512 research outputs found
Wounds That Will Not Heal Pervasive Cellular Reprogramming in Cancer
There has been an explosion of articles on epithelial-mesenchymal transition and other modes of cellular reprogramming that influence the tumor microenvironment. Many controversies exist and remain to be resolved. The interest of the pathologists in the molecular and functional parallels between wound healing and the developing tumor stroma has its earliest origin in the writings of Rudolph Virchow in the 19th century. Since then, most of the focus has been primarily on the dynamics of the extracellular matrix; however, new interest has been redirected toward deciphering and understanding the enigmatic, yet elegant, plasticity of the cellular components of the proliferating epithelia and stroma and how they are reciprocally influenced. Citing several examples from breast cancer research, we will trace how these perspectives have unfolded in the pages of The American Journal of Pathology and other investigative journals during the past century, their impact, and where the field is headed
The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network
SummaryPluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs
A single-column ocean biogeochemistry model (GOTM–TOPAZ) version 1.0
Recently, Earth system models (ESMs) have begun to
consider the marine ecosystem to reduce errors in climate simulations.
However, many models are unable to fully represent the ocean-biology-induced
climate feedback, which is due in part to significant bias in the simulated
biogeochemical properties. Therefore, we developed the Generic Ocean
Turbulence Model–Tracers of Phytoplankton with Allometric Zooplankton
(GOTM–TOPAZ), a single-column ocean biogeochemistry model that can be used
to improve ocean biogeochemical processes in ESMs. This model was developed
by combining GOTM, a single-column model that can simulate the physical
environment of the ocean, and TOPAZ, a biogeochemical module. Here, the
original form of TOPAZ has been modified and modularized to allow easy
coupling with other physical ocean models. To demonstrate interactions
between ocean physics and biogeochemical processes, the model was designed
to allow ocean temperature to change due to absorption of visible light by
chlorophyll in phytoplankton. We also added a module to reproduce upwelling
and the air–sea gas transfer process for oxygen and carbon dioxide,
which are of particular importance for marine ecosystems. The simulated
variables (e.g., chlorophyll, oxygen, nitrogen, phosphorus, silicon) of
GOTM–TOPAZ were evaluated by comparison against observations. The temporal
variability in the observed upper-ocean (0–20 m) chlorophyll is well
captured by the GOTM–TOPAZ with a correlation coefficient of 0.53 at point 107 in the Sea of Japan. The
surface correlation coefficients among GOTM–TOPAZ oxygen, nitrogen,
phosphorus, and silicon are 0.47, 0.31, 0.16, and 0.19, respectively. We
compared the GOTM–TOPAZ simulations with those from MOM–TOPAZ and found that
GOTM–TOPAZ showed relatively lower correlations, which is most likely due to
the limitations of the single-column model.
Results also indicate that source–sink terms may contribute to the biases in
the surface layer (<60 m), while initial values are important for
realistic simulations in the deep sea (>250 m). Despite this
limitation, we argue that our GOTM–TOPAZ model is a good starting point for
further investigation of key biogeochemical processes and is also useful to
couple complex biogeochemical processes with various oceanic global
circulation models.</p
Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy
The non-invasive, in vivo measurement of microvascular blood flow has the potential
to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast
cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based
on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide,
and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide
increased blood flow as early as 3 days after administration, whereas paclitaxel induced a
transient blood flow decrease at 1 day after administration. Early blood flow changes correlated
strongly with the treatmePeer ReviewedPostprint (published version
Recommended from our members
CR6-interacting factor 1 is a key regulator in Aβ-induced mitochondrial disruption and pathogenesis of Alzheimer's disease
Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-β (Aβ), yet the pathways between Aβ and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aβ-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aβ undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aβ. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aβ-treated cells. Conversely, Crif1 overexpression prevented Aβ-induced mitochondrial dysfunction and cell death. Finally, we show that Aβ-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aβ-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD
SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg
We present the results of 12CO J = 1-0 line observations of eleven Galactic
supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory
(SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO
survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs
interacting with molecular clouds. The mapping areas for the individual SNRs
are determined to cover their full extent in the radio continuum. We used
halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for
the rest. We detected CO emission towards most of the remnants. In six SNRs,
molecular clouds showed a good spatial relation with their radio morphology,
although no direct evidence for the interaction was detected. Two SNRs are
particularly interesting: G85.4+0.7, where there is a filamentary molecular
cloud along the radio shell, and 3C434.1, where a large molecular cloud appears
to block the western half of the remnant. We briefly summarize the results
obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages,
12 figures, and 3 table
Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer
epithelial reprogramming in breast cance
Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival
Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.Fil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Singhal, Sandeep K.. Columbia University; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yi, Dae Ik. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Caban, Ambar. Columbia University Medical Center; Estados UnidosFil: Jones, Alana. National Institutes of Health; Estados UnidosFil: Mukhopadhyay, Partha. Columbia University Medical Center; Estados UnidosFil: Gille, Sarah. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. No especifĂca;Fil: Newman, Lisa. No especifĂca;Fil: Davis, Melissa B.. Henry Ford Health System; Estados UnidosFil: Jenkins, Brittany D.. Henry Ford Health System; Estados UnidosFil: Sepulveda, Jorge L.. Columbia University Medical Center; Estados UnidosFil: de Siervi, Adriana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Nápoles, Anna MarĂa. National Institute On Minority Health And Health Disparities; Estados UnidosFil: Vohra, Nasreen A.. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University Medical Center; Estados Unido
- …