Novel Structurally Designed Vaccine for S. aureus α-Hemolysin: Protection against Bacteremia and Pneumonia

Staphylococcus aureus (S. aureus) is a human pathogen associated with skin and soft tissue infections (SSTI) and life threatening sepsis and pneumonia. Efforts to develop effective vaccines against S. aureus have been largely unsuccessful, in part due to the variety of virulence factors produced by this organism. S. aureus alpha-hemolysin (Hla) is a pore-forming toxin expressed by most S. aureus strains and reported to play a key role in the pathogenesis of SSTI and pneumonia. Here we report a novel recombinant subunit vaccine candidate for Hla, rationally designed based on the heptameric crystal structure. This vaccine candidate, denoted AT-62aa, was tested in pneumonia and bacteremia infection models using S. aureus strain Newman and the pandemic strain USA300 (LAC). Significant protection from lethal bacteremia/sepsis and pneumonia was observed upon vaccination with AT-62aa along with a Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) that is currently in clinical trials. Passive transfer of rabbit immunoglobulin against AT-62aa (AT62-IgG) protected mice against intraperitoneal and intranasal challenge with USA300 and produced significant reduction in bacterial burden in blood, spleen, kidney, and lungs. Our Hla-based vaccine is the first to be reported to reduce bacterial dissemination and to provide protection in a sepsis model of S. aureus infection. AT62-IgG and sera from vaccinated mice effectively neutralized the toxin in vitro and AT62-IgG inhibited the formation of Hla heptamers, suggesting antibody-mediated neutralization as the primary mechanism of action. This remarkable efficacy makes this Hla-based vaccine a prime candidate for inclusion in future multivalent S. aureus vaccine. Furthermore, identification of protective epitopes within AT-62aa could lead to novel immunotherapy for S. aureus infection

A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis

BACKGROUND: Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs). CONCLUSIONS/SIGNIFICANCE: Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice

PERBEDAAN PENGGUNAAN MEDIA VIDEO DENGAN LEAFLET TERHADAP TINGKAT PENGETAHUAN SISWA MENGENAI CUCI TANGAN PAKAI SABUN (Studi Kasus di SDN Banyuanyar 1 Sampang Tahun 2018)

Disposable hand-washing soap (CTPS) is used to reduce the microorganisms with the techniques of flow of clean water into the palm of the hand using soap. CTPS serves to eliminate/reduce microorganism that attaches on both hands to prevent diarrheal diseases, cholera, intestinal worms, and hepatitis a. Data obtained from clinics in 2016 of 1095 and in 2017 of 1374 it these show that there is a growing number of diarrhea sufferers. The results of a survey conducted to 10 students who were given a questionnaire there are 4 students who learned of the CTPS. The purpose of this research is to know the difference between video media with leaflets about the level of knowledge of students for the CTPS SD class IV and class V.The type of this research is research pre experimental research design with one group pretest posttest design. The sample in this research as much as 72 students, while for sampling techniques is Proportional Stratified Random Sampling. Data collection procedure that is done to find out the level of knowledge of students using a questionnaire. Furthermore the data that has been collected is analyzed with statistical tests is Exact Fisher.The results of the measurement of the level of knowledge of students before intervention in either category of 27.78% (10 students). Whereas after intervention by using video media of 58.33% (21 students). And media use leaflet before intervention by 25% and after the intervention of 83.33% in both categories. Fisher's exact test results obtained results of 0.034 &lt; 0.05. So there is a difference in the use of video media with leaflets for the student's level of knowledge regarding the CTPS (P &lt; 0.05). It is recommended students can obtain information about CTPS from multiple sources and get learning material with media leaflets.  Keywords: CTPS, Media, Level of Knowledge</jats:p