Identification and structural characterization functional motifs in the Porphyromonas gingivalis MFA1 short fimbria.

Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were expressed and tested for inhibition of P. gingivalis adherence to S. gordonii. Residues 225-400 of Mfa1 was identified as essential for P. gingivalis adherence. Using the three-dimensional structure of Mfa1, a putative binding cleft was identified and five small-molecule peptidomimetics based on the AgI/II peptide could be docked in this site. Site‐specific mutation of amino acids in the predicted cleft, specifically, R240A, W275A, D321A and A357P inhibited the interaction of Mfa1 with streptococci. Additionally, complementation of an Mfa1‐deficient P. gingivalis strain with wild‐type mfa1 restored adherence to streptococci, whereas complementation with the site‐specific mfa1 mutants resulted in significantly reduced levels of adherence. To develop targeted small molecule inhibitors of this protein-protein interaction, virtual screening was performed to identify compounds that exhibit structural similarity with the two functional motifs (NITVK and VQDLL) of the AgI/II peptide. Thirty-three compounds were tested for in vitro inhibition of P. gingivalis adherence, and the three most potent compounds, N7, N17 and V8, were further characterized. In vivo efficacy of these compounds was evaluated in a murine model of periodontitis. Treatment of mice with each of the compounds reduced P. gingivalis-mediated gingival inflammation as determined by IL-17 expression and significantly reduced maxillary alveolar bone resorption in infected animals. Finally, a series of cytotoxicity tests were performed with human and murine cell lines. N17 and V8 did not show any cytotoxic activity. In summary, we successfully characterized the Mfa1 binding site and identified compounds N17 and V8 as potential lead compounds that will provide the platform to design more potent therapeutic agents that may function to limit or prevent P. gingivalis colonization of the oral cavity

Magnetic studies of amorphous Fe-Dy-B ribbons

We have studied the magnetization of melt spun amorphous Fe80−xDyxB20 alloys with 0 ≤ x ≤ 7.5 under magnetic fields up to 6T, and have analyzed the results at 4.2 K on the basis of the random magnetic anisotropy model. Exchange constant and local random anisotropy KL were evaluated. Using the Sarkis´s model, the local anisotropies per atom are found to be 1.75 107 and 4 107 erg/cm3 for Fe and Dy, respectively.We have studied the magnetization of melt spun amorphous Fe80−xDyxB20 alloys with 0 ≤ x ≤ 7.5 under magnetic fields up to 6T, and have analyzed the results at 4.2 K on the basis of the random magnetic anisotropy model. Exchange constant and local random anisotropy KL were evaluated. Using the Sarkis´s model, the local anisotropies per atom are found to be 1.75 107 and 4 107 erg/cm3 for Fe and Dy, respectively

Magnetic properties in amorphous Co95­xDyxZr5 thin films

Amorphous Co95-xDyxZr5 thin films were prepared by RF sputtering and their magnetic properties were studied as a function of temperature and for the composition range 0<x<30. The mean field theory has been used to explain the temperature dependence of the magnetization. The exchange interactions between Co-Co and Dy-Co atom pairs have been evaluated. The magnetic phase diagrams are presented.Amorphous Co95-xDyxZr5 thin films were prepared by RF sputtering and their magnetic properties were studied as a function of temperature and for the composition range 0<x<30. The mean field theory has been used to explain the temperature dependence of the magnetization. The exchange interactions between Co-Co and Dy-Co atom pairs have been evaluated. The magnetic phase diagrams are presented

High-normal blood glucose levels may be associated with decreased spatial perception in young healthy adults.

The negative effects of high normal glucose on cognitive function were previously reported in euglycemic individuals of middle age and the elderly population. This study aimed at examining the effect of baseline blood glucose levels on spatial ability, specifically verticality perception on the computerized rod and frame test (CRFT) in young healthy adults. 63 healthy male medical students (age range from 18-23 years), of whom 30 were non-fasting outside the month of Ramadan and 33 fasting during Ramadan of the year 2016, were recruited in order to create varying degrees of glycemia during which verticality perception was carried out. Baseline blood glucose reading was obtained prior to commencing the CRFT test. Blood glucose levels at the time of testing decreased as the duration between the last meal and testing increased. A blood glucose range of 62-117 mg/dl was achieved among participants for this study. Linear regression analysis showed that blood glucose level at testing correlated positively with all alignment spatial error parameters, indicating a probable reduction of spatial perception ability with higher blood glucose levels. These results are consistent with other cognitive studies in older healthy humans and emphasize the critical impact of early glucose dys-homeostasis on cognitive function. They also indicate that elevated blood glucose may affect cognitive functioning outside of the usual complications of diabetes

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion

Pengaruh Lokasi dan Kualitas Pelayanan terhadap Loyalitas Konsumen pada Fotocopy Anugrah Rengat

This research was conducted on AnugrahPhotocopy in Rengat with the aim to determine the effect of Location and Service Quality to Consumer Loyalty atRengatPhotocopy in Rengat. Sampling was done by random sampling method with 98 samples as respondents. The analytical method used is a quantitative descriptive method, data analysis with partially and simultaneously act (multiple linear regression analysis with the help of the IBM SPSS Stastic program version 21.0). From the results of the research, obtained a regression equation that is Y = 9,881 + 0,243X1 + 0,321X2, it can be seen that Location and Service Quality has a positive influence to Consumer Loyalty atAnugrahPhotocopy in Rengat. In addition, simultaneous testing (Test F), has been obtained F count> F table that is equal to 6.311> 3.09. So that the two independent variables namely location and service quality together have a positive and significant effect on the dependent variable, namely Consumer Loyalty atAnugrahPhotocopy in Rengat. While the Partial Regression Test (t test) shows that location variables significantly influence to Consumer Loyalty at Anugrah Photocopyin Rengat, t arithmetic> t table of 2.554> 1.98525. Variable service quality is more dominant significant effect to Consumer Loyalty at Anugrah Photocopyin Rengat namely t arithmetic> t table of 3.447> 1.98525. In addition, the results of the multiple correlation coefficient is 0.742 which shows the level of relationship between all independent variables to the dependent variable in this research is in the criteria of high relationship closeness. The magnitude of the effect caused by these three variables together affect the consumer loyalty variable with a percentage of 55.1%. While 44.9% is influenced by other factors not included in this study

Haematological, inflammatory, and immunological responses in elite judo athletes maintaining high training loads during Ramadan

During Ramadan, Muslims abstain from food and fluid intake from dawn to sunset for 1 month. These behavioural changes that accompany Ramadan may impact upon Muslim athletes who continue to train intensely. The aim of the present study was to evaluate the effect of Ramadan intermittent fasting (RIF) on the haematological, inflammatory, and immunological measures in elite judo athletes maintaining their usual high training loads. Haematological markers of inflammation, hormones, and immune status were studied in 15 elite male judo athletes before, during, and after Ramadan. The RIF produced small but significant changes in inflammatory, hormonal, and immunological profiles in judo athletes. Serum C-reactive protein increased from 2.93 ± 0.26 mg·L-1 pre-Ramadan to 4.60 ± 0.51 mg·L-1 at the end of Ramadan. Haptoglobin and antitrypsin also significantly increased at different phases during Ramadan, whereas homocysteine and prealbumin remained relatively unchanged. Albumin decreased slightly by mid-Ramadan, then recovered. Immunoglobulin A increased from 1.87 ± 0.56 g·L-1 before Ramadan to 2.49 ± 0.75 g·L-1 at the end, and remained high 3 weeks after. There were no changes in the leucocyte cell counts throughout the study. The mean blood level of thyroid-stimulating hormone and free thyroxine increased significantly during RIF. Most of these changes were within the normal ranges. These results suggest that athletes who continue to train intensely during Ramadan are liable to experience a myriad of small fluctuations in hormones, immunoglobulins, antioxidants, and inflammatory responses