A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs

BACKGROUND: In recent years, intensive computational efforts have been directed towards the discovery of promoter motifs that correlate with mRNA expression profiles. Nevertheless, it is still not always possible to predict steady-state mRNA expression levels based on promoter signals alone, suggesting that other factors may be involved. Other genic regions, in particular 3' UTRs, which are known to exert regulatory effects especially through controlling RNA stability and localization, were less comprehensively investigated, and deciphering regulatory motifs within them is thus crucial. RESULTS: By analyzing 3' UTR sequences and mRNA decay profiles of Saccharomyces cerevisiae genes, we derived a catalog of 53 sequence motifs that may be implicated in stabilization or destabilization of mRNAs. Some of the motifs correspond to known RNA-binding protein sites, and one of them may act in destabilization of ribosome biogenesis genes during stress response. In addition, we present for the first time a catalog of 23 motifs associated with subcellular localization. A significant proportion of the 3' UTR motifs is highly conserved in orthologous yeast genes, and some of the motifs are strikingly similar to recently published mammalian 3' UTR motifs. We classified all genes into those regulated only at transcription initiation level, only at degradation level, and those regulated by a combination of both. Interestingly, different biological functionalities and expression patterns correspond to such classification. CONCLUSION: The present motif catalogs are a first step towards the understanding of the regulation of mRNA degradation and subcellular localization, two important processes which - together with transcription regulation - determine the cell transcriptome

Stable Secretaries

We define and study a new variant of the secretary problem. Whereas in the classic setting multiple secretaries compete for a single position, we study the case where the secretaries arrive one at a time and are assigned, in an on-line fashion, to one of multiple positions. Secretaries are ranked according to talent, as in the original formulation, and in addition positions are ranked according to attractiveness. To evaluate an online matching mechanism, we use the notion of blocking pairs from stable matching theory: our goal is to maximize the number of positions (or secretaries) that do not take part in a blocking pair. This is compared with a stable matching in which no blocking pair exists. We consider the case where secretaries arrive randomly, as well as that of an adversarial arrival order, and provide corresponding upper and lower bounds.Comment: Accepted for presentation at the 18th ACM conference on Economics and Computation (EC 2017

High Entropy Random Selection Protocols

In this paper, we construct protocols for two parties that do not trust each other, to generate random variables with high Shannon entropy. We improve known bounds for the trade off between the number of rounds, length of communication and the entropy of the outcome

High Entropy Random Selection Protocols

We study the two party problem of randomly selecting a common string among all the strings of length n. We want the protocol to have the property that the output distribution has high Shannon entropy or high min entropy, even when one of the two parties is dishonest and deviates from the protocol. We develop protocols that achieve high, close to n, Shannon entropy and simultaneously min entropy close to n/2. In the literature the randomness guarantee is usually expressed in terms of “resilience”. The notion of Shannon entropy is not directly comparable to that of resilience, but we establish a connection between the two that allows us to compare our protocols with the existing ones. We construct an explicit protocol that yields Shannon entropy n- O(1) and has O(log ∗n) rounds, improving over the protocol of Goldreich et al. (SIAM J Comput 27: 506–544, 1998) that also achieves this entropy but needs O(n) rounds. Both these protocols need O(n2) bits of communication. Next we reduce the number of rounds and the length of communication in our protocols. We show the existence, non-explicitly, of a protocol that has 6 rounds, O(n) bits of communication and yields Shannon entropy n- O(log n) and min entropy n/ 2 - O(log n). Our protocol achieves the same Shannon entropy bound as, also non-explicit, protocol of Gradwohl et al. (in: Dwork (ed) Advances in Cryptology—CRYPTO ‘06, 409–426, Technical Report , 2006), however achieves much higher min entropy: n/ 2 - O(log n) versus O(log n). Finally we exhibit a very simple 3-round explicit “geometric” protocol with communication length O(n). We connect the security parameter of this protocol with the well studied Kakey

A cross-country psychiatric screening of ICD-11 disorders specifically associated with stress in Kenya, Nigeria and Ghana

Background The Global Forum for Health Research, with the support of the World Health Organization, highlighted the need to prioritize mental health research in Africa. The introduction of revised descriptions of Posttraumatic Stress Disorder (PTSD) and Adjustment Disorder, along with new diagnoses of Complex PTSD and Prolonged Grief Disorder, in the ICD-11 creates a need for additional national level epidemiological studies on the prevalence of stress-related disorders.Methods The prevalence rates of these four ICD-11 stress disorders were assessed in three African countries including Nigeria (N = 1006), Kenya (N = 1018), and Ghana (N = 500). Participants completed disorder-specific measures for each disorder.Findings Across the entire sample, the current prevalence rate of probable Adjustment Disorder was 8.4% (95% C.I. = 7.4%, 9.6%), probable PTSD was 18.6% (95% C.I. = 17.2, 20.2%), probable Complex PTSD was 15.9% (95% C.I. = 14.5%, 17.4%) and probable Prolonged Grief Disorder was 3.7% (95% C.I. = 3.1%, 4.5%).Interpretation The results are applicable primarily to well-educated urban and suburban adults in these African countries. Results indicated that Adjustment Disorder, PTSD, and CPTSD are highly prevalent in these three African countries. There is now a pressing need to develop culturally sensitive interventions to enable recovery from these conditions

Metabolic networking in Brunfelsia calycina petals after flower opening

Brunfelsia calycina flowers change colour from purple to white due to anthocyanin degradation, parallel to an increase in fragrance and petal size. Here it was tested whether the production of the fragrant benzenoids is dependent on induction of the shikimate pathway, or if they are formed from the anthocyanin degradation products. An extensive characterization of the events taking place in Brunfelsia flowers is presented. Anthocyanin characterization was performed using ultraperfomance liquid chromatography–quadrupole time of flight–tandem mass specrometry (UPLC-QTOF-MS/MS). Volatiles emitted were identified by headspace solid phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS). Accumulated proteins were identified by 2D gel electrophoresis. Transcription profiles were characterized by cross-species hybridization of Brunfelsia cDNAs to potato cDNA microarrays. Identification of accumulated metabolites was performed by UPLC-QTOF-MS non-targeted metabolite analysis. The results include characterization of the nine main anthocyanins in Brunfelsia flowers. In addition, 146 up-regulated genes, 19 volatiles, seven proteins, and 17 metabolites that increased during anthocyanin degradation were identified. A multilevel analysis suggests induction of the shikimate pathway. This pathway is the most probable source of the phenolic acids, which in turn are precursors of both the benzenoid and lignin production pathways. The knowledge obtained is valuable for future studies on degradation of anthocyanins, formation of volatiles, and the network of secondary metabolism in Brunfelsia and related species

Tumor Treating Fields (TTFields) demonstrate antiviral functions in vitro, and safety for application to COVID-19 patients in a pilot clinical study

Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage

Two Notes On Genome Rearrangement

A central problem in genome rearrangement is nding a most parsimonious rearrangement scenario using certain rearrangement operations. An important problem of this type is sorting a signed genome by reversals and translocations (SBRT). Hannenhalli and Pevzner presented a duality theorem for SBRT which leads to a polynomial time algorithm for sorting a multi-chromosomal genome using a minimum number of reversals and translocations. However, there is one case for which their theorem and algorithm fail. We describe that case and suggest a correction to the theorem and the polynomial algorithm