bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conversion of non-adipogenic fibroblasts into adipocytes by a defined hormone mixture
Authors: Nie Tao , Hui Xiaoyan , Gao Xuefei , Nie Baoming , Mao Liufeng , Tang Xiaofeng , Yuan Ran , Li Kuai , Li Peng , Xu Aimin , Liu Pengtao , Ding Sheng , Han Weiping , Cooper Garth J. S. , Wu Donghai 
Published: March 2015

Obesity is accompanied by an increase in the size and the number of adipocytes. As adipocytes are thought to differentiate from pre-adipocytes, we postulate that non-adipogenic fibroblasts contribute to adipocyte formation under certain conditions such as obesity. We report for the first time that NIH-3T3 fibroblasts, which are generally considered to be non-adipogenic, can be converted into mature adipocytes by treatment with a defined hormone mixture comprising EGF (epidermal growth factor), HGF (hepatocyte growth factor), Dex (dexamethasone) and insulin. Furthermore, NIH-3T3 cells transplanted into obese immunodeficient NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice formed adipocytes in vivo. Interestingly, the mixture elicited conversion of NIH-3T3 cells directly into adipocytes without a preceding pre-adipocyte stage. Functional analysis revealed that each component of the mixture was necessary for the induction of adipogenesis, including Dex which inhibited the cell proliferation stimulated by EGF. Upon profiling the signalling pathways employed by EGF and HGF, we found STAT5 (signal transducer and activator of transcription 5) signalling to be activated, predominantly at the levels of both transcription and post-translational modification. Inhibition of the STAT5 pathway, either by genetic knockdown or a specific pharmacological agent, blocked adipogenesis in NIH-3T3 cells. Taken together, these data not only establish a newly recognized grouping of factors that can induce trans-differentiation of non-adipogenic fibroblasts into adipocytes, but also give us a greater understanding of obesity.
Implementation of high‐speed–low‐power adaptive finite impulse response filter with novel architecture
Authors: Jaiswal Manish , Sharma Sandeep , Sharma Anuj 
Published: March 2015

An energy efficient high‐speed adaptive finite impulse response filter with novel architecture is developed. Synthesis results along with novel architecture on different complementary metal–oxide semiconductor (CMOS) families are presented. Analysis is performed using Artix‐7, Spartan‐6 and Virtex‐4 for most popular adaptive least mean square filter for different orders such as N = 8, 16, 32. The presented work is done using MATLAB (2013b) and Xilinx (14.2). From the synthesis results, it can be found that CMOS (28 nm) achieves the lowest power and critical path delay compared to others, and thus proves its efficiency in terms of energy. Different parameters are considered such as look up tables and input–output blocks, along with their optimised results.
Pigeons trade efficiency for stability in response to level of challenge during confined flight
Authors: Williams C. David , Biewener Andrew A. 
Published: March 2015

Significance
The real world is a cluttered environment and animals traversing it are faced with innumerable obstacles in their normal locomotion. During normal flight, birds have to avoid hitting trees, lampposts, and other members of flocks. To investigate flight strategies used in these circumstances, we presented pigeons with a simplified challenge, a series of vertical gaps with variable spacings. The pigeons used two discrete postures. One posture granted them greater flight efficiency but was more disrupted when they collided with obstacles, and was used for traversing larger gaps. An alternate flight posture was less efficient but more stable when slight collisions occurred, and was used for traversing smaller gaps. To our knowledge, this is the first time we have seen flight strategies tuned during use in cluttered environments.
Proteome-wide analysis of mutant p53 targets in breast cancer identifies new levels of gain-of-function that influence PARP, PCNA, and MCM4
Authors: Polotskaia Alla , Xiao Gu , Reynoso Katherine , Martin Che , Qiu Wei-Gang , Hendrickson Ronald C. , Bargonetti Jill 
Published: March 2015

Significance
Mutant p53 (mtp53) is a driver oncogene of breast cancer. Here, for the first time, to our knowledge, using an inducible endogenous knockdown system, we explore the mtp53 driven proteome. We report this key data set that highlights mtp53-driven proteome diversity at the level of protein localization, as well as changes in protein levels without corresponding changes in transcription. We validated two protein pathways that include increased chromatin association of poly(ADP ribose) polymerase 1, and the increase of nuclear replication proteins minichromosome maintenance 4 and proliferating cell nuclear antigen. The addition of mtp53 proteomic targets to the previously identified transcriptional targets suggests that effective treatment of mtp53-driven breast cancers may be facilitated by new combination protocols blocking proteins of the metabolic pathways of cholesterol biosynthesis, DNA replication, and DNA repair.
Endocannabinoids are conserved inhibitors of the Hedgehog pathway
Authors: Khaliullina Helena , Bilgin Mesut , Sampaio Julio L. , Shevchenko Andrej , Eaton Suzanne 
Published: March 2015

Significance
Hedgehog proteins regulate development and tissue homeostasis. They signal through activation of the transmembrane protein Smoothened. Smoothened hyperactivation underlies development of many tumors. Smoothened activity can be modulated by several synthetic small molecules, which have shown promise in the clinic. However, occurrence of resistance-inducing mutations limits their effectiveness. Little is known about endogenous small molecules that may inhibit Smoothened in vivo. Previous work suggested that lipids present in lipoproteins are required for Smoothened inhibition in vivo. Here, we use biochemical fractionation and lipidomics to identify these lipids as endocannabinoids and show that their activity as Smoothened inhibitors has been conserved from flies to mammals. Endocannabinoids may provide useful templates for the design of new therapeutic Smoothened antagonists.
Dynamical phase transition in the open Dicke model
Authors: Klinder Jens , Keßler Hans , Wolke Matthias , Mathey Ludwig , Hemmerich Andreas 
Published: March 2015

Significance
Nonequilibrium phenomena in quantum many-body systems are not well understood to date. This applies in particular for open systems, coupled to an external bath. We use a Bose–Einstein condensate in a high-finesse optical resonator with ultralow bandwidth to emulate the open Dicke model. In well-controlled sweeps across the Hepp–Lieb–Dicke phase transition, we observe hysteretic dynamics showing power-law scaling with respect to the transition time, which suggests an interpretation in terms of a Kibble–Zurek mechanism. Our observations indicate the possibility of universal behavior in the presence of dissipation.
Evidence for recent, population-specific evolution of the human mutation rate
Authors: Harris Kelley 
Published: March 2015

Significance
Most, but not all, human genetic variation is shared between populations, and whole-genome sequencing is now making it possible to catalogue population-private mutations that occur in only one ethnic group and are especially informative about recent human history. By contrasting frequencies of mutations private to Europe, Asia, and Africa, I have revealed a previously undetected difference between Europeans and other ethnic groups: Europeans experience higher rates of a specific mutation type that has known associations with UV light exposure. Although it is not clear whether the excess mutations are harmful or directly related to the UV sensitivity of light skin, this result demonstrates that the human mutation rate has evolved on a much faster timescale than previously believed.
Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption
Authors: Xiong Lei , Jung Ji-Ung , Wu Haitao , Xia Wen-Fang , Pan Jin-Xiu , Shen Chengyong , Mei Lin , Xiong Wen-Cheng 
Published: March 2015

Significance
This study provides in vivo evidence that Lrp4 loss in osteoblast (OB)-lineage cells results in high–bone-mass deficit. Lrp4 in OB-lineage cells is required to reduce serum levels of sclerostin and to facilitate sclerostin inhibition of OB differentiation and function. These results demonstrate that Lrp4 is a critical player in bone-mass homeostasis and support a model that Lrp4 acts as a sclerostin receptor, inhibiting Wnt/β-catenin signaling and promoting receptor activator of nuclear kappa B ligand (RANKL)-induced osteoclastogenesis. As mutations in the Lrp4 gene have been identified in high–bone-mass patients, this study provides pathophysiological insight into relevant high–bone-mass disorders.
Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release
Authors: Held Katharina , Kichko Tatjana , De Clercq Katrien , Klaassen Hugo , Van Bree Rieta , Vanherck Jean-Christophe , Marchand Arnaud , Reeh Peter W. , Chaltin Patrick , Voets Thomas , Vriens Joris 
Published: March 2015

Significance
The cation channel TRPM3 is highly expressed in the sensory system, where it plays a key role in the detection of noxious heat and the development of inflammatory heat hypersensitivity. Our understanding of the physiological role of TRPM3 in the sensory system and other tissues is hampered by the lack of potent pharmacologic tools, however. This study describes CIM0216, a small-molecule TRPM3 agonist. Our results indicate that CIM0216 is much more potent than established TRPM3 agonists, particularly owing to its ability to open two distinct cation-permeable pores in TRPM3. Using CIM0216 as a pharmacologic tool, we reveal that activation of TRPM3 evokes the release of calcitonin gene-related peptide from sensory nerve terminals and of insulin from pancreatic islets.
Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system
Authors: Xie Kabin , Minkenberg Bastian , Yang Yinong 
Published: March 2015

Significance
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system has recently emerged as an efficient and versatile tool for genome editing in various organisms. However, its targeting capability and multiplex editing efficiency are often limited by the guide RNA (gRNA)-expressing device. This study demonstrates a general strategy and platform for precise processing and efficient production of numerous gRNAs in vivo from a synthetic polycistronic gene via the endogenous tRNA-processing system. This strategy is shown to significantly increase CRISPR/Cas9 multiplex editing capability and efficiency in plants and is expected to have broad applications for small RNA expression and genome engineering.
Climate change in the Fertile Crescent and implications of the recent Syrian drought
Authors: Kelley Colin P. , Mohtadi Shahrzad , Cane Mark A. , Seager Richard , Kushnir Yochanan 
Published: March 2015

Significance
There is evidence that the 2007−2010 drought contributed to the conflict in Syria. It was the worst drought in the instrumental record, causing widespread crop failure and a mass migration of farming families to urban centers. Century-long observed trends in precipitation, temperature, and sea-level pressure, supported by climate model results, strongly suggest that anthropogenic forcing has increased the probability of severe and persistent droughts in this region, and made the occurrence of a 3-year drought as severe as that of 2007−2010 2 to 3 times more likely than by natural variability alone. We conclude that human influences on the climate system are implicated in the current Syrian conflict.
Place field expansion after focal MEC inactivations is consistent with loss of Fourier components and path integrator gain reduction
Authors: Ormond Jake , McNaughton Bruce L. 
Published: March 2015

Significance
The discovery of grid cells in the entorhinal cortex quickly led to the hypothesis that grid cell inputs might be responsible for the generation of discrete place fields downstream in the hippocampus. Simulations have shown that if this conjecture is correct, then lesions of dorsal medial entorhinal cortex (MEC), which expresses the most tightly spaced grids, should cause place fields to expand, whereas lesions of ventral MEC, which expresses the most widely spaced grids, should cause fields to contract. Using muscimol to make small inactivations along the dorsoventral axis of the MEC, we tested this hypothesis. Our results deviate from the prediction but most likely result from a combination of the predicted effects and a weakening of the self-motion signal within the MEC.
The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers
Authors: Qian Jun , Hassanein Mohamed , Hoeksema Megan D. , Harris Bradford K. , Zou Yong , Chen Heidi , Lu Pengcheng , Eisenberg Rosana , Wang Jing , Espinosa Allan , Ji Xiangming , Harris Fredrick T. , Rahman S. M. Jamshedur , Massion Pierre P. 
Published: March 2015

Significance
Altered expression of RNA binding proteins might contribute to cancer development. This study reveals the functional implications and clinical relevance of FXR1, an RNA binding protein, in non-small cell lung cancer (NSCLC). Our results demonstrate that FXR1 promotes tumor progression by regulating two other oncogenes within the same chromosome 3q amplicon. To drive tumor progression, FXR1 forms a new complex with protein kinase C, iota, and posttranscriptionally stabilizes the expression of epithelial cell transforming 2. We show that increased FXR1 expression in NSCLC is a candidate biomarker predictive of poor survival and might represent a novel therapeutic target. In addition, FXR1 expression correlates with poor clinical outcome in multiple human cancers, suggesting broader implications of this RNA binding protein in cancer progression.
Macronutrient balance, reproductive function, and lifespan in aging mice
Authors: Solon-Biet Samantha M. , Walters Kirsty A. , Simanainen Ulla K. , McMahon Aisling C. , Ruohonen Kari , Ballard John William O. , Raubenheimer David , Handelsman David J. , Le Couteur David G. , Simpson Stephen J. 
Published: March 2015

Significance
A fundamental tenet of life-history theory is that reproduction and longevity trade off against one another. Experiments on invertebrates show that, rather than competing for limiting resources, reproduction and lifespan are optimized on different dietary macronutrient compositions. In mice, studies have yet to establish the relationship between macronutrient balance, reproduction, and lifespan. We evaluated the effects of macronutrients and energy on lifespan and reproductive function. Indicators of reproductive function (uterine mass, ovarian follicle number, testes mass, epididymal sperm counts) were optimized by high protein (P), low carbohydrate (C) diets whereas lifespan was greatest on low P:C diets. Corpora lutea and estrous cycling were higher in females on lower P:C diets. Macronutrient balance has profound and opposing effects on reproduction and longevity.
Anthropogenic warming has increased drought risk in California
Authors: Diffenbaugh Noah S. , Swain Daniel L. , Touma Danielle 
Published: March 2015

Significance
California ranks first in the United States in population, economic activity, and agricultural value. The state is currently experiencing a record-setting drought, which has led to acute water shortages, groundwater overdraft, critically low streamflow, and enhanced wildfire risk. Our analyses show that California has historically been more likely to experience drought if precipitation deficits co-occur with warm conditions and that such confluences have increased in recent decades, leading to increases in the fraction of low-precipitation years that yield drought. In addition, we find that human emissions have increased the probability that low-precipitation years are also warm, suggesting that anthropogenic warming is increasing the probability of the co-occurring warm–dry conditions that have created the current California drought.
Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity
Authors: Washburn Nathaniel , Schwab Inessa , Ortiz Daniel , Bhatnagar Naveen , Lansing Jonathan C. , Medeiros Amy , Tyler Steven , Mekala Divya , Cochran Edward , Sarvaiya Hetal , Garofalo Kevin , Meccariello Robin , Meador James W. , Rutitzky Laura , Schultes Birgit C. , Ling Leona , Avery William , Nimmerjahn Falk , Manning Anthony M. , Kaundinya Ganesh V. , Bosques Carlos J. 
Published: March 2015

SignificanceIgG fragment crystallizable domain (Fc) sialylation has emerged as an important but controversial concept for regulating anti-inflammatory activity of antibodies. Moreover, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for human use. We describe for the first time, to our knowledge, the development of a robust, scalable process to generate a sialylated intravenous immunoglobulin (IVIg) drug candidate with maximum Fc sialylation devoid of unwanted modifications. By using a wide panel of physicochemical analytics and in vivo models, we have validated the quality and potent anti-inflammatory activity of this clinical candidate. This report not only confirms the controversial anti-inflammatory activity of IgG-Fc sialylation, it also represents the first sialylated IVIg preparation, to our knowledge, with consistent anti-inflammatory potency suitable for clinical development.
Vapor hydrogen and oxygen isotopes reflect water of combustion in the urban atmosphere
Authors: Gorski Galen , Strong Courtenay , Good Stephen P. , Bares Ryan , Ehleringer James R. , Bowen Gabriel J. 
Published: March 2015

Significance
Human activities affect the water cycle in many ways, some of which remain difficult to measure. One such process is emission of water vapor through combustion of fossil fuels, which may be a significant part of the atmospheric water budget in urban centers. It has not previously been possible to uniquely identify combustion-derived water vapor with atmospheric measurements. We introduce a method for the measurement of combustion-derived vapor, and show that this source contributes as much as 13% of surface-level vapor in the atmosphere of one city. The new approach may help researchers monitor sources of greenhouse gas emissions from cities and study the impact of water of combustion on urban weather, quality of life, and atmospheric chemistry.
Impacts of biological globalization in the Mediterranean: Unveiling the deep history of human-mediated gamebird dispersal
Authors: Forcina Giovanni , Guerrini Monica , van Grouw Hein , Gupta Brij K. , Panayides Panicos , Hadjigerou Pantelis , Al-Sheikhly Omar F. , Awan Muhammad N. , Khan Aleem A. , Zeder Melinda A. , Barbanera Filippo 
Published: March 2015

SignificanceHuman-mediated species dispersal stretching back at least 10,000 y has left an indelible stamp on present day biodiversity. A major contributing factor to this process was the trade in a wide range of exotic species that was fueled by elite demand. The black francolin—now extinct in the western Mediterranean but once a courtly gamebird prized for its flavor, curative, and aphrodisiac qualities by European aristocracy—was one of these species. Using historical sources and DNA analysis of modern and archival specimens, we show that this bird was not native to the western Mediterranean, and document its introduction to Cyprus and westward through the Mediterranean Basin via several trade routes that reached as far east as South Asia.
Insulin resistance in brain alters dopamine turnover and causes behavioral disorders
Authors: Kleinridders Andre , Cai Weikang , Cappellucci Laura , Ghazarian Armen , Collins William R. , Vienberg Sara G. , Pothos Emmanuel N. , Kahn C. Ronald 
Published: March 2015

Significance
Both types 1 and 2 diabetes are associated with increased risks of age-related decay in cognitive function and mood disorders, especially depression. Insulin action has been shown to regulate neuronal signaling and plasticity. Here we investigate whether brain-specific knockout of insulin receptor (NIRKO) in mice causes behavioral changes and how these are mechanistically linked. We find that NIRKO mice exhibit age-related anxiety and depressive-like behavior. This is due to altered mitochondrial function, aberrant monoamine oxidase (MAO) expression, and increased dopamine turnover in the mesolimbic system, and can be reversed by treatment with Mao inhibitors. Thus, brain insulin resistance alters dopamine turnover and induces anxiety and depressive-like behaviors. These findings demonstrate a potential molecular link between central insulin resistance and behavioral disorders.
Origin of the HIV-1 group O epidemic in western lowland gorillas
Authors: D’arc Mirela , Ayouba Ahidjo , Esteban Amandine , Learn Gerald H. , Boué Vanina , Liegeois Florian , Etienne Lucie , Tagg Nikki , Leendertz Fabian H. , Boesch Christophe , Madinda Nadège F. , Robbins Martha M. , Gray Maryke , Cournil Amandine , Ooms Marcel , Letko Michael , Simon Viviana A. , Sharp Paul M. , Hahn Beatrice H. , Delaporte Eric , Mpoudi Ngole Eitel , Peeters Martine 
Published: March 2015

Significance
Understanding emerging disease origins is important to gauge future human infection risks. This is particularly true for the various forms of the AIDS virus, HIV-1, which were transmitted to humans on four independent occasions. Previous studies identified chimpanzees in southern Cameroon as the source of the pandemic M group, as well as the geographically more restricted N group. Here, we show that the remaining two groups also emerged in southern Cameroon but had their origins in western lowland gorillas. Although group P has only been detected in two individuals, group O has spread extensively throughout west central Africa. Thus, both chimpanzees and gorillas harbor viruses that are capable of crossing the species barrier to humans and causing major disease outbreaks.
Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH
Authors: Dang Shangyu , Wu Shenjie , Wang Jiawei , Li Hongbo , Huang Min , He Wei , Li Yue-Ming , Wong Catherine C. L. , Shi Yigong 
Published: March 2015

Significance
Amyloid precursor protein (APP) is cleaved by β-secretase to produce APP C99, which undergoes additional, sequential cleavages by γ-secretase to generate amyloid-β peptides including Aβ40 and Aβ42. Increased ratios of Aβ42 over Aβ40 are thought to cause Alzheimer’s disease. Screening of γ-secretase modulators is hindered by the technical challenges in expression and biochemical manipulation of γ-secretase. In this study, we demonstrate that the archaeal intramembrane protease PSH represents an excellent surrogate of γ-secretase in terms of cleavage of APP C99, ratio of Aβ42 over Aβ40, and modulation of cleavage preferences by known modulators of γ-secretase. Our finding may facilitate discovery of γ-secretase inhibitors and modulators.