Temperature-influenced ordering of mesogens in comb-like liquid-crystalline poly(methylsiloxane) macromolecules with side groups consisting of “phenyl benzoate” moieties in solution

Comb-like poly(methylsiloxane) macromolecules P4, P6, and P11, with side groups consisting of “phenyl benzoate” moieties and different alkyl spacers (from 4 to 11 C-atoms) between the backbone and the mesogenic side groups have been synthesized and investigated as well as low-molar-mass compounds M4, M6, and M11, as model molecules analogous to side chains of the macromolecule. The liquid-crystalline phase transition temperatures have been determined. Mobility of the mesogens and the macromolecule as a whole in dilute solution was studied in external fields (electric and mechanical shear field). In dilute solution under the influence of a sinusoidal electric field, the polymer behaviour is typical of flexible-chain polymer molecules where each mesogenic unit is oriented independently of the other ones. This is in contrast to the effect observed in a mechanical shear flow field. The Maxwell constant in positive for the solutions of compounds M4, M6, M11 and negative in polymers P4, P6, P11. This indicates the orientation of the macromolecule as a whole in the shear flow field, the mesogenic group main axis being oriented in the direction preferably normal to the macromolecular axis of primary polarizability. Temperature effects are also discussed.     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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Influence of neonatal short-term reduction in brainstem alpha2A-adrenergic receptors on receptor ontogenesis, acoustic startle reflex, and prepulse inhibition in rats

Neonatal treatments can disrupt prepulse inhibition (PPI) of startle response later in life. Alpha2A-adrenergic receptors (alpha2A-ARs) regulate the release of brain neurotransmitters that may influence PPI. The authors examined the effects of short-term reduction in the neonatal brainstem alpha2A-ARs on subsequent development of this receptor system and acoustic startle reflex in rats. Administration of antisense oligodeoxynucleotide complementary to the alpha2A-ARs on Days 2-4 of life reduced receptor expression in the brainstem by Day 5. The treatment increased alpha2-AR numbers in the cortex, hippocampus, and amygdala at 40 days of age, and in cortex and hypothalamus at 90 days of age. Transient increases in hippocampal and amygdalar alpha2-ARs were accompanied by attenuation of acoustic startle response and impairment of PPI.     

Self‐Assembly of Dendritic Macromolecules Based on the Ionic Interaction of Linear Chain Polyelectrolyte Cores with Oppositely Charged Focal Ionogenic Groups of Dendrons

Summary: A new principle for the design of dendritic macromolecules – the ionic binding of linear chain polyelectrolyte with oppositely charged focal ionogenic groups of dendrons – has been developed. The majority of the dendritic ionic complexes (DICs) are prepared with poly(styrenesulfonic acid) (PSS) as a polymeric core and L ‐aspartic acid dendrons of different generations. Two series of DICs were prepared using PSS and aspartic dendrons bearing terminal (located at the external periphery) methoxycarbonyl and hexyloxycarbonyl groups (C1‐n and C6‐n respectively where n is the generation number). Ionic binding of about 100% was found for dendrons of Generation 1–3. The solubility of the DICs was examined and the DICs prepared were studied by IR spectroscopy, ¹H NMR and viscometry.

Dendritic ionic complexes prepared using poly(styrenesulfonic acid) acid and aspartic dendrons bearing terminal methoxycarbonyl and hexyloxycarbonyl groups.     

Safety and immunogenicity of a prototype enterotoxigenic Escherichia coli vaccine administered transcutaneously

Transcutaneous immunization (TCI) is a new method for vaccine delivery that has been shown to induce immunity relevant to enteric disease vaccines. We evaluated the clinical safety and immunogenicity of a recombinant subunit vaccine against enterotoxigenic Escherichia coli (ETEC) delivered by TCI. Adult volunteers received patches containing the recombinant ETEC colonization factor CS6, either with heat-labile enterotoxin (LT) or patches containing CS6 alone. The vaccine was administered at 0, 1, and 3 months, and serum antibodies and antibody-secreting cells (ASCs) were assessed. Among the 26 volunteers that completed the trial, there were no responses to CS6 in the absence of LT. In the groups receiving both CS6 and LT, 68 and 53% were found to have serum anti-CS6 immunoglobulin G (IgG) and IgA, respectively; 37 and 42% had IgG and IgA anti-CS6 ASCs. All of the volunteers receiving LT had anti-LT IgG, and 90% had serum anti-LT IgA; 79 and 37% had anti-LT IgG and IgA ASCs. Delayed-type hypersensitivity (DTH), suggesting T-cell responses, was seen in 14 of 19 volunteers receiving LT and CS6; no DTH was seen in subjects receiving CS6 alone. This study demonstrated that protein antigens delivered by a simple patch could induce significant systemic immune responses but only in the presence of an adjuvant such as LT. The data suggest that an ETEC vaccine for travelers delivered by a patch may be a viable approach worthy of further evaluation.     

Suppression of serum antibody responses by pertussis toxin after respiratory tract colonization by Bordetella pertussis and identification of an immunodominant lipoprotein

Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (DeltaPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or DeltaPT strain and found that infection with the DeltaPT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the DeltaPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the DeltaPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the DeltaPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.     

Association study of seven polymorphisms in four serotonin receptor genes on suicide victims.

A number of molecular genetic studies have investigated if serotonin (5-HT) receptor subtypes are involved in the pathogenesis of depression, suicidal behavior, aggression, and impulsive behavior. Existence of many receptor subtypes for a single transmitter permits a great diversity of signaling raising the possibility that they may serve as genetic markers for suicidal behavior. Most previous studies of suicide have analyzed polymorphisms of the receptors 5-HT1A, 5-HT1B, 5-HT2A, fewer have examined 5-HT1F. We report a study of possible association between the polymorphisms in the 5-HT receptor genes (1A, 1B, 1F, and 2A) and suicidal behavior on a sample of 226 suicide victims and 225 healthy control subjects. No significant differences in genotype frequency distributions between the suicide victims and healthy control subjects were observed for four polymorphisms; three were not polymorphic. A single polymorphism, C-1420T in gene 5-HT2A, showed a slight association with suicide (chi2= 4.94, df = 2, P = 0.067), but the correlation was not statistically significant. None of the tested genetic variants of serotonin receptors appears to be associated with suicidal behavior in the Slovenian population which has a relatively high suicide rate.     

Comet-FISH using peptide nucleic acid probes detects telomeric repeats in DNA damaged by bleomycin and mitomycin C proportional to general DNA damage

For the optimal use of anticancer drugs a knowledge of the whole spectrum of side-effects is required. A potential hazard, so far only scarcely investigated, is uncontrolled effects of drugs such as bleomycin (BLM) and mitomycin C (MMC) on telomere shortening in non-cancerous tissues of the treated person. For the first time, directly labelled telomere-specific peptide nucleic acid (PNA) hybridization probes were applied in comet-FISH to detect DNA fragmentation on an intermediate scale. The effects of BLM and MMC were measured in peripheral blood cells of three human volunteers, following ex vivo incubation. Fragmentation of telomeres and subtelomeric regions was highly specifically detected by the comet-FISH assay, a combination of the comet assay and fluorescence in situ hybridization. As a technical detail, the effects of the hybridization procedure have been studied on the level of single comets. Image analysis before and after the hybridization process reveals a small decrease in the detected fragmented DNA, probably due to diffusion of small fragments. It could not only be shown that both drugs actually induce breaks in telomere-associated DNA, but also that the comet-FISH technique, as a quantitative approach, is a useful tool for the detection and evaluation of the role of sequence-specific DNA damage after mutagenic action. The breakage frequency for DNA of or adjacent to telomeric repeats was found to be proportional to that of the total DNA, which hints at random induction of DNA breaks by BLM and MMC. In terms of therapy, the results indicate that no over- or under-proportional effects on telomeres of BLM or MMC need be expected.