bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast tumor cell-specific knockout of
Twist1
inhibits cancer cell plasticity, dissemination, and lung metastasis in mice
Authors: Xu Yixiang , Lee Dong-Kee , Feng Zhen , Xu Yan , Bu Wen , Li Yi , Liao Lan , Xu Jianming 
Published: October 2017

Significance
We found that Twist1 is coexpressed with multiple other epithelial–mesenchymal transition (EMT)-inducing transcription factors (TFs) in small subsets of primary and circulating breast tumor cells. Together, they program a partial EMT and a basal-like phenotype of tumor cells, which most likely are responsible for disseminating into the circulation and metastasizing to the lung in mice. Targeting Twist1 largely diminishes all the cellular features and phenotypes of breast tumor cells, indicating Twist1 may be a target for inhibiting breast cancer metastasis. These findings are in favor of the role of partial EMT in breast cancer progression toward the metastatic state.
Nonequilibrium fluctuations of lipid membranes by the rotating motor protein F
1
F
0
-ATP synthase
Authors: Almendro-Vedia Víctor G. , Natale Paolo , Mell Michael , Bonneau Stephanie , Monroy Francisco , Joubert Frederic , López-Montero Iván 
Published: October 2017

Significance
The shape of biological membranes is constantly remodeled and maintained out of equilibrium by active proteins. The functional capacity of membrane deformation is mainly determined by the mechanical interplay between protein activity and bending elasticity. In our experiments, we find that ATP synthase, a rotating membrane protein that synthesizes the biochemical energy in cells through proton-pumping activity across the membrane, promotes localized nonequilibrium membrane fluctuations when reconstituted in giant lipid vesicles. The large membrane deformations emerge from the pumping action of rotating proteins clustered at specific emplacements in the membrane. Our results pave the way to new experimental realizations to explore the collective effects of rotating ATP synthases and their possible biological implications for biomembrane organization and protein functionality.
Marine mammal population decline linked to obscured by-catch
Authors: Meyer Stefan , Robertson Bruce C. , Chilvers B. Louise , Krkošek Martin 
Published: October 2017

Significance
Declines of marine megafauna such as turtles, pinnipeds, and whales are often related to mortality caused by capture or entanglement in fisheries gear. To help recovery of these species, trawl fisheries have implemented exclusion devices that release nontarget species. Despite decades of use, there has been no empirical evaluation of whether or not exclusion devices aid recovery of affected species. Long-term data on the endangered New Zealand sea lion and a trawl fishery in the Southern Ocean indicate that exclusion devices have paradoxically contributed to ongoing decline rather than recovery. Exclusion devices obscure the postrelease impact of elevated mortality or reproductive failure; meanwhile, reduced levels of reported by-catch may mislead management that continued decline is not associated with fisheries.
UTX-guided neural crest function underlies craniofacial features of Kabuki syndrome
Authors: Shpargel Karl B. , Starmer Joshua , Wang Chaochen , Ge Kai , Magnuson Terry 
Published: October 2017

Significance
Several chromatin-modifying enzymes are mutated in human craniofacial disorders. These factors function genome-wide to regulate accessibility and expression of extensive gene sets. Therefore, understanding chromatin-modifier function requires identification of responsible cellular origins and genomic characterization of phenotypes in primary cells. We now combine reporter flow cytometry with low cell number genomics to identify neural crest stem-cell factors as molecular targets of UTX in Kabuki syndrome. UTX demethylates histones to regulate some gene expression, but many UTX-bound regions are subject to novel mechanisms of transcriptional regulation. This study identifies UTX cellular and molecular targets in craniofacial development and this methodology is broadly adaptable to study genome distribution of other chromatin factors in neural crest disorders.
Mechanistic principles underlying regulation of the actin cytoskeleton by phosphoinositides
Authors: Senju Yosuke , Kalimeri Maria , Koskela Essi V. , Somerharju Pentti , Zhao Hongxia , Vattulainen Ilpo , Lappalainen Pekka 
Published: October 2017

Significance
Membrane phosphoinositides have emerged as key regulators of the actin cytoskeleton in cell migration, morphogenesis, cytokinesis, and endocytosis. However, the molecular mechanisms by which actin-binding proteins (ABPs) interact with phosphoinositide-rich membranes remain remarkably poorly understood. By applying a combination of biochemical, biophysical, and atomistic molecular dynamics simulation approaches on six central ABPs, we discovered that they employ multivalent electrostatic interactions for membrane binding. Strikingly, our experiments revealed that these proteins display enormous differences in their membrane interaction dynamics and in the ranges of phosphoinositide densities that they sense. These differences precisely correlate with the specific functions of these proteins in cytoskeletal dynamics. These findings uncover molecular principles by which membrane phosphoinositides regulate dynamics and architecture of the actin cytoskeleton in cells.
Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12–IFN-γ
Authors: Kundu Madhuchhanda , Roy Avik , Pahan Kalipada 
Published: October 2017

SignificanceDifferent mouse and human cancer cells produce excess p40 monomer compared with p40 homodimer, IL-12, and IL-23. The serum level of p40 monomer is also much higher in patients with prostate cancer than in healthy control subjects. Interestingly, this p40 monomer helps cancer cells to escape IL-12–IFN-γ–mediated death via suppression of IL-12 receptor-β1 internalization. This report demonstrates a biological role of p40 monomer, the so-called nonfunctional member of the IL-12 family of cytokines, in cancer cell survival. These results also delineate that neutralization of p40 monomer may be a therapeutic target in prostate and other cancers, which are associated with excessive production of p40.
Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula
Authors: Castro Daniel C. , Berridge Kent C. 
Published: October 2017

Significance
Orbitofrontal cortex, insula, and related cortical regions are implicated in pleasure and motivation. However, determining whether cortical sites help cause hedonic reactions or instead merely encode signals generated elsewhere to facilitate other functions such as cognition remains unresolved. By mapping hedonic effects of individual drug microinjections, we generate detailed anatomical maps for potential gain-of-function affective sites in rat limbic cortex. Here, we show that opioid or orexin stimulations in orbitofrontal cortex and insula causally enhance hedonic “liking” reactions to sweetness and find a third cortical site where the same neurochemical stimulations reduce positive hedonic impact. For comparison, we also map overlapping but separable regions where stimulations increase the motivation to eat.
M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer’s disease genes and improving memory
Authors: Volmar Claude-Henry , Salah-Uddin Hasib , Janczura Karolina J. , Halley Paul , Lambert Guerline , Wodrich Andrew , Manoah Sivan , Patel Nidhi H. , Sartor Gregory C. , Mehta Neil , Miles Nancy T. H. , Desse Sachi , Dorcius David , Cameron Michael D. , Brothers Shaun P. , Wahlestedt Claes 
Published: October 2017

Significance
Hundreds of failed clinical trials with Alzheimer’s disease (AD) patients over the last fifteen years demonstrate that the one-target–one-disease approach is not effective in AD. In silico, structure-based, multitarget drug design approaches to treat multifactorial diseases have not been successful in the context of AD either. Here, we show that M344, an inhibitor of class I and IIB histone deacetylases, affects multiple AD-related genes, including those related to both early- and late-onset AD. We also show that M344 improves memory in the 3xTg AD mouse model. This work endorses a shift to a multitargeted approach to the treatment of AD, supporting the therapeutic potential of a single small molecule with an epigenetic mechanism of action.
PAF promotes stemness and radioresistance of glioma stem cells
Authors: Ong Derrick Sek Tong , Hu Baoli , Ho Yan Wing , Sauvé Charles-Etienne Gabriel , Bristow Christopher A. , Wang Qianghu , Multani Asha S. , Chen Peiwen , Nezi Luigi , Jiang Shan , Gorman Claire Elizabeth , Monasterio Marta Moreno , Koul Dimpy , Marchesini Matteo , Colla Simona , Jin Eun-Jung , Sulman Erik P. , Spring Denise J. , Yung Wai-Kwan Alfred , Verhaak Roel G. W. , Chin Lynda , Wang Y. Alan , DePinho Ronald A. 
Published: October 2017

Significance
Glioblastoma multiforme (GBM) is uniformly lethal and shows resistance to all forms of therapy. Glioma stem cells (GSCs) have been shown to support GBM maintenance and exhibit enhanced resistance to ionizing radiation, a cornerstone of GBM therapy. This study establishes that proliferating cell nuclear antigen-associated factor (PAF) depletion profoundly reduces GSC frequency and tumorigenicity, in part, by down-regulating DNA replication and pyrimidine metabolism. Moreover, PAF depletion impairs error-prone DNA translesion synthesis (TLS) and enhances sensitivity of GSCs to radiation treatment. Pharmacological impairment of DNA replication and TLS diminished GSC maintenance and radioresistance, illuminating a potential GBM treatment strategy of combined TLS inhibition and radiation therapy.
Genome of wild olive and the evolution of oil biosynthesis
Authors: Unver Turgay , Wu Zhangyan , Sterck Lieven , Turktas Mine , Lohaus Rolf , Li Zhen , Yang Ming , He Lijuan , Deng Tianquan , Escalante Francisco Javier , Llorens Carlos , Roig Francisco J. , Parmaksiz Iskender , Dundar Ekrem , Xie Fuliang , Zhang Baohong , Ipek Arif , Uranbey Serkan , Erayman Mustafa , Ilhan Emre , Badad Oussama , Ghazal Hassan , Lightfoot David A. , Kasarla Pavan , Colantonio Vincent , Tombuloglu Huseyin , Hernandez Pilar , Mete Nurengin , Cetin Oznur , Van Montagu Marc , Yang Huanming , Gao Qiang , Dorado Gabriel , Van de Peer Yves 
Published: October 2017

Significance
We sequenced the genome and transcriptomes of the wild olive (oleaster). More than 50,000 genes were predicted, and evidence was found for two relatively recent whole-genome duplication events, dated at approximately 28 and 59 Mya. Whole-genome sequencing, as well as gene expression studies, provide further insights into the evolution of oil biosynthesis, and will aid future studies aimed at further increasing the production of olive oil, which is a key ingredient of the healthy Mediterranean diet and has been granted a qualified health claim by the US Food and Drug Administration.
Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence
Authors: de Morrée Antoine , van Velthoven Cindy T. J. , Gan Qiang , Salvi Jayesh S. , Klein Julian D. D. , Akimenko Igor , Quarta Marco , Biressi Stefano , Rando Thomas A. 
Published: October 2017

Significance
This work addresses a fundamental mechanism for the translational control of a master regulator of myogenic differentiation, MyoD, by the RNA binding protein Staufen1. We show that muscle stem cells express the MyoD transcript in the quiescent state in vivo but block its translation through direct repression by Staufen1. Loss of this translational repression leads to MyoD translation and cell cycle entry, highlighting a novel role for MyoD in regulating the exit from quiescence. This mechanism of direct translational repression enables the cells to exist poised for activation and cell cycle entry. These data provide insight in the translational control of muscle stem cell quiescence.
Disruption and rescue of interareal theta phase coupling and adaptive behavior
Authors: Reinhart Robert M. G. 
Published: October 2017

Significance
We show that the timing of alternating-current stimulation can couple or decouple low-frequency brain rhythms between segregated frontal cortical areas in a highly selective fashion without changing other neural frequencies, synchronization across the opposite cerebral hemisphere, or local neural activity. The up- and down-regulation of interareal neural coupling caused bidirectional changes in adaptive control and learning measured behaviorally. It was even possible to induce behavioral deficits and then immediately rescue this behavior in the same individuals in a matter of minutes. The findings suggest it is possible to intervene in the neural integration between frontal cortical structures that govern complex human behavior. The development of drug-free interventions for addressing disorders of excessive and deficient cortical connectivity is implicated.
Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates
Authors: Kim Hyo-Joong , Benner Steven A. 
Published: October 2017

Significance
Much recent research into the origins of life focuses on the hypothesis that RNA emerged on early Earth by an abiotic process, and gave Earth its first access to Darwinian evolution. This article provides a key step in this process. Here, we show that the phosphorylated ribonucleoside building blocks for RNA can be made stereoselectively under a prebiotic plausible condition with canonical and noncanonical purines, and with one noncanonical pyrimidine. It also shows that threose nucleoside phosphates can be synthesized in a similar way. This result is significant in terms of numbers of steps, high stereo- and regiochemistry, scope, involvement of minerals, and likelihood of the prebiotic availability of its starting materials.
Cardiovascular homeostasis dependence on MICU2, a regulatory subunit of the mitochondrial calcium uniporter
Authors: Bick Alexander G. , Wakimoto Hiroko , Kamer Kimberli J. , Sancak Yasemin , Goldberger Olga , Axelsson Anna , DeLaughter Daniel M. , Gorham Joshua M. , Mootha Vamsi K. , Seidman J. G. , Seidman Christine E. 
Published: October 2017

SignificanceHypertension increases the risk for development of abdominal aortic aneurysms, a silent pathology that is prone to rupture and cause sudden cardiac death. Male gender, smoking, and hypertension appear to increase risk for development of abdominal aortic aneurysms by provoking oxidative stress responses in cardiovascular tissues. Here we uncovered unexpected linkages between the calcium-sensing regulatory subunit MICU2 of the mitochondrial calcium uniporter and stress responses. We show that naiveMicu2−/−mice had abnormalities of cardiac relaxation but, with modest blood pressure elevation, developed abdominal aortic aneurysms with spontaneous rupture. These findings implicate mitochondrial calcium homeostasis as a critical pathway involved in protecting cardiovascular tissues from oxidative stress.
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen
Authors: Spurgeon Megan E. , den Boon Johan A. , Horswill Mark , Barthakur Sonalee , Forouzan Omid , Rader Janet S. , Beebe David J. , Roopra Avtar , Ahlquist Paul , Lambert Paul F. 
Published: October 2017

Significance
A subset of human papillomaviruses (HPVs) causes 5% of human cancers, including virtually all cancers of the cervix. In a mouse model of cervical cancer, estrogen is a necessary cofactor that contributes to disease by signaling through the underlying tumor microenvironment. In this study, we discovered that epithelial expression of the HPV oncoproteins reprograms the cervical tumor microenvironment and its response to estrogen. These changes involve the elicitation of paracrine-acting factors implicated in carcinogenesis, and the expression of a subset of these factors was also induced in cocultures of human cervical cancer cells and stromal fibroblasts. We hypothesize that HPV oncogenes cause cancer in part by creating a unique tumor microenvironment that synergizes with estrogen in the cervix.
Formation of most of our coal brought Earth close to global glaciation
Authors: Feulner Georg 
Published: October 2017

SignificanceThe bulk of the coal driving the Industrial Revolution and contributing to global warming today has been deposited during the Carboniferous period (359–299 million years ago), resulting in a significant drawdown of atmospheric carbon dioxide at that time. In this work, a combination of climate model simulations and recent estimates for carbon dioxide levels in the atmosphere is used to demonstrate that the cooling due to the diminished greenhouse effect brought our planet close to the limit of global glaciation∼300 million years ago. These findings highlight the climatic importance of the fossil carbon stored in Earth’s coal deposits and thus have implications for climate policy.
Competitive network determines the direction of the diversity–function relationship
Authors: Maynard Daniel S. , Crowther Thomas W. , Bradford Mark A. 
Published: October 2017

SignificanceDiverse communities typically have higher functional potential (e.g., biomass production) because species use different resources and respond to different environmental cues. Yet, in highly competitive communities, individuals often grow less efficiently together due to intense competition for shared resources. Here, we show that the structure of the competitive network (i.e., who beats who) ultimately determines whether an increase in diversity leads to an increase or a decrease in functioning. The diversity–function relationship depended both on whether communities exhibited “rock–paper–scissors” (i.e., intransitive) dynamics, and whether they comprised strong versus weak competitors. These results highlight that knowledge of the competitive network may be integral for predicting when losses in biodiversity will have positive or negative effects on ecosystem function.
Distinct ice patterns on solid surfaces with various wettabilities
Authors: Liu Jie , Zhu Chongqin , Liu Kai , Jiang Ying , Song Yanlin , Francisco Joseph S. , Zeng Xiao Cheng , Wang Jianjun 
Published: October 2017

Significance
Ice growth is essential to the final shape of ice crystals; therefore, it is of significant relevance to rich varieties of practical applications and fundamental research. A correlation between the surface wettability and ice growth has not been established, although ice often forms on solid surfaces. We discover experimentally that ice grows along surface when the contact angle of water drops on solid surfaces is below a critical value, and ice grows off surface when the contact angle is above this critical value. Our molecular dynamics simulation analysis reveals that the presence/absence of bilayer ice on solid surfaces of different surface wettabilities dictates the ice growth and therefore provides the molecular mechanism of ice growth on solid surfaces.
Dominant negative effect of the loss-of-function γ-secretase mutants on the wild-type enzyme through heterooligomerization
Authors: Zhou Rui , Yang Guanghui , Shi Yigong 
Published: October 2017

Significance
The vast majority of familial Alzheimer’s disease (AD) cases are linked to mutations in presenilin-1 (PS1) in an autosomal dominant manner. PS1 is the catalytic component of γ-secretase, which cleaves amyloid precursor protein into Aβ peptides. It remains unclear whether the causal role of PS1 mutations in AD development is effected through γ-secretase, and if yes, whether the dominant negative effect of PS1 mutant allele is effected through the proteolytic activity of γ-secretase. In this study, we provide compelling evidence to prove a dominant negative effect by the loss-of-function γ-secretase mutants on the production of Aβ42/40 by WT γ-secretase through hetero-oligomerization. These data, together with our prior knowledge on the function of γ-secretase, have important ramifications on the two key questions listed here.
Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management
Authors: Thamphiwatana Soracha , Angsantikul Pavimol , Escajadillo Tamara , Zhang Qiangzhe , Olson Joshua , Luk Brian T. , Zhang Sophia , Fang Ronnie H. , Gao Weiwei , Nizet Victor , Zhang Liangfang 
Published: October 2017

Significance
Clinical evidence has indicated that the systemic spread of endotoxins from septic infection plays a crucial role in the pathogenesis of Gram-negative bacterial sepsis. However, currently there are no effective ways to manage the diverse endotoxins released by different bacterial genus, species, and strain. Herein, we demonstrate the therapeutic potential of a macrophage-like nanoparticle for sepsis control through a powerful two-step neutralization process: endotoxin neutralization in the first step followed by cytokine sequestration in the second step. The biomimetic nanoparticles possess an antigenic exterior identical to macrophage cells, thus inheriting their capability to bind to endotoxins and proinflammatory cytokines. This detoxification strategy may provide a first-in-class treatment option for sepsis and ultimately improve the clinical outcome of patients.
Engineering sulfur storage in maize seed proteins without apparent yield loss
Authors: Planta Jose , Xiang Xiaoli , Leustek Thomas , Messing Joachim 
Published: October 2017

Significance
Poultry feed is usually prepared as a corn–soybean mixture. Because the only essential sulfur amino acid missing in this mixture is methionine, it is chemically synthesized and added separately, increasing the cost of major food supply. It appears to be difficult to circumvent the regulatory aspects of sulfur metabolism, which is controlled at many levels, without damage to plant growth. By using tissue-specific promoters to express a bacterial enzyme that increases the efficiency of assimilative sulfate reduction, seed methionine accumulation can be increased without the concomitant accumulation of toxic metabolites. We show that even in maize inbred lines with repressed seed methionine levels, sink strength can be increased to the benefit of feed consumption efficiency in chicks.