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An artificial neuron architecture based on antiambipolar organic electrochemical transistors shows responses to biological ions and neurotransmitters akin to real neurons with comparable speed. The soft and more biocompatible nature of organic semiconductors could enable applications in brain–machine interfaces and in vivo sensing.

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors in neuromorphic computing, bioelectronics and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode organic electrochemical transistors. Here, using operando optical microscopy, we image the local doping level of the transistor channel and show that turn-on occurs in two stages—propagation of a doping front, followed by uniform doping—while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics and the phenomena of carrier-density-dependent mobility. We show that ion transport limits the operation speed in our devices. Our study provides insights into the kinetics of organic electrochemical transistors and guidelines for engineering faster organic electrochemical transistors. The turn-off time is generally faster than the turn-on time in accumulation mode organic electrochemical transistors (OECTs), but the mechanism is less understood. Here the authors find different transient behaviours of turn-on and turn-off in accumulation mode OECTs, and ion transport is the limiting factor of device kinetics.

Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1 + HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1 − HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma.

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4+ cells in the colostrum are CD14+ macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.

The authors studied the effects of immunosuppressive peptide cyclosporin A (CsA) on cell fusion efficiency in cells persistently infected with measles virus (448-PI-Vero cells). Treatment of 448-PI-Vero cells with 5 µM CsA enhanced the infusion. In addition, the expression of measles virus antigen on cell surface was increased by treatment with CsA. The addition of phenothiazine, an anti-calmodulin drug, enhanced the fusion of 448-PI-Vero cells in the presence of CsA, although treatment with phenothiazine alone did not affect polykaryocyte formation. The enhancement of fusion efficiency in 448-PI-Vero cells by CsA was suppressed by oligopeptide Z-D-Phe-Phe-Gly, a synthetic oligopeptide that inhibits fusion induced by measles virus. Since the cell content of major virus-specific polypeptides, such as hemagglutinin, nucleoprotein or matrix protein is the same as in untreated controls, this fusion enhancement may be related to transport and accumulation of measles virus glycoproteins.

We study the organic electrochemical transistors (OECTs) performance of the ladder polymer, poly(benzimidazobenzophenanthroline) (BBL) in an attempt to better understand how an apparently hydrophobic side-chain-free polymer is able to operate as an OECT with favorable redox kinetics in an aqueous environment. We examine two BBLs of different molecular masses from different sources. Both BBLs show significant film swelling during the initial reduction step. By combining electrochemical quartz crystal microbalance (eQCM) gravimetry, in-operando atomic force microscopy (AFM), and both ex-situ and in-operando grazing incidence wide-angle x-ray scattering (GIWAXS), we provide a detailed structural picture of the electrochemical charge injection process in BBL in the absence of any hydrophilic side-chains. Compared with ex-situ measurements, in-operando GIWAXS shows both more swelling upon electrochemical doping than has previously been recognized, and less contraction upon dedoping. The data show that BBL films undergo an irreversible hydration driven by the initial electrochemical doping cycle with significant water retention and lamellar expansion that persists across subsequent oxidation/reduction cycles. This swelling creates a hydrophilic environment that facilitates the subsequent fast hydrated ion transport in the absence of the hydrophilic side-chains used in many other polymer systems. Due to its rigid ladder backbone and absence of hydrophilic side-chains, the primary BBL water uptake does not significantly degrade the crystalline order, and the original dehydrated, unswelled state can be recovered after drying. The combination of doping induced hydrophilicity and robust crystalline order leads to efficient ionic transport and good stability.

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors (OECTs) in neuromorphic computing and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode OECTs. Through operando optical microscopy, we image the local doping level of the transistor channel and show that device turn-on occurs in two stages, while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics, and the physical phenomena of carrier density-dependent mobility. We show that ion transport is limiting the device operation speed in our model devices. Our study provides insights into the kinetics of OECTs and guidelines for engineering faster OECTs.

ST-segment elevation myocardial infarction (STEMI) is the most acute manifestation of coronary artery disease and is associated with great morbidity and mortality. A complete thrombotic occlusion developing from an atherosclerotic plaque in an epicardial coronary vessel is the cause of STEMI in the majority of cases. Early diagnosis and immediate reperfusion are the most effective ways to limit myocardial ischaemia and infarct size and thereby reduce the risk of post-STEMI complications and heart failure. Primary percutaneous coronary intervention (PCI) has become the preferred reperfusion strategy in patients with STEMI; if PCI cannot be performed within 120 minutes of STEMI diagnosis, fibrinolysis therapy should be administered to dissolve the occluding thrombus. The initiation of networks to provide around-the-clock cardiac catheterization availability and the generation of standard operating procedures within hospital systems have helped to reduce the time to reperfusion therapy. Together with new advances in antithrombotic therapy and preventive measures, these developments have resulted in a decrease in mortality from STEMI. However, a substantial amount of patients still experience recurrent cardiovascular events after STEMI. New insights have been gained regarding the pathophysiology of STEMI and feed into the development of new treatment strategies. ST-segment elevation myocardial infarction (STEMI) is an acute coronary syndrome in which transmural ischaemia (mostly caused by the formation of a thrombus on a ruptured atherosclerotic plaque) leads to cardiomyocyte death. STEMI is associated with considerable morbidity and mortality worldwide.

We generated a library of ~1000 Drosophila stocks in which we inserted a construct in the intron of genes allowing expression of GAL4 under control of endogenous promoters while arresting transcription with a polyadenylation signal 3’ of the GAL4. This allows numerous applications. First, ~90% of insertions in essential genes cause a severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) of lethal insertions tested are rescued with a single UAS-cDNA construct. Third, loss-of-function phenotypes associated with many GAL4 insertions can be reverted by excision with UAS-flippase. Fourth, GAL4 driven UAS-GFP/RFP reports tissue and cell-type specificity of gene expression with high sensitivity. We report the expression of hundreds of genes not previously reported. Finally, inserted cassettes can be replaced with GFP or any DNA. These stocks comprise a powerful resource for assessing gene function. Determining what role newly discovered genes play in the body is an important part of genetics. This task requires a lot of extra information about each gene, such as the specific cells where the gene is active, or what happens when the gene is deleted. To answer these questions, researchers need tools and methods to manipulate genes within a living organism. The fruit fly Drosophila is useful for such experiments because a toolbox of genetic techniques is already available. Gene editing in fruit flies allows small pieces of genetic information to be removed from or added to anywhere in the animal’s DNA. Another tool, known as GAL4-UAS, is a two-part system used to study gene activity. The GAL4 component is a protein that switches on genes. GAL4 alone does very little in Drosophila cells because it only recognizes a DNA sequence called UAS. However, if a GAL4-producing cell is also engineered to contain a UAS-controlled gene, GAL4 will switch the gene on. Lee et al. used gene editing to insert a small piece of DNA, containing the GAL4 sequence followed by a ‘stop’ signal, into many different fly genes. The insertion made the cells where each gene was normally active produce GAL4, but – thanks to the stop signal – rendered the rest of the original gene non-functional. This effectively deleted the proteins encoded by each gene, giving information about the biological processes they normally control. Lee et al. went on to use their insertion approach to make a Drosophila genetic library. This is a collection of around 1,000 different strains of fly, each carrying the GAL4/stop combination in a single gene. The library allows any gene in the collection to be studied in detail simply by combining the GAL4 with different UAS-controlled genetic tools. For example, introducing a UAS-controlled marker would pinpoint where in the body the original gene was active. Alternatively, adding UAS-controlled human versions of the gene would create humanized flies, which are a valuable tool to study potential disease-causing genes in humans. This Drosophila library is a resource that contributes new experimental tools to fly genetics. Insights gained from flies can also be applied to more complex animals like humans, especially since around 65% of genes are similar across humans and Drosophila. As such, Lee et al. hope that this resource will help other researchers shed new light on the role of many different genes in health and disease.