INFLUENCE OF SALINITY AND SULFATE ON THE TOXICITY OF CHROMIUM(VI) TO THE ESTUARINE DIATOM THALASSIOSIRA PSEUDONANA1

The acute toxicity of Cr(VI) to the diatom Thalassiosira pseudonana (Hasle and Heimdal) clone 3H was determined in artificial media of 3.2 and 0.32 ppt salinity and with variations of sulfate concentration in the media independent of salinity. Inhibitory concentrations of Cr(VI) ranged from 6.6 μM for growth rate and 4.9 μM for cell yield at 3.2 ppt salinity and 2.8 μM sulfate to 0.04 μM for growth rate and 0.02 μM for cell yield at 0.32 ppt salinity and 0.019 mM sulfate. The inhibition by Cr(VI) was a function of the ratio of Cr(VI) to sulfate. Inhibition occurred when-this ratio exceeded about 500:1. It is suggested that the mechanism for the toxicity of Cr(VI) to diatoms and perhaps other aquatic organisms involves a site at which sulfate and chromate compete.     

Clearance of picoplankton-sized partides and formation of rapidly sinking aggregates by the pteropod, Limacina reiroversa

Findings from experiments showed that the web-feeding euthecosomatouspteropod, Limacina retroversa, can produce rapidly sinking,mucous aggregates. It is suggested that, by adhesion, theseaggregates scavenged picoplankton-sized particles, which werethus effectively cleared from the medium. In contrast, Calanusfinmarchicus was not able to clear these particles in our experiments.Sedimentation velocities of 10 aggregates measured in vivo wereup to 1000 m day^–1, with an average of {small tilde}300m day^–1 (not including two aggegates with neutral buoyancy).Mean velocities measured for feces of C.finmarchicus, Calanushyperboreus and Thyssnoessa sp. were consider ably lower. Wesuggest that the sedimentation of L retroversa aggregates wasthe source of mucous flocs collected in sediment traps (Bathmannet al., Deep-Sea Res., 38,1341–1360,1991) and at the seafloor at 1200 m depth in the southern Norwegian Sea. This processmay be an important mediator of sedimentation to the deep sea,when these pteropods are present in surface waters in largeabundance.     

Influence of extracellular monovalent cations on pore and gating properties of P2X7 receptor-operated single-channel currents

Using the patch-clamp method, we studied the influence of external alkali and organic monovalent cations on the single-channel properties of the adenosine triphosphate (ATP)-activated recombinant human P2X(7) receptor. The slope conductance of the hP2X(7) channel decreased and the reversal potential was shifted to more negative values as the ionic diameter of the organic test cations increased. From the relationship between single-channel conductance and the dimensions of the inward current carrier, the narrowest portion of the pore was estimated to have a mean diameter of approximately 8.5 A. Single-channel kinetics and permeation properties remained unchanged during receptor activation by up to 1 mM ATP(4-) for >1 min, arguing against a molecular correlate of pore dilation at the single P2X(7) channel level. Substitution of extracellular Na(+) by any other alkali or organic cation drastically increased the open probability of the channels by prolonging the mean open time. This effect seems to be mediated allosterically through an extracellular voltage-dependent Na(+) binding site with a K(d) of approximately 5 mM Na(+) at a membrane potential of -120 mV. The modulation of the ATP-induced hP2X(7) receptor gating by extracellular Na(+) could be well described by altering the rate constant from the open to the neighboring closed state in a C-C-C-O kinetic receptor model. We suggest that P2X(7) receptor-induced depolarization and associated K(+)-efflux may reduce Na(+) occupancy of the regulatory Na(+) binding site and thus increase the efficacy of ATP(4-) in a feed-forward manner in P2X(7) receptor-expressing cells.     

The Colposcopic Atlas of Schistosomiasis in the Lower Female Genital Tract Based on Studies in Malawi,Zimbabwe, Madagascar and South Africa

Background

Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women.

Methodology/Principal findings

Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes.

Significance

This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice.     

Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q

Common variable immunodeficiency (CVID) is an antibody deficiency syndrome that often co-occurs in families with selective IgA deficiency (IgAD). Vořechovsky et al. (Am J Hum Genet 64:1096–1109, 1999; J Immunol 164:4408–4416, 2000) ascertained and genotyped 101 multiplex IgAD families and used them to identify and fine map the IGAD1 locus on chromosome 6p. We analyzed the original genotype data in a subset of families with at least one case of CVID and present evidence of a CVID locus on chromosome 16q with autosomal dominant inheritance. The peak (model-based) LOD score for the best marker D16S518 is 2.83 at θ=0.07, and a 4-marker LOD score under heterogeneity peaks at 3.00 with α=0.68. The (model-free) NPL score using the same markers peaks at the same location with a value of 3.38 (P=0.0001).     

Multimerization of Drosophila sperm protein Mst77F causes a unique condensed chromatin structure

Despite insights on the cellular level, the molecular details of chromatin reorganization in sperm development, which involves replacement of histone proteins by specialized factors to allow ultra most condensation of the genome, are not well understood. Protamines are dispensable for DNA condensation during Drosophila post-meiotic spermatogenesis. Therefore, we analyzed the interaction of Mst77F, another very basic testis-specific protein with chromatin and DNA as well as studied the molecular consequences of such binding. We show that Mst77F on its own causes severe chromatin and DNA aggregation. An intrinsically unstructured domain in the C-terminus of Mst77F binds DNA via electrostatic interaction. This binding results in structural reorganization of the domain, which induces interaction with an N-terminal region of the protein. Via putative cooperative effects Mst77F is induced to multimerize in this state causing DNA aggregation. In agreement, overexpression of Mst77F results in chromatin aggregation in fly sperm. Based on these findings we postulate that Mst77F is crucial for sperm development by giving rise to a unique condensed chromatin structure.     

Construction and Rescue of a Molecular Clone of Deformed Wing Virus (DWV)

European honey bees are highly important in crop pollination, increasing the value of global agricultural production by billions of dollars. Current knowledge about virulence and pathogenicity of Deformed wing virus (DWV), a major factor in honey bee colony mortality, is limited. With this study, we close the gap between field research and laboratory investigations by establishing a complete in vitro model for DWV pathogenesis. Infectious DWV was rescued from a molecular clone of a DWV-A genome that induces DWV symptoms such as crippled wings and discoloration. The expression of DWV proteins, production of infectious virus progeny, and DWV host cell tropism could be confirmed using newly generated anti-DWV monoclonal antibodies. The recombinant RNA fulfills Koch’s postulates circumventing the need of virus isolation and propagation of pure virus cultures. In conclusion, we describe the development and application of a reverse genetics system for the study of DWV pathogenesis.     

Die Ultrastruktur des Juxtaglomerulären Apparates des Meerschweinchens

Zusammenfassung Der Beweis für das Vorkommen von Sekretgranula in den epitheloiden Zellen des Meerschweinchens ist bisher von keinem Autor erbracht worden. Ihre Abwesenheit ist um so erstaunlicher, als die Renin-Aktivität in der Niere dieses Tieres etwa 1/10 der der Ratte mit ihren stark granulierten Epitheloidzellen beträgt und die des Menschen sogar übertrifft. In unserem Untersuchungsgut finden wir hin und wieder einige wenige, wahrscheinlich Renin enthaltende Granula (Abb. 1–4). Anscheinend erfolgen Synthese und Ausscheidung des Enzyms im gleichen Rhythmus; zu einer geringgradigen Speicherung kommt es offenbar nur unter bestimmten funktionellen Bedingungen.Die Goormaghtighschen Zellen (Abb. 5) zeigen kein besonderes auffälliges artspezifisches Verhalten.An der Macula densa wird erstmals eine starke Erweiterung sowohl der intracytoplasmatischen Einfaltungen des basalen Plasmalemms — des basalen Labyrinthes — als auch der Interzellularspalten beschrieben (Abb. 6–9). Diese oberhalb der Basalmembran gelegenen Pseudovakuolen sind somit extrazellulär und möglicherweise als morphologisches Äquivalent einer starken Reabsorptionstätigkeit zu deuten. Es ist zur Zeit noch nicht entschieden, ob sie mit der von uns angewandten Präparationstechnik auch bei anderen Tieren und beim Menschen darstellbar sind.

---

Summary The presence of secretory granules in the epithelioid (juxtaglomerular) cells in the media of the preglomerular portion of the afferent arterioles in the kidney of the Guinea pig has not been proven by any author until now. The absence of these granules is all the more astonishing in view of the fact that the renin activity of this animal is about 1/10 of that of the rat — with its highly granulated cells — and even surpasses that of humans. In our inbread strain rare granules likely containing renin can be found from time to time (Fig. 1–4). Apparently, the synthesis and extrusion of the enzyme takes place with the same rhythm; a very low degree of accumulation occurs probably only under certain functional conditions.The Goormaghtigh Cells (Fig. 5) show no noticeable differences specific for the Guinea pig. In the Macula densa highly developed enlargements of the basal infoldings of the plasma membrane — basal labyrinthe — as well as of the intercellular spaces are described for the first time (Fig. 6–9). These enlargements (Pseudovacuoles), situated above the basement membrane, are extracellular and can possibly be interpreted as the morphological equivalent of a high degree of absorption activity. At the present time it has not been decided, if, using the authors' technique, these enlargements can be demonstrated in other animals and humans.

---

---

In Zusammenarbeit mit dem Pharmakologischen Institut der Universität Lausanne und mit Unterstützung durch die Fritz Hoffmann-La Roche-Stiftung zur Förderung wissenschaftlicher Arbeitsgemeinschaften in der Schweiz.     

Cell migration: mechanisms of rear detachment and the formation of migration tracks

Cell migration is central to many biological and pathological processes, including embryogenesis, tissue repair and regeneration as well as cancer and the inflammatory response. In general, cell migration can be usefully conceptualized as a cyclic process. The initial response of a cell to a migration-promoting agent is to polarize and extend protrusions in the direction of migration. These protrusions can be large, broad lamellipodia or spike-like filopodia, are usually driven by actin polymerization, and are stabilized by adhering to the extracellular matrix (ECM) via transmembrane receptors of the integrin family linked to the actin cytoskeleton. These adhesions serve as traction sites for migration as the cell moves forward over them, and they must be disassembled at the cell rear, allowing it to detach. The mechanisms of rear detachment and the regulatory processes involved are not well understood. The disassembly of adhesions that is required for detachment depends on a coordinated interaction of actin and actin-binding proteins, signaling molecules and effector enzymes including proteases, kinases and phosphatases. Originally, the biochemically regulated processes leading to rear detachment of migrating cells were thought not to be necessarily accompanied by any loss of cell material. However, it has been shown that during rear detachment long tubular extensions, the retracting fibers, are formed and that "membrane ripping" occurs at the cell rear. By this process, a major fraction of integrin-containing cellular material is left behind forming characteristic migration tracks that exactly mark the way a cell has taken.