Natural killer cell genes and functions after kidney transplantation

Natural Killer (NK) cells are of special interest in solid organ transplantation (SOT) because classical immunosuppressive drugs could enhance NK cells activity.We studied NK cells after kidney transplantation in three different situations. First, we analysed the peripheral repertoire reconstitution and function of NK cells after a polyclonal rabbit anti-thymocytes globulin (rATG) induction therapy, in 20 patients transplanted with living donor and with a low immunological risk. Second, we analysed the influence of KIR genes on the risk of CMV primo-infection or reactivation in 224 transplanted patients during the first year. Finally, we studied the risk of rejection and graft function during the first 5 years according to the KIR genes. Our study demonstrates that after an intial drop, NK cell reconstitution is fast with a ratio of CD56+/CD3− cells versus CD3+ cells that remains identical. The fraction of NK cells expressing the inhibitory receptor NKG2A significantly increases and the activating receptor NKG2D decreases after transplantation to retrieve the pretransplantation value after one year. The secretion of INF-f × and the cytotoxicity is maintained over time after transplantation. Then, we demonstrated that the presence of 2 KIR missing ligands and a large number of activating KIR gene protected against CMV primo-infection or reactivation during the first year post transplantation. Finally, the KIR genes and their HLA ligands do not influence the long term graft function after univariate and multivariate analysis. Our data suggest that despite the modification of the receptor repertoire, NK cell activity is preserved. NK cells are an important player of the immune response in the first year after transplantation mainly thanks to their anti-infectious activity.

Using spatially distributed parameters and multi-response objective functions to solve parameterization of complex applications of semi-distributed hydrological models

Application of semi-distributed hydrological models to large, heterogeneous watersheds deals with several problems. On one hand, the spatial and temporal variability in catchment features should be adequately represented in the model parameterization, while maintaining the model complexity in an acceptable level to take advantage of state-of-the-art calibration techniques. On the other hand, model complexity enhances uncertainty in adjusted model parameter values, therefore increasing uncertainty in the water routing across the watershed. This is critical for water quality applications, where not only streamflow, but also a reliable estimation of the surface versus subsurface contributions to the runoff is needed. In this study, we show how a regularized inversion procedure combined with a multiobjective function calibration strategy successfully solves the parameterization of a complex application of a water quality-oriented hydrological model. The final value of several optimized parameters showed significant and consistentdifferences across geological and landscape features. Although the number of optimized parameters was significantly increased by the spatial and temporal discretization of adjustable parameters, the uncertainty in water routing results remained at reasonable values. In addition, a stepwise numerical analysis showed that the effects on calibration performance due to inclusion of different data types in the objective function could be inextricably linked. Thus caution should be taken when adding or removing data from an aggregated objective function.

GAP-independent functions of DLC1 in metastasis.

Metastases are responsible for most cancer-related deaths. One of the hallmarks of metastatic cells is increased motility and migration through extracellular matrixes. These processes rely on specific small GTPases, in particular those of the Rho family. Deleted in liver cancer-1 (DLC1) is a tumor suppressor that bears a RhoGAP activity. This protein is lost in most cancers, allowing malignant cells to proliferate and disseminate in a Rho-dependent manner. However, DLC1 is also a scaffold protein involved in alternative pathways leading to tumor and metastasis suppressor activities. Recently, substantial information has been gathered on these mechanisms and this review is aiming at describing the potential and known alternative GAP-independent mechanisms allowing DLC1 to impair migration, invasion, and metastasis formation.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study.

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (<or=40 g/day) and were not genotype 3, indicated no strong evidence of excess mortality. We found little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

R functions for quantifying nonindependence in standard dyadic and SRM designs

Interdependence is the main feature of dyadic relationships and, in recent years, various statistical procedures have been proposed for quantifying and testing this social attribute in different dyadic designs. The purpose of this paper is to develop several functions for this kind of statistical tests in an R package, known as nonindependence, for use by applied social researchers. A Graphical User Interface (GUI) is also developed to facilitate the use of the functions included in this package. Examples drawn from psychological research and simulated data are used to illustrate how the software works.

Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins.

By virtue of their general ability to bind (hold) translocating or unfolding polypeptides otherwise doomed to aggregate, molecular chaperones are commonly dubbed "holdases". Yet, chaperones also carry physiological functions that do not necessitate prevention of aggregation, such as altering the native states of proteins, as in the disassembly of SNARE complexes and clathrin coats. To carry such physiological functions, major members of the Hsp70, Hsp110, Hsp100, and Hsp60/CCT chaperone families act as catalytic unfolding enzymes or unfoldases that drive iterative cycles of protein binding, unfolding/pulling, and release. One unfoldase chaperone may thus successively convert many misfolded or alternatively folded polypeptide substrates into transiently unfolded intermediates, which, once released, can spontaneously refold into low-affinity native products. Whereas during stress, a large excess of non-catalytic chaperones in holding mode may optimally prevent protein aggregation, after the stress, catalytic disaggregases and unfoldases may act as nanomachines that use the energy of ATP hydrolysis to repair proteins with compromised conformations. Thus, holding and catalytic unfolding chaperones can act as primary cellular defenses against the formation of early misfolded and aggregated proteotoxic conformers in order to avert or retard the onset of degenerative protein conformational diseases.

How do the different components of episodic memory develop? Role of executive functions and short-term feature-binding abilities.

This study investigated the development of all 3 components of episodic memory (EM), as defined by Tulving, namely, core factual content, spatial context, and temporal context. To this end, a novel, ecologically valid test was administered to 109 participants aged 4-16 years. Results showed that each EM component develops at a different rate. Ability to memorize factual content emerges early, whereas context retrieval abilities continue to improve until adolescence, due to persistent encoding difficulties (isolated by comparing results on free recall and recognition tasks). Exploration of links with other cognitive functions revealed that short-term feature-binding abilities contribute to all EM components, and executive functions to temporal and spatial context, although ability to memorize temporal context is predicted mainly by age.

Adapter and enzymatic functions of proteases in T-cell activation.

Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T-cell receptor controls T-cell proliferation through proteases such as mucosa-associated lymphoid tissue 1 (MALT1) and Caspase-8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T-cell response and represent interesting targets of therapeutic immunomodulation.

Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight.

BACKGROUND: The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM. METHODS: Examination survey in a sample representative of the entire population aged 25-64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age. RESULTS: The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI > or = 25 kg/m2) and obesity (BMI > or = 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight. CONCLUSION: We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.

Measurement of the specific heat and determination of the thermodynamic functions of relaxed amorphous silicon

The specific heat, cp, of two amorphous silicon (a-Si) samples has been measured by differential scanning calorimetry in the 100–900K temperature range. When the hydrogen content is reduced by thermal annealing, cp approaches the value of crystalline Si (c-Si). Within experimental accuracy, we conclude that cp of relaxed pure a-Si coincides with that of c-Si. This result is used to determine the enthalpy, entropy, and Gibbs free energy of defect-free relaxed a-Si. Finally, the contribution of structural defects on these quantities is calculated and the melting point of several states of a-Si is predicted

Emerging functions of myelin associated proteins during development neuronal plasticity and and neurpdegeneration.

Adult mammalian central nervous system (CNS) axons have a limited regrowth capacity following injury. Myelin-associated inhibitors (MAIs) limit axonal outgrowth and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo-A, MAG and OMgp, share two common neuronal receptors: NgR1, together with its co-receptors (p75(NTR), TROY and Lingo-1), and the recently described paired immunoglobulin-like receptor B (PirB). These proteins impair neuronal regeneration by limiting axonal sprouting. Some of the elements involved in the myelin inhibitory pathways may still be unknown, but the discovery that blocking both PirB and NgR1 activities leads to near-complete release from myelin inhibition, sheds light on one of the most competitive and intense fields of neuroregeneration study during in recent decades. In parallel with the identification and characterization of the roles and functions of these inhibitory molecules in axonal regeneration, data gathered in the field strongly suggest that most of these proteins have roles other than axonal growth inhibition. The discovery of a new group of interacting partners for myelin-associated receptors and ligands, as well as functional studies within or outside the CNS environment, highlights the potential new physiological roles for these proteins in processes such as development, neuronal homeostasis, plasticity and neurodegeneration.

Traces of functions in Fock spaces on lattices of critical density

Following a scheme of Levin we describe the values that functions in Fock spaces take on lattices of critical density in terms of both the size of the values and a cancelation condition that involves discrete versions of the Cauchy and Beurling-Ahlfors transforms.