Isolation and functional characterization of fatty acid delta5-elongase gene from the liverwort Marchantia polymorpha L

Bryophyte Marchantia polymorpha L. produces C22 very-long-chain polyunsaturated fatty acid (VLCPUFA). Thus far, no enzyme that mediates elongation of C20 VLCPUFAs has been identified in land plants. Here, we report the isolation and characterization of the gene MpELO2, which encodes an ELO-like fatty acid elongase in M. polymorpha. Heterologous expression in yeast demonstrated that MpELO2 encodes delta5-elongase, which mediates elongation of arachidonic (20:4) and eicosapentaenoic acids (20:5). Phylogenetic and gene structural analysis indicated that the MpELO2 gene is closely related to bryophyte Delta6-elongase genes for C18 fatty acid elongation and diverged from them by local gene duplication.     

Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse

Nicorandil is an orally available drug that can act as a nitric oxide donor, an antioxidant, and an ATP-dependent K channel activator. We hypothesized that it may have a beneficial role in treating diabetic nephropathy. We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle. Mice were treated for 8 wk. Histology, blood pressure, and renal function were determined. Additional studies involved examining the effects of nicorandil on cultured human podocytes. Here, we found that nicorandil did not affect blood glucose levels, blood pressure, or systemic endothelial function, but significantly reduced proteinuria and glomerular injury (mesangiolysis and glomerulosclerosis). Nicorandil protected against podocyte loss and podocyte oxidative stress. Studies in cultured podocytes showed that nicorandil likely protects against glucose-mediated oxidant stress via the ATP-dependent K channel as opposed to its NO-stimulating effects. In conclusion, nicorandil may be beneficial in diabetic nephropathy by preserving podocyte function. We recommend clinical trials to determine whether nicorandil may benefit diabetic nephropathy or other conditions associated with podocyte dysfunction.     

Platelets present antigen in the context of MHC class I

Platelets are most recognized for their vital role as the cellular mediator of thrombosis, but platelets also have important immune functions. Platelets initiate and sustain vascular inflammation in many disease conditions, including arthritis, atherosclerosis, transplant rejection, and severe malaria. We now demonstrate that platelets express T cell costimulatory molecules, process and present Ag in MHC class I, and directly activate naive T cells in a platelet MHC class I-dependent manner. Using an experimental cerebral malaria mouse model, we also demonstrate that platelets present pathogen-derived Ag to promote T cell responses in vivo, and that platelets can be used in a cell-based vaccine model to induce protective immune responses. Our study demonstrates a novel Ag presentation role for platelets.     

Intraductal polypoid growth variant of pancreatic acinar cell carcinoma metastasizing to the intrahepatic bile duct 6 years after surgery: a case report and literature review

We present the first reported case of intraductal polypoid growth (IPG) variant of pancreatic acinar cell carcinoma (ACC) metastasizing to the intrahepatic bile duct. A 58-year-old Japanese woman had previously presented with obstructive jaundice and a 7.0 cm mass in the pancreatic head. She underwent biliary drainage for 2 months followed by pancreatectomy. Histological examination revealed a carcinoma with acinar pattern, immunohistochemically positive for trypsin, and acinar cell carcinoma was diagnosed. IPGs were prominent in the main pancreatic duct and its tributaries, extending into the intrapancreatic bile duct with tumor casts in the lumen. Imaging examinations 6 years later revealed a growing lesion within the intrahepatic bile duct. Needle biopsy examination suggested metastasis of ACC, and she underwent chemoradiation therapy and partial hepatectomy. Histological examination demonstrated ACC confined to the intrahepatic bile duct. The localization of metastasis and slow growth may indicate indolent biologic behavior of the IPG variant.     

Dose profiles for lung and breast regions at prospective and retrospective CT coronary angiography using optically stimulated luminescence dosimeters on a 64-detector CT scanner

PurposeThe purpose of our study was to acquire dose profiles at critical organs of lung and breast regions using optically stimulated luminescence (OSL) dosimeters; assess the actual radiation dose delivered at retrospective and prospective computed tomography coronary angiography (CTCA).Materials and methodsUsing a chest CT phantom we applied a prospectively-gated step-and-shoot- and a retrospectively-gated helical mode on a 64-detector row CT scanner. Retrospective scan mode was used with and without electrocardiogram (ECG) based tube current modulation. OSL dosimeters were used to measure dose profiles. In the both scan modes we acquired dose profiles and determined the mean and maximum dose in left lung and in left breast regions.ResultsIn prospective mode, the mean dose was 21.53 mGy in left lung- and 23.59 mGy in left breast region. With respect to the retrospective mode, the mean dose with tube current modulation was 38.63 mGy for left lung- and 46.02 mGy for left breast region, i.e. 0.56 and 0.55 times lower than the mean dose without modulation.ConclusionThe OSL dosimeter is useful for measurement of the actual radiation dose along z-axis at lung and breast regions in the prospective and the retrospective CTCA.     

An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients

Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma TG levels in subjects of Chinese ancestry living in the United States and in a group of non-Chinese Asian ancestry. The frequency of the less common cysteine allele was 4-fold higher (15.1% vs. 3.7%) in Chinese high-TG subjects compared with a low-TG group (Chi-square = 20.2; P < 0.0001), corresponding with a 4.45 times higher risk of hypertriglyceridemia (95% confidence interval, 2.18-9.07; P < 0.001). These results were replicated in the non-Chinese Asians. Heterozygosity was associated, in the high-TG group, with a doubling of TG (P < 0.001), mainly VLDL TG (P = 0.014). All eleven TT homozygotes had severe hypertriglyceridemia, with mean TG of 2,292 +/- 447 mg/dl. Compared with controls, carriers of the T allele had lower postheparin lipoprotein lipase activity but not hepatic lipase activity. In Asian populations, this common polymorphism can lead to profound adverse effects on lipoprotein profiles, with homozygosity accounting for a significant number of cases of severe hypertriglyceridemia. This specific apoA-V variant has a pronounced effect on TG metabolism, the mechanism of which remains to be elucidated.     

EGFR signaling is required for re-establishing the proximodistal axis during distal leg regeneration in the cricket Gryllus bimaculatus nymph

Nymphs of hemimetabolous insects, such as cockroaches and crickets, possess functional legs with a remarkable capacity for epimorphic regeneration. In this study, we have focused on the role of epidermal growth factor receptor (EGFR) signaling in regeneration of a nymphal leg in the cricket Gryllus bimaculatus. We performed loss-of-function analyses with a Gryllus Egfr homolog (Gb'Egfr) and nymphal RNA interference (RNAi). After injection of double-stranded RNA for Gb'Egfr in the body cavity of the third instar cricket nymph, amputation of the leg at the distal tibia resulted in defects of normal distal regeneration. The regenerated leg lacked the distal tarsus and pretarsus. This result indicates that EGFR signaling is required for distal leg patterning in regeneration during the nymphal stage of the cricket. Furthermore, we demonstrated that EGFR signaling acts downstream of the canonical Wnt/Wg signaling and regulates appendage proximodistal (PD) patterning genes aristaless and dachshund during regeneration. Our results suggest that EGFR signaling influences positional information along the PD axis in distal leg patterning of insects, regardless of the leg formation mode.     

A new species of the genus Laboulbenia (Laboulbeniales) on Ophionea indica (Coleoptera, Carabidae, Odacanthini) from Taiwan

Laboulbenia ophioneae is described as a new species with illustrations. It is closely related to Laboulbenia celestialis and Laboulbenia asiatica because of some similarities in the morphology of appendages and perithecia. The present species from the latter two species can be distinguished by the shorter, inflated perithecia, the shorter receptacles, and the appendages consisting of more or less darkly colored, broader branches. This new species was found on elytra of Ophionea indica from Taiwan, which has been also known as a host of Laboulbenia polymorpha. A mature thallus noticed by Terada (2004) on the slide 673b (M. Ishikawa collection) and a young thallus illustrated by Sugiyama (1978, fig. 1-G as L. polymorpha) on 673d (M. Ishikawa collection) are both identified as L. ophioneae.