Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Ieukoencephalopathy, Genetic Homogeneity, and Mapping of the Locus within a 2-cM Interval

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Z_max = 37.24 at θ = .01) was obtained with marker D19S841, a new CA_n microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19pl3.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region.     

1-Nitrosomelatonin is a spontaneous NO-releasing compound.

Melatonin (N-acetyl-5-methoxytryptamin), the main hormone secreted by the pineal gland in mammals, is nitrosated by nitrite at acidic pH and by NO in the presence of oxygen under neutral conditions. Melatonin is also partly converted to 1-nitrosomelatonin by oxoperoxonitrate (ONOO-, peroxynitrite) in phosphate-buffered solutions at pH 7-10 [Blanchard, B., et al. (2000) Journal of Pineal Research 29, 184-192]. In the present report, we show that 1-nitrosomelatonin in turn behaves as an NO-donor regenerating melatonin. NO-release is evidenced by the formation of nitrite in phosphate-buffered solutions and oxidation of HbO2. No peroxynitrite was formed during that decomposition because serotonin used as a probe was converted only to 4-nitroso-serotonin as expected for a true NO-donor [Blanchard, B., et al. (2001) Free Radical Research, 34, 177-188]. The spontaneous decay of 1-nitrosomelatonin is not affected by GSH and metallic ions but its decomposition is accelerated in acidic pH or in the presence of NADH or ascorbate. Furthermore, melatonin is partially or entirely recovered in the absence or presence of ascorbate, respectively. A homolytic cleavage of 1-nitrosomelatonin is strongly suggested and discussed. Formation of 1-nitrosomelatonin from melatonin and reactive nitrogen species (RNS) followed by its decay into NO demonstrates that melatonin could reduce these RNS to NO.     

Production ofAgrobacterium-mediated transgenic fertile plants by direct somatic embryogenesis from immature zygotic embryos ofDatura innoxia

This work describes a new method to obtain transgenic somatic embryos fromAgrobacterium-infected immature zygotic embryos ofDatura innoxia. It has several advantages over previous transformation methods such as the absence of a callus phase, an average transformation rate of 76% and a high regeneration frequency. Critical steps for optimal transformation were the embryo stage and a short preculture treatment. The marker gene -glucuronidase and light microscopy were used to identify the competent embryogenic cells which, after transformation, passed through the classical stages of embryo development. The transgenes were transmitted to the progeny in a Mendelian fashion. The plants regenerated via direct somatic embryogenesis were cytologically and morphologically uniform. We also observed that: (1) wounding or wound-induced divisions were not required for zygotic embryo transformation; (2) epidermal cells were competent for both transformation and regeneration; and (3) competency forAgrobacterium infection was developmental stage-specific. This new method should facilitate the development of new strategies to routinely transform recalcitrant plant species.     

Bioconversion of glyceryl trinitrate into mononitrates by Geotrichum candidum

Glyceryl trinitrate (GTN) 2 mM was quantitatively converted into its 1 and 2 mononitrate derivatives by Geotrichum candidum, with consumption of the nitrite ions produced. The conversion proceeded at a rate independent of the addition of either organic carbon or organic nitrogen sources. Eight batches of nitrate ester, which were added every 24 hours, were successfully converted as far as during the bioconversion process GTN concentration did not exceed 2 mM. When those limiting conditions were not observed, dramatic toxicity of GTN was noticed.     

Growth and Senescence of the Successive Grass Leaves on a Tiller. Ontogenic Development and Effect of Temperature

The tiller characteristics (length and age of laminae, numberof leaves per tiller) which depend on morphogenetic characterssuch as leaf appearance and expansion rates, leaf growth durationand leaf lifespan were studied in the field over four growingseasons to gain a better understanding of the progressive changesin leaf digestibility over time, and to facilitate the developmentof predictive mathematical models. We show that, for a givenregrowth, only the number of leaves per tiller and the laminaexpansion rate remain constant throughout growth. In other words,the length of successive laminae, their growth duration andlifespan increased while their rate of appearance decreasedin such a way that the lamina expansion rate at the tiller levelremained constant. These changes were associated with an increasein sheath length which governs both the lamina appearance rateand its growth duration. As temperature increased, the averagelamina expansion rate and the number of laminae which grew bothincreased simultaneously. Therefore, high temperature acceleratesthe changes in tiller characteristics which occur as growthprogresses. Copyright 2000 Annals of Botany Company Leaf, senescence, phyllochron, lifespan, digestibility, temperature, cocksfoot, Dactylis glomerata L     

Importation route of the sickle cell trait into Portugal: contribution of molecular epidemiology.

To elucidate the origin and spread of the sickle cell trait into the Portuguese population, we examined nine polymorphic DNA markers within the beta globin gene cluster defining the haplotype. The population sample included 64 sickle-cell-gene-bearing individuals from defined Portuguese-speaking white, black, and Asian Indian populations. The nature and geographic distribution of the different beta S haplotypes in Portugal suggest that the sickle cell trait has been imported twice: between the eighth and the thirteenth centuries from the Mediterranean basin (in association with the Benin haplotype) and after the fifteenth century from black Africa over an Atlantic route (Senegal and Bantu haplotypes).     

Heritability of longevity in Large White and Landrace sows using continuous time and grouped data models

Background

Using conventional measurements of lifetime, it is not possible to differentiate between productive and non-productive days during a sow''s lifetime and this can lead to estimated breeding values favoring less productive animals. By rescaling the time axis from continuous to several discrete classes, grouped survival data (discrete survival time) models can be used instead.

Methods

The productive life length of 12319 Large White and 9833 Landrace sows was analyzed with continuous scale and grouped data models. Random effect of herd*year, fixed effects of interaction between parity and relative number of piglets, age at first farrowing and annual herd size change were included in the analysis. The genetic component was estimated from sire, sire-maternal grandsire, sire-dam, sire-maternal grandsire and animal models, and the heritabilities computed for each model type in both breeds.

Results

If age at first farrowing was under 43 weeks or above 60 weeks, the risk of culling sows increased. An interaction between parity and relative litter size was observed, expressed by limited culling during first parity and severe risk increase of culling sows having small litters later in life. In the Landrace breed, heritabilities ranged between 0.05 and 0.08 (s.e. 0.014-0.020) for the continuous and between 0.07 and 0.11 (s.e. 0.016-0.023) for the grouped data models, and in the Large White breed, they ranged between 0.08 and 0.14 (s.e. 0.012-0.026) for the continuous and between 0.08 and 0.13 (s.e. 0.012-0.025) for the grouped data models.

Conclusions

Heritabilities for length of productive life were similar with continuous time and grouped data models in both breeds. Based on these results and because grouped data models better reflect the economical needs in meat animals, we conclude that grouped data models are more appropriate in pig.     

Principal component approach in variance component estimation for international sire evaluation

Background

The dairy cattle breeding industry is a highly globalized business, which needs internationally comparable and reliable breeding values of sires. The international Bull Evaluation Service, Interbull, was established in 1983 to respond to this need. Currently, Interbull performs multiple-trait across country evaluations (MACE) for several traits and breeds in dairy cattle and provides international breeding values to its member countries. Estimating parameters for MACE is challenging since the structure of datasets and conventional use of multiple-trait models easily result in over-parameterized genetic covariance matrices. The number of parameters to be estimated can be reduced by taking into account only the leading principal components of the traits considered. For MACE, this is readily implemented in a random regression model.

Methods

This article compares two principal component approaches to estimate variance components for MACE using real datasets. The methods tested were a REML approach that directly estimates the genetic principal components (direct PC) and the so-called bottom-up REML approach (bottom-up PC), in which traits are sequentially added to the analysis and the statistically significant genetic principal components are retained. Furthermore, this article evaluates the utility of the bottom-up PC approach to determine the appropriate rank of the (co)variance matrix.

Results

Our study demonstrates the usefulness of both approaches and shows that they can be applied to large multi-country models considering all concerned countries simultaneously. These strategies can thus replace the current practice of estimating the covariance components required through a series of analyses involving selected subsets of traits. Our results support the importance of using the appropriate rank in the genetic (co)variance matrix. Using too low a rank resulted in biased parameter estimates, whereas too high a rank did not result in bias, but increased standard errors of the estimates and notably the computing time.

Conclusions

In terms of estimation''s accuracy, both principal component approaches performed equally well and permitted the use of more parsimonious models through random regression MACE. The advantage of the bottom-up PC approach is that it does not need any previous knowledge on the rank. However, with a predetermined rank, the direct PC approach needs less computing time than the bottom-up PC.