreign policy-making also reveal a shared belief in the “Anglosphere”—the purported transnational unity of white, English-speaking nations—was sustained beyond the decline of the British Empire. Nehru’s “Britishness” demonstrates how he could be tethered to the English-speaking world while simultaneously being seen as its irrational, non-white Other. This ambivalent connection helped to re-draw the boundaries of the transnational Anglosphere in the era of decolonization and to define Cold War assumptions about race, rationality, and foreign policy.

Performance of ultrasonography screening for breast cancer: a systematic review and meta-analysis

Background To provide a global profile of supplemental ultrasonography (US) screening after mammography (MAM) screening or primary US screening for breast cancers.Methods Electronic databases (PubMed, Scopus, Wed of Science, and Embase) were systematically searched to identify relevant studies published between January 2003 and May 2018. Only high-quality or fair-quality studies reporting any of the following performance values for supplemental or primary US screening were included: sensitivity, specificity, cancer detected rate (CDR), recall rate (RR), biopsy rate (BR), and proportions of invasive cancers (ProIC) or node-positive cancers (ProNPC) among screening-detected cancers.Results Twenty-three studies were included, including 12 supplemental US screening studies and 11 joint screening studies in which both MAM and US were used as primary screening methods. Meta-analyses revealed that supplemental US screening could detect 96% [95% confidential intervals (CIs): 82% to 99%] of occult breast cancers missed by MAM and identify 94% (95% CIs: 88% to 97%) of healthy women, with a CDR of 2.9/1000 (95%CIs: 1.8/1000 to 3.9/1000), RR of 8.6% (95%CIs: 4.8% to 13.5%), BR of 3.9% (95%CIs: 2.5% to 5.5%), ProICof 73.9% (95%CIs: 49.0% to 93.7%), and ProNPC of 72.6% (95%CIs: 51.9% to 90.0%). Compared with primary MAM screening, primary US screening led to the recall of significantly more women with positive screening results [1.2% (95%CIs:0.4% to 1.9%), P =0.004] and detected significantly more invasive cancers [20.2% (95%CIs: 7.2% to 33.1%), P = 0.002]. However, there were no significant differences for other performance measures between the two screening methods, including sensitivity, specificity, CDR, BR, and ProNPC.Conclusions Supplemental US screening could detect occult breast cancers missed by MAM, while primary US screening performances are comparable to those of primary MAM screening, but with a higher recall rate and a higher detection rate for invasive cancers.