DEPTOR Cell-Autonomously Promotes Adipogenesis, and Its Expression Is Associated with Obesity

DEP domain-containing mTOR-interacting protein (DEPTOR) inhibits the mechanistic target of rapamycin (mTOR), but its in vivo functions are unknown. Previous work indicates that Deptor is part of the Fob3a quantitative trait locus (QTL) linked to obesity/leanness in mice, with Deptor expression being elevated in white adipose tissue (WAT) of obese animals. This relation is unexpected, considering the positive role of mTOR in adipogenesis. Here, we dissected the Fob3a QTL and show that Deptor is the highest-priority candidate promoting WAT expansion in this model. Consistently, transgenic mice overexpressing DEPTOR accumulate more WAT. Furthermore, in humans, DEPTOR expression in WAT correlates with the degree of obesity. We show that DEPTOR is induced by glucocorticoids during adipogenesis and that its overexpression promotes, while its suppression blocks, adipogenesis. DEPTOR activates the proadipogenic Akt/PKB-PPAR-gamma axis by dampening mTORC1-mediated feedback inhibition of insulin signaling. These results establish DEPTOR as a new regulator of adipogenesis.

Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations: Stability studies and in vivo efficacy

Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid (IPAA), are often used in dermocosmetic products due to their higher stability than vitamin C free form as well as its proposed effects in skin; however, there are no studies analyzing IPAA stability or its in vivo effects when present in dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability and pre-clinical and clinical efficacy of dermocosmetic formulations containing IPAA in skin hydration and microrelief. Chemical stability of the formulations added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre-clinical evaluation, experimental formulations were topically applied on hairless skin mice during 5 days and animal skins were analyzed by non-invasive biophysic techniques (water content of stratum corneum, TEWL, viscoelasticity, and microrelief) and by histopathological studies. For clinical efficacy tests, the formulations were topically applied to the forearm and face of human volunteers, and 3 h and 15 days after applications, the skins were evaluated by the same non-invasive techniques mentioned before. Results showed that formulations containing IPAA had medium stability and had pronounced moisturizing effects on stratum corneum and on viable epidermis. These formulations also improved skin microrelief especially in relation to skin smoothness and roughness. (C) 2012 Elsevier B.V. All rights reserved.

Crotamine Pharmacology Revisited: Novel Insights Based on the Inhibition of K-V Channels

Crotamine, a 5-kDa peptide, possesses a unique biological versatility. Not only has its cell-penetrating activity become of clinical interest but, moreover, its potential selective antitumor activity is of great pharmacological importance. In the past, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltage-gated potassium (K-V) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 K-V channels and 4 Na-V channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits K-V 1.1, K-V 1.2, and K-V 1.3 channels with an IC50 of similar to 300 nM, and the key amino acids responsible for this molecular interaction are suggested. Our results demonstrate for the first time that the symptoms, which are observed in the typical crotamine syndrome, may result from the inhibition of K-V channels. The ability of crotamine to inhibit the potassium current through K-V channels unravels it as the first snake peptide with the unique multifunctionality of cell-penetrating and antitumoral activity combined with K-V channel-inhibiting properties. This new property of crotamine might explain some experimental observations and opens new perspectives on pharmacological uses.

Lack of COI variation for Clavelina oblonga (Tunicata, Ascidiacea) in Brazil: Evidence for its human-mediated transportation?

Recent studies indicate that ascidians are efficiently dispersed by human transport. We have chosen the mitochondrial gene cytochrome c oxidase subunit I (COI) to address whether Clavelina oblonga is an introduced species in the Brazilian coast. Colonies of C. oblonga were sampled in different localities along Atlantic coasts of USA, Panama, and Brazil. The sequencing of 92 colonies resulted in three haplotypes for the species, two unique to Florida and the other shared by exemplars collected in Brazil and Panama; the latter haplotype is identical to the published sequence of Azores. Our evidence, including the absence of C. oblonga in the country's northern tropical waters, its association with artificial habitats and lack of COI variation suggest that the species has been introduced in the southeastern and southern Brazilian coasts. Previous records (85 years old) suggest that it could be a relatively long-term introduction.

The effect of flex fuel vehicles in the Brazilian light road transportation

The retaking of the ethanol program in the year 2003 as a fuel for light road transportation in Brazil through the introduction of flex fuel vehicles fleet was a good strategy to overcome the difficulties of the ethanol production sector and did work to increase its market share relative to gasoline. This process, however, may cause a future disequilibrium on the food production and on the refining oil derivates structure. In order to analyze the substitution process resultant of the competition between two opponents fighting for the same market, in this case the gasoline/ethanol substitution process, a method derived from the biomathematics based on the non-linear differential equations (NLDE) system is utilized. A brief description of the method is presented. Numerical adherence of the method to explain several substitution phenomena that occurred in the past is presented in the previous author`s paper, in which the urban gas pipeline system substitution of bottled LPG in the dwelling sector and the substitution of the urban diesel transportation fleet by compressed natural gas (CNG) buses is presented. The proposed method is particularly suitable for prospective analysis and scenarios assessment. (c) 2008 Elsevier Ltd. All rights reserved.

Assessing apical transportation in curved canals: comparison between cross-sections and micro-computed tomography

The aim of this study was to compare two methods of assessing apical transportation in curved canals after rotary instrumentation, namely, cross-sections and micro-computed tomography (mu CT). Thirty mandibular molars were divided into two groups and prepared according to the requirements of each method. In G1 (cross-sections), teeth were embedded in resin blocks and sectioned at 2.0, 3.5, and 5.0 mm from the anatomic apex. Pre- and postoperative sections were photographed and analyzed. In G2 (mu CT), teeth were embedded in a rubber-base impression material and scanned before and after instrumentation. Mesiobuccal canals were instrumented with the Twisted File (TF) system (SybronEndo, Orange, USA), and mesiolingual canals, with the Endo Sequence (ES) system (Brasseler, Savannah, USA). Images were reconstructed, and sections corresponding to distances 2.0, 3.5, and 5.0 mm from the anatomic apex were selected for comparison. Data were analyzed using Mann-Whitney's test at a 5% significance level. The TF and ES instruments produced little deviation from the root canal center, with no statistical difference between them (P > 0.05). The canal transportation results were significantly lower (0.056 mm) in G2 than in G1 (0.089 mm) (p = 0.0012). The mu CT method was superior to the cross-section method, especially in view of its ability to preserve specimens and provide results that are more closely related to clinical situations.