The ABC subfamily B auxin transporter AtABCB19 is involved in the inhibitory effects of N-1-naphthyphthalamic acid on the phototropic and gravitropic responses of Arabidopsis hypocotyls

N-1-Naphthylphthalamic acid (NPA) causes the abnormal growth and development of plants by suppressing polar auxin transport. The mechanisms underlying this inhibition, however, have remained elusive. In Arabidopsis, we show that a defect in the ABC subfamily B auxin transporter AtABCB19 suppresses the inhibitory effects of NPA on hypocotyl phototropism and gravitropism, but not on hypocotyl elongation. Expression analysis using the auxin reporter gene DR5:GUS further suggests that NPA partially inhibits the asymmetric distribution of auxin in an AtABCB19-dependent manner. These data thus suggest that AtABCB19 plays an important role in the inhibitory effects of NPA on hypocotyl tropism induced by auxin.     

Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes

Fatty acid binding proteins (FABPs) are cytosolic fatty acid chaperones whose biological role and mechanisms of action are not well understood. Here, we developed mice with targeted mutations in two related adipocyte FABPs, aP2 and mal1, to resolve their role in systemic lipid, glucose, and energy metabolism. Mice lacking aP2 and mal1 exhibited a striking phenotype with strong protection from diet-induced obesity, insulin resistance, type 2 diabetes, and fatty liver disease. These mice have altered cellular and systemic lipid transport and composition, leading to enhanced insulin receptor signaling, enhanced muscle AMP-activated kinase (AMP-K) activity, and dramatically reduced liver stearoyl-CoA desaturase-1 (SCD-1) activity underlying their phenotype. Taken together with the previously reported strong protection against atherosclerosis, these results demonstrate that adipocyte/macrophage FABPs have a robust impact on multiple components of metabolic syndrome, integrating metabolic and inflammatory responses in mice and constituting a powerful target for the treatment of these diseases.     

Synip phosphorylation is required for insulin-stimulated Glut4 translocation

Previously we identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)) with serine 99 as a unique Akt2, but not Akt1 or for Akt3, substrate phosphorylation site. Although we have previously reported that serine 99 to phenylalanine (S99F-Synip) resulted in a constitutive inhibition of insulin-stimulated Glut4 translocation, a recent report indicated that Synip serine 99 to alanine mutant (S99A-Synip) failed to inhibit insulin-stimulated Glut4 translocation [H. Sano, S. Kane, E. Sano, G.E. Lienhard, Synip phosphorylation does not regulate insulin-stimulated GLUT4 translocation, Biochem. Biophys. Res. Commun. 332 (2005) 880-884]. To address this apparent discrepancy, we have now examined the S99A-Synip mutant and find that this mutant behaves essentially identical to S99F-Synip in that overexpression inhibits insulin-stimulated Glut4 translocation and is incapable of undergoing insulin-stimulated Syntaxin4 dissociation. These data are consistent with Synip serine 99 phosphorylation required for insulin-stimulated Glut4 translocation.     

Effects of gender on kidney function in magnesium-deficient rats

This study investigated the gender differences in the kidney function of magnesium (Mg)-deficient rats. Male and female rats were fed a control diet or a Mg-deficient diet for 21 d. Mg-deficient diet had no significant effect on kidney calcium (Ca) or phosphorus (P) concentration in male rats, while Ca and P concentrations in female rats were significantly higher in Mg-deficient rats than in the control rats. With regard to indicators of kidney function, no significant differences in creatinine clearance and serum urea nitrogen concentration were observed among the groups. Serum albumin concentrations were significantly lower in rats fed the Mg-deficient diet than in rats fed the control diet. In both sexes, urinary albumin excretion was significantly higher in rats fed the Mg-deficient diet than in rats fed the control diet. Gender differences had no significant influence on creatinine clearance, serum urea nitrogen concentration, serum albumin concentration and urinary albumin excretion. These results suggest that gender differences have no effect on kidney function in Mg-deficient rats under the condition used.     

Impact of brood parasitism and predation on nest survival of the fan-tailed gerygone in New Caledonia

Predation and brood parasitism are common reasons for nesting failure in passerine species and the additive impact by invasive species is a major conservation concern, particularly on tropical islands. Recognising the relative contribution of the different components of nesting failure rates is important to understand co-evolutionary interactions within brood parasite–host systems. In the remote archipelago of New Caledonia, the fan-tailed gerygone Gerygone flavolateralis is the exclusive host of the brood-parasitic shining bronze-cuckoo Chalcites lucidus. Additionally, invasive rodents also possibly have an impact on breeding success. To estimate the impact of potential nest predators, we 1) video monitored nests to identify predators, 2) estimated the probability of predation based on nest visibility and predator abundance and 3) tested the possibility that the location of experimental nests and lack of odour cues decrease the predation by rodents. In addition, we estimated nest survival rates using data collected in different habitats over the course of eight breeding seasons. Nesting success of fan-tailed gerygones was relatively low and predation was the main cause of nesting failure. We recorded mainly predation by native birds, including the shining bronze-cuckoo, whereas predation by rats was rare. In open habitats predation by cuckoos was much lower than predation by other avian predators. Neither predator activity around nests nor nest visibility influenced the probability of predation. Experimental nests in more accessible locations and containing an odorous bait were more exposed to rodent predation. Apparently, the fan-tailed gerygone has either never been specifically vulnerable to predation by rats or has developed anti-predator adaptations.     

Involvement of basal metabolic rate in determination of type of cold tolerance

This study aimed to assess the relationship between basal metabolic rate (BMR) and metabolic heat production, and to clarify the involvement of BMR in determining the phenotype of cold tolerance. Measurements of BMR, maximum oxygen uptake, and cold exposure test were conducted on ten males. In the cold exposure test, rectal (T(rec)) and mean skin temperatures (T(ms)), oxygen uptake, and blood flow at forearm (BF(arm)) were measured during exposure to cold (10 degrees C) for 90 min. Significant correlations were observed between BMR and increasing rate of oxygen uptake, as well as between decreasing rate of BF(arm) and increasing rate of oxygen uptake at the end of cold exposure. These findings suggested that individuals with a lower BMR were required to increase their metabolic heat production during cold exposure, and that those with a higher BMR were able to moderate increased metabolic heat production during cold exposure because they were able to reduce heat loss. This study showed that BMR is an important factor in determining the phenotype of cold tolerance, and that individuals with a low BMR showed calorigenic-type cold adaptation, whereas subjects with a high BMR exhibited adiabatic-type cold adaptation by peripheral vasoconstriction.     

Identification of organoselenium compounds that possess chemopreventive properties in human prostate cancer LNCaP cells

The process of cancer development consists of three sequential stages termed initiation, promotion, and progression. Oxidative stress damages DNA and introduces mutations into oncogenes or tumor suppressor genes, thus contributing to cancer development. Cancer chemoprevention is defined to prevent or delay the development of cancer by the use of natural or synthetic substances. In the present study, we synthesized a series of organoselenium compounds and evaluated their possible chemopreventive properties in human prostate cancer LNCaP cells. Among 42 organoselenium compounds tested, two compounds, 3-selena-1-dethiacephem 13 and 3-selena-1-dethiacephem 14 strongly activated the Nrf2/ARE (antioxidant response element) signaling and thus markedly increased expression of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme. Translocation of Nrf2 to the nucleus preceded HO-1 protein induction by two compounds. The intracellular ROS level was strongly reduced immediately after treatment with these compounds, showing that they are potent antioxidants. Finally, both compounds inhibited cell growth via cell cycle arrest. Our findings suggest that compounds 13 and 14 could not only attenuate oxidative stress through Nrf2/ARE activation and direct ROS scavenging but also inhibit cell growth. Thus, these compounds possess the potential as pharmacological agents for chemoprevention of human prostate cancer.     

Mechanical stimulation to stimulate formation of a physiological collagen architecture in tissue-engineered cartilage: a numerical study

The load-bearing capacity of today's tissue-engineered (TE) cartilage is insufficient. The arcade-like collagen network in native cartilage plays an important role in its load-bearing properties. Inducing the formation of such collagen architecture in engineered cartilage can, therefore, enhance mechanical properties of TE cartilage. Considering the well-defined relationship between tensile strains and collagen alignment in the literature, we assume that cues for inducing this orientation should come from mechanical loading. In this study, strain fields prescribed by loading conditions of unconfined compression, sliding indentation and a novel loading regime of compression-sliding indentation are numerically evaluated to assess the probability that these would trigger a physiological collagen architecture. Results suggest that sliding indentation is likely to stimulate the formation of an appropriate superficial zone with parallel fibres. Adding lateral compression may stimulate the formation of a deep zone with perpendicularly aligned fibres. These insights may be used to improve loading conditions for cartilage tissue engineering.     

Transformation of Terpenoids in Grape Must by Botrytis cinerea

Experiments were done to investigate the volatile components in botrytized grape must and transformation of terpenoids in terpene-supplemented grape must by Botrytis cinerea. Twenty-eight compounds were identified in the volatile concentrate of botrytized must with a combined gas chromatograph-mass spectrometer. No terpenoids were detected in the concentrate. Linalool or terpinen-4-ol decreased a lot when Botrytis cinerea was cultured in the must with these terpenes for 15 days. In linalool-supplemented botrytized must 9 identified and 3 unidentified terpenes were found, while only geranial was detected in terpinen-4-ol-supplemented botrytized must. Botrytis cinerea did not produce terpenoid in grape must without terpenes, but transformed linalool added to grape must into some other monoterpenes.     

Establishment of a Patient-Derived Orthotopic Xenograft (PDOX) Model of HER-2-Positive Cervical Cancer Expressing the Clinical Metastatic Pattern

Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient’s cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient’s cervical tumors resulted in primary growth but not metastasis.