The separation of timescales in Bayesian survival modeling of the time-varying effect of a time-dependent exposure

In this paper, we apply flexible Bayesian survival analysis methods to investigate the risk of lymphoma associated with kidney transplantation among patients with end-stage renal disease. Of key interest is the potentially time-varying effect of a time-dependent exposure: transplant status. Bayesian modeling of the baseline hazard and the effect of transplant requires consideration of 2 timescales: time since study start and time since transplantation, respectively. Previous related work has not dealt with the separation of multiple timescales. Using a hierarchical model for the hazard function, both timescales are incorporated via conditionally independent stochastic processes; smoothing of each process is specified via intrinsic conditional Gaussian autoregressions. Features of the corresponding posterior distribution are evaluated from draws obtained via a Metropolis-Hastings-Green algorithm.     

A numerical study of the blocking of migraine by Rolando sulcus

Migraine with aura is a complex phenomena, which remains still not completely understood. A striking fact is that its clinical manifestations may change from one patient to another. Migraine with aura may only consist in visual hallucinations, but may as well go on to temporary aphasy. However, for all the patients it always stops before it goes from area 3 to area 4, thus just before crossing Rolando sulcus. In this paper, we give arguments showing that the detailed geometry of Rolando sulcus in human cortex may by itself explain that migraine attack never crosses Rolando sulcus.     

Duration of fertility and hatchability of the common duck (Anas platyrhynchos) in pure- or crossbreeding with Muscovy drakes (Cairina moschata)

A total of 540 common duck dams were used for a comparison of duration of fertility and hatchability between eggs issued from common dams inseminated with sperm (175 x 10(6) dose(-1)) from either common (pure-breeding or PB) or Muscovy (crossbreeding or CB) drakes. Artificial inseminations (AI) were performed at 3 periods of the reproductive season (27-35, 39-43 and 49-56 weeks) with 2 alternate inseminations/period at 3-week intervals (one with semen from common and the other from Muscovy). Fertility was estimated from egg candling while early embryo mortality (EEM), medium embryo mortality (MEM) and late embryo mortality (LEM) was estimated on Days 0-6 (PB+CB), Days 7-25 (PB) or Day 28 (CB) of incubation, and after, respectively. Overall fertility from Days 2-12 after AI was 61.1% in PB and 42.8% in CB. The maximum duration of fertility (time interval between AI and last fertile egg) was 8.1 days in PB versus 6.4 days in CB (p<0.05). The age of the dam influenced this interval, particularly in PB, with a longer duration at 40 weeks compared to 50 (p<0.05). On average, EEM represented 2.5% of fertile eggs while MEM accounted for 5% of surviving embryos on Day 6 and LEM, for 11.5% of hatched eggs. MEM was significantly higher in CB (6.3%) compared to PB (3.9%; p<0.05). Overall, an increase in EEM and MEM was observed in both types of eggs at and after 50 weeks of age. An increase in EEM (regardless of dam's age) and in MEM (only in the oldest females) was observed with sperm storage duration. Sex ratio at hatching (49.2% males in PB vs. 53.0% in CB) was particularly unbalanced on the first fertile day (54.7% and 57.1%, respectively).     

Extracellular protease activity of different Pseudomonas strains: dependence of proteolytic activity on culture conditions

AIMS: This study investigated the effect of growth conditions on proteolytic activity of a Pseudomonas strain, named Pseudomonas sp. LBSA1, isolated from bulk raw milk. It was compared with three Pseudomonas chlororaphis and one Pseudomonas fluorescens strain from culture collections. METHODS AND RESULTS: Bacteriae were grown in a minimal salt medium. For all the strains, addition of 1% (v/v) skim milk to the growth medium was sufficient to induce protease production in 48-h culture. Addition of 1 mmol l(-1) calcium chloride permitted the detection of proteolytic activity of four strains in 48-h cultures but not for Pseudomonas sp. LBSA1. The five strains presented two patterns of proteolytic activity when grown in the minimal salt medium supplemented with 2% (v/v) skim milk at various temperatures for 48 h. Two electrophoretic protease patterns were also obtained from the zymogram of extracellular medium for the five strains. CONCLUSIONS: The growth conditions permitting protease production are variable and do not depend on the genus of the producing strain. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time a study on proteolytic activity of P. chlororaphis strains is reported. Among the tested criteria, zymograms of extracellular medium were the only ones that permitted distinguishing the P. chlororaphis strains from the P. fluorescens strain.     

Microelectrode measurement of ammonium profiles in freshwater sediments

Abstract Ammonium microprofiles in two dominant types of lake sediment were measured using ion-selective microelectrodes. These profiles enabled establishment of local fluxes and convensions. Comparison of ammonium profiles obtained from the analysis of sediment slices with those measured with microelectrodes showed the superior spatial resolution of the latter method. Flux measurements with microelectrodes were confirmed by laboratory incubation experiments. In both sediments ammonium consumption was restricted to the oxic surface layer. In sandy sediments ammonium was only consumed, while in silty sediment both ammonium production and consumption were observed. In silty sediment ammonium production by anaerobic mineralization was not balanced by ammonium consumption in the oxic surface layer.     

Ghrelin in growth and development

Exogenous administration of ghrelin increases caloric intake and stimulates growth hormone (GH) secretion, two effects that are mediated through binding of ghrelin to the GH secretagogue receptor (GHS-R). In addition, ghrelin is thought to inhibit adipogenesis by GHS-R-independent mechanisms. In adults, ghrelin is mainly produced by the stomach. In contrast, in the fetal and early postnatal period, ghrelin gene expression is abundant in the pancreas but not in the stomach. While knockout animal studies demonstrate that ghrelin is not required for perinatal development under normal nutritional conditions, the characteristics of ghrelin metabolism during fetal development suggest that ghrelin could contribute to the programming of mechanisms involved in energy balance, such as beta-cell maturation, orexigenic pathways and adipogenesis. In humans, ghrelin concentrations progressively decrease during childhood and adolescence, as well as with advancing puberty. In adolescents, similar to adults, ghrelin concentrations are inversely related to body mass index and to circulating insulin. One notable exception is the presence of elevated ghrelin concentrations in subjects with Prader-Willi syndrome, raising the possibility that ghrelin could be part of the etiology of excess food intake in this condition. These data raise a number of fascinating questions on the potential physiologic role of this hormone during growth and development.     

In vitro embryo production efficiency in cattle and its association with oocyte adenosine triphosphate content, quantity of mitochondrial DNA, and mitochondrial DNA haplogroup

Mitochondria have a broad range of functions that affect reproduction, and structural as well as quantitative variation in mtDNA has been associated with gamete quality and reproductive success. To investigate the mitochondria effect on in vitro embryo production, we collected oocytes by ultrasound-guided follicular aspiration from donor cows known to differ in the developmental capacity, measured by the blastocyst formation rate, of their oocytes. To evaluate the potential effects of mtDNA and mitochondrial function on oocyte quality, the donor cows' mtDNA control region was sequenced and, after pairwise comparisons of polymorphisms, animals were grouped into two major haplogroups. The number of mtDNA molecules per oocyte was quantified by real-time PCR, and the adenosine triphosphate (ATP) content was measured in each oocyte to identify variations between haplogroups. Overall, ATP stocks in oocytes of the two haplogroups differed significantly (P < 0.05; means +/- SEM) both at the germinal vesicle and metaphase II stages (2.8 +/- 0.06 pmol vs. 2.6 +/- 0.07 pmol and 2.9 +/- 0.1 pmol vs. 2.3 +/- 0.06 pmol, respectively). The proportion of development to blastocyst was significantly different between haplogroups (22.3 +/- 2.1 % vs. 36.7 +/- 2.9 %). The number of mtDNA molecules per oocyte was highly variable (377 327 +/- 14 104, ranging from 2.0 x 10(3) to 1.2 x 10(6)) but not significantly different between the two haplogroups; significant differences were observed between animals without any apparent relationship to blastocyst production. These data suggest that mitochondria and mtDNA haplogroup affect the developmental capacity of bovine oocytes in vitro.     

Production of heterologous and chimeric scaffoldins by Clostridium acetobutylicum ATCC 824

Clostridium acetobutylicum ATCC 824 converts sugars and various polysaccharides into acids and solvents. This bacterium, however, is unable to utilize cellulosic substrates, since it is able to secrete very small amounts of cellulosomes. To promote the utilization of crystalline cellulose, the strategy we chose aims at producing heterologous minicellulosomes, containing two different cellulases bound to a miniscaffoldin, in C. acetobutylicum. A first step toward this goal describes the production of miniCipC1, a truncated form of CipC from Clostridium cellulolyticum, and the hybrid scaffoldin Scaf 3, which bears an additional cohesin domain derived from CipA from Clostridium thermocellum. Both proteins were correctly matured and secreted in the medium, and their various domains were found to be functional.