Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Chiral drag force

We provide a holographic evaluation of novel contributions to the drag force acting on a heavy quark moving through strongly interacting plasma. The new contributions are chiral in that they act in opposite directions in plasmas containing an excess of left- or right-handed quarks and in that they are proportional to the coefficient of the axial anomaly. These new contributions to the drag force act either parallel to or antiparallel to an external magnetic field or to the vorticity of the fluid plasma. In all these respects, these contributions to the drag force felt by a heavy quark are analogous to the chiral magnetic effect on light quarks. However, the new contribution to the drag force is independent of the electric charge of the heavy quark and is the same for heavy quarks and antiquarks. We show that although the chiral drag force can be non-vanishing for heavy quarks that are at rest in the local fluid rest frame, it does vanish for heavy quarks that are at rest in a suitably chosen frame. In this frame, the heavy quark at rest sees counterpropagating momentum and charge currents, both proportional to the axial anomaly coefficient, but feels no drag force. This provides strong concrete evidence for the absence of dissipation in chiral transport, something that has been predicted previously via consideration of symmetries. Along the way to our principal results, we provide a general calculation of the corrections to the drag force due to the presence of gradients in the flowing fluid in the presence of a nonzero chemical potential. We close with a consequence of our result that is at least in principle observable in heavy ion collisions, namely an anticorrelation between the direction of the CME current for light quarks in a given event and the direction of the kick given to the momentum of all the heavy quarks and antiquarks in that event.Comment: 28 pages, small improvement to the discussion of gravitational anomaly, references adde

Analiza proteinskih adukata kao biomarkera kratkotrajne izloženosti etilen oksidu i rezultati biomonitoringa

An accidental exposure of six workers to ethylene oxide (EO) provided the rationale for a biomonitoring and follow-up study, whose aim was to analyse protein adduct kinetics and examine the differentiation between accidental and environmental exposure, e.g., from tobacco smoke. For this purpose, the decrease in the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV) was followed during a fi ve-month period after the accident, together with N-2-cyanoethylvaline (CEV) and urinary cotinine, two well-established biomarkers for smoking. The follow-up study showed that EO adduct concentrations significantly increased after a short but presumably high exposure. Initial biomonitoring revealed HEV levels above 500 pmol g-1 globin in all cases, with a maximum of about 2,400 pmol g-1 globin. This compares to a German EKA value (exposure equivalent for carcinogenic substances) for a daily 8-h-exposure to 1 ppm EO of 90 μg L-1 blood (~3,900 pmol g-1 globin). The adduct levels dropped in accordance with the expected zero-order kinetics for a single exposure. After the five-month observation interval, the HEV concentrations in blood refl ected the individual background from tobacco smoking. The results of this study show that even a short exposure to ethylene oxide may result in a signifi cant rise in haemoglobin adduct levels. Although protein adducts and their occupational-medical assessment values are considered for long-term exposure surveillance, they can also be used for monitoring accidental exposures. In these cases, the calculation of daily ‘ppm-equivalents’ may provide a means for a comparison with the existing assessment values.U radu su prikazani rezultati biomonitoringa provedenog neposredno nakon akcidentalnog izlaganja šestorice radnika etilen oksidu i studije praćenja (follow up) provedene u cilju procjene kinetike razgradnje proteinskih adukata i utvrđivanja razlika nakon kratkotrajne izloženosti i izlaganja čimbenicima iz okoliša kao što je duhanski dim. U tu smo svrhu tijekom petomjesečnoga razdoblja nakon nezgode pratili smanjenje koncentracije hemoglobinskog adukta N-2-hidroksietilvalina usporedo s mjerenjem razina N-2-cijanoetilvalina i kotinina u mokraći, koji su pouzdani biomarkeri za dokazivanje pušenja duhana. Studija praćenja je pokazala da su koncentracije adukata etilen oksida značajno porasle nakon kratkotrajnoga izlaganja visokoj razini etilen oksida. U početnom biomonitoringu svih radnika izmjerene su razine N-2-hidroksietilvalina iznad 500 pmol g-1 globina, s maksimalnom vrijednošću od oko 2400 pmol g-1 globina. Ti su podaci usporedivi s vrijednostima njemačkih normi ekvivalenata izlaganja kancerogenim tvarima (EKA) od 90 μg L-1 krvi (~3900 pmol g-1 globina) kroz osmosatno dnevno izlaganje koncentraciji od 1 ppm etilen oksida. Razine adukata smanjile su se u skladu s očekivanom kinetikom nultoga reda za jednokratno izlaganje. Koncentracije N-2-hidroksietilvalina izmjerene u krvi radnika nakon petomjesečnoga praćenja mogu se povezati s njihovim osobnim pušačkim navikama. Rezultati toga istraživanja pokazuju da čak i kratkotrajna izloženost etilen oksidu može znatno povisiti razine adukata hemoglobina. Premda se u zdravstvenom nadzoru u okviru medicine rada proteinski adukti i njihove vrijednosti razmatraju u procjeni dugotrajnoga izlaganja, oni se mogu koristiti i za praćenje akcidentalnih izlaganja. U tim slučajevima izračun dnevnih vrijednosti (tzv. ppm-ekvivalenata) može poslužiti za usporedbu s postojećim procijenjenim vrijednostima

Retropubic, laparoscopic and mini-laparoscopic radical prostatectomy : a prospective assessment of patient scar satisfaction

Published online: 26 October 2014PURPOSE: To compare patient scar satisfaction after retropubic, standard laparoscopic, mini-laparoscopic (ML) and open radical prostatectomy (RP). METHODS: Patients undergoing RP for a diagnosis of localized prostate cancer at a single academic hospital between September 2012 and December 2013 were enrolled in this prospective nonrandomized study. The patients were included in three study arms: open surgery, VLP and ML. A skin stapler was used for surgical wound closure in all cases. Demographic and main surgical outcomes, including perioperative complications, were analyzed. Surgical scar satisfaction was measured using the Patient and Observer Scar Assessment Questionnaire (POSAS) and the two Body Image Questionnaire (BIQ) scales, respectively, recorded at skin clips removal and either at 6 months after surgery. RESULTS: Overall, 32 patients were enrolled and completed the 6 month of follow-up. At clips removal, laparoscopic approaches offered better scar result than open surgery according to the POSAS. However, at 6 months, no differences were detected between VLP and open, whereas ML was still associated with a better scar outcome (p = 0.001). This finding was also confirmed by both BIQ scales, including the body image score (ML 9.8 ± 1.69, open 15.73 ± 3.47, VLP 13.27 ± 3.64; p = 0.001) and the cosmetic score (ML 16.6 ± 4.12, open 10 ± 1.9, LP 12.91 ± 3.59; p = 0.001). Small sample size and lack of randomization represent the main limitations of this study. CONCLUSIONS: ML RP offers a better cosmetic outcome when compared to both open and standard laparoscopic RP, representing a step toward minimal surgical scar. The impact of scar outcome on RP patients' quality of life remains to be determined

Verbal instructions override the meaning of facial expressions

Psychological research has long acknowledged that facial expressions can implicitly trigger affective psychophysiological responses. However, whether verbal information can alter the meaning of facial emotions and corresponding response patterns has not been tested. This study examined emotional facial expressions as cues for instructed threat-of-shock or safety, with a focus on defensive responding. In addition, reversal instructions were introduced to test the impact of explicit safety instructions on fear extinction. Forty participants were instructed that they would receive unpleasant electric shocks, for instance, when viewing happy but not angry faces. In a second block, instructions were reversed (e.g., now angry faces cued shock). Happy, neutral, and angry faces were repeatedly presented, and auditory startle probes were delivered in half of the trials. The defensive startle reflex was potentiated for threat compared to safety cues. Importantly, this effect occurred regardless of whether threat was cued by happy or angry expressions. Although the typical pattern of response habituation was observed, defense activation to newly instructed threat cues remained significantly enhanced in the second part of the experiment, and it was more pronounced in more socially anxious participants. Thus, anxious individuals did not exhibit more pronounced defense activation compared to less anxious participants, but their defense activation was more persistent

Experimental signatures of the mixed axial-gravitational anomaly in the Weyl semimetal NbP

Weyl semimetals are materials where electrons behave effectively as a kind of massless relativistic particles known asWeyl fermions. These particles occur in two flavours, or chiralities, and are subject to quantum anomalies, the breaking of a conservation law by quantum fluctuations. For instance, the number of Weyl fermions of each chirality is not independently conserved in parallel electric and magnetic field, a phenomenon known as the chiral anomaly. In addition, an underlying curved spacetime provides a distinct contribution to a chiral imbalance, an effect known as the mixed axial-gravitational anomaly, which remains experimentally elusive. However, the presence of a mixed gauge-gravitational anomaly has recently been tied to thermoelectrical transport in a magnetic field, even in flat spacetime, opening the door to experimentally probe such type of anomalies in Weyl semimetals. Using a temperature gradient, we experimentally observe a positive longitudinal magnetothermoelectric conductance (PMTC) in the Weyl semimetal NbP for collinear temperature gradients and magnetic fields (DT || B) that vanishes in the ultra quantum limit. This observation is consistent with the presence of a mixed axial-gravitational anomaly. Our work provides clear experimental evidence for the existence of a mixed axial-gravitational anomaly of Weyl fermions, an outstanding theoretical concept that has so far eluded experimental detection

Analysis of Clonal Type-Specific Antibody Reactions in Toxoplasma gondii Seropositive Humans from Germany by Peptide-Microarray

BACKGROUND: Different clonal types of Toxoplasma gondii are thought to be associated with distinct clinical manifestations of infections. Serotyping is a novel technique which may allow to determine the clonal type of T. gondii humans are infected with and to extend typing studies to larger populations which include infected but non-diseased individuals. METHODOLOGY: A peptide-microarray test for T. gondii serotyping was established with 54 previously published synthetic peptides, which mimic clonal type-specific epitopes. The test was applied to human sera (n = 174) collected from individuals with an acute T. gondii infection (n = 21), a latent T. gondii infection (n = 53) and from T. gondii-seropositive forest workers (n = 100). FINDINGS: The majority (n = 124; 71%) of all T. gondii seropositive human sera showed reactions against synthetic peptides with sequences specific for clonal type II (type II peptides). Type I and type III peptides were recognized by 42% (n = 73) or 16% (n = 28) of the human sera, respectively, while type II-III, type I-III or type I-II peptides were recognized by 49% (n = 85), 36% (n = 62) or 14% (n = 25) of the sera, respectively. Highest reaction intensities were observed with synthetic peptides mimicking type II-specific epitopes. A proportion of the sera (n = 22; 13%) showed no reaction with type-specific peptides. Individuals with acute toxoplasmosis reacted with a statistically significantly higher number of peptides as compared to individuals with latent T. gondii infection or seropositive forest workers. CONCLUSIONS: Type II-specific reactions were overrepresented and higher in intensity in the study population, which was in accord with genotyping studies on T. gondii oocysts previously conducted in the same area. There were also individuals with type I- or type III-specific reactions. Well-characterized reference sera and further specific peptide markers are needed to establish and to perform future serotyping approaches with higher resolution

Blogging the Virtual: New Geographies of Domination and Resistance In and Beyond Russia

Russia’s accelerating authoritarian turn has not ignored the internet, and in recent years, the Russian state has clamped down on internet activities that diverge from the statist line, employing a variety of strategies to dominate online spaces. Nevertheless, oppositional voices flourish on the Russian internet, taking shape in independent blogs and videos. This paper explores three political bloggers through surveillant and resistance assemblages, making sense of this contestation through an interpretation of the Deleuzian virtual that underscores the emancipatory potential of online activities for producing more egalitarian configurations, but also taking stock of the ways that these technologies have increased domination. Encompassing the blurriness between digital and corporeal spaces, the paper contributes by revealing new geographies of contestation against state strategies to dominate the Russian internet. Overlapping with but not corresponding to Russian territorial boundaries, these dynamics highlight shifting spaces of power and resistance in the increasingly illiberal world