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STUDY QUESTION What are the effects of thin ovarian grafts compared with grafts of the standard thickness on follicle loss post-transplantation? SUMMARY ANSWER Transplantation of reduced-thickness ovarian grafts led to intense activation and ‘burn-out’ a short time after transplantation resulting in significant folllicle loss. WHAT IS KNOWN ALREADY Transplantation of fresh and frozen–thawed ovarian tissue has been proved successful, but techniques vary and are not optimised, often resulting in significant follicular loss. Follicle loss is mostly related to the freezing–thawing process and to post-transplantation hypoxia. STUDY DESIGN, SIZE, DURATION Bovine ovarian tissue strips (n = 55) were prepared in two groups of conventional-thickness strips (1–2 mm) or thin strips (0.5–0.9 mm). Fresh or frozen–thawed samples were xenotransplanted into sterilized immune-deficient mice (n = 49). Non-transplanted conventional size fresh samples were used as controls (n = 6). Grafts from all study groups were recovered after 7 days for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Morphometric differential counting of follicle classes was performed by two observers. Immunohistochemistry was conducted for proliferation (Ki67), cortical fibrosis (Masson tri-chrome) and blood-vessel density (CD31). Results were expressed as the mean number of dormant or growing follicle (GF) type per section or total follicle counts per graft. Blood-vessel density was calculated per mm2. P-values <0.05 were considered statistically significant. MAIN RESULTS AND THE ROLE OF CHANCE The loss of all follicle types, and most noteably of primordial follicles (PMFs), was observed 7 days post-transplantation (P < 0.05). The relatively high number of GFs and the positive Ki67 staining in all recovered grafts indicated that follicle activation was depleting the resting follicle pool. The reduced graft thickness had an adverse effect on the number of recovered follicles, especially on the resting non-GFs in the fresh, and more so in the frozen-thawed, samples (P < 0.05). Extensive stromal fibrosis and high blood-vessel density were observed in all grafts with no advantage in the thin prepared grafts. LIMITATIONS, REASONS FOR CAUTION This study used only one species of ovaries (bovine) for xenotransplantation. The immediate post-transplantation events were not visualized directly nor were the molecules involved in follicle activation studied. WIDER IMPLICATIONS OF THE FINDINGS Follicle activation and ‘burn-out’ appear to be important in follicle loss after transplantation. Reducing graft thickness in an attempt to improve freezing conditions and reduce post-transplantation ischemia has adverse effects on the graft follicle pool due to increased activation and loss. Agents which prevent ‘burn-out’ will potentially improve follicle pool survival. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by research grants from the Israeli Science Foundation (No. 1675/10), the Israeli Jack Craps foundation and the Israel Cancer Research Fund (ICRF No. 12-3081). The authors have no competing interest to declare. [ABSTRACT FROM AUTHOR]

A new class of surface-structured RO membranes was developed with a hydrophilic brush layer of terminally anchored polymer chains resulting in fouling resistant membranes of low mineral scaling propensity and high permeability. The approach is based on free-radical graft polymerization of a suitable monomer, onto the active polyamide (PA) layer of a thin film composite (PA-TFC) membrane, post-surface activation with an impinging atmospheric pressure plasma source. Two types of nano-structured (SNS) RO membranes (SNS-PA-TFC) were synthesized based on methacrylic acid (MAA-SNS-PA-TFC) and acrylamide (AA-SNS-PA-TFC) graft polymerization. The poly(methacrylic acid) and poly(acrylamide) brush layers, on the PA surface, resulted in RO membranes of significantly lower mineral scaling propensity, evaluated with respect to the mineral scalant calcium sulfate dihydrate, compared with commercial RO membrane (LFC1) of about the same salt rejection (∼95%) and surface roughness (∼70 nm). Direct membrane surface imaging indicated that the rate of nucleation and thus mineral scaling were reduced owing to the polymer brush layer. Fouling resistance of the SNS-PA-TFC membranes was also demonstrated with respect to model foulants (the protein BSA and alginic acid). The MAA-SNS-PA-TFC and AA-SNS-PA-TFC membranes had a negatively charged and near neutral surfaces, respectively, with water contact angles somewhat lower for the former and higher for the latter membranes relative to the LFC1 membrane. The AA-SNS-PA-TFC membrane displayed lower mineral scaling propensity than the MAA based membrane, although its alginic acid fouling resistance was inferior, despite its lower surface roughness (25–33 nm) relative to the MAA-SNS-PA-RFC (∼60–80 nm) and LFC1 (∼73 nm) membranes. [ABSTRACT FROM AUTHOR]

Abstract  Although magnetic resonance imaging (MRI) is one of the most important imaging modalities of the central nervous system (CNS), one of the main drawbacks of MRI is its limited specificity. This can potentially be partially alleviated by target-specific contrast agents. In the present paper we describe a simple high yield synthesis of two such gadolinium-based spiperone targeted MRI contrast agents, 1a and 1b. The R1 relaxivities of 1a and 1b were evaluated and found to be 5.94 and 8.31 mM−1 s−1, respectively at 9.4T, while their R2 relaxivities at the same magnetic field were found to be 18.05 and 22.60 mM−1 s−1, respectively. In addition and very importantly compound 1a, which is a gadolinium-based, spiperone-targeted MRI contrast agent, was found to preserve some of the spiperone affinity toward the dopamine D2 receptor. Compounds 1a and 1b thus represent potential agents for in vitro dopamine receptor imaging using MRI in experimental models. [ABSTRACT FROM AUTHOR]

The effect of hydration repulsion on the agglomeration of nanoparticles in aqueous suspensions was investigated via the description of agglomeration by the Smoluchowski coagulation equation using constant number Monte–Carlo simulation making use of the classical DLVO theory extended to include the hydration repulsion energy. Evaluation of experimental DLS measurements for TiO2, CeO2, SiO2, and α-Fe2O3 (hematite) at high IS (up to 900 mM) or low |ζ-potential| (≥1.35 mV) demonstrated that hydration repulsion energy can be above electrostatic repulsion energy such that the increased overall repulsion energy can significantly lower the agglomerate diameter relative to the classical DLVO prediction. While the classical DLVO theory, which is reasonably applicable for agglomeration of NPs of high |ζ-potential| (∼>35 mV) in suspensions of low IS (∼<1 mM), it can overpredict agglomerate sizes by up to a factor of 5 at high IS or low |ζ-potential|. Given the potential important role of hydration repulsion over a range of relevant conditions, there is merit in quantifying this repulsion energy over a wide range of conditions as part of overall characterization of NP suspensions. Such information would be of relevance to improved understanding of NP agglomeration in aqueous suspensions and its correlation with NP physicochemical and solution properties. [ABSTRACT FROM AUTHOR]

The transcription factor forkhead box P3 (FOXP3 in humans; Foxp3 in mice) controls the development and function of regulatory T cells (Treg). In mice, CD4+CD25− T cells do not express Foxp3 following TCR activation. Whether FOXP3 is a common activation-induced molecule in human T cells—hence not Treg restricted—is currently a controversial issue. As FOXP3 can significantly modulate the function of T cells, understanding the mode (and regulation) of FOXP3 expression in human T cells is vital. Here we show that in conventional CD4+CD25− T cells, the induction of FOXP3 expression following TCR activation is both restricted to a fraction of the progeny and transient. Moreover, FOXP3 expression in vivo is particularly infrequent in activated effector CD4+ T cells that accumulate within inflamed joints. We next demonstrate that the repression of FOXP3 transcription in resting conventional human CD25− T cells is linked to complete methylation of an evolutionarily conserved intronic CpG island. The dense methylation pattern is furthermore inherited after activation by progeny. This intronic CpG island, on the other hand, is frequently unmethylated in CD4+CD25+ T cells. Importantly, blocking maintenance DNA methylation, by pharmacological inhibition of DNA methyltransferase-1, induced significant and stable activation-dependent FOXP3 expression in cycling conventional T cells, which was further amplified by co-treatment with transforming growth factor β. In contrast to natural Treg, such induced CD4+FOXP3+ T cells could produce pro-inflammatory cytokines upon activation. These results indicate that DNA methylation normally restricts FOXP3 transcription in conventional human T cells. [ABSTRACT FROM AUTHOR]