Synthetic Morphology Using Alternative Inputs

Designing the shape and size of a cell is an interesting challenge for synthetic biology. Prolonged exposure to the mating pheromone α-factor induces an unusual morphology in yeast cells: multiple mating projections. The goal of this work was to reproduce the multiple projections phenotype in the absence of α-factor using a gain-of-function approach termed “Alternative Inputs (AIs)”. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. Interestingly, none of the alternative inputs were sufficient to produce multiple projections although some produced a single projection. Then, we extended our search by creating all combinations of alternative inputs and deletions that were summarized in an AIs-Deletions matrix. We found a genetic manipulation (AI-Ste5p ste2Δ) that enhanced the formation of multiple projections. Following up this lead, we demonstrated that AI-Ste4p and AI-Ste5p were sufficient to produce multiple projections when combined. Further, we showed that overexpression of a membrane-targeted form of Ste5p alone could also induce multiple projections. Thus, we successfully re-engineered the multiple projections mating morphology using alternative inputs without α-factor

Presentations of patients of poisoning and predictors of poisoning-related fatality: Findings from a hospital-based prospective study

<p>Abstract</p> <p>Background</p> <p>Poisoning is a significant public health problem worldwide and is one of the most common reasons for visiting emergency departments (EDs), but factors that help to predict overall poisoning-related fatality have rarely been elucidated. Using 1512 subjects from a hospital-based study, we sought to describe the demographic and clinical characteristics of poisoning patients and to identify predictors for poisoning-related fatality.</p> <p>Methods</p> <p>Between January 2001 and December 2002 we prospectively recruited poisoning patients through the EDs of two medical centers in southwest Taiwan. Interviews were conducted with patients within 24 hours after admission to collect relevant information. We made comparisons between survival and fatality cases, and used logistic regressions to identify predictors of fatality.</p> <p>Results</p> <p>A total of 1512 poisoning cases were recorded at the EDs during the study period, corresponding to an average of 4.2 poisonings per 1000 ED visits. These cases involved 828 women and 684 men with a mean age of 38.8 years, although most patients were between 19 and 50 years old (66.8%), and 29.4% were 19 to 30 years. Drugs were the dominant poisoning agents involved (49.9%), followed by pesticides (14.5%). Of the 1512 patients, 63 fatalities (4.2%) occurred. Paraquat exposure was associated with an extremely high fatality rate (72.1%). The significant predictors for fatality included age over 61 years, insufficient respiration, shock status, abnormal heart rate, abnormal body temperature, suicidal intent and paraquat exposure.</p> <p>Conclusion</p> <p>In addition to well-recognized risk factors for fatality in clinical settings, such as old age and abnormal vital signs, we found that suicidal intent and ingestion of paraquat were significant predictors of poisoning-related fatality. Identification of these predictors may help risk stratification and the development of preventive interventions.</p

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases