Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins

Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. The selectivity and specificity of TJ strands are determined by the type of claudins present. An understanding of the cooperation between different claudins in various tissues is thus important. To study the possible cooperation between claudin 11 and claudin 14, we have generated claudin 11/claudin 14 double-deficient mice, which exhibit a combination of the phenotypes found in each of the singly deficient mutants, including deafness, neurological deficits, and male sterility. These two claudins have distinct and partially overlapping expression patterns in the kidney. Claudin 11 is located in both the proximal and distal convoluted tubules, whereas claudin 14 occurs in both the thin descending and thick ascending limbs of the loop of Henle and in the proximal convoluted tubules. Although daily urinary excretion of Mg(++), and to a lesser extent of Ca(++), tends to be higher in claudin 11/claudin 14 double mutants, these changes do not reach statistical significance compared with wild-type animals. Thus, under normal conditions, co-deletion of claudin 11 and claudin 14 does not affect kidney function or ion balance. Our data demonstrate that, despite the importance of each of these claudins, there is probably no functional cooperation between them. Generation of additional mouse models in which different claudins are abolished should provide further insight into the complex interactions between claudin proteins in various physiological systems.     

Primary Kaposi sarcoma of the subcutaneous tissue

Background

Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not been reported previously.

Case presentation

We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up.

Conclusion

A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed.     

Comparative resistance of Phaseolus vulgaris beans to Callosobruchus chinensis and Acanthoscelides obtectus (Coleoptera: Bruchidae): The differential digestion of soluble heteropolysaccharide

At a concentration of 1 %, a soluble heteropolysaccharide fraction derived from Phaseolus vulgaris beans prevents development of Callosobruchus chinensis but not of Acanthoscelides obtectus. At a concentration of 2 %, it partly inhibits A. obtectus. The differential response could provide a basis for selecting resistant bean varieties. The heteropolysaccharide contains arabinose, xylose, rhamnose, glucose and galactose in approximate molar proportions of 9 : 2 : 1 : 1 : 4. Its biological activity resides mainly in its integral basic structure and only to a small extent in its constituent sugars. The insensitivity of A. obtectus is due to its effectively digesting a large portion of the heteropolysaccharide, releasing most of the contained arabinose, at the larval mid-gut pH of 6.7–6.8. C. chinensis hydrolyses much less of it at its mid-gut pH of 6.4–6.6, whereby the biological activity of the polymer is retained. In vitro digestion of the heteropolysaccharide by A. obtectus enzyme results in a residue which is comparatively inactive on this beetle in vivo, but is still partly toxic for C. chinensis.

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Résumé A la concentration de 1 %, l'extrait de Phaseolus contenant l'heteropolysaccharide soluble, empêche le développement de Callosobruchus chinensis, mais non celui d'Acanthoscelides obtectus. A une concentration de 2 %, il inhibe partiellement ce dernier. Cette différence dans la réponse pourrait servir de base, en vue de la sélection de variétées de pois résistants.L'heteropolysaccharide contient de l'arabinose, du xylose, du rhamnose, du glucose et du galactose dans les proportions respectives approchées en moles 9 : 2 : 1 : 1 : 4. Son activité biologique réside principalement dans l'intégrité de sa structure fondamentale, et seulement à un faible degré dans ses sucres constitutifs. L'insensibilité de Acanthoscelides obtectus est due à ce qu'il digère effectivement une grande portion de l'heteropolysaccharide, libérant la plupart de l'arabinose contenu, cela à PH 6.7–6.8 de l'intestin moyen de la larve, Callosobruchus chinensis en hydrolyse beaucoup moins au PH 6.4–6.6 de son intestin moyen, à la suite de quoi l'activité biologique du polymère est conservée. In vitro la digestion de l'heteropolysaccharide par les enzymes d'Acanthoscelides obtectus engendre un résidu qui est comparativement inactif sur cette espèce in vivo mais est encore partiellement toxique pour Callosobruchus chinensis.

     

A theoretical model study of the comparative effectiveness of atropine and scopolamine action in the central nervous system

The molecular structural factors related to the action of atropine and scopolamine at a common biological receptor, with different apparent potencies, are studied from a theoretical viewpoint. The model molecules representing the two cholinergic antagonists are shown to possess the ability to generate an electrostatic potential field which is compatible with the “interaction pharmacophore” of acetylcholine-like molecules. A common site of action for the two types of drugs is rationalized on this basis. The effect of the differences in the molecular structure of the drugs, on their penetration ability and lipid solubility, is analyzed through the proton affinity of model compounds in the gas phase and in solution. These indicate the nature of the stronger solute-solvent interaction of scopolamine. Results from a comparative calculation of the protonation affinity of the solvated drugs are shown to reproduce the correct ratio of protonated versus free base concentrations for the two molecules, from which the reasons for the lower pKa of scopolamine and higher lipophilicity of atropine (free base) can be understood.     

Biodistribution of intracellularly acting peptides conjugated reversibly to Tat

Intracellularly acting peptide modulators of signaling enzymes provide a powerful means to regulate signaling events. Delivery of peptides into cells is facilitated by conjugation to carrier peptides, such as Tat. When peptides are irreversibly conjugated to Tat, Tat-mediated subcellular localization may predominate, resulting in mislocalization of the peptide cargo. We have used intracellularly acting peptides, conjugated to Tat by a disulfide bond, to modulate protein kinase C (PKC) signaling; these PKC-modulating peptides are released from Tat upon intracellular delivery. Previously, the distribution of these peptides within tissue and throughout the body had not been demonstrated. We show here intravascular delivery of a PKC-peptide, reversibly conjugated to Tat, resulted in distribution throughout cardiac tissue. In addition, a single injection resulted in selective modulation of PKC activity in many organs. Therefore, intracellularly acting peptide modulators of signaling enzymes, reversibly conjugated to Tat, have extensive biodistribution and can be used to modulate signaling pathways in vivo.     

Carbon Nitride/Reduced Graphene Oxide Film with Enhanced Electron Diffusion Length: An Efficient Photo‐Electrochemical Cell for Hydrogen Generation

Polymeric carbon nitride (CN) has emerged as a promising semiconductor for energy‐related applications. However, its utilization in photo‐electrochemical cells is still very limited owing to poor electron–hole separation efficiency, short electron diffusion length, and low absorption coefficient. Here the synthesis of a highly porous carbon nitride/reduced graphene oxide (CN‐rGO) film with good photo‐electrochemical properties is reported. The CN‐rGO film exhibits long electron diffusion length and high electrochemical active surface area, good charge separation, and enhanced light‐harvesting properties. The film displays a 20‐fold enhancement of photocurrent density over pristine CN, reaching up to 75 µA cm^?2 at 1.23 V versus reversible hydrogen electrode (RHE) in an alkaline solution, as well as stability over a wide pH range. Photocurrent measurements with a hole scavenger reveal a photocurrent density of 660 µA cm^?2 at 1.23 V versus RHE and a quantum efficiency of 60% at 400 nm, resulting in the production of 0.8 mol h^?1 g^?1 of hydrogen. The substantial photo‐electrochemical activity enhancement and hydrogen production together with the low price, high electrochemical surface area, long electron diffusion length, stability under harsh condition, and tunable photophysical properties of CN materials open many possibilities for their utilization in (photo)electrochemical and electronic devices.     

A model of herd grazing as a travelling wave,chemotaxis and stability

Possible constitutive models are examined for the formation of a herd, under the assumption that a herd forms a travelling wave while grazing. Under quite general conditions, it is found that the only possibility for a travelling wave is a balance between food seeking and natural dispersion, such as in chemotaxis. The stability of the travelling wave previously conjectured, is shown both for one- and two-dimensional perturbations.     

Cryogenic Transmission Electron Microscopy Nanostructural Study of Shed Microparticles

Microparticles (MPs) are sub-micron membrane vesicles (100–1000 nm) shed from normal and pathologic cells due to stimulation or apoptosis. MPs can be found in the peripheral blood circulation of healthy individuals, whereas elevated concentrations are found in pregnancy and in a variety of diseases. Also, MPs participate in physiological processes, e.g., coagulation, inflammation, and angiogenesis. Since their clinical properties are important, we have developed a new methodology based on nano-imaging that provides significant new data on MPs nanostructure, their composition and function. We are among the first to characterize by direct-imaging cryogenic transmitting electron microscopy (cryo-TEM) the near-to-native nanostructure of MP systems isolated from different cell types and stimulation procedures. We found that there are no major differences between the MP systems we have studied, as most particles were spherical, with diameters from 200 to 400 nm. However, each MP population is very heterogeneous, showing diverse morphologies. We investigated by cryo-TEM the effects of standard techniques used to isolate and store MPs, and found that either high-g centrifugation of MPs for isolation purposes, or slow freezing to –80°C for storage introduce morphological artifacts, which can influence MP nanostructure, and thus affect the efficiency of these particles as future diagnostic tools.