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

A Comparison of Donor-Acceptor Pairs for Genetically Encoded FRET Sensors: Application to the Epac cAMP Sensor as an Example

We recently reported on CFP-Epac-YFP, an Epac-based single polypeptide FRET reporter to resolve cAMP levels in living cells. In this study, we compared and optimized the fluorescent protein donor/acceptor pairs for use in biosensors such as CFP-Epac-YFP. Our strategy was to prepare a wide range of constructs consisting of different donor and acceptor fluorescent proteins separated by a short linker. Constructs were expressed in HEK293 cells and tested for FRET and other relevant properties. The most promising pairs were subsequently used in an attempt to improve the FRET span of the Epac-based cAMP sensor. The results show significant albeit not perfect correlation between performance in the spacer construct and in the Epac sensor. Finally, this strategy enabled us to identify improved sensors both for detection by sensitized emission and by fluorescent lifetime imaging. The present overview should be helpful in guiding development of future FRET sensors

Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE. NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained

Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS

Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions

Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1  fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex

Measurement of the tt¯tt¯ production cross section in pp collisions at √s=13 TeV with the ATLAS detector

A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb