Plasmodium falciparum Accompanied the Human Expansion out of Africa

Plasmodium falciparum is distributed throughout the tropics and is responsible for an estimated 230 million cases of malaria every year, with a further 1.4 billion people at risk of infection [1-3]. Little is known about the genetic makeup of P. falciparum populations, despite variation in genetic diversity being a key factor in morbidity, mortality, and the success of malaria control initiatives. Here we analyze a worldwide sample of 519 P. falciparum isolates sequenced for two housekeeping genes (63 single nucleotide polymorphisms from around 5000 nucleotides per isolate). We observe a strong negative correlation between within-population genetic diversity and geographic distance from sub-Saharan Africa (R(2) = 0.95) over Africa, Asia, and Oceania. In contrast, regional variation in transmission intensity seems to have had a negligible impact on the distribution of genetic diversity. The striking geographic patterns of isolation by distance observed in P. falciparum mirror the ones previously documented in humans [4-7] and point to a joint sub-Saharan African origin between the parasite and its host. Age estimates for the expansion of P. falciparum further support that anatomically modern humans were infected prior to their exit out of Africa and carried the parasite along during their colonization of the world.

The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and metabolism in the human pathogen Cryptococcus neoformans

Nitrogen uptake and metabolism are essential to microbial growth. Gat1 belongs to a conserved family of zinc finger containing transcriptional regulators known as GATA-factors. These factors activate the transcription of Nitrogen Catabolite Repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. Cryptococcus neoformans GAT1 is an ortholog to the Aspergillus nidulans AreA and Candida albicans GAD genes. In an attempt to define the function of this transcriptional regulator in C. neoformans, we generated null mutants (gat1 Delta) of this gene. The gat 1 mutant exhibited impaired growth on all amino acids tested as sole nitrogen sources, with the exception of arginine and proline. Furthermore, the gat1 mutant did not display resistance to rapamycin, an immunosuppressant drug that transiently mimics a low-quality nitrogen source. Gal is not required for C. neoformans survival during macrophage infection or for virulence in a mouse model of cryptococcosis. Microarray analysis allowed the identification of target genes that are regulated by Gat1 in the presence of proline, a poor and non-repressing nitrogen source. Genes involved in ergosterol biosynthesis, iron uptake, cell wall organization and capsule biosynthesis, in addition to NCR-sensitive genes, are Gat1-regulated in C. neoformans. (C) 2010 Elsevier Inc. All rights reserved.

Structure, Dynamics, and RNA Interaction Analysis of the Human SBDS Protein

Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS. (C) 2010 Elsevier Ltd. All rights reserved.

Stoichiometry and thermodynamics of the interaction between the C-terminus of human 90 kDa heat shock protein Hsp90 and the mitochondrial translocase of outer membrane Tom70

A large majority of the 1000-1500 proteins in the mitochondria are encoded by the nuclear genome, and therefore, they are translated in the cytosol in the form and contain signals to enable the import of proteins into the organelle. The TOM complex is the major translocase of the outer membrane responsible for preprotein translocation. It consists of a general import pore complex and two membrane import receptors, Tom20 and Tom70. Tom70 contains a characteristic TPR domain, which is a docking site for the Hsp70 and Hsp90 chaperones. These chaperones are involved in protecting cytosolic preproteins from aggregation and then in delivering them to the TOM complex. Although highly significant, many aspects of the interaction between Tom70 and Hsp90 are still uncertain. Thus, we used biophysical tools to study the interaction between the C-terminal domain of Hsp90 (C-Hsp90), which contains the EEVD motif that binds to TPR domains, and the cytosolic fragment of Tom70. The results indicate a stoichiometry of binding of one monomer of Tom70 per dimer of C-Hsp90 with a K(D) of 360 30 nM, and the stoichiometry and thermodynamic parameters obtained suggested that Tom70 presents a different mechanism of interaction with Hsp90 when compared with other TPR proteins investigated. (C) 2011 Elsevier Inc. All rights reserved.

The Human Figure in Drawing and Sculpture

My project as a Senior Scholar has been the study of the human figure through drawing and sculpture. I have worked directly from the model in order to understand the form and structure of the human body. The result of this concentrated study has been a sharpened sense of vision and an increased confidence in the use of materials for both two and three-dimensional representation.

In search of academic identity : physical education, sport science and the field of human movement studies

This thesis addresses the problem of the academic identity of the area traditionally referred to as physical education. The study is a critical examination of the argu ments for the justi cation of this area as an autonomous branch of knowledge. The investigation concentrates on a selected number of arguments. The data collection comprised articles books and proceedings of conferences. The preliminary assessment of these materials resulted in a classi cation of the arguments into three groups. The rst group comprises the arguments in favour of physical education as an academic discipline. The second includes the arguments supporting a science of sport. The third consists of the arguments in favour of to a eld of human movement study. The examination of these arguments produced the following results. (a) The area of physical education does not satisfy the conditions presupposed by the de nition of academic discipline. This is so because the area does not form an integrated system of scienti c theories. (b) The same di culty emerges from the examination of the ar guments for sport science. There is no science of sport because there is no integrated system of scienti c theories related to sport. (c) The arguments in favour of a eld of study yielded more productive results. However di culties arise from the de nition of human movement. The analysis of this concept showed that its limits are not well demarcated. This makes it problematic to take human movement as the focus of a eld of studies. These aspects led to the conclusion that such things as an academic discipline of physical education sport science and eld of human movement studies do not exist. At least there are not such things in the sense of autonomous branches of knowledge. This does not imply that a more integrated inquiry based on several disciplines is not possible and desirable. This would enable someone entering phys ical education to nd a more organised structure of knowledge with some generally accepted problem situations procedures and theories on which to base professional practice.

The risk-properties of human capital and the design of government policies

Whether human capital increases or decreases wage uncertainty is an open question from an empirical standpoint. Yet, most policy prescriptions regarding human capital formation are based on models that impose riskiness on this type of investment. In a two period and finite type optimal income taxation problem we derive prescriptions that are robust to the risk characteristics of human capital: savings should be discouraged, human capital investments encouraged and both types of investment driven to an efficient level from an aggregate perspective. These prescriptions are also robust to the assumptions regarding what choices are observed, despite policy instruments being not.

Open innovation and the challenges of human resource management

This paper considers challenges of Human Resource Management (HRM) in Open Innovation processes. It examines which strategies managers used to overcome these problems in the case of the Brazilian Oil and Gas company Petrobras. By conducting an inductive case study it develops a contextual model based on the use of grounded theory. It argues that the most important categories were to overcome problems of (a) the interpersonal relationship, (b) power shifting inside the organization, and (c) making people more valuable to the organization and shows how managers tackled these challenges. It contributes with a deep analysis of HRM challenges in Open Innovation that is important for a better understanding of management problems that can come along with Open Innovation processes.

Net Neutrality Compendium: Human Rights, Free Competition and the Future of the Internet

The ways in which Internet traffic is managed have direct consequences on Internet users’ rights as well as on their capability to compete on a level playing field. Network neutrality mandates to treat Internet traffic in a non-discriminatory fashion in order to maximise end users’ freedom and safeguard an open Internet. This book is the result of a collective work aimed at providing deeper insight into what is network neutrality, how does it relates to human rights and free competition and how to properly frame this key issue through sustainable policies and regulations. The Net Neutrality Compendium stems from three years of discussions nurtured by the members of the Dynamic Coalition on Network Neutrality (DCNN), an open and multistakeholder group, established under the aegis of the United Nations Internet Governance Forum (IGF).

On paternalistic leadership fit: exploring cross-cultural endorsement, leader-follower fit, and the boundary role of organizational culture

Although cross-cultural leadership research has thrived in international business literature, little attention has been devoted to understanding the effectiveness of non-western theories beyond their original contexts. The purpose of this study is to examine the cross-cultural endorsement of paternalistic leadership, an emerging non-western leadership theory, using data from GLOBE project. Using multigroup confirmatory factor analyses we found measurement equivalence of a scale derived from GLOBE’s data, which enabled us to compare the endorsement of paternalistic leadership dimensions across 10 cultural clusters and 55 societies. Our study revealed that there are significant differences in the importance societies give to each dimension, suggesting that paternalism as leadership style is not universally nor homogeneously endorsed. Furthermore, results suggest that different patterns of endorsement of each of these dimensions give rise to idiosyncratic shades of paternalistic leadership across societies. Implications for theory and future research on international business are discussed.

In vitro culture, PCR , and nested PCR for the detection of Theileria equi in horses submitted to exercise

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)