A New Role for Translation Initiation Factor 2 in Maintaining Genome Integrity

Escherichia coli translation initiation factor 2 (IF2) performs the unexpected function of promoting transition from recombination to replication during bacteriophage Mu transposition in vitro, leading to initiation by replication restart proteins. This function has suggested a role of IF2 in engaging cellular restart mechanisms and regulating the maintenance of genome integrity. To examine the potential effect of IF2 on restart mechanisms, we characterized its influence on cellular recovery following DNA damage by methyl methanesulfonate (MMS) and UV damage. Mutations that prevent expression of full-length IF2-1 or truncated IF2-2 and IF2-3 isoforms affected cellular growth or recovery following DNA damage differently, influencing different restart mechanisms. A deletion mutant (del1) expressing only IF2-2/3 was severely sensitive to growth in the presence of DNA-damaging agent MMS. Proficient as wild type in repairing DNA lesions and promoting replication restart upon removal of MMS, this mutant was nevertheless unable to sustain cell growth in the presence of MMS; however, growth in MMS could be partly restored by disruption of sulA, which encodes a cell division inhibitor induced during replication fork arrest. Moreover, such characteristics of del1 MMS sensitivity were shared by restart mutant priA300, which encodes a helicase-deficient restart protein. Epistasis analysis indicated that del1 in combination with priA300 had no further effects on cellular recovery from MMS and UV treatment; however, the del2/3 mutation, which allows expression of only IF2-1, synergistically increased UV sensitivity in combination with priA300. The results indicate that full-length IF2, in a function distinct from truncated forms, influences the engagement or activity of restart functions dependent on PriA helicase, allowing cellular growth when a DNA–damaging agent is present

Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-), 'intermediate' (CD14brightCD16+), and 'non-classical' (CD14dimCD16+) monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S) products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection

Vulnerability of Brazilian municipalities to hantavirus infections based on multi‑criteria decision analysis

Background: Hantavirus infection is an emerging zoonosis transmitted by wild rodents. In Brazil, high case-fatality rates among humans infected with hantavirus are of serious concern to public health authorities. Appropriate preventive measures partly depend on reliable knowledge about the geographical distribution of this disease. Methods: Incidence of hantavirus infections in Brazil (1993–2013) was analyzed. Epidemiological, socioeconomic, and demographic indicators were also used to classify cities’ vulnerability to disease by means of multi-criteria decision analysis (MCDA). Results: From 1993 to 2013, 1752 cases of hantavirus were registered in 16 Brazilian states. The highest incidence of hantavirus was observed in the states of Mato Grosso (0.57/100,000) and Santa Catarina (0.13/100,000). Based on MCDA analysis, municipalities in the southern, southeastern, and midwestern regions of Brazil can be classified as highly vulnerable. Most municipalities in northern and northeastern Brazil were classified as having low vulnerability to hantavirus cardiopulmonary syndrome. Conclusions: Although most human infections by hantavirus registered in Brazil occurred in the southern region of the country, a greater vulnerability to hantavirus was found in the Brazilian Midwest. This result reflects the need to strengthen surveillance where the disease has thus far gone unreported

Urban malaria and associated risk factors in Jimma town, south-west Ethiopia

<p>Abstract</p> <p>Background</p> <p>Malaria kills millions around the world. Until recently it was believed to be a disease of rural areas, since the <it>Anopheles </it>mosquito, which transmits <it>Plasmodium </it>species breeds in rural areas. Urban malaria is emerging as a potential, but "avertable" crisis, in Africa. In view of the rapidly growing number of small and medium-sized towns in Ethiopia there is a pressing need to improve the understanding of the epidemiology of malaria. Therefore, the aim of this study was to determine malaria prevalence and associated risk factors in Jimma town.</p> <p>Methods</p> <p>A cross-sectional study was carried out in Jimma town from April 1 to May 28, 2010. 804 study participants were included from 291 households for microscopic examination of malaria parasites. Socio-demography data and risk factors were collected using structured questionnaires. Logistic regression analysis was done using SPSS 15.0 statistical software.</p> <p>Results</p> <p>From a total of 804 study participants in current survey only 42 (5.2%) were positive for malaria parasites. <it>Plasmodium vivax, Plasmodium falciparum </it>and mixed infection accounted 71.4%, 26.2% and 2.4%, respectively. Higher malaria prevalence rate was observed among under-five children (11%). Those who do not use insecticide-treated bed nets (ITN) were more likely to be infected with malaria (OR = 13.6; 95% CI 4.9-37.2, p < 0.001) compared with those who use the ITN. Living in areas where stagnant water existed (OR = 2.1; 95% CI 1.00-4.2, p = 0.047) and its distance of existence <1 km from the house(OR = 2.1; 95% CI 2.0-15.8, p = 0.001) were more likely to be infected with malaria parasite compared with those who live away from stagnant at a distance greater than 1 km.</p> <p>Conclusion</p> <p>Malaria is a major health problem with <it>P. vivax </it>becoming a predominant species in the town. The prevalence was strongly associated with proximity of residence to potential mosquito breeding sites. Malaria is affecting significant proportions of the urban settlers and human activities nevertheless play an important role in bringing the mosquito breeding sites closer to residences.</p

Feeling of pleasure to high-intensity interval exercise is dependent of the number of work bouts and physical activity status

Objectives: To examine the affective responses during a single bout of a low-volume HIIE in active and insufficiently active men. Materials and methods: Fifty-eight men (aged 25.3 ± 3.6 years) volunteered to participate in this study: i) active (n = 29) and ii) insufficiently active (n = 29). Each subject undertook i) initial screening and physical evaluation, ii) maximal exercise test, and iii) a single bout of a low-volume HIIE. The HIIE protocol consisted of 10 x 60s work bouts at 90% of maximal treadmill velocity (MTV) interspersed with 60s of active recovery at 30% of MTV. Affective responses (Feeling Scale, -5/+5), rating of perceived exertion (Borg's RPE, 6-20), and heart rate (HR) were recorded during the last 10s of each work bout. A two-factor mixed-model repeated measures ANOVA, independent-samples t test, and chi-squared test were used to data analysis. Results: There were similar positive affective responses to the first three work bouts between insufficiently active and active men (p > 0.05). However, insufficiently active group displayed lower affective responses over time (work bout 4 to 10) than the active group (p 0.05). Conclusions: Insufficiently active and active men report feelings of pleasure to few work bouts (i.e., 3-4) during low-volume HIIE, while the affective responses become more unpleasant over time for insufficiently active subjects. Investigations on the effects of low-volume HIIE protocols including a fewer number of work bouts on health status and fitness of less active subjects would be interesting, especially in the first training weeks