Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

The Point system of selection of immigrants in Quebec

The present paper is aimed at identifying what are the effects of the Point System of Selection of immigrants in Quebec. I defend that the distribution of points results in a different composition of immigrant stocks in terms of origin mix and not in terms of labour skills. To do so, I carry out a longitudinal descriptive analysis on the national composition of immigrants in Quebec and two other significant provinces (Ontario and British Columbia), as well as an analysis of the distribution of points in Quebec and in the rest of Canada.

Iowa Public Employees' Retirement System Performance Report, FY 2004

Agency Performance Report

Iowa Public Employees' Retirement System Performance Report, FY 2005

Agency Performance Report

Born to be bee, fed to be worker? The caste system of a primitively eusocial insect.

ABSTRACT: INTRODUCTION: Primitively eusocial halictid bees are excellent systems to study the origin of eusociality, because all individuals have retained the ancestral ability to breed independently. In the sweat bee Halictus scabiosae, foundresses overwinter, establish nests and rear a first brood by mass-provisioning each offspring with pollen and nectar. The mothers may thus manipulate the phenotype of their offspring by restricting their food provisions. The first brood females generally help their mother to rear a second brood of males and gynes that become foundresses. However, the first brood females may also reproduce in their maternal or in other nests, or possibly enter early diapause. Here, we examined if the behavioural specialization of the first and second brood females was associated with between-brood differences in body size, energetic reserves and pollen provisions. RESULTS: The patterns of variation in adult body size, weight, fat content and food provisioned to the first and second brood indicate that H. scabiosae has dimorphic females. The first-brood females were significantly smaller, lighter and had lower fat reserves than the second-brood females and foundresses. The first-brood females were also less variable in size and fat content, and developed on homogeneously smaller pollen provisions. Foundresses were larger than gynes of the previous year, suggesting that small females were less likely to survive the winter. CONCLUSIONS: The marked size dimorphism between females produced in the first and second brood and the consistently smaller pollen provisions provided to the first brood suggest that the first brood females are channelled into a helper role during their pre-imaginal development. As a large body size is needed for successful hibernation, the mother may promote helping in her first brood offspring by restricting their food provisions. This pattern supports the hypothesis that parental manipulation may contribute to promote worker behaviour in primitively eusocial halictids.

Trait decoupling promotes evolutionary diversification of the trophic and acoustic system of damselfishes.

Trait decoupling, wherein evolutionary release of constraints permits specialization of formerly integrated structures, represents a major conceptual framework for interpreting patterns of organismal diversity. However, few empirical tests of this hypothesis exist. A central prediction, that the tempo of morphological evolution and ecological diversification should increase following decoupling events, remains inadequately tested. In damselfishes (Pomacentridae), a ceratomandibular ligament links the hyoid bar and lower jaws, coupling two main morphofunctional units directly involved in both feeding and sound production. Here, we test the decoupling hypothesis by examining the evolutionary consequences of the loss of the ceratomandibular ligament in multiple damselfish lineages. As predicted, we find that rates of morphological evolution of trophic structures increased following the loss of the ligament. However, this increase in evolutionary rate is not associated with an increase in trophic breadth, but rather with morphofunctional specialization for the capture of zooplanktonic prey. Lineages lacking the ceratomandibular ligament also shows different acoustic signals (i.e. higher variation of pulse periods) from others, resulting in an increase of the acoustic diversity across the family. Our results support the idea that trait decoupling can increase morphological and behavioural diversity through increased specialization rather than the generation of novel ecotypes.

Governmental surveillance system of healthcare-associated infection in Brazil


Objective: This study aimed to describe the structure of governmental surveillance systems for Healthcare Associated Infection (HAI) in the Brazilian Southeastern and Southern States. Method: A cross-sectional, descriptive and exploratory study, with data collection by means of two-phases: characterization of the healthcare structure and of the HAI surveillance system. Results: The governmental teams for prevention and control of HAI in each State ranged from one to six members, having at least one nurse. All States implemented their own surveillance system. The information systems were classified into chain (n=2), circle (n=4) or wheel (n=1). Conclusion: Were identified differences in the structure and information flow from governmental surveillance systems, possibly limiting a nationwide standardization. The present study points to the need for establishing minimum requirements in public policies, in order to guide the development of HAI surveillance systems.


Social organization and mating system of free-ranging, greater white-toothed shrews, Crocidura russula

Indirect evidence from trapping suggests that Crocidura russula is less solitary and territorial than other shrews. To study the social organization and mating system, free-ranging adult and juvenile C. russula were tracked simultaneously throughout the year using a radioactive tracking technique. Coincident rest, coincident activity and home range overlap were measured. During winter, all individuals used the same communal nest and spent on average 84% of their total rest in coincident rest. This led to a large home range overlap (52% on average). Coincident activity was low (2% on average). At the onset of the reproductive season the females became, territorial and shared their nest with only one male. During pair formation, coincident activity and home range overlap were significantly greater between than within sexes. The social organization of C. russula appeared to be strongly influenced by season and differed in this respect from the other species in the genus Sorex which are territorial throughout the year.

Iowa Public Employees' Retirement System Performance Report, FY 2007

Agency Performance Report

Effect on blood pressure and the renin-angiotensin system of repeated doses of the converting enzyme inhibitor CGS 14824A.

A new, orally active angiotensin converting enzyme (ACE) inhibitor, CGS 14824A, was evaluated in 12 healthy male volunteers. Two groups each of 6 volunteers were given 5 or 10 mg once daily p.o. for 8 days. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone and plasma converting enzyme activity had fallen, while blood angiotensin I and plasma renin activity had risen. Throughout the study, more than 90% inhibition of ACE was found immediately before giving either the 5 or 10 mg dose and 50% blockade was still present 72 h following the last dose. Based on the determination of ACE, there was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed during the course of the study. CGS 14824A was an effective, orally active, long-lasting and well tolerated converting enzyme inhibitor.

Diversity and regional inequalities: Assessing the outcomes of the Spanish 'System of Health Care Services'

The consolidation of a universal health system coupled with a process of regionaldevolution characterise the institutional reforms of the National Health System(NHS) in Spain in the last two decades. However, scarce empirical evidence hasbeen reported on the effects of both changes in health inputs, outputs andoutcomes, both at the country and at the regional level. This paper examinesthe empirical evidence on regional diversity, efficiency and inequality ofthese changes in the Spanish NHS using cross-correlation, panel data andexpenditure decomposition analysis. Results suggest that besides significantheterogeneity, once we take into account region-specific needs there is evidenceof efficiency improvements whilst inequalities in inputs and outcomes, althoughmore visible , do not appear to have increased in the last decade. Therefore,the devolution process in the Spanish Health System offers an interesting casefor the experimentation of health reforms related to regional diversity butcompatible with the nature of a public NHS, with no sizeable regionalinequalitiest.

Iowa Public Employees’ Retirement System Performance Plan, FY 2009

Agency Performance Plan, Iowa Public Employees’ Retirement System

Iowa Public Employees Retirement System Strategic Plan, 2007-2010

This report outlines the strategic plan for Iowa Public Employees Retirement System, goals and mission.

The semi-presidential system of Cape Verde: the relationship between the executive and the legislative powers = O sistema semi-presidencialista caboverdiano: a relação entre os poderes executivo e legislativo

e article analyses the relationship established between the executive and legislative powers in the Cape Verdean government system where researchers seek to understand it, taking into account their theoretical and constitutional setting practice. It should be noted the prominence of the debate and studies undertaken to understand how the scienti c academy seeks to eradicate this problem. Two issues are relevant in this debate: the rst reporting to the theoretical and constitutional con guration of Cape Verdean government system and the other to its policy and legislative practice. Keywords: Cape Verde. Semi-presidential System. Systems of Government. Legislative and Executive Powers.

Iowa Public Employees’ Retirement System An Annual Summary for the Fiscal Year Ended June 30, 2011, FY 2011

Report on the Iowa Public Employees’ Retirement System (IPERS) for the year ended June 30, 2011