Summary of ST-MA deliverables for LHC

The ST/MA group is responsible for the monitoring of the CERN Technical Infrastructure as well as the design, installation and maintenance of personnel protection system such as access control system, fire and gas leak detection, safety alarm monitoring systems and radiation monitoring systems (in collaboration with TIS). This paper provides an overview of the main projects and services managed in the group and outlines the scope, the organisation and the planning of the main deliverables for LHC

Učinkovitost u zadacima fine motorike i prostornih odnosa tijekom menstrualnog ciklusa

Various studies have shown fl uctuations in task performance during the menstrual cycle. The aim of this study was to see the effects of the menstrual cycle on performing fi ne motor and spatial tasks of different level of complexity in twenty students aged 18 to 21 years, with regular menstrual cycle (28 to 30 days). The students performed O’Connor Finger Dexterity Test and mental rotation test during the menstrual, late follicular, and midluteal phase. Before the tests were performed, we administered Spielberger’s State-Trait Anxiety Inventory for each phase. After the tasks were completed, the subjects ranked their diffi culty on Borg’s scale. The results showed the best performance in both tests in the midluteal phase (with sex hormones at their peak). The anxiety level and task diffi culty ranking were the highest in the menstrual phase, when the hormone levels were the lowest.Različita su istraživanja pokazala promjene učinkovitosti tijekom menstrualnog ciklusa. U zadacima u kojima su uspješnije žene, najveća učinkovitost događa se tijekom kasne folikularne ili srednje lutealne faze. U zadacima u kojima su pak uspješniji muškarci najveća je učinkovitost nađena u menstrualnoj fazi. Na osnovi uporabe zadataka fi ne motorike i prostornih zadataka različitih razina kompleksnosti, cilj ovog istraživanja bio je ispitati utjecaj menstrualnog ciklusa na kognitivne funkcije. U istraživanju je sudjelovalo dvadeset ispitanica, dobi od 18 do 21 godinu, s redovitim menstrualnim ciklusima (28 do 30 dana). Ispitanice su izvodile O’Connorov deksterimetar i zadatke mentalne rotacije tijekom menstrualne, kasne folikularne i srednje lutealne faze. Prije izvođenja zadataka, u svakoj fazi ciklusa primijenjen je Spielbergerov upitnik stanja anksioznosti. Nakon izvođenja zadataka, ispitanice su procjenjivale njihovu težinu na Borgovoj skali. Rezultati su pokazali najbolju učinkovitost u oba zadatka u fazi visokih razina spolnih hormona (srednja lutealna faza). Stanje anksioznosti i procijenjene težine zadataka bili su najviši u menstrualnoj fazi, kada su razine spolnih hormona najniže

Validation of <i>N</i>-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of <i>Trypanosoma cruzi</i>

BACKGROUND:Trypanosoma cruzi causes Chagas disease, an endemic and debilitating illness in Latin America. Lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. The two clinically available drugs for the chemotherapy of Chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. The development of new anti-T. cruzi agents is therefore imperative. The enzyme N-myristoyltransferase (NMT) has recently been biochemically characterized, shown to be essential in Leishmania major, Trypanosoma brucei, and T. cruzi¸ and proposed as promising chemotherapeutic target in these trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS:Here, using high-content imaging we assayed eight known trypanosomatid NMT inhibitors, against mammal-dwelling intracellular amastigote and trypomastigote stages and demonstrated that three of them (compounds 1, 5, and 8) have potent anti-proliferative effect at submicromolar concentrations against T. cruzi, with very low toxicity against human epithelial cells. Moreover, metabolic labeling using myristic acid, azide showed a considerable decrease in the myristoylation of proteins in parasites treated with NMT inhibitors, providing evidence of the on-target activity of the inhibitors. CONCLUSIONS/SIGNIFICANCE:Taken together, our data point out to the potential use of NMT inhibitors as anti-T. cruzi chemotherapy

Heat-Killed Trypanosoma cruzi Induces Acute Cardiac Damage and Polyantigenic Autoimmunity

Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially fatal cardiomyopathy often associated with cardiac autoimmunity. T. cruzi infection induces the development of autoimmunity to a number of antigens via molecular mimicry and other mechanisms, but the genesis and pathogenic potential of this autoimmune response has not been fully elucidated. To determine whether exposure to T. cruzi antigens alone in the absence of active infection is sufficient to induce autoimmunity, we immunized A/J mice with heat-killed T. cruzi (HKTC) emulsified in complete Freund's adjuvant, and compared the resulting immune response to that induced by infection with live T. cruzi. We found that HKTC immunization is capable of inducing acute cardiac damage, as evidenced by elevated serum cardiac troponin I, and that this damage is associated with the generation of polyantigenic humoral and cell-mediated autoimmunity with similar antigen specificity to that induced by infection with T. cruzi. However, while significant and preferential production of Th1 and Th17-associated cytokines, accompanied by myocarditis, develops in T. cruzi-infected mice, HKTC-immunized mice produce lower levels of these cytokines, do not develop Th1-skewed immunity, and lack tissue inflammation. These results demonstrate that exposure to parasite antigen alone is sufficient to induce autoimmunity and cardiac damage, yet additional immune factors, including a dominant Th1/Th17 immune response, are likely required to induce cardiac inflammation