bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Spotlight: Summer heat waves to be a routine occurrence
Authors: Kumar Mohi , Ofori Leslie , Tretkoff Ernie
Published: October 2011

This year has been the hottest on record globally, with many areas around the world experiencing extremely hot conditions this summer. According to Diffenbaugh et al., extreme heat waves can be expected to be a more common occurrence over the next 30 years as greenhouse gas concentrations continue to rise.

The scientists used a new high‐resolution climate model simulation for the United States and compared their results with multiple global climate models. The models showed that there are likely to be increasingly frequent hot extremes during the next 3 decades, including more record‐breaking heat waves and hot seasons in many parts of the United States, especially in the west. These hot conditions would pose a threat not only to the environment but also to human health.
Research Spotlight: How does emissions mitigation policy affect ocean acidification?
Authors: Ofori Leslie , Tretkoff Ernie
Published: October 2011

The anthropogenic release of carbon dioxide (CO2) has increased significantly in recent years. Some of this CO2 is absorbed by the ocean, increasing its acidity (lowering its pH). Studies have shown that since 1750 the absorption of CO2 has caused a decrease of 0.1 in the ocean's pH level. The biological impact of this increasing acidity is uncertain, but scientists believe that increasing acidity could adversely affect marine organisms and degrade ocean habitats.
Research Spotlight: Measuring the rate of mountain building in New Zealand
Authors: Tretkoff Ernie
Published: October 2011

For the past 20 million years, the Southern Alps Mountains, on the South Island of New Zealand, have been growing as continental plates converge. Beavan et al. used 10 years of Global Positioning System data to measure the present‐day rates of vertical movement across the Southern Alps. They found that the highest uplift rates, about 5 millimeters per year, occur near the crest of the mountains, about 20–30 kilometers southeast of the Alpine Fault, while the mountains are growing at a slower rate at lower elevations.
Research Spotlight: Estimating forest rainfall interception from satellite observations
Authors: Tretkoff Ernie
Published: October 2011

Although most rainfall over continents reaches the ground, a significant portion is caught by the forest canopy and evaporates directly. To better understand feedbacks between evaporation and climate and to estimate the effects of climate change and deforestation on water resources, scientists need to know how much rainfall is intercepted by the canopy. Miralles et al. applied satellite rainfall data to an existing model to create global maps of estimated forest rainfall interception.
Research Spotlight: Coriolis forces affect flow in submarine channels
Authors: Tretkoff Ernie
Published: October 2011

Coriolis forces due to the Earth's rotation deflect winds and ocean flows to the right in the Northern Hemisphere and to the left in the Southern Hemisphere. In sinuous submarine channels, Coriolis forces can drive secondary circulation of turbidity currents and determine where erosion and sediment deposition occur.

Cossu and Wells conducted laboratory experiments with a channel in a rotating tank to study the conditions under which Coriolis forces dominate the channel flow and investigate how these forces affect sediment deposition. They found that channels at high latitudes and those with large bends are dominated by Coriolis forces, while channels at lower latitudes and those with smaller bends are less influenced by Coriolis forces.
Research Spotlight: High‐resolution measurements of lunar topography
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Selection of landing sites for potential human or robotic lunar missions requires precise knowledge of lunar topography. Contributing to that knowledge, Smith et al. present initial observations from the Lunar Orbiter Laser Altimeter (LOLA) on board the Lunar Reconnaissance Orbiter.

The LOLA measurements provide a high‐resolution global model of lunar topography based on more observations and observations with greater accuracy than previous lunar topography maps. LOLA also collected high‐resolution data on the slope, roughness, and reflectance of the lunar surface.
Research Spotlight: Why do clouds prevent heat from escaping Earth in a warming climate?
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Clouds affect Earth's surface temperature in two key ways: They exert a cooling influence on the planet by reflecting solar (shortwave) radiation back to space and a warming influence on the planet by reducing the amount of infrared (longwave) radiation emitted to space. The balance between these two forces helps to govern climate conditions. A changing climate may influence cloud height, thickness, and frequency, which in turn could dramatically affect how clouds balance cooling and warming.
Research Spotlight: Mapping moisture recycling and global water resources
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Water that falls as precipitation in one region may have originated in a distant region, or it may be recycled moisture that originated as evaporation within the region. Global wind patterns, topography, and land cover all play a role in moisture recycling patterns and the distribution of global water resources. Land use changes such as irrigation, dams, and deforestation can alter evaporation patterns in a region, potentially affecting water resources in distant regions.
Research Spotlight: Model of Earth's gravity field developed from combined satellite data
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Models of Earth's gravity field show how the planet's density varies in its interior and on its surface, depending on topography and geologic composition. For instance, dense mountains create an area of stronger gravitational pull. Pail et al. developed a new model of Earth's gravity field using measurements from both the Gravity Recovery and Climate Experiment (GRACE) satellites and the Gravity Field and Steady‐State Ocean Circulation Explorer (GOCE) satellite.
Research Spotlight: Laboratory experiments help to better define stream erosion and deposition
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Streams and rivers, through eroding banks and depositing sediment, are primary agents of change to Earth' landscapes. At a fundamental level, such erosion and deposition are dependent on bed load transport—the motion of particles rolling, sliding, or traveling in a succession of slow jumps, or saltations, along the bed of a stream. Bed load transport governs processes such as river bed morphology and the rate at which a river incises relief. Yet despite the importance of bed load transport, little is known about the physics behind erosion and deposition at the grain scale.
Research Spotlight: Split tectonic plate beneath western Japan explains earthquake activity
Authors: Tretkoff Ernie
Published: October 2011

Western Japan, a densely populated region, is prone to large earthquakes and volcanic eruptions, but the tectonics of the underlying region is not well understood. The shape of the Philippine Sea plate subducting beneath western Japan is a key factor in understanding the spatial distribution of earthquakes.
Research Spotlight: Satellite data show inland water bodies warming
Authors: Kumar Mohi , Tretkoff Ernie
Published: October 2011

Many studies of global climate have used air temperature measurements to characterize recent warming trends. A new study shows that inland water bodies such as lakes have also been warming steadily in recent decades.

Schneider and Hook analyzed satellite nighttime thermal infrared imagery of 167 large inland water bodies around the world during the period 1985–2009. They found that mean nighttime surface water temperature for these inland water bodies has been rising at an average rate of about 0.045°C per year, with rates as high as 0.1°C per year in some places.
Cisplatin resistance induced by decreased apoptotic activity in non‐small‐cell lung cancer cell lines
Authors: Cetintas Vildan B. , Kucukaslan Ali S. , Kosova Buket , Tetik Aslı , Selvi Nur , Cok Gursel , Gunduz Cumhur , Eroglu Zuhal
Published: October 2011

We have investigated defective steps in apoptosis that might account for the development of resistance. For this purpose, A549 and Calu1 NSCLC (non‐small‐cell lung cancer) cell lines were treated with cisplatin to obtain resistant sub‐lines. Gene expression profiles and the phosphorylation status of the BAD (Bcl‐2/Bcl‐XL‐antagonist, causing cell death) protein were determined for each cell line. Cell death and cytochrome c release were analysed after treating cell lines with their appropriate cisplatin doses. Gene expression of BAD, Bid, caspases 4 and 6 were clearly decreased in the resistant cell lines, and the differential phosphorylation status of BAD also seemed to play a role in the development of cisplatin resistance. Since this is a new cisplatin‐resistant Calu1 cell line, it is noteworthy that DNA fragmentation, apoptotic cell ratio and cytochrome c levels were most decreased in the CR‐Calu1 cell line.
Rietveld analysis, dielectric and magnetic properties of Sr and Ti codoped BiFeO3 multiferroic
Authors: Reetu  , Agarwal Ashish , Sanghi Sujata , Ashima
Published: October 2011

Polycrystalline Bi0.8Sr0.2Fe1 − xTixO3 (x = 0.0, 0.1, 0.2) multiferroics were synthesized via the conventional solid state reaction method. The structure, dielectric relaxation, and magnetic properties of as prepared samples were investigated. The crystal structure examined via XRD and Rietveld analysis confirmed a single phase rhombohedral (space group R3c no. 161) structure. In the Rietveld refinement, good agreement between the observed and calculated pattern was observed. The dielectric response of these multiferroics was analyzed in the frequency range of 10 Hz to 5 MHz at different temperatures. All the samples showed dispersion in dielectric constant (έ) and dielectric loss factor (tan δ) values. The temperature dependence of έ and tan δ showed broad peaks. A reduction in the values of έ and tan δ was observed upon the incorporation of Ti. Magnetic measurements were carried out at room temperature up to a field of 20 kOe. Magnetic hysteresis loops revealed a significant increase in magnetization with Ti substitution. A remnant magnetization (Mr) of 33.428 memu/g and a coercive field (Hc) of 1.724 kOe were observed in the sample with x = 0.2.
Simultaneous sample and spatial coherence characterisation using diffractive imaging
Authors: Clark Jesse N. , Peele Andrew G.
Published: October 2011

We demonstrate an algorithm that reconstructs the complex transmission function of an object from experimental X-ray diffraction data using partially coherent 1.4 keV X-rays that does not require a priori input of the coherence function. The quality of the reconstruction is significantly better than that obtained by assuming that the illumination is fully coherent. Our approach can be readily applied to diffraction imaging problems where a model for the spatial coherence can be assumed.
Room-temperature organic-based spin polarizer
Authors: Li Bin , Kao Chi-Yueh , Lu Yu , Yoo Jung-Woo , Prigodin Vladimir N. , Epstein Arthur J.
Published: October 2011

We report a magnetic tunnel junction operating at room-temperature with organic magnetic semiconductor V[TCNE]x (x ∼ 2, TCNE: tetracyanoethylene) and Fe as the spin polarizer and analyzer while 10 nm rubrene layer serves as the tunnel barrier between them. At room-temperature, the magnetoresistance (MR) presents 16.7% of its peak value at 100 K. We observed sign inversion of MR with increasing temperature, while the sign of the MR is independent of the polarity of the bias voltages. Our results suggest that V[TCNE]x is a promising material for room-temperature spintronic applications.
Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory
Authors: Feredoes Eva , Heinen Klaartje , Weiskopf Nikolaus , Ruff Christian , Driver Jon
Published: October 2011

Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance of memory targets or suppress processing of distracters. To adjudicate between these possibilities, we applied time-locked transcranial magnetic stimulation (TMS) during functional MRI, an approach that permits causal assessment of a stimulated brain region's influence on connected brain regions, and evaluated how this influence may change under different task conditions. Participants performed a visual WM task requiring retention of visual stimuli (faces or houses) across a delay during which visual distracters could be present or absent. When distracters were present, they were always from the opposite stimulus category, so that targets and distracters were represented in distinct posterior cortical areas. We then measured whether DLPFC-TMS, administered in the delay at the time point when distracters could appear, would modulate posterior regions representing memory targets or distracters. We found that DLPFC-TMS influenced posterior areas only when distracters were present and, critically, that this influence consisted of increased activity in regions representing the current memory targets. DLPFC-TMS did not affect regions representing current distracters. These results provide a new line of causal evidence for a top-down DLPFC-based control mechanism that promotes successful maintenance of relevant information in WM in the presence of distraction.
Resistance to thyroid hormone is modulated in vivo by the nuclear receptor corepressor (NCOR1)
Authors: Fozzatti Laura , Lu Changxue , Kim Dong Wook , Park Jeong Won , Astapova Inna , Gavrilova Oksana , Willingham Mark C. , Hollenberg Anthony N. , Cheng Sheue-yann
Published: October 2011

Mutations in the ligand-binding domain of the thyroid hormone receptor β (TRβ) lead to resistance to thyroid hormone (RTH). These TRβ mutants function in a dominant-negative fashion to interfere with the transcription activity of wild-type thyroid hormone receptors (TRs), leading to dysregulation of the pituitary–thyroid axis and resistance in peripheral tissues. The molecular mechanism by which TRβ mutants cause RTH has been postulated to be an inability of the mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone (TH)-mediated transcription activity. To test this hypothesis in vivo, we crossed

Thrb
PV

mice (a model of RTH) expressing a human TRβ mutant (PV) with mice expressing a mutant
Ncor1
allele (

Ncor1
ΔID

mice) that cannot recruit a TR or a PV mutant. Remarkably, in the presence of NCOR1ΔID, the abnormally elevated thyroid-stimulating hormone and TH levels found in

Thrb
PV

mice were modestly but significantly corrected. Furthermore, thyroid hyperplasia, weight loss, and other hallmarks of RTH were also partially reverted in mice expressing NCOR1ΔID. Taken together, these data suggest that the aberrant recruitment of NCOR1 by RTH TRβ mutants leads to clinical RTH in humans. The present study suggests that therapies aimed at the TR–NCOR1 interaction or its downstream actions could be tested as potential targets in treating RTH.
New methods devised specify the size and color of the spots monkeys see when striate cortex (area V1) is electrically stimulated
Authors: Schiller Peter H. , Slocum Warren M. , Kwak Michelle C. , Kendall Geoffrey L. , Tehovnik Edward J.
Published: October 2011

Creating a prosthetic device for the blind is a central future task. Our research examines the feasibility of producing a prosthetic device based on electrical stimulation of primary visual cortex (area V1), an area that remains intact for many years after loss of vision attributable to damage to the eyes. As an initial step in this effort, we believe that the research should be carried out in animals, as it has been in the creation of the highly successful cochlear implant. We chose the rhesus monkey, whose visual system is similar to that of man. We trained monkeys on two tasks to assess the size, contrast, and color of the percepts created when single sites in area V1 are stimulated through microelectrodes. Here, we report that electrical stimulation within the central 5° of the visual field representation creates a small spot that is between 9 and 26 min of arc in diameter and has a contrast ranging between 2.6% and 10%. The dot generated by the stimulation in the majority of cases was darker than the background viewed by the animal and was composed of a variety of low-contrast colors. These findings can be used as inputs to models of electrical stimulation in area V1. On the basis of these findings, we derive what kinds of images would be expected when implanted arrays of electrodes are stimulated through a camera attached to the head whose images are converted into electrical stimulation using appropriate algorithms.
Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity
Authors: Chang Aram , Singh Shanteri , Helmich Kate E. , Goff Randal D. , Bingman Craig A. , Thorson Jon S. , Phillips George N.
Published: October 2011

Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.
Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload
Authors: Shimano Masayuki , Ouchi Noriyuki , Nakamura Kazuto , van Wijk Bram , Ohashi Koji , Asaumi Yasuhide , Higuchi Akiko , Pimentel David R. , Sam Flora , Murohara Toyoaki , van den Hoff Maurice J. B. , Walsh Kenneth
Published: October 2011

Factors secreted by the heart, referred to as “cardiokines,” have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis.
Direct activation of antigen-presenting cells is required for CD8+T-cell priming and tumor vaccination
Authors: Kratky Wolfgang , Reis e Sousa Caetano , Oxenius Annette , Spörri Roman
Published: October 2011

Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that APCs could be activated indirectly by proinflammatory mediators synthesized by PAMP-exposed cells. However, data obtained with CD4+T cells suggest that inflammatory signals often cannot substitute for direct pattern recognition in APC activation for the priming of T helper responses. To test whether the same is true for CD8+T cells, we studied cytotoxic T lymphocyte development in vitro and in mixed chimeric mice in which coexisting APCs can either present a preprocessed model antigen or directly recognize a given PAMP, but not both. We show that indirectly activated APCs promote antigen-specific proliferation of naïve CD8+T cells but fail to support their survival and cytotoxic T lymphocyte differentiation. Furthermore, CD8+T cells primed by indirectly activated APCs are unable to reject tumors. Thus, inflammation cannot substitute for direct recognition of single PAMPs in CD8+T-cell priming. These findings have important practical implications for vaccine design, indicating that adjuvants must be judiciously chosen to trigger the relevant pattern recognition receptors in APCs.
Locating an extracellular K+-dependent interaction site that modulates betaine-binding of the Na+-coupled betaine symporter BetP
Authors: Ge Lin , Perez Camilo , Waclawska Izabela , Ziegler Christine , Muller Daniel J.
Published: October 2011

BetP, a trimeric Na+-coupled betaine symporter, senses hyperosmotic stressviaits cytoplasmic C-terminal domain and regulates transport activity in dependence of the cytoplasmic K+-concentration. This transport regulation of BetP depends on a sophisticated interaction network. Using single-molecule force spectroscopy we structurally localize and quantify these interactions changing on K+-dependent transport activation and substrate-binding. K+significantly strengthened all interactions, modulated lifetimes of functionally important structural regions, and increased the mechanical rigidity of the symporter. Substrate-binding could modulate, but not establish most of these K+-dependent interactions. A pronounced effect triggered by K+was observed at the periplasmic helical loop EH2. Tryptophan quenching experiments revealed that elevated K+-concentrations akin to those BetP encounters during hyperosmotic stress trigger the formation of a periplasmic second betaine-binding (S2) site, which was found to be at a similar position reported previously for the BetP homologue CaiT. In BetP, the presence of the S2 site strengthened the interaction between EH2, transmembrane α-helix 12 and the K+-sensing C-terminal domain resulting in a K+-dependent cooperative betaine-binding.
Mutation of a single allele of the cancer susceptibility gene
BRCA1
leads to genomic instability in human breast epithelial cells
Authors: Konishi Hiroyuki , Mohseni Morassa , Tamaki Akina , Garay Joseph P. , Croessmann Sarah , Karnan Sivasundaram , Ota Akinobu , Wong Hong Yuen , Konishi Yuko , Karakas Bedri , Tahir Khola , Abukhdeir Abde M. , Gustin John P. , Cidado Justin , Wang Grace M. , Cosgrove David , Cochran Rory , Jelovac Danijela , Higgins Michaela J. , Arena Sabrina , Hawkins Lauren , Lauring Josh , Gross Amy L. , Heaphy Christopher M. , Hosokawa Yositaka , Gabrielson Edward , Meeker Alan K. , Visvanathan Kala , Argani Pedram , Bachman Kurtis E. , Park Ben Ho
Published: October 2011

Biallelic inactivation of cancer susceptibility gene
BRCA1
leads to breast and ovarian carcinogenesis. Paradoxically,
BRCA1
deficiency in mice results in early embryonic lethality, and similarly, lack of
BRCA1
in human cells is thought to result in cellular lethality in view of
BRCA1
's essential function. To survive homozygous
BRCA1
inactivation during tumorigenesis, precancerous cells must accumulate additional genetic alterations, such as
p53
mutations, but this requirement for an extra genetic “hit” contradicts the two-hit theory for the accelerated carcinogenesis associated with familial cancer syndromes. Here, we show that heterozygous
BRCA1
inactivation results in genomic instability in nontumorigenic human breast epithelial cells in vitro and in vivo. Using somatic cell gene targeting, we demonstrated that a heterozygous
BRCA1
185delAG mutation confers impaired homology-mediated DNA repair and hypersensitivity to genotoxic stress. Heterozygous mutant
BRCA1
cell clones also showed a higher degree of gene copy number loss and loss of heterozygosity in SNP array analyses. In
BRCA1
heterozygous clones and nontumorigenic breast epithelial tissues from
BRCA
mutation carriers, FISH revealed elevated genomic instability when compared with their respective controls. Thus,
BRCA1
haploinsufficiency may accelerate hereditary breast carcinogenesis by facilitating additional genetic alterations.
Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia
Authors: Yamamoto-Sugitani Mio , Kuroda Junya , Ashihara Eishi , Nagoshi Hisao , Kobayashi Tsutomu , Matsumoto Yosuke , Sasaki Nana , Shimura Yuji , Kiyota Miki , Nakayama Ryuko , Akaji Kenichi , Taki Tomohiko , Uoshima Nobuhiko , Kobayashi Yutaka , Horiike Shigeo , Maekawa Taira , Taniwaki Masafumi
Published: October 2011

Bone marrow (BM) microenvironment (BMME) constitutes the sanctuary for leukemic cells. In this study, we investigated the molecular mechanisms for BMME-mediated drug resistance and BM lodgment in chronic myelogenous leukemia (CML). Gene-expression profile as well as signal pathway and protein analyses revealed that galectin-3 (Gal-3), a member of the β-gal–binding galectin family of proteins, was specifically induced by coculture with HS-5 cells, a BM stroma cell-derived cell line, in all five CML cell lines examined. It was also found that primary CML cells expressed high levels of Gal-3 in BM. Enforced expression of Gal-3 activated Akt and Erk, induced accumulation of Mcl-1, and promoted in vitro cell proliferation, multidrug resistance to tyrosine kinase inhibitors for Bcr-Abl and genotoxic agents as a result of impaired apoptosis induction, and chemotactic cell migration to HS-5–derived soluble factors in CML cell lines independently of Bcr-Abl tyrosine kinase. The conditioned medium from Gal-3–overexpressing CML cells promoted in vitro cell proliferation of CML cells and HS-5 cells more than did the conditioned medium from parental cells. Moreover, the in vivo study in a mice transplantation model showed that Gal-3 overexpression promoted the long-term BM lodgment of CML cells. These results demonstrate that leukemia microenvironment-specific Gal-3 expression supports molecular signaling pathways for disease maintenance in BM and resistance to therapy in CML. They also suggest that Gal-3 may be a candidate therapeutic target to help overcome BMME-mediated therapeutic resistance.
Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis
Authors: Park Eun Sung , Kim Sun Jin , Kim Seung Wook , Yoon Se-Lyun , Leem Sun-Hee , Kim Sang-Bae , Kim Soo Mi , Park Yun-Yong , Cheong Jae-Ho , Woo Hyun Goo , Mills Gordon B. , Fidler Isaiah J. , Lee Ju-Seog
Published: October 2011

Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior.
Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection
Authors: Hara Yuji , Kanagawa Motoi , Kunz Stefan , Yoshida-Moriguchi Takako , Satz Jakob S. , Kobayashi Yvonne M. , Zhu Zihan , Burden Steven J. , Oldstone Michael B. A. , Campbell Kevin P.
Published: October 2011

α-dystroglycan is a highly
O
-glycosylated extracellular matrix receptor that is required for anchoring of the basement membrane to the cell surface and for the entry of Old World arenaviruses into cells. Like-acetylglucosaminyltransferase (LARGE) is a key molecule that binds to the N-terminal domain of α-dystroglycan and attaches ligand-binding moieties to phosphorylated
O
-mannose on α-dystroglycan. Here we show that the LARGE modification required for laminin- and virus-binding occurs on specific Thr residues located at the extreme N terminus of the mucin-like domain of α-dystroglycan. Deletion and mutation analyses demonstrate that the ligand-binding activity of α-dystroglycan is conferred primarily by LARGE modification at Thr-317 and -319, within the highly conserved first 18 amino acids of the mucin-like domain. The importance of these paired residues in laminin-binding and clustering activity on myoblasts and in arenavirus cell entry is confirmed by mutational analysis with full-length dystroglycan. We further demonstrate that a sequence of five amino acids, Thr
317
ProThr
319
ProVal, contains phosphorylated
O
-glycosylation and, when modified by LARGE is sufficient for laminin-binding. Because the N-terminal region adjacent to the paired Thr residues is removed during posttranslational maturation of dystroglycan, our results demonstrate that the ligand-binding activity resides at the extreme N terminus of mature α-dystroglycan and is crucial for α-dystroglycan to coordinate the assembly of extracellular matrix proteins and to bind arenaviruses on the cell surface.
p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair
Authors: Perdiguero Eusebio , Sousa-Victor Pedro , Ruiz-Bonilla Vanessa , Jardí Mercè , Caelles Carme , Serrano Antonio L. , Muñoz-Cánoves Pura
Published: October 2011

Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlling macrophage phenotypic transitions necessary for appropriate muscle stem cell–dependent tissue repair. By restricting p38 MAPK activation, MKP-1 allows the early pro- to antiinflammatory macrophage transition and the later progression into a macrophage exhaustion-like state characterized by cytokine silencing, thereby permitting resolution of inflammation as tissue fully recovers. p38 hyperactivation in macrophages lacking MKP-1 induced the expression of microRNA-21 (miR-21), which in turn reduced PTEN (phosphatase and tensin homologue) levels, thereby extending AKT activation. In the absence of MKP-1, p38-induced AKT activity anticipated the acquisition of the antiinflammatory gene program and final cytokine silencing in macrophages, resulting in impaired tissue healing. Such defects were reversed by temporally controlled p38 inhibition. Conversely, miR-21–AKT interference altered homeostasis during tissue repair. This novel regulatory mechanism involving the appropriate balance of p38, MKP-1, miR-21, and AKT activities may have implications in chronic inflammatory degenerative diseases.
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated
Authors: Liao Hua-Xin , Chen Xi , Munshaw Supriya , Zhang Ruijun , Marshall Dawn J. , Vandergrift Nathan , Whitesides John F. , Lu Xiaozhi , Yu Jae-Sung , Hwang Kwan-Ki , Gao Feng , Markowitz Martin , Heath Sonya L. , Bar Katharine J. , Goepfert Paul A. , Montefiori David C. , Shaw George C. , Alam S. Munir , Margolis David M. , Denny Thomas N. , Boyd Scott D. , Marshal Eleanor , Egholm Michael , Simen Birgitte B. , Hanczaruk Bozena , Fire Andrew Z. , Voss Gerald , Kelsoe Garnett , Tomaras Georgia D. , Moody M. Anthony , Kepler Thomas B. , Haynes Barton F.
Published: October 2011

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non–HIV-1 antigens.
A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates
Authors: Kari Laszlo , Whitmire William M. , Olivares-Zavaleta Norma , Goheen Morgan M. , Taylor Lacey D. , Carlson John H. , Sturdevant Gail L. , Lu Chunxue , Bakios Lauren E. , Randall Linnell B. , Parnell Michael J. , Zhong Guangming , Caldwell Harlan D.
Published: October 2011

Blinding trachoma is an ancient neglected tropical disease caused by Chlamydia trachomatis for which a vaccine is needed. We describe a live-attenuated vaccine that is safe and efficacious in preventing trachoma in nonhuman primates, a model with excellent predictive value for humans. Cynomolgus macaques infected ocularly with a trachoma strain deficient for the 7.5-kb conserved plasmid presented with short-lived infections that resolved spontaneously without ocular pathology. Multiple infections with the attenuated plasmid-deficient strain produced no inflammatory ocular pathology but induced an anti-chlamydial immune response. Macaques vaccinated with the attenuated strain were either solidly or partially protected after challenge with virulent plasmid-bearing organisms. Partially protected macaques shed markedly less infectious organisms than controls. Immune correlates of protective immunity were not identified, but we did detect a correlation between MHC class II alleles and solid versus partial protection. Epidemiological models of trachoma control indicate that a vaccine with this degree of efficacy would significantly reduce the prevalence of infection and rates of reinfection, known risk factors which drive blinding disease.
The Origins of the Cultural Revolution
Authors: MacFarquhar Roderick
Published: October 2011

This is the final volume in a trilogy which examines the politics, personalities, economics, culture, and international relations of China from the mid-1950s to the mid-1960s. The book uses a multitude of new Chinese sources to answer the question: Why did Chairman Mao Zedong launch the Cultural Revolution which plunged China into chaos and almost destroyed its Communist Party? This book begins with the great famine of the early 1960s, which resulted in tens of millions of deaths, setting in train a series of emergency measures which increasingly divided Mao from his comrades-in-arms. The Chairman's anger that they were prepared to adopt ‘capitalist’ methods to rescue the country was sharpened by his belief that Moscow was denouncing his revolutionary diplomacy because the Soviet leadership had gone capitalist and sold out to the ‘imperialist’ West. From 1961 to 1966, the increasingly urgent question for Mao was how to prevent a similar revolutionary deterioration in China. The Cultural Revolution, in which tens of thousands of loyal party veterans were publicly disgraced to make way for a supposedly more leftist generation of Red Guards, was his answer. Ironically, after it all ended with Mao's death, one survivor, Deng Xiaoping, was so appalled at the destructiveness of the Chairman's final cataclysm that he actually did turn to capitalism to revive the country.
The Dispute over Collectivization
Authors: MacFarquhar Roderick
Published: October 2011

This chapter examines the dispute among Chinese political leaders on the issue of whether or not to bring in further drastic modifications of the structures of the rural collectivization in order to stimulate agriculture. Most political leaders believed that this was probably the central issue of Chinese politics for Mao Zedong. One of the major conflicts in the collectivization issue occurred in the East China province of Anhui under the leadership of Zeng Xisheng.
War in the Himalayas, Crisis in the Caribbean
Authors: MacFarquhar Roderick
Published: October 2011

This chapter examines the impact of the war in the Himalayas and the crisis in the Caribbean region on the government policy of Chinese leader Mao Zedong. It suggests that the dual of Kang Sheng in Mao's campaign against revisionism at home and abroad symbolized the close relationship between Chinese domestic and foreign policy. It contends that Mao considered the Chinese revolution to be part of a worldwide series of events, and that he was particularly concerned about the implications of Soviet revisionism for Chinese domestic politics.
Symbol, Allegory, Causality, and the Phenomenal Flux
Authors: Prunty Wyatt
Published: October 2011

This chapter explores the shift in Robert Lowell’s poetry. It argues that the shift was more dialectical than an act of abandonment, meaning that the significance of his later poetics was in reference to what had preceded it. It then discusses how, in its second phase, Lowell’s poetry coincides in certain important ways with some of the proposals made by the phenomenologist Husserl in his Cartesian Meditations. It shows that Lowell did not copy Husserl’s method. He simply arrived at a point in his life which presented him with many of the same problems Husserl had encountered in a less personal way earlier in this century; and in large part Lowell developed modes of thought in response to those problems that were similar to the modes that Husserl had already described.
Southern Crossing
Authors: Ayers Edward L.
Published: October 2011

This book represents an abridgement of previous work, Promise of the New South, which tells the history of the American South between the 1870s and the 1900s. It offers a glimpse into a society undergoing the sudden confrontation with the promises, costs, and consequences of modern life. Ranging from the Georgia coast to the Tennessee Mountains, from the power brokers to tenant farmers, the book depicts a land of startling contrasts—a time of progress and repression, of new industries and old ways. It takes us from remote Southern towns, revolutionized by the spread of the railroads, to the statehouses where Democratic “Redeemers” swept away the legacy of Reconstruction; from the small farmers, trapped into growing nothing but cotton, to the new industries of Birmingham; from abuse and intimacy in the family to tumultuous public meetings of the prohibitionists. It explores every aspect of society, politics, and the economy, detailing the importance of each in the emerging New South. Here is the local Baptist congregation, the country store, the tobacco-stained second-class railroad car, the rise of Populism. Central to the entire story is the role of race relations, from alliances and friendships between blacks and whites to the spread of Jim Crow laws and disenfranchisement. The book weaves all these details into the contradictory story of the New South, showing how the region developed the patterns it was to follow for the next fifty years.
Alliances
Authors: Ayers Edward L.
Published: October 2011

This chapter discusses the alliances formed by the people of the New South. Of particular importance was the Patrons of Husbandry with almost a quarter of a million members. They were also known as the Grange. Some of their most active offshoots were the Agricultural Wheel and the Brothers of Freedom from Arkansas which later joined to form the group called the Wheel. Other groups were formed called the Farmer's Alliance and Knights of Labor which became dominant alliances during that time. This chapter discusses the effects that these alliances had on the New South. Farmers wielded more power due to such alliances. The newspapers had a big hand in aiding alliances by publishing the reforms and statements of importance, thus, making it foremost in the minds of the members.
Faith
Authors: Ayers Edward L.
Published: October 2011

Religious faith and language permeated every aspect of life in the New South. From politics to courtship and even child-rearing, religion provided the backbone for dealing with the issues of life. Southerners worshipped in a lot of ways. Some people were Southern Baptist and others were Southern Methodist. However, there also were Lutherans, Quakers, and even Jews. This chapter discusses the hardships experienced by churches during that time, mostly financial but sometimes social. The Baptists, Methodists, and Presbyterians were stricter in their beliefs while the Protestants were seen as more lax. However church membership dwindled as time went by as a result of disagreements between the members and other social factors such as population movement. Discipline inside the churches was also affected by a variety of factors such as stronger law enforcement or growing tolerance for the world among young members.
Antislavery and Antidespotism: 1760–1771
Authors: Peabody Sue
Published: October 2011

This chapter contains the description of events that elapsed between the Admiralty's ordinance of 1762 and the 1777 Police des Noirs. This period is a crucial period for slavery in France. First, the number of blacks suing for their freedom in the Paris Admiralty Court increased radically. Second, some of the renowned authors adopted the metaphor of slavery to defy the excesses of monarchic government in France. The political context in which the lawsuits and discourse propagated was radicalized from 1770 to 1774 when Louis XV's chancellor Maupeou instituted a series of dramatic judicial reforms. A judicial memoire by Henrion de Pansey on behalf of the slave Roc circulated extensively, linking the injustice of Roc's slavery to the influence of Maupeou on the king.
Coda: “Speaking from the Grave”
Authors: Lowry Richard S.
Published: October 2011

Twain puts in Life on the Mississippi (1883) that writers are “manacled servants of the public.” During the last decade of his life, the intention in making his autobiography was to escape the manacles of his reading audience. In other words, this last work was his final attempt to put down his pen and stop writing. The result was to give its maker complete freedom in composition. Mark Twain wanted to preserve this freedom and guarantee that this was true by allowing his autobiography to be published after his death. He then starts his autobiography addressing the reader that they should keep in mind that he is “speaking from the grave.” He ends his final installment with his account of the Whittier Birthday banquet.
Printers and Publishers: The Merchants of Venice
Authors: Bernstein Jane A.
Published: October 2011

Venice offered an ideal center for the printing of books. It boasted the best and most advanced distribution system in the world. The first book was not printed in Venice until 1469 when a German immigrant named Johannes de Spira obtained a five-year monopoly from the Venetian Senate. Printing became a boom industry, in which many competed but few survived. One of them, the Frenchman Nicolas Jenson, became the most celebrated publisher in Venice during this period. Jenson and Johannes de Spira's firm, now headed by Johannes's brother Wendelin and by Johannes de Colonia, formed two syndicates that dominated the industry.
Liberalism and the Jews: Historical Affinities, Contemporary Necessities
Authors: Walzer Michael
Published: October 2011

This chapter offers a brief account of the forms of liberalism that have historically been most attractive to the Jews. Liberal politics is characterized by two sets of commitments: first, to individual freedom, civil liberty, religious toleration, and a pluralist society; second, to social justice, the welfare state, and the idea of mutuality or solidarity that, however attenuated in the modern world, underlies welfarist commitments. The relevant liberalism is that of the New Deal and the Great Society. In theoretical terms, it is the liberalism of John Stuart Mill and John Dewey. It is strongly individualist but not libertarian. Most Jews have supported commitments to both liberty and justice for a long time. Historically, the religious culture of the Jews is no more a liberal culture than is that of Catholics, say, or Muslims. However, liberalism as one knows it today is among the Jews, a product of emancipation—or, more precisely, of emancipation in exile.
French Jews: Between Citizenship and Community
Authors: Birnbaum Pierre
Published: October 2011

Since the time of the French Revolution, the French state, regarding itself as the sole source of rationality, has looked with ill favor on all forms of community organization that could cast doubt on the wholehearted allegiance of its citizens. It is in this new context that the status of French Jewry today should be considered. From the time of the French Revolution, Jews in France traditionally had a special relationship with the state that had emancipated them in accordance with its own principles of liberty and equality, displaying an enthusiastic allegiance to this “strong” state that had not only brought them citizenship so quickly but had ensured a protective public order. In the view of many historians, French Judaism illustrates the way in which emancipation provided a fertile soil for assimilation and the emergence of “Israelites” devoted to the republican state and increasingly detached from their internal communal ties.