EAM会议专刊辑述评——气候变化下旱区农业生态系统的可持续性

农业生产是将自然资源不断转化为农产品的过程。简单的说就是将阳光、空气、水和土壤等无机资源转化为可以供人类消费的有机产物。农业生态系统必须对全球气候变化、市场竞争、自然环境的恶化、经济等政策法规和人民的需求等因素做出灵活的应对策略,同时还要保证自然生态系统的稳定性。在发展中国家,有超过20亿的人口每天收入低于2美元,他们收入中绝大部分都用于解决温饱。这些人大部分生活在干旱、半干旱地区,并以农业生产作为生活的主要来源。由于这些地区水资源匮乏、土壤贫瘠,粮食安全问题一直是该地区人类生存的关键。中澳两国都把干旱、半干旱地区的农牧业发展作为研究的重点。两国的专家都致力于恢复和维护干旱半干旱地区脆弱的农业生态系统。气候变化正在使农业生态系统可持续发展面临严峻挑战。因此,迫切需要农学,生态学,环境学,社会经济学等多学科的共同发展和融合解决这一问题。2010年7月20—25日在兰州大学举办了以“气候变化和旱区农业生态系统管理”为主题的“第二届生态系统评估与管理（EAM）国际会议”。国内外众多知名专家参与了此次会议,并共同讨论在全球气候变化背景下如何提高干旱半干旱地区脆弱农业生态系统生产力与可持续性。本次会议的议题是：(1）半干旱地区旱作雨养农业生态系统评估与管理,(2）干旱地区绿洲农业生态系统评估与管理。此次会议由兰州大学和澳大利亚西澳大学联合主办,中国科学院生态环境研究中心协办,由国家教育部和国家外专局联合支持、兰州大学干旱与草地生态教育部重点实验室承担的“旱寒生态学”学科创新引智基地和西澳大学农业研究院、FAO属下的叙利亚国际旱地农业研究中心(ICARDA)联合提供资金支持。会议期间,25位专家就干旱、半干旱地区植物土壤互作关系作了报告。另外还有18位在干旱半干旱地区科研一线工作的青年学者汇报了研究进展,并与专家进行了广泛交流。报告会之后,大会组织专家分别对典型旱区农业进行了考察,分别是兰州大学黄土高原旱地农业生态实验站(榆中)和甘肃武威市民勤绿洲农业生态系统。此次大会遴选出35篇学术论文,以专刊的形式发表于《生态学报》第31卷第9期。会议遴选出的其它英文文章将于2011年在《Plant and Soil》和《Crop and Pasture Science》上发表,敬请期待。我们相信,本专刊的出版将会对气候变化背景下旱区农业生态系统的研究和发展产生重要的推动作用。     

Does a High‐protein Diet Improve Weight Loss in Overweight and Obese Children?

Objective: To evaluate the effect of a high‐protein diet on anthropometry, body composition, subjective appetite, and mood sensations in overweight and obese children attending a residential weight‐loss camp. Research Methods and Procedures: Children (120; BMI, 33.1 ± 5.5 kg/m²; age, 14.2 ± 1.9 years) were randomly assigned to either a standard or high‐protein diet group (15% vs. 22.5% protein, respectively). All children were assessed at baseline and at the end of the camp for anthropometry, body composition, blood pressure, biochemical variables (n = 27), and subjective appetite and mood sensations (n = 50). Results: Attendance at the weight‐loss camp resulted in significant improvements in most measures. Campers lost 5.5 ± 2.9 kg in body weight (p < 0.001) and 3.8 ± 5.4 kg in fat mass (p < 0.001) and reduced their BMI standard deviation score by 0.27 ± 0.1 (p < 0.001) and their waist circumference by 6.6 ± 2.8 cm (p < 0.001). Subjective sensations of hunger increased significantly over the camp duration, but no other changes in appetite or mood were observed. There were no significant differences between the two diets on any physical or subjective measures. Discussion: Weight‐loss camps are effective in assisting children to lose weight and improve on a range of health outcomes, independently of the protein content of the diet. The implications of an increase in hunger associated with weight loss needs to be considered. Further work is warranted to investigate whether higher levels of dietary protein are feasible or effective in longer‐term weight‐loss interventions of this type.     

Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy

Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F)-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM) to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC) polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.     

Discovery of thieno[2,3-c]pyridines as potent COT inhibitors

Evaluation of hit chemotypes from high throughput screening identified a novel series of 2,4-disubstituted thieno[2,3-c]pyridines as COT kinase inhibitors. Structural modifications exploring SAR at the 2- and 4-positions resulting in inhibitors with improved enzyme potency and cellular activity are disclosed.     

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.     

The Hsp40 J‐domain modulates Hsp70 conformation and ATPase activity with a semi‐elliptical spring

Regulatory protein interactions are commonly attributed to lock‐and‐key associations that bring interacting domains together. However, studies in some systems suggest that regulation is not achieved by binding interactions alone. We report our investigations on specific physical characteristics required of the Hsp40 J‐domain to stimulate ATP hydrolysis in the Hsp40‐Hsp70 molecular chaperone machine. Biophysical analysis using isothermal titration calorimetry, and nuclear magnetic resonance spectroscopy reveals the importance of helix rigidity for the maintenance of Hsp40 function. Our results suggest that the functional J‐domain acts like a semi‐elliptical spring, wherein the resistance to bending upon binding to the Hsp70 ATPase modulates the ATPase domain conformational change and promotes ATP hydrolysis.     

Lack of an Efficient Endoplasmic Reticulum-localized Recycling System Protects Peroxiredoxin IV from Hyperoxidation

Typical 2-Cys peroxiredoxins are required to remove hydrogen peroxide from several different cellular compartments. Their activity can be regulated by hyperoxidation and consequent inactivation of the active-site peroxidatic cysteine. Here we developed a simple assay to quantify the hyperoxidation of peroxiredoxins. Hyperoxidation of peroxiredoxins can only occur efficiently in the presence of a recycling system, usually involving thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared with either the cytosolic or mitochondrial enzymes. Each enzyme is equally sensitive to hyperoxidation in the presence of a robust recycling system. Our results demonstrate that peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation.     

2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: Identification, stereochemistry and initial SAR

This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds.     

The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event

Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium.