The effect of cadmium on the bovine in vitro oocyte maturation and early embryo development

Common pollutants such as heavy metals and cadmium is among those with high environmental concerns. In vivo studies had shown that cadmium (Cd) causes oocyte degeneration and embryo mortality, and lowers pregnancy rates in mammals. However, there is limited information available about direct effects of Cd on oocyte maturation and/or embryo development. This study was aimed to investigate if Cd has any effect on the oocyte maturation and/or embryo development in vitro. Bovine COCs were collected from the slaughter house and cultured for 24 h in serum-free media only (Controls) or supplemented with 0.2, 2.0 and 20.0 μM CdCl2. At 24 h cumulus cell expansion was assessed in all COCs. COCs were either denuded and stained for determination of nuclear maturation or fertilized for assessment of subsequent embryo development. Cd at the lowest concentration (0.2 μM) did not affect any of the parameters studied. However, at higher concentrations (2.0 and 20.0 μM) it significantly (P < 0.05) reduced the percentage of fully-expanded COCs and significantly (P < 0.05) increased the percentage of partially and/or non-expanded COCs compared to controls and 0.2 μM. Cadmium at higher concentrations (2.0 and 20.0 μM) also significantly (P < 0.01) reduced the percentage of oocytes reaching metaphase II stage compared to controls and 0.2 μM. Post-fertilization cleavage rate in presumptive zygotes and blastocyst development significantly (P < 0.05) reduced 0.2, 2.0 and 20.0 μM CdCl2 compared to the controls (0.0 μM). In conclusion, these results suggest that Cd had direct detrimental effects on the bovine oocyte maturation and its developmental competence

Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

Blood DCs activated with R848 and poly(I:C) induce antigen-specific immune responses against viral and tumor-associated antigens

Monocyte-derived Dendritic cells (DCs) have successfully been employed to induce immune responses against tumor-associated antigens in patients with various cancer entities. However, objective clinical responses have only been achieved in a minority of patients. Additionally, generation of GMP-compliant DCs requires time- and labor-intensive cell differentiation. In contrast, Blood DCs (BDCs) require only minimal ex vivo handling, as differentiation occurs in vivo resulting in potentially better functional capacities and survival. We aimed to identify a protocol for optimal in vitro activation of BDCs including the three subsets pDCs, cDC1s, and cDC2s. We evaluated several TLR ligand combinations and demonstrated that polyinosinic:polycytidylic acid poly(I:C) and R848, ligands for TLR3 and TLR7/8, respectively, constituted the optimal combination for inducing a positive co-stimulatory profile in all BDC subsets. In addition, TLR3 and TLR7/8 activation led to high secretion of IFN-α and IL-12p70. Simultaneous as opposed to separate tailored activation of pDCs and cDCs increased immunostimulatory capacities, suggesting that BDC subsets engage in synergistic cross-talk during activation. Stimulation of BDCs with this protocol resulted in enhanced migration, high NK-cell activation, and potent antigen-specific T-cell induction.We conclude that simultaneous activation of all BDC subsets with a combination of R848 + poly(I:C) generates highly immunostimulatory DCs. These results support further investigation and clinical testing, as standalone or in conjunction with other immunotherapeutic strategies including adoptive T-cell transfer and checkpoint inhibition

First US Performance Measurements of Next Generation 3D USCT 2.5 Transducers

The KIT’s 3D Ultrasound Computer Tomography (USCT) II system has a multistatic setup of 2041 ultrasound transducers with approx. 1.5 MHz 6dB bandwidth and 36◦ 3 dB opening angle for 2.5 MHz. To increase the region of interest for a next USCT generation, the opening angle should be increased to approx. 60◦ and the bandwidth doubled. To increase the opening angle the size of the transducer elements was decreased to approximately half the size. A circular aperture was chosen for homogenicity of the radiation pattern in 3D. The transducer design utilizes piezo-fibres by the established Fraunhofer IMT piezo-fibre composite technology. The fibres were fabricated from PZT powder using the polysulfone spinning process. 17 fibres were positioned with a mechanical mask and filled with a matrix of epoxy. From this rod piezo composite discs were sawed and polarized. Electrodes were generated by silver-filled epoxy adhesive on the top and bottom side. Materials for acoustic backing is a Tungsten-Polyurethane composite and for acoustic matching ia aluminium oxide composite material (TMM4). Ultrasound characteristics were evaluated quantitatively with a Onda HNC-400 hydrophone in a 3-axis water tank for a randomly selected sample transducer (see Fig. a.)). Characteristics evaluated were the pressure field as function over frequency and angle in the far-field (see Fig. b.)), following the use-case. For excitation a linear encoded chirp was used, for SNR improvements averaging of measurements (64 to 256 times) was conducted. The analysis compensated for the hydrophon’s frequency and angular damping characteristics. The presented results show that the desired characteristics were mostly achieved: the 6 dB bandwidth could be vastly improved by roughly 200% (see Fig. d.)). The 6 dB pressure opening angle was approx. 50◦ (see Fig. c.)), not completly fullfilling the simulated expectations, an improvement by 31% was achieved. The results are promising for the next 3D USCT III generation

Reservoir fracture characterizations from seismic scattered waves

The measurements of fracture parameters, such as fracture orientation, fracture density and fracture compliance, in a reservoir is very important for field development and exploration. Traditional seismic methods for fracture characterization include shear wave birefringence (Gaiser and Dok, 2001; Dok et al., 2001; Angerer et al., 2002; Vetri et al., 2003) and amplitude variations with offset and azimuth (AVOA) (Ruger, 1998; Shen et al., 2002; Hall et al., 2003; Liu et al., 2010; Lynn et al., 2010). These methods are based on the equivalent medium theory with the assumption that fracture dimension and spacing are small relative to the seismic wave length, so a fracture zone behaves like an equivalent anisotropic medium. But fractures on the order of seismic wave length are also very important for enhanced oil recovery, and they are one of the important subsurface scattering sources that generate scattered seismic waves. Willis et al. (2006) developed the Scattering Index method to extract the fracture scattering characteristics by calculating the transfer funtion of a fracture zone. Fang et al. (2011) proposed a modification of the SI method (the Fracture Transfer Function (FTF) method) that leads to a more robust fracture characterization. In this paper, we use both laboratory data and field data to explore the capability of the FTF method.Eni-MIT Energy Initiative Founding Member Progra

Mackintosh lecture: Association and cognition: two processes, one system

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.There is another ORE record for this item: http://hdl.handle.net/10871/33264This paper argues that the dual-process position can be a useful first approximation when studying human mental life, but it cannot be the whole truth. Instead, we argue that cognition is built on association, in that associative processes provide the fundamental building blocks that enable propositional thought. One consequence of this position is to suggest that humans are able to learn associatively in a similar fashion to a rat or a pigeon, but another is that we must typically suppress the expression of basic associative learning in favour of rule-based computation. This stance conceptualizes us as capable of symbolic computation, but acknowledges that, given certain circumstances, we will learn associatively and, more importantly, be seen to do so. We present three types of evidence that support this position: The first is data on human Pavlovian conditioning that directly supports this view. The second is data taken from task switching experiments that provides convergent evidence for at least two modes of processing, one of which is automatic and carried out “in the background”. And the last suggests that when the output of propositional processes is uncertain, then the influence of associative processes on behaviour can manifest

Expanding Access to Treatment for Hepatitis C in Resource-Limited Settings: Lessons From HIV/AIDS

This article summarizes key lessons from scaling up care and treatment for human immunodeficiency virus/AIDS during the last decade to support increased access to treatment and care for hepatitis C virus infection in resource-limited setting

Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis

Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner. This reduction in exocytotic speed was consistent for two observed modes of exocytosis, full and partial release. Partial release events, which only occurred in the bleb cell model due to the higher tension in the system, exhibited amperometric spikes with three distinct shapes. In addition to the classic transient, some spikes displayed a current ramp or plateau following the maximum peak current. These post spike features represent neurotransmitter release from a dilated pore before constriction and show that enhancing membrane rigidity via cholesterol adds resistance to a dilated pore to re-close. This implies that the cholesterol dependent biophysical properties of the membrane directly affect the exocytosis kinetics and that membrane tension along with membrane rigidity can influence the fusion pore dynamics and stabilization which is central to regulation of neurochemical release

Nan-O-Style – experiments and arts

In this project, high school students (aged 16-17) tested various protocols of experiments in nanotechnology and evaluated them whether such experiments could also be performed by middle school students (aged 11-15) or even elementary school students (aged 6-10). Protocols pre-selected and provided by the instructing team consisting of Sciencetainment and the Department of Biosciences, University of Salzburg were applied. Laboratory techniques such as thin-layer chromatography, measuring the contact angle by high-resolution 3D microscopy and analyzing and constructing surface layers represented some of the experiments performed. Moreover, students produced short video clips and images and designed photo-collages out of microscopic and electron microscopic pictures. Hence, the school students acquired a number of soft skills during this special science day