The beauty of symmetry: siRNA phosphorodithioate modifications reduce stereocomplexity, ease analysis, and can improve potency.

Phosphorothioates (PSs) can be essential in stabilizing therapeutic oligonucleotides against enzymatic degradation. However, unless synthesis is performed with stereodefined amidites, each PS introduces a chemically undefined stereocenter, resulting in 2 unique molecules in the final product and affecting downstream analytics and purification. Replacing the second non-bridging oxygen with sulfur results in phosphorodithioate (PS2) linkages, thereby removing the stereocenter.

Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2.

The retrograde transport inhibitor Retro-2 has a protective effect on cells and in mice against Shiga-like toxins and ricin. Retro-2 causes toxin accumulation in early endosomes and relocalization of the Golgi SNARE protein syntaxin-5 to the endoplasmic reticulum. The molecular mechanisms by which this is achieved remain unknown.

MicroRNA 199a-5p Attenuates Retrograde Transport and Protects against Toxin-Induced Inhibition of Protein Biosynthesis.

Retrograde transport (RT) allows cells to retrieve receptors and other cellular cargoes for delivery to the Golgi apparatus, contributing to the maintenance of cellular homeostasis. This transport route is also commonly used by several bacterial toxins to exert their deleterious actions on eukaryotic cells. While the retrograde transport process has been well characterized, the contribution of microRNAs (miRNAs) in regulating this cellular transport mechanism remains unknown.

Retrograde transport is not required for cytosolic translocation of the B-subunit of Shiga toxin.

Antigen-presenting cells have the remarkable capacity to transfer exogenous antigens to the cytosol for processing by proteasomes and subsequent presentation on major histocompatibility complex class-I (MHC-I) molecules, a process termed cross-presentation. This is the target of biomedical approaches that aim to trigger a therapeutic immune response. The receptor-binding B-subunit of Shiga toxin (STxB) has been developed as an antigen delivery tool for such immunotherapy applications.

The pattern of ocular dominance columns in cat primary visual cortex: intra- and interindividual variability of column spacing and its dependence on genetic background.

We present a comprehensive analysis of the intrinsic variability of the periodicity of ocular dominance columns in cat primary visual cortex (area 17) and its relationship to genetic background and visual experience. We characterized the intra-areal and interindividual variability of column spacing in a large set (n = 49) of ocular dominance patterns adapting a recently developed technique for the two-dimensional analysis of orientation column patterns. Patterns were obtained from three different cat colonies (termed F, M and D), the cats having either normal visual experience or experimentally induced strabismus.

The growth of cat cerebral cortex in postnatal life: a magnetic resonance imaging study.

To follow up the development of an individual brain over time and to measure its growth we have analysed the brains of individual cats from postnatal day 12 to adulthood using magnetic resonance imaging. From the anatomical images, four parameters were calculated: anteroposterior extent of the telencephalon, brain volume, neocortical surface area and neocortical volume. The development of the anteroposterior extent was similar in all cats.

Postnatal growth and column spacing in cat primary visual cortex.

The primary visual cortex (area 17) of cats continues to grow substantially during early postnatal development. To assess the implications of this growth for the organization of visual cortical maps, we analysed both postnatal growth of area 17 and the spacing of ocular dominance columns in the same animals using 2-deoxyglucose autoradiography to label cortical activation patterns. Quantitative analyses of area size and column spacing were performed on flat-mount sections of the cortical hemispheres.

Two-dimensional analysis of the spacing of ocular dominance columns in normally raised and strabismic kittens.

In the primary visual cortex of cats, ferrets and macaque monkeys, the thalamocortical afferents conveying signals from the two eyes terminate in alternating regions of layer IV known as ocular dominance columns. Previous experiments have indicated that the periodicity of these columns can be influenced by visual experience: compared to normally raised animals both strabismic cats and cats raised with alternating monocular exposure displayed an increased spacing of adjacent ocular dominance columns in the primary visual cortex (area 17). However, recently it was shown that the formation of ocular dominance columns begins much earlier than previously supposed, indicating that early visual experience might only have a limited influence on the development of the spatial pattern of ocular dominance columns.