Experimental formation of podocytes in the parietal layer of the Bowman's capsule

Summary A metaplasic transformation of the parietal layer of the Bowman's capsule into podocytes is described in glomerular cysts induced by postnatal injection of methylprednisolone acetate to rabbits. Both the anomalous location of podocytes and their utility for the study of the biology of these cells are discussed.This work was supported by a grant of the Fondo Nacional para el Desarrollo de la Investigación Cientifica from the spanish-government and a grant from the Marcelino Botín Foundation, Santander, Spain.     

Distinct functions of Crumbs regulating slit diaphragms and endocytosis in <Emphasis Type="Italic">Drosophila</Emphasis> nephrocytes

Mammalian podocytes, the key determinants of the kidney’s filtration barrier, differentiate from columnar epithelial cells and several key determinants of apical–basal polarity in the conventional epithelia have been shown to regulate podocyte morphogenesis and function. However, little is known about the role of Crumbs, a conserved polarity regulator in many epithelia, for slit-diaphragm formation and podocyte function. In this study, we used Drosophila nephrocytes as model system for mammalian podocytes and identified a conserved function of Crumbs proteins for cellular morphogenesis, nephrocyte diaphragm assembly/maintenance, and endocytosis. Nephrocyte-specific knock-down of Crumbs results in disturbed nephrocyte diaphragm assembly/maintenance and decreased endocytosis, which can be rescued by Drosophila Crumbs as well as human Crumbs2 and Crumbs3, which were both expressed in human podocytes. In contrast to the extracellular domain, which facilitates nephrocyte diaphragm assembly/maintenance, the intracellular FERM-interaction motif of Crumbs is essential for regulating endocytosis. Moreover, Moesin, which binds to the FERM-binding domain of Crumbs, is essential for efficient endocytosis. Thus, we describe here a new mechanism of nephrocyte development and function, which is likely to be conserved in mammalian podocytes.     

Podocalyxin enhances the adherence of cells to platelets

Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium, progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed in glycomutant CHO cells deficient in sialic acid. Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007     

Inhibition of Rho-associated kinase relieves C5a-induced proteinuria in murine nephrotic syndrome

Childhood nephrotic syndrome is mainly caused by minimal change disease which is named because only subtle ultrastructural alteration could be observed at electron microscopic level in the pathological kidney. Glomerular podocytes are presumed to be the target cells whose protein sieving capability is compromised by a yet unidentified permeability perturbing factor. In a cohort of children with non-hereditary idiopathic nephrotic syndrome, we found the complement fragment C5a was elevated in their sera during active disease. Administration of recombinant C5a induced profound proteinuria and minimal change nephrotic syndrome in mice. Purified glomerular endothelial cells, instead of podocytes, were demonstrated to be responsible for the proteinuric effect elicited by C5a. Further studies depicted a signaling pathway involving Rho/Rho-associated kinase/myosin activation leading to endothelial cell contraction and cell adhesion complex breakdown. Significantly, application of Rho-associated kinase inhibitor, Y27632, prevented the protein leaking effects observed in both C5a-treated purified endothelial cells and mice. Taken together, our study identifies a previously unknown mechanism underlying nephrotic syndrome and provides a new insight toward identifying Rho-associated kinase inhibition as an alternative therapeutic option for nephrotic syndrome.     

Eine bisher unbekannte endokrine Drüse im Kopf vonScutigera coleoptrata L. (Chilopoda,Notostigmophora)

Summary A hitherto unknown endocrine gland in the head ofScutigera coleoptrata is described. It is attached to a small blood vessel. Its cells are typical podocytes. Between the pedicells and along the lateral cell membranes, there are many intercellulary spaces. The fine structure of the gland is very similar to that of the collar gland in the diplopodPolyxenus lagurus.     

Eine bisher unbekannte endokrine Drüse vonPolyxenus lagurus (L.) (Diplopoda,Penicillata)

Summary A hitherto unidentified endocrine glandula perioesophagealis inPolyxenus lagurus is described. Its cells are typical podocytes. Between the pedicells there are many intercellulary spaces. In animals close to molting, the gland cells are activated.     

Nephrin in human lymphoid tissues

When nephrin, the protein product of NPHS1, was cloned, it was proposed to be specific for the kidney glomerular podocytes. Recently, however, new reports have emerged verifying additional nephrin expression sites, particularly the insulin-producing β cells of the pancreas, as well as the central nervous system. In this study, we demonstrate nephrin expression in lymphoid tissues, specifically the tonsil, adenoid and lymph node. Nephrin mRNA expression levels were 4-fold higher in tonsils and adenoids than in thymus or B lymphocytes, and 20-fold higher than in T lymphocytes or monocytes, as shown by quantitative RT-PCR analysis. Anti-nephrin antibodies recognised a specific 165-kDa band in lysates of tonsil and adenoid. In immunofluorescence and immunohistochemichal stainings of adenoid and lymph node sections, nephrin-positive cells were detected in the germinal centres of the lymphoid follicles in a staining pattern typical for interdigitating cells. These results indicate a definite and additional presence of nephrin in lymphoid tissue. Received 17 October 2005; received after revision 22 November 2005; accepted 20 December 2005     

The parvins

The parvins are a family of proteins involved in linking integrins and associated proteins with intracellular pathways that regulate actin cytoskeletal dynamics and cell survival. Both α-parvin (PARVA) and β-parvin (PARVB) localize to focal adhesions and function in cell adhesion, spreading, motility and survival through interactions with partners, such as integrin-linked kinase (ILK), paxillin, α-actinin and testicular kinase 1. A complex of PARVA with ILK and the LIM protein PINCH-1 is critical for cell survival in a variety of cells, including certain cancer cells, kidney podocytes and cardiac myocytes. While PARVA inhibits the activities of Rac1 and testicular kinase 1 and cell spreading, PARVB binds αPIX and α-actinin, and can promote cell spreading. In contrast to PARVA, PARVB inhibits ILK activity and reverses some of its oncogenic effects in cancer cells. This review focuses on the structure and function of the parvins and some possible roles in human diseases. Received 5 August 2005; received after revision 5 September 2005; accepted 22 September 2005     

On the epistemological foundations of the law of the lever

In this paper I challenge Paolo Palmieri’s reading of the Mach—Vailati debate on Archimedes’ proof of the law of the lever. I argue that the actual import of the debate concerns the possible epistemic (as opposed to merely pragmatic) role of mathematical arguments in empirical physics, and that construed in this light Vailati carries the upper hand. This claim is defended by showing that Archimedes’ proof of the law of the lever is not a way of appealing to a non-empirical source of information, but a way of explicating the mathematical structure that can represent the empirical information at our disposal in the most general way.     

Melatonin decreases the amplitude of the b-wave of the human electroretinogram

In a double-blind placebo crossover study of 13 healthy volunteers, the pineal hormone melatonin (10 mg) was given at 4 pm, and the electroretinogram measured under conditions of dark and light adaptation. A significant diminution of b-wave amplitude was found under both photopic (=5.4 V, p<0.05) and scotopic conditions (=7.4 V, p<0.01). These data indicate that melatonin may transduce the dark signal at the level of the retina as well as the pineal. Acute administration of melatonin decreases sensitivity to light.     

Development of the innervation of the urogenital complex in the fetal mouse

The developing urogenital complex of the fetal mouse was studied by means of silver impregnation and electron microscopy. These studies showed that: 1) the mesonephric field is innervated during prenatal stages (Wolffian nerve); 2) nerve penetration precedes the differentiation of the gonads and related ducts; and 3) the Wolffian nerve arises during the earliest stages from the first pair of abdominal rami communicantes. The identity between the fetal Wolffian nerve and the nerve of the suspensory ligament (higher pathway) of the adult is discussed.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p<0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p<0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.To whom requests of reprints should be addressed.This work was supported by grants from the National Aeronautics and Space Administration (NSG 2183 and NAG-2-411), a grant from the National Institutes of Health (NIH Grant RR0811) and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR03020).     

Development of the innervation of the urogenital complex in the fetal mouse

Summary The developing urogenital complex of the fetal mouse was studied by means of silver impregnation and electron microscopy. These studies showed that: 1) the mesonephric field is innervated during prenatal stages (Wolffian nerve); 2) nerve penetration precedes the differentiation of the gonads and related ducts; and 3) the Wolffian nerve arises during the earliest stages from the first pair of abdominal rami communicantes. The identity between the fetal Wolffian nerve and the nerve of the suspensory ligament (higher pathway) of the adult is discussed.     

Cytotaxonomy of the myobatrachid frogs of the genusLimnodynastes

Summary 4 of the 5 species ofLimnodynastes of theperoni group show 2n=24. Onlysalmini has 2n=22, thus resembling the species ofPlatyplectron (thedorsalis andornatus complexes) which all show 22 chromosomes. This 2nd group also includes species (ornatus) with very low DNA amounts. From a karyological point of view, the species of thePlatyplectron (plus eventuallysalmini) group appear more differentiated than the species of theperoni group, from which they have probably arisen.Research partly supported by a contribution from C.N.R., Rome.     

On the adenosintriphosphatase activity of the particulates of the egg of the sea urchinParacentrotus lividus

Riassunto I particolati delle uova vergini di riccio di mare possono essere separati, a mezzo della centrifugazione differenziale, in due frazioni, una fortemente ed una scarsamente pigmentata. La prima mostra una attività ATPasica attivata da Mg con un massimo a pH 8.2; il massimo della seconda è invece a pH 6.4. Nelle preparazioni contenenti i due tipi di particolati si ritrovano i due massimi.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p less than 0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p less than 0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.     

Longitudinal continuity of the subrhabdomeric cisternae in the photoreceptors of the compound eye of the drone, Apis mellifera

It is shown that the subrhabdomeric cisternae of the honey bee drone photoreceptor cell constitute a single structure with a continuous lumen, that extends over at least 15 micron and perhaps the whole length of the cell. In this case, the structure of the cisternae might subserve the propagation of light adaptation along the cell.     

Application of the electroprecipitin test to the detection of the virus of canine distemper

Résumé La production d'un anticorps contre le virus de l'encéphalite canine a été démontrée par électroprécipitation sur l'acétate de cellulose dans une dilution de 18. Une bande de précipitation bien définie a été obtenue dans un intervalle de temps très court, ce qui indiquerait que le test pourrait servir à l'identification de l'antigène encéphalitique chez les chiens suspectés d'en être atteints.

---

---

The author wishes to thank Dr. C. M.Sheldon of the Eli Lilly Co. for performing the serum neutralization test. This work was supported in part by PHS Research Grant No. FR00437-01A1 from the Animal Resources Branch of the Division of Research Facilities and Resources.     

Variations in the hydrothermic contraction of the rat skin as a function of the age of the animals]

The tension developed in Rat skin by hydrothermal shrinkage is modified with ageing of the animals: the temperature of maximum tension decreases from birth to 1 month, then very slowly increases with age. At higher temperatures than that of maximum tension a relaxation occurs very rapidly in young Rats and in not yet senescent adult skins. These modifications appeared to be related to those of the nature of the intermolecular collagen cross-links with ageing.