Regulation of Mg2+ homeostasis by insulin in perfused rat livers and isolated hepatocytes

Several recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in Mg2+ homeostasis. As insulin counter-regulates many of the metabolic consequences of adrenergic receptor stimulation, we evaluated the potential influence of insulin on Mg2+ movements in response to adrenergic stimulation. The data demonstrate that insulin is able to block the Mg2+ efflux from perfused rat livers stimulated by isoproterenol or 8-Br-cAMP, but has little or no effect on epinephrine or phenylephrine induced Mg2+ efflux. Thus, evidence is provided demonstrating that there are redundant adrenergic pathways regulating Mg2+ efflux from liver tissue. One of these pathways, the beta-adrenergic component, is selectively blocked by insulin. Furthermore, these findings may provide a cellular explanation for hypomagnesemia associated with diabetes.     

A 10-GB/s SONET-compliant CMOS transceiver with low crosstalk and intrinsic jitter

A 4:1 SERDES IC suitable for SONET OC-192 and 10-Gb/s Ethernet is presented. The receiver, which consists of a limiting amplifier, a clock and data recovery unit, and a demultiplexer, locks automatically to all data rates in the range 9.95-10.7 Gb/s. At a bit error rate of less than 10/sup -12/, it has a sensitivity of 20 mV. The transmitter comprises a clock multiplying unit and a multiplexer. The jitter of the transmitted data signal is 0.2 ps RMS. This is facilitated by a novel notched inductor layout and a special power supply concept, which reduces cross-coupling between the transmitter and receiver. Integrated in a 0.13-/spl mu/m CMOS technology, the total power consumption from both 1.2- and 2.5-V supplies is less than 1 W.     

IL-10 is required for development of protective Th1 responses in IL-12-deficient mice upon Candida albicans infection

IL-12 is both required and prognostic for Th1 development in mice with Candida albicans infection. To delineate further the physiologic role of IL-12 in antifungal immunity, mice deficient for this cytokine were assessed for susceptibility to C. albicans infections, and for parameters of innate and adaptive immunity. IL-12-deficient mice were highly susceptible to gastrointestinal infection or to reinfection and showed elevated production of Candida-specific IgE and IL-4 and defective production of IFN-gamma. The failure to mount protective Th1 responses occurred despite the presence of an unimpaired innate antifungal immune response, which correlated with unaltered IFN-gamma production, but defective production of, and responsiveness to, inhibitory IL-10. IL-10 or IL-12 neutralization increased the innate antifungal resistance in wild-type mice. However, in IL-12-deficient mice, treatment with exogenous IL-12 or IL-10 impaired IL-4 production and increased resistance to infection, through a negative effect on the CTLA-4/B7-2 costimulatory pathway. These results confirm the obligatory role of IL-12 in the induction of anticandidal Th1 responses, and indicate the existence of a positive regulatory loop between IL-12 and IL-10 that may adversely affect the innate antifungal response, but is required for optimal costimulation of IL-12-dependent CD4+ Th1 cells.     

Complexity measures for matrix multiplication algorithms

A new class of algorithms for the computation of bilinear forms has been recently introduced [1, 3]. These algorithms approximate the result with an arbitrarily small error. Such approximate algorithms may have a multiplicative complexity smaller than exact ones. On the other hand any comparison between approximate and exact algorithms has to take into account the complexity-stability relations. In this paper some complexity measures for matrix multiplication algorithms are discussed and applied to the evaluation of exact and approximate algorithms. Multiplicative complexity is shown to remain a valid comparison test and the cost of approximation appears to be only a logarithmic factor.     

On the fast synchronization of tree connected networks

In extending the Firing Squad Synchronization problem to the case of tree connected networks and applying the controlled synchronization of linear arrays, we obtain the optimal time for trees with a bounded number of nodes.We also investigate methods for synchronizing general trees and show how to apply them to networks arbitrarily connected.     

On hash techniques in a paged environment

The performance of techniques for hash tables management in paged environments is examined. Classical methods as open addressing and chaining are considered as well as some new techniques performed on doubly linked chained hash tables. A comparison and an evaluation of the efficiency of the above methods are made in regard to the average search length, the average memory access and, more important, the average page faults.     

Neurological findings in the normal elderly: prevalence and relationships with memory performance

Portal hypertension is a result of chronic liver disease in the majority of cases. Rare, potentially curable causes of portal hypertension include vascular conditions such as hepatic or portal venous thrombosis and arterio-portal fistulas. We present the rare case of a spontaneous splenic arterio-venous fistula in a 40 year old multiparous woman. The young woman presented with massive diarrhea, ascites, abdominal pain, and an abdominal machinery type bruit and represents the second ever reported case with diarrhea as presenting symptom of splenic arterio-venous fistula. The diagnosis was confirmed by color Doppler ultrasound. Transfemoral aortography was performed to assess the possibility of catheter embolization. Surgical intervention was initially complicated by collateral arterial tributaries of the fistula and finally resulted in a dramatic recovery with persistent resolution of all symptoms. This case report demonstrates a curable form of portal hypertension that must be considered in acute onset portal hypertension in multiparous women and in the absence of liver disease. A machinery type bruit in the upper left abdominal quadrant represents an important and simple diagnostic symptom found by auscultation. Color Doppler ultrasound represents a non invasive, universally applicable and fast method of establishing the diagnosis. The literature and management of splenic arterio-venous fistulas are reviewed.     

Effects of Lipidation on a Proline-Rich Antibacterial Peptide

The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in E. coli after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents.     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.