Litter Decomposition Rates of Biocrust-Forming Lichens Are Similar to Those of Vascular Plants and Are Affected by Warming

Ecosystems - Despite the high relevance of communities dominated by lichens, mosses and cyanobacteria living on the soil surface (biocrusts) for ecosystem functioning in drylands, no study to date...     

Detecting taxonomic signal in an under-utilised character system: geometric morphometrics of the forcipular coxae of Scutigeromorpha (Chilopoda)

To date, the forcipules have played almost no role in determining the systematics of scutigeromorph centipedes though in his 1974 review of taxonomic characters Markus Würmli suggested some potentially informative variation might be found in these structures. Geometric morphometric analyses were used to evaluate Würmli's suggestion, specifically to determine whether the shape of the forcipular coxa contains information useful for diagnosing species. The geometry of the coxae of eight species from the genera Sphendononema, Scutigera, Dendrothereua, Thereuonema, Thereuopoda, Thereuopodina, Allothereua and Parascutigera was characterised using a combination of landmark- and semi-landmark-based sampling methods to summarize group-specific morphological variation. Canonical variates analysis of shape data characterizing the forcipular coxae indicates that these structures differ significantly between taxa at various systematic levels. Models calculated for the canonical variates space facilitate identification of the main shape differences between genera, including overall length/width, curvature of the external coxal margin, and the extent to which the coxofemoral condyle projects laterally. Jackknifed discriminant function analysis demonstrates that forcipular coxal training-set specimens were assigned to correct species in 61% of cases on average, the most accurate assignments being those of Parascutigera (Parascutigera guttata) and Thereuonema (Thereuonema microstoma). The geographically widespread species Thereuopoda longicornis, Sphendononema guildingii, Scutigera coleoptrata, and Dendrothereua linceci exhibit the least diagnostic coxae in our dataset. Thereuopoda longicornis populations sampled from different parts of East and Southeast Asia were significantly discriminated from each other, suggesting that, in this case, extensive synonymy may be obscuring diagnosable inter-species coxal shape differences.     

Expression of CD26 and its Association with Dipeptidyl Peptidase IV Activity in Lymphocytes of Type 2 Diabetes Patients

Immune response and inflammation were suggested to play certain roles in the development and complications of type 2 diabetes mellitus. The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. These parameters were assessed in 25 T2DM patients and 20 control subjects. We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. Meanwhile, a significant negative correlation was observed between CD26 expression and DPP-IV activity in lymphocytes of T2DM patients. Moreover, a positive correlation was found between DPPIV and ADA activities. The results suggest that the reduction of CD26 expression may be associated in the regulation of DPP-IV in T2DM patients.     

Efficient cellular delivery of β-galactosidase mediated by NrTPs, a new family of cell-penetrating peptides

Nucleolar targeting peptides (NrTPs), a recently developed family of cell-penetrating peptides, have been shown to be very efficient in entering cells and accumulating in their nucleoli. In this work, we have used conjugates of NrTP6 (YKQSHKKGGKKGSG) covalently linked to β-galactosidase in order to demonstrate the capacity of NrTP for intracellular delivery of large molecules. NrTP6/β-galactosidase conjugates, prepared by maleimide-based chemistry, were stable and enzymatically active on the standard 4-methylumbelliferyl β-d-galactopyranoside substrate. Their translocation into HeLa cells, monitored by β-galactosidase activity as a readout of the uptake, showed efficient cellular entry and thus demonstrated the potential of NrTPs for intracellular delivery of large-size cargos with preservation of biological activity.     

Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss

Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities.     

Juvenile animal studies in the development of pediatric medicines: experience from European medicines and pediatric investigation plans

INTRODUCTION: The need for early consideration of pediatric investigation plans (PIP) to support an indication in pediatric population has led to an increased focus on the relevance of nonclinical studies in juvenile animals (JAS). The usefulness of JAS is not yet established and a criterion for request is still a learning process. OBJECTIVE: This article compares data from JAS in all medicines approved by European centralized procedure before Pediatric Regulation (1995–2005) and data from JAS in the nonclinical information on all approved PIP (2007–2009). RESULTS: Of the 226 substances licensed by centralized procedure in 10 years, 31.9% were considered for children and 31 JAS were described in 9.7%. Since 2007, of the 205 PIP decisions, 50 PIP (24.3%) have 87 JAS planned or requested. The mean number of JAS in each medicine or PIP, increased from 1.4 to 1.7 between the two periods and the juvenile rat remained as the prevalent species. CONCLUSIONS: Results demonstrate that JAS planned/performed in EU environment has significantly increased. Birth Defects Res (Part B) 92:353–358, 2011. © 2011 Wiley‐Liss, Inc.     

Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor

A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occurs through activation of REDD1 expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1-TSC2 complex. The antiviral activity of naphthalimides was abolished in REDD1(-/-) cells. Inhibition of REDD1 expression by viruses resulted in activation of the mTORC1 pathway. REDD1(-/-) cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of REDD1 downregulated the amount of viral protein. Thus, REDD1 is a new host defense factor, and chemical activation of REDD1 expression represents a potent antiviral intervention strategy.     

Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the "intrinsic reactivity" of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant ("Tier 2-like") viruses, globally sensitive ("Tier 1") viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4.     

Mean arterial pressure nonlinearity in an elastic circulatory system subjected to different hematocrits

The level of hematocrit (Hct) is known to affect mean arterial pressure (MAP) by influencing blood viscosity. In the healthy population, an increase in Hct (and corresponding increase in viscosity) tends to raise MAP. However, data from a clinical study of type 2 diabetic patients indicate that this relationship is not universal. Instead, individuals in the lower levels of Hct range display a decrease in MAP for a given rise in Hct. After reaching a minimum, this trend is reversed, so that further increases in Hct lead to increases in MAP. We hypothesize that this anomalous behavior occurs due to changes in the circulatory autoregulation mechanism. To substantiate this hypothesis, we develop a physically based mathematical model that incorporates autoregulation mechanisms. Our model replicates the anomalous U-shaped relationship between MAP and Hct found in diabetic patients in the same range of Hct variability.