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A series of acylsulfenyl iodides (RCOSI) were synthesized by the reactions of carbothioic acid group 11–16 element derivatives with iodine or N-iodosuccinimides in moderate to good yields.

Mild heat stimulation is defined as a stimulation that occurs several degrees above optimal cell culture or body temperatures. Muscle hypertrophy in C2C12 cells is reportedly facilitated by 39 °C mild heat stimulation. However, the underlying molecular mechanisms by which 39 °C mild heat stimulation promotes muscle hypertrophy remains elusive. In this study, we aimed at understanding the details of these mechanisms. First, we found that 39 °C mild heat stimulation has little or no effect on Myogenesis-Related Factor (MRF) expression both in C2C12 and mouse primary satellite cells. Therefore, we hypothesized that 39 °C mild heat stimulation promotes muscle hypertrophy through myokines, essential components in myogenesis. Interestingly, we observed muscle hypertrophy in the group cultured at 37 °C in conditioned medium from 39 °C compared to the group cultured at 37 °C in conditioned medium from 37 °C in the case of both C2C12 and mouse primary satellite cells. These results suggest that 39 °C mild heat stimulation promotes muscle hypertrophy through myokines, once released in the culture medium. Finally, we identified Decorin as a hypertrophy-inducing myokine candidate. Therefore, in this study, we demonstrated that 39 °C mild heat stimulation contributes to muscle hypertrophy through enhancing Decorin gene expression in C2C12 and mouse primary satellite cells.

Consecutive treatment of 2-(2-lithiophenyl)pyridine with chalcogen tetrachlorides (ChCl4; Ch = Se and Te) and KPF6 afforded the hexafluorophosphate salts of tris[2-(2-pyridyl)phenyl]selenonium [(pp...

The dynamic and static nature of the XH-∗-π and YX-∗-π (X = F, Cl, Br, and I; Y = X and F) interactions in the distorted π-system of corannulene (π(C20H10)) is elucidated with a QTAIM dual functional analysis (QTAIM-DFA), where asterisks emphasize the presence of bond critical points (BCPs) on the interactions. The static and dynamic nature originates from the data of the fully optimized and perturbed structures, respectively, in QTAIM-DFA. On the convex side, H in F–H-∗-π(C20H10) and each X in Y–X-∗-π(C20H10) join to C of the central five-membered ring in π(C20H10) through a bond path (BP), while each H in X–H-∗-π(C20H10) does so to the midpoint of C=C in the central five-membered ring for X = Cl, Br, or I. On the concave side, each X in F–X-∗-π(C20H10) also joins to C of the central five-membered ring with a BP for X = H, Cl, Br, and I; however, the interactions in other adducts are more complex than those on the convex side. Both H and X in X–H-∗-π(C20H10) (X = Cl and Br) and both Fs in F–F-∗-π(C20H10) connect to the three C atoms in each central five-membered ring (with three BPs). Two, three, and five BPs were detected for the Cl–Cl, I–H, Br–Br, and I–I adducts, where some BPs do not stay on the central five-membered ring in π(C20H10). The interactions are predicted to have a vdW to CT-MC nature. The interactions on the concave side seem weaker than those on the convex side for X–H-∗-π(C20H10), whereas the inverse trend is observed for Y–X-∗-π(C20H10) as a whole. The nature of the interactions in the π(C20H10) adducts of the convex and concave sides is examined in more detail, employing the adducts with X–H and F–X placed on their molecular axis together with the π(C24H12) and π(C6H6) adducts.

The nature of Br4σ(4c–6e) of the BBr-∗-ABr-∗-ABr-∗-BBr form is elucidated for SeC12H8(Br)SeBr---Br-Br---BrSe(Br)C12H8Se, the selenanthrene system, and the models with QTAIM dual functional analysis (QTAIM-DFA). Asterisks (∗) are employed to emphasize the existence of bond critical points on the interactions in question. Data from the fully optimized structure correspond to the static nature of interactions. In our treatment, data from the perturbed structures, around the fully optimized structure, are employed for the analysis, in addition to those from the fully optimized one, which represent the dynamic nature of interactions. The ABr-∗-ABr and ABr-∗-BBr interactions are predicted to have the CT-TBP (trigonal bipyramidal adduct formation through charge transfer) nature and the typical hydrogen bond nature, respectively. The nature of Se2Br5σ(7c–10e) is also clarified typically, employing an anionic model of [Br-Se(C4H4Se)-Br---Br---Br-Se(C4H4Se)-Br]−, the 1,4-diselenin system, rather than (BrSeC12H8)Br---Se---Br-Br---Br-Se(C12H8Se)-Br, the selenanthrene system.

The intrinsic dynamic and static nature of each HB in the multi-HBs between nucleobase pairs (Nu–Nu′) is elucidated with QTAIM dual functional analysis (QTAIM-DFA). Perturbed structures generated using coordinates derived from the compliance constants (Cii) are employed for QTAIM-DFA. The method is called CIV. Two, three, or four HBs are detected for Nu–Nu′. Each HB in Nu–Nu′ is predicted to have the nature of CT-TBP (trigonal bipyramidal adduct formation through charge transfer (CT)), CT-MC (molecular complex formation through CT), or t-HBwc (typical HB with covalency), while the vdW nature is predicted for the C–H⋯X interactions, for example. Energies for the formation of the pairs (ΔE) are linearly correlated with the total values of Cii−1 in Nu–Nu′. The total Cii−1 values are obtained by summing each Cii−1 value, similarly to the case of Ohm's law for the parallel connection in the electric resistance. The total ΔE value for a nucleobase pair could be fractionalized to each HB, based on each Cii−1 value. The perturbed structures generated with CIV are very close to those generated with the partial optimization method, when the changes in the interaction distances are very small. The results provide useful insights for better understanding DNA processes, although they are highly enzymatic.

Myoblast differentiation is an ordered multistep process that includes withdrawal from the cell cycle, elongation, and fusion to form multinucleated myotubes. Id3, a member of the Id family, plays a crucial role in cell cycle exit and differentiation. However, in muscle cells after differentiation induction, the detailed mechanisms that diminish Id3 function and cause the cells to withdraw from the cell cycle are unknown. Induction of myoblast differentiation resulted in decreased expression of Id3 and increased expression of XBP1u, and XBP1u accelerated proteasomal degradation of Id3 in C2C12 cells. The expression levels of the cyclin-dependent kinase inhibitors p21, p27, and p57 were not increased after differentiation induction of XBP1-knockdown C2C12 cells. Moreover, knockdown of Id3 rescued myogenic differentiation of XBP1-knockdown C2C12 cells. Taken together, these findings provide evidence that XBP1u regulates cell cycle exit after myogenic differentiation induction through interactions with Id3. To the best of our knowledge, this is the first report of the involvement of XBP1u in myoblast differentiation. These results indicate that XBP1u may act as a “regulator” of myoblast differentiation under various physiological conditions.

In QTAIM dual-functional analysis, Hb(rc) is plotted versus Hb(rc) − Vb(rc)/2 for the interactions, where Hb(rc) and Vb(rc) are the total electron energy densities and potential energy densities, respectively, at the bond critical points (BCPs) on the interactions in question. The plots are analyzed by the polar (R, θ) coordinate representation for the data from the fully optimized structures, while those from the perturbed structures around the fully optimized structures are analyzed by (θp, κp). θp corresponds to the tangent line of the plot, and κp is the curvature; θ and θp are measured from the y-axis and y-direction, respectively. The normal and inverse behavior of interactions is proposed for the cases of θp > θ and θp < θ, respectively. The origin and the mechanism for the behavior are elucidated. Interactions with θp < θ are typically found, although seldom for [F–I-∗-F]−, [MeS-∗-TeMe]2+, [HS-∗-TeH]2+ and CF3SO2N-∗-IMe, where the asterisks emphasize the existence of BCPs in the interactions and where [Cl–Cl-∗-Cl]− and CF3SO2N-∗-BrMe were employed as the reference of θp > θ. The inverse behavior of the interactions is demonstrated to arise when Hb(rc) − Vb(rc)/2 and when the corresponding Gb(rc), the kinetic energy densities at BCPs, does not show normal behavior.

Myoblast differentiation is an ordered multistep process that includes withdrawal from the cell cycle, elongation, and fusion to form multinucleated myotubes. Id3, a member of the Id family, plays a crucial role in cell cycle exit and differentiation. However, in muscle cells after differentiation induction, the detailed mechanisms that diminish Id3 function and cause the cells to withdraw from the cell cycle are unknown. Induction of myoblast differentiation resulted in decreased expression of Id3 and increased expression of XBP1u, and XBP1u accelerated proteasomal degradation of Id3 in C2C12 cells. The expression levels of the cyclin-dependent kinase inhibitors p21, p27, and p57 were not increased after differentiation induction of XBP1-knockdown C2C12 cells. Moreover, knockdown of Id3 rescued myogenic differentiation of XBP1-knockdown C2C12 cells. Taken together, these findings provide evidence that XBP1u regulates cell cycle exit after myogenic differentiation induction through interactions with Id3. To the best of our knowledge, this is the first report of the involvement of XBP1u in myoblast differentiation. These results indicate that XBP1u may act as a "regulator" of myoblast differentiation under various physiological conditions.

The aim of this study was to determine the effect of thermal stimulation at 39°C on the fusion and elongation of skeletal muscle cells. During a 5 day differentiation process of C2C12 cells, nine groups subjected to varying lengths of thermal stimulation at 39°C were established. Afterward, all groups were immunostained using anti-muscle heavy-chain antibody to test for myotube formation. Quantification of the myotube area demonstrated a significant increase in the group subjected to thermal stimulation at 39°C during the latter half of the differentiation compared with the control group, but the fusion index was significantly higher in the group that received hyperthermic treatment during the first half of the differentiation period. Moreover, the longitudinal length of myotubes was significantly increased in the groups that were subjected to thermal stimulation at 39°C during the latter half of the differentiation period. The distance between the center of myotubes and the nucleus farthest away from the center was substantially extended in the group receiving thermal stimulation at 39°C only on the fourth day of the differentiation. Together, these results demonstrate that thermal stimulation at 39°C facilitates myoblast fusion and elongation.

The dynamic and static nature of each hydrogen bond (HB) in acetic acid dimer (1), acetamide dimer (2a), thio- and seleno-derivatives of 2a (2b and 2c, respectively), and acetic acid–acetamide mixe...

The intrinsic dynamic and static natures of the E⋯E′ interactions at the 1,8-positions of 1-(MeE)–8-(MeE′)C10H6 [1a–1f (E ≠ E′) and 1g–1j (E = E′)] were elucidated with QTAIM-DFA, after structural determination of 1-(PhE)–8-(PhE′)C10H6 (3a–3f), where (E, E′: x) = (O, S: a), (O, Se: b), (O, Te: c), (S, Se: d), (S, Te: e), (Se, Te: f), (O, O: g), (S, S: h), (Se, Se: i) and (Te, Te: j) (χE ≥ χE′). While the AB structures are confirmed for 3a, 3b and 3d–3f, which consist of the np(E)⋯σ*(E′–CPh) interactions, the structure was BB for 3c, where the E–CR/E′–CR (R = Ph) bond is perpendicular to the naphthyl plane in A and it is placed on the plane in B. While the AB structures are determined by the p(E)–π(Ph) conjugations, the BB structure is by the crystal packing effect. The BA structure with np(E′)⋯σ*(E–CPh) was not detected. While the nature of a typical hydrogen bond with covalency was predicted for BB, AA and BA, with the CT-MC (molecular complex formation through charge transfer) nature for AB in 1e and 1f (R = Me for E–CR/E′–CR), the CT-MC nature was predicted for all conformers of 1j, for example. NBO analysis for 1a–1f revealed that the acceptor orbitals contribute much more than the donor orbitals and the order is σ*(O–CMe

The intrinsic dynamic and static nature of the non-covalent Br-*-Br interactions in the neutral polybromine clusters is elucidated for Br4–Br12, applying QTAIM dual functional analysis (QTAIM-DFA). The asterisk (*) emphasizes the existence of the bond critical point (BCP) on the interaction in question. Data from the fully optimized structures correspond to the static nature of interactions. The intrinsic dynamic nature is originated from those of the perturbed structures generated using the coordinates derived from the compliance constants for the interactions and the fully optimized structures. The non-covalent Br-*-Br interactions in the L-shaped clusters of the Cs symmetry are predicted to have the typical hydrogen bond nature without covalency, although the first ones in the sequences have the vdW nature. The L-shaped clusters are stabilized by the n(Br)->σ*(Br–Br) interactions. The compliance constants for the corresponding non-covalent interactions are strongly correlated to the E(2) values based on NBO. Indeed, the MO energies seem not contribute to stabilize Br4 (C2h) and Br4 (D2d), but the core potentials stabilize them, relative to the case of 2Br2, maybe due to the reduced nuclear-electron distances in the average for the dimmers.

Insulin-like growth factor-1 (IGF-1) plays a key role in proliferation and galactopoiesis in mammary epithelial cells (MEC), but its definitive functions on endoplasmic reticulum (ER) during protein synthesis remain unknown. The present study aimed to elucidate the effects of IGF-1 on ER biogenesis in MEC in vitro and examined the expression of ER biogenesis-associated genes in the mammary gland during early lactation. We treated mammary alveolar cells–large T antigen cells (immortalized bovine MEC line established via stable transfection with simian virus-40 large T-antigen) with IGF-1 and examined ER biogenesis using the fluorescence intensity of an ER tracker and quantitative real-time PCR. We found IGF-1 significantly increased ER tracker staining and upregulated mRNA levels of ER biogenesis-related genes, such as CHKA (choline kinase α), PCYT1A (choline-phosphate cytidylyltransferase A), and SURF4 (surfeit locus protein 4). We focused on unfolded protein response to explore molecular mechanisms by which IGF-1 induces ER biogenesis. We found IGF-1 significantly increased mRNA levels of the XBP1 splicing form (XBP1s). Based on western blot analysis, IGF-1 induced the expression of (inositol-requiring kinase 1 α) protein, upstream of XBP1s, and phosphorylated-IRE1α. The inhibition of IRE1 endoribonuclease activity with 4-methylumbelliferone 8-carbaldehyde (4μ8C) significantly suppressed the increase in ER tracker fluorescence and ER biogenesis-related gene expression induced by IGF-1. Also, IGF-1–induced XBP1s and ER biogenesis-associated gene expression was inhibited by rapamycin, an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), indicating that IRE1-XBP1 activation by IGF-1 is mediated by mTORC1. Moreover, to clarify the expression of XBP1s and ER biogenesis-associated genes expression under normal physiological conditions, mammary gland tissue from biopsies of dairy cows during late gestation and lactation were analyzed. In vivo data highlighted the significant increases in the mRNA levels of XBP1s and ER biogenesis-related genes in mammary gland tissue immediately after calving through 6 wk of lactation. The mRNA levels of IGF1R (IGF-1 receptor) in mammary glands increased during 6 wk of lactation. Therefore, the present study indicated for the first time that IGF-1 induces ER biogenesis by activating the IRE1-XBP1 axis under the regulation of mTORC1 in bovine MEC line.

The dynamic and static nature of XH-*-π and YX-*-π in the coronene π-system (π(C24H12)) is elucidated by QTAIM dual functional analysis, where * emphasizes the presence of bond critical points (BCPs) in the interactions. The nature of the interactions is elucidated by analysing the plots of the total electron energy densities Hb(rc) versus Hb(rc) − Vb(rc)/2 [=(ħ2/8m)∇2ρb(rc)] for the interactions at BCPs, where Vb(rc) are the potential energy densities at the BCPs. The data for the perturbed structures around the fully optimized structures are employed for the plots in addition to those of the fully optimized structures. The plots are analysed using the polar coordinate of (R, θ) for the data of the fully optimized structures, while those containing the perturbed structures are analysed using (θp, κp), where θp corresponds to the tangent line of each plot and κp is the curvature. Whereas (R, θ) show the static nature, (θp, κp) represent the dynamic nature of the interactions. All interactions in X–H-*-π(C24H12) (X = F, Cl, Br and I) and Y–X-*-π(C24H12) (Y–X = F–F, Cl–Cl, Br–Br, I–I, F–Cl, F–Br and F–I) are classified by pure CS (closed shell) interactions and are characterized as having the vdW nature, except for X–H = F–H and Y–X = F–Cl, F–Br and F–I, which show the typical-HB nature without covalency. The structural features of the complexes are also discussed.

Invited for this month's cover picture is the group of Dr. Satoko Hayashi at Faculty of Systems Engineering and Chemistry at Wakayama University. The cover picture shows the linear Se(16) σ(16c–30e) interactions, illustrated by the molecular graph type on the optimized structure of the dicationic octamer of 1,5‐(diselena)cane. HOMO‐1 of ψ(462) is drawn on the structure, which is located predominantly on the Se atoms. The optimized structure is stable, due to the nice engagement between the (CH(2))(3) moieties. The contour maps of ρ(r) are also drawn on the molecular C (s) planes of the dicationic dimer and trimer to demonstrate clearly the existence of the interactions between Se atoms. Read the full text of their Full Paper at 10.1002/open.202100017.

Indirect one-bond nuclear spin-spin couplings between M and C [1 J(M,C)] in Me4 M, Me3 M- , Ph4 M, and Ph3 M- (M=Pb, Sn, Ge, Si, C) are analyzed with consideration of the relativistic effect and by employing Slater-type basis sets. The evaluated total values 1 JTL (M,C) reproduced the observed values with some systematic calculation errors. Fermi contact terms 1 JFC (M,C) contribute predominantly to 1 JTL (M,C) (≈99 %). A distinct relativistic effect on 1 J(Pb,C) is predicted for Me3 Pb- and Ph3 Pb- . The mechanisms for the distinct effect are elucidated by using the comparison between Me3 Pb- and Me4 Pb as an example. The contributions to 1 JFC (M,C) [or 1 JSD+FC (M,C), where SD denotes the spin-dipolar term] are decomposed into those of occupied orbitals and occupied-to-unoccupied transitions. The s-type lone-pair orbitals are demonstrated to contribute to the distinct relativistic effect on 1 J(Pb,C) of Me3 Pb- (and Ph3 Pb- ). The results are in sharp contrast to the cases of 1 J(M,C) for M atoms lighter than Pb, such as Si, and are explained by the s character of the M-C bonds. This treatment enables visualization and clear recognition the origin of the nuclear couplings for the species exhibiting a relativistic effect.

The nature ofE2X2σ(4c–6e) of theX-*-E-*-E-*-Xtype is elucidated for 1-(8-XC10H6)E–E(C10H6X-8′)-1′ [(1)E,X= S, Cl; (2) S, Br; (3) Se, Cl; (4) Se, Br] after structural determination of (1), (3) and (4), together with modelA[MeX---E(H)—E(H)---XMe (E= S and Se;X= Cl and Br)]. The quantum theory of atoms-in-molecules dual functional analysis (QTAIM-DFA) is applied. The total electron energy densitiesHb(rc) are plottedversus Hb(rc) –Vb(rc)/2 for the interactions at the bond critical points (BCPs; *), whereVb(rc) show the potential energy densities at the BCPs. Data for the perturbed structures around the fully optimized structures are employed for the plots, in addition to those of the fully optimized structures. The plots were analysed using the polar coordinate (R, θ) representation of the data of the fully optimized structures. Data containing the perturbed structures were analysed by (θp, κp), where θpcorresponds to the tangent line of the plot and κpis the curvature. Whereas (R, θ) shows the static nature, (θp, κp) represents the dynamic nature of interactions.E-*-Eare all classified as shared shell (S) interactions for (1)–(4) and as weak covalent (Cov-w) in nature (S/Cov-w). The nature ofpureCS (closed shell)/typical-HB (hydrogen bond) with no covalency is predicted forE-*-Xin (1) and (3),regularCS/typical-HB nature with covalency is predicted for (4), and an intermediate nature is predicted for (2). The NBO energies evaluated forE-*-Xin (1)–(4) are substantially larger than those in modelAdue the shortened length at the naphthalene 1,8-positions. The nature ofE2X2of σ(4c–6e) is well elucidatedviaQTAIM-DFA.

The accumulation of misfolded proteins in the ER provokes ER stress by increasing the demand for energy, chaperones, and other proteins that are needed to fold client proteins or to degrade unfoldable secretory cargo. This stress activates a signaling network called the unfolded protein response (UPR). However, recent accumulated data suggested that the UPR also provides important signals for regulating cell differentiation and maturation. However, the relationship between UPR and mammary gland development has not been fully elucidated. To define the involvement of the UPR in mammary gland development, mammary glands were collected from non-pregnant mice, at days 5, 10 and 15 of pregnancy, at days 1 and 7 of lactation, and the expression patterns of UPR-related genes were determined by real-time PCR. We found that the mRNA expression of ATF4 and XBP1 significant increased during pregnancy. Moreover, we found that both ATF4 and XBP1 proteins are expressed in mammary epithelial cells by immunohistological analysis. In order to know the role of ATF4 and XBP1 in the differentiation of mammary epithelial cell, we performed gene knockdown experiment using HC11 cells. We found that ATF4 or XBP1 knockdown suppressed the mRNA expression of beta-casein and lactogenic hormone receptor in differentiating HC11 cells. Our results demonstrate that XBP1 and ATF4, which are UPR-related transcription factors, directly or indirectly participate in cell differentiation mechanisms through the regulation of the expression of lactogenic hormone receptors in mouse mammary epithelial cells.

Dynamic and static nature of intramolecular π-π interactions between ethylene moieties in diethenodihydronaphthanaphtalene (1 b) and derivatives (2 b–12 b) are elucidated by employing QTAIM-DFA (QTAIM dual functional analysis). During the course of the investigations, doubly degenerated bond paths were detected between carbon atoms in opposite benzene rings of dibenzo-derivative of 1 b with an etheno-bridge on the backside (11 b). It must be very curious, since one BP should correspond to an interaction between two carbon atoms. Intramolecular π-π interactions in 1 b–12 b are all classified by the pure CS (closed shell) interactions. The interactions between ethylene groups, with no substituents as in 1 b–8 b, are predicted to have the van der Waals (vdW) nature. Those for 9 b–12 b have the hydrogen bond (HB) nature with no covalency, where the ethylene moieties are included in one or two benzene ring(s), except for 10 b, if evaluated with MP2/6-311G(3d). The character in 10 b is close to the borderline area between the vdW and HB nature with no covalency, although should be the vdW type. The interactions in 2 b–12 b evaluated with MP2/6-311G(3d) are predicted to be somewhat stronger than the case with MP2/6-311G(d), as a whole.

Citrus Sudachi is the special local product of Tokushima Prefecture, and over 98% of Sudachi consumed in Japan every year is produced in Tokushima Prefecture. In this study, we evaluated the function of sudachi peel extract (SPE) using an animal model of obesity. C57BL/6 mice were fed a high-fat diet containing 1% SPE powder. Treatment with SPE significantly decreased body weight compared to that of mice fed a high-fat diet. A significant difference in body weight was observed between the control and SPE groups from 7 weeks after the start of the experiment, the significant difference continued until the end of the 14-week experiment. Reduction of blood glucose levels following insulin administration in SPE-treated mice was grater than that in control mice. Determination of mRNA expression in adipose tissue showed that the expression level of TNF-α in the SPE group was significantly decreased compared to that on the control group. These results suggest that SPE potentially has the ability to attenuate body weight gain. J. Med. Invest. 64: 20-23, February, 2017.

The nature of EH2-*-π(C14H10) interactions (E = O, S, Se and Te) of an anthracene system was elucidated by applying QTAIM dual functional analysis (QTAIM-DFA) after clarification of the structural features with quantum chemical (QC) calculations. π-HB (hydrogen bond) interactions were detected for E = O, S, Se and Te, whereas π-EB (chalcogen bond) interactions were observed for E = O in (EH2)-*-π(C14H10), where the bond paths connected H in EH2 to C14H10 in π-HB, and they connected E in EH2 to C10H8 in π-EB. The QTAIM-DFA parameters of (R, θ) and (θp, κp) were evaluated for the interactions via analysing the plots of Hb(rc) versus Hb(rc) − Vb(rc)/2 for the interactions at the bond critical points. Data obtained from the perturbed structures around the fully optimized structures were employed for the plots, in addition to the fully optimized structures. Data obtained from the fully optimized structures were analysed using (R, θ), which corresponded to the static nature, and those obtained from the perturbed structures were analysed using (θp, κp), which represented the dynamic nature of the interactions, where θp corresponds to the tangent line of the plot and κp is the curvature. The θ and θp values are less than 90° for all the interactions examined, except for the iH-*-11C(π) interaction in TeH2-*-C14H10 (C1: IIBAtc), where iH is located closer to the centre of C14H10. Therefore, the interactions examined were predicted to have vdW nature, appeared in the pure-CS (closed shell) interaction region, although iH-*-11C(π) was predicted to have the pure-CS/typical-HB nature without covalency. Additionally, the π-HB interaction seems to be slightly stronger than π-EB in (OH2)-*-π(C14H10).

Fatty acids play important roles in the regulation of endoplasmic reticulum (ER) stress-induced apoptosis in different cells. Currently, the effects of fatty acids on bovine mammary epithelial cells (MEC) remain unknown. Our study examined bovine MEC viability and measured unfolded protein response (UPR)-related gene and protein expressions following fatty acid treatments. To evaluate the role of fatty acids, we treated MAC-T cells (a line of MEC) with 100 to 400 μM of saturated (palmitic and stearic acid) and unsaturated (palmitoleic, oleic, linoleic, and linolenic acid) fatty acids and 1 to 5 mM of short- and medium-chain fatty acids (acetic, propionic, butyric, and octanoic acid). Thereafter, we determined UPR-related gene expression using quantitative real-time PCR. Palmitic acid stimulated expression of XBP1s, ATF4, ATF6A, and C/EBP homologous protein (CHOP). Stearic acid increased expression of XBP1s and CHOP and decreased expression of ATF4 and ATF6A. Results of Western blot analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that palmitic and stearic acid reduced MAC-T cell viability and induced extreme ER stress by increasing the protein expression of ER stress markers, such as phospho-PKR-like endoplasmic reticulum kinase, phospho-eIF2α, cleaved CASP-3, and CHOP. Among unsaturated long-chain fatty acids, palmitoleic acid increased expression of ATF4 and ATF6A. Oleic acid increased expression of XBP1s, ATF4, and ATF6A. Linoleic and linolenic acids increased expression of XBP1s, ATF4, and ATF6A but decreased expression of XBP1s and ATF6A at the highest dose. Although palmitoleic, oleic, and linoleic acid decreased CHOP expression, only palmitoleic acid increased MAC-T cell viability. Therefore, unsaturated long-chain fatty acids did not induce severe ER stress. Acetic, propionic, and butyric acids decreased expression of ATF4, ATF6A, and CHOP and increased XBP1s expression. Although only octanoic acid increased ATF4 and ATF6A expressions, it lowered expression of XBP1s and CHOP. Although fatty acid treatment did not increase the levels of ER stress proteins, butyric and octanoic acids reduced cell viability, possibly because of early differentiation. These results suggest that saturated fatty acids play important roles in MEC viability by inducing severe ER stress compared with unsaturated fatty acids. In addition, acetic and propionic acids (short- and medium-chain fatty acids) reduced ER stress. Therefore, the present study reflects the new insight that serum fatty acid concentration plays an important role in maintaining the lactation physiology of dairy cows.

The intrinsic dynamic and static nature of G-*-E-*-Y σ(3c-4e) interactions was elucidated with the quantum theory of atoms in molecules dual functional analysis (QTAIM-DFA), employing

The intrinsic dynamic and static nature of intramolecular OH–*–π interactions is elucidated using a QTAIM dual functional analysis (QTAIM-DFA) after clarifying the structural features. Asterisks (*) are employed to emphasize the presence of bond critical points (BCPs) on the bond paths (BPs), which correspond to the interactions in question. Data from the fully optimized structures correspond to the static nature of the interactions. In our treatment, data from the perturbed structures, which are based around the fully optimized structure, are employed for the analysis in addition to those from the fully optimized structure, which represent the dynamic nature of the interaction. Seven intramolecular OH–*–C(π) interactions were detected in six-membered rings, with six BPs and BCPs for each, among the 72 conformers of the species examined here (1–15). The interactions are predicted to have a vdW or t-HBnc (typical hydrogen bonds with no covalency) nature, which appeared in the pure closed shell region. They appear to be stronger than the corresponding intermolecular interactions. Nine BPs with BCPs were also detected for the intramolecular O–*–X interactions (X = C(π) and H(π), joined to C(π)) in the 5–7-membered rings. The E(2) values of the interactions, as obtained by NBO, are discussed in relation to the stabilities of the conformers and the BPs with BCPs.

The nature of Br4σ(4c–6e) of the BBr-∗-ABr-∗-ABr-∗-BBr form is elucidated for SeC12H8(Br)SeBr---Br-Br---BrSe(Br)C12H8Se, the selenanthrene system, and the models with QTAIM dual functional analysis (QTAIM-DFA). Asterisks (∗) are employed to emphasize the existence of bond critical points on the interactions in question. Data from the fully optimized structure correspond to the static nature of interactions. In our treatment, data from the perturbed structures, around the fully optimized structure, are employed for the analysis, in addition to those from the fully optimized one, which represent the dynamic nature of interactions. The ABr-∗-ABr and ABr-∗-BBr interactions are predicted to have the CT-TBP (trigonal bipyramidal adduct formation through charge transfer) nature and the typical hydrogen bond nature, respectively. The nature of Se2Br5σ(7c–10e) is also clarified typically, employing an anionic model of [Br-Se(C4H4Se)-Br---Br---Br-Se(C4H4Se)-Br]−, the 1,4-diselenin system, rather than (BrSeC12H8)Br---Se---Br-Br---Br-Se(C12H8Se)-Br, the selenanthrene system.

The intrinsic dynamic and static nature of G–*–E–*–Y σ(3c–4e) interactions was elucidated with the quantum theory of atoms in molecules dual functional analysis (QTAIM-DFA), employing o-MenGCH2C6H4EY (MenG = Me2N and MeE; E = O, S, Se and Te; Y = F, Cl, Br, I, EMe and Me). Asterisks (*) are employed to emphasize the existence of bond critical points (BCPs) on the bond paths (BPs), corresponding to the interactions in question. Data from the fully optimized structure correspond to the static nature of interactions. The dynamic nature is called the intrinsic dynamic nature if the perturbed structures are generated using the coordinates derived from the compliance constants. Basis sets of the Sapporo-TZP type with diffusion functions are employed for the heteroatoms at the MP2 level. The noncovalent G–*–E interactions in GEY σ(3c–4e) are predicted to demonstrate van der Waals bonding to CT-TBP (trigonal bipyramidal adduct formation through charge transfer) nature, while the E–*–Y bonds have the covalent nature. Some E–F bonds show strong ionic character when G–*–E is predicted to be stronger than E–*–Y. The contributions of the CT terms to the G–*–E interactions, evaluated with NBO, are discussed in relation to the predicted nature. The E(2) values based on NBO are strongly correlated to the compliance constants for the G–*–E interactions if suitably treated separately.

The nature of halogen bonds of the Y-X-✶-π(C6 H6 ) type (X, Y=F, Cl, Br, and I) have been elucidated by using the quantum theory of atoms in molecules (QTAIM) dual-functional analysis (QTAIM-DFA), which we proposed recently. Asterisks (✶) emphasize the presence of bond-critical points (BCPs) in the interactions in question. Total electron energy densities, Hb (rc ), are plotted versus Hb (rc )-Vb (rc )/2 [=(ħ(2) /8m)∇(2) ρb (rc )] for the interactions in QTAIM-DFA, in which Vb (rc ) are potential energy densities at the BCPs. Data for perturbed structures around fully optimized structures were used for the plots, in addition to those of the fully optimized ones. The plots were analyzed by using the polar (R, θ) coordinate for the data of fully optimized structures with (θp , κp ) for those that contained the perturbed structures; θp corresponds to the tangent line of the plot and κp is the curvature. Whereas (R, θ) corresponds to the static nature, (θp , κp ) represents the dynamic nature of the interactions. All interactions in Y-X-✶-π(C6 H6 ) are classified by pure closed-shell interactions and characterized to have vdW nature, except for Y-I-✶-π(C6 H6 ) (Y=F, Cl, Br) and F-Br-✶-π(C6 H6 ), which have typical hydrogen-bond nature without covalency. I-I-✶-π(C6 H6 ) has a borderline nature between the two. Y-F-✶-π(C6 H6 ) (Y=Br, I) were optimized as bent forms, in which Y-✶-π interactions were detected. The Y-✶-π interactions in the bent forms are predicted to be substantially weaker than those in the linear F-Y-✶-π(C6 H6 ) forms.

The nature of extended hypervalent interactions of the BE–*–AE–*–AE–*–BE type is elucidated for 1-(8-MeBEC10H6)AE–AE(C10H6BEMe-8′)-1′, (1 (AE, BE) = (S, S), 2 (S, Se), 3 (Se, S) and 4 (Se, Se)) and models A–D, BR2BE⋯(AR)AE–AE(AR)⋯BEBR2 (AR, BR = H and Me). QTAIM dual functional analysis, which we proposed recently, is applied to the analysis. Total electron energy densities Hb(rc) are plotted versus Hb(rc) − Vb(rc)/2 for the interactions at bond critical points (BCPs; *), where Vb(rc) show potential energy densities at BCPs. Data for the perturbed structures around the fully optimized structures are employed for the plots, in addition to those of the fully optimized ones. While the data for the fully optimized structures are analysed by the polar coordinate (R, θ) representation, those containing the perturbed structures are by (θp, κp): θp corresponds to the tangent line for the plot and κp is the curvature. While (R, θ) show the static nature, (θp, κp) represent the dynamic nature of interactions. All AE–*–AE interactions in 1–4 and models A–D are classified by the shard shell interactions and have the character of a weak covalent nature. The AE–*–BE interactions in 1–4 are all classified by the regular closed shell interactions. They are predicted to have the typical HB (hydrogen bond) nature with covalency for 1 and 2 but the nature of the molecular complex formation through CT for 3 and 4. The AE–*–BE interactions in models A–D are predicted to be weaker than those in 1–4.

The nature of the π–interactions in the 1 : 1 and 2 : 1 adducts of EH2 with the naphthalene π-system (E = O, S, Se and/or Te) is elucidated by applying QTAIM-DFA (QTAIM dual functional analysis). The H–*–π interactions are detected in EH2–*–π(C10H8) and (EH2)2–*–π(C10H8) for E = S, Se and Te, whereas E–*–π interactions are in OH2–*–π(C10H8), (OH2)2–*–π(C10H8) and HE–H–*–π(C10H8) (denoted by HHE–*–C10H8) (E = S, Se and Te). Asterisks * emphasize the existence of bond critical points (BCPs) on the interactions in question. Hb(rc) are plotted versus Hb(rc) − Vb(rc)/2 at the BCPs in QTAIM-DFA. Plots for the fully optimized structures are analyzed using the polar coordinate (R, θ) representation. Those containing the perturbed structures are by (θp, κp): θp corresponds to the tangent line of the plot and κp is the curvature. While (R, θ) describe the static nature, (θp, κp) represent the dynamic nature of interactions. The θ and θp values are less than 90° for all interactions in question, examined in this work, except for θp = 90.6° for HHTe–*–π(C10H8). Therefore, all interactions examined are classified by the pure-CS (closed shell) interactions and predicted to have vdW-nature, except for HHTe–*–π(C10H8), which should have the character of the typical HB-nature without covalency. The π–EB interaction in HHS–*–C10H8 is predicted to have the border character between the vdW-nature and the typical HB-nature without covalency, since θp = 89.8°. The nature of four interactions appeared between 2H in TeH2 and C10H8 in TeH2–*–π(C10H8) is also clarified well using QTAIM-DFA.

Mild heat stress (39 &deg, C&ndash, 40 &deg, C) can positively regulate cell proliferation and differentiation. Indeed, mild heat treatment at 39 &deg, C enhances the less-permeable tight junctions (TJs) formation and milk production in mammary epithelial cells. However, the molecular mechanisms of this response have not yet been delineated. In this study, the involvement of temperature-sensitive transient receptor potential vanilloid 4 (TRPV4) in the increase of &beta, casein and TJ protein-encoding gene expression in response to mild heat treatment (39 &deg, C) has been explored using HCll mouse mammary epithelial cells. Severe heat treatment (41 &deg, C) induced the transcriptional level of Chop (C/EBP homologous protein, proapoptotic marker) and reduced the cell viability. It is speculated that the difference in unfolded protein response (UPR) gene expression upon stimulation at 39 &deg, C vs. 41 &deg, C controls cell survival vs. cell death. The accumulation of Trpv4 mRNA was significantly higher in 39 &deg, C heat treatment cells. The &beta, casein, Zo-1 (zona occludens-1), Ocln (occludin), and Cldn3 (claudin 3) transcript levels were significantly increased in response to the addition of a selective TRPV4 channel agonist (GSK1016790A) at 37 &deg, C. TRPV4 stimulation with GSK1016790A also increased the X-box-binding protein 1 splicing form (Xbp1s) at the transcript level. The increase in the mRNA levels of &beta, casein, Zo-1, Ocln, and Cldn3 in response to 39 &deg, C heat treatment was suppressed by XBP1 knockdown. Moreover, the transcript level of Trpv4 was significantly increased at Day 15 of gestation, and its expression declined after 1 day of lactation. TRPV4 is activated not only by temperature but also by mechanical forces, such as cell stretching and shear stress, which guide mammary epithelial development in a normal mammary gland. These findings provide new insights of the possible function of TRPV4 in mammary gland development.

The nature of the transannular E-∗-E' interactions in neutral, radical cationic, and dicationic forms of cyclo-E(CH2CH2CH2)2E' (1) (E, E' = S, Se, Te, and O) (1, 1(•+), and 1(2+), respectively) is elucidated by applying QTAIM dual functional analysis (QTAIM-DFA). Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 for the data of E-∗-E' at BCPs in QTAIM-DFA, where ∗ emphasizes the existence of BCP. Plots for the fully optimized structures are analyzed by the polar coordinate (R, θ) representation. Those containing the perturbed structures are by (θp, κp): θp corresponds to the tangent line of the plot, and κp is the curvature. While (R, θ) describes the static nature, (θp, κp) represents the dynamic nature of interactions. The nature is well-specified by (R, θ) and (θp, κp). E-∗-E' becomes stronger in the order of 1 < 1(•+) < 1(2+), except for O-∗-O. While E-∗-E' (E, E' = S, Se, and Te) in 1(2+) are characterized as weak covalent bonds, except for S-∗-Te (MC nature through CT) and Se-∗-Te (TBP nature through CT), O-∗-E' seems more complex. The behavior of E-∗-E' in 1(2+) is very close to that of cyclo-E(CH2CH2CH2)E' (E, E' = S, Se, Te, and O), except for O-∗-O.

Atoms-in-molecules dual functional analysis (AIM-DFA) is applied to the E–E′ bonds (E, E′ = S and Se) in R-cystine (1) and the derivatives of 1, together with MeEE′Me. Hb(rc) are plotted versus Hb(rc) − Vb(rc)/2 at bond critical points (BCPs), where Hb(rc) − Vb(rc)/2 = (ħ2/8m)∇2ρb(rc). The plots are analyzed by the polar coordinate (R, θ) representation. Data of perturbed structures around the fully optimized structures are also plotted in this treatment. Perturbed structures are generated using NIV (normal coordinates of internal vibrations). Each plot for an interaction with data of a fully optimized and four perturbed structures gives a curve, which supplies important information. It is expressed by (θp, κp): θp corresponds to the tangent line for the plot measured from the y-direction and κp is the curvature. While (R, θ) correspond to the static nature of interactions, (θp, κp) represent the dynamic nature. The behavior of the E–E′ bonds is well described by (R, θ) and (θp, κp).

An extended hypervalent S

Indirect one-bond nuclear spin-spin couplings between M and C [

Citrus Sudachi is the special local product of Tokushima Prefecture, and over 98% of Sudachi consumed in Japan every year is produced in Tokushima Prefecture. In this study, we evaluated the function of sudachi peel extract (SPE) using an animal model of obesity. C57BL/6 mice were fed a high-fat diet containing 1% SPE powder. Treatment with SPE significantly decreased body weight compared to that of mice fed a high-fat diet. A significant difference in body weight was observed between the control and SPE groups from 7 weeks after the start of the experiment, the significant difference continued until the end of the 14-week experiment. Reduction of blood glucose levels following insulin administration in SPE-treated mice was grater than that in control mice. Determination of mRNA expression in adipose tissue showed that the expression level of TNF-α in the SPE group was significantly decreased compared to that on the control group. These results suggest that SPE potentially has the ability to attenuate body weight gain. J. Med. Invest. 64: 20-23, February, 2017.

The dynamic and static nature of extended hypervalent interactions of the BE···AE···AE···BE type are elucidated for four center–seven electron interactions (4c–7e) in the radical cationic dimers (1·+) and 4c–6e in the dicationic dimers (12+) of 1,5-(dichalcogena)canes (2: AE(CH2CH2CH2)2BE: AE, BE = S, Se, Te, and O). The quantum theory of atoms-in-molecules dual functional analysis (QTAIM-DFA) is applied for the analysis. Total electron energy densities Hb(rc) are plotted versus Hb(rc) – Vb(rc)/2 [= (ℏ2/8m)∇2ρb(rc)] at bond critical points (BCPs) of the interactions, where Vb(rc) values show potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature of the interactions. Those from the perturbed structures around the fully optimized ones are also plotted, in addition to those of the fully optimized ones, which represent the dynamic nature of interactions. The BE···AE–AE···BE interactions in 12+ are stronger than the corresponding ones in 1·+, respectively. ...

The nature of the E-*-E' bonds in neutral, monoanionic, monocationic, and dicationic forms of HEE'H (1), MeEE'Me (2), and cyclo-1,2-EE'(CH2)3 (3) (E, E' = O, S, Se, Te) is investigated by applying AIM (atoms-in-molecules method) dual functional analysis. Hb(rc) are plotted versus Hb(rc) – Vb(rc)/2 for the data of E-*-E' at bond critical points (BCPs) of fully optimized structures and perturbed structures around the fully optimized ones. Plots for the fully optimized structures are analyzed by the polar coordinate (R, θ) representation. The (θp, κp) parameters are derived from those of the perturbed structures: θp corresponds to the tangent line of each plot, and κp is the curvature. While (R, θ) correspond to the static nature, (θp, κp) represent the dynamic nature of interactions. The nature of E-*-E' in the neutral and charged species is classified by comparing their θ and θp values with those of the standard interactions as a reference. Data for E-*-E' in the neutral forms of 1–3 appear in the shared-shell (SS) region (180° < θ), except for MeS-*-TeMe (2c), which does in the regular closed-shell (CS) region (90° < θ < 180°). The E–E' bonds in the monoanionic forms of 1–3 become much longer and weakened. Therefore, data of the monoanionic forms appear in the regular CS. On the other hand, the strengths of E-*-E' in the mono- and dicationic forms are almost equal to those in the neutral forms of 1–3 in the plots, irrespective of the shorter E-*-E' lengths in the cationic forms, relative to the neutral forms.

To systematically elucidate molecular and electronic structures of aromatic selenoic acid salts and their heavier congeners, they were synthesized by reacting selenoic, selenothioic, and diselenoic...

The relativistic effects on absolute magnetic shielding tensors [σ(Z: Z = Te, Se and S)] are explicitly evaluated for various tellurium, selenium and sulfur species using the DFT(BLYP)-GIAO method. Calculations of σ(Te), σ(Se) and σ(S) are performed under the spin–orbit ZORA relativistic (Rlt-so) and nonrelativistic (Non) conditions with the Slater-type basis sets of the quadruple zeta all electron with four polarization functions (QZ4Pae). Structures optimized at the MP2 level under nonrelativistic conditions are employed for the evaluations. While the range of the relativistic effects on the total shielding tensors for Te (Δσt(Te)Rlt-so = σt(Te)Rlt-so − σd+p(Te)Non) is predicted to be −55 to 658 ppm, that for Δσt(S) is predicted to be 5 to 32 ppm, except for Me2SBr2 (TBP), where Δσt(S)Rlt-so = −29 ppm. The range for Δσt(Se) is 2 to 153 ppm. The magnitudes of the relativistic effects on σt(Te), σt(Se) and σt(S) are about 25 : 5 : 1. The applicability of σt(Te)Rlt-so to analyze δ(Te)obsd is also examined, mainly with the OPBE//OPBE method under the spin–orbit ZORA relativistic conditions with QZ4Pae, in addition to the above method.

The nature of E

Dynamic and static behavior of the interactions in the EH2 adducts of a benzene π-system (E = O, S, Se and Te) is elucidated by applying QTAIM-DFA (QTAIM dual functional analysis). Two types of H-*-π and E-*-π interactions are detected in the adducts, where the asterisk (*) emphasizes the existence of the bond critical point (BCP) on the interaction in question. Total electron energy densities Hb(rc) are plotted versus Hb(rc) -Vb(rc)/2 [=(ℏ(2)/8m)∇(2)ρb(rc)] at BCPs in QTAIM-DFA, where Vb(rc) are the potential energy densities at BCPs. Data from the fully optimized structures are analyzed by polar (R, θ) coordinate representation. Each plot for an interaction, containing data from the perturbed structures with those of the fully optimized one, shows a specific curve, which provides important information. The plot is expressed by (θp, κp): θp corresponds to the tangent line for the plot and κp is the curvature. θ and θp are measured from the y-axis and y-direction, respectively. Moreover, (R, θ) corresponds to the static nature, (θp, κp) represents the dynamic nature of interactions. While θ classifies the interaction in question, θp characterizes it. Both values are less than 90° for all H-*-π and E-*-π interactions examined in this study; therefore, they are all classified by the pure closed-shell interactions and predicted to have the character of vdW nature. However, it is suggested that E-*-π has the nature of the stronger interaction than the case of H-*-π for dynamic behavior in the same species evaluated at the MP2 and M06-2X levels. The nature of the interactions is well analyzed and specified by applying QTAIM-DFA.