Influence of amphotericin B deoxycholate or amphotericin B colloidal dispersion on renal tubule epithelium in rat

Amphotericin B deoxycholate (AmB) or Amphotericin B colloidal dispersion (ABCD) are used in clinics for the treatment of systemic fungal infections. The goal of our study was to compare the nephrotoxicity of these drugs in rat kidney. The effects of AmB and ABCD on the ultrastructure of the epithelium of renal tubules were studied and evaluated using morphometric and statistical methods. Two groups of 3 animals were established: group 1 was treated with AmB desoxycholate and group 2, to which ABCD was applied. AmB caused more than ABCD ultrastructural changes in the cytoplasm of the epithelial cells: damage to mitochondria, vacuolation of cytoplasm, and increased values of volume density of peroxisomes. However, we failed to observe significant differences in morphology and density of the other cell organelles. The proximal tubules seemed to be more sensitive to the nephrotoxic influence of both formulas than the distal tubules of rat kidney. Although, AmB causes more severe damage than ABCD, both drugs cause damage to renal tubuli.     

In vitro scavenging activity for reactive oxygen species by N-substituted indole-2-carboxylic acid esters.

The hydroxyl radical (HO*)- and superoxide anion radical (O* (2))-scavenging activity, as well as the singlet oxygen ((1)O(2))-quenching property of N-substituted indole-2-carboxylic acid esters (INDs) were investigated by deoxyribose degradation assay, a chemiluminescence method and the electron spin resonance (ESR) spin-trapping technique. This novel group of compounds was developed as a search for cyclooxygenase-2 (COX-2)-selective enzyme inhibitors. The results obtained demonstrated that of the 16 compounds examined, five inhibited light emission from the superoxide anion radical (O* (2))-DMSO system by at least 60% at a concentration of 1 mmol/L, nine prevented the degradation of deoxyribose induced by the Fenton reaction system (range 3-78%) or scavenged hydroxyl radicals (HO*) directly (range 8-93%) and 14 showed the (1)O(2)-quenching effect (range 10-74%). These results indicate that majority of the indole esters tested possess the ability to scavenge O(-) (2) and HO radicals and to quench (1)O(2) directly, and consequently may be considered effective antioxidative agents.     

MOLECULAR PHYLOGENY OF SELECTED MEMBERS OF THE ORDER THALASSIOSIRALES (BACILLARIOPHYTA) AND EVOLUTION OF THE FULTOPORTULA1

Recent phylogenetic studies of the diatoms indicate that members of the order Thalassiosirales occupy an interesting position in the diatom evolutionary tree. Despite their radial morphology and scaly auxospores, they are consistently recovered in molecular analyses as a member of subdivision Bacillariophytina and a sister clade to non‐fultoportulate and non‐radial lithodesmioids. This study included 46 species from nine traditionally accepted extant genera, and analyzed 43 nuclear small subunit (SSU) rRNA sequences in parallel with a survey of the variation in fultoportula structure. Three possible scenarios leading to the evolution of the fultoportula are discussed in the context of molecular and morphological similarities between the examined Thalassiosirales and their SSU rRNA sister clade Lithodesmiales. We speculate that the fultoportula might be derived by a modification of either a cribrum in an areola (fultoportula within an areola), or structures similar to marginal ridges now seen in lithodesmioids around a cluster of poroids (fultoportula in a tube), or finally, that the central fultoportula may have an origin different from the marginal fultoportulae. Our data confirm that fultoportula‐bearing diatoms constitute a natural phylogenetic group. The families Thalassiosiraceae, Skeletonemaceae, and Stephanodiscaceae and the genus Thalassiosira Cleve were unexpectedly found to be paraphyletic. Further, Cyclotella Kutz. and Stephanodiscus Ehr. may not be closely related and some species of these genera are more closely allied to other species of Thalassiosira. The generitype, T. nordenskioeldii, is embedded within a large poorly structured cluster of species that includes several members of Thalassiosira, Planktoniella sol, Minidiscus trioculatus, and two members of Stephanodiscus. An emendment of the order Lithodesmiales and the family Lauderiaceae are proposed.     

MATH domain proteins represent a novel protein family in Arabidopsis thaliana, and at least one member is modified in roots during the course of a plant–microbe interaction

The basidiomycete Piriformospora indica interacts with Arabidopsis roots and mimics an arbuscular mycorrhiza. A MATH [meprin and TRAF (tumour necrosis factor receptor-associated factor) homology] domain-containing (MATH) protein at the plasma membrane of Arabidopsis roots is one of the first components to respond to the presence of this fungus. MATH proteins are involved in nodule formation in Medicago and protein degradation in the Arabidopsis cytosol. They exhibit sequence similarities to meprins, extracellular peptidases which cleave (signal) peptides, and to TRAFs, intracellular proteins which interact with receptor kinases at the plasma membrane. Fifty-nine genes for MATH proteins are present in the Arabidopsis genome. Members of this protein family are predicted to be found in the ER–plasma membrane–extracellular space continuum, in the nucleus–cytosol compartment and in organelles. In this article, we describe this novel class of plant genes. We also use MS-MS analyses to identify the subcellular localization of individual members of the MATH protein family in Arabidopsis thaliana .     

The Pleckstrin homology like domain family member,TDAG51, is temporally regulated during skeletal muscle regeneration

The capacity for skeletal muscle to repair from daily insults as well as larger injuries is a vital component to maintaining muscle health over our lifetime. Given the importance of skeletal muscle for our physical and metabolic well-being, identifying novel factors mediating the growth and repair of skeletal muscle will thus build our foundational knowledge and help lead to potential therapeutic avenues for muscle wasting disorders. To that end, we investigated the expression of T-cell death associated gene 51 (TDAG51) during skeletal muscle repair and studied the response of TDAG51 deficient (TDAG51^-/-) mice to chemically-induced muscle damage.TDAG51 mRNA and protein expression within uninjured skeletal muscle is almost undetectable but, in response to chemically-induced muscle damage, protein levels increase by 5 days post-injury and remain elevated for up to 10 days of regeneration. To determine the impact of TDAG51 deletion on skeletal muscle form and function, we compared adult male TDAG51^-/- mice with age-matched wild-type (WT) mice. Body and muscle mass were not different between the two groups, however, in situ muscle testing demonstrated a significant reduction in force production both before and after fatiguing contractions in TDAG51^-/- mice.During the early phases of the regenerative process (5 days post-injury), TDAG51^-/- muscles display a significantly larger area of degenerating muscle tissue concomitant with significantly less regenerating area compared to WT (as demonstrated by embryonic myosin heavy chain expression). Despite these early deficits in regeneration, TDAG51^-/- muscles displayed no morphological deficits by 10 days post injury compared to WT mice.Taken together, the data presented herein demonstrate TDAG51 expression to be upregulated in damaged skeletal muscle and its absence attenuates the early phases of muscle regeneration.     

IgG glycosylation and DNA methylation are interconnected with smoking

Background

Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic.

The cephalic labial gland secretions of two socially parasitic bumblebees Bombus hyperboreus (Alpinobombus) and Bombus inexspectatus (Thoracobombus) question their inquiline strategy

Social parasitic Hymenopterans have evolved morphological, chemical, and behavioral adaptations to overcome the sophisticated recognition and defense systems of their social host to invade host nests and exploit their worker force. In bumblebees, social parasitism appeared in at least 3 subgenera independently: in the subgenus Psithyrus consisting entirely of parasitic species, in the subgenus Alpinobombus with Bombus hyperboreus, and in the subgenus Thoracobombus with B. inexspectatus. Cuckoo bumblebee males utilize species‐specific cephalic labial gland secretions for mating purposes that can impact their inquiline strategy. We performed cephalic labial gland secretions in B. hyperboreus, B. inexspectatus and their hosts. Males of both parasitic species exhibited high species specific levels of cephalic gland secretions, including different main compounds. Our results showed no chemical mimicry in the cephalic gland secretions between inquilines and their host and we did not identify the repellent compounds already known in other cuckoo bumblebees.     

Late Quaternary climate legacies in contemporary plant functional composition

The functional composition of plant communities is commonly thought to be determined by contemporary climate. However, if rates of climate‐driven immigration and/or exclusion of species are slow, then contemporary functional composition may be explained by paleoclimate as well as by contemporary climate. We tested this idea by coupling contemporary maps of plant functional trait composition across North and South America to paleoclimate means and temporal variation in temperature and precipitation from the Last Interglacial (120 ka) to the present. Paleoclimate predictors strongly improved prediction of contemporary functional composition compared to contemporary climate predictors, with a stronger influence of temperature in North America (especially during periods of ice melting) and of precipitation in South America (across all times). Thus, climate from tens of thousands of years ago influences contemporary functional composition via slow assemblage dynamics.     

Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK

Podocyte insulin sensitivity is critical for glomerular function, and the loss of appropriate insulin signaling leads to alterations and disorders featuring diabetic nephropathy. Energy-sensing pathways, such as AMP-dependent protein kinase (AMPK) and protein deacetylase SIRT1, have been shown to play an important role in insulin resistance. The absence of a stimulating effect of insulin on glucose uptake into podocytes after exposure to hyperglycemic conditions has been demonstrated to be related to a decreased level and activity of SIRT1 protein, leading to reduced AMPK phosphorylation.The present work was undertaken to investigate metformin's ability to restore the insulin responsiveness of podocytes by regulating SIRT1 and AMPK activities.Primary rat podocytes cultured with standard or high glucose concentrations for 5 days were transfected with siRNAs targeting SIRT1, AMPKα1, or AMPKα2. SIRT1 activity was measured by a fluorometric method. Insulin-stimulated changes in glucose uptake were used to detect insulin resistance. Podocyte permeability was measured by a transmembrane albumin flux assay to examine podocytes functioning.Our results demonstrated that metformin activated SIRT1 and AMPK, prevented hyperglycemia-induced reduction of SIRT1 protein levels, ameliorated glucose uptake into podocytes, and decreased glomerular filtration barrier permeability. Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation. Therefore, the potentiating effect of metformin on insulin-resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity, establishing multilateral effects of metformin action.