Ascending curbs of progressively higher height increases forward trunk flexion along with upper extremity mechanical and muscular demands in manual wheelchair users with a spinal cord injury

High upper extremity (U/E) demands are required when manual wheelchair users (MWUs) with spinal cord injury (SCI) ascend curbs; this may contribute to the risk of developing U/E musculoskeletal impairments. The aim of this study was to compare movement strategies (kinematics), mechanical loads (kinetics) and muscular demand (EMG) at the non-dominant U/E among 15 MWUs with SCI when ascending curbs of 4 cm (3 trials), 8 cm (3 trials) and 12 cm high (3 trials) from a starting line set 3 m before the curb. Biomechanical data was collected during three trials for each height. The curb ascent task was divided into three adjustment phases: caster pop, rear-wheel ascent and post-ascent. The greatest effort was generated by the shoulder flexors and internal rotators as well as the elbow flexors. A significant difference (p < 0.0167) between the curb heights was found for most outcome measures studied: movement excursion, net joint moments and muscular utilization ratio (MUR) of the main muscles increased with the higher curb heights, mainly around the shoulder joint. These results provide insight that aside from adhering to a highly structured training method for wheelchair curb ascent, rehabilitation professionals need to propose task-specific strength training programs based on the demands documented in this study and continue to advocate for physically accessible environments.     

A Highlights from MBoC Selection: Apical sorting of lysoGPI-anchored proteins occurs independent of association with detergent-resistant membranes but dependent on their N-glycosylation

Most glycosylphosphatidylinositol-anchored proteins (GPI-APs) are located at the apical surface of epithelial cells. The apical delivery of GPI-APs is believed to result from their association with lipid rafts. We find that overexpression of C-terminally tagged PGAP3 caused predominant production of lysoGPI-APs, an intermediate precursor in the GPI lipid remodeling process in Madin–Darby canine kidney cells. In these cells, produced lysoGPI-APs are not incorporated into detergent-resistant membranes (DRMs) but still are delivered apically, suggesting that GPI-AP association with DRMs is not necessary for apical targeting. In contrast, apical transport of both fully remodeled and lyso forms of GPI-APs is dependent on N-glycosylation, confirming a general role of N-glycans in apical protein transport. We also find that depletion of cholesterol causes apical-to-basolateral retargeting not only of fully remodeled GPI-APs, but also of lysoGPI-APs, as well as endogenous soluble and transmembrane proteins that would normally be targeted to the apical membrane. These findings confirm the essential role for cholesterol in the apical protein targeting and further demonstrate that the mechanism of cholesterol-dependent apical sorting is not related to DRM association of GPI-APs.     

Synthesis and Initial Results for MAO-B Inhibition by New N-Propargyl-3-pyrrol-1-ylindanamine Derivatives,Analogues of Rasagiline

The synthesis of new N-propargyl-3-pyrrol-1-ylindanamine derivatives, analogues of rasagiline, is described in ten steps starting from the corresponding arylaldehydes via the corresponding cis-3-pyrrol-1-ylindanamines. The cis-configuration of some intermediates has been established using X-ray analysis and NOE experiments. The new N-propargyl-3-pyrrol-1-ylindanamine derivatives were evaluated for their potential MAO-B inhibitor activity in an in vivo model of MPTP-induced Parkinsonism in mice with respect to the potent MAO-B inhibitor rasagiline.     

8-Amino-5-nitro-6-phenoxyquinolines: Potential Non-peptidic Neuropeptide Y Receptor Ligands

The synthesis and pharmacological evaluation of analogues of PD 160170, a neuropeptide Y1 (NPY) receptor antagonist are reported. Phamacomodulation of this 8-amino-5-nitro-6-phenylsulfonylquinoline was carried out by replacing the sulfone moiety by oxygen. The corresponding ethers 11 - 16 were obtained by nucleophilic substitution of 8-acetamido-6-chloro-5-nitroquinoline 4 with phenols, followed by acidic hydrolysis of the intermediary amides 5 - 10. The test compounds 11 - 16 exerted no appreciable Y1 activity and they were also inactive in terms of Y5 receptor binding; their IC 50 values were >1 μM and 10 μM, respectively. The dramatic decrease in potency resulting from replacement of the sulfone function by an ether was confirmed by IP administration of 16 to ob / ob mice; after a 4-day administration, no decrease in food consumption or weight was observed.     

New data on the Dyrosauridae (Crocodylomorpha) from the Paleocene of Togo

Following our fieldwork in Paleogene deposits of Togo, we herein report cranial as well as postcranial elements belonging to the family Dyrosauridae. This assemblage is dated to the Late Paleocene (Thanetian) from two quarries in southern Togo. The specimens include a partial skull presenting two large supratemporal fossae and a massive occipital condyle; long and slender isolated teeth; amphicoelous vertebrae including several articulated ones; and two osteoderms devoid of carina. The morphology of the partial skull reveals similarities with some African longirostrine forms such as Rhabdognathus spp., although this attribution cannot be confirmed. Longirostrine forms, known in the late Paleocene and early Eocene of the Iullemmeden basin (Nigeria, Niger, Mali, Algeria) and in the phosphates of Morocco and Tunisia, is only represented in Thanetian levels in Togo. Different palaeoenvironmental settings seem to have characterized the various African basins during the lower Eocene, with consequences for the geographic distribution of dyrosaurids. These dyrosaurid remains confirm the presence of the family in Togo during the Paleocene and underline the fossiliferous potential of the coastal sedimentary basin in Togo and in the bay of Benin.