Symmetrical and asymmetrical gaits in the mouse: patterns to increase velocity

The gaits of the adult SWISS mice during treadmill locomotion at velocities ranging from 15 to 85 cm s^–1 have been analysed using a high-speed video camera combined with cinefluoroscopic equipment. The sequences of locomotion were analysed to determine the various space and time parameters of limb kinematics. We found that velocity adjustments are accounted for differently by the stride frequency and the stride length if the animal showed a symmetrical or an asymmetrical gait. In symmetrical gaits, the increase of velocity is provided by an equal increase in the stride length and the stride frequency. In asymmetrical gaits, the increase in velocity is mainly assured by an increase in the stride frequency in velocities ranging from 15 to 29 cm s^–1. Above 68 cm s^–1, velocity increase is achieved by stride length increase. In velocities ranging from 29 to 68 cm s^–1, the contribution of both variables is equal as in symmetrical gaits. Both stance time and swing time shortening contributed to the increase of the stride frequency in both gaits, though with a major contribution from stance time decrease. The pattern of locomotion obtained in a normal mouse should be used as a template for studying locomotor control deficits after lesions or in different mutations affecting the nervous system.     

A genome-wide analysis of the flax (<Emphasis Type="Italic">Linum usitatissimum</Emphasis> L.) dirigent protein family: from gene identification and evolution to differential regulation

Key message

Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress.

Abstract

Dirigent proteins (DIRs) were discovered during 8-8′ lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (?)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset of genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8′ linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (?)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.

     

Mismatch repair during pneumococcal transformation of small deletions produced by site-directed mutagenesis

Summary The genetic behaviour of short non-homologous regions has been studied during transformation of Streptococcus pneumoniae. Amethopterin-resistant mutants belonging to the amiA locus were used for these investigations. Five mutants deleted for 1–5 bp were obtained by oligonucleotide-direcrted mutagenesis. Their efficiency of transformation was measured using recipient strains either able to excise and repair mismatched bases (Hex⁺) or Hex^- derivatives. Deletions or insertions of 1 and 2 bp are fully recognized by the Hex system, and are efficiently repaired whereas 3-bp deletions or insertions are only partially excised and repaired. The efficiency of repair is inversely related to the size of the non-homology. Markers with 5-bp deletions or insertions are poorly repaired and thus transform at very high frequency: similar results are obtained in reciprocal crosses. It is proposed that 1-or 2-bp deletions or insertions are included in the heteroduplex structure as transition mutations. The Hex system would detect only small deviations from the normal DNA structure.     

Steroid hormone receptors: intracellular distribution

Recent reports, both biochemical and morphological, have challenged the widely accepted two-step model of steroid hormone action. This model proposed that steroid hormone receptors existed under two different forms: the unliganded receptor in the cytoplasm and the hormone-bound receptor complex in the nucleus. A nuclear translocation mechanism was hypothesized as a necessary link between the two forms. In contradiction with this model, new studies have concluded to the absence of receptor in the cytoplasm and its presence in the nucleus under all hormonal conditions, thus rendering the hypothetical nuclear translocation unnecessary. In this review, we discuss how our concept of the mechanism of action of steroid hormone ought to be revised in the light of the new data.     

Productivity and Growth of a Natural Population of the Smallest Free-Living Eukaryote under Nitrogen Deficiency and Sufficiency

The influence of dissolved inorganic nitrogen (DIN) enrichments on cell-normalized carbon uptake rate, chlorophyll a content, and apparent cell size of a picoeukaryote (<1 m) (Ostreococcus tauri, the smallest eukaryotic cell) from a natural summer phytoplanktonic assemblage (<200 m) in a northern Mediterranean Lagoon (Thau Lagoon) was studied in 20-L enclosures in June 1995. The natural planktonic community was incubated in situ for 24 h with initial ammonium and nitrate enrichments and compared to a control without enrichment. O. tauri cell-normalized productivity was estimated from the combination of flow cytometric (FCM) enumeration and 2-h (radioactive) carbonate incorporation measured on post-incubation size fractions (<1m). No difference between the effects of the two DIN sources of enrichment on the studied biological parameters was measured during this experiment. Growth of natural O. tauri was perturbed by the low DIN availability in the control with drastic changes in cell productivity, chlorophyll content, and cell cycle (from the variations in apparent cell size) as compared to the DIN sufficiency conditions. On the other hand, a very high specific growth rate for natural O. tauri, up to 8 day^–1 under DIN enrichments, has been estimated from production and abundance data obtained during this experiment. This supports values measured in culture and suggests that the yearly high contribution of picophytoplankton to the total primary production in Thau Lagoon is likely to be due to their high growth rate rather than the previously suggested lack of grazing pressure.     

New N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides as antituberculous agents with improved pharmacokinetics

Infections caused by multidrug-resistant Mycobacterium tuberculosis (MT) and non-tuberculous mycobacteria are difficult to treat and, indeed, new therapeutic agents are being sought. As a part of an ongoing research in our laboratories, novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides have been synthesized and evaluated against several strains of MT and Mycobacterium avium complex (MAC). The pharmacokinetics and relative bioavailability after intravenous administration of three derivatives have been investigated. Introduction of a hydroxyl or a tertiary amino group in the N-alkyl chain resulted in an improved pharmacokinetic profile without affecting sensitively the antituberculous potency.     

Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

Through linkage analysis and candidate gene sequencing, we identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin. Both mutations decrease signal sequence hydrophobicity and are predicted by bioinformatic analyses to damage targeting and cotranslational translocation of preprorenin into the endoplasmic reticulum (ER). Transfection and in vitro studies confirmed that both mutations affect ER translocation and processing of nascent preprorenin, resulting either in reduced (p.Leu16del) or abolished (p.Leu16Arg) prorenin and renin biosynthesis and secretion. Expression of renin and other components of the renin-angiotensin system was decreased accordingly in kidney biopsy specimens from affected individuals. Cells stably expressing the p.Leu16del protein showed activated ER stress, unfolded protein response, and reduced growth rate. It is likely that expression of the mutant proteins has a dominant toxic effect gradually reducing the viability of renin-expressing cells. This alters the intrarenal renin-angiotensin system and the juxtaglomerular apparatus functionality and leads to nephron dropout and progressive kidney failure. Our findings provide insight into the functionality of renin-angiotensin system and stress the importance of renin analysis in families and individuals with early onset hyperuricemia, anemia, and progressive kidney failure.     

Relationships between dental microwear and diet in Carnivora (Mammalia) — Implications for the reconstruction of the diet of extinct taxa

Food consumption causes distinct microwear patterns on teeth, especially in mammals that actively masticate food. Here we perform a microwear analysis to assess the relationships between diet and microwear features of diverse Carnivora. Our database includes approximately 230 individuals of 17 extant species having different diets. We analyse both slicing and grinding facets of M1 and m1. The proposed method is reproducible and allows the differentiation, especially on slicing facets, of microwear poles that are significantly distinct from one another. In carnivorans, the microwear features mainly result from their foraging behavior and the proportion of certain food items consumed. We applied our method to extinct taxa such as the amphicyonid Amphicyon major. The results on the m1 slicing facet indicate dietary similarities between this large Miocene predator and the extant red fox; results from the m1 grinding facet do not have equivalent in extant taxa, however.     

Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008

Background

To diagnose multiple sclerosis (MS), evidence for dissemination in space and time is required. There is no clear definition on how symptoms and signs of a patient indicate clinical dissemination in space. To provide a uniform approach on this subject, a clinical classification system was described recently differentiating patients with mono- and multifocal clinical presentation. Here we assess the predictive value of clinically defined dissemination in space at first presentation for time to clinically definite MS (CDMS).

Methods

Four hundred and sixty-eight patients with a first episode suggestive of MS were classified as clinically mono- or multifocal by two neurologists blinded to magnetic resonance imaging (MRI) results. These patients were part of the BENEFIT study in which 292 patients were randomized to interferon beta-1b (IFNB-1b) and 176 to placebo. By using Kaplan-Meier statistics the risk for CDMS was studied in mono- and multifocal patients of the placebo group, both with and without taking into account MRI measures of potential prognostic relevance.

Results

Time to CDMS was similar in monofocal and multifocal patients. In monofocal patients, the risk for CDMS over 2 years was significantly higher when ≥ 9 T2 lesions or at least one Gd-enhancing lesion were present at the first event or 3 or 6 months after the first event. In patients with multifocal presentation, these MRI measures had no significant added value in predicting time to CDMS.

Conclusion

These data indicate that a carefully performed neurological assessment of symptoms and signs, combined with lesions on MRI, is important for defining the risk of conversion to CDMS.

Trial Registration

The Benefit trial has been registered under NCT00185211 http://www.clinicaltrials.gov