Prevalence and clinical significance of anti-C1q antibodies in cutaneous and systemic lupus erythematosus

Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Anti-C1q antibodies are strongly associated with lupus nephritis. The aim of this study was to determine the prevalence of anti-C1q antibodies in Egyptian lupus patients as well as to evaluate the associations between anti C1q antibodies and clinical and serologic parameters of patients with cutaneous and systemic lupus erythematosus. Fifty-eight patients of lupus erythematosus were recruited in the study, and they were divided into 3 groups according to their clinical presentations and laboratory investigations; group (1) consists of 20 patients with musculoskeletal manifestations, mainly arthritis (34.5%), group (2) consists of 12 patients with lupus nephritis (20%), and group (3) consists of 26 patients with cutaneous lupus (44.8%). Fourteen age and sex matched healthy subjects served as controls. Complete blood picture, kidney function tests, liver function tests and anti-double stranded DNA were done for all the studied patients. Anti-C1q antibodies were determined by immunometric enzyme immunoassay for all the studied subjects. Anti-C1q antibodies were positive in (63.8%) of lupus erythematosus (LE) patients and (0%) of controls. Moreover, the serum anti-C1q antibodies titers were significantly higher (P < 0.001) in all lupus erythematosus patients (both systemic and cutaneous) when compared to healthy controls. Surprisingly, serum anti-C1q antibodies were significantly higher in patients with cutaneous lupus than those with lupus nephritis (P <0.001). Anti-C1q titers were significantly correlated with levels of anti–double stranded DNA (P <0.001), as well as with proteinuria (<0.05) in lupus nephritis patients. It was concluded that anti C1q antibodies might play a pathogenic role in the pathogenesis of cutaneous lupus and could positively be associated with evolution to SLE. Moreover, it could predict patients who subsequently develop nephritis, thus early use of immune modulators in cutaneous lupus could improve patients’ prognosis by decreasing the possibility of evolution to systemic lupus complications, mainly nephritis.Keywords: Anti-C1q; Systemic lupus erythematosus; Cutaneous lupus erythematosus; Lupus nephritis; Complement; Proteinuri

Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved insulin sensitivity, hyperinsulinemic-euglycemic clamp studies did not detect enhanced insulin action in response to 7ACC2 treatment. Rather, our data suggest acute glucose-lowering effects of MPC inhibition may be due to suppressed hepatic gluconeogenesis. Finally, we used reporter sensitive to pyruvate to screen a chemical library of drugs and identified 35 potentially novel MPC modulators. Using available evidence, we generated a pharmacophore model to prioritize which hits to pursue. Our analysis revealed carsalam and six quinolone antibiotics, as well as 7ACC1, share a common pharmacophore with 7ACC2. We validated that these compounds are novel inhibitors of the MPC and suppress hepatocyte glucose production and demonstrated that one quinolone (nalidixic acid) improved glucose tolerance in obese mice. In conclusion, these data demonstrate the feasibility of therapeutic targeting of the MPC for treating diabetes and provide scaffolds that can be used to develop potent and novel classes of MPC inhibitors

Influence of aerial seed banks on germination response in three desert plant species

© The Author 2016. Aims To determine if the germination response of desert plant species to a period of aerial storage in field conditions (i.e. mature seeds that remain attached to the parent plant) is comparable to seeds harvested at maturity and stored in ambient laboratory conditions, to better understand the role of aerial seed bank in the germination ecology of desert plants, using one annual and two perennial species. Methods Seeds of three desert plants (Anastatica hierochuntica, Blepharis ciliaris and Scrophularia deserti) that matured in June 2014, were collected from wild plants in June and November 2014, and germinated under two photoperiods (0, 12 hours light) and three thermoperiods (night/day temperatures of 15/25, 20/30 and 25/35°C). Important Findings Seeds of B. ciliaris and S. deserti had significantly higher germination percentages when harvested and stored for five months, compared to being stored in the aerial seed bank. Germination percentages of these two species increased with decreasing temperature and in the presence of light. These results indicate that these species use a combination of aerial and soil seed banks to maintain a percentage of viable seeds through favourable germination periods. Germination percentages of A. hierochuntica were high under all tested circumstances, indicating that this species relies mainly on the aerial seed bank to maintain a percentage of viable seeds through favourable germination periods. This study shows that the population survival strategies of an aerial seed bank are species-specific. These results have practical implications for conservation and habitat restoration for these species, and also for their propagation since early collection of mature fruits and ex situ storage will result in greater germination percentages of some species

Postsynthesis modification of a cellulose acetate ultrafiltration membrane for applications in water and wastewater treatment

A technique for postsynthesis modification of a cellulose acetate ultrafiltration membrane with possible application in water and wastewater treatment is studied. The technique used an oxidizing agent (persulfate) to develop free radicals on the membrane surface, and that was expected to promote grafting of hydrophilic macromolecules (polyethylene glycol). A chain-transfer agent (2-mercaptoethanol) was tested to control the grafting process, avoiding the formation of long chains that usually lead to high permeability losses in other graft techniques. The modifications aimed at the decrease of the fouling susceptibility of the membrane studied. The possibility of an increase in rejection was also investigated. The membrane was characterized before and after modification, by attenuated total reflectance-Fourier transform-infrared spectroscopy, scanning electron microscopy, atomic force microscopy, and in terms of the rejection of neutral reference solutes. The information given by the different techniques of characterization provided strong evidences of the occurrence of modification, although permeation of (real) foulants was the decisive test. To obtain information about the fouling tendency of the nonmodified and modified membranes, two different kinds of foulants were used: a humic acid (usually found in surface waters) and textile auxiliaries (representing one of the most important industries in Portugal). The results showed an increase in the rejections of the humic acid, and significant improvements in the performance of the membrane with respect to fouling tendency in the case of the textile auxiliarie

Soft Coral Sarcophyton (Cnidaria: Anthozoa: Octocorallia) Species Diversity and Chemotypes

Research on the soft coral genus Sarcophyton extends over a wide range of fields, including marine natural products and the isolation of a number of cembranoid diterpenes. However, it is still unknown how soft corals produce this diverse array of metabolites, and the relationship between soft coral diversity and cembranoid diterpene production is not clear. In order to understand this relationship, we examined Sarcophyton specimens from Okinawa, Japan, by utilizing three methods: morphological examination of sclerites, chemotype identification, and phylogenetic examination of both Sarcophyton (utilizing mitochondrial protein-coding genes MutS homolog: msh1) and their endosymbiotic Symbiodinium spp. (utilizing nuclear internal transcribed spacer of ribosomal DNA: ITS- rDNA). Chemotypes, molecular phylogenetic clades, and sclerites of Sarcophyton trocheliophorum specimens formed a clear and distinct group, but the relationships between chemotypes, molecular phylogenetic clade types and sclerites of the most common species, Sarcophyton glaucum, was not clear. S. glaucum was divided into four clades. A characteristic chemotype was observed within one phylogenetic clade of S. glaucum. Identities of symbiotic algae Symbiodinium spp. had no apparent relation to chemotypes of Sarcophyton spp. This study demonstrates that the complex results observed for S. glaucum are due to the incomplete and complex taxonomy of this species group. Our novel method of identification should help contribute to classification and taxonomic reassessment of this diverse soft coral genus

Immunophenotyping of Circulating T Helper Cells Argues for Multiple Functions and Plasticity of T Cells In Vivo in Humans - Possible Role in Asthma

BACKGROUND: The immune process driving eosinophilic and non-eosinophilic asthma is likely driven by different subsets of T helper (Th) cells. Recently, in vitro studies and animal studies suggest that Th cell subsets displays plasticity by changing their transcription factor or by expressing multiple transcription factors. Our aim was to determine whether individuals with asthma and elevated circulating eosinophils express signs of different regulatory immune mechanisms compared with asthmatics with low blood eosinophils and non-asthmatic control subjects. In addition, determine the relationship between eosinophilia and circulating Th cell subsets. METHODOLOGY/PRINCIPAL FINDINGS: Participants were selected from a random epidemiological cohort, the West Sweden Asthma Study. Immunophenotypes of fresh peripheral blood cells obtained from stable asthmatics, with and without elevated eosinophilic inflammation (EOS high and EOS low respectively) and control subjects, were determined by flow cytometry. No differences in the number of Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt) or Treg (FOXP3) cells were observed between the groups when analysing each subset separately. However, in all groups, each of the Th subsets showed expression of additional canonical transcription factors T-bet, GATA-3, RORγt and FOXP3. Furthermore, by in vitro stimulation with anti-CD3/anti-CD28 there was a significant increase of single expressing GATA-3(+) and co-expressing T-bet(+)GATA-3(+) cells in the EOS high asthmatics in comparison with control subjects. In addition, T-bet(-)GATA-3(+)RORγt(+)FOXP3(+) were decreased in comparison to the EOS low asthmatics. Finally, in a group of control subjects we found that the majority of proliferating Th cells (CD4(+)CD25(+)Ki67(+)) expressed three or four transcription factors. CONCLUSIONS: The ability of human Th cells to express several regulatory transcription factors suggests that these cells may display plasticity in vivo

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice

BACKGROUND: Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. METHODS: Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 μg and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. RESULTS: Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B(1), B(2), G(1) and G(2)) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon β-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. CONCLUSION: Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora

Mapping Differentiation under Mixed Culture Conditions Reveals a Tunable Continuum of T Cell Fates

Cell differentiation is typically directed by external signals that drive opposing regulatory pathways. Studying differentiation under polarizing conditions, with only one input signal provided, is limited in its ability to resolve the logic of interactions between opposing pathways. Dissection of this logic can be facilitated by mapping the system's response to mixtures of input signals, which are expected to occur in vivo, where cells are simultaneously exposed to various signals with potentially opposing effects. Here, we systematically map the response of naïve T cells to mixtures of signals driving differentiation into the Th1 and Th2 lineages. We characterize cell state at the single cell level by measuring levels of the two lineage-specific transcription factors (T-bet and GATA3) and two lineage characteristic cytokines (IFN-γ and IL-4) that are driven by these transcription regulators. We find a continuum of mixed phenotypes in which individual cells co-express the two lineage-specific master regulators at levels that gradually depend on levels of the two input signals. Using mathematical modeling we show that such tunable mixed phenotype arises if autoregulatory positive feedback loops in the gene network regulating this process are gradual and dominant over cross-pathway inhibition. We also find that expression of the lineage-specific cytokines follows two independent stochastic processes that are biased by expression levels of the master regulators. Thus, cytokine expression is highly heterogeneous under mixed conditions, with subpopulations of cells expressing only IFN-γ, only IL-4, both cytokines, or neither. The fraction of cells in each of these subpopulations changes gradually with input conditions, reproducing the continuous internal state at the cell population level. These results suggest a differentiation scheme in which cells reflect uncertainty through a continuously tuneable mixed phenotype combined with a biased stochastic decision rather than a binary phenotype with a deterministic decision