A lipoprotein signal peptide encoded by the staphylococcal conjugative plasmid pSK41 exhibits an activity resembling that of Enterococcus faecalis pheromone cAD1.

The traH gene of the staphylococcal conjugative plasmid pSK41 has recently been shown to encode a lipoprotein (N. Firth, K. P. Ridgway, M. E. Byrne, P. D. Fink, L. Johnson, I. T. Paulsen, and R. A. Skurray, Gene 136:13-25, 1993). Here we report that traH encodes a product recognized as a pheromone by Enterococcus faecalis cells harboring the conjugative plasmid pAD1. The mature traH product is not essential for this phenomenon, as expression of pheromone-like activity was found to require sequences encoding only the pro-TraH signal peptide.     

Distribution and properties of an adenosine triphosphatase in the tanycyte ependyma of the IIIrd ventricle of the rat.

The distribution, histochemical properties and ultrastructural localization of adenosine triphosphate (ATP) hydrolyzing enzymes in the tanycyte ependyma of the third ventricle have been studied in female Wistar rats. Using a calcium-cobalt procedure and a lead capture technique, splitting of ATP could be demonstrated in perikarya and processes of tanycytes in the region of the ventromedial nucleus. The reaction showed no dependence on magnesium or sodium ions, did not occur with other monodi-, and tri-phosphates as substrates, and was inhibited by p-chlormercuribenzoate (PCMB) and sodium fluoride, but not by ouabain. With the calcium-cobalt method the highest intensity of reaction was found at pH 9.4, whereas the lead method gave optimal results at pH 6--8. At the ultrastructural level, the reaction product was found at the outer surface of the plasma membranes of tanycytes and reached its highest concentrations in the region of the region of the apical microvilli; From the findings it is concluded that splitting of ATP in tanycytes is due to a true ATPase. The enzyme might be involved in an active transport of substances by tanycytes.     

The growing field of digital psychiatry: current evidence and the future of apps,social media,chatbots, and virtual reality

As the COVID‐19 pandemic has largely increased the utilization of telehealth, mobile mental health technologies – such as smartphone apps, vir­tual reality, chatbots, and social media – have also gained attention. These digital health technologies offer the potential of accessible and scalable interventions that can augment traditional care. In this paper, we provide a comprehensive update on the overall field of digital psychiatry, covering three areas. First, we outline the relevance of recent technological advances to mental health research and care, by detailing how smartphones, social media, artificial intelligence and virtual reality present new opportunities for “digital phenotyping” and remote intervention. Second, we review the current evidence for the use of these new technological approaches across different mental health contexts, covering their emerging efficacy in self‐management of psychological well‐being and early intervention, along with more nascent research supporting their use in clinical management of long‐term psychiatric conditions – including major depression; anxiety, bipolar and psychotic disorders; and eating and substance use disorders – as well as in child and adolescent mental health care. Third, we discuss the most pressing challenges and opportunities towards real‐world implementation, using the Integrated Promoting Action on Research Implementation in Health Services (i‐PARIHS) framework to explain how the innovations themselves, the recipients of these innovations, and the context surrounding innovations all must be considered to facilitate their adoption and use in mental health care systems. We conclude that the new technological capabilities of smartphones, artificial intelligence, social media and virtual reality are already changing mental health care in unforeseen and exciting ways, each accompanied by an early but promising evidence base. We point out that further efforts towards strengthening implementation are needed, and detail the key issues at the patient, provider and policy levels which must now be addressed for digital health technologies to truly improve mental health research and treatment in the future.     

Permeability of the foetal capillary endothelium of the guinea-pig placenta to haem proteins of various molecular sizes

Summary Haem proteins of different molecular sizes were perfused into the foetal circulation of the guinea-pig placenta to study the permeability of the foetal endothelium.The smallest molecules tested, microperoxidase (a_e 1.0 nm) and cytochrome C (a_e 1.5 nm), readily penetrated the endothelium; tracer-reaction product was found in the subendothelial space of the capillaries. However, there was no uptake of these two tracers into the syncytiotrophoblast layer of the placenta. An intermediate-sized molecule, myoglobin (a_e 1.7 nm), produced only a weak reaction product in the subendothelial space even when perfused at high concentration. The largest molecule tested, haemoglobin (a_e 2.8 nm), did not penetrate the foetal endothelium at any of the concentrations employed.The foetal capillary endothelium thus provided a barrier to protein penetration from the foetal circulation, dependent on molecular size. There was evidence that the site of this barrier was located in the lateral intercellular spaces between the endothelial cells.The syncytiotrophoblast of this haemomonochorial placenta provided an almost absolute barrier to protein penetration from the foetal circulation. As other workers have described maternal-to-foetal transmission of proteins across this layer in the guinea-pig, a working hypothesis of the role of endothelium and syncytiotrophoblast in maternal/foetal protein exchange is discussed.     

The Directed Differentiation of Human iPS Cells into Kidney Podocytes

The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm’s tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.     

Ultrastructural study of the permeability of the guinea-pig placenta to horseradish peroxidase

Summary Horseradish peroxidase (HRP) was used to study macromolecule permeation into the guinea-pig placenta perfused in situ. When tissue culture medium 199 (TC 199) was used as fetal-side perfusate, the tracer reaction product was found only lining the fetal endothelium. When a longer period of perfusion with HRP in TC 199 was used, a small amount of reaction product was found in the subendothelial space and syncytiotrophoblastic vesicles, but not in maternal lacunae. In similar experiments using a Krebs bicarbonate Ringer (KRBG) as perfusate the tracer was found (i) lining the fetal endothelium, (ii) in the lateral intercellular spaces of the endothelium, (iii) in the subendothelial space, and (iv) in the maternal lacunae.It is therefore evident that the vehicle influenced the permeability of the guinea-pig placenta to horseradish peroxidase. As other studies have shown that perfusion of the fetal side with salt solution increases pore size, the results with TC 199 are regarded as more representative of the situation in the intact animal. It is therefore suggested that the fetal endothelium of the guinea-pig placenta may be largely impermeable to molecules of the size of horseradish peroxidase (4 nm) or larger.