Hypohidrotic ectodermal dysplasia: clinical and molecular review

Hypohidrotic Ectodermal Dysplasia (HED) is a genetic human disorder which affects structures of ectodermal origin. Although there are autosomal recessive and dominant forms, X‐linked (XL) is the most frequent form of the disease. This XL‐HED phenotype is associated with mutations in the gene encoding the transmembrane protein ectodysplasin‐1 (EDA1), a member of the TNFα‐related signaling pathway. The proteins from this pathway are involved in signal transduction from ectoderm to mesenchyme leading to the development of ectoderm‐derived structures in the fetus such as hair, teeth, skin, nails, and eccrine sweat glands. The aim of this review was to update the main clinical characteristics of HED regarding to recent molecular advances in the comprehension of all the possible genes involved in this group of disorders since it is known that Eda‐A1‐Edar signaling has multiple roles in ectodermal organ development, regulating their initiation, morphogenesis, and differentiation steps. The knowledge of the biological mechanisms that generate HED is needed for both a better detection of possible cases and for the design of efficient prevention and treatment approaches.     

Object recognition in acquired and developmental prosopagnosia

Whether face and object recognition are dissociated in prosopagnosia continues to be debated: a recent review highlighted deficiencies in prior studies regarding the evidence for such a dissociation. Our goal was to study cohorts with acquired and developmental prosopagnosia with a complementary battery of tests of object recognition that address prior limitations, as well as evaluating for residual effects of object expertise. We studied 15 subjects with acquired and 12 subjects with developmental prosopagnosia on three tests: the Old/New Tests, the Cambridge Bicycle Memory Test, and the Expertise-adjusted Test of Car Recognition. Most subjects with developmental prosopagnosia were normal on the Old/New Tests: for acquired prosopagnosia, subjects with occipitotemporal lesions often showed impairments while those with anterior temporal lesions did not. Ten subjects showed a putative classical dissociation between the Cambridge Face and Bicycle Memory Tests, seven of whom had normal reaction times. Both developmental and acquired groups showed reduced car recognition on the expertise-adjusted test, though residual effects of expertise were still evident. Two subjects with developmental prosopagnosia met criteria for normal object recognition across all tests. We conclude that strong evidence for intact object recognition can be found in a few subjects but the majority show deficits, particularly those with the acquired form. Both acquired and developmental forms show residual but reduced object expertise effects.     

Antisickling effects of 2,3-diphosphoglycerate depletion

Elevation of 2,3-bisphosphoglycerate (2,3-DPG) in sickle erthrocytes (SS RBCs) and concomitant acidification of the cell interior promote polymerization by decreasing the solubility (csat) of deoxyhemoglobin S. The antisickling effect of 2,3-DPG depletion was evaluated after activation of the 2,3-DPG phosphatase activity of bisphosphoglycerate mutase by glycolate-2-phosphate, leading to rapid loss of intracellular 2,3-DPG. To ensure its maximal reduction in a physiologic medium, isosmotic CO2/bicarbonate-buffered saline, pH 7.0, was used. Substitution of K+ for Na+ as the major extracellular cation suppressed K:Cl cotransport, prevented cell shrinkage, and allowed demonstration of the full antisickling effect of 2,3-DPG depletion. The modest effect on solubility per se of removing intraerythrocytic 2,3-DPG (delta Csat = 1.6 g/dL) was amplified into a much larger antisickling effect by interaction with three other cellular variables affecting solubility and polymer content (intracellular pH, O2 saturation, and mean cell hemoglobin concentration). Acting in concert, these four antisickling effects (three solubilizing, one osmotic) reduced polymer fraction of glycolate-treated SS RBCs by 32% to 63%, with a concomitant decrease in sickling of 46% to 95% at the nominal pO2 of the microcirculation (20 mm Hg). A decrement in sickling of this magnitude should significantly ameliorate the vasoocclusive severity of sickle cell disease.