Hfq binding changes the structure of Escherichia coli small noncoding RNAs OxyS and RprA, which are involved in the riboregulation of rpoS

OxyS and RprA are two small noncoding RNAs (sRNAs) that modulate the expression of rpoS, encoding an alternative sigma factor that activates transcription of multiple Escherichia coli stress-response genes. While RprA activates rpoS for translation, OxyS down-regulates the transcript. Crucially, the RNA binding protein Hfq is required for both sRNAs to function, although the specific role played by Hfq remains unclear. We have investigated RprA and OxyS interactions with Hfq using biochemical and biophysical approaches. In particular, we have obtained the molecular envelopes of the Hfq–sRNA complexes using small-angle scattering methods, which reveal key molecular details. These data indicate that Hfq does not substantially change shape upon complex formation, whereas the sRNAs do. We link the impact of Hfq binding, and the sRNA structural changes induced, to transcript stability with respect to RNase E degradation. In light of these findings, we discuss the role of Hfq in the opposing regulatory functions played by RprA and OxyS in rpoS regulation

The critical window for the classical Ramsey-Tur\'an problem

The first application of Szemer\'edi's powerful regularity method was the following celebrated Ramsey-Tur\'an result proved by Szemer\'edi in 1972: any K_4-free graph on N vertices with independence number o(N) has at most (1/8 + o(1)) N^2 edges. Four years later, Bollob\'as and Erd\H{o}s gave a surprising geometric construction, utilizing the isoperimetric inequality for the high dimensional sphere, of a K_4-free graph on N vertices with independence number o(N) and (1/8 - o(1)) N^2 edges. Starting with Bollob\'as and Erd\H{o}s in 1976, several problems have been asked on estimating the minimum possible independence number in the critical window, when the number of edges is about N^2 / 8. These problems have received considerable attention and remained one of the main open problems in this area. In this paper, we give nearly best-possible bounds, solving the various open problems concerning this critical window.Comment: 34 page

A Hypergraph Dictatorship Test with Perfect Completeness

A hypergraph dictatorship test is first introduced by Samorodnitsky and Trevisan and serves as a key component in their unique games based \PCP construction. Such a test has oracle access to a collection of functions and determines whether all the functions are the same dictatorship, or all their low degree influences are $o(1).$ Their test makes $q\geq3$ queries and has amortized query complexity $1+O(\frac{\log q}{q})$ but has an inherent loss of perfect completeness. In this paper we give an adaptive hypergraph dictatorship test that achieves both perfect completeness and amortized query complexity $1+O(\frac{\log q}{q})$.Comment: Some minor correction

Small doubling in groups

Let A be a subset of a group G = (G,.). We will survey the theory of sets A with the property that |A.A| <= K|A|, where A.A = {a_1 a_2 : a_1, a_2 in A}. The case G = (Z,+) is the famous Freiman--Ruzsa theorem.Comment: 23 pages, survey article submitted to Proceedings of the Erdos Centenary conferenc

Expansion in perfect groups

Let Ga be a subgroup of GL_d(Q) generated by a finite symmetric set S. For an integer q, denote by Ga_q the subgroup of Ga consisting of the elements that project to the unit element mod q. We prove that the Cayley graphs of Ga/Ga_q with respect to the generating set S form a family of expanders when q ranges over square-free integers with large prime divisors if and only if the connected component of the Zariski-closure of Ga is perfect.Comment: 62 pages, no figures, revision based on referee's comments: new ideas are explained in more details in the introduction, typos corrected, results and proofs unchange

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

Bounds for graph regularity and removal lemmas

We show, for any positive integer k, that there exists a graph in which any equitable partition of its vertices into k parts has at least ck^2/\log^* k pairs of parts which are not \epsilon-regular, where c,\epsilon>0 are absolute constants. This bound is tight up to the constant c and addresses a question of Gowers on the number of irregular pairs in Szemer\'edi's regularity lemma. In order to gain some control over irregular pairs, another regularity lemma, known as the strong regularity lemma, was developed by Alon, Fischer, Krivelevich, and Szegedy. For this lemma, we prove a lower bound of wowzer-type, which is one level higher in the Ackermann hierarchy than the tower function, on the number of parts in the strong regularity lemma, essentially matching the upper bound. On the other hand, for the induced graph removal lemma, the standard application of the strong regularity lemma, we find a different proof which yields a tower-type bound. We also discuss bounds on several related regularity lemmas, including the weak regularity lemma of Frieze and Kannan and the recently established regular approximation theorem. In particular, we show that a weak partition with approximation parameter \epsilon may require as many as 2^{\Omega(\epsilon^{-2})} parts. This is tight up to the implied constant and solves a problem studied by Lov\'asz and Szegedy.Comment: 62 page

Treatment of psychoses in patients with epilepsy: an update.

Psychotic disorders represent a relatively rare but serious comorbidity in epilepsy. Current epidemiological studies are showing a point prevalence of 5.6% in unselected samples of people with epilepsy going up to 7% in patients with temporal lobe epilepsy, with a pooled odds ratio of 7.8 as compared with the general population. This is a narrative review of the most recent updates in the management of psychotic disorders in epilepsy, taking into account the clinical scenarios where psychotic symptoms occur in epilepsy, interactions with antiepileptic drugs (AEDs) and the risk of seizures with antipsychotics. Psychotic symptoms in epilepsy can arise in a number of different clinical scenarios from peri-ictal symptoms, to chronic interictal psychoses, comorbid schizophrenia and related disorders to the so-called forced normalization phenomenon. Data on the treatment of psychotic disorders in epilepsy are still limited and the management of these problems is still based on individual clinical experience. For this reason, guidelines of treatment outside epilepsy should be adopted taking into account epilepsy-related issues including interactions with AEDs and seizure risk. Second-generation antipsychotics, especially risperidone, can represent a reasonable first-line option because of the low propensity for drug-drug interactions and the low risk of seizures. Quetiapine is burdened by a clinically significant pharmacokinetic interaction with enzyme-inducing drugs leading to undetectable levels of the antipsychotic, even for dosages up to 700 mg per day

Expansion in SL_d(Z/qZ), q arbitrary

Let S be a fixed finite symmetric subset of SL_d(Z), and assume that it generates a Zariski-dense subgroup G. We show that the Cayley graphs of pi_q(G) with respect to the generating set pi_q(S) form a family of expanders, where pi_q is the projection map Z->Z/qZ

Label-free electrochemical monitoring of DNA ligase activity

This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase