Trajectory Discrimination and Peripersonal Space Perception in Newborns

The ability to discriminate the trajectories of moving objects is highly adaptive and fundamental for physical and social interactions. Therefore, we could reasonably expect sensitivity to different trajectories already at birth, as a precursor of later communicative and defensive abilities. To investigate this possibility, we measured newborns' looking behavior to evaluate their ability to discriminate between visual stimuli depicting motion along different trajectories happening within the space surrounding their body. Differently from previous studies, we did not take into account defensive reactions, which may not be elicited by impending collision as newborns might not categorize approaching stimuli as possible dangers. In two experiments, we showed that newborns display a spontaneous visual preference for trajectories directed toward their body. We found this visual preference when visual stimuli depicted motion in opposite directions (approaching vs. receding) as well as when they both moved toward the peripersonal space and differed only in their specific target (i.e., the body vs. the space around it). These findings suggest that at birth human infants seem to be already equipped with visual mechanisms predisposing them to perceive their presence in the environment and to adaptively focus their attention on the peripersonal space and their bodily self

Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study

BACKGROUND: The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). METHODS: All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. RESULTS: 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p < 0.0001). The most frequently prescribed antiretrovirals were zidovudine with lamivudine (149; 25 %) and efavirenz [329, 55 %] at HCB and emtricitabine with tenofovir (899; 51 %) and efavirenz [681, 39 %] at RFH. At HCB, a median of 2 CD4 count measurements in the first year of cART were taken, compared to 5 at RFH (p < 0.0001). Median (IQR) CD4 cell increase after 12 months was +211 (+86, +359) and +212 (+105, +318) respectively. 287 (48 %) individuals from HCB and 1452 (82 %) from RFH had an available viral load measurement, of which 271 (94 %) and 1280 (88 %) were <400 copies/mL (p < 0.0001). After 36 months, comparable percentages had made at least one antiretroviral switch (77 % HCB vs. 78 % RFH; p = 0.23). However, switches for toxicity/patient choice were more common at RFH. After 12 and 36 months of cART 3 % and 8 % of individuals died at HCB, versus 2 % and 4 % at RFH (p < 0.0001). CONCLUSION: In middle-income countries, cART is usually started at an advanced stage of HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens

Contact complete integrability

Complete integrability in a symplectic setting means the existence of a Lagrangian foliation leaf-wise preserved by the dynamics. In the paper we describe complete integrability in a contact set-up as a more subtle structure: a flag of two foliations, Legendrian and co-Legendrian, and a holonomy-invariant transverse measure of the former in the latter. This turns out to be equivalent to the existence of a canonical $\R\ltimes \R^{n-1}$ structure on the leaves of the co-Legendrian foliation. Further, the above structure implies the existence of $n$ contact fields preserving a special contact 1-form, thus providing the geometric framework and establishing equivalence with previously known definitions of contact integrability. We also show that contact completely integrable systems are solvable in quadratures. We present an example of contact complete integrability: the billiard system inside an ellipsoid in pseudo-Euclidean space, restricted to the space of oriented null geodesics. We describe a surprising acceleration mechanism for closed light-like billiard trajectories

Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation

Copyright © 2006 Company of BiologistsOocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-ß (TGFß) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFß1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFß superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFß1 and activin-A bioactivity, demonstrating its specificity. The TGFßR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFß1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFß superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This cell-signalling pathway may also have relevance in the hypothalamic-pituitary axis and in germ-somatic cell interactions in the testis.Robert B. Gilchrist, Lesley J. Ritter, Samu Myllymaa, Noora Kaivo-Oja, Rebecca A. Dragovic, Theresa E. Hickey, Olli Ritvos and David G. Mottershea

The quality of sliced carrots affected by modified polyethylene foil and storage temperatures

The aim of this study was to examine the influence of different additive contents for oxygen absorption (5, 10 and 15%) in low-density polyethylene (PELD) plastic foils and storage temperatures (4 and 28 °C) on the quality and shelf-life of sliced carrots during storage. Quality and storage-life of packaged carrots slices were determined by observing changes of mass, total carotenoide pigments, microbial counts (mesophilic aerobic bacteria, enterobacteria, sulphite-reducing clostridia, yeast and moulds), sensory quality and texture by the use of penetrometer. The PELD foils modified with 10 and 15% of oxygen absorber (O2, CO2 and N2 permeability at 4 °C of around 700 ml m-2d-1atm-1) were the most suitable for the storage and prevention of deterioration of minimally processed carrots. Findings indicated that in these foils the best quality and shelf-life of carrot were maintained by 6 days of storage at 4 °C, without significant changes in parameters studied. The absorber for oxygen added to the foil had no influence on the permeability to CO2, O2and N2. The permeability of foils, which were used for carrot packaging increased by the increase of storage temperature to 28 °C and decreased by decreasing the temperature to 4 °C, and was not significantly affected by the additive content either. In the same time the diffusion constants of unused and used PELD foils for carrot packaging at 4 °C and 28 °C changed according to the change of film permeability during storage at those temperatures

On Nonperturbative Calculations in Quantum Electrodynamics

A new approach to nonperturbative calculations in quantum electrodynamics is proposed. The approach is based on a regular iteration scheme for solution of Schwinger-Dyson equations for generating functional of Green functions. The approach allows one to take into account the gauge invariance conditions (Ward identities) and to perform the renormalization program. The iteration scheme can be realized in two versions. The first one ("perturbative vacuum") corresponds to chain summation in the diagram language. In this version in four-dimensional theory the non-physical singularity (Landau pole) arises which leads to the triviality of the renormalized theory. The second version ("nonperturbative vacuum") corresponds to ladder summation and permits one to make non-perturbative calculations of physical quantities in spite of the triviality problem. For chiral-symmetrical leading approximation two terms of the expansion of the first-step vertex function over photon momentum are calculated. A formula for anomalous magnetic moment is obtained. A problem of dynamical chiral symmetry breaking (DCSB) is considered, the calculations are performed for renormalized theory in Minkowsky space. In the strong coupling region DCSB-solutions arise. For the renormalized theory a DCSB-solution is also possible in the weak coupling region but with a subsidiary condition on the value of $\alpha$.Comment: 31 pages, Plain LaTex, no figures. Journal version: some discussion and refs. are adde

Cardiac and Pulmonary Dosimetric Parameters in Lung Cancer Patients Undergoing Post-Operative Radiation Therapy in the Real-World Setting

Purpose/Objective(s): The recently published Lung ART trial reported increased rates of cardiac and pulmonary toxicity in the post-operative radiation therapy arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of real-world practice. The purpose of this study is to examine heart and lung dose exposure in patients receiving post-operative radiation therapy for non-small cell lung cancer (NSCLC) across a statewide consortium. Materials/Methods: From 2012 to 2020, 377 patients at 27 academic and community centers within the Michigan Radiation Oncology Quality Consortium (MROQC) underwent surgical resection followed by post-operative radiation therapy for non-metastatic NSCLC. Demographic and dosimetric data were prospectively collected for these patients. Rates of 3D-CRT and IMRT use were analyzed. Mean heart dose (MHD), heart V5, heart V35, mean lung dose (MLD), lung V20, target volume and minimum dose to 95% PTV were calculated for these patients and the reported dosimetric parameters were stratified by treatment modality. Results: 51% of patients in this cohort had N2 disease at the time of surgery, 18% had a positive margin. 65.8% of patients were treated with IMRT compared to 32.1% treated with 3D-CRT. Average MHD for all patients was 10.3 Gy, mean Heart V5 was 40.3% and mean heart V35 was 12.6%. Average MLD was 11.2 Gy and mean lung V20 was 18.9%. These dosimetric parameters did not significantly differ based on treatment modality, with MHD and MLD 9.9 Gy and 10.1 Gy, respectively, for patients treated with 3D-CRT compared to 10.6 Gy and 11.8 Gy for patients treated with IMRT. Conclusion: Cardiac and lung dosimetric parameters for patients receiving post-operative radiation therapy for NSCLC are similar to the dosimetric characteristics reported in Lung ART. The mean heart and mean lung doses observed are slightly lower (MHD 10.3 Gy, MLD 11.2 Gy) compared to Lung ART (MHD 13 Gy, MLD 13 Gy), possibly owing to increased use of IMRT. These data support application of Lung ART\u27s findings outside of the clinical trial setting

Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition

Release of oxidizing fluids in subduction zones recorded by iron isotope zonation in garnet

Subduction zones are key regions of chemical and mass transfer between the Earth’s surface and mantle. During subduction, oxidized material is carried into the mantle and large amounts of water are released due to the breakdown of hydrous minerals such as lawsonite. Dehydration accompanied by the release of oxidizing species may play a key role in controlling redox changes in the subducting slab and overlying mantle wedge. Here we present measurements of oxygen fugacity, using garnet–epidote oxybarometry, together with analyses of the stable iron isotope composition of zoned garnets from Sifnos, Greece. We find that the garnet interiors grew under relatively oxidized conditions whereas garnet rims record more reduced conditions. Garnet δ56Fe increases from core to rim as the system becomes more reduced. Thermodynamic analysis shows that this change from relatively oxidized to more reduced conditions occurred during lawsonite dehydration. We conclude that the garnets maintain a record of progressive dehydration and that the residual mineral assemblages within the slab became more reduced during progressive subduction-zone dehydration. This is consistent with the hypothesis that lawsonite dehydration accompanied by the release of oxidizing species, such as sulfate, plays an important and measurable role in the global redox budget and contributes to sub-arc mantle oxidation in subduction zones

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion