Structure-activity relationship study of nitrogen signaling factors.

We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces pombe, and evaluated their structure-activity relationships with the aim of developing molecular probes for NSFs. We found that the OH or OAc group at C10 could be replaced with a compact amide (17) or carbamate (19). Introducing an alkyne as a detection tag at C10 led to decreased, though still sufficient, activity. Introducing an alkyne at the C18 position showed a similar trend, suggesting tolerance is relatively low even for compact functional groups such as alkynes. Although introduction of a diazirine moiety as a photoreactive group at the C5 position decreased the activity, we found that introducing diazirine at the C13 position was acceptable, and compound 38 exhibited potent NSF activity. These findings will be helpful in the development of molecular probes for NSFs.

Leaf-inspired luminescent solar concentrator based on two-stage photoconversion.

Geometrical gain of a luminescent solar concentrator is drastically increased by laying out a luminescent fiber in a luminescent plate with air gap around it and attaching a photovoltaic (PV) cell to the tip of the fiber. The plate converts an incident photon to a first photoluminescence (PL) photon, and the fiber converts it to a second PL photon. Thus, the fiber carries the optical power as a leaf vein transports water and nutrients. The probability of the first PL photon resulting in the second PL photon reaching the PV cell can be measured by exciting a single spot on the plate with a laser beam. In experiment, 2 mm-thick, 50 mm-square and 50 mm-diameter circular devices were assembled with off-the-shelf components. For each case, geometrical gain exceeded 1000 and this probability averaged over the incident area was of the order of 0.01. Connecting multiple small-area devices to a single PV cell with a clear fiber would increase geometrical gain further and alleviate the absorption and scattering of PL photons during waveguiding.

A Case of NAA10-related Syndrome With Prolonged QTc Treated With a Subcutaneous Implantable Cardioverter Defibrillator After Ventricular Fibrillation.

NAA10 is an enzyme involved in the N-terminal acetylation of proteins. NAA10-related syndrome is caused by a pathogenic variant of NAA10 on X chromosome, resulting in several phenotypes, including mental retardation, hypotonia, growth retardation, and various external malformations, with varying degrees of severity. With regard to cardiac diseases, hypertrophic cardiomyopathy is a possible complication. Some mutations are also associated with long QT syndrome. Herein, we describe the case of a 7-year-old boy with a novel NAA10 mutation who experienced cardiopulmonary arrest possibly due to long QT syndrome and was implanted with a subcutaneous implantable cardioverter defibrillator.

La NAA10 est une enzyme qui intervient dans l'acétylation N-terminale des protéines. Le syndrome lié au gène NAA10 est causé par un variant pathogène du NAA10 sur le chromosome X qui entraîne plusieurs phénotypes, comme une déficience intellectuelle, une hypotonie, un retard de croissance ou différentes malformations externes, et ce, à divers degrés de sévérité. En ce qui concerne les maladies cardiaques, une cardiomyopathie hypertrophique est une complication possible. Certaines mutations sont également associées au syndrome du QT long. Nous décrivons ici le cas d'un garçon âgé de sept ans qui présente une nouvelle mutation du gène NAA10 et qui a fait un arrêt cardiorespiratoire, possiblement en raison d'un syndrome du QT long. L'enfant a reçu un défibrillateur cardiaque implantable sous-cutané.

Luminance, color gamut, and energy-harvesting characteristics of luminescent layers placed above a solar cell.

One can display images and harvest energy by utilizing ambient light with a stack of an optical shutter array, a luminescent layer and a solar cell. In our experiment, a luminescent layer and a corresponding color filter were attached to a polycrystalline Si solar cell with 13% power conversion efficiency. For each configuration using BBOT, Coumarin 6 and Lumogen F Red 305, the power conversion efficiency was measured to be 6.7%, 8.0% and 8.9%, respectively. The luminance of these configurations was proportional to the illuminance in all cases. Its color gamut was comparable to the National Television System Committee standard.

Intratumoral heterogeneity of glutaminase and lactate dehydrogenase A protein expression in colorectal cancer.

The high expression of metabolic enzymes, including glutaminase (GA) and lactate dehydrogenase A (LDHA), which contribute to bioenergetics and biosynthesis of mammalian cells, has been identified in a variety of cancer types. The current study indicated intratumoral heterogeneity with respect to protein expression of the metabolic enzymes in colorectal cancer (CRC). GA protein expression was determined using immunohistochemistry in 98 cases of surgically resected T3 CRC. A total of 75 cases (74%) exhibited moderate to strong immunopositivity of GA based on whole-section examination. A significant correlation was demonstrated between GA expression and clinicopathological features, including histological type and tumor budding in a patient population. Detailed histological analysis revealed the upregulation of GA protein expression at the invasive margin, including tumor budding of CRC tissues. Semi-quantitative examination revealed a significant difference in immunoexpression level of GA between the invasive margin and central CRC. However, LDHA expression exhibited an opposite pattern, with expression elevated at the center and significantly decreased at the tumors invasive margin. Immunohistochemical expression of another glycolytic enzyme hexokinase II was equivalent in both regions. Furthermore, gene silencing of GLS1, which encodes GA protein, and GA inhibitor treatment significantly inhibited cell growth of CRC cell lines. Therefore, the results of the present study demonstrated that the alteration in GA and LDHA expression is more prominent at the invasive margin, which involves tumor budding in CRC.

Widely Dispersed Intermolecular Valence Bands of Epitaxially Grown Perfluoropentacene on Pentacene Single Crystals.

Strong intermolecular electronic coupling and well-ordered molecular arrangements enable efficient transport of both charge carriers and excitons in semiconducting π-conjugated molecular solids. Thus, molecular heteroepitaxy to form crystallized donor-acceptor molecular interfaces potentially leads to a novel strategy for creating efficient organic optoelectronic devices via the concomitance of these two requirements. In the present study, the crystallographic and electronic structures of a heteroepitaxial molecular interface, perfluoropentacene (PFP, C22F14) grown on pentacene single crystals (Pn-SCs, C22H14), were determined by means of grazing-incidence X-ray diffraction (GIXD) and angle-resolved ultraviolet photoelectron spectroscopy (ARUPS), respectively. GIXD revealed that PFP uniquely aligned its primary axis along the [11̅0] axis of crystalline pentacene to form well-crystallized overlayers. Valence band dispersion (at least 0.49 eV wide) was successfully resolved by ARUPS. This indicated a significant transfer integral between the frontier molecular orbitals of the nearest-neighbor PFP molecules.

Evolution of crystallinity at a well-defined molecular interface of epitaxial C60 on the single crystal rubrene.

Uniform and well-defined interfaces are required for clarification of fundamental processes at internal interfaces between donor and acceptor molecules constituting organic optoelectronic devices. In this study, evolution of a well-ordered molecular interface, epitaxially grown C60 on the single crystal rubrene (C42H28) surface, was accurately investigated by grazing incidence x-ray diffraction (GIXD) techniques. Contrasting to the case of C60 on the single crystal pentacene forming uniquely aligned epitaxial interfaces, coexistence of two inequivalent crystalline domains of C60 was identified on the single crystal rubrene. Nevertheless, crystallinity of C60/rubrene exhibited even more remarkable improvement to extend its in-plane average crystallite size up to 250 nm as the growth temperature was raised. Probable leading factors determining the structures and crystallinity of the well-defined molecular interfaces are discussed based on close comparison of the present results with the C60/pentacene interfaces. The techniques presented herein for enhancement of the crystallinity in epitaxial molecular interfaces are potentially applicable to development in the photoelectric power conversion efficiency of organic photovoltaics (OPVs) via improved charge carrier mobility in donor-acceptor interfaces.

Power-law decay in the nonadiabatic photodissociation dynamics of alkali halides due to quantum wavepacket interference.

The nonadiabatic photodissociation dynamics of alkali halide molecules excited by a femtosecond laser pulse in the gas phase are investigated theoretically, and it is shown that the population of the photoexcited molecules exhibits power-law decay with exponent -1/2, in contrast to exponential decay, which is often assumed in femtosecond spectroscopy and unimolecular reaction theory. To elucidate the mechanism of the power-law decay, a diagrammatic method that visualizes the structure of the nonadiabatic reaction dynamics as a pattern of occurrence of dynamical events, such as wavepacket bifurcation, turning, and dissociation, is developed. Using this diagrammatic method, an analytical formula for the power-law decay is derived, and the theoretical decay curve is compared with the corresponding numerical decay curve computed by a wavepacket dynamics simulation in the case of lithium fluoride. This study reveals that the cause of the power-law decay is the quantum interference arising from the wavepacket bifurcation and merging due to nonadiabatic transitions.

Pharmacokinetics of insulin disappearance after massive overdosing.

Long-term glucose supplementation is required to prevent hypoglycemia after massive insulin overdosing. We fitted the blood insulin concentration-time profile to the model: I = A·exp(-a·t) + B·exp(-b·t), where I (µU/mL) is the serum/plasma insulin concentration, A (µU/mL) and B (µU/mL) are the peak insulin concentrations of each component, a (time-1) and b (time-1) are the time constants of each component, and t (h) is the time elapsed from the peak of blood insulin level. Additional components were considered as needed. Patient 1 had auto-injected 600 U NovoRapid® 30Mix, and Patient 2 had auto-injected 300 U Novolet®R (regular) and 1,800 U NovoLet®N (NPH). We used the disappearance of therapeutic doses of the respective insulin in healthy individuals as controls, and we obtained parameters by Excel solver. In Patient 1, the parameter values were A = 1490.04 and a = 0.15 for insulin aspart and B = 60.66 and b = 0.04 for protaminated aspart. In Patient 2, the values were A = 784.45 and a = 0.38 for regular insulin and B = 395.84 and b = 0.03 for NPH. Compared with controls, the half-lives (t1/2) for insulin aspart and protaminated aspart were 4 and 2 times longer, respectively, in Patient 1. In Patient 2, the t1/2 for regular and NPH insulin were 2 and 7 times longer than those in the controls, respectively. In conclusion, the t1/2 for insulin was elongated 2 to 7 times after massive overdosing, explaining why glucose supplementation is needed for long periods in these cases.

A study of the effect of introduction of JTAS in the emergency room.

Aim: The purpose of this study was to better understand the effects of introducing the Japan Triage and Acuity Scale (JTAS) in the emergency room for walk-in patients. Methods: A simple triage was used in Term A (from April 2006 to December 2010, 4 years and 9 months) and the JTAS was introduced in Term B (from January 2011 to September 2015, 4 years and 9 months). The number of patients who had a sudden turn for the worse after arrival in the emergency room and the time between attendance and emergency catheterization (TBAEC) due to acute coronary syndrome were reviewed. Results: There were 653 patients in Term A and 626 patients in Term B who were finally diagnosed as having serious causes. There was no significant difference in the frequency of a sudden turn for the worse between the two terms. There were 182 patients in Term A and 167 patients in Term B who underwent emergency catheterization due to acute coronary syndrome. When ST elevation was recognized in the first electrocardiogram, the median time between attendance and medical attention during Term B improved significantly, by 4.5 min. However, there was no significant difference in medians for TBAEC. When ST elevation was not recognized, there was no significant difference between the two terms, neither in terms of median time between attendance and medical attention, nor TBAEC. Conclusion: The data suggests that the effects of introducing the JTAS in the emergency room were restrictive in these two aspects.

Diagnosis of Ingested Foreign Body in the Stomach by Point-of-Care Ultrasound in the Upright and Slightly Forward Tilting Position (Bowing Position).

We report a case involving accidental ingestion of a marble that was detected by point-of-care ultrasonography of the abdomen with the patient in the upright and slightly forward tilting position, which we term the "bowing position." Using this position for abdominal ultrasonography may be more useful than the usual supine position for such patients.

Characterization of lysine acetylation of a phosphoenolpyruvate carboxylase involved in glutamate overproduction in Corynebacterium glutamicum.

Protein Nε-acylation is emerging as a ubiquitous post-translational modification. In Corynebacterium glutamicum, which is utilized for industrial production of l-glutamate, the levels of protein acetylation and succinylation change drastically under the conditions that induce glutamate overproduction. Here, the acylation of phosphoenolpyruvate carboxylase (PEPC), an anaplerotic enzyme that supplies oxaloacetate for glutamate overproduction was characterized. It was shown that acetylation of PEPC at lysine 653 decreased enzymatic activity, leading to reduced glutamate production. An acetylation-mimic (KQ) mutant of K653 showed severely reduced glutamate production, while the corresponding KR mutant showed normal production levels. Using an acetyllysine-incorporated PEPC protein, we verified that K653-acetylation negatively regulates PEPC activity. In addition, NCgl0616, a sirtuin-type deacetylase, deacetylated K653-acetylated PEPC in vitro. Interestingly, the specific activity of PEPC was increased during glutamate overproduction, which was blocked by the K653R mutation or deletion of sirtuin-type deacetylase homologues. These findings suggested that deacetylation of K653 by NCgl0616 likely plays a role in the activation of PEPC, which maintains carbon flux under glutamate-producing conditions. PEPC deletion increased protein acetylation levels in cells under glutamate-producing conditions, supporting the hypothesis that PEPC is responsible for a large carbon flux change under glutamate-producing conditions.

Single-Crystal Pentacene Valence-Band Dispersion and Its Temperature Dependence.

The electronic structures of the highest occupied molecular orbital (HOMO) or the HOMO-derived valence bands dominate the transport nature of positive charge carriers (holes) in organic semiconductors. In the present study, the valence-band structures of single-crystal pentacene and the temperature dependence of their energy-momentum dispersion relations are successfully demonstrated using angle-resolved ultraviolet photoelectron spectroscopy (ARUPS). For the shallowest valence band, the intermolecular transfer integral and effective mass of the holes are evaluated as 43.1 meV and 3.43 times the electron rest mass, respectively, at room temperature along the crystallographic direction for which the widest energy dispersion is expected. The temperature dependence of the ARUPS results reveals that the transfer integral values (hole effective mass) are enhanced (reduced) by ∼20% on cooling the sample to 110 K.

Nonadiabatic dynamics in intense continuous wave laser fields and real-time observation of the associated wavepacket bifurcation in terms of spectrogram of induced photon emission.

We propose a theoretical principle to directly monitor the bifurcation of quantum wavepackets passing through nonadiabatic regions of a molecule that is placed in intense continuous wave (CW) laser fields. This idea makes use of the phenomenon of laser-driven photon emission from molecules that can undergo nonadiabatic transitions between ionic and covalent potential energy surfaces like Li+ F- and LiF. The resultant photon emission spectra are of anomalous yet characteristic frequency and intensity, if pumped to an energy level in which the nonadiabatic region is accessible and placed in a CW laser field. The proposed method is designed to take the time-frequency spectrogram with an appropriate time-window from this photon emission to detect the time evolution of the frequency and intensity, which depends on the dynamics and location of the relevant nuclear wavepackets. This method is specifically designed for the study of dynamics in intense CW laser fields and is rather limited in scope than other techniques for femtosecond chemical dynamics in vacuum. The following characteristic features of dynamics can be mapped onto the spectrogram: (1) the period of driven vibrational motion (temporally confined vibrational states in otherwise dissociative channels, the period and other states of which dramatically vary depending on the CW driving lasers applied), (2) the existence of multiple nuclear wavepackets running individually on the field-dressed potential energy surfaces, (3) the time scale of coherent interaction between the nuclear wavepackets running on ionic and covalent electronic states after their branching (the so-called coherence time in the terminology of the theory of nonadiabatic interaction), and so on.

Epitaxial Growth of an Organic p-n Heterojunction: C60 on Single-Crystal Pentacene.

Designing molecular p-n heterojunction structures, i.e., electron donor-acceptor contacts, is one of the central challenges for further development of organic electronic devices. In the present study, a well-defined p-n heterojunction of two representative molecular semiconductors, pentacene and C60, formed on the single-crystal surface of pentacene is precisely investigated in terms of its growth behavior and crystallographic structure. C60 assembles into a (111)-oriented face-centered-cubic crystal structure with a specific epitaxial orientation on the (001) surface of the pentacene single crystal. The present experimental findings provide molecular scale insights into the formation mechanisms of the organic p-n heterojunction through an accurate structural analysis of the single-crystalline molecular contact.

Stark-assisted quantum confinement of wavepackets. A coupling of nonadiabatic interaction and CW-laser.

When a nonadiabatic system that has an ionic state (large dipole moment) and a covalent state (small dipole moment) is located in a strong laser field, the crossing point of the two potential energy curves is forced to oscillate due to the oscillating laser field and to meet wavepackets moving on the potential curves many times. This leads to additional transitions between the two states, and under favorable conditions, the wavepacket may be confined in a spatial region rich in nonadiabatic interaction. In this paper, taking the LiF molecule system in a continuous-wave driving field as a prototypical example, the dynamical origins of the wavepacket confinement are theoretically investigated.

A perturbation theoretic approach to the Riccati equation for the Floquet energies, spectral intensities, and cutoff energy of harmonic generation in photon emission from nonadiabatic electron-transfer dynamics driven by infrared CW laser fields.

A complicated yet interesting induced photon emission can take place by a nonadiabatic intramolecular electron transfer system like LiF under an intense CW laser [Y. Arasaki, S. Scheit, and K. Takatsuka, J. Chem. Phys. 138, 161103 (2013)]. Behind this phenomena, the crossing point between two potential energy curves of covalent and ionic natures in diabatic representation is forced to oscillate, since only the ionic potential curve is shifted significantly up and down repeatedly (called the Dynamical Stark effect). The wavepacket pumped initially to the excited covalent potential curve frequently encounters such a dynamically moving crossing point and thereby undergoes very complicated dynamics including wavepacket bifurcation and deformation. Intramolecular electron transfer thus driven by the coupling between nonadiabatic state-mixing and laser fields induces irregular photon emission. Here in this report we discuss the complicated spectral features of this kind of photon emission induced by infrared laser. In the low frequency domain, the photon emission is much more involved than those of ultraviolet/visible driving fields, since many field-dressed states are created on the ionic potential, which have their own classical turning points and crossing points with the covalent counterpart. To analyze the physics behind the phenomena, we develop a perturbation theoretic approach to the Riccati equation that is transformed from coupled first-order linear differential equations with periodic coefficients, which are supposed to produce the so-called Floquet states. We give mathematical expressions for the Floquet energies, frequencies, and intensities of the photon emission spectra, and the cutoff energy of their harmonic generation. Agreement between these approximate quantities and those estimated with full quantum calculations is found to be excellent. Furthermore, the present analysis provides with notions to facilitate deeper understanding for the physical and mathematical mechanisms of the present photon emission.

Altered acetylation and succinylation profiles in Corynebacterium glutamicum in response to conditions inducing glutamate overproduction.

The bacterium Corynebacterium glutamicum is utilized during industrial fermentation to produce amino acids such as L-glutamate. During L-glutamate fermentation, C. glutamicum changes the flux of central carbon metabolism to favor L-glutamate production, but the molecular mechanisms that explain these flux changes remain largely unknown. Here, we found that the profiles of two major lysine acyl modifications were significantly altered upon glutamate overproduction in C. glutamicum; acetylation decreased, whereas succinylation increased. A label-free semi-quantitative proteomic analysis identified 604 acetylated proteins with 1328 unique acetylation sites and 288 succinylated proteins with 651 unique succinylation sites. Acetylation and succinylation targeted enzymes in central carbon metabolic pathways that are directly related to glutamate production, including the 2-oxoglutarate dehydrogenase complex (ODHC), a key enzyme regulating glutamate overproduction. Structural mapping revealed that several critical lysine residues in the ODHC components were susceptible to acetylation and succinylation. Furthermore, induction of glutamate production was associated with changes in the extent of acetylation and succinylation of lysine, suggesting that these modifications may affect the activity of enzymes involved in glutamate production. Deletion of phosphotransacetylase decreased the extent of protein acetylation in nonproducing condition, suggesting that acetyl phosphate-dependent acetylation is active in C. glutamicum. However, no effect was observed on the profiles of acetylation and succinylation in glutamate-producing condition upon disruption of acetyl phosphate metabolism or deacetylase homologs. It was considered likely that the reduced acetylation in glutamate-producing condition may reflect metabolic states where the flux through acid-producing pathways is very low, and substrates for acetylation do not accumulate in the cell. Succinylation would occur more easily than acetylation in such conditions where the substrates for both acetylation and succinylation are limited. This is the first study investigating the acetylome and succinylome of C. glutamicum, and it provides new insight into the roles of acyl modifications in C. glutamicum biology.

Induced photoemission from driven nonadiabatic dynamics in an avoided crossing system.

When vibrational dynamics on an ionic state (large dipole moment) is coupled to that on a neutral state (small dipole moment) such as at an avoided crossing in the alkali halide system, the population transfer between the states cause oscillation of the molecular dipole, leading to dipole emission. Such dynamics may be driven by an external field. We study how the coupled wavepacket dynamics is affected by the parameters (intensity, frequency) of the driving field with the aim of making use of the photoemission as an alternative detection scheme of femtosecond and subfemtosecond vibrational and electronic dynamics or as a characteristic optical source.

Selective development of myogenic mesenchymal cells from human embryonic and induced pluripotent stem cells.

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are promising sources for the cell therapy of muscle diseases and can serve as powerful experimental tools for skeletal muscle research, provided an effective method to induce skeletal muscle cells is established. However, the current methods for myogenic differentiation from human ES cells are still inefficient for clinical use, while myogenic differentiation from human iPS cells remains to be accomplished. Here, we aimed to establish a practical differentiation method to induce skeletal myogenesis from both human ES and iPS cells. To accomplish this goal, we developed a novel stepwise culture method for the selective expansion of mesenchymal cells from cell aggregations called embryoid bodies. These mesenchymal cells, which were obtained by dissociation and re-cultivation of embryoid bodies, uniformly expressed CD56 and the mesenchymal markers CD73, CD105, CD166, and CD29, and finally differentiated into mature myotubes in vitro. Furthermore, these myogenic mesenchymal cells exhibited stable long-term engraftment in injured muscles of immunodeficient mice in vivo and were reactivated upon subsequent muscle damage, increasing in number to reconstruct damaged muscles. Our simple differentiation system facilitates further utilization of ES and iPS cells in both developmental and pathological muscle research and in serving as a practical donor source for cell therapy of muscle diseases.