Embedding mRNA Stability in Correlation Analysis of Time-Series Gene Expression Data

Current methods for the identification of putatively co-regulated genes directly from gene expression time profiles are based on the similarity of the time profile. Such association metrics, despite their central role in gene network inference and machine learning, have largely ignored the impact of dynamics or variation in mRNA stability. Here we introduce a simple, but powerful, new similarity metric called lead-lag R2 that successfully accounts for the properties of gene dynamics, including varying mRNA degradation and delays. Using yeast cell-cycle time-series gene expression data, we demonstrate that the predictive power of lead-lag R2 for the identification of co-regulated genes is significantly higher than that of standard similarity measures, thus allowing the selection of a large number of entirely new putatively co-regulated genes. Furthermore, the lead-lag metric can also be used to uncover the relationship between gene expression time-series and the dynamics of formation of multiple protein complexes. Remarkably, we found a high lead-lag R2 value among genes coding for a transient complex

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

A transient assay for rapid functional analysis of transcription factors in arabidopsis

We have modified the biolistic process to establish a transient assay for rapid analysis of transcription factors in arabidopsis. ATHB-1, an arabidopsis HD-Zip protein, was used as a transacting factor in particle bombardment experiments with arabidopsis leaves, and was found to transactivate a reporter gene in a binding site-specific manner. The experiments show the feasibility of using microprojectile-mediated gene transfer for rapid functional analysis of transcription factors in arabidopsis

Massive Pulmonary-embolism - Clinical Aspects and Treatment

The frequency of pulmonary embolization seems to be increasing. Venostasis, intimal damage and hypercoagulability of blood are the more recognized causes of pulmonary thromboembolism. It is especially threatening to the elderly, obese, immobilized (for an accident or an operation) patients. Pulmonary isotopic scans or angiograms are most often relied upon to establish the diagnosis. A properly performed pulmonary angiography is necessary to establish or refute the diagnosis in almost every case. With the exception of the patients suddenly dying for a massive pulmonary embolism, the period of time between onset of symptoms and death is usually adequate for substantiating a diagnosis and promptly beginning a fit anticoagulation therapy using continuous intravenous heparin or fibrinolytic agents infusion. Although it is not proper to separate surgical and medical treatment of thromboembolism, the Authors, on the ground of their experience on 5 patients affected by massive pulmonary embolism, in 3 of whom was performed a successful embolectomy, think that heparin anticoagulation treatment is at any rate to apply for treating pulmonary embolism, but in patients in whom the shock is unresponsive to vasopressors or in whom anticoagulation therapy is controindicated, the surgical removal of pulmonary emboly, with the support of a pump oxygenator, is the treatment of choice for the acute massive pulmonary thromboembolism

Phytochrome A, phytochrome B and other phytochrome(s) regulate ATHB-2 gene expression in etiolated and green Arabidopsis plants

The expression of the Arabidopsis ATHB-2 gene is light-regulated both in seedlings and in adult plants, The gene is expressed at high levels in rapidly elongating etiolated seedlings and is down-regulated by a pulse of red light (R) through the action of a phytochrome other than phytochrome A or B, or by a pulse of far-red light (FR) through the action of phytochrome A, In green plants, the expression of the ATHB-2 gene is rapidly and strongly enhanced by lowering the R:FR ratio perceived by a phytochrome other than A or B, Returning the plant to a high R:FR ratio results in an equally rapid decrease of the ATHB-2 mRNA, Consistently, plants overproducing ATHB-2 show developmental phenotypes characteristic of plants grown in low R:FR: elongated petioles, reduced leaf area, early flowering, and reduced number of rosette leaves, Taken together, the data strongly suggest a direct involvement of ATHB-2 in light-regulated growth phenomena throughout Arabidopsis development

19 Year Experience On the Treatment of Aneurysms of the Abdominal-aorta - A Survey of 832 Consecutive Cases

832 patients with abdominal aortic aneurysm were admitted to our Hospital, at the University of Milan, from 1965 to 1983. 238 patients were operated on as an emergency for rupture of the aneurysm while 541 underwent elective surgery. The overall postoperative mortality was 7% for the patients operated on electively and 54.3% for the ruptured aneurysm operated on as an emergency