ArgR is an essential local transcriptional regulator of the arcABC-operon in Streptococcus suis and crucial for biological fitness in acidic environment

Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance very little is known about the factors contributing to its virulence. Recently, we identified a new putative virulence factor in Streptococcus suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC-operon, which enables Streptococcus suis to survive in acidic environment. In this study, we focused on ArgR, an ADS associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knock-out strain we could show that ArgR is essential for arcABC-operon expression and necessary for the biological fitness of Streptococcus suis. By cDNA expression microarray analyses and quantitative real time RT-PCR we found that the arcABC-operon is the only gene cluster regulated by ArgR, which is in contrast to many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from -147 to 72 bp upstream of the transcriptional start point. Overall our results show that in Streptococcus suis ArgR is an essential, system specific transcriptional regulator of the ADS directly interacting with the arcABC promoter in vivo

Phase Transitions in High Purity Zr Under Dynamic Compression

We present results from ramp compression experiments on high-purity Zr that show the $\alpha \rightarrow \omega$, $\omega \rightarrow \beta$, as well as reverse $\beta \rightarrow \omega$ phase transitions. Simulations with a multi-phase equation of state and phenomenological kinetic model match the experimental wave profiles well. While the dynamic $\alpha \rightarrow \omega$ transition occurs $\sim 9$ GPa above the equilibrium phase boundary, the $\omega \rightarrow \beta$ transition occurs within 0.9~GPa of equilibrium. We estimate that the dynamic compression path intersects the equilibrium $\omega - \beta$ line at $P= 29.2$ GPa, and $T = 490$ K. The thermodynamic path in the interior of the sample lies $\sim 100$ K above the isentrope at the point of the $\omega \rightarrow \beta$ transition. Approximately half of this dissipative temperature rise is due to plastic work, and half is due to the non-equilibrium $\alpha \rightarrow \omega$ transition. The inferred rate of the $\alpha \rightarrow \omega$ transition is several orders of magnitude higher than that measured in dynamic diamond anvil cell (DDAC) experiments in an overlapping pressure range. We discuss a model for the influence of shear stress on the nucleation rate. The small fractional volume change $\Delta V/V \approx 0.1$ at the $\alpha \rightarrow \omega$ transition amplifies the effect of shear stress, and we estimate that for this case shear stress is equivalent to a pressure increase in the range of several GPa. Correcting our transition rate to a hydrostatic rate brings it approximately into line with the DDAC results, suggesting that shear stress plays a significant role in the transformation rate

Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis

Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10¿ccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10¿ccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis

Lattice Dynamics and the High Pressure Equation of State of Au

Elastic constants and zone-boundary phonon frequencies of gold are calculated by total energy electronic structure methods to twofold compression. A generalized force constant model is used to interpolate throughout the Brillouin zone and evaluate moments of the phonon distribution. The moments are used to calculate the volume dependence of the Gruneisen parameter in the fcc solid. Using these results with ultrasonic and shock data, we formulate the complete free energy for solid Au. This free energy is given as a set of closed form expressions, which are valid to compressions of at least V/V_0 = 0.65 and temperatures up to melting. Beyond this density, the Hugoniot enters the solid-liquid mixed phase region. Effects of shock melting on the Hugoniot are discussed within an approximate model. We compare with proposed standards for the equation of state to pressures of ~200 GPa. Our result for the room temperature isotherm is in very good agreement with an earlier standard of Heinz and Jeanloz.Comment: 13 pages, 8 figures. Accepted by Phys. Rev.

Modelling concept prototype competencies using a developmental memory model

The use of concepts is fundamental to human-level cognition, but there remain a number of open questions as to the structures supporting this competence. Specifically, it has been shown that humans use concept prototypes, a flexible means of representing concepts such that it can be used both for categorisation and for similarity judgements. In the context of autonomous robotic agents, the processes by which such concept functionality could be acquired would be particularly useful, enabling flexible knowledge representation and application. This paper seeks to explore this issue of autonomous concept acquisition. By applying a set of structural and operational principles, that support a wide range of cognitive competencies, within a developmental framework, the intention is to explicitly embed the development of concepts into a wider framework of cognitive processing. Comparison with a benchmark concept modelling system shows that the proposed approach can account for a number of features, namely concept-based classification, and its extension to prototype-like functionality

Underreporting of meningococcal disease incidence in the Netherlands: results from a capture-recapture analysis based on three registration sources with correction for false positive diagnoses.

In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture-recapture method. Data over 1993-1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture-recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture-recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture-recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs

The use of typing methods and infection prevention measures to control a bullous impetigo outbreak on a neonatal ward

<p>Abstract</p> <p>Background</p> <p>We describe an outbreak of Bullous Impetigo (BI), caused by a (methicillin susceptible, fusidic acid resistant) <it>Staphylococcus aureus</it> (SA) strain, <it>spa-</it>type t408, at the neonatal and gynaecology ward of the Jeroen Bosch hospital in the Netherlands, from March-November 2011.</p> <p>Methods</p> <p>We performed an outbreak investigation with revision of the hygienic protocols, MSSA colonization surveillance and environmental sampling for MSSA including detailed typing of <it>SA</it> isolates. <it>Spa</it> typing was performed to discriminate between the SA isolates. In addition, Raman-typing was performed on all t408 isolates.</p> <p>Results</p> <p>Nineteen cases of BI were confirmed by SA positive cultures. A cluster of nine neonates and three health care workers (HCW) with <it>SA</it> t408 was detected. These strains were MecA^-, PVL^-, Exfoliative Toxin (ET)A^-, ETB⁺, ETAD^-, fusidic acid-resistant and methicillin susceptible. Eight out of nine neonates and two out of three HCW t408 strains yielded a similar Raman type. Positive t408 HCW were treated and infection control procedures were reinforced. These measures stopped the outbreak.</p> <p>Conclusions</p> <p>We conclude that treatment of patients and HCW carrying a predominant SA t408, and re-implementing and emphasising hygienic measures were effective to control the outbreak of SA t408 among neonates.</p

Does the fat tailed Damara ovine breed have a distinct lipid metabolism leading to a high concentration of branched chain fatty acids in tissues?

Articles in International JournalsFat tailed sheep breeds are known for their adaptation to nutritional stress, among other harsh production conditions. Damara sheep, native to Southern Africa, have recently been exported to other areas of the world, particularly Australia, aiming to produce lamb in semi-arid regions. Damaras have a unique hanging fat tail, a fat depot able to be mobilized under nutritional stress. In this article we perform an in-depth characterization of the fatty acid profiles of the fat tail in underfed and control Damara rams. Profiles were very similar between experimental groups, with the exception of palmitic acid (16:0) that was lower (P = 0.014) in underfed animals. However, the most striking result was the very high proportions of non-terminal branched chain fatty acids found in the fat tail adipose tissue, as well as the gastrocnemius muscle of Damara rams. The muscle of Dorper and Merino rams used in the same experiment did not present non-terminal branched chain fatty acids, suggesting that Damara rams have a unique lipid metabolism. Herein, we interpret this trait relating it to a higher ability of Damara sheep to digest fibrous fodder and to putative differences in the propionate metabolism by comparison to other sheep breeds

Serum IgA Responses against Pertussis Proteins in Infected and Dutch wP or aP Vaccinated Children: An Additional Role in Pertussis Diagnostics

BACKGROUND: Whooping cough is a respiratory disease caused by Bordetella pertussis, which induces mucosal IgA antibodies that appear to be relevant in protection. Serum IgA responses are measured after pertussis infection and might provide an additional role in pertussis diagnostics. However, the possible interfering role for pertussis vaccinations in the induction of serum IgA antibodies is largely unknown. METHODS/PRINCIPAL FINDINGS: We compared serum IgA responses in healthy vaccinated children between 1 and 10 years of age with those in children who despite vaccinations recently were infected with Bordetella pertussis. All children have been vaccinated at 2, 3, 4 and 11 months of age with either the Dutch whole-cell pertussis (wP) vaccine or an acellular pertussis (aP) vaccine and additionally received an aP booster vaccination at 4 years of age. Serum IgA responses to pertussis toxin (PT), filamentous heamagglutinin (FHA) and pertactin (Prn) were measured with a fluorescent multiplex bead-based immuno-assay. An ELISPOT-assay was used for the detection of IgA-memory B-cells specific to these antigens. Serum IgA levels to all pertussis vaccine antigens were significantly higher in infected children compared with healthy children. High correlations between anti-PT, anti-FHA or anti-Prn IgA and IgG levels were found in infected children and to some degree in wP primed children, but not at all in aP primed children. Highest numbers of IgA-pertussis-specific memory B-cells were observed after infection and generally comparable numbers were found after wP and aP vaccination. CONCLUSIONS: This study provides new insight in the diagnostic role for serum IgA responses against PT in vaccinated children. Since aP vaccines induce high serum IgG levels that interfere with pertussis diagnostics, serum IgA-PT levels will provide an additional diagnostic role. High levels of serum IgA for PT proved specific for recent pertussis infection with reasonable sensitivity, whereas the role for IgA levels against FHA and Prn in diagnosing pertussis remains controversial

Update on Streptococcus suis research and prevention in the era of antimicrobial restriction: 4th International Workshop on S. suis

Streptococcus suis is a swine pathogen and a zoonotic agent afflicting people in close contact with infected pigs or pork meat. Sporadic cases of human infections have been reported worldwide. In addition, S. suis outbreaks emerged in Asia, making this bacterium a primary health concern in this part of the globe. In pigs, S. suis disease results in decreased performance and increased mortality, which have a significant economic impact on swine production worldwide. Facing the new regulations in preventive use of antimicrobials in livestock and lack of effective vaccines, control of S. suis infections is worrisome. Increasing and sharing of knowledge on this pathogen is of utmost importance. As such, the pathogenesis and epidemiology of the infection, antimicrobial resistance, progress on diagnosis, prevention, and control were among the topics discussed during the 4th International Workshop on Streptococcus suis (held in Montreal, Canada, June 2019). This review gathers together recent findings on this important pathogen from lectures performed by lead researchers from several countries including Australia, Canada, France, Germany, Japan, Spain, Thailand, The Netherlands, UK, and USA. Finally, policies and recommendations for the manufacture, quality control, and use of inactivated autogenous vaccines are addressed to advance this important field in veterinary medicine