Genetics of schizophrenia and bipolar disorder: recent success of linkage studies with evidence of specific and shared susceptibility loci

Results claiming linkage on two chromosomes for schizophrenia (SZ) and bipolar affective disorder (BP) were prematurely published in Nature at the end of the '80s. This ended up into disappointment. The knowledge accumulated from the first generation of unsuccessful molecular genetics studies of SZ and BP provided a stronger basis for the following generation of linkage studies that are now yielding encouraging converging results. Hence, we report several genomics susceptibility loci for SZ and BP, some of them being probably shared by the two major psychiatric illnesses whereas others could be specific to each.     

Experimentation in persons wtih a neurodegenerative disease

Neurodegenerative diseases, of which the Alzheimer's disease, are more and more frequently the object of researches and new experiments. One wishes these experiments to be promising. Experiment with persons affected by a degenerative disease can begin at a moment when the subject is capable, and can be pursued beyond his incapacity. Law authorizes that a person of full age incapable of giving consent be subject of experiment. On the other hand, from the report of the incapacity, consent has to come from the legal representative: the mandatary, tutor or curator. The mandate given in anticipation of the mandator's incapacity empowers another person (the mandatary) to represent her. The use of this mandate confines the inconveniences of the mandator's incapacity to an interruption of the experiment for a duration of some weeks.     

Glucocorticoids, 11 beta-hydroxysteroid dehydrogenase type 1, and visceral obesity

Glucocorticoids are implicated as a pathophysiological mediator of obesity and its accompanying metabolic and cardiovascular complications. Obese patients exhibit normal circulating cortisol levels, related to increased glucocorticoid production and degradation. However, it has been demonstrated that local production of active cortisol from inactive cortisone driven by 11 beta-hydroxysteroid dehydrogenase type 1 is exaggerated in adipose tissue of obese subjects. Such local hypercortisolism may be responsible for increased adipocyte differentiation and enhanced secretion of free fatty acids and other substances involved in the metabolic and cardiovascular complications observed in obesity.     

Ancistrolikokine D,a 5,8'-coupled naphthylisoquinoline alkaloid,and related natural products from Ancistrocladus likoko

A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A. likoko to other Central African Ancistrocladus species. The compounds show moderate activities against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei rhodesiense.     

Orbitoblepharophimosis syndrome: a 16-year perspective

The orbitoblepharophimosis syndrome is a congenital malformation of the orbitopalpebral region. It is an autosomal-dominant condition typified by palpebral and orbital phimosis, ptosis, epicanthus inversus with telecanthus, and enophthalmia. It has three forms: minor, major, and extreme. It is a rare malformation affecting both sexes. The gene responsible is 3q21-24. Surgical treatment involves three to four operations: orbital remodeling by burring and grafting (intraorbital and extraorbital), epicanthus correction, and ptosis operation. Results varied depending on the severity of the form and the quality of the tissues. The authors present a series of 50 patients who were treated for this syndrome over the past 16 years.     

Characterization of sterol uptake in leaf tissues of sugar beet

The uptake of cholesterol has been characterized in leaf discs from mature leaves of sugar beet (Beta vulgaris L.). This transport system exhibited a simple saturable phase with an apparent Michaelis constant ranging from 30 to 190 M depending on the sample. When present at 10 M excess, other sterols were able to inhibit cholesterol uptake. Moreover, binding assays demonstrated the presence of high-affinity binding sites for cholesterol in purified plasma membrane vesicles. In the range 1–60 M, cholesterol uptake showed an active component evidenced by action of the protonophore carbonyl cyanide m-chlorophenylhydrazone. Energy was required as shown by the inhibition of uptake induced by respiration inhibitors (NaN₃), darkness and photosynthesis inhibitors [3-(3,4-dichlorophenyl)-1,1-dimethylurea, methyl viologen]. Moreover, the process was strongly dependent on the experimental temperature. Uptake was optimal at acidic pH (4.0), sensitive to ATPase modulators, inhibited by thiol reagents (N-ethylmaleimide, p-chloromercuribenzenesulfonic acid, Mersalyl) and by the histidyl-group reagent diethyl pyrocarbonate. The addition of cholesterol did not modify H⁺ flux from tissues, indicating that H⁺-co-transport was unlikely to be involved. MgATP did not increase the uptake, arguing against involvement of an ABC cassette-type transporter. By contrast, cryptogein, a sterol carrier protein from the Oomycete Phytophtora cryptogea, greatly increased absorption. Taken together, the results reported in this work suggest that plant cells contain a specific plasma membrane transport system for sterols.Abbreviations CCCP carbonyl cyanide m-chlorophenylhydrazone - PCMBS p-chloromercuribenzenesulfonic acid - PMV plasma membrane vesicle - TLC thin-layer chromatography     

Adjacent and spontaneous neurotization after distal digital replantation in children

In an exclusively pediatric population, this retrospective study examined the functional and aesthetic results after distal replantation without nerve suture. The aim was to demonstrate, in the child, the presence of spontaneous nervous regeneration resulting in a fingertip pulp with discriminatory sensation. Eight amputations in eight children with a mean age of 9 years and 2 months on the day of the accident were reviewed. The cases were managed by a single surgeon over a period of 8 years and were collected from two different hand centers. The patients were then examined by a different surgeon, and the data were collected. Sensibility was evaluated using the Weber, Semmes-Weinstein, and wrinkle tests. The results were excellent, with mean values of 4.6 mm for the Weber test, 3.3 for the Semmes-Weinstein test, and a positive wrinkle test in all subjects. All patients thus recovered discriminatory sensation with minimal aesthetic sequelae. The usual factors adversely affecting the results of the replantation (ischemic time, level and mechanism of the amputation, and quality of the venous return) were examined, but no statistical analysis was performed because of the small sample size. This study demonstrates the presence of the clinical phenomenon of adjacent neurotization in the absence of nerve repair. It thus confirms that children are excellent candidates for replantation of the distal extremities, even when nerve suture is not performed.     

Characterization of a radish introgression carrying the Ogura fertility restorer gene Rfo in rapeseed,using the Arabidopsis genome sequence and radish genetic mapping

The radish Rfo gene restores male fertility in radish or rapeseed plants carrying Ogura cytoplasmic male-sterility. This system was first discovered in radish and was transferred to rapeseed for the production of F1 hybrid seeds. We aimed to identify the region of the Arabidopsis genome syntenic to the Rfo locus and to characterize the radish introgression in restored rapeseed. We used two methods: amplified consensus genetic markers (ACGMs) in restored rapeseed plants and construction of a precise genetic map around the Rfo gene in a segregating radish population. The use of ACGMs made it possible to detect radish orthologs of Arabidopsis genes in the restored rapeseed genome. We identified radish genes, linked to Rfo in rapeseed and whose orthologs in Arabidopsis are carried by chromosomes 1, 4 and 5. This indicates several breaks in colinearity between radish and Arabidopsis genomes in this region. We determined the positions of markers relative to each other and to the Rfo gene, using the progeny of a rapeseed plant with unstable meiotic transmission of the radish introgression. This enabled us to produce a schematic diagram of the radish introgression in rapeseed. Markers which could be mapped both on radish and restored rapeseed indicate that at least 50 cM of the radish genome is integrated in restored rapeseed. Using markers closely linked to the Rfo gene in rapeseed and radish, we identified a contig spanning six bacterial artificial chromosome (BAC) clones on Arabidopsis chromosome 1, which is likely to carry the orthologous Rfo gene.Electronic Supplementary Material Supplementary material is available in the online version of this article at Communicated by H. C. BeckerS. Giancola and S. Marhadour contributed equally to this work     

The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function

Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF and its val/met polymorphism in human memory and hippocampal function and suggest val/met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.