Wild-type and mutant ferroportins do not form oligomers in transfected cells

Ferroportin [FPN; Slc40a1 (solute carrier family 40, member 1)] is a transmembrane iron export protein expressed in macrophages and duodenal enterocytes. Heterozygous mutations in the FPN gene result in an autosomal dominant form of iron overload disorder, type-4 haemochromatosis. FPN mutants either have a normal iron export activity but have lost their ability to bind hepcidin, or are defective in their iron export function. The mutant protein has been suggested to act as a dominant negative over the wt (wild-type) protein by multimer formation. Using transiently transfected human epithelial cell lines expressing mouse FPN modified by the addition of a haemagglutinin or c-Myc epitope at the C-terminus, we show that the wtFPN is found at the plasma membrane and in Rab5-containing endosomes, as are the D157G and Q182H mutants. However, the delV162 mutant is mostly intracellular in HK2 cells (human kidney-2 cells) and partially addressed at the cell surface in HEK-293 cells (human embryonic kidney 293 cells). In both cell types, it is partially associated with the endoplasmic reticulum and with Rab5-positive vesicles. However, this mutant is complex-glycosylated like the wt protein. D157G and G323V mutants have a defective iron export capacity as judged by their inability to deplete the intracellular ferritin content, whereas Q182H and delV162 have normal iron export function and probably have lost their capacity to bind hepcidin. In co-transfection experiments, the delV162 mutant does not co-localize with the wtFPN, does not prevent its normal targeting to the plasma membrane and cannot be immunoprecipitated in the same complex, arguing against the formation of FPN hetero-oligomers.     

Early Triassic Archosaur-Dominated Footprint Assemblage from the Argana Basin (Western High Atlas,Morocco)

An assemblage of abundant and well-preserved tetrapod footprints has been discovered in the Tanamert Member (T3) of the Triassic Timezgadiouine Formation (Argana basin, western High Atlas, Morocco). It is the first fossil record from T3. Surfaces from different localities show a uniform tetrapod ichnofauna that consists of chirotherian and small lacertoid forms. The chirotherians are assigned to the plexus Protochirotherium—Synaptichnium, their trackmakers interpreted as basal archosaurs. The lacertoid imprints show close affinities with Rhynchosauroides and may reflect archosauromorphs or lepidosauromorphs. Protochirotherium—Synaptichnium assemblages are characteristic of the Early Triassic and were known previously only from units of this age in central Europe. Biostratigraphically, the European record implies a wide-spread pre-Anisian Protochirotherium—Synaptichnium dominated assemblage preceding the first appearance of Chirotherium barthii near the Olenekian-Anisian boundary. The stratigraphic position of T3 between Late Permian (uppermost T2) and Middle Triassic (T4) and the European correlatives suggest an Early Triassic age of this unit. It is the first record of Early Triassic continental deposits in Morocco. The surfaces from T3 open up perspectives for further contributions to ecology, biogeography and locomotion of early archosaurs. Furthermore, excellent outcrops and quality of footprint preservation in the Argana basin offer a potential for clarification of ichnotaxonomic and biostratigraphic issues.     

Environmental and economic issues arising from the pooling of SMEs’ supply chains: case study of the food industry in western France

Supply chains pooling is an emergent strategy for improving logistical performance. The pooling concept consists in transferring the effort of coordination for consolidating independent operators’ flows towards an ad hoc pooled system. This organisation results from a design of a pooled logistics network by merging different supply chains to share transport and logistics resources in order to improve logistics performance. In this case study, the pooling concept is applied to a collection of small and medium-sized western France food suppliers serving the same retail chain. In order to demonstrate the efficiency of the pooling, the existing transport organisation was compared to various pooling scenarios. The methodology consisted in accessing a current situation through a survey of the flow of goods at one of the main distribution centre of the studied supply network, then comparing this situation with three other pooling scenarios. Using supply network optimisation models, these scenarios were assessed considering cost and CO₂ emission levels. This study demonstrates the interest of transport pooling in the case independent shipping networks of Small and Medium Enterprises compared to the partially know existing strategies adopted by logistics service providers for less than truckload shipments. Moreover, it suggests that there is no dominant supply organisation and that transport pooling is a new stimulus for network design. These results also bring new research perspectives for generalisation of pooling and gain sharing within large coalitions.     

Evaluation of genetic variability of sorghum (Sorghum bicolor L. Moench) in northwestern Morocco by ISSR and RAPD markers

The study of the genetic variability of the Moroccan landraces of sorghum constitutes a necessary step that can be exploited in the programs of improvement and valorisation of this marginalized species. The aim of this investigation is to evaluate the variability of sorghum populations and to establish their phylogenetic relations using RAPD and ISSR markers. Sampling was taken in 33 fields of northern regions where this species is most cultivated. Individual plants (398) were collected in 13, 11, 5, and 4 fields of Larache, Tangier, Chefchaouen, and Tetouan, respectively. Thirty-eight RAPD primers and four ISSR primers were used. The percentage of polymorphic fragments revealed with ISSR (98%) is higher than the one revealed with RAPD (85%). The level of the variability obtained through the two techniques is very high. Nevertheless, ISSR markers revealed more diversity than RAPD (0.995+/-0.006 against 0.946+/-0.031). The classification based on Jaccard's similarity index distinguished the totality of fields. Data analysis revealed a genetic structure that is closely related to the micro-geographical repartition of the different fields.     

Morning caffeine ingestion increases cognitive function and short-term maximal performance in footballer players after partial sleep deprivation

The aim of the present study was to evaluate the effects of caffeine ingestion and partial sleep deprivation at the end of night on cognitive and physical performance. In randomised order, fourteen football players (age: 23.57 ± 1.98 years; body weight: 59.57 ± 4.29 kg; height: 174.35 ± 5.07 cm) completed four test sessions at 08:00 h: after placebo or 3 mg·kg^?1 of caffeine ingestion during a reference night, RN (bed time: from 22:30 h to 07:00 h) or a night of partial sleep deprivation, PSD (bed time: from 22:30 h to 03:00 h). During each test session, participants assessed vigilance and reaction times and performed a series of tests: cancelation test, squat jumps (SJ), and the 30-s Wingate test (for the measurement of peak power, PP, and mean power, PM). During RN, results showed that PP, PM, SJ, and vigilance increased after caffeine ingestion in comparison with placebo (p < 0.001). Moreover, both simple and choice reactions were significantly better after caffeine ingestion in comparison with placebo ingestion (p < 0.05 and p < 0.001, respectively). Results showed that reaction time, vigilance, and SJ were affected by PSD, even though PP, PM, and SJ were not affected, the following day at 08:00 h. During the PSD condition, PP, PM, SJ, and vigilance were significantly higher after caffeine ingestion in comparison with placebo ingestion (p < 0.001). However, both simple and choice reaction times were significantly poorer during PSD in comparison with RN (p < 0.05 and p < 0.001, respectively). Therefore, ingesting caffeine is an effective strategy to maintain physical and cognitive performances after PSD.     

HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system. Mutations in the 27-kDa small heat-shock protein gene (HSPB1) cause axonal CMT or distal hereditary motor neuropathy (distal HMN). We developed and characterized transgenic mice expressing two different HSPB1 mutations (S135F and P182L) in neurons only. These mice showed all features of CMT or distal HMN dependent on the mutation. Expression of mutant HSPB1 decreased acetylated α-tubulin abundance and induced severe axonal transport deficits. An increase of α-tubulin acetylation induced by pharmacological inhibition of histone deacetylase 6 (HDAC6) corrected the axonal transport defects caused by HSPB1 mutations and rescued the CMT phenotype of symptomatic mutant HSPB1 mice. Our findings demonstrate the pathogenic role of α-tubulin deacetylation in mutant HSPB1-induced neuropathies and offer perspectives for using HDAC6 inhibitors as a therapeutic strategy for hereditary axonopathies.     

The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to <Emphasis Type="Italic">ex vivo</Emphasis> studies

Osteoarthritis is the most prevalent form of arthritis in the world. With the progressive ageing of the population, it is becoming a major public health problem. The involvement of certain signaling pathways, such as the Notch pathway, during cartilage pathology has been reported. In this review, we report on studies that investigated the expression pattern of the Notch family members in articular cartilage and the eventual involvement of this pathway in the modulation of the physiology and pathology of chondrocytes. Temporal and/or spatial modulation of this signaling pathway may help these cells to synthesize a new functional extracellular matrix and restore the functional properties of the articular cartilage.