Microenvironments Matter:Advances in Brain-on-Chip

To highlight the particular needs with respect to modeling the unique and complex organization of the human brain structure, we reviewed the state-of-the-art in devising brain models with engineered instructive microenvironments. To acquire a better perspective on the brain’s working mechanisms, we first summarize the importance of regional stiffness gradients in brain tissue, varying per layer and the cellular diversities of the layers. Through this, one can acquire an understanding of the essential parameters in emulating the brain in vitro. In addition to the brain’s organizational architecture, we addressed also how the mechanical properties have an impact on neuronal cell responses. In this respect, advanced in vitro platforms emerged and profoundly changed the methods of brain modeling efforts from the past, mainly focusing on animal or cell line research. The main challenges in imitating features of the brain in a dish are with regard to composition and functionality. In neurobiological research, there are now methods that aim to cope with such challenges by the self-assembly of human-derived pluripotent stem cells (hPSCs), i.e., brainoids. Alternatively, these brainoids can be used stand-alone or in conjunction with Brain-on-Chip (BoC) platform technology, 3D-printed gels, and other types of engineered guidance features. Currently, advanced in vitro methods have made a giant leap forward regarding cost-effectiveness, ease-of-use, and availability. We bring these recent developments together into one review. We believe our conclusions will give a novel perspective towards advancing instructive microenvironments for BoCs and the understanding of the brain’s cellular functions either in modeling healthy or diseased states of the brain.</p

Probability distributions of mineral dissolution rates: the role of lattice defects

The correct quantification of mineral dissolution rates is a critical task for macroscopic reactive transport modeling. Previous studies showed a substantial rate variability of about two orders of magnitude, which cannot be explained by variance of external environmental parameters alone. If the rate cannot be predicted as a constant parameter, then the critical question is whether it can be predicted as a stable reproducible probability distribution. Although a large variety of factors may contribute to the overall variance across the scales, the effect of defect density and defect spatial distribution can be considered as one of the key variance sources. Here, we tested the reproducibility of probability distributions for Kossel crystals with a different amount and spatial configurations of lattice dislocations. We ran several tests on systems with the same configurations and calculated the probabilities of material flux. Surprisingly, we discovered that the density of dislocations has minimal impact on the probability distributions. However, the spatial location of dislocations has a substantial influence on the rate distributions reproducibility. In cases where multiple etch pits operate simultaneously, reproducible rate distributions are found regardless of the number of dislocations. In cases where dislocations formed clusters, one large etch pit controlled the entire surface, and sets of reproducible probability distributions were detected. Then, more complex statistical behavior is expected, since the result is path-dependent. These results have serious consequences for the implementation of rate distributions in reactive transport models. Further studies, however, are needed to provide clear guidance on relating surface morphologies, dislocation distributions, and dissolution rate variance. The role of material-specific properties, such as crystallographic structure and bonding, in rate distributions, should be additionally addressed. The role of grain boundaries, crystal size and crystal habit, including nanoparticulate forms, in rate variance, also should be addressed for practical applications

Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir.

Unbiased shRNA library screens revealed that the estrogen receptor-1 (ESR-1) is a key factor regulating HIV-1 latency. In both Jurkat T cells and a Th17 primary cell model for HIV-1 latency, selective estrogen receptor modulators (SERMs, i.e., fulvestrant, raloxifene, and tamoxifen) are weak proviral activators and sensitize cells to latency-reversing agents (LRAs) including low doses of TNF-α (an NF-κB inducer), the histone deacetylase inhibitor vorinostat (soruberoylanilide hydroxamic acid, SAHA), and IL-15. To probe the physiologic relevance of these observations, leukapheresis samples from a cohort of 12 well-matched reproductive-age women and men on fully suppressive antiretroviral therapy were evaluated by an assay measuring the production of spliced envelope (env) mRNA (the EDITS assay) by next-generation sequencing. The cells were activated by T cell receptor (TCR) stimulation, IL-15, or SAHA in the presence of either β-estradiol or an SERM. β-Estradiol potently inhibited TCR activation of HIV-1 transcription, while SERMs enhanced the activity of most LRAs. Although both sexes responded to SERMs and β-estradiol, females showed much higher levels of inhibition in response to the hormone and higher reactivity in response to ESR-1 modulators than males. Importantly, the total inducible RNA reservoir, as measured by the EDITS assay, was significantly smaller in the women than in the men. We conclude that concurrent exposure to estrogen is likely to limit the efficacy of viral emergence from latency and that ESR-1 is a pharmacologically attractive target that can be exploited in the design of therapeutic strategies for latency reversal

Drought-stress-induced up-regulation of CAM in seedlings of a tropical cactus, Opuntia elatior, operating predominantly in the C3 mode

Immediately after unfolding, cotyledons of the tropical platyopuntoid cactus, Opuntia elatior Mill., exhibited a C3-type diel CO2 exchange pattern characterized by net CO2 uptake in the light. Significant nocturnal increases in titratable acidity typical of crassulacean acid metabolism (CAM) were not detected at this early developmental stage. As cotyledons matured and the first cladode (flattened stem) developed, features of CAM were observed and the magnitude of CAM increased. Nonetheless, in well-watered seedlings up to 10 cm tall, C3 photosynthetic CO2 fixation in the light remained the major pathway of carbon fixation. Reduced soil water availability led to an up-regulation of net dark CO2 fixation and greater nocturnal increases in tissue acidity, consistent with facultative CAM. These observations demonstrate that C3 photosynthesis, drought-stress-related facultative CAM, and developmentally controlled constitutive CAM can all contribute to the early growth of O. elatior. The strong C3 component and facultative CAM features expressed in young O. elatior contrast with mature plants in which obligate CAM is the major pathway of carbon acquisition

Collective Excitations of (154)Sm nucleus at FEL{gamma}+LHC Collider

The production of collective excitations of the (154)Sm at FEL{gamma}+LHC collider is investigated. We show that this machine will be a powerful tool for investigation of high energy level excitations.Comment: 6 pages, 1 figure, 4 table

Production and characterization of miro- and nano-features in biomedical alumina and zirconia ceramics using a tape casting route

A process of micromolding, delivering micro- and nanopatterned ceramic surfaces for biomaterial applications is described in this work. To create the desired structures, tape casting of ceramic slurries on microfabricated silicon mold was used. Several tape casting slurry compositions were tested to evaluate the feasibility of transferring micro- and nano-features from silicon molds. Used ceramics were alumina (α-Al2O3) and yttria stabilized zirconia. Three types of polymeric binders for the green tape (PVB, PES, and PVP) were investigated using three different solvents (ethanol, n-methyl-pyrrolidone, water). Well-defined features in shapes of wells with diameters down to 2.4 μm and a depth of 10 μm and pillars with diameters down to 1.7 μm and a height of 3 μm were obtained. Morphology, grain size and porosity of the sintered bodies were characterized. Finally fibroblast cells were cultured on the surfaces in order to observe their morphology under influence of the microstructured surfaces