Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Why are there Different Age Related Trends for Different Chemicals?

Persistent organic pollutants (POPs) such as dioxins, PCBs, persistent organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) as well as perfluorinated compounds (PFCs) and triclosan are ubiquitous in the human population. In Australia, we have pooled and subsequently analysed over 10 000 human serum samples for the determination of these chemicals by age group (0–0.5; 0.6–1; 1.1–1.5; 1.6–2; 2.1–2.5; 2.6–3; 3.1–3.5; 3.6–4; 4.1–6; 6.1–9; 9.1–12; 12.1–15; 16–30; 31–45; 46–60 and >60 years) and gender. The results of this analysis were then used to assess the trends of these different chemicals as a function of age, gender and to a lesser extent region. Our data demonstrate clear chemical specific age trends. In particular we demonstrate that for the traditional POPs there is an increase in body burden with age whereas the opposite is true for chemicals such as PBDEs. For PFCs we find chemical specific age trends that vary from compound to compound. For triclosan we show that no apparent age trend is observable. The results of the study and its implications to the collection and archiving of samples for retrospective analysis are discussed.

Chemical synthesis and structure elucidation of bovine K-casein (1-44)

The caseins (αs1, αs2, β, and κ) are phosphoproteins present in bovine milk that have been studied for over a century and whose structures remain obscure. Here we describe the chemical synthesis and structure elucidation of the N-terminal segment (1–44) of bovine κ-casein, the protein which maintains the micellar structure of the caseins. κ-Casein (1–44) was synthesised by highly optimised Boc solid-phase peptide chemistry and characterised by mass spectrometry. Structure elucidation was carried out by circular dichroism and nuclear magnetic resonance spectroscopy. CD analysis demonstrated that the segment was ill defined in aqueous medium but in 30% trifluoroethanol it exhibited considerable helical structure. Further, NMR analysis showed the presence of a helical segment containing 26 residues which extends from Pro8 to Arg34. This is the first report which demonstrates extensive secondary structure within the casein class of proteins.

Do barro ao pó, estudos sobre a tecnologia, processo de trabalho e saúde ocupacional nas olarias

Neste artigo trato do trabalho familiar nas olarias, com especial destaque para o trabalho da mulher. Analiso a posição da mulher na divisão do trabalho e estudo as conseqüências do trabalho para o corpo, bem como a percepção dessas conseqüências pelas trabalhadoras das olarias. Estas, mantidas há gerações na condição de manufaturas, caracterizam-se, na região, pela clandestinidade.

Le-yôm ševîʿî û-šmînî šel Pesaḥ

Digitalisat der Ausg. Rödelheim, 1800

Vigarello, George. Corregir el cuerpo. Historia de un poder pedagógico

Fil: Levoratti, Alejo. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Vigarello, George. Corregir el cuerpo. Historia de un poder pedagógico

Fil: Levoratti, Alejo. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Train scheduling and rolling stock assignment in high speed trains

The Train Timetabling Problem (TTP) has been widely studied for freight and passenger rail systems. A lesser effort has been devoted to the study of high-speed rail systems. A modeling issue that has to be addressed is to model departure time choice of passengers on railway services. Passengers who use these systems attempt to travel at predetermined hours due to their daily life necessities (e.g., commuter trips). We incorporate all these features into TTP focusing on high-speed railway systems. We propose a Rail Scheduling and Rolling Stock (RSch-RS) model for timetable planning of high-speed railway systems. This model is composed of two essential elements: i) an infrastructure model for representing the railway network: it includes capacity constraints of the rail network and the Rolling-Stock constraints; and ii) a demand model that defines how the passengers choose the departure time. The resulting model is a mixed-integer programming model which objective function attempts to maximize the profit for the rail operator