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Bioprinting technology offers unprecedented opportunities to construct in vitro tissue models that recapitulate the 3D morphology and functionality of native tissue. Yet, it remains difficult to obtain adequate functional readouts from such models. In particular, it is challenging to position sensors in desired locations within pre‐fabricated 3D bioprinted structures. At the same time, bioprinting tissue directly onto a sensing device is not feasible due to interference with the printer head. As such, a multi‐sensing platform inspired by origami that overcomes these challenges by "folding" around a separately fabricated 3D tissue structure is proposed, allowing for the insertion of electrodes into precise locations, which are custom‐defined using computer‐aided‐design software. The multi‐sensing origami platform (MSOP) can be connected to a commercial multi‐electrode array (MEA) system for data‐acquisition and processing. To demonstrate the platform, how integrated 3D MEA electrodes can record neuronal electrical activity in a 3D model of a neurovascular unit is shown. The MSOP also enables a microvascular endothelial network to be cultured separately and integrated with the 3D tissue structure. Accordingly, how impedance‐based sensors in the platform can measure endothelial barrier function is shown. It is further demonstrated the device's versatility by using it to measure neuronal activity in brain organoids. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is characterized by social and neurocognitive impairments, with mutations of the SHANK3 gene being prominent in patients with monogenic ASD. Using the InsG3680 mouse model with a Shank3 mutation seen in humans, we revealed an unknown role for Shank3 in postsynaptic oligodendrocyte (OL) features, similar to its role in neurons. This was shown by impaired molecular and physiological glutamatergic traits of InsG3680-derived primary OL cultures. In vivo, InsG3680 mice exhibit significant reductions in the expression of key myelination-related transcripts and proteins, along with deficits in myelin ultrastructure, white matter, axonal conductivity, and motor skills. Last, we observed significant impairments, with clinical relevance, in induced pluripotent stem cell-derived OLs from a patient with the InsG3680 mutation. Together, our study provides insight into Shank3's role in OLs and reveals a mechanism of the crucial connection of myelination to ASD pathology. [ABSTRACT FROM AUTHOR]

Four different methods are described for detecting sulfoxides produced by whole-cell biocatalysts, three of which are used for high-throughput screening. The method based on acid activation of omeprazole has proved to be efficient, but no positive variants are found, whereas the one based on selective inhibition of horse liver alcohol dehydrogenase (HLADH) is useful for detecting mutants with high activity and enantioselectivity in the oxidation of methyl p-tolyl sulfide.

Over the last two decades, the diagnosis and treatment of breast cancer patients have considerably improved. However, brain metastases remain a major clinical challenge and a leading cause of mortality. Thus, a better understanding of the pathways involved in the metastatic cascade is essential. To this end, we have investigated the reciprocal effects of astrocytes and breast cancer cells, employing traditional 2-dimensional cell culture and our unique 3-dimensional multicellular tumoroid models. Our findings revealed that astrocytes enhance the proliferation, migration, and invasion of breast cancer cells, suggesting a supportive role for astrocytes in breast cancer outgrowth to the brain. Elucidating the key players in astrocyte-breast cancer cells crosstalk, we found that CCL2 is highly expressed in breast cancer brain metastases tissue sections from both patients and mice. Our in vitro and in vivo models further confirmed that CCL2 has a functional role in brain metastasis. Given their aggressive nature, we sought additional immune checkpoints for rationale combination therapy. Among the promising candidates were the adhesion molecule P-selectin, which we have recently shown to play a key role in the crosstalk with microglia cells, and the co-inhibitory receptor PD-1, the main target of currently approved immunotherapies. Finally, combining CCL2 inhibition with immunomodulators targeting either PD-1/PD-L1 or P-selectin/P-Selectin Ligand-1 axes in our human 3-dimensional tumoroid models and in vivo presented more favorable outcomes than each monotherapy. Taken together, we propose that CCL2-CCR2/CCR4 is a key pathway promoting breast cancer brain metastases and a promising target for an immunotherapeutic combination approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Heme-oxygenase 1 is an endoplasmic reticulum-anchored enzyme that breaks down heme into iron, carbon monoxide and biliverdin. Heme is a hydrophobic co-factor in many proteins, including hemoglobin. Free heme is highly cytotoxic and, therefore, both heme synthesis and breakdown are tightly regulated. During turnover of heme proteins, heme is released in the phago-lysosomal compartment or the cytosol. The subcellular location of the heme-oxygenase 1 active site has not been clarified. Using constructs of heme-oxygenase 1 with fluorescent proteins, and the endogenous heme-oxygenase 1 in two variations of protease protection assays, we determined that heme-oxygenase 1 is membrane-bound and faces the cytosol in non-activated macrophages in vivo. These findings imply that in quiescent macrophages, heme breakdown products are generated in the cytosol. This facilitates iron recycling to ferroportin for iron export and to ferritin for iron storage.