Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy

Auditory neuropathy is a particular type of hearing impairment in which neural transmission of the auditory signal is impaired, while cochlear outer hair cells remain functional. Here we report on DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is a paralog of DFNA5, a protein of unknown function also involved in deafness. By immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for the R183W variant identified in one DFNB59 family, show abnormal auditory brainstem responses indicative of neuronal dysfunction along the auditory pathway. Unlike previously described sensorineural deafness genes, all of which underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in nonsyndromic deafness due to a neuronal defect.     

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer’s disease

β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer’s disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer’s disease.     

A Proposal for the Automatic Computation of Envelopes of Families of Plane Curves

Journal of Systems Science and Complexity - The idea of envelope of a family of plane curves is an elementary notion in differential geometry. As such, its implementation in dynamic geometry...     

Which is the use of systems theory in literature analysis?: The discovery of the place in La Mancha in Don Quixote

The use of systems theory to attempt to determine which ''place in La Mancha'' was the one whose name Cervantes could not quite recall in his universal novel, appears to be ordained to change certain attitudes towards science held in Cervantine literature. The reason: after four centuries of literary analysis, systemic methodology has proven able to identify the famous ''place'' with acceptable accuracy. Nonetheless, certain reasonable doubts persist around the suitability of a strictly scientific analysis of literature. In light of those doubts, the present article aims primarily to facilitate critique both of the systemic approach adopted and its outcome.     

New findings of Hexalona-branch representatives in Brazil,with a description of Prenda gen. nov. (Crustacea: Anomopoda: Aloninae)

Altogether, Coronatella and Hexalona-branches are considered the main lineages of Aloninae – a subfamily of common bottom-dwelling microcrustaceans in freshwater environments. Although the taxonomic features of Brazilian members of the Hexalona-branch have been summarised for species from the costata-group and affinis-group, a revision of other widely distributed species in the world is still lacking in this country. The aim of this paper was to study the morphology of Brazilian populations from the guttata-group and intermedia-group, and to describe a new genus from the Hexalona-branch. The parthenogenetic females of Alona cf. guttata from Brazil have similar morphology when compared to data from the literature, but the armature of the terminal claw of its males seems to be different from those of Alona guttata sensu stricto, Alona barbulata and Alona werestschagini. The intermedia-group is formed by Alona elisae sp. nov., which seems to be endemic to the Cerrado of Brazil Central, and Alona isabellae sp. nov., which is widely distributed in Brazil; this species has a labral keel armed with 2–4 setulae, and postabdomen with setulae of lateral fascicles longer than the level of marginal denticles, morphological traits that differentiate it from Alona elisae sp. nov. Another endemic species from the Hexalona-branch is Prenda arvensis gen. nov. and sp. nov., which has two main head pores, a reduced seta on endite 1 of the first limb, sixth limb is a wide lobe. The potential of biodiversity from the Hexalona-branch from Brazil is still underestimated, and a global revision of the guttata-group and intermedia-group is very important for the progress of Aloninae taxonomy and systematics.

http://zoobank.org/urn:lsid:zoobank.org:pub:0A2E4A30-0C9C-43E8-8E72-1DEDA6AFF3C3     

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9

ADAM17/TACE is a metalloproteinase responsible for the shedding of the proinflammatory cytokine TNF-α and many other cell surface proteins involved in development, cell adhesion, migration, differentiation, and proliferation. Despite the important biological function of ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report here that the tetraspanin CD9 and ADAM17 partially co-localize on the surface of endothelial and monocytic cells. In situ proximity ligation, co-immunoprecipitation, crosslinking, and pull-down experiments collectively demonstrate a direct association between these molecules. Functional studies reveal that treatment with CD9-specific antibodies or neoexpression of CD9 exert negative regulatory effects on ADAM17 sheddase activity. Conversely, CD9 silencing increased the activity of ADAM17 against its substrates TNF-α and ICAM-1. Taken together, our results show that CD9 associates with ADAM17 and, through this interaction, negatively regulates the sheddase activity of ADAM17.