How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Does the inclusion of 'professional development' teaching improve medical students' communication skills?

Background: This study investigated whether the introduction of professional development teaching in the first two years of a medical course improved students' observed communication skills with simulated patients. Students' observed communication skills were related to patient-centred attitudes, confidence in communicating with patients and performance in later clinical examinations.Methods: Eighty-two medical students from two consecutive cohorts at a UK medical school completed two videoed consultations with a simulated patient: one at the beginning of year 1 and one at the end of year 2. Group 1 (n = 35) received a traditional pre-clinical curriculum. Group 2 (n = 47) received a curriculum that included communication skills training integrated into a 'professional development' vertical module. Videoed consultations were rated using the Evans Interview Rating Scale by communication skills tutors. A subset of 27% were double-coded. Inter-rater reliability is reported.Results: Students who had received the professional development teaching achieved higher ratings for use of silence, not interrupting the patient, and keeping the discussion relevant compared to students receiving the traditional curriculum. Patient-centred attitudes were not related to observed communication. Students who were less nervous and felt they knew how to listen were rated as better communicators. Students receiving the traditional curriculum and who had been rated as better communicators when they entered medical school performed less well in the final year clinical examination.Conclusions: Students receiving the professional development training showed significant improvements in certain communication skills, but students in both cohorts improved over time. The lack of a relationship between observed communication skills and patient-centred attitudes may be a reflection of students' inexperience in working with patients, resulting in 'patient-centredness' being an abstract concept. Students in the early years of their medical course may benefit from further opportunities to practise basic communication skills on a one-to-one basis with patients

Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP−) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain- specific effect of ATD Moja-De on anxiety-like behavior

Wasp-Waist Interactions in the North Sea Ecosystem

Background In a “wasp-waist” ecosystem, an intermediate trophic level is expected to control the abundance of predators through a bottom-up interaction and the abundance of prey through a top-down interaction. Previous studies suggest that the North Sea is mainly governed by bottom-up interactions driven by climate perturbations. However, few studies have investigated the importance of the intermediate trophic level occupied by small pelagic fishes. Methodology/Principal Findings We investigated the numeric interactions among 10 species of seabirds, two species of pelagic fish and four groups of zooplankton in the North Sea using decadal-scale databases. Linear models were used to relate the time series of zooplankton and seabirds to the time series of pelagic fish. Seabirds were positively related to herring (Clupea harengus), suggesting a bottom-up interaction. Two groups of zooplankton; Calanus helgolandicus and krill were negatively related to sprat (Sprattus sprattus) and herring respectively, suggesting top-down interactions. In addition, we found positive relationships among the zooplankton groups. Para/pseudocalanus was positively related to C. helgolandicus and C. finmarchicus was positively related to krill. Conclusion/Significance Our results indicate that herring was important in regulating the abundance of seabirds through a bottom-up interaction and that herring and sprat were important in regulating zooplankton through top-down interactions. We suggest that the positive relationships among zooplankton groups were due to selective foraging and switching in the two clupeid fishes. Our results suggest that “wasp-waist” interactions might be more important in the North Sea than previously anticipated. Fluctuations in the populations of pelagic fish due to harvesting and depletion of their predators might accordingly have profound consequences for ecosystem dynamics through trophic cascades

Comparative Proteomic Analysis of the PhoP Regulon in Salmonella enterica Serovar Typhi Versus Typhimurium

Background: S. Typhi, a human-restricted Salmonella enterica serovar, causes a systemic intracellular infection in humans (typhoid fever). In comparison, S. Typhimurium causes gastroenteritis in humans, but causes a systemic typhoidal illness in mice. The PhoP regulon is a well studied two component (PhoP/Q) coordinately regulated network of genes whose expression is required for intracellular survival of S. enterica. Methodology/Principal Findings: Using high performance liquid chromatography mass spectrometry (HPLC-MS/MS), we examined the protein expression profiles of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro and compared these results to profiles of $phoP^−/Q^−$ mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Our analysis identified 53 proteins in S. Typhimurium LT2 and 56 proteins in S. Typhi that were regulated in a PhoP-dependent manner. As expected, many proteins identified in S. Typhi demonstrated concordant differential expression with a homologous protein in S. Typhimurium. However, three proteins (HlyE, STY1499, and CdtB) had no homolog in S. Typhimurium. HlyE is a pore-forming toxin. STY1499 encodes a stably expressed protein of unknown function transcribed in the same operon as HlyE. CdtB is a cytolethal distending toxin associated with DNA damage, cell cycle arrest, and cellular distension. Gene expression studies confirmed up-regulation of mRNA of HlyE, STY1499, and CdtB in S. Typhi in PhoP-inducing conditions. Conclusions/Significance: This study is the first protein expression study of the PhoP virulence associated regulon using strains of Salmonella mutant in PhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499) that are not present in the genome of the wide host-range Typhimurium, and includes the first protein expression profiling of a live attenuated bacterial vaccine studied in humans (Ty800)

Large-Scale Brain Networks in Board Game Experts: Insights from a Domain-Related Task and Task-Free Resting State

Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior