Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Assemblage variability and bifacial points in the lowermost Sibudan layers at Sibudu, South Africa

Building on the important work of Lyn Wadley at Sibudu, archeologists from the University of Tübingen have excavated the upper stratigraphic units of the Middle Stone Age (MSA) sequence down to the Howiesons Poort (HP). Here, we present the main results from lithic analyses of the lowest part of the Sibudan sequence to assess its overall variability and taxonomic status. Based on the new findings, we also discuss the implications for archeological systematics and the cultural evolution of modern humans in MIS 3 from a more general perspective. The Sibudan deposits encompass over 20 archeological horizons that span a 1.2-m-thick, well-stratified sequence whose base and top have been dated to ∼58 ka (MIS 3). In contrast to the upper stratigraphic units, the lower Sibudan assemblages that we analyzed here show much higher use of local sandstone, quartz, and quartzite. These older units are characterized by frequent use of expedient core reduction methods, bipolar reduction of locally available quartz and quartzite, less retouch of blanks, and lower find densities. Tongati and Ndwedwe tools, which feature abundantly in the upper part of the Sibudan sequence, are entirely absent, as are unifacial points. Instead, notched and denticulated tools are common. Surprisingly, knappers manufactured small bifacial points, mainly made from quartz, by means of alternating shaping in the course of the oldest occupations. The results highlight the great diversity of human technological behavior over even short periods during the MSA, raising important questions about the mechanisms of behavioral change, cultural taxonomy, appropriate scales of lithic analyses, and the relationship between the HP and the Sibudan. Our findings further erode the old idea that bifacial technology in southern Africa is limited to the Still Bay. Research is increasingly showing that bifacial points come and go in different forms and contexts of African Late Pleistocene technology, impeding their use as chrono-cultural markers

HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a

Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may play an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that 1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, 2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, 3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression, and 4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain