Ancestral animal genomes reconstruction

Reconstructing the evolutionary history of all species is an essential objective for evolutionary biologists. Much effort has been devoted to ancestral genome reconstruction. Numbered genome sequencing of current and extinct organisms enables evolutionary biologists to compare genomic data and reconstruct ancestral genomes. Long-term conservation of karyotype, gene order or gene sequence are clues to the heritage of each species and these data can be used by evolutionary biologists to synthesize distant ancestral genomes. In this review, we referred to the recent advances in ancestral genomes reconstruction and the insight it gives on genome evolution. Special attention is devoted to the use of this knowledge to understand the evolution of the immune system genes.     

Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.     

Role of Silica Properties in the Polymerisation of Ethylene Using Supported Metallocene Catalysts

The role of certain morphological properties of different silica used as supports for metallocene catalysts was investigated in order to quantify their eventual influence on the kinetics of ethylene polymerisation in heptane slurry, as well as on the polymer properties. It was shown that there is no clear link between porosity and observed activity with some highly porous silica producing relatively inactive supported catalysts. It was further shown that within a batch of silica, the particle size had a significant impact on observed kinetics. While it appears that there is possibly some diffusion resistance encountered in the larger particles, it was also shown that prolonged contact between the support and the alkylating agent could increase reaction rates in the larger particles.

     

Immunological efficacy of a three-dose schedule of hepatitis A vaccine in HIV-infected adults: HEPAVAC study

BACKGROUND: The immunogenicity of vaccines, including vaccine against hepatitis A virus (HAV), is impaired in patients with HIV infection, requiring revised immunization regimens. METHODS: We evaluated the immunological efficacy and safety of a 3-dose schedule of hepatitis A vaccine in HIV-infected adults. HAV-seronegative HIV-infected adults were randomized to receive either 3 doses of 1440 UI of hepatitis A vaccine (HAVRIX; GlaxoSmithKline, Marly le Roi, France) at weeks 0, 4, and 24 (46 patients) or 2 doses 24 weeks apart (49 patients). RESULTS: At week 28, seroconversion, defined as an anti-HAV antibody >or=20 mIU/mL, occurred in 82.6% and 69.4% of patients in the 3-dose and the 2-dose group, respectively (P = 0.13, intent-to-treat analysis, missing data = nonresponder), and in 88.4% and 72.3% of patients in the 3-dose and the 2-dose group, respectively (P = 0.06, observed analysis). Only 37.9% of patients experienced seroconversion after 1 vaccine dose (intent-to-treat analysis). Anti-HAV antibody geometric mean titers were 323 and 132 mIU/mL in the 3-dose group and 138 and 67 mIU/mL in the 2-dose group, respectively, 28 (P = 0.03) and 72 weeks (P = 0.05) after the first vaccine dose. There were no serious adverse events associated with the vaccine. Multivariate analysis showed no treatment group effect but indicated that absence of tobacco smoking (odds ratio = 2.92, 95% confidence interval: 1.07 to 7.97; P = 0.04) was an independent predictor of response to HAV vaccine. CONCLUSIONS: In HIV-infected adults, immunogenicity of hepatitis A vaccine is poor. Three doses of vaccine were safe and increased antibody titers.     

Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays

Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities.     

Panmictic structure of the genetic diversity of apomictic Meloidogyne nematodes (Nematoda: Tylenchida)

Species delineation in parthenogenetic tropical species of Meloidogyne nematodes is particularly difficult although they are strictly apomictic. In fact, parthenogenesis in Meloidogyne nematodes is a recent phenomenon and the structure of the genetic diversity is mainly explained by crosses prior to the establishment of parthenogenesis. Under such hypothesis, increasing the size of a characterized sample by adding individuals should result in the decrease of the diversity structure. Twelve individuals from different geographical origins were added to the initial pool of 26 lines characterized in a previous study and an AFLP study was conducted on the whole set of 38 lines. As expected under the panmixy hypothesis, this resulted in a loss of genetic structure. This confirms thus that the genetic structure of tropical parthenogenetic Meloidogyne is due to crosses anterior to the establishment of apomixy.     

Clinical IR in Canada: The Evolution of a Revolution

Purpose

To investigate the current status and evolution of both the interventional radiologist’s role as a clinician and the practice of interventional radiology (IR) over the past decade in Canada.

A signal detection–item response theory model for evaluating neuropsychological measures

Introduction: Models from signal detection theory are commonly used to score neuropsychological test data, especially tests of recognition memory. Here we show that certain item response theory models can be formulated as signal detection theory models, thus linking two complementary but distinct methodologies. We then use the approach to evaluate the validity (construct representation) of commonly used research measures, demonstrate the impact of conditional error on neuropsychological outcomes, and evaluate measurement bias.

Method: Signal detection–item response theory (SD–IRT) models were fitted to recognition memory data for words, faces, and objects. The sample consisted of U.S. Infantry Marines and Navy Corpsmen participating in the Marine Resiliency Study. Data comprised item responses to the Penn Face Memory Test (PFMT; N = 1,338), Penn Word Memory Test (PWMT; N = 1,331), and Visual Object Learning Test (VOLT; N = 1,249), and self-report of past head injury with loss of consciousness.

Results: SD–IRT models adequately fitted recognition memory item data across all modalities. Error varied systematically with ability estimates, and distributions of residuals from the regression of memory discrimination onto self-report of past head injury were positively skewed towards regions of larger measurement error. Analyses of differential item functioning revealed little evidence of systematic bias by level of education.

Conclusions: SD–IRT models benefit from the measurement rigor of item response theory—which permits the modeling of item difficulty and examinee ability—and from signal detection theory—which provides an interpretive framework encompassing the experimentally validated constructs of memory discrimination and response bias. We used this approach to validate the construct representation of commonly used research measures and to demonstrate how nonoptimized item parameters can lead to erroneous conclusions when interpreting neuropsychological test data. Future work might include the development of computerized adaptive tests and integration with mixture and random-effects models.     

Effect of systemic kynurenine on cortical spreading depression and its modulation by sex hormones in rat

BackgroundThe aura symptoms in migraine are most likely due to cortical spreading depression (CSD). CSD is favored by NMDA receptor activation and increased cortical excitability. The latter probably explains why migraine with aura may appear when estrogen levels are high, like during pregnancy. Kynurenic acid, a derivative of tryptophan metabolism, is an endogenous NMDA receptor antagonist whose cerebral concentrations can be augmented by systemic administration of its precursor l-kynurenine.ObjectiveTo determine if exogenous administration of l-kynurenine is able to influence KCl-induced CSD in rat, if the effect is sex-dependent and if it differs in females between the phases of the estrous cycle.MethodsAdult Sprague–Dawley rats (n = 8/group) received intraperitoneal (i.p.) injections of l-kynurenine (L-KYN, 300 mg/kg), L-KYN combined with probenecid (L-KYN + PROB) that increases cortical concentration of KYNA by blocking its excretion from the central nervous system, probenecid alone (PROB, 200 mg/kg) or NaCl. Cortical kynurenic acid concentrations were determined by HPLC (n = 7). Thirty minutes after the injections, CSDs were elicited by application of 1 M KCl over the occipital cortex and recorded by DC electrocorticogram. In NaCl and L-KYN groups, supplementary females were added and CSD frequency was analyzed respective to the phases of the estrous cycle determined by vaginal smears.ResultsIn both sexes, PROB, L-KYN and L-KYN + PROB increased cortical kynurenic acid level. PROB, L-KYN and L-KYN + PROB with increasing potency decreased CSD frequency in female rats, while in males such an effect was significant only for L-KYN + PROB. The inhibitory effect of L-KYN on CSD frequency in females was most potent in diestrus.Conclusionl-Kynurenine administration suppresses CSD, most likely by increasing kynurenic acid levels in the cortex. Females are more sensitive to this suppressive effect of l-kynurenine than males. These results emphasize the role of sex hormones in migraine and open interesting novel perspectives for its preventive treatment.     

Cortical and subcortical projections to primary visual cortex in anophthalmic,enucleated and sighted mice

The purpose of this study was to identify and compare the afferent projections to the primary visual cortex in intact and enucleated C57BL/6 mice and in ZRDCT/An anophthalmic mice. Early loss of sensory‐driven activity in blind subjects can lead to activations of the primary visual cortex by haptic or auditory stimuli. This intermodal activation following the onset of blindness is believed to arise through either unmasking of already present cortical connections, sprouting of novel cortical connections or enhancement of intermodal cortical connections. Studies in humans have similarly demonstrated heteromodal activation of visual cortex following relatively short periods of blindfolding. This suggests that the primary visual cortex in normal sighted subjects receives afferents, either from multisensory association cortices or from primary sensory cortices dedicated to other modalities. Here cortical afferents to the primary visual cortex were investigated to determine whether the visual cortex receives sensory input from other modalities, and whether differences exist in the quantity and/or the structure of projections found in sighted, enucleated and anophthalmic mice. This study demonstrates extensive direct connections between the primary visual cortex and auditory and somatosensory areas, as well as with motor and association cortices in all three animal groups. This suggests that information from different sensory modalities can be integrated at early cortical stages and that visual cortex activations following visual deprivations can partly be explained by already present intermodal corticocortical connections.