Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis

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Repeated visitations of spermatophores and polyandry in females of eriophyoid mites

Eriophyoid females store sperm either asymmetrically in one spermatheca, or symmetrically in both spermathecae. Previous studies have suggested that species in which females store sperm asymmetrically pick up sperm from only one spermatophore, while those with symmetrical sperm storage pick up sperm from two or more spermatophores during their lifetime. The aim of this study was to examine spermatophore visitation behaviour and symmetry of sperm storage in Aculops allotrichus from the black locust tree and Cecidophyopsis hendersoni from the yucca. This would indicate monandry or polyandry in these species. In both eriophyoids, the spermatophore visitation consisted of three phases: mounting, lying on the spermatophore and dismounting. Aculops allotrichus stored sperm asymmetrically. However, nearly one-third of the observed females visited two spermatophores, rather than only one in their lives. When A. allotrichus females visited two spermatophores they spent a similar amount of time at the first and at the second visitation. Also, the times of visitation of the first of the two spermatophores and the single spermatophore in a female lifetime did not differ significantly. This would suggest that apart from monandry, double insemination also occurs in this species. By contrast, C. hendersoni females were polyandrous. They stored sperm symmetrically and visited several spermatophores, on average 1.54 (max 6) per day, and up to 33 spermatophores in their lives. The benefits of repeated spermatophore visitation and the possible mechanisms of sperm storage in both species are discussed.     

Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion

Targeted angiostatic therapy receives major attention for the treatment of cancer and exudative age‐related macular degeneration (AMD). Photodynamic therapy (PDT) has been used as an effective clinical approach for these diseases. As PDT can cause an angiogenic response in the treated tissue, combination of PDT with anti‐angiogenic compounds should lead to improved therapy. This study was undertaken to test the clinically used small molecule kinase inhibitors Nexavar® (sorafenib), Tarceva® (erlotinib) and Sutent® (sunitinib) for this purpose, and to compare the results to the combination of Visudyne®‐PDT with Avastin® (bevacizumab) treatment. When topically applied to the chicken chorioallantoic membrane at embryo development day (EDD) 7, a clear inhibition of blood vessel development was observed, with sorafenib being most efficient. To investigate the combination with phototherapy, Visudyne®‐PDT was first applied on EDD11 to close all <100 μm vessels. Application of angiostatics after PDT resulted in a significant decrease in vessel regrowth in terms of reduced vessel density and number of branching points/mm². As the 50% effective dose (ED50) for all compounds was approximately 10‐fold lower, Sorafenib outperformed the other compounds. In vitro, all kinase inhibitors decreased the viability of human umbilical vein endothelial cells. Sunitinib convincingly inhibited the in vitro migration of endothelial cells. These results suggest the therapeutic potential of these compounds for application in combination with PDT in anti‐cancer approaches, and possibly also in the treatment of other diseases where angiogenesis plays an important role.     

Melanosome–iron interactions within retinal pigment epithelium‐derived cells

Melanosomes were recently shown to protect ARPE‐19 cells, a human retinal pigment epithelium (RPE) cell line, against oxidative stress induced by hydrogen peroxide. One postulated mechanism of antioxidant action of melanin is its ability to bind metal ions. The aim here was to determine whether melanosomes are competent to bind iron within living cells, exhibiting a property previously shown only in model systems. The outcomes indicate retention of prebound iron and accumulation of iron by granules after iron delivery to cells via the culture medium, as determined by both colorimetric and electron spin resonance analyses for bound‐to‐melanosome iron. Manipulation of iron content did not affect the pigment's ability to protect cells against H₂O₂, but the function of pigment granules within RPE cells should be extended beyond a role in light irradiation to include participation in iron homeostasis.     

Evaluation of Agar Candida ID2 (bioMerieux) a chromogenic medium for yeasts differentiation

Invasive diagnostic and therapeutic methods, widespread antibiotic therapy and rising percent of the immunocompromised patients cause incrementation of frequency of occurrence of the yeast infection. C. albicans is the most commonly isolated species of Candida from clinical samples. However, recently growth of frequency of isolation Candida non - albicans from clinical specimens have been observed. Yeast-like fungi different from C. albicans have become serious clinical problem. Conventional methods of identification of the yeast-like fungi carry away a lot time enough. Employment of chromogenic agar shortens latency on result. We decided to examine the usefulness ofAgar Candida ID2 (CAN2) (bioMérieux) in the identification of Candida species. The subjects within the study were 146 of Candida spp strains which were isolated from the clinical specimens of patients hospitalized at the University Hospital in Bydgoszcz. Germ tube test. Api 20C AUX test (bioMérieux) and Agar Candida ID2 (bioMérieux) were used. We have ascertained correspondence of identifying species amounted to 82.2% of analyzed Candida species between API 20C AUX test and kind of growth on CAN2 medium. Divergence of results received between CAN2 medium and API 20C AUX test suggests necessity of conducting of verification data with other methods. In conclusion, our study shows that Agar Candida ID2 is an effective medium for the isolation yeast-like fungi and in preliminary identification of Candida species direct from clinical materials.     

Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB

Intracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for l‐Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB – a bifunctional enzyme catalyzing the last two steps in l‐Trp synthesis. TrpA (subunit α) converts indole‐3‐glycerol phosphate into indole and glyceraldehyde‐3‐phosphate (α reaction). The former compound is subsequently used by TrpB (subunit β) to produce l‐Trp in the presence of l‐Ser and a pyridoxal 5′‐phosphate cofactor (β reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yet remains associated with TrpB to support the β reaction. Here, we provide detailed analysis of the TrpAB from C. trachomatis D/UW‐3/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four‐fold. The side chain of non‐conserved βArg267 functions as cation effector, potentially rendering the enzyme less susceptible to the solvent ion composition. The observed structural and functional changes detected herein were placed in a broader evolutionary and genomic context, allowing identification of these mutations in relation to their trp gene contexts in which they occur. Moreover, in agreement with the in vitro data, partial relaxation of purifying selection for TrpA, but not for TrpB, was detected, reinforcing a partial loss of TrpA functions during the course of evolution.     

The stepwise specification of embryonic stem cells to hematopoietic fate is driven by sequential exposure to Bmp4, activin A, bFGF and VEGF

The differentiation of embryonic stem (ES) cells offers a powerful approach to study mechanisms implicated in cell fate decision. A major hurdle, however, is to promote the directed and efficient differentiation of ES cells toward a specific lineage. Here, we define in serum-free media the minimal factor requirement controlling each step of the differentiation process, resulting in the production of highly enriched hematopoietic progenitors. Four factors - Bmp4, activin A, bFGF (Fgf2) and VEGF (VegfA) - are sufficient to drive the selective and efficient differentiation of mouse ES cells to hematopoiesis. Each of these factors appears to regulate a step of the process: Bmp4 promotes the very efficient formation of mesoderm; bFGF and activin A induce the differentiation of these mesodermal precursors to the hemangioblast fate; and VEGF is required for the production of fully committed hematopoietic progenitors. The stimulation of mesodermal precursors by bFGF and activin A switches on very rapidly the hematopoietic program, allowing us to dissect the molecular events leading to the formation of the hemangioblast. Runx1, Scl (Tal1) and Hhex expression is upregulated within 3 hours of stimulation, whereas upregulation of Lmo2 and Fli1 is observed later. Interestingly, increased expression levels of genes such as cMyb, Pu.1 (Sfpi1), Gata1 and Gata2 are not observed at the onset of hemangioblast commitment. This stepwise control of differentiation is extremely efficient, giving rise to a very high frequency of hematopoietic precursors, and provides an optimal system for understanding the molecular machineries involved in blood progenitor commitment.     

Studies on the removal of Cd ions by gastrointestinal lactobacilli

Applied Microbiology and Biotechnology - Accumulation of toxic metal ions in food and water is nowadays a growing health-related problem. One detoxification method involves the use of...