Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat

Alzheimer’s disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid β oligomers (AβO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AβO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aβ, microglia, and cholinergic neurons. Rats exposed to AβO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aβ was only observed in the corpus callosum surrounding the lateral ventricles. AβO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AβO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AβO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.     

Association and dissociation kinetics of bobwhite quail lysozyme with monoclonal antibody HyHEL-5

The anti-hen egg lysozyme monoclonal antibody HyHEL-5 and itscomplexes with various species-variant and mutant lysozymeshave been the subject of considerable experimental and theoreticalinvestigation. The affinity of HyHEL-5 for bobwhite quail lysozyme(BWQL) is over 1000-fold lower than its affinity for the originalantigen, hen egg lysozyme (HEL). This difference is believedto arise almost entirely from the replacement in BWQL of thestructural and energetic epitope residue Arg68 by lysine. Inthis study, the association and dissociation kinetics of BWQLwith HyHEL-5 were investigated under a variety of conditionsand compared with previous results for HEL. HyHEL-5–BWQLassociation follows a bimolecular mechanism and the dissociationof the antibody–antigen complex is a first-order process.Changes in ionic strength (from 27 to 500 mM) and pH (from 6.0to 10.0) produced about a 2-fold change in the association anddissociation rates. The effect of viscosity modifiers on theassociation reaction was also studied. The large differencein the HEL and BWQL affinities for HyHEL-5 is essentially dueto differences in the dissociation rate constant.     

Chimeras of the homing endonuclease PI-SceI and the homologous Candida tropicalis intein: a study to explore the possibility of exchanging DNA-binding modules to obtain highly specific endonucleases with altered specificity

Homing endonucleases are extremely specific endodeoxyribonucleases. In vivo, these enzymes confer mobility on their genes by inducing a very specific double-strand cut in cognate alleles that lack the cooling sequence for the homing endonuclease; the cellular repair of the double-strand break with the endonuclease-containing allele as a template leads to integration of the endonuclease gene, completing the homing process. As a result of their extreme sequence specificity, homing endonucleases are promising tools for genome engineering. For this purpose, it is desirable to design enzymes with defined new specificities. To analyse which DNA-binding elements are potential candidates for use in the design of enzymes with modified or even new specificity, we produced several chimeric proteins derived from the Saccharomyces cerevisiae VMA1 intein (PI-SceI) and the related Candida tropicalis VMA1 intein. Although the mature Candida intein is devoid of endonucleolytic activity, the exchange of two DNA-binding modules of PI-SceI with the homologous elements from the Candida intein results in an active endonuclease. The low sequence homology in these modules indicates that different protein-DNA contacts are responsible for the recognition of related DNA sequences. This flexibility in DNA recognition should, in principle, allow endonucleases to be produced with new specificities useful for genome engineering.     

Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP⁺ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP⁺ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP⁺ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP⁺ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP⁺ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP⁺ chondrocytes in the cranial base synchondrosis.     

Inhibition of Fatty Acid Synthase by Orlistat Accelerates Gastric Tumor Cell Apoptosis in Culture and Increases Survival Rates in Gastric Tumor Bearing Mice In Vivo

Orlistat, an anti-obesity drug, is a potent inhibitor of fatty acid synthase (FAS) and tumor cell viability. It can also induce apoptotic cancer cell death. We examined the effects of Orlistat on cultured NUGC-3 gastric cancer cells. We identified that inhibition of FAS via Orlistat exposure results in rapid cellular damage preceded by a direct but short-lived autophagic response. The Orlistat induced damage can be reversed through the addition of lipid containing media in a process that normally leads to cell death. By limiting exogenous lipid availability and inhibiting FAS using Orlistat, we demonstrated both a greater sensitivity and amplified cancer cell death by activation of apoptosis. We have identified “windows of opportunity” at which time apoptosis can be aborted and cells can be reversed from the death pathway. However, when challenged beyond the window of recovery, cell death becomes all but certain as the ability to be rescued decreases considerably. In vivo examination of Orlistat’s ability to inhibit gastrointestinal cancer was examined using heterozygous male C57BL/6J APC-Min mice, which spontaneously develop a fatal gastrointestinal cancer. Mice were fed either a high fat (11%) or low fat (1.2%) diet containing no Orlistat or 0.5 mg Orlistat/g of chow. Orlistat treated mice fed the high fat, but not low fat diet, survived 7–10% longer than the untreated controls.     

The impact of cross-training on team effectiveness.

The authors examined the role of cross-training in developing shared team-interaction mental models, coordination, and performance in a 2-experiment study using computer simulation methodology (for Experiment 1, N=45 teams; for Experiment 2, N=49 teams). Similar findings emerged across the 2 experiments. First, cross-training enhanced the development of shared team-interaction models. Second, coordination mediated the relationship between shared mental models and team performance. However, there was some inconsistency in the findings concerning the depth of cross-training necessary for improving shared mental models. Results are discussed in terms of the impact of different levels of cross-training on team effectiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

能源发展四大趋势

两年前,剑桥能源研究协会曾经预测油价将在120美元到150美元之间徘徊。如今,油价在一路起起伏伏的过程中印征了剑桥的预言。随着油价的走势,能源市场也面临着巨大的冲击。石油行业未来的发展趋势是什么？投资的主导方向又在哪里？剑桥能源研究协会高级主任Shawn Carraher先生一一解答了这些问题,并指出了能源发展的四大趋势。     

Mothers' and children's expectations for adolescence: The impact of perceptions of an older sibling's experience.

The present study examined the role of perceived experience with an older child in mothers' expectations for subsequent children's adolescence as well as the impact of perceived experience with an older sibling on young adolescent children's expectations for their own adolescence. Participants were 305 sixth- and seventh-grade adolescents and 287 of their mothers. Participants were interviewed via telephone. For both mothers and children, the quality of experience with an older child/sibling was a better predictor of target-based expectations for the young adolescent than was the simple presence or absence of an older sibling. In some cases the link between quality of experience with an earlier born adolescent and mothers' expectations for the target child's adolescence was modified by the target child's temperament. In general, the results support a modeling hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and electrospun fiber mats of low Tg poly(propylene fumerate‐co‐propylene maleate)

Many publications have examined the biodegradable polymer poly(propylene fumate) (PPF) for use in tissue engineering applications. We have examined a similar crosslinkable polymer system, poly(propylene fumerate)‐co‐(propylene maleate) (PPFcPM), derived from maleic anhydride (MA) and 1,2‐propylene diol (PD). This copolymer system uses a less expensive monomer as well as leads to varied ratios of fumerate to maleate groups, allowing tuning of the crosslinked polymer properties such as degradation rate. Two different reaction conditions were used to synthesize the copolymer from MA and PD. In the first case (Method A), toluene was used as a solvent to azeotropically (85°C) remove water to drive the acid catalyzed esterification reaction. In the second case (Method B), the initial ring opening reaction was conducted, followed by addition of catalyst and removal of water to produce polymer of higher molecular weight. Both polymer systems had glass transition temperatures (T_g) below room temperature. The low T_g PPFcPM was dissolved in chloroform along with the photoinitiator phenylbis(2,4,6‐trimethylbenzoyl)‐phosphine oxide (BAPO) and electrospun. The polymer fibers were crosslinked soon after they formed to produce noncalendaring 3D porous scaffolds. Control experiments without the BAPO photoinitiator did not produce fiber mats. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Energy efficiency as a resource in the ISO New England Forward Capacity Market

ISO New England, which oversees New England’s bulk electric power system and wholesale electricity markets, recently established a Forward Capacity Market (FCM) that will pay suppliers to ensure sufficient capacity is available to meet future peak loads. Under the FCM, ISO New England projects the needs of the power system 3 years in advance and then holds an annual auction to purchase the resources necessary to satisfy the future regional requirements. This market is groundbreaking in that it was the first to allow energy efficiency and other demand resources to compete directly with generators. In the first auction, held in February 2008, demand resources contributed substantially to eliminating the need for new generating capacity in the near term and to providing low-cost resources to the region’s ratepayers. Two additional successful auctions have now been held. Participating in the FCM requires a considerable and complex bid, financial assurance, and claim activities. Meeting new intensive measurement, tracking, and verification requirements adds new costs. For efficiency portfolio administrators, participation raises policy questions regarding ownership of capacity credits, appropriate disposition of revenues, increasing emphasis on peak savings, and whether traditionally short-term budget cycles should change to enable the longer-term planning necessary to bid resources several years into the future. On the other hand, revenues from the FCM can provide needed funding for additional efficiency investments. This paper describes the FCM, examines the experience and trade-offs involved in participating for efficiency programs, and reviews the benefits of such participation for the program and the region, including the positive value from increased exposure of the part that efficiency can play in our energy mix.