bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice
Authors: Tanger Paul , Klassen Stephen , Mojica Julius P. , Lovell John T. , Moyers Brook T. , Baraoidan Marietta , Naredo Maria Elizabeth B. , McNally Kenneth L. , Poland Jesse , Bush Daniel R. , Leung Hei , Leach Jan E. , McKay John K. 
Published: February 2017

AbstractTo ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.
Notch1-promoted TRPA1 expression in erythroleukemic cells suppresses erythroid but enhances megakaryocyte differentiation
Authors: Chen Ji-Lin , Ping Yueh-Hsin , Tseng Min-Jen , Chang Yuan-I , Lee Hsin-Chen , Hsieh Rong-Hong , Yeh Tien-Shun 
Published: February 2017

AbstractThe Notch1 pathway plays important roles in modulating erythroid and megakaryocyte differentiation. To screen the Notch1-related genes that regulate differentiation fate of K562 and HEL cells, the expression of transient receptor potential ankyrin 1 (TRPA1) was induced by Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor. N1IC and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1) bound to TRPA1 promoter region to regulate transcription in K562 cells. Transactivation of TRPA1 promoter by N1IC depended on the methylation status of TRPA1 promoter. N1IC and Ets-1 suppressed the DNA methyltransferase 3B (DNMT3B) level in K562 cells. Inhibition of TRPA1 expression after Notch1 knockdown could be attenuated by nanaomycin A, an inhibitor of DNMT3B, in K562 and HEL cells. Functionally, hemin-induced erythroid differentiation could be suppressed by TRPA1, and the reduction of erythroid differentiation of both cells by N1IC and Ets-1 occurred via TRPA1. However, PMA-induced megakaryocyte differentiation could be enhanced by TRPA1, and the surface markers of megakaryocytes could be elevated by nanaomycin A. Megakaryocyte differentiation could be reduced by Notch1 or Ets-1 knockdown and relieved by TRPA1 overexpression. The results suggest that Notch1 and TRPA1 might be critical modulators that control the fate of erythroid and megakaryocyte differentiation.
Anti-inflammatory and anti-excitoxic effects of diethyl oxopropanamide, an ethyl pyruvate bioisoster, exert robust neuroprotective effects in the postischemic brain
Authors: Lee Hye-Kyung , Kim Il-Doo , Kim Seung-Woo , Lee Hahnbie , Park Ju-Young , Yoon Sung-Hwa , Lee Ja-Kyeong 
Published: February 2017

AbstractEthyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust neuroprotective effects via its anti-inflammatory, anti-oxidative, and anti-apoptotic functions. In an effort to develop novel EP derivatives with greater protective potencies than EP, we generated four EP isosteres, among them the neuroprotective potency of N,N-diethyl-2-oxopropanamide (DEOPA), in which the ethoxy group of EP was replaced with diethylamine, was far greater than that of EP. When DEOPA was administered intravenously (5 mg/kg) to rat middle cerebral artery occlusion (MCAO) model at 6 hrs post-surgery, it suppressed infarct formation, ameliorated neurological and sensory/motor deficits, and inhibited microglial activation and neutrophil infiltrations in the postischemic brain more effectively than EP. In particular, DEOPA markedly suppressed LPS-induced nitrite production and cytokine/chemokine inductions in microglia, neutrophils, and endothelial cells and these effects are attributable to inhibition of the activity of NF-κB by suppressing IκB-α degradation and p65 to DNA binding. In addition, DEOPA suppressed NMDA-induced neuronal cell death in primary cortical neuron cultures by NAD replenishment and suppression of NF-κB activity. Together, these results indicate DEOPA has multi-modal protective effects against ischemic brain damage targeting numerous cell types in the brain and also against other inflammation-related diseases.
Pan-neurexin perturbation results in compromised synapse stability and a reduction in readily releasable synaptic vesicle pool size
Authors: Quinn Dylan P. , Kolar Annette , Wigerius Michael , Gomm-Kolisko Rachel N. , Atwi Hanine , Fawcett James P. , Krueger Stefan R. 
Published: February 2017

AbstractNeurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis. To address the role of neurexin in synapse formation and function, we disrupted the function of all α- and β-neurexins in cultured hippocampal neurons by shRNA knockdown or by overexpressing a neurexin mutant that is unable to bind to postsynaptic neurexin ligands. We show that neurexin perturbation results in an attenuation of neurotransmitter release that is in large part due to a reduction in the number of readily releasable synaptic vesicles. We also find that neurexin perturbation fails to alter the ability of neurons to form synapses, but rather leads to more frequent synapse elimination. These experiments suggest that neurexins are dispensable for the formation of initial synaptic contacts, but play an essential role in the stabilization and functional maturation of synapses.
Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery
Authors: Vazquez-Cintron Edwin J. , Beske Phillip H. , Tenezaca Luis , Tran Bao Q. , Oyler Jonathan M. , Glotfelty Elliot J. , Angeles Christopher A. , Syngkon Aurelia , Mukherjee Jean , Kalb Suzanne R. , Band Philip A. , McNutt Patrick M. , Shoemaker Charles B. , Ichtchenko Konstantin 
Published: February 2017

AbstractBotulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1. To test if BoNT/C1 ad retains neuron-specific targeting without concomitant toxic host responses, we evaluated the localization, activity, and toxicity of BoNT/C1 ad in vitro and in vivo. In neuronal cultures, BoNT/C1 ad light chain is rapidly internalized into presynaptic compartments, but does not cleave SNARE proteins nor impair spontaneous neurotransmitter release. In mice, systemic administration resulted in the specific co-localization of BoNT/C1 ad with diaphragmatic motor nerve terminals. The mouse LD50 of BoNT/C1 ad is 5 mg/kg, with transient neurological symptoms emerging at sub-lethal doses. Given the low toxicity and highly specific neuron-targeting properties of BoNT/C1 ad, these data suggest that BoNT/C1 ad can be useful as a molecular vehicle for drug delivery to the neuronal cytoplasm.
Sensitivity of chemical weathering and dissolved carbon dynamics to hydrological conditions in a typical karst river
Authors: Zhong Jun , Li Si-liang , Tao Faxiang , Yue Fujun , Liu Cong-Qiang 
Published: February 2017

AbstractTo better understand the mechanisms that hydrological conditions control chemical weathering and carbon dynamics in the large rivers, we investigated hydrochemistry and carbon isotopic compositions of dissolved inorganic carbon (DIC) based on high-frequency sampling in the Wujiang River draining the carbonate area in southwestern China. Concentrations of major dissolved solute do not strictly follow the dilution process with increasing discharge, and biogeochemical processes lead to variability in the concentration-discharge relationships. Temporal variations of dissolved solutes are closely related to weathering characteristics and hydrological conditions in the rainy seasons. The concentrations of dissolved carbon and the carbon isotopic compositions vary with discharge changes, suggesting that hydrological conditions and biogeochemical processes control dissolved carbon dynamics. Biological CO2 discharge and intense carbonate weathering by soil CO2 should be responsible for the carbon variability under various hydrological conditions during the high-flow season. The concentration of DICbio (DIC from biological sources) derived from a mixing model increases with increasing discharge, indicating that DICbio influx is the main driver of the chemostatic behaviors of riverine DIC in this typical karst river. The study highlights the sensitivity of chemical weathering and carbon dynamics to hydrological conditions in the riverine system.
Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III
Authors: Ma Dennis , Pignanelli Christopher , Tarade Daniel , Gilbert Tyler , Noel Megan , Mansour Fadi , Adams Scott , Dowhayko Alexander , Stokes Kyle , Vshyvenko Sergey , Collins Jonathan , Hudlicky Tomas , McNulty James , Pandey Siyaram 
Published: February 2017

AbstractEnhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics. They disrupted mitochondrial function, activated the intrinsic apoptotic pathway, and reduced growth of tumor xenografts in vivo. Interestingly, the pro-apoptotic effects of SVTH-7 on cancer cells and mitochondria were abrogated with the inhibition of mitochondrial complex II and III, suggesting mitochondrial or metabolic vulnerabilities may be exploited by this analog. This work provides a scaffold for characterizing distinct mitochondrial and metabolic features of cancer cells and reveals several lead compounds with high therapeutic potential.
TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes
Authors: Hasei Joe , Teramura Takeshi , Takehara Toshiyuki , Onodera Yuta , Horii Takuro , Olmer Merissa , Hatada Izuho , Fukuda Kanji , Ozaki Toshifumi , Lotz Martin K. , Asahara Hiroshi 
Published: February 2017

AbstractThe objective was to investigate the levels of TWIST1 in normal and OA cartilage and examine its role in regulating gene expression in chondrocytes. Human cartilage tissues and chondrocytes were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee arthroplasty. TWIST1 expression was increased in human OA knee cartilage compared to normal knee cartilage. TWIST1 induced matrix metalloproteinase 3 (MMP3) expression without direct binding to MMP3 promoter and increased the 5-hydroxymethylcytosine (5hmC) level at the MMP3 promoter. The effect of TWIST1 on expression of TET family (TET1, 2 and 3) was measured in stable TWIST1 transfected TC28 cells, and TET1 expression was up-regulated. TWIST1 dependent upregulation of Mmp3 expression was suppressed in Tet triple KO fibroblast derived from mouse ES cells. Increased TWIST1 expression is a feature of OA-affected cartilage. We identified a novel mechanism of catabolic reaction where TWIST1 up-regulates MMP3 expression by enriching 5hmC levels at the MMP3 promoter via TET1 induction. These findings implicate TWIST1 as an important factor regulating OA related gene expression. Clarifying epigenetic mechanisms of 5hmC induced by TWIST1 is a critical molecule to understanding OA pathogenesis.
CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca2+ entry-stimulated respiration
Authors: González-Sánchez Paloma , Pla-Martín David , Martínez-Valero Paula , Rueda Carlos B. , Calpena Eduardo , del Arco Araceli , Palau Francesc , Satrústegui Jorgina 
Published: February 2017

AbstractGDAP1 is an outer mitochondrial membrane protein involved in Charcot-Marie-Tooth (CMT) disease. Lack of GDAP1 gives rise to altered mitochondrial networks and endoplasmic reticulum (ER)-mitochondrial interactions resulting in a decreased ER-Ca2+ levels along with a defect on store-operated calcium entry (SOCE) related to a misallocation of mitochondria to subplasmalemmal sites. The defect on SOCE is mimicked by MCU silencing or mitochondrial depolarization, which prevent mitochondrial calcium uptake. Ca2+ release from de ER and Ca2+ inflow through SOCE in neuroblastoma cells result in a Ca2+-dependent upregulation of respiration which is blunted in GDAP1 silenced cells. Reduced SOCE in cells with CMT recessive missense mutations in the α-loop of GDAP1, but not dominant mutations, was associated with smaller SOCE-stimulated respiration. These cases of GDAP1 deficiency also resulted in a decreased ER-Ca2+ levels which may have pathological implications. The results suggest that CMT neurons may be under energetic constraints upon stimulation by Ca2+ mobilization agonists and point to a potential role of perturbed mitochondria-ER interaction related to energy metabolism in forms of CMT caused by some of the recessive or null mutations of GDAP1.
Comparing the survival rate of juvenile Chinook salmon migrating through hydropower systems using injectable and surgical acoustic transmitters
Authors: Deng Z. D. , Martinez J. J. , Li H. , Harnish R. A. , Woodley C. M. , Hughes J. A. , Li X. , Fu T. , Lu J. , McMichael G. A. , Weiland M. A. , Eppard M. B. , Skalski J. R. , Townsend R. L. 
Published: February 2017

AbstractAcoustic telemetry is one of the primary technologies for studying the behavior and survival of fishes throughout the world. The size and performance of the transmitter are key limiting factors. The newly developed injectable transmitter is the first acoustic transmitter that can be implanted via injection instead of surgery. A two-part field study was conducted to evaluate the performance of the injectable transmitter and its effect on the survival of implanted fish. The injectable transmitter performed well and similarly to the proceeding generation of commercially-available JSATS transmitters tested concurrently. Snake River subyearling Chinook salmon smolts implanted with the injectable transmitter had a higher survival probability from release to each of eleven downstream detection arrays, because reach-specific survival estimates were significantly higher for the injectable group in three of the eleven reaches examined. Overall, the injectable group had a 0.263 (SE = 0.017) survival probability over the entire 500 km study area compared to 0.199 (0.012) for the surgically implanted group. The reduction in size and ability to implant the new transmitter via injection has reduced the tag or tagging effect bias associated with studying small fishes. The information gathered with this new technology is helping to evaluate the impacts of dams on fishes.
Prognostic Value of Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma: a Meta-analysis
Authors: Fan Zhaona , Li Mianxiang , Chen Xiaobing , Wang Juan , Liang Xueyi , Wang Hongfei , Wang Zhi , Cheng Bin , Xia Juan 
Published: February 2017

AbstractBmi-1, CD133, Nanog and Oct-4 have been reported as cancer stem cell (CSC) markers in head and neck squamous cell carcinoma (HNSCC). However, the prognostic value of them in HNSCC remains controversial. Hence, this meta-analysis was conducted to access the association between the four CSC markers and survival outcome of HNSCC patients. A total of 22 articles with 27 studies met the inclusion criteria and the combined hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated. Data analysis showed that high expression of CSC markers was associated with poor overall survival (OS) (HR = 1.93; 95% CI: 1.46–2.55, P < 0.001) and disease free survival (DFS) (HR = 4.78; 95% CI: 2.95–7.75, P < 0.001) but not disease specific survival (DSS) (HR = 1.17; 95% CI: 0.74–1.84, P = 0.50) of HNSCC patients. Subgroup analysis indicted that high expression of CD133 (HR = 2.33, 95%CI: 1.42–3.83, P < 0.001), Oct-4(HR = 2.10, 95%CI: 1.36–3.22, P = 0.007) and Nanog (HR = 2.49, 95%CI: 1.66–3.72, P < 0.001) could predict poor OS in HNSCC patients respectively whereas overexpression of Bmi-1 was not related to the reduced OS in HNSCC patients (HR = 1.32, 95%CI: 0.66–2.65, P = 0.43). Therefore, we concluded that CSC markers, especially CD133, Nanog and Oct-4, might be predictive factors in HNSCC patients.
A novel role of the organizer gene Goosecoid as an inhibitor of Wnt/PCP-mediated convergent extension in Xenopus and mouse
Authors: Ulmer Bärbel , Tingler Melanie , Kurz Sabrina , Maerker Markus , Andre Philipp , Mönch Dina , Campione Marina , Deißler Kirsten , Lewandoski Mark , Thumberger Thomas , Schweickert Axel , Fainsod Abraham , Steinbeißer Herbert , Blum Martin 
Published: February 2017

AbstractGoosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role ofGscin the organizer has remained enigmatic. Using conditional gain-of-function approaches inXenopusand mouse to maintainGscexpression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc inXenopusanimal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenousGscfunctions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects inXenopusand misalignment of inner ear hair cells in mouse. Our results assign a novel function toGscas an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizerGscrepresses CE as well:Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like theGsc-negative notochordal cells, which subsequently emerge from the organizer. In this model,Gscprovides a switch between cell migration and CE, i.e. cell intercalation.
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
Authors: Milella Michele , Falcone Italia , Conciatori Fabiana , Matteoni Silvia , Sacconi Andrea , De Luca Teresa , Bazzichetto Chiara , Corbo Vincenzo , Simbolo Michele , Sperduti Isabella , Benfante Antonina , Del Curatolo Anais , Cesta Incani Ursula , Malusa Federico , Eramo Adriana , Sette Giovanni , Scarpa Aldo , Konopleva Marina , Andreeff Michael , McCubrey James Andrew , Blandino Giovanni , Todaro Matilde , Stassi Giorgio , De Maria Ruggero , Cognetti Francesco , Del Bufalo Donatella , Ciuffreda Ludovica 
Published: February 2017

AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN-loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies.
Other-regarding attention focus modulates third-party altruistic choice: An fMRI study
Authors: David Bastian , Hu Yang , Krüger Frank , Weber Bernd 
Published: February 2017

AbstractThird-party altruistic decision-making has been shown to be modulated by other-regarding attention (e.g., focusing on the offender’s crime or the victim’s situation especially in judicial judgment). However, the neural mechanisms underlying this modulation remain poorly understood. In this fMRI study, participants voluntarily decided if they wanted to punish the first-party offender or help the second-party victim using their own monetary endowment in an unfair context. Particularly, before deciding they were asked to focus on the (un)fairness of the offender proposing the offer (offender-focused block, OB), the feeling of the victim receiving this offer (victim-focused block, VB), or without any specific focus (baseline block, BB). We found that compared to BB participants punished more frequently and prolonged help choices in OB, whereas they helped more frequently in VB. These findings were accompanied by an increased activation in the temporo-parietal junction (TPJ) during decision making in OB and VB. Moreover, regions relevant to cognitive control (esp. IFG/AI and the dorsal anterior cingulate cortex) were strongly recruited during specific choices conflicting the attention focus (e.g., choosing help in OB). Our findings revealed how other-regarding attention modulates third-party altruistic decision-making at the neural level.