Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Neutral Polymeric Surfactants Derived from Dextran: A Study of Their Aqueous Solution Behavior

Summary: Amphiphilic polysaccharides are obtained by hydrophobic modification of a neutral bacterial polysaccharide, dextran. By reacting the polysaccharide with aliphatic epoxides (epoxyoctane and epoxydodecane) in dimethyl sulfoxide, a series of amphiphilic polymers is obtained which covers a large range of structural parameters (length of the polysaccharide, number and nature of hydrocarbon moieties). The solution behavior of dextran derivatives is first characterized by viscometric measurements in dilute and semi‐dilute domains. The effects of molecular parameters on polymer viscosity behavior are evidenced and discussed. Information on the state of aggregation of polymers is obtained by the use of static and dynamic light scattering. The presence of aggregates in the dilute domain is clearly evidenced and their structural characteristics are estimated (size, molecular weight and number of aggregation). The aggregates are shown to account for the viscometric results in the examined concentration range, relating their chemical parameters (hydrodynamic radius and molecular weight) to the macroscopic behavior of the solutions.

     

Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency

Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele.     

Hydrophobically Modified Poly(acrylic acid) Using 3‐Pentadecylcyclohexylamine: Synthesis and Rheology

Summary: Hydrophobically modified poly(acrylic acid) was synthesized using 3‐pentadecylcyclohexylamine (3‐PDCA), which was in turn synthesized from 3‐pentadecylphenol, one of the components of cashew‐nut shell liquid (CNSL), a renewable resource material. ¹H NMR spectra confirmed the incorporation of 3‐PDCA onto PAA and a series of HMPs with three different molar concentrations, viz ? 3, 5 and 7 mol‐% of 3‐PDCA, were synthesized. An increase in viscosity with increasing hydrophobic content was observed by rheological measurements. The critical association concentrations were determined using an Ubbelohde viscometer and a controlled stress rheometer. The stability of HMPs towards temperature and shear was studied. Rheological measurements showed that there was a steady increase in viscosity with increase in hydrophobe content due to the formation of reversible networks. These polymers exhibited gel‐like behavior at low concentrations (≥2 wt.‐%) with an apparent yield stress (ca. 10 Pa) and showed shear thinning properties (non‐Newtonian). However, below a critical concentration, c [η], they showed Newtonian behavior.

η_sp of unmodified and modified PAA‐Na at various polymer concentrations.     

Immune recognition of a molecule naturally presented as a monomeric or an oligomeric structure: the model of the human chorionic gonadotropin alpha subunit.

The immune recognition of a molecule naturally presented as a monomeric or an oligomeric structure is analyzed using the human chorionic gonadotropin alpha subunit (hCG-alpha) as a model. Indeed, hCG-alpha circulates as either a free subunit or combined to the beta subunit (hCG-beta) to form the dimeric hCG hormone. A T cell study was performed in BALB/c (H-2d) mice which were found to be high responders to hCG-alpha. Mice were immunized with the free hCG-alpha or the dimeric hCG alpha/beta, and their lymph node cells were challenged in vitro with either alpha subunits from different species, hCG or peptides spanning the entire primary structure of hCG-alpha. Proliferation and IL-2 assays demonstrated that hCG-alpha-primed lymph node cells responded equally well to hCG-alpha and hCG alpha/beta, suggesting that both the free and combined hCG-alpha subunits are processed in a similar way. Among the various synthetic peptides used, only those mimicking the hCG-alpha(59-92) C-terminus portion were able to stimulate hCG-alpha-primed lymph node cells, demonstrating that this region contains immunodominant T cell recognition site(s). The hCG-alpha(23-43) and (32-59) peptides, although incapable of stimulating T cells primed with hCG-alpha, elicited a T cell response when used as immunogens. These regions encompassed cryptic epitopes which were not generated during hCG-alpha processing in H-2d mice. The T cell epitopes of hCG-alpha above described as immunodominant or cryptic on the free alpha subunit, had similar characteristics when the alpha/beta dimer was used as the immunogen. In contrast, T cells primed with peptides mimicking immunodominant sites recognized differently the hCG-alpha and the hCG alpha/beta antigens. Moreover, the analysis of the B cell response to all the immunogenic hCG-alpha peptides indicated that they bear B and T cell epitopes as well. Antibodies elicited against the hCG-alpha(59-92) or (32-59) peptide were capable of recognizing the alpha subunit in its free form but not in the alpha/beta hCG dimer. Such study deserves attention for the comprehensive mechanisms of the immune response to hCG as well as for the design of anti-hCG vaccines.     

Relapsing diabetes can result from moderately activating mutations in KCNJ11

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro.     

Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice

An early step in the development of autoimmune diabetes is lymphocyte infiltration into the islets of Langerhans of the pancreas, or insulitis. The infiltrate contains both CD4⁺ and CD8⁺ T cells and both are required for progression to diabetes in non-obese diabetic (NOD) mice. It has been thought that the CD4⁺ lymphocytes are the initiators of the disease, the islet invaders, while CD8⁺ cells are the effectors, the islet destroyers. We question this interpretation because NOD mice lacking MHC class I molecules, hence CD8⁺ T cells, do not display even insulitis when expected.     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.