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MIT Open Access Articles
Mostrando recursos 41 - 60 de 13,840
Retinoic Acid Activates Two Pathways Required for Meiosis in Mice - Koubova, Jana; Hu, Yueh-Chiang; Bhattacharyya, Tanmoy; Soh, Ying Qi Shirleen; Gill, Mark E.; Goodheart, Mary L.; Hogarth, Cathryn A.; Griswold, Michael D.; Page, David C.
In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase. Here we report that RA also activates transcription of Rec8, which encodes a component of the cohesin complex that accumulates during meiotic S phase, and which is essential for chromosome synapsis and segregation. This RA induction of Rec8 occurs in parallel with the induction of Stra8, and independently of Stra8 function, and it is conserved...
Long-Term Reproducible Expression in Human Fetal Liver Hematopoietic Stem Cells with a UCOE-Based Lentiviral Vector - Dighe, Niraja; Khoury, Maroun; Mattar, Citra; Chong, Mark; Choolani, Mahesh; Chen, Jianzhu; Antoniou, Michael N.; Chan, Jerry K. Y.
Hematopoietic Stem Cell (HSC) targeted gene transfer is an attractive treatment option for a number of hematopoietic disorders caused by single gene defects. However, extensive methylation of promoter sequences results in silencing of therapeutic gene expression. The choice of an appropriate promoter is therefore crucial for reproducible, stable and long-term transgene expression in clinical gene therapy. Recent studies suggest efficient and stable expression of transgenes from the ubiquitous chromatin opening element (UCOE) derived from the human HNRPA2B1-CBX3 locus can be achieved in murine HSC. Here, we compared the use of HNRPA2B1-CBX3 UCOE (A2UCOE)-mediated transgene regulation to two other frequently used...
The role of flow in green chemistry and engineering - Newman, Stephen G.; Jensen, Klavs F.
Flow chemistry and continuous processing can offer many ways to make synthesis a more sustainable practice. These technologies help bridge the large gap between academic and industrial settings by often providing a more reproducible, scalable, safe and efficient option for performing chemical reactions. In this review, we use selected examples to demonstrate how continuous methods of synthesis can be greener than batch synthesis on a small and a large scale.
Retino-hypothalamic regulation of light-induced murine sleep - Muindi, Fanuel; Zeitzer, Jamie M.; Heller, Horace Craig
The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications...
The contribution of fungal spores and bacteria to regional and global aerosol number and ice nucleation immersion freezing rates - Spracklen, D. V.; Heald, Colette L.
Primary biological aerosol particles (PBAPs) may play an important role in aerosol–climate interactions, in particular by affecting ice formation in mixed phase clouds. However, the role of PBAPs is poorly understood because the sources and distribution of PBAPs in the atmosphere are not well quantified. Here we include emissions of fungal spores and bacteria in a global aerosol microphysics model and explore their contribution to concentrations of supermicron particle number, cloud condensation nuclei (CCN) and immersion freezing rates. Simulated surface annual mean concentrations of fungal spores are ~ 2.5 × 10[superscript 4] m[superscript −3] over continental midlatitudes and 1 ×...
Ecosystem fluxes of hydrogen: a comparison of flux-gradient methods - Meredith, Laura Kelsey; Commane, R.; Munger, J. W.; Dunn, A.; Tang, J.; Wofsy, S. C.; Prinn, Ronald G.
Our understanding of biosphere–atmosphere exchange has been considerably enhanced by eddy covariance measurements. However, there remain many trace gases, such as molecular hydrogen (H[subscript 2]), that lack suitable analytical methods to measure their fluxes by eddy covariance. In such cases, flux-gradient methods can be used to calculate ecosystem-scale fluxes from vertical concentration gradients. The budget of atmospheric H[subscript 2] is poorly constrained by the limited available observations, and thus the ability to quantify and characterize the sources and sinks of H[subscript 2] by flux-gradient methods in various ecosystems is important. We developed an approach to make nonintrusive, automated measurements of...
Impact of external industrial sources on the regional and local SO[subscript 2] and O[subscript 3] levels of the Mexico megacity - Almanza, Victor; Molina, Luisa Tan; Li, G.; Fast, J.; Sosa, G.
The air quality of megacities can be influenced by external emission sources on both global and regional scales. At the same time their outflow emissions can exert an impact to the surrounding environment. The present study evaluates an SO2 peak observed on 24 March 2006 at the suburban supersite T1 and at ambient air quality monitoring stations located in the northern region of the Mexico City Metropolitan Area (MCMA) during the Megacity Initiative: Local and Global Research Observations (MILAGRO) field campaign. We found that this peak could be related to an important episodic emission event coming from Tizayuca region, northeast...
Type XVIII collagen is essential for survival during acute liver injury in mice - Duncan, Michael B.; Yang, Changqing; Tanjore, Harikrishna; Boyle, Patrick M.; Keskin, Doruk; Sugimoto, Hikaru; Zeisberg, Michael; Olsen, Bjorn R.; Kalluri, Raghu
The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death. The type-XVIII-collagen-dependent response to liver injury is mediated by survival signals induced by α1β1 integrin, integrin linked kinase and the Akt pathway, and mice deficient in either...
The landscape of human STR variation - Willems, Thomas Frederick; Gymrek, Melissa A.; Highnam, Gareth; 1000 Genomes Project Consortium; Mittelman, David; Erlich, Yaniv
Short tandem repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population. Here, we report the largest-scale analysis of human STR variation to date. We collected information for nearly 700,000 STR loci across more than 1000 individuals in Phase 1 of the 1000 Genomes Project. Extensive quality controls show that reliable allelic spectra can be...
Systems consequences of amplicon formation in human breast cancer - Inaki, Koichiro; Menghi, Francesca; Woo, Xing Yi; Wagner, Joel Patrick; Jacques, Pierre-Étienne; Lee, Yi Fang; Shreckengast, Phung Trang; Soon, Wendy WeiJia; Malhotra, Ankit; Teo, Audrey S.M.; Hillmer, Axel M.; Khng, Alexis Jiaying; Ruan, Xiaoan; Ong, Swee Hoe; Bertrand, Denis; Nagarajan, Niranjan; Karuturi, R. Krishna Murthy; Miranda, Alfredo Hidalgo; Liu, Edison T.
Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor...
Site-Specific Chemoenzymatic Labeling of Aerolysin Enables the Identification of New Aerolysin Receptors - Wuethrich, Irene; Peeters, Janneke G. C.; Blom, Annet E. M.; Theile, Christopher S.; Li, Zeyang; Spooner, Eric; Ploegh, Hidde; Guimaraes, Carla P.
Aerolysin is a secreted bacterial toxin that perforates the plasma membrane of a target cell with lethal consequences. Previously explored native and epitope-tagged forms of the toxin do not allow site-specific modification of the mature toxin with a probe of choice. We explore sortase-mediated transpeptidation reactions (sortagging) to install fluorophores and biotin at three distinct sites in aerolysin, without impairing binding of the toxin to the cell membrane and with minimal impact on toxicity. Using a version of aerolysin labeled with different fluorophores at two distinct sites we followed the fate of the C-terminal peptide independently from the N-terminal part...
De-Differentiation Confers Multidrug Resistance Via Noncanonical PERK-Nrf2 Signaling - Del Vecchio, Catherine A.; Feng, Yuxiong; Sokol, Ethan Samuel; Tillman, Erik J.; Sanduja, Sandhya; Reinhardt, Ferenc; Gupta, Piyush
Malignant carcinomas that recur following therapy are typically de-differentiated and multidrug resistant (MDR). De-differentiated cancer cells acquire MDR by up-regulating reactive oxygen species (ROS)–scavenging enzymes and drug efflux pumps, but how these genes are up-regulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional profiling to identify ROS-induced genes that are already up-regulated in de-differentiated cells, even in the absence of oxidative damage. Using this approach, we found that the Nrf2 transcription factor, which is the master regulator of cellular responses to oxidative stress, is preactivated in de-differentiated cells. In de-differentiated cells, Nrf2...
HOGgles: Visualizing Object Detection Features - Vondrick, Carl Martin; Khosla, Aditya; Malisiewicz, Tomasz; Torralba, Antonio
We introduce algorithms to visualize feature spaces used by object detectors. The tools in this paper allow a human to put on 'HOG goggles' and perceive the visual world as a HOG based object detector sees it. We found that these visualizations allow us to analyze object detection systems in new ways and gain new insight into the detector's failures. For example, when we visualize the features for high scoring false alarms, we discovered that, although they are clearly wrong in image space, they do look deceptively similar to true positives in feature space. This result suggests that many of...
Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes - Jones, Richard Bradley; O'Connor, Rachel; Mueller, Stefanie; Foley, Maria Hottelet; Szeto, Gregory Lee; Karel, Dan; Lichterfeld, Mathias; Kovacs, Colin; Ostrowski, Mario A.; Trocha, Alicja; Irvine, Darrell J.; Walker, Bruce D.
Resting memory CD4[superscript +] T-cells harboring latent HIV proviruses represent a critical barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to induce HIV expression in these resting cells. Recently, it has been demonstrated that the low levels of viral gene expression induced by a candidate HDACi may be insufficient to cause the death of infected cells by viral cytopathic effects, necessitating their elimination by immune effectors, such as cytotoxic T-lymphocytes (CTL). Here, we study the impact of three HDACis in clinical development on T-cell effector functions. We report two...
The Neural Bases of Directed and Spontaneous Mental State Attributions to Group Agents - Jenkins, Adrianna C.; Dodell-Feder, David; Saxe, Rebecca R.; Knobe, Joshua
In daily life, perceivers often need to predict and interpret the behavior of group agents, such as corporations and governments. Although research has investigated how perceivers reason about individual members of particular groups, less is known about how perceivers reason about group agents themselves. The present studies investigate how perceivers understand group agents by investigating the extent to which understanding the ‘mind’ of the group as a whole shares important properties and processes with understanding the minds of individuals. Experiment 1 demonstrates that perceivers are sometimes willing to attribute a mental state to a group as a whole even when...
Facile synthesis of mononuclear early transition-metal complexes of κ[superscript 3]cyclo-tetrametaphosphate ([P[subscript 4]O[subscript 12]][superscript 4−]) and cyclo-trimetaphosphate ([P[subscript 3]O[subscript 9]][superscript 3−]) - Manna, Cesar M.; Nassar, Mostafa Y.; Tofan, Daniel; Chakarawet, Khetpakorn; Cummins, Christopher C.
We herein report the preparation of several mononuclear-metaphosphate complexes using simple techniques and mild conditions with yields ranging from 56% to 78%. Treatment of cyclo-tetrametaphosphate ([TBA]4[P4O12]·5H2O, TBA = tetra-n-butylammonium) with various metal sources including (CH3CN)3Mo(CO)3, (CH3CN)2Mo(CO)2(η3-C3H5)Cl, MoO2Cl2(OSMe2)2, and VOF3, leads to the clean and rapid formation of [TBA]4[(P4O12)Mo(CO)3]·2H2O, [TBA]3[(P4O12)Mo(CO)2(η3-C3H5)], [TBA]3[(P4O12)MoO2Cl] and [TBA]3[(P4O12)VOF2]·Et2O salts in isolated yields of 69, 56, 68, and 56% respectively. NMR spectroscopy, NMR simulations and single crystal X-ray studies reveal that the [P4O12]4− anion behaves as a tridentate ligand wherein one of the metaphosphate groups is not directly bound to the metal. cyclo-Trimetaphosphate-metal complexes were prepared using...
Effect of polymer chemistry on globular protein–polymer block copolymer self-assembly - Chang, Dongsook; Tang, Shengchang; Olsen, Bradley D.; Lam, Christopher Nguyen
Bioconjugates of the model red fluorescent protein mCherry and synthetic polymer blocks with different hydrogen bonding functionalities show that the chemistry of the polymer block has a large effect on both ordering transitions and the type of nanostructures formed during bioconjugate self-assembly. The phase behaviours of mCherry-b-poly(hydroxypropyl acrylate) (PHPA) and mCherry-b-poly(oligoethylene glycol acrylate) (POEGA) in concentrated aqueous solution show that changes in polymer chemistry result in increase in the order–disorder transition concentrations (C[subscript ODT]s) by approximately 10–15 wt% compared to a previously studied globular protein–polymer block copolymer, mCherry-b-poly(N-isopropylacrylamide) (PNIPAM). The C[subscript ODT]s are always minimized for symmetric bioconjugates, consistent with...