Meiotic recombination hot spots and human DNA diversity

Meiotic recombination plays a key role in the maintenance of sequence diversity in the human genome. However, little is known about the fine-scale distribution and processes of recombination in human chromosomes, or how these impact on patterns of human diversity. We have therefore developed sperm typing systems that allow human recombination to be analysed at very high resolution. The emerging picture is that human crossovers are far from randomly distributed but instead are targeted into very narrow hot spots that can profoundly influence patterns of haplotype diversity in the human genome. These hot spots provide fundamental information on processes of human crossover and gene conversion, as well as evidence that they can violate basic rules of Mendelian inheritance.     

海岱地区大汶口文化时期人口死亡年龄的统计分布特征

人口死亡年龄是揭示一个族群健康状况和社会经济条件的重要指标。本文根据海岱地区大汶口文化时期九个墓地人骨遗存的发掘报告,运用定量统计的方法检验了人口死亡年龄分布特征。发现该区大汶口文化时期人口的死亡年龄分布近似服从正态分布。最后探讨了造成人口低死亡年龄的可能原因,并给出了这一概率分布的数学意义以及在史前人口学中的应用前景。     

陆栖哺乳动物的地理隔离研究进展

地理隔离是驱动物种分布格局形成的主要因素之一。本文回顾和总结了近几十年来地理隔离影响陆栖哺乳动物空间分布的研究成果, 从自然因素和人为因素两方面就地理隔离对物种分布的影响研究进展进行了综述。自然因素包括山脉、水体、沙漠和其他极端环境、气候变化等, 这些要素通常是在陆栖哺乳动物的缓慢演化进程中发挥作用; 人为因素侧重于因人类活动参与导致的物种分布变化, 包括景观结构变化、交通设施建设等, 在短短几百年甚至几十年内, 可以使物种分布特征发生显著变化。地理隔离对陆栖哺乳动物分布的作用是普遍而相对的, 长期存在且处于动态变化中。多种地理隔离因素之间的尺度效应不同, 哺乳动物在适应地理隔离的过程中表现出了生物个体和种群的响应过程。最后, 建议今后重点开展以下几方面的研究: (1)基于历史动物地理学与生态动物地理学, 深入研究地理隔离与动物地理边界形成的原因; (2)微观尺度下, 借助分子生物学和各种组学技术探讨地理隔离对物种遗传和适应机制的影响; (3)借鉴其他动物类群的研究经验, 加强对我国陆生哺乳动物的跟踪监测; (4)以数据驱动为导向, 将动物地理学与数据科学相结合, 以更好地分析动物分布的变迁史。     

高寒牧区村域生态足迹——以甘南州合作市为例

高寒牧区是一类特殊的地域,其生态环境本底和压力明显区别于其它地域类型。从自然本底上讲,"高寒"特征造成生态系统结构单一、节律缓慢、功能稳定性差,因此,脆弱性强,而修复难度大;从压力上讲,"高寒"又一定程度上屏蔽了外界要素的过分介入,导致人口分布的高度离散性和稀疏性,人地矛盾转化为更直观的草畜矛盾。论文结合高寒牧区的特质,对生态足迹模型和生态承载力模型进行了修正,强调了高寒牧区生态承载力的主控因素———牲畜特征、人口特征、生境特征和地域特征,以甘南州合作市为案例,具体测算和分析了41个行政单元的生态足迹和生态承载力。结果表明:(1)人口生态足迹和牲畜生态足迹分布格局大致呈反向态势,说明在高寒牧区,人口与牲畜对环境造成的压力存在着显著的空间差异。(2)从人口生态足迹和牲畜生态足迹对总生态足迹的贡献度上看,总生态足迹的高低主要取决于牲畜生态足迹,说明牲畜是主控因素。(3)从地均生态承载力分布态势看,低承载区主要分布于北部海拔较高的广大牧区,这里生态结构非常单一,主要以高寒草甸草原和沼泽草原生态类型为主,寒冻风化作用异常强烈,生物有效生长期非常短。而高承载区分布在市区周围和南部洮河谷地沿岸,生态系统除草地生态系统外,还有森林生态系统。从而说明人为条件的改善、自然生态系统结构的复杂程度和自然环境的严酷程度是决定高寒牧区承载力高低的主要因素。(4)从生态盈余与赤字的空间分布态势看,赤字区域主要集中分布在广大的纯牧区,超载过牧是生态状况的关键性致因。因此提高生态承载力、减少生态赤字的关键集结于草畜关系上。有鉴于此,需要采取以下措施:一是根据天然草场的承载能力,建立适宜的草畜平衡关系,将超载的牲畜转移出去;二是科学合理的提高草场的生产能力和承载能力,这就需要加强草原生态保护建设;三是调整经济结构,减少社会经济发展对天然放牧业的高度依赖性,推进传统草地畜牧业向现代畜牧业转型。     

Probing the oligomeric assemblies of pea porphobilinogen synthase by analytical ultracentrifugation

The enzyme porphobilinogen synthase (PBGS) can exist in different nonadditive homooligomeric assemblies, and under appropriate conditions, the distribution of these assemblies can respond to ligands such as metals or substrate. PBGS from most organisms was believed to be octameric until work on a rare allele of human PBGS revealed an alternate hexameric assembly, which is also available to the wild-type enzyme at elevated pH [Breinig, S., et al. (2003) Nat. Struct. Biol. 10, 757-763]. Herein, we establish that the distribution of pea PBGS quaternary structures also contains octamers and hexamers, using both sedimentation velocity and sedimentation equilibrium experiments. We report results in which the octamer dominates under purification conditions and discuss conditions that influence the octamer:hexamer ratio. As predicted by PBGS crystal structures from related organisms, in the absence of magnesium, the octameric assembly is significantly destabilized, and the oligomeric distribution is dominated largely by the hexameric assembly. Although the PBGS hexamer-to-octamer oligomeric rearrangement is well documented under some conditions, both assemblies are very stable (under AU conditions) in the time frame of our ultracentrifuge experiments.     

鸿雁迁徙对停歇地的选择特征

建立合理的湿地水鸟保护地是缓解水鸟栖息地丧失和种群下降的重要手段。以往的保护地设计中,由于越冬地和和繁殖地水鸟停留时间长、种群数量大,受到较多的关注。分析湿地水鸟对停歇地的选择偏好,掌握停歇地的自然条件和人类活动特征可为水鸟保护网络优化和保护地管理提供决策依据。而在水鸟迁徙过程中,停歇地作为保护网络的重要节点也发挥了重要作用。因此选择鸿雁为伞护种,获取了29只鸿雁项圈追踪数据,分析蒙古国Khukh湖-中国东北鸭绿江口秋季迁徙路线对停歇地生境选择偏好,识别了鸿雁在湿地周边不同距离梯度下的活动频率变化。根据鸿雁停歇数据共识别停歇地63处,以此为基础分析停歇的自然条件和人类活动因素特征。结果表明,鸿雁除选择湖泊和沼泽为停歇地外,周边250m内的裸地和草地也是重要栖息地;当鸿雁停歇地人类活动较少时,鸿雁倾向于选择土壤肥沃、食物丰富区,而人类活动强度加大时,栖息地植被条件提高能够为鸿雁提供遮避条件,也吸引了更多鸿雁停歇。研究建议,在水鸟迁徙重要廊道区应增加水鸟停歇地保护区,保护区的设计应根据关键保护对象活动频率加强对湿地周边的栖息地保护,减少水滨人类活动对鸿雁停歇的负面影响;在人类活动强度较大的地区设立水鸟保护地,还应加强对植被的保护,在水鸟利用频率较高的停歇地周边进行植被修复。     

Human impacts and the global distribution of extinction risk

Understanding the global geographical distribution of extinction risk is a key challenge in conservation biology. It remains controversial, however, to what extent areas become threat hotspots simply because of high human impacts or due to predisposing ecological conditions. Limits to the taxonomic and geographical extent, resolution and quality of previously available data have precluded a full global assessment of the relative roles of these factors. Here, we use a new global database on the geographical distributions of birds on continents and continental islands to show that, after controlling for species richness, the best predictors of the global pattern of extinction risk are measures of human impact. Ecological gradients are of secondary importance at a global scale. The converse is true for individual biogeographic realms, within which variation in human impact is reduced and its influence on extinction risk globally is therefore underestimated. These results underline the importance of a global perspective on the mechanisms driving spatial patterns of extinction risk, and the key role of anthropogenic factors in driving the current extinction crisis.     

Using bird species community occurrence to prioritize forests for old growth restoration

Conservation often focuses on ‘ecologically intact’ habitats with little human influence. But where all such habitats have been lost or modified, identifying promising restoration targets is a key goal. We describe a direct approach to identify high conservation value targets using predictive distribution maps of taxa that, based on habitat affinity, ease of detection and abundance can be used to infer native species richness and prioritize conservation investment. We used 1169 avian point counts in a 1560 km2 study area, remote‐sensed data and models incorporating imperfect detectability to predict habitat occupancy in 18 widely‐distributed native birds; 12 of which were determined by experts to be positive indicators of old‐forest conditions. Forest‐association scores for these 12 species where then used as weights in a composite distribution map of the probability of community occurrence, which corresponded well with the occurrence of old forest stands mapped by aerial photography. Our results indicate that composite maps of widespread indicators improve site prioritization by incorporating the behavioural and demographic responses of a diverse range of indicators to variation in patch size, configuration and adjacent human land use.     

Presence and localization of the 60 KD calicin in human spermatozoa presenting postacrosomal sheath defects: preliminary results

Using an indirect immunofluorescence technique, we studied the anticalicin antibody distribution in four teratozoospermic human sperm samples with a high rate of spermatozoa with incomplete postacrosomal sheath structure (PAS) detected at the ultrastructural level. The calicin distribution obtained in these samples is compared with the distribution obtained in two normal human sperm samples with a high proportion of normal PAS and in 3 human sperm samples without PAS ("round-headed syndrome"). In contrast to the homogeneous calicin distribution found in the majority of the normal group, similar to that reported by Longo et al. (J Cell Biol 105:1105-1120, 1987) and Paranko et al. (Differentiation 38:21-27, 1988), and the absence of calicin in the three non-PAS samples, we observed new patterns of calicin distribution in the four sperm samples studied. In the light of these preliminary results, the use of anticalicin antibody as a tool for human postacrosomal region evaluation is discussed.     

Selective bone targeting 5-fluorouracil prodrugs: synthesis and preliminary biological evaluation

Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP .The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs.     

Organization and genomic distribution of “82H” alpha satellite DNA

Summary We have investigated the organization and genomic distribution of sequences homologous to p82H, a cloned human alpha satellite sequence purported, based on previous in situ hybridization experiments, to exist at the centromere of each human chromosome. We report here that, using Southern blotting analysis under conditions of high stringency, p82H hybridizes solely to a low-copy or single-copy alphoid domain located at or near the centromeric region of human chromosome 14. In contrast, conditions of reduced hybridization stringency permit extensive cross-hybridization with nonidentical, chromosome-specific alpha satellite subsets found elsewhere in the human genome. Thus, the previously described ubiquity of 82H human centromeric sequences reflects the existence of diverse alpha satellite subsets located at the centromeric region of each human chromosome.     

Use of 1H-NMR to determine the distribution of lecithin between the micellar and vesicular phases in model bile

Biliary cholesterol/phospholipid vesicles play an important role in the pathogenesis of gallstone disease. A prerequisite for the study of the lipid composition and stability of these vesicles is a reliable method to quantify the amount of vesicular lipid. In the present report we show that NMR can be used to determine the distribution of biliary lecithin between the micellar and vesicular phases. The relatively large size of the vesicles leads to such a broadening of the lipid resonances that they are no longer visible in high resolution 1H-NMR spectra. Since micelles are much smaller, lipid present in the micellar phase does give rise to sharp peaks in 1H-NMR spectra. Micellar lecithin can easily be quantified in these spectra. The resonances of cholesterol are masked by the closely related bile acid that is present in a much higher concentration. By determining the difference between chemically and NMR estimated lecithin, the distribution of this phospholipid between the micellar phase and vesicular phase can be assessed. We have compared the results of NMR with gel permeation and density gradient ultracentrifugation. Using standard fractionation conditions, both gel permeation and density gradient ultracentrifugation lead to an underestimation of vesicular lecithin, the difference being minor at relatively high total lipid concentrations (10 g/dl) but large in diluted model bile. We conclude that 1H-NMR can be used to determine the distribution of lecithin in model bile.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasmodium-infected blood cells analyzed and sorted by flow fluorimetry with the deoxyribonucleic acid binding dye 33258 Hoechst.

Red cells from Plasmodium berghei infected mouse blood can be sorted on the basis of their DNA content with the bisbenzimidazole dye 33258 Hoechst. The optimal conditions for dye uptake have been established and with these conditions uninfected cells are nonfluorescent and can be completely separated from infected cells which exhibit fluorescence in almost direct proportion to the number of parasite nuclei (i.e. DNA) they contain. The number of fluorescent cells detected and their fluorescence intensity is shown to be dependent on the dye concentration and the incubation medium being used. At least a proportion of the infected cells sorted from each fluorescence peak in the cell distribution retain their infectivity in vivo with some, but not all, conditions of labeling. This technique is being used to separate minor cell populations from infected blood for biochemical and immunochemical analyses and to screen human samples for malaria infected cells.     

Why decadal to century timescale palaeoclimate data are needed to explain present‐day patterns of biological diversity and change

The current distribution of species, environmental conditions and their interactions represent only one snapshot of a planet that is continuously changing, in part due to human influences. To distinguish human impacts from natural factors, the magnitude and pace of climate shifts, since the Last Glacial Maximum, are often used to determine whether patterns of diversity today are artefacts of past climate change. In the absence of high‐temporal resolution palaeoclimate reconstructions, this is generally done by assuming that past climate change occurred at a linear pace between widely spaced (usually, ≥1,000 years) climate snapshots. We show here that this is a flawed assumption because regional climates have changed significantly across decades and centuries during glacial–interglacial cycles, likely causing rapid regional replacement of biota. We demonstrate how recent atmosphere‐ocean general circulation model (AOGCM) simulations of the climate of the past 21,000 years can provide credible estimates of the details of climate change on decadal to centennial timescales, showing that these details differ radically from what might be inferred from longer timescale information. High‐temporal resolution information can provide more meaningful estimates of the magnitude and pace of climate shifts, the location and timing of drivers of physiological stress, and the extent of novel climates. They also produce new opportunities to directly investigate whether short‐term climate variability is more important in shaping biodiversity patterns rather than gradual changes in long‐term climatic means. Together, these more accurate measures of past climate instability are likely to bring about a better understanding of the role of palaeoclimatic change and variability in shaping current macroecological patterns in many regions of the world.     

Co-populated conformational ensembles of beta2-microglobulin uncovered quantitatively by electrospray ionization mass spectrometry

Ordered assembly of monomeric human beta(2)-microglobulin (beta(2)m) into amyloid fibrils is associated with the disorder hemodialysis-related amyloidosis. Previously, we have shown that under acidic conditions (pH <5.0 at 37 degrees C), wild-type beta(2)m assembles spontaneously into fibrils with different morphologies. Under these conditions, beta(2)m populates a number of different conformational states in vitro. However, this equilibrium mixture of conformationally different species is difficult to resolve using ensemble techniques such as nuclear magnetic resonance or circular dichroism. Here we use electrospray ionization mass spectrometry to resolve different species of beta(2)m populated between pH 6.0 and 2.0. We show that by linear deconvolution of the charge state distributions, the extent to which each conformational ensemble is populated throughout the pH range can be determined and quantified. Thus, at pH 3.6, conditions under which short fibrils are produced, the conformational ensemble is dominated by a charge state distribution centered on the 9+ ions. By contrast, under more acidic conditions (pH 2.6), where long straight fibrils are formed, the charge state distribution is dominated by the 10+ and 11+ ions. The data are reinforced by investigations on two variants of beta(2)m (V9A and F30A) that have reduced stability to pH denaturation and show changes in the pH dependence of the charge state distribution that correlate with the decrease in stability measured by tryptophan fluorescence. The data highlight the potential of electrospray ionization mass spectrometry to resolve and quantify complex mixtures of different conformational species, one or more of which may be important in the formation of amyloid.     

Coupling of proadipocyte growth arrest and differentiation. I. Induction by heparinized medium containing human plasma

The differentiation of proadipocytes in vitro typically required prolonged culture of cells as a high density in high concentrations of serum and added hormones. With such culture conditions it is difficult to design experiments to determine the mechanisms that control the differentiation process. We now describe the rapid and parasynchronous growth arrest and differentiation of low density murine proadipocytes in heparinized medium containing only human plasma. When low density cells are cultured under these conditions, growth arrest at a distinct state in the G1 phase of the cell cycle occurs within 2 d and the differentiation of 80-100% of the cell population occurs within 4 d thereafter. The factors in human plasma which promote growth arrest and differentiation are heat labile and can be separated by barium adsorption. In the following paper we have used these methods to show that there are five separate phases which regulate the coupling of proadipocyte growth arrest and differentiation. The data reported in this paper establish that: (a) high cell density and extensive cell-to- cell contact are not required for adipocyte differentiation, (b) prolonged culture is not required for adipocyte differentiation, and (c) high concentrations of serum and/or added hormones are not required for adipocyte differentiation.     

Geographic disparities and moral hazards in the predicted impacts of climate change on human populations

Aim It has been qualitatively understood for a long time that climate change will have widely varying effects on human well‐being in different regions of the world. The spatial complexities underlying our relationship to climate and the geographical disparities in human demographic change have, however, precluded the development of global indices of the predicted regional impacts of climate change on humans. Humans will be most negatively affected by climate change in regions where populations are strongly dependent on climate and favourable climatic conditions decline. Here we use the relationship between the distribution of human population density and climate as a basis to develop the first global index of predicted impacts of climate change on human populations. Location Global. Methods We use spatially explicit models of the present relationship between human population density and climate along with forecasted climate change to predict climate vulnerabilities over the coming decades. We then globally represent regional disparities in human population dynamics estimated with our ecological niche model and with a demographic forecast and contrast these disparities with CO₂ emissions data to quantitatively evaluate the notion of moral hazard in climate change policies. Results Strongly negative impacts of climate change are predicted in Central America, central South America, the Arabian Peninsula, Southeast Asia and much of Africa. Importantly, the regions of greatest vulnerability are generally distant from the high‐latitude regions where the magnitude of climate change will be greatest. Furthermore, populations contributing the most to greenhouse gas emissions on a per capita basis are unlikely to experience the worst impacts of climate change, satisfying the conditions for a moral hazard in climate change policies. Main conclusions Regionalized analysis of relationships between distribution of human population density and climate provides a novel framework for developing global indices of human vulnerability to climate change. The predicted consequences of climate change on human populations are correlated with the factors causing climate change at the regional level, providing quantitative support for many qualitative statements found in international climate change assessments.     

Towards proteome-wide production of monoclonal antibody by phage display

Sequencing of the human genome reveals that there are approximately 30,000 genes that encode an even greater number of proteins which comprise the human proteome. Characterization of gene products at the genome-wide scale requires the development of high throughput methods to generate temporo-spatial information on each and every protein in the cell under normal and pathological conditions. Monoclonal antibodies are important reagents for these studies. We have developed a method to generate human monoclonal antibodies by selecting phage antibody libraries directly on antigen blotted onto poly(vinylidene fluoride) membranes. Cellular proteins are first separated by two dimensional (2D) gel electrophoresis, Western blotted onto poly(vinylidene fluoride) membranes, and used to select phage antibody libraries. Monoclonal antibodies can be generated against individual protein spots on a 2D gel. The antibodies are functional in Western blotting, ELISA, and immunohistochemistry. Automation of this process should allow high throughput production of monoclonal phage antibodies against cellular proteins as well as proteins that are uniquely expressed under pathological conditions.     

A review of indicators of climate change for use in Ireland

Impact indicators are systems/organisms, the vitality of which alters in response to changes in environmental condition. The indicators assessed in this review fall within the impact category of the driver-pressure-state-impact-response (DPSIR) framework. Instrumental records have shown unequivocal changes in climatic conditions over the past 30 years at a global level but impact indicators allow these changes to be monitored at a finer resolution. Our main aim was to review sets of indicators of climate change currently used in various countries and to make recommendations for their use in the Irish environment. We review a preliminary set of climate change impact indicators in five sectors: agriculture; plant and animal distribution patterns; phenology; palaeoecology and human health. Currently, the most effective impact indicators of climate change have proved to be phenological observations of tree developmental stages. The strongest factor limiting the use of indicators is the lack of long-term data sets from which a climatic signal can be extracted.