Evidence for disparity detecting neurones in the human visual system

1. It is known that adaptation to a grating pattern causes a rise in the contrast threshold for test gratings of similar spatial frequency and orientation.

2. We find this after-effect also to be disparity-specific. Adaptation to a grating at zero horizontal disparity (at the same distance as the fixation point) causes a greater elevation of threshold for patterns at the same disparity than for those at nearby disparities, closer or more distant than the fixation point.

3. Adaptation to a grating at some disparity other than zero causes a disparity-specific elevation of threshold centred on the adapting disparity.

4. This finding also applies if the observer adapts to a grating but single bright bars are used as the test stimuli.

5. The disparity-specific `tuning curves' revealed by these techniques are quite broad, having a half-width at half-amplitude of several min of disparity.

6. Adaptation to a grating at one disparity causes an apparent change in the distance of test gratings at nearby disparities.

7. We compare these psychophysical experiments with the properties of disparity-selective binocular neurones in the visual cortex of cats and monkeys.

     

Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: Implications for the possible role of dietary fibre in the prevention of large-bowel cancer

The purpose of this study was to determine whether cultured colonic adenoma and carcinoma cells undergo apoptosis (programmed cell death) in vitro and whether specific growth and dietary factors, thought to be involved in the control of growth and differentiation of human colonic cells, could induce cell death through apoptosis. In cell lines originating from 6 colorectal adenomas and 7 carcinomas, spontaneous apoptosis was observed. Sodium butyrate, a naturally occurring fatty acid, is present in the human large bowel in millimolar amounts as a result of bacterial fermentation of dietary fibre. Sodium butyrate, at physiological concentrations, induced apoptosis in 2 adenoma cell lines, RG/C2 and AA/C1, and in the carcinoma cell line PC/JW/F1. In contrast, transforming growth factor β₁, which is thought to have an important role in the control of growth in colonic epithelium, did not induce apoptosis. Neither RG/C2 nor PC/JW/F1 contain wild-type p53, therefore this tumour-suppressor gene is not required to mediate signals for the induction of apoptosis in colonic tumour cells. Our studies report the induction of apoptosis in colonic tumour cells by the naturally occurring fatty acid sodium butyrate. Since sodium butyrate is produced by bacterial fermentation of dietary fibre, the observation that this fatty acid can induce apoptosis could, in part, explain why a high-fibre diet appears to be protective against colon cancer. Escape from the induction of programmed cell death may be an important event in colorectal carcinogenesis.     

Multidetector Computed Tomography to Facilitate Transcatheter Aortic Valve Implantation

Minimally invasive balloon expandable transcatheter aortic valve replacement (TAVR) is currently the standard of care for patients with inoperable severe symptomatic aortic stenosis and is an acceptable alternative to traditional aortic valve replacement in selected high-risk operable patients. Multidetector computed tomography (MDCT) is an integral component of diagnostic workup prior to TAVR. We review the pivotal role of MDCT in patient selection by discussing pre-procedural assessment of iliofemoral, aortic root, and annular geometry. We summarize how MDCT can help guide percutaneous vascular access as well as accurately determine the correct co-axial valve plane and transcatheter valve size. Finally, we discuss how MDCT provides important information about long-term valve durability by assessing valve eccentricity, leaflet and stent integrity, valve recoil, and valve migration.     

Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages

Background and purpose:

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo.

Experimental approach:

Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation.

Key results:

Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-κB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor PP2.

Conclusions and implications:

Our findings suggest a selective role for NOD1 in VSM cells, and highlight NOD1 as a potential novel therapeutic target for the treatment of vascular inflammation.