Glycemic Excursion and Insulin Action Revealed in a Rare Case of Type 1 Diabetes Complicated with Short Bowel Syndrome.

We herein report a 52-year-old woman with a rare combination of short bowel syndrome due to massive resection of the small intestine and complete loss of endogenous insulin due to type 1 diabetes. To provide nutritional support, she was treated with total parenteral nutrition with co-administration of insulin, requiring careful matching of insulin and glucose levels. This case report provides insights on glycemic excursion and insulin action in type 1 diabetes, even when both insulin and glucose are administered directly into circulation, and the usual obstacles caused by subcutaneous injection of insulin and oral intake of nutrients are eliminated.

Single-Component Organic Solar Cells Based on Intramolecular Charge Transfer Photoabsorption.

Conjugated donor-acceptor molecules with intramolecular charge transfer absorption are employed for single-component organic solar cells. Among the five types of donor-acceptor molecules, the strong push-pull structure of DTDCPB resulted in solar cells with high JSC, an internal quantum efficiency exceeding 20%, and high VOC exceeding 1 V with little photon energy loss around 0.7 eV. The exciton binding energy (EBE), which is a key factor in enhancing the photocurrent in the single-component device, was determined by quantum chemical calculation. The relationship between the photoexcited state and the device performance suggests that the strong internal charge transfer is effective for reducing the EBE. Furthermore, molecular packing in the film is shown to influence photogeneration in the film bulk.

A Rare Case of Adrenal Cysts Associated With Bilateral Incidentalomas and Diffuse Hyperplasia of the Zona Glomerulosa.

Characterization of adrenocortical disorders is challenging because of varying origins, laterality, the presence or absence of hormone production, and unclarity about the benign or malignant nature of the lesion. Histopathological examination in conjunction with immunohistochemistry is generally considered mandatory in this characterization. We report a rare case of bilateral adrenocortical adenomas associated with unilateral adrenal endothelial cysts in a 65-year-old woman whose condition was not diagnosed before surgery. Detailed histological examination of the resected adrenal glands revealed hyperplasia in the zona glomerulosa. Despite hyperplasia, the patient had normal serum aldosterone levels and renin activity without clinical evidence of hypertension. The patient was treated with a sodium-glucose cotransporter protein 2 (SGLT2) inhibitor. This may have stimulated the renin-angiotensin-aldosterone system. To the best of our knowledge, this is the first case in which both relatively large bilateral adrenocortical adenomas and unilateral adrenal endothelial cysts were detected. This case also highlights the complexity and difficulty of preoperative diagnosis. Furthermore, this case reports the first detailed histopathological examination of adrenal lesions with SGLT2 treatment and the possibility of SGLT2 inhibitor treatment resulting in histological hyperplasia in the zona glomerulosa; however, it is difficult to prove a causative relationship between SGLT2 inhibitors and hyperplasia of the zona glomerulosa based on the data of this case. It can be confirmed only under limited conditions; therefore, further studies on adrenal gland histology employing SGLT2 inhibition are warranted.

Identification of kit-ligand a as the Gene Responsible for the Medaka Pigment Cell Mutant few melanophore.

The body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. The few melanophore (fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identify kit-ligand a (kitlga) as the gene whose mutation gives rise to the fm phenotype. This identification was confirmed by generation of kitlga knockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue the fm mutant phenotype. We also found that expression of sox5, pax7a, pax3a, and mitfa genes is down-regulated in both fm and kitlga knockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit-related pigmentation disorders such as piebaldism in humans, and our kitlga knockout medaka may prove useful as a tool for drug screening.

Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients.

Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150-200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24-0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection.

Loss of the six3/6 controlling pathways might have resulted in pinhole-eye evolution in Nautilus.

Coleoid cephalopods have an elaborate camera eye whereas nautiloids have primitive pinhole eye without lens and cornea. The Nautilus pinhole eye provides a unique example to explore the module of lens formation and its evolutionary mechanism. Here, we conducted an RNA-seq study of developing eyes of Nautilus and pygmy squid. First, we found that evolutionary distances from the common ancestor to Nautilus or squid are almost the same. Although most upstream eye development controlling genes were expressed in both species, six3/6 that are required for lens formation in vertebrates was not expressed in Nautilus. Furthermore, many downstream target genes of six3/6 including crystallin genes and other lens protein related genes were not expressed in Nautilus. As six3/6 and its controlling pathways are widely conserved among molluscs other than Nautilus, the present data suggest that deregulation of the six3/6 pathway led to the pinhole eye evolution in Nautilus.

Grating-assisted spectrally-narrowed emissions from an organic slab crystal excited with a mercury lamp.

We report spectrally-narrowed emissions that take place from an organic semiconductor slab crystal of 2,5-bis(4-biphenylyl)thiophene (BP1T) under a low excitation-intensity regime. These emissions are caused with a mercury lamp that operates on a household power supply with an electric current approximately 1 A. The BP1T slab crystal is equipped with a distributed Bragg reflector. To complete this structure the slab crystal is attached to a diffraction grating that is engraved on a surface of a quartz glass substrate. The diffraction gratings have precisely been formed using a focused ion beam with a nanometer-defined precision. The spectral narrowing accompanied by the emission intensity increment is related to the strong mode-coupling between the forward electromagnetic wave and the backward (i.e., reflected) wave within the grating zone. Using a laser we also carried out the emission measurements on the BP1T crystals under a high excitation-intensity regime. The emissions are characterized as the longitudinal multimode laser oscillation, enabling us to determine the group refractive index of 4.56 for the BP1T slab crystal. Under both the low and high excitation-intensity regimes excitons are dominant species of the emission. Their participation in the spectrally-narrowed emissions is briefly discussed.

Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein.

Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage recognition in global genome nucleotide excision repair (NER). The protein forms in vivo a heterotrimeric complex involving one of the two human homologs of Saccharomyces cerevisiae Rad23p and centrin 2, a centrosomal protein. Because centrin 2 is dispensable for the cell-free NER reaction, its role in NER has been unclear. Binding experiments with a series of truncated XPC proteins allowed the centrin 2 binding domain to be mapped to a presumed alpha-helical region near the C terminus, and three amino acid substitutions in this domain abrogated interaction with centrin 2. Human cell lines stably expressing the mutant XPC protein exhibited a significant reduction in global genome NER activity. Furthermore, centrin 2 enhanced the cell-free NER dual incision and damaged DNA binding activities of XPC, which likely require physical interaction between XPC and centrin 2. These results reveal a novel vital function for centrin 2 in NER, the potentiation of damage recognition by XPC.

UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.

The xeroderma pigmentosum group C (XPC) protein complex plays a key role in recognizing DNA damage throughout the genome for mammalian nucleotide excision repair (NER). Ultraviolet light (UV)-damaged DNA binding protein (UV-DDB) is another complex that appears to be involved in the recognition of NER-inducing damage, although the precise role it plays and its relationship to XPC remain to be elucidated. Here we show that XPC undergoes reversible ubiquitylation upon UV irradiation of cells and that this depends on the presence of functional UV-DDB activity. XPC and UV-DDB were demonstrated to interact physically, and both are polyubiquitylated by the recombinant UV-DDB-ubiquitin ligase complex. The polyubiquitylation altered the DNA binding properties of XPC and UV-DDB and appeared to be required for cell-free NER of UV-induced (6-4) photoproducts specifically when UV-DDB was bound to the lesion. Our results strongly suggest that ubiquitylation plays a critical role in the transfer of the UV-induced lesion from UV-DDB to XPC.

Waves in a reaction-transport system with memory, long-range interactions, and transmutations.

We develop a theory of wave propagation into an unstable state for a system of integral equations with memory, long-range interactions, and transmutations. In particular we use continuous-time random walk theory to describe the transport and transmutation processes. We use a hyperbolic scaling and Hamilton-Jacobi formalism to derive formulas for the speed of propagation of the traveling wave generated by the system in the long-time large-distance limit. Our theory is valid for arbitrary waiting-time, jump-length and, transmutation probability density functions and the propagation speed can generally be found numerically. However, we illustrate our theory by considering an example where analytic results are possible--that is, for a system of Markovian reaction-transport equations. We derive formulas to determine the propagation speed in both the so-called weakly coupled and strongly coupled cases.

Relative levels of the two mammalian Rad23 homologs determine composition and stability of the xeroderma pigmentosum group C protein complex.

Mammalian cells express two Rad23 homologs, HR23A and HR23B, which have been implicated in regulation of proteolysis via the ubiquitin/proteasome pathway. Recently, the proteins have been shown to stabilize xeroderma pigmentosum group C (XPC) protein that is involved in DNA damage recognition for nucleotide excision repair (NER). Because the vast majority of XPC forms a complex with HR23B rather than HR23A, we investigated possible differences between the two Rad23 homologs in terms of their effects on the XPC protein. In wild-type mouse embryonic fibroblasts (MEFs), endogenous XPC was found to be relatively stable, while its steady-state level and stability appeared significantly reduced by targeted disruption of the mHR23B gene, but not by that of mHR23A. Loss of both mHR23 genes caused a strong further reduction of the XPC protein level. Quantification of the two mHR23 proteins revealed that in normal cells mHR23B is actually approximately 10 times more abundant than mHR23A. In addition, overexpression of mHR23A in the mHR23A/B double knock out cells restored not only the steady-state level and stability of the XPC protein, but also cellular NER activity to near wild-type levels. These results indicate that the two Rad23 homologs are largely functionally equivalent in NER, and that the difference in expression levels explains for a major part the difference in complex formation with as well as stabilization effects on XPC.

Non-Markovian random processes and traveling fronts in a reaction-transport system with memory and long-range interactions.

The problem of finding the propagation rate for traveling waves in reaction-transport systems with memory and long-range interactions has been considered. Our approach makes use of the generalized master equation with logistic growth, hyperbolic scaling, and Hamilton-Jacobi theory. We consider the case when the waiting-time distribution for the underlying microscopic random walk is modeled by the family of gamma distributions, which in turn leads to non-Markovian random processes and corresponding memory effects on mesoscopic scales. We derive formulas that enable us to determine the front propagation rate and understand how the memory and long-range interactions influence the propagation rate for traveling fronts. Several examples involving the Gaussian and discrete distributions for jump densities are presented.