Identification of amino acids in transmembrane domains of mutated cytokine receptor-like factor 2 and interleukin-7 receptor α required for constitutive signal transduction.

Cytokine receptor-like factor 2 (CRLF2) and interleukin-7 receptor α (IL-7Rα) form a receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation consisting of the substitution of five amino acids (SLLLL) in the transmembrane domain of CRLF2 with three amino acids, including glutamic acid, isoleucine, and methionine (insEIM), which has been identified in acute lymphocytic leukemia, causes the TSLP-independent dimerization with IL-7Rα and activation. However, the dimerization mechanism remains unclear.

StayGold variants for molecular fusion and membrane-targeting applications.

Although StayGold is a bright and highly photostable fluorescent protein, its propensity for obligate dimer formation may hinder applications in molecular fusion and membrane targeting. To attain monovalent as well as bright and photostable labeling, we engineered tandem dimers of StayGold to promote dispersibility. On the basis of the crystal structure of this fluorescent protein, we disrupted the dimerization to generate a monomeric variant that offers improved photostability and brightness compared to StayGold.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs, in at least one case there is evidence for an extreme magneto-ionic local environment and a compact persistent radio source. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.

PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice.

Protein kinase C-delta (PKCδ) has a caspase-3 recognition sequence in its structure, suggesting its involvement in apoptosis. In addition, PKCδ was recently reported to function as an anti-cancer factor. The generation of a PKCδ knockout mouse model indicated that PKCδ plays a role in B cell homeostasis.

Coupling delay controls synchronized oscillation in the segmentation clock.

Individual cellular activities fluctuate but are constantly coordinated at the population level via cell-cell coupling. A notable example is the somite segmentation clock, in which the expression of clock genes (such as Hes7) oscillates in synchrony between the cells that comprise the presomitic mesoderm (PSM). This synchronization depends on the Notch signalling pathway; inhibiting this pathway desynchronizes oscillations, leading to somite fusion.

Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in .

Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli.

The host galaxy of a fast radio burst.

In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts. These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations. Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates.

Molecular spies for bioimaging--fluorescent protein-based probes.

Convergent advances in optical imaging and genetic engineering have fueled the development of new technologies for biological visualization. Those technologies include genetically encoded indicators based on fluorescent proteins (FPs) for imaging ions, molecules, and enzymatic activities "to spy on cells," as phrased by Roger Tsien, by sneaking into specific tissues, cell types, or subcellular compartments, and reporting on specific intracellular activities. Here we review the current range of unimolecular indicators whose working principle is the conversion of a protein conformational change into a fluorescence signal.

Improved detection of electrical activity with a voltage probe based on a voltage-sensing phosphatase.

  One of the most awaited techniques in modern physiology is the sensitive detection of spatiotemporal electrical activity in a complex network of excitable cells. The use of genetically encoded voltage probes has been expected to enable such analysis. However, in spite of recent progress, existing probes still suffer from low signal amplitude and/or kinetics too slow to detect fast electrical activity.

The increasing cesarean rate globally and what we can do about it.

Cesarean sections sometimes save the lives of mothers and babies; however, they are excessively used compared to medical necessity, which is influenced by various factors that are explored in this article. Since, in most cases the risks of cesarean sections are greater than the benefits, particularly in cesareans that are not medically indicated, it is astonishing that cesarean surgery is the most common surgical procedure, taking away resources from medically necessary care. While economic incentive is counted among the reasons for the increasing cesarean trend, the situation is not so simple since many factors interact to cause the trend.

Blue fluorescent cGMP sensor for multiparameter fluorescence imaging.

Cyclic GMP (cGMP) regulates many physiological processes by cooperating with the other signaling molecules such as cyclic AMP (cAMP) and Ca(2+). Genetically encoded sensors for cGMP have been developed based on fluorescence resonance energy transfer (FRET) between fluorescent proteins. However, to analyze the dynamic relationship among these second messengers, combined use of existing sensors in a single cell is inadequate because of the significant spectral overlaps.

Cell-based in vivo dual imaging probes using genetically expressed tags and chemical contrast agents.

We report a method for specifically labelling the surface of cells with two kinds of chemical probes (near-infrared (NIR) fluorescent probes and magnetic resonance (MR) imaging probes) via two genetically expressed tags, and demonstrate the application for in vitro and in vivo dual imaging.

Simultaneous live cell imaging using dual FRET sensors with a single excitation light.

Fluorescence resonance energy transfer (FRET) between fluorescent proteins is a powerful tool for visualization of signal transduction in living cells, and recently, some strategies for imaging of dual FRET pairs in a single cell have been reported. However, these necessitate alteration of excitation light between two different wavelengths to avoid the spectral overlap, resulting in sequential detection with a lag time. Thus, to follow fast signal dynamics or signal changes in highly motile cells, a single-excitation dual-FRET method should be required.

[Implementation of discharge planning in the care of hospitalized older adults. Focus on involvement of home care providers at hospitals].

Objectives: The present study was conducted to assess current implementation of discharge planning in the care of hospitalized older adults, and to examine the association between implementation and involvement of home care providers at hospitals.

Methods: The subjects were 434 hospitals with 100 beds or more for general patients, nationwide. We conducted a questionnaire survey by mail of hospital staff responsible for the discharge planning, and assessed to what extent home care providers were associated with the implementation of discharge planning in the hospitals.

Ca(2+) influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites.

In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca(2+) imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca(2+) increase, following cofilin rods' formation.

New PKCdelta family members, PKCdeltaIV, deltaV, deltaVI, and deltaVII are specifically expressed in mouse testis.

We isolated and characterized four new PKCdelta isoforms, PKCdeltaIV, deltaV, deltaVI, and deltaVII, specifically expressed in the mouse testis. These isoforms possess neither V1 nor C2-like domains. Moreover, PKCdeltaVI and deltaVII have a different last exon as their V5 domain.

Expression level of MDR1 message in peripheral blood leukocytes from healthy adults: a competitive nucleic acid sequence-based amplification assay for its determination.

Accurate quantification of multidrug resistance-1 gene (MDR1) expression in target cells would be of important therapeutic value in predicting cellular response to anticancer drugs. Because certain normal cells in peripheral blood physiologically express MDR1, increasing the sensitivity of the detection methods might result in confounding low-degree expression in tumor cells with physiologic expression in normal cells. The purpose of this study was to determine MDR1 mRNA expression levels in peripheral blood leukocytes obtained from healthy adult volunteers using a competitive nucleic acid sequence-based amplification (NASBA) assay.

Galactosylceramide expression factor-1 induces myogenesis in MDCK and C3H10T1/2 cells.

We previously reported that galactosylceramide expression factor-1 (GEF-1), a rat homolog of hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs/Hgs), induces galactosylceramide and/or sulfatide expression and morphological changes in epithelial cells. Here, we show that GEF-1 induces myogenesis in MDCK and C3H10T1/2 cells. GEF-1 overexpression in MDCK cells (MDCK/GEF-1) appeared to promote trans-differentiation to myoblasts that expressed MyoD and myosin heavy chain (MHC).

Effect of substituents on the thermal decomposition of diazirines: experimental and computational studies.

The thermal decomposition of phenylchlorodiazirine (1), phenyl-n-butyldiazirine (2), and 2-adamantane-2,3'-[3H]diazirine (3) has been studied in solution in the presence of C(60). The C(60) probe technique indicates that in the decomposition diazirine 1 yielded exclusively phenylchlorocarbene, diazirine 2 yielded mainly a diazo intermediate, and diazirine 3 yielded a mixture of carbene and diazo compound. In the case of diazirine 2, 13% of (E)-1-phenyl-1-pentene resulted from the direct thermal rearrangement of diazirine without the participation of a carbene.

PKC zeta II, a small molecule of protein kinase C zeta, specifically expressed in the mouse brain.

Protein kinase C zeta (PKCzeta) plays critical roles in neural development. In the brain, many PKCzeta-related transcripts are expressed but they do not code the native 75 kDa PKCzeta molecule. We examined the significance of such transcripts in intact cells.

A nonspectroscopic method to determine the photolytic decomposition pathways of 3-chloro-3-alkyldiazirine: carbene, diazo and rearrangement in excited state.

C(60) acts as a mechanistic probe for the formation of carbene, diazo compound, and for the rearranged product via the excited state in the photolysis of 3-chloro-3-isopropyldiazirine and 3-chloro-3-chloromethyldiazirine. The carbene adds to C(60) to form methanofullerene, whereas the diazo compound adds to C(60) to form fulleroid. The olefin product arises as a result of the rearrangement in the excited state.

New mu-opioid receptor agonists with phenoxyacetic acid moiety.

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide.