Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human alt="agr" align="BASELINE" BORDER="0">-lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004     

Role of Cys221 and Asn116 in the zinc-binding sites of the Aeromonas hydrophila metallo-β-lactamase

The CphA metallo-alt="beta" align="MIDDLE" BORDER="0">-lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003     

多项式模上全次数除法及其在CAGD中的应用(Ⅰ)

本首先介绍了利用Ｇｒｏｅｂｎｅｒ基求解Ｓｙｚｙｇｙ模生成元的方法,在对方法做出进一步分析的基础上,给出了一元模上的多项式辗转相除法,这种除法相对于已有的方法有许多优点。     

Age distribution of circulatingα-interferon

Summary A sensitive radioimmunoassay showed that circulating alt="agr" align="BASELINE" BORDER="0">-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating alt="agr" align="BASELINE" BORDER="0">-interferon was 0.201±0.059 ng/ml in males (n=19) and 0.184±0.076 ng/ml in females (n=14) at ages 30–39 years old. It was noted that circulating alt="agr" align="BASELINE" BORDER="0">-interferon was maintained up to a certain level even in elderly individuals.     

The susceptibility to exercise-induced muscle damage increases as rats grow larger

Summary Glucose-6-phosphate dehydrogenase and N-acetyl-alt="beta" align="MIDDLE" BORDER="0">-glucosaminidase activities were both elevated after eccentric exercise indicating that this type of exercise causes muscle damage. Muscle damage as measured by glucose-6-phosphate dehydrogenase activity in the vastus intermedius was greater and occurred later in larger rats indicating that the susceptibility to muscle damage is increased and the repair process delayed in older and larger animals.     

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsonalt="rsquo" align="BASELINE" BORDER="0">s disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004     

“Unfolding” Natural Resource-Use Information Systems: Fieldwork in Botswana

My research examines the performance of natural resource-use information systems. I question why such systems, despite receiving substantial financial and human investment, appear to have a weak impact on projects, programs, and policy intended for rural poverty alleviation in developing countries. Drawing on my understanding of the alt="ldquo" align="MIDDLE" BORDER="0">process of unfoldingalt="rdquo" align="MIDDLE" BORDER="0"> introduced by C. West Churchman, and its particular relationship to Habermasian constitutive interests, I reflect on my experiences of using the concept during fieldwork undertaken in Botswana. The concept is found useful on two fronts: first, it provides a purposeful guide for gathering and processing information/knowledge—what I have termed an epistemological intent; second, it provides a useful template for evaluating other information systems; in particular, the role of expertise—what I have termed an ontological intent. The process of unfolding, as I understand it, also provides an invitation for constructive (rather than self-indulgent) personal reflection: what might be termed a constitutive reflexive intent. By making information gathering and knowledge generation less mystical and a more transparent social activity, the conceptual and practical application of the process of unfolding can help toward retrieving inquiry as being a purposeful, openly political, and thereby less deceptive engagement: features which I believe are found particularly wanting in the business of rural development information gathering.     

准噶尔盆地北缘山前带湿地扇沉积特征及控藏作用

综合野外露头、岩心、钻测井以及分析测试资料等,对准噶尔盆地北缘哈拉阿拉特山山前带侏罗系八道湾组开展了系统的沉积相研究。结果表明:八道湾组一段沉积时期,受构造背景、古物源、古气候的综合影响,哈山南缘山前带发育一套典型的湿地扇沉积,可识别出扇根、扇中、扇缘三种亚相,扇中可进一步分为辫状水道和泥炭沼泽两类微相;在明确了相类型及其展布特征的基础上,建立研究区湿地扇沉积相模式,其在岩性特征、沉积序列、平面规模、微相组合等方面均与洪积扇有明显区别;山前带湿地扇沉积区具有良好的勘探潜力,有利的微相、岩石相以及原始沉积组构共同控制着油藏分布,其中扇中辫状水道砂砾岩相和粗砂岩相为原油富集的有利储集相带。