Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

Deforestation and Reforestation of Latin America and the Caribbean (2001–2010)

Forest cover change directly affects biodiversity, the global carbon budget, and ecosystem function. Within Latin American and the Caribbean region (LAC), many studies have documented extensive deforestation, but there are also many local studies reporting forest recovery. These contrasting dynamics have been largely attributed to demographic and socio‐economic change. For example, local population change due to migration can stimulate forest recovery, while the increasing global demand for food can drive agriculture expansion. However, as no analysis has simultaneously evaluated deforestation and reforestation from the municipal to continental scale, we lack a comprehensive assessment of the spatial distribution of these processes. We overcame this limitation by producing wall‐to‐wall, annual maps of change in woody vegetation and other land‐cover classes between 2001 and 2010 for each of the 16,050 municipalities in LAC, and we used nonparametric Random Forest regression analyses to determine which environmental or population variables best explained the variation in woody vegetation change. Woody vegetation change was dominated by deforestation (?541,835 km²), particularly in the moist forest, dry forest, and savannas/shrublands biomes in South America. Extensive areas also recovered woody vegetation (+362,430 km²), particularly in regions too dry or too steep for modern agriculture. Deforestation in moist forests tended to occur in lowland areas with low population density, but woody cover change was not related to municipality‐scale population change. These results emphasize the importance of quantitating deforestation and reforestation at multiple spatial scales and linking these changes with global drivers such as the global demand for food.     

Pollution in mediterranean-climate rivers

This review examines information generated over the past decade on the pollution of rivers in regions with a mediterranean-type climate (med-climate). Pollution has clearly increased in the last 100 years and is correlated with the development of industry, agriculture and human population. Important efforts have been made in some med-climate countries in order to characterise the chemical status of rivers. In addition, the number of chemical substances detectable in mediterranean-climate rivers (med-rivers), as well as the limits of detection, have improved from the development of better analytical methods. New substances detected in rivers are gaining attention. We discuss available knowledge regarding real and potential effects of pollutants on the biota and ecosystems in med-rivers, taking into account natural environmental characteristics of these rivers. The extreme seasonal conditions in med-rivers add to the potential risk because these characteristics can enhance pollutant effects. Efforts and policies to prevent or reduce pollution effects on med-rivers are linked to the knowledge about pollution pressures associated with the degree of economic development. Aquatic communities in med-rivers are more sensitive to pollutants because they are exposed to strong natural and human stressors.     

Divergence in coloration and ecological speciation in the Anolis marmoratus species complex

Adaptive divergence in coloration is expected to produce reproductive isolation in species that use colourful signals in mate choice and species recognition. Indeed, many adaptive radiations are characterized by differentiation in colourful signals, suggesting that divergent selection acting on coloration may be an important component of speciation. Populations in the Anolis marmoratus species complex from the Caribbean island of Guadeloupe display striking divergence in the colour and pattern of adult males that occurs over small geographic distances, suggesting strong divergent selection. Here we test the hypothesis that divergence in coloration results in reduced gene flow among populations. We quantify variation in adult male coloration across a habitat gradient between mesic and xeric habitats, use a multilocus coalescent approach to infer historical demographic parameters of divergence, and examine gene flow and population structure using microsatellite variation. We find that colour variation evolved without geographic isolation and in the face of gene flow, consistent with strong divergent selection and that both ecological and sexual selection are implicated. However, we find no significant differentiation at microsatellite loci across populations, suggesting little reproductive isolation and high levels of contemporary gene exchange. Strong divergent selection on loci affecting coloration probably maintains clinal phenotypic variation despite high gene flow at neutral loci, supporting the notion of a porous genome in which adaptive portions of the genome remain fixed whereas neutral portions are homogenized by gene flow and recombination. We discuss the impact of these findings for studies of colour evolution and ecological speciation.     

猪VHL基因克隆及敲低克隆胚胎的构建

通过在细胞和胚胎水平对猪Von Hippel-Lindau(VHL)基因进行了基因敲低研究,以便为建立VHL疾病模型猪奠定基础.研究首先通过 3'RACE和5'RACE克隆得到猪VHL基因cDNA全长序列(2 725 bp),Real-time PCR结果表明VHL基因广泛表达于猪的各种组织器官,其中在肾上腺、肝脏、胰腺、心脏和睾丸等组织器官高量表达.进一步在猪iPS细胞中对5条干扰片段进行筛选,获得2条高效的干扰片段,干扰效率分别达到72％(P=0.0012)和64％ (P＜ 0.01).以稳定干扰VHL基因的猪胎儿成纤维细胞为核供体,构建克隆胚胎,结果表明,克隆胚胎的发育能力与对照组相比没有明显差异,而且在克隆囊胚中VHL基因的干扰效率达到71％ (P＜ 0.01).综上所述,文中获得了猪VHL基因全长序列并获得该基因稳定敲低的猪细胞和胚胎,从而为VHL疾病模型猪的构建奠定了良好的基础.     

绵地花菌(Albatrellus ovinus)中的grifolin及其衍生物

本文对高等真菌绵地花(Albatrellus ovinus)进行了化学成分的研究。利用各种柱色谱方法(包括正相硅胶、反相硅胶、Sephadex LH-20凝胶色谱、中压液相色谱、半制备HPLC等),分离得到grifolin及其它的5个衍生物。分别为grifolin(1)、neogrifolin(2)、grifolinone A(3)、grifolinone C(4)、confluentin(5)和4-O-methylgrifolic acid(6)。这些化合物的结构通过波谱学方法以及与文献数据对照进行确定。化合物3～6为首次从该种高等真菌中分离得到。化合物4为一个真菌色素,它是一个由一分子的grifolin和一分子苯醌化的grifolin以头对头的方式聚合而成的二聚体。     

Triple mutated antibody scFv2F3 with high GPx activity: insights from MD, docking, MDFE, and MM-PBSA simulation

By combining computational design and site-directed mutagenesis, we have engineered a new catalytic ability into the antibody scFv2F3 by installing a catalytic triad (Trp²⁹–Sec⁵²–Gln⁷²). The resulting abzyme, Se-scFv2F3, exhibits a high glutathione peroxidase (GPx) activity, approaching the native enzyme activity. Activity assays and a systematic computational study were performed to investigate the effect of successive replacement of residues at positions 29, 52, and 72. The results revealed that an active site Ser⁵²/Sec substitution is critical for the GPx activity of Se-scFv2F3. In addition, Phe²⁹/Trp–Val⁷²/Gln mutations enhance the reaction rate via functional cooperation with Sec⁵². Molecular dynamics simulations showed that the designed catalytic triad is very stable and the conformational flexibility caused by Tyr¹⁰¹ occurs mainly in the loop of complementarity determining region 3. The docking studies illustrated the importance of this loop that favors the conformational shift of Tyr⁵⁴, Asn⁵⁵, and Gly⁵⁶ to stabilize substrate binding. Molecular dynamics free energy and molecular mechanics-Poisson Boltzmann surface area calculations estimated the pK _a shifts of the catalytic residue and the binding free energies of docked complexes, suggesting that dipole–dipole interactions among Trp²⁹–Sec⁵²–Gln⁷² lead to the change of free energy that promotes the residual catalytic activity and the substrate-binding capacity. The calculated results agree well with the experimental data, which should help to clarify why Se-scFv2F3 exhibits high catalytic efficiency.     

Caffeine-containing energy drink improves sprint performance during an international rugby sevens competition

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure^®, ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P < 0.05), and pace at sprint velocity (4.6 ± 3.3 vs. 6.1 ± 3.4 m/min, P < 0.05). However, the energy drink did not affect maximal running speed during the repeated sprint test (25.0 ± 1.5 vs. 25.0 ± 1.7 km/h). The ingestion of the energy drink resulted in a higher post-competition urine caffeine concentration than the placebo (3.3 ± 0.7 vs. 0.2 ± 0.1 μg/mL; P < 0.05). In summary, 3 mg/kg of caffeine in the form of a commercially available energy drink considerably enhanced physical performance during a women’s rugby sevens competition.     

Construction of novel chimeric proteins through the truncation of SEC2 and Sak from Staphylococcus aureus

It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44?kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2–ΔSak and ΔSak–ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29?kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic.     

The ALK-1/Smad1 pathway in cardiovascular physiopathology. A new target for therapy?

Activin receptor-like kinase-1 or ALK-1 is a type I cell surface receptor for the transforming growth factor-β (TGF-β) family of proteins. The role of ALK-1 in endothelial cells biology and in angiogenesis has been thoroughly studied by many authors. However, it has been recently suggested a possible role of ALK-1 in cardiovascular homeostasis.ALK-1 is not only expressed in endothelial cells but also in smooth muscle cells, myofibroblast, hepatic stellate cells, chondrocytes, monocytes, myoblasts, macrophages or fibroblasts, but its role in these cells have not been deeply analyzed. Due to the function of ALK-1 in these cells, this receptor plays a role in several cardiovascular diseases. Animals with ALK-1 haploinsufficiency and patients with mutations in Acvrl1 (the gene that codifies for ALK-1) develop type-2 Hereditary Hemorrhagic Telangiectasia. Moreover, ALK-1 heterozygous mice develop pulmonary hypertension. Higher levels of ALK-1 have been observed in atherosclerotic plaques, suggesting a possible protector role of this receptor. ALK-1 deficiency is also related to the development of arteriovenous malformations (AVMs). Besides, due to the ability of ALK-1 to regulate cell proliferation and migration, and to modulate extracellular matrix (ECM) protein expression in several cell types, ALK-1 has been now demonstrated to play an important role in cardiovascular remodeling.In this review, we would like to offer a complete vision of the role of ALK-1 in many process related to cardiovascular homeostasis, and the involvement of this protein in the development of cardiovascular diseases, suggesting the possibility of using the ALK-1/smad-1 pathway as a powerful therapeutic target.