Oligomers that contain both alpha - and beta -amino acid residues, or " alpha / beta -peptides", have emerged as promising mimics of signal-bearing polypeptides that can inhibit or augment natural ...protein-protein interactions. alpha / beta -Peptides that contain a sufficient proportion of beta residues evenly distributed along the sequence can be highly resistant to enzymatic degradation, which is favorable with regard to in vivo applications. Little is known, however, about recognition of alpha / beta -peptides by the immune system. Prior studies have focused almost entirely on examples that contain a single beta residue; such alpha / beta -peptides frequently retain the immunological profile of the analogous alpha -peptide. We have conducted alpha -peptide vs alpha / beta -peptide comparisons involving higher beta residue content, focusing on molecules with alpha alpha alpha beta and alpha alpha beta alpha alpha alpha beta backbone repeat patterns. Among analogues of an 18-mer derived from the Bim BH3 domain and an 8-mer derived from secreted phospholipase-2 (sPLA2), we find that recognition by antibodies raised against the prototype alpha -peptide is suppressed by periodic alpha arrow right beta replacements. Complementary studies reveal that antibodies raised against Bim BH3- or sPLA2-derived alpha / beta -peptides fail to recognize prototype alpha -peptides displaying identical side chain repertoires. Because polypeptides containing d- alpha -amino acid residues are of growing interest for biomedical applications, we included the enantiomer of the sPLA2-derived alpha -peptide in these studies; this d-peptide is fully competent as a hapten, but the resulting antibodies do not cross react with the enantiomeric peptide. Among analogues of the 9-mer CD8+ T-cell viral epitope GP33, we observe that periodic alpha arrow right beta replacements suppress participation in the MHC I + peptide + T-cell receptor ternary complexes that activate cytotoxic T-lymphocytes, due in part to disruption of MHC binding.
Glucose-inhibited division (GidA) protein is widely distributed in nature, and is highly conserved among bacteria and eukarya. In our previous study, a gidA mutant was attenuated in both in vitro and ...in vivo models of Salmonella infection. Furthermore, deletion of gidA resulted in a marked reduction in the expression of many virulence genes and proteins, suggesting a role for GidA in the regulation of Salmonella virulence. In this study, the effect of different environmental conditions (glucose, EDTA, and pH 5) on GidA expression in Salmonella was examined. Transcriptional analysis using real-time RT-PCR and a β-galactosidase assay, displayed no differences in gidA transcription and promoter activity in different environmental conditions. Conversely, semiquantitative Western blot analysis revealed a significant increase in the GidA expression in Salmonella when grown under different environmental conditions. Salmonella in vitro virulence assays showed an increased virulence potential in the environmental conditions correlating to the increase in GidA expression. Together, our data indicate that GidA expression is modulated under different environmental conditions which correlate to increased Salmonella in vitro virulence.
Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKCε) ...transgenic mice on FVB/N background, which overexpress PKCε protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKCε and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKCε FVB/N transgenic mice with SKH-1 hairless mice to generate PKCε-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCε SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1–2KJm−2) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKCε overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKCε level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis.
The laser flash photolysis resonance fluorescence technique was used to monitor atomic Cl kinetics. Loss of Cl following photolysis of CCl4 and NaCl was used to determine k(Cl + C6H6) = 6.4 × 10-12 ...exp(−18.1 kJ mol-1/RT) cm3 molecule-1 s-1 over 578−922 K and k(Cl + C6D6) = 6.2 × 10-12 exp(−22.8 kJ mol-1/RT) cm3 molecule-1 s-1 over 635−922 K. Inclusion of literature data at room temperature leads to a recommendation of k(Cl + C6H6) = 6.1 × 10-11 exp(−31.6 kJ mol-1/RT) cm3 molecule-1 s-1 for 296−922 K. Monitoring growth of Cl during the reaction of phenyl with HCl led to k(C6H5 + HCl) = 1.14 × 10-12 exp(+5.2 kJ mol-1/RT) cm3 molecule-1 s-1 over 294−748 K, k(C6H5 + DCl) = 7.7 × 10-13 exp(+4.9 kJ mol-1/RT) cm3 molecule-1 s-1 over 292−546 K, an approximate k(C6H5 + C6H5I) = 2 × 10-11 cm3 molecule-1 s-1 over 300−750 K, and an upper limit k(Cl + C6H5I) ≤ 5.3 × 10-12 exp(+2.8 kJ mol-1/RT) cm3 molecule-1 s-1 over 300−750 K. Confidence limits are discussed in the text. Third-law analysis of the equilibrium constant yields the bond dissociation enthalpy D 298(C6H5−H) = 472.1 ± 2.5 kJ mol-1 and thus the enthalpy of formation Δf H 298(C6H5) = 337.0 ± 2.5 kJ mol-1.
The constant social upheaval of capitalism has provoked repeated waves of nostalgic response since at least the early nineteenth century. In a now-common description of postmodern consumer culture, ...nostalgia itself became big business in the late twentieth century, and the past became no more than a plaything of the culture industries. But we may also see in the huge efflorescence of nostalgia—or rather nostalgias plural—in mass society since the 1970s one aspect of a new configuration of social forces, a new arena of struggle even, matched to the structures of capitalism that have emerged. Environmentalist movements, consumer movements,
One year has passed since the earthquake and tsunami in Tōhoku. How should we as scholars approach, think about, and teach about the disaster? In generations hence, will 2011 be treated as a ...historical turning point on a par with 1945? Will it appear more significant than the Great Kantō Earthquake of 1923, despite the far greater loss of life in that event? We have a long process of analysis and contextualization ahead before the traumatic events of March 2011 have sedimented into history. Meanwhile, the nuclear disaster continues. When the Japanese government announced in December that complete decommissioning of the Fukushima Daiichi reactors would take forty years, it became clear that even in the most optimistic scenario the world would be living with this disaster for a long time to come.
In the large body of research on the relationship between cities and their hinterlands, the role of bodies of water as productive resources has often been overlooked. Tokyo presents the case of a ...city whose bay has played an indispensable role in the growth of the city, in perceptions
of the cityscape and, most importantly, in provisioning the urban population. This essay examines the management of bay fisheries from the seventeenth through the nineteenth centuries to show how the character of the political regime governing the city shaped the way that fishing communities
and the urban consumer population exploited and enjoyed the urban aquascape.
To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we ...compared PKCε transgenic (TG) mice and their wild-type (WT) littermates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSCs) and (2) HSCs proliferation. The percent of double HSCs (CD34+ and α6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m2) resulted in an increase in the frequency of double positive HSCs in PKCε TG mice as compared to their WT littermates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2′-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSCs retaining BrdU label was 28.4±0.6% compared to 4.0±0.06% for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKCε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells.
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