Peptides with Dual Antimicrobial-Anticancer Activity Derived from the N-terminal Region of H. pylori Ribosomal Protein L1 (RpL1)

International Journal of Peptide Research and Therapeutics - Whereas the traditional approaches of cancer therapy including radiotherapy, chemotherapy, and immunotherapy have failed to properly...     

Tolerance of low pH in Schizosaccharomyces pombe requires a functioning pub1 ubiquitin ligase

A strain of Schizosaccharomyces pombe carrying a disrupted Na⁺/H⁺ antiporter gene (sod2::sup3-5), in addition to the common auxotrophic mutations, ade6-216, ura4-D18 and leu1-32, is highly sensitive to media adjusted to pH 6.9. Reversion analysis of this strain yielded a group of revertants capable of growth at pH 6.9. Two of the revertants elongated and failed to form colonies at pH 3.5. Genetic characterization of one of the pH-sensitive elongated strains, J227, showed the presence of two independently segregating mutations. One, pub1 ( protein ubiquitin ligase 1), has recently been reported as an E3 protein ubiquitin ligase involved in cdc25 turnover. The second has been named elp3-1 (elongated at low pH). Genetic dissection of the original strain revealed that poor growth at high pH was due to the presence of the auxotrophic markers, suggesting a possible inhibitory effect of high pH on the function of permeases responsible for uptake of the necessary nutrients. Suppression of the high pH sensitivity required the presence of both the pub1-1 and elp3-1 mutations. While the pub1-1 mutation reduced the capacity of cells to tolerate relatively moderate concentrations of LiCl (3 mM) in liquid culture, it was capable of partially suppressing the extreme Li⁺ sensitivity caused by the sod2 disruption. Under these conditions, the growth of pub1-1 sod2::ura4 double mutant cells was improved over that of either pub1-1 or sod2::ura4 cells. The elp3-1 mutation had no effect on the Li⁺ tolerance in either wild-type or sod2::ura4 backgrounds. pub1-1 cells are elongated and incapable of colony formation at pH 3.5. In contrast, elp3-1 cells are elongated at pH 3.5 and pH␣5.5 (the normal pH of minimal medium) but can form colonies under both conditions. J227 cells are significantly longer than either single mutant at pH 3.5 and do not form colonies but are visually similar to elp3-1 cells at pH 5.5. Complementation cloning in the J227 background yielded a genomic clone of pub1, allowing us to define the intron-exon structure of the gene. Sequences with high homology to the predicted amino acid sequence of pub1 have been identified in Saccharomyces cerevisiae (RSP5/NPI1), human (hRPF1), mouse (mNedd4), and rat (rNedd4). Based on the nature of our mutant selection, the pH-sensitive phenotype of the strains selected, and the known involvement of RSP5/NPI1 in membrane permease turnover in S. cerevisiae, we hypothesize a role for pub1, either directly or indirectly, in regulating membrane transport processes. This is further supported by the broad range of effects that the pub1-1 mutation exerts on overall performance of cells at high and low external pH, and in the presence of toxic levels of Li⁺. Received: 12 September 1996 / Accepted: 19 December 1996     

Association of T/A polymorphism in miR-1302 binding site in CGA gene with male infertility in Isfahan population

Infertility occurs in 10–15% of couples worldwide and close to half of it is caused by male factors. One of the genes that can affect male infertility is CGA. Polymorphisms in CGA gene may affect gene expression, therefore affecting male infertility by disrupting the regulation of this gene. One of the polymorphisms is the substitution of T with A in the miR-1302 binding site in the 3′ untranslated region of the CGA gene. In this study, we explored this polymorphism in Isfahan population. In this case-control study, by the use of Tetra primer-ARMS–PCR technique, rs6631 has been investigated in 224 infertile men and 196 controls. Infertile men were recruited from Isfahan Fertility and Infertility Center. Analysis of genotype and allele frequencies indicated that the differences between case and control populations were significant for rs6631 because P?=?0.00 which is above the threshold. We found a significant relationship between this polymorphism and male infertility. This study which performed for the first time in Iran suggests that polymorphism in CGA gene can affect male infertility. Also, this polymorphism has high heterozygosity, so it can be used for further studies in different populations.     

TB trifusion antigen adsorbed on calcium phosphate nanoparticles stimulates strong cellular immunity in mice

Among various vaccine candidates, subunit vaccines play an important role in immune protection against tuberculosis (TB). Calcium phosphate (CP) is considered as a strong inorganic adjuvant due to its great potential in increasing immune responses. The purpose of this study was to evaluate specific immune responses following the administration of trifusion-CP nanoparticles. The physiochemical properties of these nanoparticles, including morphology, particle size, zeta potential and adsorption rate, were measured in vitro. Subcutaneous immunization was performed three times on days 0, 14, and 28. Two weeks after the last administration, IFN-gamma, IL-4, and TGF-beta levels were measured by indirect enzyme linked immunosorbent assay (ELISA). The trifusion protein was successfully adsorbed onto calcium phosphate nanoparticles. The mean sizes of the resultant trifusion- CPN and CPN were 97.84 ± 12.08 and 67 ± 11.85 nm, respectively. CPN containing trifusion had stronger ability to induce IFN-gamma than the control groups. IL-4 and TGF-beta secretions in trifusion and trifusion-CPN groups were higher than those in the PBS group. However, there was no significant (p > 0.05) difference in IL-4 and TGFbeta concentrations between trifusion group and trifusion- CPN group. Therefore, calcium phosphate nanoparticles are good candidates for immunization against TB because antigen can be easily adsorbed onto CPN and strong cellular immune responses against CPN-antigen can be stimulated.     

Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling

Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand, clones distant from hair follicles were slow cycling, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non‐hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far‐reaching implications for epidermal homeostasis, wound repair and cancer development.