Syntactic sequencing in Hebbian cell assemblies

Hebbian cell assemblies provide a theoretical framework for the modeling of cognitive processes that grounds them in the underlying physiological neural circuits. Recently we have presented an extension of cell assemblies by operational components which allows to model aspects of language, rules, and complex behaviour. In the present work we study the generation of syntactic sequences using operational cell assemblies timed by unspecific trigger signals. Syntactic patterns are implemented in terms of hetero-associative transition graphs in attractor networks which cause a directed flow of activity through the neural state space. We provide regimes for parameters that enable an unspecific excitatory control signal to switch reliably between attractors in accordance with the implemented syntactic rules. If several target attractors are possible in a given state, noise in the system in conjunction with a winner-takes-all mechanism can randomly choose a target. Disambiguation can also be guided by context signals or specific additional external signals. Given a permanently elevated level of external excitation the model can enter an autonomous mode, where it generates temporal grammatical patterns continuously.     

How Daphnia cope with algae selected for inedibility in long- running microcosms

Macro video records of restrained feeding Daphnia enabled usto measure simultaneously carapace gape, claw rejection rate,filter limb beat rate, and mandible movement rate. We comparedthe effects of high and low concentrations of highly ediblealgae and of inedible algae, the latter selected by long-termDaphnia grazing in oligotrophic microcosms. Inedible algae slowedthe filtering process and influenced the carapace gape (wideningat low concentration and narrowing at high), but did not affectthe rejection rate.     

Three-dimensional cancer cell culture in high-yield multiscale scaffolds by shear spinning

Polymeric scaffolds comprising two size scales of microfibers and submicron fibers can better support three-dimensional (3D) cell growth in tissue engineering, making them an important class of healthcare material. However, a major manufacturing barrier hampers their translation into wider practical use: scalability. Traditional production of two-scale scaffolds by electrospinning is slow and costly. For day-to-day cell cultures, the scaffolds need to be affordable, made in high yield to drive down cost. Combining expertise from academia and industry from the United Kingdom and United States, this study uses a new series of high-yield, low-cost scaffolds made by shear spinning for tissue engineering. The scaffolds comprise interwoven submicron fibers and microfibers throughout as observed under scanning electron microscopy and demonstrate good capability to support cell culturing for tumor modeling. Three model human cancer cell lines (HEK293, A549 and MCF-7) with stable expression of GFP were cultured in the scaffolds and found to exhibit efficient cell attachment and sustained 3D growth and proliferation for 30 days. Cryosection and multiphoton fluorescence microscopy confirmed the formation of compact 3D cell clusters throughout the scaffolds. In addition, comparative growth curves of 2D and 3D cultures show significant cell-type-dependent differences. This work applies high-yield shear-spun scaffolds in mammalian tissue engineering and brings practical, affordable applications of multiscale scaffolds closer to reality. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2750, 2019.     

Centrosome defects cause microcephaly by activating the 53BP1‐USP28‐TP53 mitotic surveillance pathway

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53‐mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53‐mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non‐centrosomal protein SMC5 is also TP53‐dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain.     

Immunogenetic analysis of microsomal and non-microsomal lipoproteins from normal and malignannt mouse tissues for histocompatibility-2 (H-2) antigens

The H-2 antigenic properties of lipoprotein fractions from malignant (L-5178Y leukemia) and normal (spleen, thymus, liver, kidney) mouse tissues have been studied by serological and immunological tests, and the results compared to the previously described activities of these fractions in homograft-sensitization tests. Although, in general, the relative activities in the different assays parallel each other some notable exceptions were found. The non-microsomal lipoproteins from leukemic tissue, inactive in homograft-sensitization tests, did elicit H-2 antibody. Also, the liver microsomal lipoproteins, which are inactive in homograft-sensitization tests in amounts 400 × the minimal effective doses of spleen preparations, exhibited, in in vitro agglutinin-inhibition tests, approximately one-fourth the H-2 activity of the latter. Other findings of note include the high antibody-eliciting potency of the spleen and leukemia microsomal lipoproteins (15 μg protein was sufficient to initiate primary immunization and 1 μg protein to cause an anamnestic response); and the quantitive identity of H-2 antigen activity of the microsomal lipoproteins from spleen and thymus.     

Direct characterization of beta-adrenoceptors in membranes of immature red blood cells from rats.

By means of the radioactive antagonist ligand (3H)(-) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized as beta-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temperature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited by beta-adrenergic antagonists (pindolol greater than alprenolol greater than or equal to propranolol greater than practolol) and agonists (isoprenaline greater than adrenaline). The (-) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80% treatment of the animals with increasing doses of acetyl phenylhydrazine.     

Genetic structure in peripheral populations of the natterjack toad, <Emphasis Type="Italic">Bufo calamita</Emphasis>, as revealed by AFLP

Decreased fitness due to loss of genetic variation is a well recognised issue in conservation biology. Along the Swedish west coast, the endangered natterjack toad (Bufo calamita) occurs on, for the species, highly unusual habitat of rocky islands. Although the toads inhabit a restricted geographical area (maximum distance between the populations is 71 km), the fragmented nature of the landscape makes the genetic properties of the populations of conservation interest. However, lack of genetic variation found using conventional methods (microsatellites) has impeded genetic studies within these peripheral populations so far. In this study we assess population structure and genetic variation among seven of these fringe populations using 105 polymorphic Amplified Fragment Length Polymorphism (AFLP) loci. We found a well-defined population structure without evidence for isolation by distance, implying restricted gene flow between populations. Additionally, the populations differed in their amount of genetic variation, emphasizing the need to monitor genetically impoverished populations for possible declines mediated by inbreeding depression and reduced adaptive potential. Conservation implications for these unique populations are discussed in the light of our results.