Collecting duct cells that lack normal cilia have mislocalized vasopressin-2 receptors

Polycystic kidney disease (PKD) is a ciliopathy characterized by renal cysts and hypertension. These changes are presumably due to altered fluid and electrolyte transport in the collecting duct (CD). This is the site where vasopressin (AVP) stimulates vasopressin-2 receptor (V2R)-mediated aquaporin-2 (AQP2) insertion into the apical membrane. Since cysts frequently occur in the CD, we studied V2R and AQP2 trafficking and function in CD cell lines with stunted and normal cilia [cilia (-), cilia (+)] derived from the orpk mouse (hypomorph of the Tg737/Ift88 gene). Interestingly, only cilia (-) cells grown on culture dishes formed domes after apical AVP treatment. This observation led to our hypothesis that V2R mislocalizes to the apical membrane in the absence of a full-length cilium. Immunofluorescence indicated that AQP2 localizes to cilia and in a subapical compartment in cilia (+) cells, but AQP2 levels were elevated in both apical and basolateral membranes in cilia (-) cells after apical AVP treatment. Western blot analysis revealed V2R and glycosylated AQP2 in biotinylated apical membranes of cilia (-) but not in cilia (+) cells. In addition, apical V2R was functional upon apical desmopressin (DDAVP) treatment by demonstrating increased cAMP, water transport, and benzamil-sensitive equivalent short-circuit current (I(sc)) in cilia (-) cells but not in cilia (+) cells. Moreover, pretreatment with a PKA inhibitor abolished DDAVP stimulation of I(sc) in cilia (-) cells. Thus we propose that structural or functional loss of cilia leads to abnormal trafficking of AQP2/V2R leading to enhanced salt and water absorption. Whether such apical localization contributes to enhanced fluid retention and hypertension in PKD remains to be determined.     

Responses of riparian trees to interannual variation in ground water depth in a semi-arid river basin

We investigated the physiological and growth responses of native (Populus fremontii S. Wats. and Salix gooddingii Ball) and exotic (Tamarix chinensis Lour.) riparian trees to ground water availability at the free‐flowing Hassayampa River, Arizona, during dry (1997) and wet (1998) years. In the drier year, all species experienced considerable water stress, as evidenced by low shoot water potentials, low leaf gas exchange rates and large amounts of canopy dieback. These parameters were significantly related to depth of ground water (DGW) in the native species, but not in T. chinensis, in 1997. Canopy dieback was greater in the native species than in T. chinensis when ground water was deep in 1997, and dieback increased rapidly at DGW > 2·5–3·0 m for the native species. Analysis of combined data from wet and dry years for T. chinensis tentatively suggests a similar physiological sensitivity to water availability and a similar DGW threshold for canopy dieback. In 1998, shoot water potential and leaf gas exchange rates were higher and canopy dieback was lower for all species because of increased water availability. However, T. chinensis showed a much larger increase in leaf gas exchange rates in the wet year than the native species. High leaf gas exchange rates, growth when water is abundant, drought tolerance and the maintenance of a viable canopy under dry conditions are characteristics that help explain the ability of T. chinensis to thrive in riparian ecosystems in the south‐western United States.     

The genetic or mythical ancestry of descent groups: lessons from the Y chromosome

Traditional societies are often organized into descent groups called "lineages," "clans," and "tribes." Each of these descent groups claims to have a common ancestor, and this ancestry distinguishes the group's members from the rest of the population. To test the hypothesis of common ancestry within these groups, we compared ethnological and genetic data from five Central Asian populations. We show that, although people from the same lineage and clan share generally a recent common ancestor, no such common ancestry is observed at the tribal level. Thus, a tribe might be a conglomerate of clans who subsequently invented a mythical ancestor to strengthen group unity.     

Hell-und Dunkeladaptation der Augen vonPieris brassicae L. (Lepidoptera)

Summary The compound eyes ofPieris brassicae L. have a tiered retina. During light and dark adaptation, ultrastructural changes have been observed throughout the length of the ommatidia in the latero-ventral region of the eyes. These changes have been quantitated by mapping at distinct levels of the ommatidia, and plotted as histograms. Both in visual cells and secondary pigment cells and at the attachment region between crystalline cone and rhabdome such ultrastructural changes have been found to be correlated to the state of adaptation.Distal and proximal photoreceptor cells show different adaptation mechanisms. Whereas the distal cells show a clear pupil mechanism in their distal parts, there is only very little horizontal movement of pigment granules in the proximal cells. In the proximal cells, multivesicular bodies (MVB) are always abundant, while in the distal cells their number is small and increases slightly during light adaptation. In the proximal cells light adaptation causes pigment granules, located in the distal process, to move proximally. Increasing the light intensity from 160 to 1600 W/cm² results in more intense migration of pigments.In the secondary pigment cells, a slight but significant distal movement of pigment granules is observed at high light intensity. If continued this condition causes the granules to aggregate in the vicinity of the apical cell membrane, and to move up to the distal inflated extensions of the distal processes formed by these cells. In dark adapted eyes, these processes are nearly devoid of pigment and the pigment granules beneath the apical membrane disperse. In addition to these structural changes, there is a tendency for retinal movements at the attachment from crystalline cone to rhabdome. — The various adaptation mechanisms are not equally well developed in different regions of the compound eye.

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Hell-und Dunkeladaptation der Augen vonPieris brassicae L. (Lepidoptera)

Zusammenfassung Die Retina vonPieris brassicae L. ist mehrreihig. Erstmals wurden feinstrukturelle Veränderungen während der Hell und Dunkeladaptation über die gesamte Länge der Ommatidien des latero-ventralen Augenbereichs anhand von Kartierungen in vergleichbaren Höhen der Ommatidien untersucht und in Histogrammen wiedergegeben. — Sowohl in den Sehzellen als auch Nebenpigmentzellen und am Übergang von Kristallkegel zum Rhabdom wurden feinstrukturelle Veränderungen in Korrelation mit der Adaptation gefunden.Die Adaptation erfolgt bei distalen und proximalen Sehzellen jeweils auf andere Art. Während die distalen Sehzellen in ihrem distalsten Bereich sehr gut die Pupillenreaktion zeigen, adaptieren die proximalen Sehzellen nur geringfügig mit horizontaler Pigmentwanderung. Auch die Anzahl der multivesikulären Körper (MVB), die in den proximalen Sehzellen immer groß ist, steigt bei Helladaptation (HA) nur in den distalen Sehzellen etwas an. In den proximalen Sehzellen wandern die Pigmentgranula bei HA geringfügig aus dem distalen Fortsatz dieser Sehzellen proximalwärts. Intensitätssteigerung auf das 10fache (von 160 auf 1600W/cm²) bewirkt eine Verstärkung der genannten Pigmentwanderungs-Reaktionen in den Sehzellen.Die Granula der Nebenpigmentzellen wandern bei HA mit starker Intensität etwas distalwärts. — Bei starker langer HA häufen sich diese Granula unter der apikalen Membran dieser Nebenpigmentzellen und wandern bis in die distalen kleinen Erweiterungen der distalen Fortsätze dieser Zellen. Bei Dunkeladaptation (DA) sind diese Fortsätze nahezu frei von Pigment; unter der apikalen Zellmembran verteilen sich die Pigmente locker. Außerdem besteht am Übergang von Kristallkegel zu Rhabdom die Tendenz zur Retinomotorik. — In den verschiedenen Augenbereichen erfolgen die genannten Adaptationsreaktionen unterschiedlich gut.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft und der Stiftung Volkswagenwerk

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Herrn Prof. Dr. Kurt Hamdorf (Bochum) danken wir für kritische Diskussion und Fräulein Althaus für die graphischen Darstellungen     

Identification of the Bacillus anthracis (gamma) phage receptor

Bacillus anthracis, a gram-positive, spore-forming bacterium, is the etiological agent of anthrax. It belongs to the Bacillus cereus group, which also contains Bacillus cereus and Bacillus thuringiensis. Most B. anthracis strains are sensitive to phage gamma, but most B. cereus and B. thuringiensis strains are resistant to the lytic action of phage gamma. Here, we report the identification of a protein involved in the bacterial receptor for the gamma phage, which we term GamR (Gamma phage receptor). It is an LPXTG protein (BA3367, BAS3121) and is anchored by the sortase A. A B. anthracis sortase A mutant is not as sensitive as the parental strain nor as the sortase B and sortase C mutants, whereas the GamR mutant is resistant to the lytic action of the phage. Electron microscopy reveals the binding of the phage to the surface of the parental strain and its absence from the GamR mutant. Spontaneous B. anthracis mutants resistant to the phage harbor mutations in the gene encoding the GamR protein. A B. cereus strain that is sensitive to the phage possesses a protein similar (89% identity) to GamR. B. thuringiensis 97-27, a strain which, by sequence analysis, is predicted to harbor a GamR-like protein, is resistant to the phage but nevertheless displays phage binding.     

A double-headed cathepsin B inhibitor devoid of warhead

Most synthetic inhibitors of peptidases have been targeted to the active site for inhibiting catalysis through reversible competition with the substrate or by covalent modification of catalytic groups. Cathepsin B is unique among the cysteine peptidase for the presence of a flexible segment, known as the occluding loop, which can block the primed subsites of the substrate binding cleft. With the occluding loop in the open conformation cathepsin B acts as an endopeptidase, and it acts as an exopeptidase when the loop is closed. We have targeted the occluding loop of human cathepsin B at its surface, outside the catalytic center, using a high-throughput docking procedure. The aim was to identify inhibitors that would interact with the occluding loop thereby modulating enzyme activity without the help of chemical warheads against catalytic residues. From a large library of compounds, the in silico approach identified [2-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethylamino]-2-oxoethyl] 2-(furan-2-carbonylamino) acetate, which fulfills the working hypothesis. This molecule possesses two distinct binding moieties and behaves as a reversible, double-headed competitive inhibitor of cathepsin B by excluding synthetic and protein substrates from the active center. The kinetic mechanism of inhibition suggests that the occluding loop is stabilized in its closed conformation, mainly by hydrogen bonds with the inhibitor, thus decreasing endoproteolytic activity of the enzyme. Furthermore, the dioxothiazolidine head of the compound sterically hinders binding of the C-terminal residue of substrates resulting in inhibition of the exopeptidase activity of cathepsin B in a physiopathologically relevant pH range.     

Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis

Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial.     

Us and them: From prejudice to racism. An original analysis of race and racism

This paper present the content of the Musée de l'Homme exhibition “Us and them: from prejudice to racism” and provides a detailed explanation of how this content has been presented to the public. In a second section of this paper we explain some of the analysis and concepts, from a biological anthropology perspective, that were the foundation of the exhibition and provides some information about the current situation in France.     

Differences in heritable trait variation among populations of varying size in the perennial herb Phyteuma spicatum

Habitat fragmentation may affect trait evolution in plants through changes in the environment. Evolutionary change, however, may be limited when fragmented populations suffer from genetic or environmental deterioration. In this study, we examined the potential of plants in fragmented populations to respond to altered selective pressures by estimating the amount of heritable variation in several phenotypic traits, using Phyteuma spicatum as study species. We grew offspring of plants of ten natural populations of varying size under common environmental conditions and assessed if population trait means or heritability estimates were related to the size and abiotic environmental conditions of the populations of origin. All traits differed significantly among populations and maternal families, suggesting that genetic effects were responsible for the observed trait variation. Narrow-sense heritabilities (h ² ) ranged between 0 and 1.13, depending on trait and population of origin. Size and/or environmental conditions of the populations of origin affected means and h ² -estimates of some of the measured traits. Heritabilities for flowering duration and mean seed mass decreased with decreasing population size, suggesting that plants in small populations may have a reduced capacity to respond and adapt to changes in the environment which alter selective pressures on these traits. Still, mean h ² -estimates were in some cases low, and patterns were generally quite variable. Further studies are therefore needed to gain more conclusive insights into the adaptive potential of small plant populations. Such knowledge is important if we want to understand how habitat fragmentation and associated changes in the environment affect trait evolution.