Isometric size-scaling of metabolic rate and the size abundance distribution of phytoplankton

The relationship between phytoplankton cell size and abundance has long been known to follow regular, predictable patterns in near steady-state ecosystems, but its origin has remained elusive. To explore the linkage between the size-scaling of metabolic rate and the size abundance distribution of natural phytoplankton communities, we determined simultaneously phytoplankton carbon fixation rates and cell abundance across a cell volume range of over six orders of magnitude in tropical and subtropical waters of the Atlantic Ocean. We found an approximately isometric relationship between carbon fixation rate and cell size (mean slope value: 1.16; range: 1.03-1.32), negating the idea that Kleiber's law is applicable to unicellular autotrophic protists. On the basis of the scaling of individual resource use with cell size, we predicted a reciprocal relationship between the size-scalings of phytoplankton metabolic rate and abundance. This prediction was confirmed by the observed slopes of the relationship between phytoplankton abundance and cell size, which have a mean value of -1.15 (range: -1.29 to -0.97), indicating that the size abundance distribution largely results from the size-scaling of metabolic rate. Our results imply that the total energy processed by carbon fixation is constant along the phytoplankton size spectrum in near steady-state marine ecosystems.     

雄安新区生态系统服务需求空间分布格局预测

设立雄安新区是千年大计、国家大事。明晰生态系统服务需求的空间分布及时间变化趋势,有助于探究雄安新区生态系统服务对社会经济发展的促进和制约作用,支持生态系统服务管理和政策的执行。在已有对单一时间维度的生态系统服务研究基础上,增加了对时空变异性的关注,对雄安新区未来时间节点生态系统服务需求的时空分布特征进行预测,首先选取土地利用开发程度、人口密度、经济密度3个指标建立了生态系统服务需求预测模型,然后根据综合增长率法和地区类比法预测土地利用格局、人口密度和经济密度,最后叠加分析得到雄安新区2035年和2050年生态系统服务需求空间分布格局。预测结果表明,2035年起步区人口密度和经济密度将大幅增加,进而带动生态系统服务需求的增加;本世纪中叶,新区人口密度和经济密度的绝对值将大幅度提高,生态系统服务需求高值区主要集中在"一主、五辅"城区范围,与城乡空间布局相呼应。基于研究结果,提出优化土地利用结构、加强白洋淀保护与修复和建设宏观-中观-微观多尺度生态基础设施几条建议,以期为未来的生态系统服务供给、生态基础设施建设和城市规划布局等提供指导。     

Cooperation is less likely to evolve in a finite population with a highly skewed distribution of family size

In the context of the finitely repeated Prisoner's Dilemma with the possibility of cooperating or defecting each time, the strategy tit-for-tat (TFT) consists in cooperating the first time and copying the strategy previously used by the opponent the next times. Assuming random pairwise interactions in a finite population of always defecting individuals, TFT can be favoured by selection to go to fixation following its introduction as a mutant strategy. We deduce the condition for this to be the case under weak selection in the framework of a general reproduction scheme in discrete time. In fact, we show when and why the one-third rule for the evolution of cooperation holds, and how it extends to a more general rule. The condition turns out to be more stringent when the numbers of descendants left by the individuals from one time-step to the next may substantially differ. This suggests that the evolution of cooperation is made more difficult in populations with a highly skewed distribution of family size. This is illustrated by two examples.     

Effect of Quadrat and Core Sizes on Determining the Spatial Pattern of Criconemella sphaerocephalus

An unmanaged pasture was sampled on four occasions (A, B, C, D) with five different quadrat sizes for Criconemella sphaerocephalus by removing a constant soil core volume of 75 cm³ (A) and 300 cm³ (C) from increasing quadrat areas of 0.5-8 m², and removing soil core volumes of increasing size - 75-1,200 cm³ (B) and 300-4,800 cm³ (D) - proportionally with an increase in quadrat area (0.5-8 m²). Frequency counts of C. sphaerocephalus were fitted to six probability distributions. The index of aggregation (b) for Taylor''s power law and Morisita''s index of dispersion were also calculated where appropriate. Twelve of nineteen of the sampling combinations were best described by negative binomial distribution (P = 0.05). Criconemella sphaerocephalus appeared more highly aggregated when sampled with constant soil core volumes (A and C) than from increasing soil core volumes (B and D) based on Taylor''s index of aggregation (b). Morisita''s index of dispersion indicated aggregation at the smallest quadrat area (0.5 m²) for all sampling occasions (A, B, C, D).     

The cognitive neuroscience of constructive memory: remembering the past and imagining the future

Episodic memory is widely conceived as a fundamentally constructive, rather than reproductive, process that is prone to various kinds of errors and illusions. With a view towards examining the functions served by a constructive episodic memory system, we consider recent neuropsychological and neuroimaging studies indicating that some types of memory distortions reflect the operation of adaptive processes. An important function of a constructive episodic memory is to allow individuals to simulate or imagine future episodes, happenings and scenarios. Since the future is not an exact repetition of the past, simulation of future episodes requires a system that can draw on the past in a manner that flexibly extracts and recombines elements of previous experiences. Consistent with this constructive episodic simulation hypothesis, we consider cognitive, neuropsychological and neuroimaging evidence showing that there is considerable overlap in the psychological and neural processes involved in remembering the past and imagining the future.     

Autophagy and human diseases

Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized.     

胡焕庸线存在性的大数据分析——中国人口分布特征的生态学及新经济地理学认识

基于大数据分析思路和数据挖掘工具,在县级尺度上,利用2010年第六次人口普查数据,计算各县的平均人口密度,以及合成海拔(地带性因素)、环境脆弱性、人生气候指数、农业生产潜力、适宜水资源偏离度、交通便捷性、区位指数等,克鲁格曼Krugman所谓的区域地理本性特征,对胡焕庸线的存在的地理基础和生态学基础进行了分析。研究结果表明:(1)中国人口密度与合成海拔、环境脆弱性、人生气候指数、适宜水资源偏离度、农业生产潜力等生态学因素密切相关,与交通便捷性、GDP和区位指数等显著相关。(2)对大多数省的人口密度的影响的贡献率排在强烈的是合成海拔、农业生产潜力和和水资源适应度,其次是交通便捷性和区位指数;它们是克鲁格曼Krugman新经济地理学认识的第一次区域本性和第二次地理本性因素。(3)新疆、山东、宁夏、内蒙古、黑龙江、江苏、北京和天津的人口分布比较独特,还需引入新的因子来解释其人口分布的影响因素;(4)胡焕庸线沿线是一个生态脆弱地带。研究基本展现了中国人口的空间分布的胡焕庸线的地理学与生态基础。     

Effect of amyloids on the vesicular machinery: implications for somatic neurotransmission

Certain neurodegenerative diseases are thought to be initiated by the aggregation of amyloidogenic proteins. However, the mechanism underlying toxicity remains obscure. Most of the suggested mechanisms are generic in nature and do not directly explain the neuron-type specific lesions observed in many of these diseases. Some recent reports suggest that the toxic aggregates impair the synaptic vesicular machinery. This may lead to an understanding of the neuron-type specificity observed in these diseases. A disruption of the vesicular machinery can also be deleterious for extra-synaptic, especially somatic, neurotransmission (common in serotonergic and dopaminergic systems which are specifically affected in Alzheimer''s disease (AD) and Parkinson''s disease (PD), respectively), though this relationship has remained unexplored. In this review, we discuss amyloid-induced damage to the neurotransmitter vesicular machinery, with an eye on the possible implications for somatic exocytosis. We argue that the larger size of the system, and the availability of multi-photon microscopy techniques for directly visualizing monoamines, make the somatic exocytosis machinery a more tractable model for understanding the effect of amyloids on all types of vesicular neurotransmission. Indeed, exploring this neglected connection may not just be important, it may be a more fruitful route for understanding AD and PD.     

Stochastic multiplicative population growth predicts and interprets Taylor's power law of fluctuation scaling

Taylor''s law (TL) asserts that the variance of the density (individuals per area or volume) of a set of comparable populations is a power-law function of the mean density of those populations. Despite the empirical confirmation of TL in hundreds of species, there is little consensus about why TL is so widely observed and how its estimated parameters should be interpreted. Here, we report that the Lewontin–Cohen (henceforth LC) model of stochastic population dynamics, which has been widely discussed and applied, leads to a spatial TL in the limit of large time and provides an explicit, exact interpretation of its parameters. The exponent of TL exceeds 2 if and only if the LC model is supercritical (growing on average), equals 2 if and only if the LC model is deterministic, and is less than 2 if and only if the LC model is subcritical (declining on average). TL and the LC model describe the spatial variability and the temporal dynamics of populations of trees on long-term plots censused over 75 years at the Black Rock Forest, Cornwall, NY, USA.     

Protein interaction network for Alzheimer's disease using computational approach

Alzheimer''s disease (AD) is the most common form of dementia. It is the sixth leading cause of death in old age people. Despiterecent advances in the field of drug design, the medical treatment for the disease is purely symptomatic and hardly effective. Thusthere is a need to understand the molecular mechanism behind the disease in order to improve the drug aspects of the disease. Weprovided two contributions in the field of proteomics in drug design. First, we have constructed a protein-protein interactionnetwork for Alzheimer''s disease reviewed proteins with 1412 interactions predicted among 969 proteins. Second, the diseaseproteins were given confidence scores to prioritize and then analyzed for their homology nature with respect to paralogs andhomologs. The homology persisted with the mouse giving a basis for drug design phase. The method will create a new drug designtechnique in the field of bioinformatics by linking drug design process with protein-protein interactions via signal pathways. Thismethod can be improvised for other diseases in future.     

The neural and cognitive correlates of aimed throwing in chimpanzees: a magnetic resonance image and behavioural study on a unique form of social tool use

It has been hypothesized that neurological adaptations associated with evolutionary selection for throwing may have served as a precursor for the emergence of language and speech in early hominins. Although there are reports of individual differences in aimed throwing in wild and captive apes, to date there has not been a single study that has examined the potential neuroanatomical correlates of this very unique tool-use behaviour in non-human primates. In this study, we examined whether differences in the ratio of white (WM) to grey matter (GM) were evident in the homologue to Broca's area as well as the motor-hand area of the precentral gyrus (termed the KNOB) in chimpanzees that reliably throw compared with those that do not. We found that the proportion of WM in Broca's homologue and the KNOB was significantly higher in subjects that reliably throw compared with those that do not. We further found that asymmetries in WM within both brain regions were larger in the hemisphere contralateral to the chimpanzee's preferred throwing hand. We also found that chimpanzees that reliably throw show significantly better communication abilities than chimpanzees that do not. These results suggest that chimpanzees that have learned to throw have developed greater cortical connectivity between primary motor cortex and the Broca's area homologue. It is suggested that during hominin evolution, after the split between the lines leading to chimpanzees and humans, there was intense selection on increased motor skills associated with throwing and that this potentially formed the foundation for left hemisphere specialization associated with language and speech found in modern humans.     

Myotonia congenita: novel mutations in CLCN1 gene

Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations of CLCN1gene, which encodes human skeletal muscle chloride channel 1. It can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we have sequenced all 23 exons and exon-intron boundaries of the CLCN1 gene, in a panel of 5 unrelated Chinese patients with myotonia congenita (2 with dominant and 3 with recessive form). In addition, detailed clinical analysis was performed in these patients to summarize their clinical characteristics in relation to their genotypes. Mutational analyses revealed 7 different point mutations. Of these, we have found 3 novel mutations including 2 missense (R47W, V229M), one splicing (IVS19+2T>C), and 4 known mutations (Y261C,G523D, M560T, G859D). Our data expand the spectrum of CLCN1 mutations and provide insights for genotype–phenotype correlations of myotonia congenita in the Chinese population.     

Discovery of catalytically active orthologues of the Parkinson's disease kinase PINK1: analysis of substrate specificity and impact of mutations

Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since the human enzyme displays such low kinase activity in vitro. We have discovered that, in contrast to mammalian PINK1, insect orthologues of PINK1 we have investigated-namely Drosophila melanogaster (dPINK1), Tribolium castaneum (TcPINK1) and Pediculus humanus corporis (PhcPINK1)-are active as judged by their ability to phosphorylate the generic substrate myelin basic protein. We have exploited the most active orthologue, TcPINK1, to assess its substrate specificity and elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that can be employed to quantify PINK1 kinase activity. Analysis of PINKtide variants reveal that PINK1 phosphorylates serine or threonine, but not tyrosine, and we show that PINK1 exhibits a preference for a proline at the +1 position relative to the phosphorylation site. We have also, for the first time, been able to investigate the effect of Parkinson's disease-associated PINK1 missense mutations, and found that nearly all those located within the kinase domain, as well as the C-terminal non-catalytic region, markedly suppress kinase activity. This emphasizes the crucial importance of PINK1 kinase activity in preventing the development of Parkinson's disease. Our findings will aid future studies aimed at understanding how the activity of PINK1 is regulated and the identification of physiological substrates.     

Myeloablative therapy against high risk Ewing's sarcoma: A single institution experience and literature review

Background

Attempts to improve survival outcomes of patients with high risk Ewing''s sarcoma (ES) have focused on chemotherapy dose intensification strategies.

Aim

The objective of this study is to retrospectively evaluate clinical characteristics and outcome of pediatric patients with high risk ES treated at a single institution.

Materials and methods

From 1995 to 2008, seventeen patients (male:female, 14:3) were treated with dose-intensive therapy in our institution. Median age at diagnosis was 10 years (range: 2–15). Seven patients had metastases at diagnosis (lung in 6 cases and bone in one case). Eleven patients presented with unresectable disease. Fifteen (88.2%) received the Spanish Society of Pediatric Oncology protocol which includes six cycles of vincristine, doxorubicin, ifosfamide and etoposide. Two out of the six cases that were resectable received postoperative radiation. In addition, eleven patients received definitive radiation therapy. Finally, twelve (70.5%) out of 17 patients received myeloablative therapy with melphalan/etoposide. The rest of patients (N = 5) received busulfan/melphalan.

Results

Median follow-up was 78 months (range: 15–155 months). Initial responses were complete in all patients, but 9 of them developed progression disease. Seven patients became long-term event-free survivors. No patient died of toxicity after transplantation. The 2- and 5-year overall survival rates for all patients were 93% and 73%, respectively. Event-free survival rates were 74% and 54% at 2 and 5 years, respectively.

Conclusion

This single-institution experience suggests that myeloablative therapy against high risk ES is effective and safe.     

基于生态系统服务供需的景感尺度特征分析和应用

自然生态系统与人类感知的交互作用是景感生态学关注的焦点,与生态系统服务的供需紧密关联。生态系统、生态过程、生态系统服务以及人的需求均具有一定的时空尺度特征,因此,由这些过程产生的"景感"也具有时空尺度特征,并依赖于这个过程的尺度特征相互作用。梳理生态系统服务供需关系与景感营造规划的尺度特征,探索二者相互联系,进而提出基于景感生态学理论,通过景感营造实现生态系统服务供需平衡的多尺度实现路径。从空间维度,体现从"社区-城市-流域-区域"的多尺度景感规划框架,从应用维度,体现从生态系统服务需求探索-关键指标体系识别-多源谜码数据感知-景感营造与规划设计的具体流程。通过多尺度的联合景感营造,调整自然供给水平与人类不同尺度的生态系统服务需求以期达到平衡,从而实现人类生存环境福利与居民福祉提升的目标。在此基础上,结合雄安新区规划建设实例,从多尺度景感营造的角度为城市绿色生态建设与可持续发展提出优化建议。主要结论:(1)基于"社区-城市-流域-区域"的多尺度景感分析框架,将景感要素与生态系统服务供需思想融入城市规划,在不同尺度上趋善优化,对于实现可持续发展城市规划和管理具有重要指示意义;(2)雄安新...     

PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65

Missense mutations in PTEN-induced kinase 1 (PINK1) cause autosomal-recessive inherited Parkinson's disease (PD). We have exploited our recent discovery that recombinant insect PINK1 is catalytically active to test whether PINK1 directly phosphorylates 15 proteins encoded by PD-associated genes as well as proteins reported to bind PINK1. We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser(65). We show that human PINK1 is specifically activated by mitochondrial membrane potential (Δψm) depolarization, enabling it to phosphorylate Parkin at Ser(65). We further show that phosphorylation of Parkin at Ser(65) leads to marked activation of its E3 ligase activity that is prevented by mutation of Ser(65) or inactivation of PINK1. We provide evidence that once activated, PINK1 autophosphorylates at several residues, including Thr(257), which is accompanied by an electrophoretic mobility band-shift. These results provide the first evidence that PINK1 is activated following Δψm depolarization and suggest that PINK1 directly phosphorylates and activates Parkin. Our findings indicate that monitoring phosphorylation of Parkin at Ser(65) and/or PINK1 at Thr(257) represent the first biomarkers for examining activity of the PINK1-Parkin signalling pathway in vivo. Our findings also suggest that small molecule activators of Parkin that mimic the effect of PINK1 phosphorylation may confer therapeutic benefit for PD.     

Size,longevity and cancer: age structure

There is significant recent interest in Peto''s paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto''s paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms.