N-phenyl ureidobenzenesulfonates,a novel class of promising human dihydroorotate dehydrogenase inhibitors

N-phenyl ureidobenzenesulfonates (PUB-SOs) is a new class of promising anticancer agents inducing replication stresses and cell cycle arrest in S-phase. However, the pharmacological target of PUB-SOs was still unidentified. Consequently, the objective of the present study was to identify and confirm the pharmacological target of the prototypical PUB-SO named 2-ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) leading to the cell cycle arrest in S-phase. The antiproliferative and the cytotoxic activities of SFOM-0046 were characterized using the NCI-60 screening program and its fingerprint was analyzed by COMPARE algorithm. Then, human dihydroorotate dehydrogenase (hDHODH) colorimetric assay, uridine rescuing cell proliferation and molecular docking in the brequinar-binding site were performed. As a result, SFOM-0046 exhibited a mean antiproliferative activity of 3.5 μM in the NCI-60 screening program and evidenced that leukemia and colon cancer cell panels were more sensitive to SFOM-0046. COMPARE algorithm showed that the SFOM-0046 cytotoxic profile is equivalent to the ones of brequinar and dichloroallyl lawsone, two inhibitors of hDHODH. SFOM-0046 inhibited the hDHODH in the low nanomolar range (IC₅₀ = 72 nM) and uridine rescued the cell proliferation of HT-29, HT-1080, M21 and MCF-7 cancer cell lines in the presence of SFOM-0046. Finally, molecular docking showed a binding pose of SFOM-0046 interacting with Met43 and Phe62 present in the brequinar-binding site. In conclusion, PUB-SOs and notably SFOM-0046 are new small molecules hDHODH inhibitors triggering replication stresses and S-phase arrest.     

Galanin Signaling in the Brain Regulates Color Pattern Formation in Zebrafish

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Biology and host preference of Selitrichodes neseri: A potential biological control agent of the Eucalyptus gall wasp,Leptocybe invasa

Selitrichodes neseri (Hymenoptera: Eulophidae) is a parasitoid of the invasive gall-forming wasp Leptocybe invasa (Hymenoptera: Eulophidae), which has caused serious damage to Eucalyptus plantations in many parts of the world. S. neseri is a recently discovered parasitoid considered to be a potentially important biological control agent of L. invasa. The aim of this study was to provide the first basic data on the biology of S. neseri, which is essential for its application in biological control. S. neseri was shown to be a biparental ectoparasitoid. Observation from dissected galls indicated that the parasitoid developed on late larvae, pupae and callow adults, although development did occur in a range of gall ages. Observed nominal parasitism in captivity ranged from 9.7% to 71.8%. Adult S. neseri specimens, fed with honey-water and galled Eucalyptus leaves, survived an average of 26 days at 26 °C. The average developmental time from oviposition to emergence was 19.3 days ± 0.2 days. There was no pre-oviposition period. A single female produced a maximum of thirty-nine offspring, with a maximum of ten per day. Dissection of the ovaries showed that twelve ovarioles were present. The sex ratio of S. neseri observed in this study was 1:3.43 males:females. Galls of native insects most closely related to L. invasa and to galls of similar morphology to L. invasa-induced galls, were not suitable for S. neseri oviposition. S. neseri showed considerable potential as a biological control agent of L. invasa due to its relatively short developmental time, long adult life span when supplemented with carbohydrates, ability to utilize a range of gall ages and the fact that it has a high level of host specificity.     

Control of mammalian locomotion by ventral spinocerebellar tract neurons

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A multiscale analysis of ecosystem services supply in the NW Iberian Peninsula from a functional perspective

In recent years, the assessment of ecosystem services (ES) supply has been based on the use of Land Use/Land Cover (LULC) data as proxies for spatial representation of ecosystems. Nevertheless, some shortcomings of this method, such as uncertainties derived from generalization of the ecosystem types and assumptions of invariance across spatial scales, indicate the need for new approaches. Such approaches could be aimed at improving knowledge of the relationships between ecosystem services and landscape structure and the spatial characteristics of ES patterns. In this study, we propose an integrative approach that involves the generation and analysis of continuous maps representing the supply of five ES potentially related to the amount of biomass. Five remote sensing images of the Northwestern Iberian Peninsula, obtained with Landsat-5 TM, were used to generate a proxy for net primary production by combining the normalized difference vegetation index (NDVI) of each image to calculate a ΣNDVI index that could act as a potential indicator of some ecosystem services. This information was combined with three variables – terrain slope, population density and occurrence of protected areas – to produce spatial models for the five ES and eventually a series of five supply maps. Food, materials and energy provision services showed a clustered pattern, with high supply values in flat zones and areas with high population densities. In contrast, mass flow and climate regulation services were more widely distributed throughout the study area. The five ecosystem service patterns were analyzed at different scales by two methods: lacunarity and four term local quadrat variance (4TLQV) analysis. These methods revealed differences in the spatial pattern: lacunarity analysis was useful for detection of scale thresholds at the local level, whereas 4TLQV was more sensitive to scale thresholds at larger spatial levels. Thus, the variance analysis yielded higher values for larger windows sizes, particularly for provisioning services. The results demonstrated the suitability of the proposed approach for the spatially explicit modeling of ecosystem services, avoiding the uncertainty of other assessments such as those based on LULC data, and for the exploratory analysis of ES supply from a spatial point of view.     

Impact of landscape patterns on ecological vulnerability and ecosystem service values: An empirical analysis of Yancheng Nature Reserve in China

In this study, an ecological vulnerability assessment indicator system was constructed using the “exposure–climate sensitivity–adaptive capacity” framework according to the theory of ecological vulnerability. An improved ecosystem service value calculation model was proposed based on empirical parameters. Using Yancheng Nature Reserve in China as an example, we employed remote sensing data to conduct an empirical analysis of the changes in the spatiotemporal pattern, ecological vulnerability, and ecosystem services of typical landscape types over the period from 1987 to 2013. The statistical results derived from landscape pattern indices (LPIs) showed that during the investigation period, three natural wetland landscape types (i.e., Spartina alterniflora, Suaeda glauca, and Phragmites australis) showed gradually increased fragmentation in the study area. The ecological vulnerability scores of the major landscape types (in descending order) were P. australis (0.053), farmland (0.047), S. alterniflora (0.042), S. glauca (0.031), and bare mud flat (0.002). The results derived from the ecosystem service value fluctuation index (ESVFI) showed that from 1987 to 1997, the value of the ecosystem services provided by S. glauca and P. australis wetlands decreased, whereas that of S. alterniflora wetlands increased continuously. From 2002 to 2013, the value of the ecosystem services provided by all three types of natural wetland showed a downward trend. In conclusion, the combined effects of human and natural factors, including the expansion of farmland and the invasion of S. alterniflora, and changes in seawater erosion and deposition led to changes in the landscape patterns, ecological vulnerability, and ecosystem services of the Yancheng Nature Reserve during the investigation period. The results indicate that a “dual adaptive” management system based on natural succession and supplemented by appropriate manual intervention should be implemented, and the management efficiency and flexibility should be improved to meet the common needs of biodiversity conservation and economic development.     

20世纪90年代以来中国生态空间演化的时空格局和梯度效应

改革开放以来中国经济和城市化的快速发展促使生产和生活空间挤占大量生态空间，系统认识和评估我国生态空间演化的宏观格局和过程对于生态文明建设具有重要的理论和现实意义。为揭示全国生态空间变化的时空过程，在对生态空间内涵进行界定的基础上，结合全国尺度时序土地利用数据构建生态空间分类体系，并评估1990-2015年中国生态空间演化特征。结果表明：1990-2015年中国生态用地面积持续减少，主要向半生态用地转变，发生在重要的粮食生产区域及周边；半生态用地面积波动明显，前期主要表现为不断扩张，后期大量转换为弱生态用地，发生在主要城市群地区；弱生态用地持续扩张，与城镇化进程不断加速相关。中国生态空间演变过程表现出一定的区域差异和梯度效应，不同区域生态空间变化发生的拐点时间有所不同，呈现"自东向西、由南到北"的3级梯度特征，区域生态空间状况与经济发展战略及生态空间管控具有较强的相关性。本研究对于国家生态空间管控近远期战略方案制订具有一定启示，建议处于不同梯度的各地区应基于区域生态空间演化所处阶段和不同驱动机制，确定分区域生态空间安全红线目标和生态空间管控方案。     

The role of nutrition on epigenetic modifications and their implications on health

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later.     

Brain evolution in Old World monkeys.

Sulcal patterns of 14 genera of Old World monkeys were analyzed from 107 endocasts. Colobines and cercopithecines differ in patterns of cerebral convolutions, and functional and evolutionary hypotheses are here proposed regarding those differences. The cercopithecine pattern seems to be the more derived since it suggests relative expansion of prefrontal, and inferior temporal integration cortices as compared to the colobine pattern.