Examination of the TIGIT, CD226, CD112, and CD155 Immune Checkpoint Molecules in Peripheral Blood Mononuclear Cells in Women Diagnosed with Early-Onset Preeclampsia

Early-onset preeclampsia is a common obstetrical disease with a potential genetic back- ground and is characterized by the predominance of Th1 immune response. However, although many studies investigated the immunological environment in preeclamptic patients, no information is available about the potential role of the TIGIT/CD226/CD112/CD155 immune checkpoint pathway. A total of 37 pregnant women diagnosed with early-onset preeclampsia and 36 control women with appropriately matched gestational age were enrolled in this study. From venous blood, mononu- clear cells were isolated and stored in the freezer. Using multicolor flow cytometry T-, NK cell and monocyte subpopulations were determined. After characterization of the immune cell subsets, TIGIT, CD226, CD112, and CD155 surface expression and intracellular granzyme B content were determined by flow cytometer. Significantly decreased CD226 expression and increased CD112 and CD155 sur- face expression were detected in almost all investigated T-cell, NK cell, and monocyte subpopulations in women diagnosed with preeclampsia compared to the healthy group. Furthermore, reduced TIGIT and granzyme B expression were measured only in preeclamptic CD8+ T cells compared to healthy pregnant women. A decreased level of the activatory receptor CD226 in effector lymphocytes accompanied with an elevated surface presence of the CD112 and CD155 ligands in monocytes could promote the TIGIT/CD112 and/or TIGIT/CD155 ligation, which mediates inhibitory signals. We assume that the inhibition of the immune response via this immune checkpoint pathway might contribute to compensate for the Th1 predominance during early-onset preeclampsia

Genomic Fingerprints of Palaeogeographic History: The Tempo and Mode of Rift Tectonics Across Tropical Africa Has Shaped the Diversification of the Killifish Genus Nothobranchius (Teleostei: Cyprinodontiformes)

This paper reports a phylogeny of the African killifishes (Genus Nothobranchius, Order Cyprinodontiformes) informed by five genetic markers (three nuclear, two mitochondrial) of 80 taxa (seven undescribed and 73 of the 92 recognized species). These short-lived annual fishes occupy seasonally wet habitats in central and eastern Africa, and their distribution coincides largely with the East African Rift System (EARS). The fossil dates of sister clades used to constrain a chronometric tree of all sampled Nothobranchius recovered the origin of the genus at ~13.27 Mya. It was followed by the radiations of six principal clades through the Neogene. An ancestral area estimation tested competing biogeographical hypotheses to constrain the ancestral origin of the genus to the Nilo-Sudan Ecoregion, which seeded a mid-Miocene dispersal event into the Coastal ecoregion, followed closely (~10 Mya) by dispersals southward across the Mozambique coastal plain into the Limpopo Ecoregion. Extending westwards across the Tanzanian plateau, a pulse of radiations through the Pliocene were associated with dispersals and fragmentation of wetlands across the Kalahari and Uganda Ecoregions. We interpret this congruence of drainage rearrangements with dispersals and cladogenic events of Nothobranchius to reflect congruent responses to recurrent uplift and rifting. The coevolution of these freshwater fishes and wetlands is attributed to ultimate control by tectonics, as the EARS extended southwards during the Neogene. Geobiological consilience of the combined evidence supports a tectonic hypothesis for the evolution of Nothobranchius

Photoproduction at collider energies: from RHIC and HERA to the LHC

We present the mini-proceedings of the workshop on ``Photoproduction at collider energies: from RHIC and HERA to the LHC'' held at the European Centre for Theoretical Studies in Nuclear Physics and Related Areas (ECT*, Trento) from January 15 to 19, 2007. The workshop gathered both theorists and experimentalists to discuss the current status of investigations of high-energy photon-induced processes at different colliders (HERA, RHIC, and Tevatron) as well as preparations for extension of these studies at the LHC. The main physics topics covered were: (i) small-$x$ QCD in photoproduction studies with protons and in electromagnetic (aka. ultraperipheral) nucleus-nucleus collisions, (ii) hard diffraction physics at hadron colliders, and (iii) photon-photon collisions at very high energies: electroweak and beyond the Standard Model processes. These mini-proceedings consist of an introduction and short summaries of the talks presented at the meeting

First results from the Cassini radio occultations of the Titan ionosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95691/1/jgra19260.pd

The Future of Child and Adolescent Clinical Psychopharmacology: A Systematic Review of Phase 2, 3, or 4 Randomized Controlled Trials of Pharmacologic Agents Without Regulatory Approval or for Unapproved Indications

The pace of development and implementation of novel medications in child and adolescent psychiatry has remained slow. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010 to 08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia. We also included RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥1 primary outcome, 43 (19%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010–08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes

Global 30–240 keV proton precipitation in the 17–18 April 2002 geomagnetic storms: 3. Impact on the ionosphere and thermosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94894/1/jgra18704.pd

Global parameterization and validation of a two-leaf light use efficiency model for predicting gross primary production across FLUXNET sites:TL-LUE Parameterization and Validation

Light use efficiency (LUE) models are widely used to simulate gross primary production (GPP). However, the treatment of the plant canopy as a big leaf by these models can introduce large uncertainties in simulated GPP. Recently, a two-leaf light use efficiency (TL-LUE) model was developed to simulate GPP separately for sunlit and shaded leaves and has been shown to outperform the big-leaf MOD17 model at six FLUX sites in China. In this study we investigated the performance of the TL-LUE model for a wider range of biomes. For this we optimized the parameters and tested the TL-LUE model using data from 98 FLUXNET sites which are distributed across the globe. The results showed that the TL-LUE model performed in general better than the MOD17 model in simulating 8 day GPP. Optimized maximum light use efficiency of shaded leaves (εmsh) was 2.63 to 4.59 times that of sunlit leaves (εmsu). Generally, the relationships of εmsh and εmsu with εmax were well described by linear equations, indicating the existence of general patterns across biomes. GPP simulated by the TL-LUE model was much less sensitive to biases in the photosynthetically active radiation (PAR) input than the MOD17 model. The results of this study suggest that the proposed TL-LUE model has the potential for simulating regional and global GPP of terrestrial ecosystems, and it is more robust with regard to usual biases in input data than existing approaches which neglect the bimodal within-canopy distribution of PAR

Search for New Physics Using Quaero: A General Interface to D0 Event Data

We describe Quaero, a method that i) enables the automatic optimization of searches for physics beyond the standard model, and ii) provides a mechanism for making high energy collider data generally available. We apply Quaero to searches for standard model WW, ZZ, and ttbar production, and to searches for these objects produced through a new heavy resonance. Through this interface, we make three data sets collected by the D0 experiment at sqrt(s)=1.8 TeV publicly available.Comment: 7 pages, submitted to Physical Review Letter