Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca2+ER perturbation in hepatocellular carcinoma

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr990 to enhance its activity. Mutation of SERCA2-Tyr990 disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca2+ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca2+ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr990 in HCC.

Mycolicibacterium fortuitum genomic epidemiology, resistome and virulome

BACKGROUND Mycolicibacterium fortuitum is an opportunistic pathogen associated with human and animal infection worldwide. Studies concerning this species are mainly represented by case reports, some of them addressing drug susceptibility with a focus on a specific geographic region, so there is a gap in relation to the global epidemiological scenario. OBJECTIVES We aimed determine the global epidemiological scenario of M. fortuitum and analyse its traits associated with pathogenicity. METHODS Based on publicly available genomes of M. fortuitum and a genome from Brazil (this study), we performed a genomic epidemiology analysis and in silico and in vitro characterisation of the resistome and virulome of this species. FINDINGS Three main clusters were defined, one including isolates from the environment, human and animal infections recovered over nearly a century. An apparent intrinsic resistome comprises mechanisms associated with macrolides, beta-lactams, aminoglycosides and antitubercular drugs such as rifampin. Besides, the virulome presented Type VII secretion systems (T7SS), including ESX-1, ESX-3, ESX-4 and ESX-4-bis, some of which play a role on the virulence of Mycobacteriaceae species. MAIN CONCLUSIONS Here, M. fortuitum was revealed as a reservoir of an expressive intrinsic resistome, as well as a virulome that may contribute to its success as a global opportunist pathogen.

Produção e caracterização físico-química de fermentado de umbu / Production and physicochemical characterization of fermented umbu

O objetivo deste trabalho foi desenvolver um fermentado de umbu visando a agregar valor a esse fruto e contribuir para a melhoria de renda das famílias do semiárido nordestino. A polpa utilizada nos experimentos foi submetida a análises físico-químicas e microbiológicas. Para a produção da bebida, a polpa foi diluída em água, sendo necessário realizar uma chaptalização com sacarose até atingir 20,5°Brix. A levedura vínica comercial utilizada foi Saccharomyces cerevisiae. A fermentação foi conduzida a 18°C durante 18 dias e posteriormente a bebida foi submetida a uma estabilização com auxílio de agentes de sedimentação, gelatina e bentonita, por 14 dias a 1°C. Após a estabilização, o fermentado de umbu foi filtrado em filtro prensa. O fermentado de umbu obtido apresentou teor alcoolico de 11,20°GL. A bebida foi analisada quanto às suas características físico-químicas e todos os parâmetros estavam em conformidade com a legislação vigente.

The objective of this study was to develop a fermented umbu drink aiming at adding value to this fruit and contribute for improving the families income in Brazil northeast semiarid region. The pulp used in the experiments was subjected to physico-chemical and microbiological analysis. For the production of liquor, the pulp was diluted with water, and needed a sugaring with sucrose up to 20.5°Brix. A commercial Saccharomyces cerevisiae wine yeast was used. The fermentation was conducted at 18°C for 18 days and subsequently underwent a drink with the aid of stabilizing agents of sedimentation, gelatin and bentonite, for 14 days at 1°C. After stabilizing the fermented umbu drink was subjected to filtered in filter press. The fermented alcoholic umbu drink showed an alcohol contents of 11.20°GL. The drink was analyzed for their physicochemical characteristics and all parameters were in accordance with current legislation.

Estabilidade da cor de doces em massa de polpa de umbu (Spondias tuberosa arr. cam.) no estádio de maturação verde / Color stability of marmalade made from pulp of unripe umbu

Os frutos de umbu (Spondias tuberosa Arr. Cam.) maduros são altamente perecíveis, e o aproveitamento deles no estádio de maturação verde, sob a forma de doce é uma interessante alternativa econômica, para o semi-árido nordestino. A conservação da cor, durante o armazenamento, constitui um fator de qualidade dos mais importantes para o consumo, e o presente trabalho objetivou avaliar sua alteração em função de diferentes formulações, embalagens (polipropileno e celofane) e temperaturas (33 e 43°C), por 90 dias de armazenamento. A adição de pectina e/ou xarope de glicose não alterou a luminosidade (L*), mas diminuiu os valores de a* ( intensidade do vermelho ) e b*. ( intensidade do amarelo). Verificou-se diminuição dos valores de L* a* e b*, notadamente para os doces armazenados à temperatura de 43°C e para a formulação sem adição de pectina. A embalagem não exerceu efeito significativo sobre L*( luminosidade), mas afetou a* e b* aos 90 dias de estocagem, em ambas as temperaturas. Os resultados globais indicaram o uso de pectina e xarope de glicose, embalagens de polipropileno e estocagem à temperaturas mais baixas como sendo as condições mais adequadas para preservação da cor.

Ripe umbu (Spondias tuberosa Arr. Cam.) is highly perishable, thus using unripe umbu to make marmalade is an interesting economic alternative for the semi arid northeastern region in Brazil. Color conservation during storage is one of the major quality factors for consumption. This work aimed to evaluate color alteration in function of different formulations, packagings (polypropylene and cellophane) and temperatures (33 and 43°C) over 90 storage days. Pectin and/or glucose syrup adittion did not alter luminosity (L*), but decreased a* (red intensity) and b*(yellow intensity) values. L* (luminosity), a* ( red intensity) and b* (yellow intensity) values were found to decrease, especially for marmalade stored at 43°C and formulation without pectin addition. The package did not influenced the L* (luminosity), but at 90 days of storage, this factor influenced the values of a* and b* parameters em both temperatures. The overall results indicated the use pectin-and glucose syrup-added formulation , packaging in polypropylene pots and storage at lower temperatures as being the most adequate conditions for color preservation.

Clinical and Radiological Results of Revision Acetabular Arthroplasty using an Acetabular Roof Reinforcement Ring / 대한정형외과학회잡지

PURPOSE: We evaluated the clinical and radiological results of acetabular reconstructions using an acetabular roof reinforcement ring (ARR). MATERIALS AND METHODS: From May 1993 to November 1999, 18 hips revised with ARR were evaluated. The mean age at operation was 53 years. The average follow-up period was 51 months (24-94 months). Acetabular defects were classified based on the AAOS classification system. There was one case of type IIA defect, six cases of type IIB defect, ten cases of type III defect and one case of type IV defect. All were treated with morselized allografts and autografts, and three were reconstructed with additional structural autografts. RESULTS: The average Harris hip score improved from 54 preoperatively to 76 postoperatively, but five patients complained of intermittent hip pain. On the last follow-up radiographs, the bone grafts were united and remodeled in all cases, but only partial resorption was observed in two hips. We found evidence of osteolysis in four hips and observed cup migration in three hips. Three hips, in which Muller rings were used, were re-revised during the follow-up period. CONCLUSION: Acetabular reconstruction using ARR led to good clinical and radiological results, but a relative high rate of rerevision was shown in the cases fitted with the Muller ring. Appropriate ARR should be used depending on the extent of the acetabular defect.

Cloning of adriamycin-resistant related (arr) gene in an adriamycin-resistant L1210 variant

A partial fragment of novel sequence (arr, adriamycin-resistant related) was previously identified using the differential display (DD)-PCR technique with adriamycin-resistant L1210 variant (L1210AdR), which shows a typical multidrug resistant (MDR) phenotypes. The present research shows the isolation of full length arr cDNA sequence. To clone the full length cDNA of arr gene, DD-PCR fragments were subjected to 5'- and 3'-Rapid Amplification of cDNA End (RACE) method. The cloned arr cDNA consisted of 770 bases and contained an open reading frame of 153 bases, encoding a protein of 51 amino acid with the molecular mass of 4 kDa by in vitro translation reactions. Northern blot analysis showed that a 770 bases transcript arr gene was overexpressed in adriamycin-resistant L1210 variant, but not in the parent suggesting that the arr gene may be involved in the adriamycin-resistant phenotypes.