抗血管生成因子Angiostatin与Endostatin作用下肿瘤血管生成的二维数值模拟

目的数值模拟抗血管生成因子Angiostatin和Endostatin对肿瘤血管生成的影响。方法建立肿瘤内外血管生成的二维离散数学模型。模型耦合两种抗血管生成因子Angiostatin和Endostatin的抑制效应,数值模拟在促血管生成因子诱导下肿瘤微血管网生成,讨论血管生成抑制因子的影响。结果抗血管生成因子Angiostatin对肿瘤内外血管网络生成的速度和成熟度有抑制作用。抗血管生成因子Angiostatin和Endostatin耦合作用时,在肿瘤血管生成的早期有明显的抑制效应;在肿瘤血管生成的中后期,它们可以降低肿瘤血管化程度。结论本文模型能够较好的模拟抗血管生成因子Angiostatin和Endostatin对内皮细胞迁移和增殖的抑制作用。     

Anatomical Mapping and Density of Merkel Cells in Skin and Mucosae of the Dog

Merkel cells (MCs) are specialized cutaneous receptor cells involved with tactile sense. Although the distribution of MCs has been extensively studied in humans and rodents, their precise distribution and density throughout skin in the dog has not previously been determined. Knowledge of their distribution could facilitate understanding of their functions. By using of immunohistochemistry, density, and anatomical mapping of the MCs population in the dog skin was determined. Assessment of the MCs innervation was also achieved. Different patterns were noted in epidermis, hair follicles, or mucosa, including variable‐sized clusters, linear or horse‐shaped arrangements, and scattered and individualized cells. MCs revealed great variations in density and distribution over the body surface, with the highest numbers in oral mucosa and facial skin. There was no correlation of MCs density with age, sex, type of breed, coat type or pigmentation. Between 41 and 65% of MCs in hairy and glabrous skin and 8–18% of MCs in oral mucosa were in intimate contact with intraepithelial axon terminals. These findings indicate that canine MCs are numerous in sensory receptive areas and may be associated with the tactile sense in the dog. The present article enhances the knowledge of the skin structure in this species. Anat Rec, 299:1157–1164, 2016. © 2016 Wiley Periodicals, Inc.     

Biodiversity and infrastructure interact to drive tourism to and within Costa Rica

Nature-based tourism has potential to sustain biodiversity and economic development, yet the degree to which biodiversity drives tourism patterns, especially relative to infrastructure, is poorly understood. Here, we examine relationships between different types of biodiversity and different types of tourism in Costa Rica to address three questions. First, what is the contribution of species richness in explaining patterns of tourism in protected areas and country-wide in Costa Rica? Second, how similar are the patterns for birdwatching tourism compared to those of overall tourism? Third, where in the country is biodiversity contributing more than other factors to birdwatching tourism and to overall tourism? We integrated environmental data and species occurrence records to build species distribution models for 66 species of amphibians, reptiles, and mammals, and for 699 bird species. We used built infrastructure variables (hotel density and distance to roads), protected area size, distance to protected areas, and distance to water as covariates to evaluate the relative importance of biodiversity in predicting birdwatching tourism (via eBird checklists) and overall tourism (via Flickr photographs) within Costa Rica. We found that while the role of infrastructure is larger than any other variable, it alone is not sufficient to explain birdwatching and tourism patterns. Including biodiversity adds predictive power and alters spatial patterns of predicted tourism. Our results suggest that investments in infrastructure must be paired with successful biodiversity conservation for tourism to generate the economic revenue that countries like Costa Rica derive from it, now and into the future.

The tourism sector is well-poised to generate win–win approaches to biodiversity conservation and sustainable development given its nonextractive nature and its dependence on scenic beauty (1). However, for sustainable tourism to succeed as a strategy for biodiversity conservation, the role that biodiversity plays in driving tourism patterns needs to be better understood. On one hand, wildlife and nature motivate a significant portion of global tourism (2), and protected areas with higher species richness tend to attract more tourists and yield higher economic benefits (3). On the other hand, tourism hotspots also tend to occur in places where more human-built infrastructure (e.g., hotels, roads, and airports) enables access (4, 5). Studies have reached mixed conclusions on the relative importance of biodiversity and accessibility for tourism, and little is known about how they work in concert (6–11). Given the potential negative impacts of infrastructure on biodiversity conservation, their relative contributions to tourism deserves explicit study, particularly in developing countries where both biodiversity conservation and sustainable development are urgently needed (7, 12).Drivers of tourism patterns across landscapes have been explored through questionnaire surveys and structured interviews that ask tourists about their affinity for landscape features (13–15) and through spatial models that predict recreation using photographs (e.g., geographically weighted regression, MaxEnt) (16, 17). Recently, geo-tagged photographs and species lists shared on social media platforms have become popular tools for tourism-focused research (18–22). These studies, however, typically focus narrowly on the role of single taxa (22, 23) and landscape attributes without accounting for species diversity (14, 20), or they focus only on the role of infrastructure as a driver of tourism (5). Recent advances in satellite Earth observations make it possible to capture more of the ecosystem heterogeneity that can drive variability in species distributions, compared to more conventional modeling based on land cover (24–26). An integrated approach is needed, linking species richness of multiple taxa along with infrastructure variables, both modeled and mapped through high resolution Earth observations. Such an approach could be scaled up to larger regions and applied globally, helping to identify where biodiversity is playing a significant role in driving tourism, such that governments and the tourism sector can prioritize investments in biodiversity conservation.Here, we ask three questions in the iconic case of Costa Rica. First, what is the contribution of species richness (of vertebrate taxa) in explaining patterns of tourism in protected areas and also country-wide? Second, how similar are the patterns for birdwatching tourism compared to those of overall tourism? Third, where in the country is biodiversity contributing more than other factors to birdwatching tourism and to overall tourism? We predict that vertebrate species richness is more important for driving tourism in protected areas than in the rest of the country, because nature-seeking tourists often go to protected areas to find wildlife (3). We also expect that birdwatching tourism is predicted by richness of threatened and endemic bird species rather than total species richness, given birdwatchers’ preferences for rare birds (27). We predict a saturating relationship between species richness and tourism, because beyond a large number of species additional species are unlikely to contribute more to tourism (28). Finally, we predict that national-level tourism is better explained by infrastructure (such as roads and hotels) and distance to water than by biodiversity, because tourists going to Costa Rica often seek activities such as surfing and relaxing in beach resorts (29, 30). We predict nonlinear effects of proximity to roads and water, because a place is deemed inaccessible if it is further away from roads, and a beach tourist destination is also either close to water or not a destination at all. Access diminishes rapidly over a few miles (31).To answer our research questions, we analyze patterns of tourism at two different spatial scales. First, we analyze tourism patterns in protected areas only. Many protected areas provide reliable data on visitation rates and biodiversity tends to be higher inside than outside protected areas (29). However, given that they are often visited by tourists who are already interested in biodiversity, protected areas are not representative of all tourism patterns (30). Second, we evaluate the relative importance of biodiversity to all tourism across Costa Rica (excluding offshore islands). Investigating tourism across the whole nation may give a better understanding of how biodiversity contributes to tourism writ large and not only for tourists with a predisposition for finding wildlife. At both the protected area and national scales, we use a modified MaxEnt model that integrates species distribution models for 66 terrestrial vertebrate species (including amphibians, reptiles, and mammals) and 699 bird species, based on remotely sensed climate and habitat variables, with spatial patterns of infrastructure (hotel density and distance to roads) and distance to water. We measure tourism in two ways for both scales: using eBird checklists as a proxy for birdwatching (32), and using Flickr photographs as a proxy for all international and domestic tourism (19).Costa Rica is an ideal country to explore these questions because tourism represents 7% of the national gross domestic product and employs 3% of the working population directly and a further 9% indirectly (33). Approximately 70% of all international visitors to Costa Rica state that the wildlife, dramatic scenery, and opportunities for adventure sports are the main motivation for visiting the country (33, 34). However, the importance of biodiversity as a factor that influences tourism to, or domestically within, the country has not been evaluated (apart from very local studies) (35, 36). The Central Bank of Costa Rica is currently piloting a nature-based tourism account under the United Nations System of Environmental Economic Accounts (UN SEEA). The state of the art with this methodology is to attribute value to different ecosystems, which may vary widely in their biodiversity. Understanding the relationships between biodiversity and tourism in Costa Rica is a key step toward maintaining the vibrant ecotourism industry and can serve as an example for other biodiverse nations that often look to Costa Rica as a leader in sustainable development (37).     

Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1^st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2^nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1^st group received microwave exposure. The 2^nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

Association of cell-free plasma DNA with perioperative mortality in patients with suspected acute mesenteric ischemia

BackgroundDiagnosing patients with acute mesenteric ischemia (AMI) in the emergency ward is challenging. This study assesses the usefulness of plasma DNA in patients with clinically suspected AMI.Methods130 consecutive patients who underwent laparotomy were studied. Cell-free plasma DNA was measured by real-time quantitative PCR assay for the β-globin gene. The primary endpoint was the accuracy of plasma DNA for predicting 30-day mortality.ResultsSurgery revealed AMI in 99 patients and alternative diagnoses in 31 patients. Forty-six patients with AMI died (46.6%) as compared to 6 (19.4%) in the non-AMI group (p < 0.05). The DNA concentration at admission was significantly higher in patients with AMI (median 7340 GE/ml, versus, 2735 GE/ml, p < 0.01) and in AMI patients who died (8830 GE/ml, versus 4970 GE/ml, p < 0.05). The area under the ROC curves for plasma DNA as a marker for mesenteric ischemia and independent predictor for 30-day mortality were 0.708 (95% CI 0.701–0.890) and 0.815 (95% CI 0.735–0.894). Multiple logistic regression analysis showed that the risk of hospital mortality increased 1.52-fold for every 1000 GE/ml increase in plasma DNA.ConclusionsPlasma DNA levels may be a useful biomarker in predicting the outcome of patients with AMI.     

Role of endothelium-derived relaxing factors in adrenomedullin-induced vasodilation in the rat kidney

The present study aimed to evaluate the contributions of endothelium-derived hyperpolarizing factor (EDHF), the nitric oxide (NO)-cGMP pathway, and prostaglandins to adrenomedullin-induced vasodilation in isolated rat kidney. Inhibition of the NO-cGMP pathway with N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo-[4,3a]quinoxalin-1-one (ODQ) reduced the maximal vasodilator response to adrenomedullin by approximately 50%. Pretreatment of the vessels with the potassium channel inhibitor, tetraethylammonium or increased extracellular K(+), also decreased the maximal response to adrenomedullin by approximately 50%. The simultaneous administration of blockers of both endothelium-derived relaxing factors had a combined effect that almost suppressed adrenomedullin-induced vasodilation. The administration of indomethacin did not modify the renal response to adrenomedullin. Our results suggest that the vasodilator response to adrenomedullin in the isolated perfused kidney of rats is mediated by EDHF and NO to a similar extent. Our data also provide evidence that prostaglandins play no role in the vasodilator response to adrenomedullin in the renal vasculature.