Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Microalbuminuria in IDDM is associated with increased expression of monocyte procoagulant activity

Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth, influencing foetal cell division and differentiation and possibly metabolic regulation. The mature 67 amino acid peptide shares sequence homology with both insulin and IGF-I. The liver is the main endocrine source of IGFs, but autocrine/paracrine activity is found in most tissues. The type 1 receptor mediates most of the biological effects of IGF-I and IGF-II; the type 2 receptor is involved with IGF-II degradation. Binding proteins may both localise IGFs to the receptors and regulate their activities. The IGF2 gene is maternally imprinted in mouse and human. Relaxation of IGF2 imprinting occurs in the Beckwith-Wiedemann syndrome of somatic overgrowth, sporadic Wilms' tumour and a number of other cancers. In the general adult population, the IGF2-INS gene cluster may also influence body weight, in which case IGF-II function could become a target for therapeutic intervention in obesity.     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.     

On Approximate Majority and Probabilistic Time

We prove new results on the circuit complexity of approximate majority, which is the problem of computing the majority of a given bit string whose fraction of 1’s is bounded away from 1/2 (by a constant). We then apply these results to obtain new relationships between probabilistic time, BPTime (t), and alternating time, ∑_O(1)Time (t). Our main results are the following:

Synchronizing automata with finitely many minimal synchronizing words

A synchronizing word for a given synchronizing DFA is called minimal if none of its proper factors is synchronizing. We characterize the class of synchronizing automata having only finitely many minimal synchronizing words (the class of such automata is denoted by FG). Using this characterization we prove that any such automaton possesses a synchronizing word of length at most 3n-5. We also prove that checking whether a given DFA A is in FG is co-NP-hard and provide an algorithm for this problem which is exponential in the number of states A.     

EEG signal preprocessing for biometric recognition

Electroencephalography (EEG) has been recently investigated as a biometric modality for automatic people recognition purposes. Several studies have shown that brain signals possess subject-specific traits that allow distinguishing people. Nonetheless, extracting discriminative characteristics from EEG recordings may be a challenging task, due to the significant presence of artifacts in the acquired data. In order to cope with such issue, in this paper we evaluate the effectiveness of some preprocessing techniques in automatically removing undesired EEG contributions, with the aim of improving the achievable recognition rates. Specifically, methods based on blind source separation and sample entropy estimation are here investigated. An extensive set of experimental tests, performed over a large database comprising recordings taken from 50 healthy subjects during three distinct sessions spanning a period of about one month, in both eyes-closed and eyes-open conditions, is carried out to analyze the performance of the proposed approaches.     

Sensorless supervision of linear dynamical systems: The Feed-Forward Command Governor approach

This paper proposes a novel class of Command Governor (CG) strategies for input and state-related constrained discrete-time LTI systems subject to bounded disturbances in the absence of explicit state or output measurements. While in traditional CG schemes the set-point manipulation is undertaken on the basis of either the actual measure of the state or its suitable estimation, it is shown here that the CG design problem can be solved, with limited performance degradation and with similar properties, also in the case that such an explicit measure is not available. This approach, which will be referred to as the Feed-Forward CG (FF-CG) approach, may be a convenient alternative CG solution in all situations whereby the cost of measuring the state may be a severe limitation, e.g. in distributed or decentralized applications. In order to evaluate the method proposed here, numerical simulations on a physical example have been undertaken and comparisons with the standard state-based CG solution reported.     

Trade-offs Between the Size of Advice and Broadcasting Time in Trees

We study the problem of the amount of information required to perform fast broadcasting in tree networks. The source located at the root of a tree has to disseminate a message to all nodes. In each round each informed node can transmit to one child. Nodes do not know the topology of the tree but an oracle knowing it can give a string of bits of advice to the source which can then pass it down the tree with the source message. The quality of a broadcasting algorithm with advice is measured by its competitive ratio: the worst case ratio, taken over n-node trees, between the time of this algorithm and the optimal broadcasting time in the given tree. Our goal is to find a trade-off between the size of advice and the best competitive ratio of a broadcasting algorithm for n-node trees. We establish such a trade-off with an approximation factor of O(n ^ε ), for an arbitrarily small positive constant ε. This is the first communication problem for which a trade-off between the size of advice and the efficiency of the solution is shown for arbitrary size of advice.