The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis

The main autocrine/paracrine role of the active metabolite of vitamin D₃, 1α,25-dihydroxyvitamin D₃ (1,25-D₃), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D₃ 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D₃, we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D₃ availability, decreasing its antiproliferative effect. (J Histochem Cytochem 58:277–285, 2010)     

衰老相关异染色质聚集——细胞衰老生物学新标志

染色质重塑是调控基因时序性表达的重要环节.衰老的人二倍体成纤维细胞核中有呈点状聚集的异染色质结构,这种特征性现象被称为衰老相关异染色质聚集(SAHF).K9M-H3和HP1是SAHF的标志性蛋白.在SAHF的形成过程中,p16INK4a/Rb途径和高迁移率蛋白A(high-mobility group A protein,HMGA protein)等许多因素起着非常重要的作用.最近研究表明,SAHF能够抑制E2F靶基因的表达,从而使细胞维持于稳定的衰老状态.SAHF的发现为细胞衰老的研究提供了一个新的生物学标志,并为细胞衰老状态的稳定维持提出了一种分子机制.     

Leukemic Stem Cell Frequency: A Strong Biomarker for Clinical Outcome in Acute Myeloid Leukemia

Introduction

Treatment failure in acute myeloid leukemia is probably caused by the presence of leukemia initiating cells, also referred to as leukemic stem cells, at diagnosis and their persistence after therapy. Specific identification of leukemia stem cells and their discrimination from normal hematopoietic stem cells would greatly contribute to risk stratification and could predict possible relapses.

Results

For identification of leukemic stem cells, we developed flow cytometric methods using leukemic stem cell associated markers and newly-defined (light scatter) aberrancies. The nature of the putative leukemic stem cells and normal hematopoietic stem cells, present in the same patient''s bone marrow, was demonstrated in eight patients by the presence or absence of molecular aberrancies and/or leukemic engraftment in NOD-SCID IL-2Rγ-/- mice. At diagnosis (n = 88), the frequency of the thus defined neoplastic part of CD34+CD38- putative stem cell compartment had a strong prognostic impact, while the neoplastic parts of the CD34+CD38+ and CD34- putative stem cell compartments had no prognostic impact at all. After different courses of therapy, higher percentages of neoplastic CD34+CD38- cells in complete remission strongly correlated with shorter patient survival (n = 91). Moreover, combining neoplastic CD34+CD38- frequencies with frequencies of minimal residual disease cells (n = 91), which reflect the total neoplastic burden, revealed four patient groups with different survival.

Conclusion and Perspective

Discrimination between putative leukemia stem cells and normal hematopoietic stem cells in this large-scale study allowed to demonstrate the clinical importance of putative CD34+CD38- leukemia stem cells in AML. Moreover, it offers new opportunities for the development of therapies directed against leukemia stem cells, that would spare normal hematopoietic stem cells, and, moreover, enables in vivo and ex vivo screening for potential efficacy and toxicity of new therapies.     

Axial Optical Traps: A New Direction for Optical Tweezers

Optical tweezers have revolutionized our understanding of the microscopic world. Axial optical tweezers, which apply force to a surface-tethered molecule by directly moving either the trap or the stage along the laser beam axis, offer several potential benefits when studying a range of novel biophysical phenomena. This geometry, although it is conceptually straightforward, suffers from aberrations that result in variation of the trap stiffness when the distance between the microscope coverslip and the trap focus is being changed. Many standard techniques, such as back-focal-plane interferometry, are difficult to employ in this geometry due to back-scattered light between the bead and the coverslip, whereas the noise inherent in a surface-tethered assay can severely limit the resolution of an experiment. Because of these complications, precision force spectroscopy measurements have adapted alternative geometries such as the highly successful dumbbell traps. In recent years, however, most of the difficulties inherent in constructing a precision axial optical tweezers have been solved. This review article aims to inform the reader about recent progress in axial optical trapping, as well as the potential for these devices to perform innovative biophysical measurements.     

Serum N-Glycans: A New Diagnostic Biomarker for Light Chain Multiple Myeloma

The aim of this study was to evaluate the diagnostic and differential diagnostic power of serum N-glycans for light chain multiple myeloma (LCMM). A total of 167 cases of subjects, including 42 LCMM, 42 IgG myeloma, 41 IgA myeloma, and 42 healthy controls were recruited in this study. DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) was applied to determine the quantitive abundance of serum N-glycans. The core fucosylated, bisecting and sialylated modifications were analyzed in serum of LCMM patients (n=20) and healthy controls (n=20) randomly selected from the same cohort by lectin blot. Moreover, serum sialic acid (SA) level was measured by enzymatic method. We found two N-glycan structures (NG1A2F, Peak3; NA2FB, Peak7) showed the optimum diagnostic efficacy with area under the ROC curve (AUC) 0.939 and 0.940 between LCMM and healthy control. The sensitivity and specificity of Peak3 were 88.1% and 92.9%, while Peak7 were 92.9% and 97.6%, respectively. The abundance of Peak3 could differentiate LCMM from IgG myeloma with AUC 0.899, sensitivity 100% and specificity 76.2%, and Peak7 could be used to differentiate LCMM from IgA myeloma with AUC 0.922, sensitivity 92.9% and specificity 82.9%. Serum SA level was significantly higher in patients with LCMM than that in healthy controls. Moreover, the decreased core fucosylation, bisecting and increased sialylation characters of serum glycoproteins were observed in patients with LCMM. We concluded that serum N-glycan could provide a simple, reliable and non-invasive biomarker for LCMM diagnosis and abnormal glycosylation might imply a new potential therapeutic target in LCMM.     

Accuracy of Two Motor Assessments during the First Year of Life in Preterm Infants for Predicting Motor Outcome at Preschool Age

Aim

The primary aim of this study was to investigate the accuracy of the Alberta Infant Motor Scale (AIMS) and Neuro-Sensory Motor Developmental Assessment (NSMDA) over the first year of life for predicting motor impairment at 4 years in preterm children. The secondary aims were to assess the predictive value of serial assessments over the first year and when using a combination of these two assessment tools in follow-up.

Method

Children born <30 weeks’ gestation were prospectively recruited and assessed at 4, 8 and 12 months’ corrected age using the AIMS and NSMDA. At 4 years’ corrected age children were assessed for cerebral palsy (CP) and motor impairment using the Movement Assessment Battery for Children 2^nd-edition (MABC-2). We calculated accuracy of the AIMS and NSMDA for predicting CP and MABC-2 scores ≤15^th (at-risk of motor difficulty) and ≤5^th centile (significant motor difficulty) for each test (AIMS and NSMDA) at 4, 8 and 12 months, for delay on one, two or all three of the time points over the first year, and finally for delay on both tests at each time point.

Results

Accuracy for predicting motor impairment was good for each test at each age, although false positives were common. Motor impairment on the MABC-2 (scores ≤5^th and ≤15^th) was most accurately predicted by the AIMS at 4 months, whereas CP was most accurately predicted by the NSMDA at 12 months. In regards to serial assessments, the likelihood ratio for motor impairment increased with the number of delayed assessments. When combining both the NSMDA and AIMS the best accuracy was achieved at 4 months, although results were similar at 8 and 12 months.

Interpretation

Motor development during the first year of life in preterm infants assessed with the AIMS and NSMDA is predictive of later motor impairment at preschool age. However, false positives are common and therefore it is beneficial to follow-up children at high risk of motor impairment at more than one time point, or to use a combination of assessment tools.

Trial Registration

ACTR.org.au ACTRN12606000252516     

New Data on Axial Locomotion in Fishes: How Speed Affects Diversity of Kinematics and Motor Patterns

Despite considerable recent progress in understanding the functionof the axial muscles and skeleton in fishes, generalizing fromthese results has been hindered by the great phylogenetic diversityof taxa, the lack of quantitative morphometric data on axialmusculoskeletal structure, and limited analysis of the fullrange of locomotor behaviors exhibited within any one taxon.This paper reviews novel results from our studies of two taxawithin a single monophyletic clade, the sunfish family Centrarchidae.Integrated analyses of lateral displacement, lateral bending,and axial muscle activity reveal widespread effects of swimmingspeed both within a particular mode of swimming and among differentbehavioral modes. The longitudinal position along the body ofthe fish also commonly affects kinematics, muscle activity andthe timing of electromyograms (EMGs) relative to kinematics.EMGs and kinematic events propagate from head to tail for bothsteady and kick and glide swimming. In contrast, during theescape response, the onset of EMGs forms a standing wave pattern,whereas kinematic events are propagated. Several novel featuresof the axial motor pattern are summarized for the kick and glidemode of unsteady swimming. For example, the onset of white fiberEMGs lags significantly behind that of the red fibers at thesame longitudinal position, and red fibers are inactivated athigher unsteady swimming speeds. Muscle activity propagatesposteriorly via the sequential activation of myomeres, but thereare statistically significant differences in the timing of EMGsfrom the contractile tissue opposite a single vertebra. Duringrelatively slow kick and glide swimming, the extreme dorsaland ventral portions of myomeres are not active. Estimates ofthe longitudinal extent of the fish with simultaneous muscleactivity indicate that EMGs from an individual myomere usuallyhave temporal overlap with more than 20 neighboring myomereson the same side of the fish. Consequently, the functional unitsfor axial locomotion of fishes do not correspond simply to theanatomical units of individual myomeres. Rather the in vivomotor pattern is a primary determinant of the functional unitsinvolved in swimming.     

Collagen Peptides in Urine: A New Promising Biomarker for the Detection of Colorectal Liver Metastases

Introduction

For both patients and the outpatient clinic the frequent follow-up visits after a resection of colorectal cancer (CRC) are time consuming and due to large patient numbers expensive. Therefore it is important to develop an effective non-invasive test for the detection of colorectal liver metastasis (CRLM) which could be used outside the hospital. The urine proteome is known to provide detailed information for monitoring changes in the physiology of humans. Urine collection is non-invasive and urine naturally occurring peptides (NOPs) have the advantage of being easily accessible without labour-intensive sample preparation. These advantages make it potentially useful for a quick and reliable application in clinical settings. In this study, we will focus on the identification and validation of urine NOPs to discriminate patients with CRLM from healthy controls.

Materials and Methods

Urine samples were collected from 24 patients with CRLM and 25 healthy controls. In the first part of the study, samples were measured with a nano liquid chromatography (LC) system (Thermo Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific, Bremen, Germany). A discovery set was used to construct the model and consecutively the validation set, being independent from the discovery set, to check the acquired model. From the peptides which were selected, multiple reaction monitoring (MRM''s) were developed on a UPLC-MS/MS system.

Results

Seven peptides were selected and applied in a discriminant analysis a sensitivity of 84.6% and a specificity of 92.3% were established (Canonical correlation:0.797, Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for further quantitative analysis which showed a sensitivity of 88% and a specificity of 88%.

Conclusion

Urine proteomic analysis revealed two very promising peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non-invasive manner.     

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives

To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.

Methods

Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997–2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley –test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis.

Results

Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4–4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5–15.9] and 3.2 [0.7–14.7], respectively.

Conclusions

We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram –negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.     

Global DNA Hypomethylation in Liver Cancer Cases and Controls: A Phase I Preclinical Biomarker Development Study

Background: Global genomic DNA hypomethylation is a feature of genomic DNA derived from solid and hematologic tumors in animal models and human carcinogenesis. Global genomic DNA hypomethylation may be the earliest epigenetic change from a normal to a pre-malignant cell. Objectives: To test if global hypomethylation is a good marker for early detection of cancer we used a novel quantification method of 2’-deoxynucleosides to evaluate DNA methylation in liver cancer cases and controls. Methods: Frozen tissue from liver cancer patients and controls were obtained from the Cooperative Human Tissue Network. DNA was extracted using standard methods. Genomic DNA samples were boiled and treated with nuclease P1 and alkaline phosphatase. Global genomic DNA methylation patterns were obtained using HPLC for fraction separation and mass spectrometry for quantification. A two-sample t test was performed using Welch’s approximation for samples with unequal variances. A Wilcoxon rank sum test was also performed. Results: A global genomic DNA methylation index measuring methylated cytidine relative to global cytidine in the genome was significantly lower (p-value = 0.001) for all cases, mean = 2.43 (95% CI, 2.08, 2.78), when compared to controls, mean = 3.55 (95% CI, 3.16, 3.93). Discussion: A correlation between global genomic DNA methylation patterns and type of liver tissue was observed. These results add to the accumulating body of evidence suggesting that global DNA hypomethylation may be a useful biomarker to distinguish between liver cancer cases and controls.     

Human Voltage-Gated Proton Channel Hv1: A New Potential Biomarker for Diagnosis and Prognosis of Colorectal Cancer

Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s). The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA) and Zn²⁺ respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.     

自然需要一半：全球自然保护地新愿景

在全球尺度上,自然保护地的现状规模和“爱知目标11”不足以减缓生物多样性的下降趋势,因此亟须为全球自然保护地设立更高目标,并进一步扩大自然保护地面积。2009年,荒野基金会发起“自然需要一半”倡议（Nature Needs Half,NNH倡议）,建议将地球至少50%的陆地和50%的海洋区域作为某种形式的自然保护地,并增强连通性。系统梳理并介绍了NNH倡议的背景和发展历程,从思想萌芽、正式提出和近期发展3个阶段分析了NNH倡议的主要内容。进一步从理论、政策和实践3个角度讨论了NNH倡议的可行性。最后,建议中国积极参与并在NNH倡议和制定“2020后全球生物多样性框架”中发挥更大作用。     

Global Expanded Nutrient Supply (GENuS) Model: A New Method for Estimating the Global Dietary Supply of Nutrients

Insufficient data exist for accurate estimation of global nutrient supplies. Commonly used global datasets contain key weaknesses: 1) data with global coverage, such as the FAO food balance sheets, lack specific information about many individual foods and no information on micronutrient supplies nor heterogeneity among subnational populations, while 2) household surveys provide a closer approximation of consumption, but are often not nationally representative, do not commonly capture many foods consumed outside of the home, and only provide adequate information for a few select populations. Here, we attempt to improve upon these datasets by constructing a new model—the Global Expanded Nutrient Supply (GENuS) model—to estimate nutrient availabilities for 23 individual nutrients across 225 food categories for thirty-four age-sex groups in nearly all countries. Furthermore, the model provides historical trends in dietary nutritional supplies at the national level using data from 1961–2011. We determine supplies of edible food by expanding the food balance sheet data using FAO production and trade data to increase food supply estimates from 98 to 221 food groups, and then estimate the proportion of major cereals being processed to flours to increase to 225. Next, we estimate intake among twenty-six demographic groups (ages 20+, both sexes) in each country by using data taken from the Global Dietary Database, which uses nationally representative surveys to relate national averages of food consumption to individual age and sex-groups; for children and adolescents where GDD data does not yet exist, average calorie-adjusted amounts are assumed. Finally, we match food supplies with nutrient densities from regional food composition tables to estimate nutrient supplies, running Monte Carlo simulations to find the range of potential nutrient supplies provided by the diet. To validate our new method, we compare the GENuS estimates of nutrient supplies against independent estimates by the USDA for historical US nutrition and find very good agreement for 21 of 23 nutrients, though sodium and dietary fiber will require further improvement.     

硫氧还蛋白还原酶：一种新型有效的胃癌化疗疗效监测标志物

胃癌是国际上发病率较高的肿瘤,寻找新型有效的肿瘤标志物用于胃癌的诊断和疗效评估,对于胃癌的临床治疗有较大的帮助。本研究选取经临床确诊的155例胃癌患者为研究对象,探究血浆硫氧还蛋白还原酶（thioredoxin reductase, TR）在胃癌化疗后临床获益人群与未获益人群中检测水平的差异,以及其与治疗效果的关系。结果显示,未获益组TR阳性率为82.67%,显著高于获益组TR阳性率（48.94%）。受试者操作特征曲线（receiver operating characteristic curve,ROC）分析显示,未获益组人群与获益组人群的TR活性诊断阈值为8.95 U/mL,ROC曲线下面积（area under the curve,AUC）为0.8423,明显优于常规胃癌标志物癌胚抗原（carcinoembryonic antigen,CEA）,肿瘤特异性抗原（cancer antigen,CA）19-9和CA72-4。同时,TR与常规胃癌标志物的联合检测提高阳性检出率至98.49%。TR被认为是一种新型的胃癌临床化疗疗效监测标志物,与临床疗效评价具有较高的一致性。     

硫氧还蛋白还原酶：一种新型有效的胃癌化疗疗效监测标志物

胃癌是国际上发病率较高的肿瘤,寻找新型有效的肿瘤标志物用于胃癌的诊断和疗效评估,对于胃癌的临床治疗有较大的帮助。本研究选取经临床确诊的155例胃癌患者为研究对象,探究血浆硫氧还蛋白还原酶（thioredoxin reductase, TR）在胃癌化疗后临床获益人群与未获益人群中检测水平的差异,以及其与治疗效果的关系。结果显示,未获益组TR阳性率为82.67%,显著高于获益组TR阳性率（48.94%）。受试者操作特征曲线（receiver operating characteristic curve,ROC）分析显示,未获益组人群与获益组人群的TR活性诊断阈值为8.95 U/mL,ROC曲线下面积（area under the curve,AUC）为0.8423,明显优于常规胃癌标志物癌胚抗原（carcinoembryonic antigen,CEA）,肿瘤特异性抗原（cancer antigen,CA）19-9和CA72-4。同时,TR与常规胃癌标志物的联合检测提高阳性检出率至98.49%。TR被认为是一种新型的胃癌临床化疗疗效监测标志物,与临床疗效评价具有较高的一致性。     

Pentraxin3 in Chronic Thromboembolic Pulmonary Hypertension: A New Biomarker for Screening from Remitted Pulmonary Thromboembolism

Background

Pentraxin3 (PTX3) is a protein, which has multifaceted effects on innate immunity, angiogenesis, and vascular remodeling then could be a disease marker of acute myocardial infarction, heart failure, vasculitis. In addition, PTX3 has been recognized as a biomarker for pulmonary arterial hypertension, however whether it is the case in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. Therefore, we investigated whether PTX3 would be a useful biomarker for detecting CTEPH with respect to differentiation from stable pulmonary thromboembolism (PTE), in comparison to other biomarkers.

Methods

Plasma PTX3 and brain natriuretic peptide (BNP) levels were measured in 70 patients with CTEPH at their first diagnostic right heart catheterization (CTEPH group) and in 20 patients with clinically stable PTE more than three months after the acute episode (control group). The levels of plasma C-reactive protein (CRP) and heart-type fatty acid-binding protein (H-FABP) were also analyzed to compare the diagnostic ability of these biomarkers.

Results

The mean level of PTX3 (ng/mL) was significantly higher in the CTEPH group than in the control group (5.51±4.53 versus 2.01±0.96, respectively), and PTX3 levels had mild negative correlation with cardiac output. BNP levels were also higher in the CTEPH group and better correlated with pulmonary hemodynamics than PTX3. However, a receiver operating characteristic (ROC) curve showed PTX3 levels were better for detecting CTEPH, and could detect CTEPH patients with less severe pulmonary hemodynamics and low plasma BNP levels. There was no significant increase in CRP and H-FABP levels in the CTEPH patients.

Conclusions

Plasma PTX3 level was the most sensitive biomarker of CTEPH. Although plasma PTX3 levels did not correlate with the severity of the pulmonary hemodynamics compared to BNP, high levels in clinically stable patients following PTE should prompt a further work-up for CTEPH, which may lead to an early diagnosis.     

Wetlands as Sinks for Reactive Nitrogen at Continental and Global Scales: A Meta-Analysis

Wetlands support physical and ecological functions that result in valuable services to society, including removal of reactive nitrogen (Nr) from surface water and groundwater. We compiled published data from wetland studies worldwide to estimate total Nr removal and to evaluate factors that influence removal rates. Over several orders of magnitude in wetland area and Nr loading rates, there is a positive, near-linear relationship between Nr removal and Nr loading. The linear model (null hypothesis) explains the data better than either a model of declining Nr removal efficiency with increasing Nr loading, or a Michaelis–Menten (saturation) model. We estimate that total Nr removal by major classes of wetlands in the contiguous U.S. is approximately 20–21% of the total anthropogenic load of Nr to the region. Worldwide, Nr removal by wetlands is roughly 17% of anthropogenic Nr inputs. Historical loss of 50% of native wetland area suggests an equivalent loss of Nr removal capacity. Expanded protection and large-scale restoration of wetlands should be considered in strategies to re-balance the global nitrogen cycle and mitigate the negative consequences of excess Nr loading.     

24p3-24p3受体系统：一种新的铁转运途径

小鼠24p3是脂质运载蛋白lipocalin家族的成员之一,可在白介素3(interleukin-3,IL-3)缺乏时诱导细胞发生凋亡,并参与细胞的铁转运过程.最近,Devireddy等又成功克隆到了24p3的细胞表面受体(24p3 receptor,24p3R),进一步确定了24p3-24p3R这一新的铁转运途径.该途径的发现不仅增加了对铁转运理论新的认识,更重要的是,这一发现为铁代谢调控细胞凋亡理论的建立奠定了基础.