A qualitative mathematical model of the ontogeny of a circadian rhythm in crayfish

Based on experimental work on the ontogeny of the electroretinogram circadian rhythm in crayfish, we present a mathematical model simulating changes in both frequency and amplitude of the electroretinogram oscillation during several developmental stages until shortly before the adult age. Simultaneously, we propose a hypothetical oscillation in the hormonal release whose frequency is imposed on the electroretinogram oscillation. The model consists of two coupled nonlinear oscillators in which a dynamical response is obtained mainly through an Andronov-Hopf bifurcation. Through the construction of the model, a biological hypothesis about the essential elements underlying the ERG circadian rhythm and their interrelations is formulated and discussed.     

Speciation in the Artemia genus: Mitochondrial DNA analysis of bisexual and parthenogenetic brine shrimps

From the cloned mitochondrial DNAs (mtDNAs) isolated from two bisexual species, one Mediterranean, Artemia salina, and one American, Artemia franciscana, and two parthenogenetic (diploid and tetraploid) strains of Artemia parthenogenetica collected in Spain, physical maps have been constructed and compared. They are extremely different among themselves, much more than the differences between Drosophila melanogaster and D. yakuba and in the same range of different mammalian species such as mouse/rat or man/cow. The nucleotide sequences of two regions of mtDNA encoding parts of the cytochrome c oxidase subunit I (COI) and cytochrome b (Cytb) genes have been determined in the two bisexual species and the two parthenogenetic strains. Comparisons of these sequences have revealed a high degree of divergence at the nucleotide level, averaging more than 15%, in agreement with the differences found in the physical maps. The majority of the nucleotide changes are silent and there is a strong bias toward transitions, with the CT substitutions being highly predominant. The evolutionary distance between the two Artemia parthenogenetica is high and there is no clear relationship with any of the bisexual species, including the one present nowadays in Spain. Using a combination of molecular (mtDNA) and morphological markers it is possible to conclude that all of these Artemia isolates should be actually considered as belonging to different species, even the two Artemia parthenogenetica diploidica and tetraploidica.On sabbatical leave from Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madridearly Italian artemiologists to designate the Medi-Beatriz Batuecas died in an accident during the Christmas holy days of 1988 after she had initiated this workCorrespondence to: R. Garesse     

Sexual dimorphism of body size and sternopleural bristle number: a comparison of geographic populations of an invasive cosmopolitan drosophilid

Zaprionus indianus is a cosmopolitan drosophilid, of Afrotropical origin, which has recently colonized South America. The sexual dimorphism (SD) of body size is low, males being almost as big as females. We investigated 10 natural populations, 5 from America and 5 from Africa, using the isofemale line technique. Three traits were measured on each fly: wing and thorax length and sternopleural bristle number. Two indices of SD were compared, and found to be highly correlated (r > 0.99). For the sake of simplicity, only the female/male (F/M) ratio was further considered. A significant genetic variability of SD was found in all cases, although with a low heritability (intra-class correlation of 0.13), about half the value found for the traits themselves. For size SD, we did not find any variation among continents or any latitudinal trend, and average values were 1.02 for wing length and 1.01 for thorax length. Bristle number SD was much greater (1.07). Among mass laboratory strains, SD was genetically much more variable than in recently collected populations, a likely consequence of laboratory drift. Altogether, SD, although genetically variable and prone to laboratory drift, is independent of size variations and presumably submitted to a stabilizing selection in nature.     

Impact of long‐term chromosomal shuffling on the multispecies coalescent analysis of two anthropoid primate lineages

Multispecies coalescent (MSC) theory assumes that gene trees inferred from individual loci are independent trials of the MSC process. As genes might be physically close in syntenic associations spanning along chromosome regions, these assumptions might be flawed in evolutionary lineages with substantial karyotypic shuffling. Neotropical primates (NP) represent an ideal case for assessing the performance of MSC methods in such scenarios because chromosome diploid number varies significantly in this lineage. To this end, we investigated the effect of sequence length on the theoretical expectations of MSC model, as well as the results of coalescent‐based tree inference methods. This was carried out by comparing NP with hominids, a lineage in which chromosome macrostructure has been stable for at least 15 million years. We found that departure from the MSC model in Neotropical primates decreased with smaller sequence fragments, where sites sharing the same evolutionary history were more frequently found than in longer fragments. This scenario probably resulted from extensive karyotypic rearrangement occurring during the radiation of NP, contrary to the comparatively stable chromosome evolution in hominids.     

Resurgence of HIV Infection among Men Who Have Sex with Men in Switzerland: Mathematical Modelling Study

Background

New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis.

Methodology/Principal Findings

The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate.

Conclusions/Significance

The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.     

Host Modulators of H1N1 Cytopathogenicity

Influenza A virus infects 5-20% of the population annually, resulting in ～35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.     

Photosynthetic electron transport interaction of xanthorrhizol isolated from Iostephane heterophylla and its derivatives

A bioactivity-guided chemical study of Iostephane heterophylla (Asteraceae) led to the isolation of xanthorrhizol (1) as the compound that causes inhibition of ATP synthesis, H⁺-uptake and electron flow from water to methylviologen (basal, phosphorylating and uncoupled) in freshly lysed spinach chloroplasts, thus acting as an inhibitor of the Hill reaction. Acetyl (2), dihydro (3) and acetyl-dihydro (4) derivatives were synthesized. It was found that 4 was less active than 1 and 2 in ATP synthesis, whereas 3 was the most potent inhibitor of the Hill reaction and was also an inhibitor of H⁺-ATPase. Studies of the photosynthetic partial redox reactions from PQ to MV indicated that 1 partially inhibited the PQ pool, but that 3 did not. However, both inhibited the uncoupled electron transport in PSII from water to DCBQ. Uncoupled electron flow from water to silicomolybdate was completely inhibited by 3 and partially by 1. The reaction from DPC to DCPIP was inhibited by both 1 and 3. These results indicate that the inhibition site is located within PSII for 1 and 3 as was corroborated by fluorescence decay data.     

A Predominant Multidrug-Resistant Salmonella enterica Serovar Saintpaul Clonal Line in German Turkey and Related Food Products

Recently, Salmonella enterica subsp. enterica serovar Saintpaul has increasingly been observed in several countries, including Germany. However, the pathogenic potential and epidemiology of this serovar are not very well known. This study describes biological attributes of S. Saintpaul isolates obtained from turkeys in Germany based on characterization of their pheno- and genotypic properties. Fifty-five S. Saintpaul isolates from German turkeys and turkey-derived food products isolated from 2000 to 2007 were analyzed by using antimicrobial agent, organic solvent, and disinfectant susceptibility tests, isoelectric focusing, detection of resistance determinants, plasmid profiling, pulsed-field gel electrophoresis (PFGE), and hybridization experiments. These isolates were compared to an outgroup consisting of 24 S. Saintpaul isolates obtained from humans and chickens in Germany and from poultry and poultry products (including turkeys) in Netherlands. A common core resistance pattern was detected for 27 German turkey and turkey product isolates. This pattern included resistance (full or intermediate) to ampicillin, amoxicillin-clavulanic acid, gentamicin, kanamycin, nalidixic acid, streptomycin, spectinomycin, and sulfamethoxazole and intermediate resistance or decreased susceptibility to ciprofloxacin (MIC, 2 or 1 μg/ml, respectively) and several third-generation cephalosporins (including ceftiofur and cefoxitin [MIC, 4 to 2 and 16 to 2 μg/ml, respectively]). These isolates had the same core resistance genotype, with bla_TEM-1, aadB, aadA2, sul1, a Ser83→Glu83 mutation in the gyrA gene, and a chromosomal class 1 integron carrying the aadB-aadA2 gene cassette. Their XbaI, BlnI, and combined XbaI-BlnI PFGE patterns revealed levels of genetic similarity of 93, 75, and 90%, respectively. This study revealed that a multiresistant S. Saintpaul clonal line is widespread in turkeys and turkey products in Germany and was also detected among German human fecal and Dutch poultry isolates.Over the last few decades, the emergence and spread of antimicrobial agent-resistant zoonotic bacteria has become a serious public health concern (2, 23). The widespread use of antimicrobial agents for disease control, including at the farm level, has increased selection of antimicrobial agent-resistant Salmonella isolates (1, 23, 44). Food animals are considered an important reservoir for resistant bacteria. These animals and food products derived from them are traded worldwide, which contributes to the global spread of zoonotic agents and antimicrobial resistance. In the last few years, several monitoring activities were initiated in order to generate baseline data on antimicrobial resistance in bacteria isolated from livestock and food derived from animals that could be used in future assessments of the risk of antimicrobial resistance (10).According to European Union (EU) Zoonoses Regulation (EC) no. 2160/2003 on the control of Salmonella and other specified food-borne zoonotic agents, a European Community target for reducing the prevalence of Salmonella in turkey flocks had to be established. Consequently, EU Commission decision 2006/662/EC was released, and a baseline survey of the prevalence of Salmonella in turkey flocks was carried out in all European countries, including Germany, over a 1-year period starting on 1 October 2006 (http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178706574172.htm). The main objective of this study was to estimate the prevalence of Salmonella in commercial flocks of turkeys. The data showed that at the EU level Salmonella enterica serovar Bredeney was the serovar reported most frequently for fattening turkey flocks and occurred in 17.2% of the samples from Salmonella-positive flocks (1,084 of 3,702 flocks were positive), followed by S. enterica serovar Hadar, S. enterica serovar Derby, and then S. enterica serovar Saintpaul (14.0%, 11.3%, and 10.4% of the samples from positive flocks, respectively). In this study, S. Saintpaul was detected in fattening turkeys in 12 countries, reflecting the wide spread of this serovar. Recently, S. Saintpaul has been increasingly observed in several countries, including Germany. According to Enter-Net reports (data on Salmonella human isolates identified by European national reference centers), for the last quarter of the year 2006 S. Saintpaul was the fourth most common serovar (1.6%) and, in contrast to the data for previous years, was one of the most frequent causes of human salmonellosis in Europe. After this, its prevalence was 1.2% and 0.6% in the first quarters of 2007 and 2008, respectively, among the Salmonella serotypes implicated in human disease (http://ecdc.europa.eu/en/publications/Pages/Surveillance_Reports.aspx). During the period from 2001 to 2009 in Germany, 463 cases of human salmonellosis related to S. Saintpaul (0.09% of all cases; the maximum prevalence was 0.15% in 2008, the prevalence was 0.1% in 2002, 2005, 2006, and 2009 and 0.06% in 2004, and the minimum prevalence was 0.05% in 2007) were reported to the Robert Koch Institute (Berlin, Germany) (www3.rki.de/SurvStat). In Germany, S. Saintpaul attracted public attention particularly in 1993, when it caused a nationwide food-borne outbreak (27). This serotype has often been related to outbreaks in other countries, and in 2008 it was implicated in a large multistate human outbreak associated with various vegetables in the United States (4).Previous studies showed that isolates of S. Saintpaul are often multidrug resistant (33, 35), but little is known about the mechanisms underlying antimicrobial resistance or about the pathogenic potential and epidemiology of isolates belonging to this serotype. The goals of this study were to obtain information about the resistance characteristics of isolates collected between 2000 and 2007 in Germany and to assess possible clonal relationships. The isolates used originated from turkey feces collected during the German Salmonella baseline study (in 2006 and 2007) or from diagnostic samples, including samples of turkey feces and turkey-related food products. These isolates were compared with German strains isolated from humans and chickens and with poultry strains isolated in Netherlands.