A complex pathway for 3 ' processing of the yeast U3 snoRNA

Mature U3 snoRNA in yeast is generated from the 3′-extended precursors by endonucleolytic cleavage followed by exonucleolytic trimming. These precursors terminate in poly(U) tracts and are normally stabilised by binding of the yeast La homologue, Lhp1p. We report that normal 3′ processing of U3 requires the nuclear Lsm proteins. On depletion of any of the five essential proteins, Lsm2–5p or Lsm8p, the normal 3′-extended precursors to the U3 snoRNA were lost. Truncated fragments of both mature and pre-U3 accumulated in the Lsm-depleted strains, consistent with substantial RNA degradation. Pre-U3 species were co-precipitated with TAP-tagged Lsm3p, but the association with spliced pre-U3 was lost in strains lacking Lhp1p. The association of Lhp1p with pre-U3 was also reduced on depletion of Lsm3p or Lsm5p, indicating that binding of Lhp1p and the Lsm proteins is interdependent. In contrast, a tagged Sm-protein detectably co-precipitated spliced pre-U3 species only in strains lacking Lhp1p. We propose that the Lsm2–8p complex functions as a chaperone in conjunction with Lhp1p to stabilise pre-U3 RNA species during 3′ processing. The Sm complex may function as a back-up to stabilise 3′ ends that are not protected by Lhp1p

Markup cyclicality, competition and liquidity constraints: Evidence from a panel VAR analysis

© 2020 The Author. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The main scope of this study is to investigate the effects of competition and liquidity constraints on the cyclical behaviour of the markup ratio. In particular, 79 2-digit NACE Rev.2 sectors across the UK manufacturing and services industry over 2008-2017 are taken into account in order to observe markup cyclicality and whether pricing decisions are significantly influenced by the degree of competition and liquidity restrictions. A panel VAR framework is used to take into account the presence of cross-section dependence and heterogeneity amongst the constituent regressors of the model. The empirical results provide the following significant insights: (i) the markup ratio across the UK sectors follows a countercyclical pattern, (ii) concentrated sectors tend to charge countercyclical price-cost margins as they attempt to increase their market share in normal periods, and (iii) sectors with liquidity constrained firms charge countercyclical markups in order to substitute lack of funding with additional revenue. Complementary findings also suggest that more profitable firms charge procyclical markup ratios, thus validating the predatory pricing strategy in more concentrated sectors.Peer reviewe

Sequence-aware watermark design for soft IP embedded processors

This paper describes a design approach for incorporating sequence-aware watermarks in soft IP embedded processors. The influence of watermark sequence parameters on detection, area and power overheads is examined, and consequently a sequence-aware method for incorporating sequence-aware watermarks in soft IP Embedded Processors is proposed. The intrinsic parameters of sequences, such as the activity factor and the overlapping factor are introduced, and their impact on correlation results is demonstrated. Measurement experimental results from FPGA and ASIC validate the design approach and demonstrate the resulting IP protection and subsequent costs for constrained embedded processors. Results presented in this paper show that the tradeoff occurs between the watermark robustness against third party IP attacks and hardware implementation costs. The analysis of this tradeoff is provided and an application specific watermark implementation is proposed

Nuclear fate of yeast snoRNA is determined by co-transcriptional Rnt1 cleavage

Small nucleolar RNA (snoRNA) are conserved and essential non-coding RNA that are transcribed by RNA Polymerase II (Pol II). Two snoRNA classes, formerly distinguished by their structure and ribonucleoprotein composition, act as guide RNA to target RNA such as ribosomal RNA, and thereby introduce specific modifications. We have studied the 5'end processing of individually transcribed snoRNA in S. cerevisiae to define their role in snoRNA biogenesis and functionality. Here we show that pre-snoRNA processing by the endonuclease Rnt1 occurs co-transcriptionally with removal of the m7G cap facilitating the formation of box C/D snoRNA. Failure of this process causes aberrant 3'end processing and mislocalization of snoRNA to the cytoplasm. Consequently, Rnt1-dependent 5'end processing of box C/D snoRNA is critical for snoRNA-dependent methylation of ribosomal RNA. Our results reveal that the 5'end processing of box C/D snoRNA defines their distinct pathway of maturation

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs