Center for Life science

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Center for Life science

Boston, MA, United States

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Ma Y.,National University of Singapore | Ma Y.,Center for Life science | Fang C.,National University of Singapore | Fang C.,Center for Life science | And 5 more authors.
Advanced Materials | Year: 2013

Fe-doped MnxOy with hierarchical porosity is prepared from a nanocasting technique using amine-functionalized bromomethylated poly (2,6-dimethyl-1,4-phenylene oxide) (BPPO) membranes as the sacrificial template. The synergistic coupling of a percolating macroporous network, uniformly distributed mesopores, and optimal iron doping is used to improve the electronic and ionic wirings of manganese oxides for Li+ storage via the conversion reaction. Very impressive Li+ storage capabilities are shown. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Welner R.S.,Harvard Stem Cell Institute | Amabile G.,Harvard Stem Cell Institute | Bararia D.,National University of Singapore | Czibere A.,Harvard Stem Cell Institute | And 11 more authors.
Cancer Cell | Year: 2015

Leukemic cells disrupt normal patterns of blood cell formation, but little is understood about the mechanism. We investigated whether leukemic cells alter functions of normal hematopoietic stem and progenitor cells. Exposure to chronic myelogenous leukemia (CML) caused normal mouse hematopoietic progenitor cells to divide more readily, altered their differentiation, and reduced their reconstitution and self-renewal potential. Interestingly, the normal bystander cells acquired gene expression patterns resembling their malignant counterparts. Therefore, much of the leukemia signature is mediated by extrinsic factors. Indeed, IL-6 was responsible for most of these changes. Compatible results were obtained when human CML were cultured with normal human hematopoietic progenitor cells. Furthermore, neutralization of IL-6 prevented these changes and treated the disease. © 2015 Elsevier Inc.


Proulle V.,Beth Israel Deaconess Medical Center | Furie R.A.,North Shore Long Island Jewish Health System | Merrill-Skoloff G.,Beth Israel Deaconess Medical Center | Furie B.C.,Beth Israel Deaconess Medical Center | And 2 more authors.
Blood | Year: 2014

Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-β2- glycoprotein-1 autoantibodies (anti-β2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-β2GP1 autoantibody/β2GP1 complex invivo werestudied using a laserinduced thrombosis model of APS in a live mouse and human anti-β2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled β2GP1 and anti-β2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-β2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, monitored by intercellular adhesion molecule-1 expression. When eptifibatide was infused to block platelet thrombus formation, enhanced fibrin generation and endothelial cell activation were eliminated. Thus, the anti-β2GP1 autoantibody/β2GP1 complex binds to the thrombus, enhancing platelet activation, and platelet secretion leads to enhanced endothelium activation and fibrin generation. These results lead to a paradigm shift away from the concept that binding of the anti-β2GP1 autoantibody/β2GP1 complex activates both endothelial cells and platelets toward one in which activation of platelets in response to anti-β2GP1 autoantibody/β2GP1 complex binding leads to subsequent enhanced endothelium activation and fibrin generation. © 2014 by The American Society of Hematology.


Calderwood S.K.,Center for Life science | Calderwood S.K.,Beth Israel Deaconess Medical Center
Sub-Cellular Biochemistry | Year: 2015

The co-chaperone p50/Cdc37 is an important partner for Hsp90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. The Hsp90/Cdc37complex controls the folding of a large proportion of protein kinases and thus stands at the hub of a multitude of intracellular signalling networks. Its effects thus reach beyond the housekeeping pathways of protein folding into regulation of a wide range of cellular processes. Due to its influence in cell growth pathways Cdc37 has attracted much attention as a potential intermediate in carcinogenesis. Cdc37 is an attractive potential target in cancer due to: (1) it may be expressed to high level in some types of cancer and (2) Cdc37 controls multiple signaling pathways. This indicates a potential for: (1) selectivity due to its elevated expression and (2) robustness as the co-chaperone may control multiple growth signalling pathways and thus be less prone to evolution of resistance than other oncoproteins. Cdc37 may also be involved in other aspects of pathophysiology. Protein aggregation disorders have been linked to molecular chaperones and to age related declines in molecular chaperones and co-chaperones. Cdc37 appears to be a potential agent in longevity due to its links to protein folding and autophagy and it will be informative to study the role of Cdc37 maintenance/decline in aging organisms. © Springer International Publishing Switzerland 2015.


Lin S.,CAS Beijing National Laboratory for Molecular | Zhang Z.,CAS Beijing National Laboratory for Molecular | Xu H.,China National Institute of Biological Sciences | Li L.,China National Institute of Biological Sciences | And 5 more authors.
Journal of the American Chemical Society | Year: 2011

Enteric bacterial pathogens are known to effectively pass through the extremely acidic mammalian stomachs and cause infections in the small and/or large intestine of human hosts. However, their acid-survival strategy and pathogenesis mechanisms remain elusive, largely due to the lack of tools to directly monitor and manipulate essential components (e.g., defense proteins or invasive toxins) participating in these processes. Herein, we have extended the pyrrolysine-based genetic code expansion strategy for encoding unnatural amino acids in enteric bacterial species, including enteropathogenic Escherichia coli, Shigella, and Salmonella. Using this system, a photo-cross-linking amino acid was incorporated into a Shigella acid chaperone HdeA (shHdeA), which allowed the identification of a comprehensive list of in vivo client proteins that are protected by shHdeA upon acid stress. To further demonstrate the application of our strategy, an azide-bearing amino acid was introduced into a Shigella type 3 secretion effector, OspF, without interruption of its secretion efficiency. This site-specifically installed azide handle allowed the facile detection of OspF's secretion in bacterial extracellular space. Taken together, these bioorthogonal functionalities we incorporated into enteric pathogens were shown to facilitate the investigation of unique and important proteins involved in the pathogenesis and stress-defense mechanisms of pathogenic bacteria that remain exceedingly difficult to study using conventional methodologies. © 2011 American Chemical Society.


Inceoglu O.,Center for Life science | van Overbeek L.S.,Plant Research International | Salles J.F.,Center for Life science | van Elsas J.D.,Center for Life science
Applied and Environmental Microbiology | Year: 2013

In this study, the impacts of six potato (Solanum tuberosum) cultivars with different tuber starch allocations (including one genetically modified [GM] line) on the bacterial communities in field soil were investigated across two growth seasons interspersed with 1year of barley cultivation, using quantitative PCR, clone library, and PCR-denaturing gradient gel electrophoresis (DGGE) analyses. It was hypothesized that the modifications in the tuber starch contents of these plants, yielding changed root growth rates and exudation patterns, might have elicited altered bacterial communities in the soil. The data showed that bacterial abundances in the bulk soil varied over about 2 orders of magnitude across the 3 years. As expected, across all cultivars, positive potato rhizosphere effects on bacterial abundances were noted in the two potato years. The bulk soil bacterial community structures revealed progressive shifts across time, and moving-window analysis revealed a 60% change over the total experiment. Consistent with previous findings, the community structures in the potato rhizosphere compartments were mainly affected by the growth stage of the plants and, to a lesser extent, by plant cultivar type. The data from the soil under the non-GM potato lines were then taken to define the normal operating range (NOR) of the microbiota under potatoes. Interestingly, the bacterial communities under the GM potato line remained within this NOR. In regard to the bacterial community compositions, particular bacterial species in the soil appeared to be specific to (i) the plant species under investigation (barley versus potato) or, with respect to potatoes, (ii) the plant growth stage. Members of the genera Arthrobacter, Streptomyces, Rhodanobacter, and Dokdonella were consistently found only at the flowering potato plants in both seasons, whereas Rhodoplanes and Sporosarcina were observed only in the soil planted to barley. © 2013, American Society for Microbiology.


Inceoglu O.,Center for Life science | Sablayrolles C.,ENSIACET | van Elsas J.D.,Center for Life science | Falcao Salles J.,Center for Life science
Applied Soil Ecology | Year: 2013

Desulfonation is an important process in the sulfur cycle, through which organic sulfur compounds are mineralized, releasing S. Desulfonating bacteria are known to respond to inorganic S soil amendments. However, the extent to which these communities shift as a response to the addition of organic sulfur in the soil remains elusive. Here, we investigated how amendments of soil with inorganic or organic sulfur compounds influence the bacterial communities associated with potato, in a microcosm experiment. The soil was amended with two doses of linear alkylbenzene sulfonate (LAS), here used as a model aromatic sulfonate compound, or with sulfate. Degradation of LAS was observed already at the young plant stage, as in all treatments 10- to 50-fold reductions of the initial (background) LAS concentrations were noted. Quantitative PCR analyses showed no significant effects of treatment on the bacterial abundances, which tended to increase from the young plant to the flowering stages of plant development. The bacterial community structures, determined via PCR-DGGE, were strongly affected by the presence of plants. This rhizosphere effect became more apparent at the flowering stages. Both the bacterial and β-proteobacterial community structures were affected by the presence of LAS, but dose-related effects were not observed. LAS also caused significant changes in the community structures, as compared to those in inorganic sulfate amended soil. Sulfate did not influence the bacterial community structures and only affected the β-proteobacterial ones at the flowering stage. Surprisingly, the presence of LAS did not exert any significant effect on the abundance of the Variovorax asfA gene, although clone libraries revealed a dominance of Variovorax types in the rhizosphere, especially in the high-level LAS treatment. Our results suggest that rhizosphere communities are key players in LAS degradation in soils, and that desulfonator Variovorax spp. plays a minor role in the mineralization of aromatic sulfonates in soil cropped with potato. © 2012 Elsevier B.V.


Zhang X.,Harvard University | Burstein R.,Harvard University | Levy D.,Harvard University | Levy D.,Center for Life Science
Cephalalgia | Year: 2012

Background: Peripheral nociceptive action of the proinflammatory cytokines IL-1β and IL-6 has been implicated in the pathogenesis of numerous pain syndromes. An increase in the level of these cytokines in jugular venous blood has been reported during migraine attacks, suggesting their potential involvement in mediating the intracranial headache of migraine. Methods: In this work we examined, using in vivo single-unit recording of meningeal nociceptors in the trigeminal ganglion of anesthetized rats, whether the peripheral actions of IL-1β and IL-6 can promote the activation and sensitization of nociceptors that innervate the intracranial meninges, two neural processes that are believed to play a key role in promoting the intracranial throbbing pain of migraine.Results: We found that meningeal application of IL-1β leads to the activation and mechanical sensitization of about 70% and 45% of the nociceptors respectively. In contrast, IL-6 was a very poor modulator of meningeal nociceptors' response properties affecting overall only about 20% of the nociceptors. Conclusions: Our study provides for the first time in vivo electrophysiological evidence that meningeal action of IL-1β can promote the activation and increased mechanosensitivity of intracranial meningeal nociceptors and that IL-6 generally lacks these properties. Future studies are required to examine the mechanism that plays a role in mediating the nociceptive effects of IL-1β on meningeal nociceptors, which may serve as a target for migraine therapy. © International Headache Society 2011.


Inceoglu O.,Center for Life science | Salles J.F.,Center for Life science | van Elsas J.D.,Center for Life science
Microbial Ecology | Year: 2012

The rhizospheres of five different potato cultivars (including a genetically modified cultivar) obtained from a loamy sand soil and two from a sandy peat soil, next to corresponding bulk soils, were studied with respect to their community structures and potential function. For the former analyses, we performed bacterial 16S ribosomal RNA genebased PCR denaturing gradient gel electrophoresis (PCR-DGGE) on the basis of soil DNA; for the latter, we extracted microbial communities and subjected these to analyses in phenotype arrays (PM1, PM2, and PM4, Biolog), with a focus on the use of different carbon, sulfur and phosphorus sources. In addition, we performed bacterial PCR-DGGE on selected wells to assess the structures of these substrate-responsive communities. Effects of soil type, the rhizosphere, and cultivar on the microbial community structures were clearly observed. Soil type was the most determinative parameter shaping the functional communities, whereas the rhizosphere and cultivar type also exerted an influence. However, no genetically modified plant effect was observed. The effects were imminent based on general community analysis and also single-compound analysis. Utilization of some of the carbon and sulfur sources was specific per cultivar, and different microbial communities were found as defined by cultivar. Thus, both soil and cultivar type shaped the potato root-associated bacterial communities that were responsive to some of the substrates in phenotype arrays. © 2011 The Author(s).


Inceoglu O.,Center for Life science | Al-Soud W.A.,Copenhagen University | Salles J.F.,Center for Life science | Semenov A.V.,Center for Life science | van Elsas J.D.,Center for Life science
PLoS ONE | Year: 2011

Background: Plants selectively attract particular soil microorganisms, in particular consumers of root-excreted compounds. It is unclear to what extent cultivar type and/or growth stage affect this process. Methodology/Principal Findings: DNA-based pyrosequencing was used to characterize the structure of bacterial communities in a field cropped with potato. The rhizospheres of six cultivars denoted Aveka, Aventra, Karnico, Modena, Premiere and Desiree, at three growth stages (young, flowering and senescence) were examined, in addition to corresponding bulk soils. Around 350,000 sequences were obtained (5,700 to 38,000 per sample). Across all samples, rank abundance distributions best fitted the power law model, which indicates a community composed of a few highly dominant species next to numerous rare species. Grouping of the sequences showed that members of the Actinobacteria, Alphaproteobacteria, next to as-yet-unclassified bacteria, dominated. Other groups that were consistently found, albeit at lower abundance, were Beta-, Gamma- and Deltaproteobacteria and Acidobacteria. Principal components analyses revealed that rhizosphere samples were significantly different from corresponding bulk soil in each growth stage. Furthermore, cultivar effects were found in the young plant stage, whereas these became insignificant in the flowering and senescence stages. Besides, an effect of time of season was observed for both rhizosphere and bulk soils. The analyzed rhizosphere samples of the potato cultivars were grouped into two groups, in accordance with the allocation of carbon to starch in their tubers, i.e. Aveka, Aventra and Karnico (high) versus Premiere and Desiree (low) and thus replicates per group were established. Conclusions: Across all potato cultivars, the young plant stages revealed cultivar-dependent bacterial community structures, which disappeared in the flowering and senescence stages. Furthermore, Pseudomonas, Beta-, Alpha- and Deltaproteobacteria flourished under different ecological conditions than the Acidobacteria. © 2011 Inceoǧlu et al.

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