Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.

ABSTRACT: BACKGROUND: Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus. RESULTS: We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon. CONCLUSION: Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB

Why Nature has made a choice of one time and three space coordinates?

We propose a possible answer to one of the most exciting open questions in physics and cosmology, that is the question why we seem to experience four- dimensional space-time with three ordinary and one time dimensions. We have known for more than 70 years that (elementary) particles have spin degrees of freedom, we also know that besides spin they also have charge degrees of freedom, both degrees of freedom in addition to the position and momentum degrees of freedom. We may call these ''internal degrees of freedom '' the ''internal space'' and we can think of all the different particles, like quarks and leptons, as being different internal states of the same particle. The question then naturally arises: Is the choice of the Minkowski metric and the four-dimensional space-time influenced by the ''internal space''? Making assumptions (such as particles being in first approximation massless) about the equations of motion, we argue for restrictions on the number of space and time dimensions. (Actually the Standard model predicts and experiments confirm that elementary particles are massless until interactions switch on masses.) Accepting our explanation of the space-time signature and the number of dimensions would be a point supporting (further) the importance of the ''internal space''.Comment: 13 pages, LaTe

Fed, but not Fasted, Adrenalectomized Rats Survive the Stress of Hemorrhage and Hypovolemia

We have recently shown that conscious adrenalectomized rats exhibit nearly normal recovery of arterial blood pressure during the 5 h after hemorrhage. In those experiments, it appeared that a previous reduction in food intake might have compromised the recovery of blood pressure and increased mortality. These experiments were designed to test in conscious sham-adrenalectomized (control) and adrenalectomized rats prepared with indwelling arterial and venous cannulae: 1. The effects of a 20- to 24-h fast (compared to rats fed ab libitum) on the mobilization of plasma substrates and recovery of arterial blood pressure after a 15 ml/kg - 5 min hemorrhage, and 2. Vascular responsivity to pressor agents in fed or fasted groups before or 2 h after hemorrhage. In all rats hemorrhage resulted in decreased arterial pressure and heart rate. Arterial pressure recovered to near normal in both fed and fasted control groups and in the led adrenalectomized rats, and all of these rats survived for 24 h after stress. By contrast, in the fasted adrenalectomized rats, arterial pressure recovered only during the first 1.5 - 2 h and then failed, resulting in 100% mortality by 3-5 h. Compared to the other three groups, in which substrate levels either increased or remained fairly stable, plasma glucose and beta-hydoxybutyrate concentrations fell steadily, from 1.5-2 h after hemorrhage until death occurred in the fasted adrenalectomized rats. Basal ACTH concentrations were elevated cormpared to control values in both adrenalectomized groups (fed and fasted). Hemorrhage caused increases in plasma ACTH in all groups; the magnitude of the responses did not differ among the groups. The dilution of Evans' blue dve after hemorrhage (used as an index of fluid movement into the vascular space) was not different in contol and adrenalectomized rats (either fed or fasted). There were no differences in pressor responses to phenylephrine, vasopressin, or angiotensin-II between the fed and fasted condition in the control rats either before or after hemorrhage. There was a fasting-associated decrease in vascular responsivity, to vasopressin, but normal responsivity to phenylephrine and angiotensin-II, in the adrenal-ectomized rats both before and after hemorrhage. We conclude that: (1) since fed adrenalectomized rats all survived the stress, adrenal hormones are not required for survival unless fasting is a prior condition; (2) vascular responsiveness to phenylephrine and angiotensin-II is not altered by fasting and is, therefore, probably not the proximate cause of cardiovascular svstem failure; and (3) from these data we cannot distinguish between a failure in substrate supply and a failure in some component of the cardiovascular svstem, other than vascular responsivity, that results in death after hemorrhage in fasted adrenalectomized rats

Balancing Minimum Spanning and Shortest Path Trees

This paper give a simple linear-time algorithm that, given a weighted digraph, finds a spanning tree that simultaneously approximates a shortest-path tree and a minimum spanning tree. The algorithm provides a continuous trade-off: given the two trees and epsilon > 0, the algorithm returns a spanning tree in which the distance between any vertex and the root of the shortest-path tree is at most 1+epsilon times the shortest-path distance, and yet the total weight of the tree is at most 1+2/epsilon times the weight of a minimum spanning tree. This is the best tradeoff possible. The paper also describes a fast parallel implementation.Comment: conference version: ACM-SIAM Symposium on Discrete Algorithms (1993

GP attitudes and self-reported behaviour in primary care consultations for low back pain

Background. The implementation of guideline recommendations in primary care has become widespread. The treatment of low back pain (LBP) has followed suite. Research shows that the use of LBP guidelines is influenced by the believability of the underlying evidence, the GPs consultation style and uncertainties surrounding diagnosis and treatment

On the S-matrix renormalization in effective theories

This is the 5-th paper in the series devoted to explicit formulating of the rules needed to manage an effective field theory of strong interactions in S-matrix sector. We discuss the principles of constructing the meaningful perturbation series and formulate two basic ones: uniformity and summability. Relying on these principles one obtains the bootstrap conditions which restrict the allowed values of the physical (observable) parameters appearing in the extended perturbation scheme built for a given localizable effective theory. The renormalization prescriptions needed to fix the finite parts of counterterms in such a scheme can be divided into two subsets: minimal -- needed to fix the S-matrix, and non-minimal -- for eventual calculation of Green functions; in this paper we consider only the minimal one. In particular, it is shown that in theories with the amplitudes which asymptotic behavior is governed by known Regge intercepts, the system of independent renormalization conditions only contains those fixing the counterterm vertices with $n \leq 3$ lines, while other prescriptions are determined by self-consistency requirements. Moreover, the prescriptions for $n \leq 3$ cannot be taken arbitrary: an infinite number of bootstrap conditions should be respected. The concept of localizability, introduced and explained in this article, is closely connected with the notion of resonance in the framework of perturbative QFT. We discuss this point and, finally, compare the corner stones of our approach with the philosophy known as ``analytic S-matrix''.Comment: 28 pages, 10 Postscript figures, REVTeX4, submitted to Phys. Rev.

A One Month Review of the Types of Medical Emergencies and their Treatment Outcomes at Two Urban Public Health Clinics.

INTRODUCTION Our study was to examine prevalence and treatment outcomes of medical emergencies at two urban public health clinics in the Petaling district, Selangor, Malaysia. METHODS A prospective universal sampling was employed to recruit all emergencies over one month period (12 April to 11 May 2011). A structured case record form was used to capture demographic data, whether the index case was selfpresenting or decided by health care workers as a medical emergency, presenting complaints, diagnoses, concurrent chronic diseases and their treatment outcomes at the clinic level. Emergency presentations and diagnoses were classified according to the International Classification of Primary Care, revised second edition (ICPC-2-R). RESULTS A total of 125 medical emergencies with 276 presenting complaints were recorded. The mean age was 30.7 years old (SD 19.9). The prevalence of medical emergency was 0.56% (125/22,320). Chief complaints were mainly from ICPC-2-R chapter R (respiratory system) and chapter A (general and unspecified), 40.0% and 28.0% respectively. The most common diagnosis was acute exacerbation of bronchial asthma (34.6%). Forty percent were referred to hospitals. After adjusting for age and gender, patients who presented with painful emergency (OR 4.9 95% CI 2.0 to 11.7), cardiovascular emergency (OR 63.4 95% CI 12.9 to 310.4) and non-respiratory emergency were predictors of hospital referral (OR 4.6 95% CI 1.1 to 19.1). CONCLUSION There was about one medical emergency for every 200 patients presenting to these urban public polyclinics which were mainly acute asthma. More than half were discharged well and given a follow-up

Tree amplitudes of noncommutative U(N) Yang-Mills Theory

Following the spirit of S-matrix program, we proposed a modified Britto-Cachazo-Feng-Witten recursion relation for tree amplitudes of noncommutative U(N) Yang-Mills theory. Starting from three-point amplitudes, one can use this modified BCFW recursion relation to compute or analyze color-ordered tree amplitudes without relying on any detail information of noncommutative Yang-Mills theory. After clarifying the color structure of noncommutative tree amplitudes, we wrote down the noncommutative analogies of U(1)-decoupling, Kleiss-Kuijf and Bern-Carrasco-Johansson relations for color-ordered tree amplitudes, and proved them using the modified BCFW recursion relation.Comment: 24 pages, 3 figures. v2 References added. v3 some typos correcte

Depression predicts future emergency hospital admissions in primary care patients with chronic physical illness

PublishedObjective More than 15 million people currently suffer from a chronic physical illness in England. The objective of this study was to determine whether depression is independently associated with prospective emergency hospital admission in patients with chronic physical illness. Method 1860 primary care patients in socially deprived areas of Manchester with at least one of four exemplar chronic physical conditions completed a questionnaire about physical and mental health, including a measure of depression. Emergency hospital admissions were recorded using GP records for the year before and the year following completion of the questionnaire. Results The number of patients who had at least one emergency admission in the year before and the year after completion of the questionnaire were 221/1411 (15.7%) and 234/1398 (16.7%) respectively. The following factors were independently associated with an increased risk of prospective emergency admission to hospital; having no partner OR 1.49 (95% CI 1.04 to 2.15); having ischaemic heart disease OR 1.60 (95% CI 1.04 to 2.46); having a threatening experience OR 1.16 (95% CI 1.04 to 1.29) per experience; depression OR 1.58 (95% CI 1.04 to 2.40); emergency hospital admission in year prior to questionnaire completion OR 3.41 (95% CI (1.98 to 5.86). Conclusion To prevent potentially avoidable emergency hospital admissions, greater efforts should be made to detect and treat co-morbid depression in people with chronic physical illness in primary care, with a particular focus on patients who have no partner, have experienced threatening life events, and who have had a recent emergency hospital admission.National Institute for Health Research (NIHR

Interleukin-13 Genetic Variants, Household Carpet Use and Childhood Asthma

10.1371/journal.pone.0051970PLoS ONE81