Insulin depletion leads to adipose-specific cell death in obese but not lean mice

Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory "overexpression" of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.     

Binding and lysing of blood clots using MRX-408

RATIONALE AND OBJECTIVES: A thrombus-specific ultrasound contrast agent, MRX-408, has been developed recently. This agent consists of phospholipid-coated microbubbles with a ligand capable of targeting the GPIIb/IIIa receptor, thereby allowing the microbubbles to bind with thrombi rich in activated platelets. In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombolysis using this agent compared with a nontargeted agent. METHODS: For clot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope. Change in backscatter signals from the blood clots after binding was examined by both an ultrasound scanner and two single-element transducers arranged in a transmitter-receiver pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase. RESULTS: Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the "acoustic signature", or properties, of blood clots changed after binding. Clots became more echogenic and nonlinear. In vivo fundamental ultrasound imaging confirmed that as a result of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable. Under 1-MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 34% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION: The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.     

Auditory system plasticity in children after long periods of complete deafness

Separation and identification of proteins by two-dimensional (2-D) electrophoresis can be used for protein-based gene expression analysis. In this report single protein spots, from polyvinylidene difluoride blots of micropreparative E. coli 2-D gels, were rapidly and economically identified by matching their amino acid composition, estimated pI and molecular weight against all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2-D map were analyzed and identities assigned. Three of the proteins were unknown. By protein sequencing analysis, 20 of the 27 proteins were correctly identified. Importantly, correct identifications showed unambiguous "correct" score patterns. While incorrect protein identifications also showed distinctive score patterns, indicating that protein must be identified by other means. These techniques allow large-scale screening of the protein complement of simple organisms, or tissues in normal and disease states. The computer program described here is accessible via the World Wide Web at URL address (http:@expasy.hcuge.ch/).     

Laparoscopic versus open appendectomy

BACKGROUND: Clinical manifestations and course of sickle-cell anemia are variable. Knowledge about the factors, possibly geographic, that influence prognosis are still scanty. POPULATION AND METHODS: Data of hospitalization and management of children with sickle-cell disease were studied during two years (1992-1993) in the Pediatric Unit of Libreville Hospital. They concerned 205 admissions of 171 children and 131 outpatients. RESULTS: The main causes of hospitalization were: acute anemia (36 cases before the age of 5 years); painful crisis whose frequency increased with age (23% before 5 years, 35% between 5 and 10, 42% after 10 years); infections, essentially pulmonary occurring early, and bone infections at any age. Eight children died (because a complication of their disease). Among the 131 outpatients, half were detected because pyrexia, anemia and/or more often "hand-foot syndrome". More than 60% had hepatomegaly, one third still had splenomegaly after five years of age and more than one third was icteric. More than half children older than ten years had growth disorders. Mean hemoglobin level was 7 g/dL. 21 of the 83 tested children for HBsAg were positive and only one out of 79 was positive for HIV. CONCLUSIONS: Clinical manifestations and course of sickle-cell anemia in our patients are similar to those reported in Congolese children. Genetic and environmental factors may be responsible for differences with children from other, in particular French, cohorts.     

Metabolic role of glutamine and its importance in nutritional therapy

The advances in the field of nutritional support have made certain nutrients very relevant, which, although they have been known for a long time, at present represent an important chapter in nutrition, entering into what is known as "nutritional pharmacology". Among these nutrients is glutamine, an amino acid classified as non-essential, but which in certain circumstances may become to be considered as an "essential nutrient". In the present review, a review is made of its metabolic role, synthesis and degradation, metabolic routes and functions under normal conditions as well as under critical conditions. It is known that glutamine stimulates the synthesis and inhibits the degradation of proteins, it is an important vehicle for the transport of nitrogen and carbon within the tissues, it stimulates the synthesis of hepatic glycogen, it is an energy source for cell division, for the growth of different cells of rapid replication, such as enterocytes, colonocytes, and fibroblasts, as well as for other cells of the immune system, such as lymphocytes and macrophages. Thus its role in the maintenance of structure, in metabolism and function of the intestinal mucosa, and in dysfunctions of the immune system. In parenteral nutrition, at present there are no preparations which include it, given the stability problems which it presents, although attempts have been made to resolve this, using different possibilities, such as di-peptides. However, in enteral nutrition, the diets tend to include it, although in a small proportion. Nevertheless, having recognized its beneficial role in a certain type of patients, at present there are diets which contain glutamine in higher doses, with the object of attempting to cover the increased demands of glutamine which shall arise in these situations. The inclusion of glutamine in nutritional therapy is supported by multiple studies which reflect the beneficial effect of this nutrient, both in enteral nutrition as in parenteral nutrition.     

Finding an Euclidean anti--centrum location of a set of points

An obnoxious facility is to be located inside a polygonal region of the plane, maximizing the sum of the k smallest weighted Euclidean distances to n given points, each protected by some polygonal forbidden region. For the unweighted case and k fixed an O(n²logn) time algorithm is presented. For the weighted case a thorough study of the relevant structure of the multiplicatively weighted order-k-Voronoi diagram leads to the design of an O(kn³+n³logn) time algorithm for finding an optimal solution to the anti-t-centrum problem for every t=1,…,k, simultaneously.     

Simultaneous algorithm for trajectory planning

This paper addresses the solution of smooth trajectory planning for industrial robots in environments with obstacles using a direct method, creating the trajectory gradually as the robot moves. The presented method deals with the uncertainties associated with the lack of knowledge of kinematic properties of intermediate via‐points since they are generated as the algorithm evolves looking for the solution. Several cost functions are also proposed, which use the time that has been calculated to guide the robot motion. The method has been applied successfully to a PUMA 560 robot and four operational parameters (execution time, computational time, distance travelled and number of configurations) have been computed to study the properties and influence of each cost function on the trajectory obtained. Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Parallax cues in the design of graphics used in technical education to illustrate complex spatial problems

The explanation of certain 3D concepts is based on 2D drawings. These drawings should contain certain depth cues, such as perspective and overlapping. Until recently, parallax has not been used as a depth cue. Nevertheless, new technologies allow it to be incorporated. This forms the background to our study of the design of interactive educational resources and stereoscopic graphics. The results obtained demonstrate that (1) the use of parallax cues improves the interpretation of the figures and (2) that the assistance they afford is most appreciated by the students with less highly developed spatial perception.     

The STATFLUX code: a statistical method for calculation of flow and set of parameters, based on the Multiple-Compartment Biokinetical Model

The code STATFLUX, implementing a new and simple statistical procedure for the calculation of transfer coefficients in radionuclide transport to animals and plants, is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. Flow parameters were estimated by employing two different least-squares procedures: Derivative and Gauss-Marquardt methods, with the available experimental data of radionuclide concentrations as the input functions of time. The solution of the inverse problem, which relates a given set of flow parameter with the time evolution of concentration functions, is achieved via a Monte Carlo simulation procedure.

Program summary

Title of program:STATFLUXCatalogue identifier:ADYS_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYS_v1_0Program obtainable from: CPC Program Library, Queen's University of Belfast, N. IrelandLicensing provisions: noneComputer for which the program is designed and others on which it has been tested:Micro-computer with Intel Pentium III, 3.0 GHzInstallation:Laboratory of Linear Accelerator, Department of Experimental Physics, University of São Paulo, BrazilOperating system:Windows 2000 and Windows XPProgramming language used:Fortran-77 as implemented in Microsoft Fortran 4.0. NOTE: Microsoft Fortran includes non-standard features which are used in this program. Standard Fortran compilers such as, g77, f77, ifort and NAG95, are not able to compile the code and therefore it has not been possible for the CPC Program Library to test the program.Memory required to execute with typical data:8 Mbytes of RAM memory and 100 MB of Hard disk memoryNo. of bits in a word:16No. of lines in distributed program, including test data, etc.:6912No. of bytes in distributed program, including test data, etc.:229 541Distribution format:tar.gzNature of the physical problem:The investigation of transport mechanisms for radioactive substances, through environmental pathways, is very important for radiological protection of populations. One such pathway, associated with the food chain, is the grass-animal-man sequence. The distribution of trace elements in humans and laboratory animals has been intensively studied over the past 60 years [R.C. Pendlenton, C.W. Mays, R.D. Lloyd, A.L. Brooks, Differential accumulation of iodine-131 from local fallout in people and milk, Health Phys. 9 (1963) 1253-1262]. In addition, investigations on the incidence of cancer in humans, and a possible causal relationship to radioactive fallout, have been undertaken [E.S. Weiss, M.L. Rallison, W.T. London, W.T. Carlyle Thompson, Thyroid nodularity in southwestern Utah school children exposed to fallout radiation, Amer. J. Public Health 61 (1971) 241-249; M.L. Rallison, B.M. Dobyns, F.R. Keating, J.E. Rall, F.H. Tyler, Thyroid diseases in children, Amer. J. Med. 56 (1974) 457-463; J.L. Lyon, M.R. Klauber, J.W. Gardner, K.S. Udall, Childhood leukemia associated with fallout from nuclear testing, N. Engl. J. Med. 300 (1979) 397-402]. From the pathways of entry of radionuclides in the human (or animal) body, ingestion is the most important because it is closely related to life-long alimentary (or dietary) habits. Those radionuclides which are able to enter the living cells by either metabolic or other processes give rise to localized doses which can be very high. The evaluation of these internally localized doses is of paramount importance for the assessment of radiobiological risks and radiological protection. The time behavior of trace concentration in organs is the principal input for prediction of internal doses after acute or chronic exposure. The General Multiple-Compartment Model (GMCM) is the powerful and more accepted method for biokinetical studies, which allows the calculation of concentration of trace elements in organs as a function of time, when the flow parameters of the model are known. However, few biokinetics data exist in the literature, and the determination of flow and transfer parameters by statistical fitting for each system is an open problem.Restriction on the complexity of the problem:This version of the code works with the constant volume approximation, which is valid for many situations where the biological half-live of a trace is lower than the volume rise time. Another restriction is related to the central flux model. The model considered in the code assumes that exist one central compartment (e.g., blood) that connect the flow with all compartments, and the flow between other compartments is not included.Typical running time:Depends on the choice for calculations. Using the Derivative Method the time is very short (a few minutes) for any number of compartments considered. When the Gauss-Marquardt iterative method is used the calculation time can be approximately 5-6 hours when ∼15 compartments are considered.     

Structure and evolutionary implications of a "cysteine-rich" Campoletis sonorensis polydnavirus gene family

For successful parasitization, the female Campoletis sonorensis endoparasitic wasp injects a polydnavirus into its host, Heliothis virescens, during oviposition. Viral gene expression induces immunosuppression and alters development of the host. We report here that three abundantly expressed genes, VHv1.1, WHv1.0, and WHv1.6, describes a polydnavirus "cysteine-rich" gene family which may be important in inducing these host manifestations. These genes have a similar primary gene structure and their proteins contain cysteine motifs characteristic of snail ion-channel ligands, the omega-conotoxins. Like the omega-conotoxins, the intercysteine amino acid residues are hypervariable with only three identical amino acids in all motifs. The conservation of this domain in the three viral genes may reflect an important functional role for these viral proteins in the parasitization of H. virescens. The three genes also contain introns similar in sequence at comparable positions in their 5' untranslated leaders and coding sequences. VHv1.1 contains two cysteine motifs, and each motif is interrupted by an intron at the same position as in the cysteine motifs of WHv1.0 and WHv1.6. Intron 2 sequences of WHv1.0 and WHv1.6 are 92% identical, while the immediately flanking exon sequences encoding the cysteine motifs are only 76% identical. This provides an example of nuclear pre-mRNA introns which are more conserved than flanking exons among members of a gene family.