Carrying capacity in a heterogeneous environment with habitat connectivity

A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non‐diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments.     

锌转运体ZNT7在Alzheimer病动物模型APP/PS1转基因鼠脑内的表达

目的研究阿尔茨海默病（Alzheimer disease,AD）模型小鼠APP/PS1转基因小鼠脑内锌转运体ZNT7的分布和表达,探讨ZNT7参与Aβ老年斑形成的机理。方法应用免疫组织化学染色观察ZNT7在脑内分布情况,应用Western Blot方法分析ZNT7在APP/PS1转基因小鼠大脑内的表达。结果ZNT7免疫阳性反应产物主要分布在APP/PS1转基因小鼠大脑皮层、纹状体和海马的老年斑内,强阳性的ZNT7免疫产物定位于老年斑的核心。Western Blot分析结果表明ZNT7在APP/PS1转基因小鼠大脑内的表达明显高于野生型小鼠。结论ZNT7在APP/PS1转基因小鼠大脑内的高表达以及在Aβ老年斑的定位,提示ZNT7可能参与了锌离子在老年斑内的聚集,进而参与了APP/PS1转基因小鼠大脑内老年斑的形成。     

Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors

A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.     

AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity

1. Download high-res image (216KB)
2. Download full-size image

     

OxLDL-induced macrophage cytotoxicity is mediated by lysosomal rupture and modified by intralysosomal redox-active iron

Oxidized low density lipoprotein (oxLDL) is believed to play a central role in atherogenesis. LDL is oxidized in the arterial intima by mechanisms that are still only partially understood. OxLDL is then taken up by macrophages through scavenger receptor-mediated endocytosis, which then leads to cellular damage, including apoptosis. The complex mechanisms by which oxLDL induces cell injury are mostly unknown. This study has demonstrated that oxLDL-induced damage of macrophages is associated with iron-mediated intralysosomal oxidative reactions, which cause partial lysosomal rupture and ensuing apoptosis. This series of events can be prevented by pre-exposing cells to the iron-chelator, desferrioxamine (DFO), whereas it is augmented by pretreating the cells with a low molecular weight iron complex. Since both DFO and the iron complex would be taken up by endocytosis, and thus directed to the lysosomal compartment, the results suggest that the normal contents of lysosomal low molecular weight iron may play an important role in oxLDL-induced cell damage, presumably by catalyzing intralysosomal fragmentation of lipid peroxides and the formation of toxic aldehydes and oxygen-centered radicals.     

钾通道在培养大鼠海马神经元凋亡性容积减少中的作用

为探讨钾通道参与神经元凋亡的可能机制,在星形孢菌素（STS)诱导的培养海马神经元凋亡模型上,研究了凋亡时神经细胞容积的动态变化及钾通道在其中的作用.实验结果显示,钾通道阻断剂四乙铵或升高细胞外K⁺均能够明显抑制STS诱导的神经元凋亡,并且大电导钙激活钾通道（BK）选择性阻断剂iberiotoxin和paxilline具有同样程度的抗细胞凋亡作用,表明钾通道（可能主要是BK通道）参与了STS诱导的培养海马神经元凋亡.在STS诱导神经元凋亡的早期就出现了细胞容积的显著减少,而钾通道阻断剂或升高细胞外K⁺均可阻断该细胞容积减少.研究结果提示细胞内钾离子的外流可能参与了凋亡性细胞容积减少,这也可能是钾通道介导细胞凋亡的重要机制之一.     

Kinetic FP-TDI assay for SNP allele frequency determination

Strategies for identifying genetic risk factors in complex diseases by association studies require the comparison of allele frequencies of numerous SNPs between affected and control populations. Theoretically, hundreds of thousands of SNP markers across the genome will have to be genotyped in these studies. Genotyping SNPs one sample at a time is extremely costly and time consuming. To streamline whole genome association studies, some have proposed to screen SNPs by pooling the DNA samples initially for allele frequency determination and perform individual genotyping only when there is a significant discrepancy in allele frequencies between the affected and control populations. Here we describe a new method for determining the allele frequency of SNPs in pooled DNA samples using a two-color primer extension assay with real-time monitoring of fluorescence polarization (named kinetic FP-TDI assay). By comparing the ratio of the rate of incorporation of the two allele-specific dye-terminators, one can calculate the relative amounts of each allele in the pooled sample. The accuracy of allele frequency determination with pooled samples is within 3.3 +/- 0.8% of that determined by genotyping individual samples that make up the pool.     

Sequence, distribution and quantification of the motilin precursor in the cat

Due to motilin's relation to the migrating motor complex (MMC), the physiology of motilin has been mostly studied in man and dog. The cat does not have an MMC pattern, and little is known about cat motilin. Therefore we identified the cat motilin precursor (GenBank accession no. AF127917) and developed a quantitative polymerase chain reaction (PCR) to explore its distribution in the gastrointestinal tract and in the central nervous system (CNS). The precursor is closely related to the dog precursor and consists of an open reading frame of 348bp encoding the signal peptide (25 amino acids), the motilin sequence (22 amino acids) and the motilin associated peptide (69 amino acids). One amino acid of the signal peptide was subject to gene polymorphism. Quantification of motilin messenger RNA (mRNA) was for the first time achieved. It is most abundant in the gastrointestinal tract, with the highest concentration in the duodenum, the lowest in the colon and is not detectable in the corpus. However an important expression was also observed in several regions of the CNS, except the striatum and cerebral cortex. The highest level was in the hypothalamus (although 23-fold lower than in the duodenum), the lowest level in the pons. Moderate levels were found in the thyroid. These data suggest that the physiological role of motilin may extend beyond its effect on gastrointestinal motility.     

Molecular mapping of a major gene conferring resistance to maize mosaic virus

 The objective of this study was to determine the genetic basis of resistance to maize mosaic virus (MMV). Molecular markers were used to map resistance loci to MMV in a set of 91 maize (Zea mays L.) recombinant inbred lines (RILs), derived from the cross between Hi31 (a B68 conversion resistant to MMV) and Kil4 (a Thai inbred susceptible to MMV). The RILs were evaluated for MMV resistance in disease nurseries in Hawaii in the winter of 1993 and the summer of 1994. Twenty-eight highly susceptible RILs were chosen for gene mapping using the pooled-sampling approach. Initial evidence from the pooled DNA indicated that restriction fragment length polymorphism (RFLP) probes on chromosome 3 near the centromere were biased to the susceptible parent allele. Analysis of 91 RILs at 103 RFLP loci confirmed the presence of a major MMV resistance gene on chromosome 3. The resistant allele at this locus, previously named Mv1, is present in the resistant parent Hi31 and traces back to the Argentine parent used in conferring common rust resistance to B68. We conclude that resistance to MMV in B68 and Caribbean flints involves a major gene mv1 on chromosome 3 located between RFLP markers umc102 and php20508. Received: 12 June 1996 / Accepted: 5 July 1996