Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization

Molecular Engineered Hole-Extraction Materials to Enable Dopant-Free, Efficient p-i-n Perovskite Solar Cells

Two hole-extraction materials (HEMs), TPP-OMeTAD and TPP-SMeTAD, have been developed to facilitate the fabrication of efficient p-i-n perovskite solar cells (PVSCs). By replacing the oxygen atom on HEM with sulfur (from TPP-OMeTAD to TPP-SMeTAD), it effectively lowers the highest occupied molecular orbital of the molecule and provides stronger Pb-S interaction with perovskites, leading to efficient charge extraction and surface traps passivation. The TPP-SMeTAD-based PVSCs exhibit both improved photovoltaic performance and reduced hysteresis in p-i-n PVSCs over those based on TPP-OMeTAD. This work not only provides new insights on creating perovskite-HEM heterojunction but also helps in designing new HEM to enable efficient organic–inorganic hybrid PVSCs

Single-Junction Binary-Blend Nonfullerene Polymer Solar Cells with 12.1% Efficiency

A new fluorinated nonfullerene acceptor, ITIC-Th1, has been designed and synthesized by introducing fluorine (F) atoms onto the end-capping group 1,1-dicyanomethylene-3-indanone (IC). On the one hand, incorporation of F would improve intramolecular interaction, enhance the push–pull effect between the donor unit indacenodithieno[3,2-b]thiophene and the acceptor unit IC due to electron-withdrawing effect of F, and finally adjust energy levels and reduce bandgap, which is beneficial to light harvesting and enhancing short-circuit current density (JSC). On the other hand, incorporation of F would improve intermolecular interactions through C-F···S, C-F···H, and C-F···π noncovalent interactions and enhance electron mobility, which is beneficial to enhancing JSC and fill factor. Indeed, the results show that fluorinated ITIC-Th1 exhibits redshifted absorption, smaller optical bandgap, and higher electron mobility than the nonfluorinated ITIC-Th. Furthermore, nonfullerene organic solar cells (OSCs) based on fluorinated ITIC-Th1 electron acceptor and a wide-bandgap polymer donor FTAZ based on benzodithiophene and benzotriazole exhibit power conversion efficiency (PCE) as high as 12.1%, significantly higher than that of nonfluorinated ITIC-Th (8.88%). The PCE of 12.1% is the highest in fullerene and nonfullerene-based single-junction binary-blend OSCs. Moreover, the OSCs based on FTAZ:ITIC-Th1 show much better efficiency and better stability than the control devices based on FTAZ:PC71BM (PCE = 5.22%)

Karriere-Handbuch

We design and synthesize four fused-ring electron acceptors based on 6,6,12,12-tetrakis(4-hexylphenyl)- indacenobis(dithieno[3,2-b;2′,3′-d]thiophene) as the electron- rich unit and 1,1-dicyanomethylene-3-indanones with 0− 2 fluorine substituents as the electron-deficient units. These four molecules exhibit broad (550−850 nm) and strong absorption with high extinction coefficients of (2.1−2.5) × 105 M−1 cm−1. Fluorine substitution downshifts the LUMO energy level, red-shifts the absorption spectrum, and enhances electron mobility. The polymer solar cells based on the fluorinated electron acceptors exhibit power conversion efficiencies as high as 11.5%, much higher than that of their nonfluorinated counterpart (7.7%). We investigate the effects of the fluorine atom number and position on electronic properties, charge transport, film morphology, and photovoltaic properties

Opioid regulation of the mouse -opioid receptor expressed in human embryonic kidney 293 cells. Mol Pharmacol 52:272

SUMMARY Opioid analgesics are used extensively in the management of pain. Although the clinically effective opioids bind with high affinity to the -opioid receptor, studies have suggested that the ␦-opioid agonists might represent more ideal analgesic agents, with fewer side effects. A limitation to opiate effectiveness is the development of tolerance, an event that has been linked to opioid receptor desensitization. To gain a better understanding of ␦-receptor agonist regulation, the cloned mouse ␦ receptor was stably expressed in human embryonic kidney 293 cells, and the functional effects of agonist pretreatment were examined. With a 3-hr pretreatment protocol, the ␦-selective agonists [D-Pen ]enkephalin, and etorphine treatments also caused a pronounced internalization of the epitope-tagged ␦ receptor, suggesting that the desensitization and internalization may be related. In contrast, levorphanol pretreatment did not internalize the receptor but still resulted in a 400-fold reduction in potency, suggesting that prolonged treatment with levorphanol only uncoupled the ␦ receptor from adenylyl cyclase. In contrast to the desensitization induced by peptide-selective ␦ agonists, pretreatment with the ␦-selective nonpeptide agonist 7-spiroindanyloxymorphone and morphine sensitized the opioid inhibition of forskolin-stimulated cAMP accumulation. This differential regulation of the ␦ receptor may be due to variations in the ability of agonists to bind to the receptor. This hypothesis was supported by the finding that a point mutation that converted Asp128 to Asn128 (D128N) diminished the ability of ␦-selective agonists to inhibit cAMP accumulation while increasing the potency of morphine to reduce cAMP accumulation. In particular, a lack of desensitization of the ␦ receptor by morphine may contribute to our understanding of the molecular basis of development of morphine-induced tolerance and dependence. Since Serturner reported the isolation of a pure substance from opium, which he named morphine in 1805, morphine and its derivatives have been extensively used in the clinical management of pain (1, 2). Considerable evidence has accumulated that analgesia can be mediated via the three major classes of opioid receptors: the -, ␦-, and -opioid receptors. All of the currently used opioid analgesics bind with high affinity to the -opioid receptor (3), but the clinical effectiveness of these opioids is limited by serious side effects, such as the development of tolerance and physical dependence (2). A primary goal of contemporary opioid research is the discovery of opioids that would provide effective analgesia devoid of unwanted side effects (4). Several studies have suggested that ␦ receptor opioid agonists might represent a more ideal analgesic than those currently available because ␦ receptors have been proposed to mediate analgesia (5) with a diminished opioid dependence (6, 7), making these receptors a promising target for drug design. Behavioral studies have reinforced this notion. For example, the selective blockade of ␦ receptors by intracerebroventricular administration of the ␦-selective antagonist naltrindole inhibited the development of morphine dependence in rats without compromising the antinociceptive actions of morphine (8). In addition, the ␦ receptor-selective antagonist H-Tyr-Tic(CH 2 -NH)Phe-Phe-OH suppressed the development of morphine tolerance and dependence in rats, indicating that the activation of ␦ receptors may be critical in the development of morphine-induced tolerance and dependence (9). Although the development of opioid tolerance is thought to be complex (10), one potential molecular component of opioid tolerance is receptor desensitization. To gain cellular insights into the role of ␦ receptors in opioid tolerance, in vitro models of ␦-opioid receptor function have been studied. Recent research has focused primarily on NG108 -15 cells

Construction of Recombinant <i>Escherichia coli</i> with a High L-Phenylalanine Production Yield from Glucose

L-phenylalanine is an important aromatic amino acid that is widely used in the area of feed, food additives, and pharmaceuticals. Among the different strategies of L-phenylalanine synthesis, direct microbial fermentation from raw substrates has attracted more and more attention due to its environment friendly process and low-cost raw materials. In this study, a rational designed recombinant Escherichia coli was constructed for L-phenylalanine production. Based on wild type E. coli MG1655, multilevel engineering strategies were carried out, such as directing more carbon flux into the L-phenylalanine synthetic pathway, increasing intracellular level of precursors, blocking by-product synthesis pathways and facilitating the secretion of L-phenylalanine. During 5 L fed batch fermentation, recombinant E. coli MPH-3 could produce 19.24 g/L of L-phenylalanine with a yield of 0.279 g/g glucose. To the best of our knowledge, this is one of the highest yields of L-phenylalanine producing E. coli using glucose as the sole carbon source in fed-batch fermentation

Some details of experiments

The file includes 1. Synthesis of P(PDI-DTT) 2. Schematic of gold-layer sticking technique 3. More photographs of nanotube

Data from: Convenient fabrication of conjugated polymer semiconductor nanotubes and their application in organic electronics

Organic heterojunction is indispensable in organic electronic devices, such as organic solar cells (OSCs), organic light-emitting diodes (OLEDs) and so on. Fabrication of core-shell nanostructure provides feasible and novel way to prepare organic heterojunction, which is beneficial for miniaturization and integration of organic electronic devices. Fabrication of nanotubes which constitute the core-shell structure in large quantity is the key for the realization of application. In this work, a simple and convenient method to prepare nanotubes utilizing conjugated copolymer of perylene diimide and dithienothiophene (P(PDI-DTT)) was demonstrated. The relationship between preparation condition (solvent atmosphere, solution concentration and pore diameter of templates) and morphology of nanostructure was studied systematically. P(PDI-DTT) nanotubes could be fabricated in regular shape and large quantity by preparing the solution with appropriate concentration and placing Anodic Aluminum Oxide (AAO) template with nanopore diameter of 200 nm in the solvent atmosphere. The tubular structure was confirmed by scanning electron microscope (SEM). P(PDI-DTT) nanotubes exhibited electron mobility of 0.02 cm2V-1s–1 in field effect transistors under ambient condition. Light emitting nanostructures were successfully fabricated by incorporating tetraphenyl ethylene (TPE) into polymer nanotubes

Data from: Convenient fabrication of conjugated polymer semiconductor nanotubes and their application in organic electronics

Organic heterojunction is indispensable in organic electronic devices, such as organic solar cells (OSCs), organic light-emitting diodes (OLEDs) and so on. Fabrication of core-shell nanostructure provides feasible and novel way to prepare organic heterojunction, which is beneficial for miniaturization and integration of organic electronic devices. Fabrication of nanotubes which constitute the core-shell structure in large quantity is the key for the realization of application. In this work, a simple and convenient method to prepare nanotubes utilizing conjugated copolymer of perylene diimide and dithienothiophene (P(PDI-DTT)) was demonstrated. The relationship between preparation condition (solvent atmosphere, solution concentration and pore diameter of templates) and morphology of nanostructure was studied systematically. P(PDI-DTT) nanotubes could be fabricated in regular shape and large quantity by preparing the solution with appropriate concentration and placing Anodic Aluminum Oxide (AAO) template with nanopore diameter of 200 nm in the solvent atmosphere. The tubular structure was confirmed by scanning electron microscope (SEM). P(PDI-DTT) nanotubes exhibited electron mobility of 0.02 cm2V-1s–1 in field effect transistors under ambient condition. Light emitting nanostructures were successfully fabricated by incorporating tetraphenyl ethylene (TPE) into polymer nanotubes

Data from: Convenient fabrication of conjugated polymer semiconductor nanotubes and their application in organic electronics

Organic heterojunction is indispensable in organic electronic devices, such as organic solar cells (OSCs), organic light-emitting diodes (OLEDs) and so on. Fabrication of core-shell nanostructure provides feasible and novel way to prepare organic heterojunction, which is beneficial for miniaturization and integration of organic electronic devices. Fabrication of nanotubes which constitute the core-shell structure in large quantity is the key for the realization of application. In this work, a simple and convenient method to prepare nanotubes utilizing conjugated copolymer of perylene diimide and dithienothiophene (P(PDI-DTT)) was demonstrated. The relationship between preparation condition (solvent atmosphere, solution concentration and pore diameter of templates) and morphology of nanostructure was studied systematically. P(PDI-DTT) nanotubes could be fabricated in regular shape and large quantity by preparing the solution with appropriate concentration and placing Anodic Aluminum Oxide (AAO) template with nanopore diameter of 200 nm in the solvent atmosphere. The tubular structure was confirmed by scanning electron microscope (SEM). P(PDI-DTT) nanotubes exhibited electron mobility of 0.02 cm2V-1s–1 in field effect transistors under ambient condition. Light emitting nanostructures were successfully fabricated by incorporating tetraphenyl ethylene (TPE) into polymer nanotubes