Cloning and characterization of DNA polymerase η from Trypanosoma cruzi: Roles for translesion bypass of oxidative damage

We report the cloning and characterization of the DNA polymerase η gene from Trypanosoma cruzi (TcPolη), the causative agent of Chagas disease. This protein, which can bypass cyclobutane pyrimidine dimers, contains motifs that are conserved between Y family polymerases. In vitro assays showed that the recombinant protein is capable of synthesizing DNA in undamaged primer‐templates. Intriguingly, T. cruzi overexpressing TcPolη does not increase its resistance to UV‐light (with or without caffeine) or cisplatin, despite the ability of the protein to enhance UV resistance in a RAD30 mutant of Saccharomyces cerevisiae. Parasites overexpressing TcPolη are also unable to restore growth after treatment with zeocin or gamma irradiation. T. cruzi overexpressing TcPolη are more resistant to treatment with hydrogen peroxide (H₂O₂) compared to nontransfected cells. The observed H₂O₂ resistance could be associated with its ability to bypass 8‐oxoguanine lesions in vitro. The results presented here suggest that TcPolη is able to bypass UV and oxidative lesions. However the overexpression of the gene only interferes in response to oxidative lesions, possibly due to the presence of these lesions during the S phase. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Spiral and target patterns in bivalve nacre manifest a natural excitable medium from layer growth of a biological liquid crystal

Nacre is an exquisitely structured biocomposite of the calcium carbonate mineral aragonite with small amounts of proteins and the polysaccharide chitin. For many years, it has been the subject of research, not just because of its beauty, but also to discover how nature can produce such a superior product with excellent mechanical properties from such relatively weak raw materials. Four decades ago, Wada [Wada K (1966) Spiral growth of nacre. Nature 211:1427] proposed that the spiral patterns in nacre could be explained by using the theory Frank [Frank F (1949) The influence of dislocations on crystal growth. Discuss Faraday Soc 5:48–54] had put forward of the growth of crystals by means of screw dislocations. Frank''s mechanism of crystal growth has been amply confirmed by experimental observations of screw dislocations in crystals, but it is a growth mechanism for a single crystal, with growth fronts of molecules. However, the growth fronts composed of many tablets of crystalline aragonite visible in micrographs of nacre are not a molecular-scale but a mesoscale phenomenon, so it has not been evident how the Frank mechanism might be of relevance. Here, we demonstrate that nacre growth is organized around a liquid-crystal core of chitin crystallites, a skeleton that the other components of nacre subsequently flesh out in a process of hierarchical self-assembly. We establish that spiral and target patterns can arise in a liquid crystal formed layer by layer through the Burton–Cabrera–Frank [Burton W, Cabrera N, Frank F (1951) The growth of crystals and the equilibrium structure of their surfaces. Philos Trans R Soc London Ser A 243:299–358] dynamics, and furthermore that this layer growth mechanism is an instance of an important class of physical systems termed excitable media. Artificial liquid crystals grown in this way may have many technological applications.     

Suture Rupture in Acromioclavicular Joint Dislocations Treated With Flip Buttons

Acute acromioclavicular joint dislocations (ACDs) may be treated arthroscopically with flip buttons. This extra-articular fixation is easy to implant and is well tolerated. Between 2007 and 2009, 20 ACD patients (2 women and 18 men; mean age, 32 years) had surgery by the arthroscopic TightRope technique (Arthrex, Naples, FL). The main complication of this technique that has been reported is the partial loss of reduction at follow-up due to clavicular osteolysis under the superior flip button. We describe 4 cases with loss of reduction due to rupture of the sutures running across the buttons: 2 women with joint hyperlaxity and acute Rockwood grade IV ACD and 2 men, heavy manual workers, with joint hyperlaxity and acute Rockwood grade IV ACD. The use of flip buttons might not be indicated in patients with joint hyperlaxity because they are able to obtain immediate stability only on the vertical plane and not on the horizontal plane. Anteroposterior movements of the acromioclavicular joint might rub the suture against the bone tunnels leading to wear and cutting.     

Bilateral whirlbone necrosis in a young multiple sclerosis patient

A case of avascular necrosis of whirlbone in a young man affected by multiple sclerosis and treated with high doses of corticosteroids is described. The authors discuss the causes of this collateral effect underlining the risks of underevaluating the symptoms.     

Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases,with special emphasis on Jessner's lymphocytic infiltrate of the skin and cutaneous lupus erythematosus

Background: Plasmacytoid dendritic cells (PDC) play a pivotal role in the induction of autoimmune diseases and other skin diseases. The present study focuses on the distribution patterns of PDC in patients with cutaneous lupus erythematosus (LE) and Jessner's lymphocytic infiltrate (LI) of the skin and compares them with other skin diseases. The goal was to scrutinize the involvement of PDC in LI, and to show that PDC present a specific pattern of distribution in various cutaneous disorders. Methods: 353 skin biopsies of LE (various subtypes), LI, and other inflammatory skin diseases as well as two halo melanocytic nevi and 10 epithelial tumors were immunohistochemically investigated for the presence of PDC by employing antibodies against CD123 and CD2AP. Results: PDC were constantly detected as distinct perivascular and periadnexal clusters in LE and LI. In other forms of dermatitis, PDC could be found as single cells or scattered throughout the infiltrate or beneath the epidermis. Conclusions: Our data suggest that the distribution of PDC in tumid LE and LI is identical, and this observation suggests that both designations signify one disease. The distinct PDC arrangement in LE represents as useful diagnostic tool in the differential diagnosis with other forms of dermatitis. Tomasini D, Mentzel T, Hantschke M, Cerri A, Paredes B, Rütten A, Schärer L, Kutzner H. Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases, with special emphasis on Jessner's lymphocytic infiltrate of the skin and cutaneous lupus erythematosus.     

Where does the lactate come from? A rare cause of reversible inhibition of mitochondrial respiration

Biguanide poisoning is associated with lactic acidosis. The exact mechanism of biguanide-induced lactic acidosis is not well understood. In the previous issue of Critical Care, Protti and colleagues demonstrated that biguanide-induced lactic acidosis may be due in part to a reversible inhibition of mitochondrial respiration. Thus, in the absence of an antidote, increased drug elimination through dialysis is logical.     

In vivo 3D morphology of astrocyte–vasculature interactions in the somatosensory cortex: implications for neurovascular coupling

Astrocytes are increasingly believed to play an important role in neurovascular coupling. Recent in vivo studies have shown that intracellular calcium levels in astrocytes correlate with reactivity in adjacent diving arterioles. However, the hemodynamic response to stimulation involves a complex orchestration of vessel dilations and constrictions that spread rapidly over wide distances. In this work, we study the three-dimensional cytoarchitecture of astrocytes and their interrelations with blood vessels down through layer IV of the mouse somatosensory cortex using in vivo two-photon microscopy. Vessels and astrocytes were visualized through intravenous dextran-conjugated fluorescein and cortically applied sulforhodamine 101 (SR101), respectively. In addition to exploring astrocyte density, vascular proximity, and microvascular density, we found that sheathing of subpial vessels by astrocyte processes was continuous along all capillaries, arterioles, and veins, comprising a highly interconnected pathway through which signals could feasibly be relayed over long distances via gap junctions. An inner SR101-positive sheath noted along pial and diving arterioles was determined to be nonastrocytic, and appears to represent selective SR101 staining of arterial endothelial cells. Our findings underscore the intimate relationship between astrocytes and all cortical blood vessels, and suggest that astrocytes could influence neurovascular regulation at a range of sites, including the capillary bed and pial arterioles.     

Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring

Endometriosis is a chronic gynecological disease characterized by the growth of endometrial tissue outside the uterine cavity. Exposure to endocrine disruptors during critical period of development causes long-lasting effects, being the genital system one of the targets. This study describes the effects on female genital system caused by developmental exposure to the endocrine-disrupting chemical bisphenol A (BPA) during pre- and peri-natal development in mice. To this end, timed pregnant Balb-C mice were treated from day 1 of gestation to 7 days after delivery with BPA (100, or 1000 μg/kg/day). After delivery, pups were held for 3 months; then, pelvic organs were analyzed in their entirety and livers of both pups and moms were studied for the presence of BPA. We found in the adipose tissue surrounding the genital tracts of a consistent number of treated animals, endometriosis-like structure with the presence of both glands and stroma and expressing both estrogen receptor and HOXA-10. Moreover, cystic ovaries, adenomatous hyperplasia with cystic endometrial hyperplasia and atypical hyperplasia were significantly more frequent in treated animals respect to the controls. Finally, BPA was found in the livers of exposed moms and female offspring. In conclusion, we describe for the first time an endometriosis-like phenotype in mice, elicited by pre-natal exposition to BPA. This observation may induce to thoroughly reconsider the pathogenesis and treatment of endometriosis, considering the high incidence of endometriosis and the problems caused by associated infertility.