bluuebunny/crossref_metadata_2025_split huggingface dataset:
The R2R3‐MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple
Authors: Hu Da‐Gang , Li Yuan‐Yuan , Zhang Quan‐Yan , Li Ming , Sun Cui‐Hui , Yu Jian‐Qiang , Hao Yu‐Jin 
Published: April 2017

SummaryMalate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate‐metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA‐B1, MdVHA‐E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum‐activated malate transporter 9), MdVHA‐A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple.
Quantification of near‐attomole gibberellins in floral organs dissected from a single Arabidopsis thaliana flower
Authors: Li Dongmei , Guo Zhenpeng , Liu Cuimei , Li Jincheng , Xu Wenzhong , Chen Yi 
Published: April 2017

SummaryThere remains a methodological bottleneck in the quantification of ultra‐trace plant hormones in very tiny plant organs at fresh weights below a milligram. The challenge becomes even more serious in the determination of endogenous gibberellins (GAs), which are a class of compounds that are difficult to separate and detect. Herein, a quantification method using ultra‐high‐performance liquid chromatography–tandem mass spectrometry was developed, combined with a derivatization technique in which GAs react with N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide in ethanol. The method was validated as capable of determining GAs in floral organs (about 80–250 μg) – pistil, stamens, petals, sepals and receptacle – which were dissected from only one flower of Arabidopsis thaliana. Substantially different abundance patterns of GAs were measured from the floral organs at floral stages 13, 14 and 15 along the non‐13‐hydroxylation pathway and the early 13‐hydroxylation pathway in plants. This allows sub‐flower‐level insights into how GAs affect floral development. The method exhibited excellent limit of detection and limit of quantification down to 5.41 and 18.0 attomole, respectively, and offered a fairly wide linear range from 0.01 to 25 femtomole with linear coefficients above 0.9961. The precision of the method was evaluated with relative standard deviations below 10.6% for intra‐day and 11.4% for inter‐day assays, and recoveries ranged from 64.0% to 107%.
Obesity is Associated With Altered Plantar Pressure Distribution in Older Women
Authors: Neri Silvia Gonçalves Ricci , Gadelha André Bonadias , Correia Ana Luiza Matias , Pereira Juscélia Cristina , de David Ana Cristina , Lima Ricardo M. 
Published: April 2017

Increased plantar pressure has been found to be related with greater risk of falling. Although there is evidence suggesting that obesity is linked to foot disorders, the association between obesity and plantar pressure of older adults has been poorly investigated. The purpose of this study was to examine the association between obesity and plantar pressure distribution and to explore its relationship with body fat distribution. Two hundred and eleven older women took part in this cross-sectional study. Body mass index was taken for obesity classification. Whole body, android, and gynoid fat percentage was assessed using dual-energy x-ray absorptiometry. Peak plantar pressure was evaluated during gait using an Emed AT-4 pressure platform. Obese volunteers generated greater peak pressure at midfoot (187.26 kPa) compared to both normal weight (128.52 kPa, p < .001) and overweight (165.74 kPa, p < .001). Peak plantar pressure at midfoot was also greater in overweight compared to normal weight (p < .001). At forefoot, peak pressure was higher in the obese (498.15 kPa) compared to normal weight volunteers (420.41 kPa, p = .007). Additionally, whole body, android, and gynoid fat percentage were significantly associated with peak pressure at midfoot and forefoot. Therefore, clinicians dealing with falls should consider the effect of increased body weight on plantar pressure.
Deciphering the Regulatory Network between the SREBP Pathway and Protein Secretion in
Neurospora crassa
Authors: Qin Lina , Wu Vincent W. , Glass N. Louise 
Published: April 2017

ABSTRACT

Sterol regulatory element binding proteins (SREBPs) are conserved from yeast to mammalian cells and function in the regulation of sterol homeostasis. In fungi, the SREBP pathway has been implicated in the adaptation to hypoxia and in virulence. In
Neurospora crassa
and
Trichoderma reesei
, the SREBP pathway also negatively regulates protein secretion under lignocellulolytic conditions. Here we utilized global transcriptional profiling combined with genetic and physiological analyses to address the regulatory link between the SREBP pathway and protein secretion in
N. crassa
. Our results demonstrated that the function of the SREBP pathway in ergosterol biosynthesis and adaptation to hypoxia was conserved in
N. crassa
. Under lignocellulolytic conditions, the SREBP pathway was highly activated, resulting in the reduced expression of lytic polysaccharide monooxygenases, which require molecular oxygen for catalytic activity. Additionally, activation of the SREBP pathway under lignocellulolytic conditions repressed a set of genes predicted to be involved in the endoplasmic reticulum stress response. Here we show that the inability of a
hac-1
mutant, which bears a deletion of the major regulator of the unfolded protein response (UPR), to efficiently produce cellulases and utilize cellulose was suppressed by mutations in the SREBP pathway. The analyses presented here demonstrated new SREBP pathway functions, including linkages to the UPR, and provide new clues for genetic engineering of filamentous fungi to improve their production of extracellular proteins.

IMPORTANCE
The role of SREBP transcription factors in the regulation of sterol biosynthesis is conserved from humans to yeast. In filamentous fungi, this pathway regulates the secretion of lignocellulolytic enzymes during plant biomass deconstruction. Here we show that the SREBP pathway in
Neurospora crassa
regulates the production of specific cellulases, lytic polysaccharide monooxygenases that utilize molecular oxygen. Via global transcriptional profile and genetic analyses, a relationship between the SREBP pathway and the unfolded protein response (UPR) pathway was revealed, suggesting a regulatory interplay of these two pathways in the trafficking of plant biomass-degrading enzymes. These findings have implications for our understanding of the cross talk of the SREBP and UPR pathways in other organisms and will guide the rational engineering of fungal strains to improve cellulolytic enzyme production.
New Mechanism by Which Human Cytomegalovirus MicroRNAs Negate the Proinflammatory Response to Infection
Authors: Yurochko Andrew D. 
Published: April 2017

ABSTRACT

Viruses have evolved many novel mechanisms to promote infection and to mitigate the host cell response to that infection. In the article by M. H. Hancock et al. (mBio 8:e00109-17, 2017,
https://doi.org/10.1128/mBio.00109-17
), the authors describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs; miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The authors document that these two viral miRNAs downregulate the NF-κB response through direct targeting of the IKKα and IKKβ mRNAs, which in turn, through diminished IκB kinases (IKKs), block production of proinflammatory cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF-α]). Because most signaling pathways that promote NF-κB activation and nuclear translocation ultimately converge on the activation of the IKK complex, this new study documents that HCMV can strongly dictate how infected cells respond to internal and/or external stimuli and thus positively influence the outcome of both lytic and latent infection.
Synergistic Internal Ribosome Entry Site/MicroRNA-Based Approach for Flavivirus Attenuation and Live Vaccine Development
Authors: Tsetsarkin Konstantin A. , Liu Guangping , Volkova Evgeniya , Pletnev Alexander G. 
Published: April 2017

ABSTRACT
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3′ noncoding region (NCR) and expressed under translational control from an IRES. Engineered bicistronic LGTVs carrying multiple target sequences for brain-specific miRNAs were stable in Vero cells and induced adaptive immunity in mice. Importantly, miRNA-targeted bicistronic LGTVs were not pathogenic for either newborn mice after intracranial inoculation or adult immunocompromised mice (SCID or type I interferon receptor knockout) after intraperitoneal injection. Moreover, bicistronic LGTVs were restricted for replication in tick-derived cells, suggesting an interruption of viral transmission in nature by arthropod vectors. This approach is suitable for reliable attenuation of many flaviviruses and may enable development of live attenuated flavivirus vaccines.

IMPORTANCE
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Allied separately attenuating approaches based on (i) microRNA genome targeting and (ii) internal ribosome entry site insertion are not sufficient for relievable attenuation of neurotropic flavivirus pathogenesis. Here, we describe a novel dual strategy that combines the specificity of miRNA-based and the effectiveness of IRES-based attenuating approaches, allowing us to overcome these critical limitations. This developed approach provides a robust platform for reliable attenuation of many flaviviruses and may enable development of live flavivirus vaccines.
Education achievement and type 2 diabetes—what mediates the relationship in older adults? Data from the ESTHER study: a population-based cohort study
Authors: Steele Christopher J , Schöttker Ben , Marshall Adele H , Kouvonen Anne , O'Doherty Mark G , Mons Ute , Saum Kai-Uwe , Boffetta Paolo , Trichopoulou Antonia , Brenner Hermann , Kee Frank 
Published: April 2017

ObjectiveThe study aims to identify the mediating factors of the relationship between education achievement and incident type 2 diabetes mellitus (T2DM) in older adults.DesignPopulation-based cohort study.SettingParticipants were recruited from the German federal state of Saarland.ParticipantsParticipants were excluded if they had prevalent T2DM or missing data on prevalent T2DM, missing or zero follow-up time for incident T2DM or were under 50 years of age. The total sample consisted of 7462 individuals aged 50–75 years (42.8% men, mean age 61.7 years) at baseline (2000–02). The median follow-up time was 8.0 years.MethodsCox proportional hazards regression was initially used to determine the direct association between education achievement and incident T2DM. Using the Baron and Kenny approach, we then investigated the associations between education achievement and incident T2DM with the potential mediators. The contribution of each of the putative mediating variables was then calculated.ResultsA clear socioeconomic gradient was observed with regard to T2DM incidence with the lowest educated individuals at a greater risk of developing the disease during the follow-up period: HR (95% CI) high education: 0.52 (0.34 to 0.80); medium education: 0.80 (0.66 to 0.96). Seven of the variables considered explained a proportion of the education–T2DM relationship (body mass index, alcohol consumption, hypertension, fasting triglycerides, high-density lipoprotein (HDL) cholesterol, physical activity and smoking status), where the contribution of the variables ranged from 1.0% to 17.7%. Overall, the mediators explained 31.7% of the relationship.ConclusionBy identifying the possible mediating factors of the relationship between education achievement and incident T2DM in older adults, the results of this study can be used to assist with the development of public health strategies that aim to reduce socioeconomic inequalities in T2DM.
An Adaptive EM Algorithm for the Maximum Likelihood Estimation of Non-Homogeneous Poisson Process Software Reliability Growth Models
Authors: Nagaraju Vidhyashree , Fiondella Lance , Zeephongsekul Panlop , Wandji Thierry 
Published: April 2017

Non-homogeneous Poisson process (NHPP) software reliability growth models (SRGMa) enable quantitative metrics to guide decisions during the software engineering life cycle, including test resource allocation and release planning. However, many SRGM possess complex mathematical forms that make them difficult to apply. Specifically, traditional procedures solve a system of nonlinear equations to identify the numerical parameters that best characterize failure data. Recently, researchers have developed expectation-maximization (EM) algorithms for NHPP SRGM that exhibit better convergence properties and can therefore find maximum likelihood estimates with greater ease.This paper presents an adaptive EM (AEM) algorithm, which combines an earlier EM algorithm for NHPP SRGM with unconstrained search of the model parameter space. Our performance analysis shows that the AEM outperforms state-of-the-art EM algorithms for NHPP SRGM with very strong statistical significance, which is as much as hundreds of times faster on some data sets. Thus, the approach can fit SRGM very quickly. We also incorporate this high performance adaptive EM algorithm into a heuristic nested model selection procedure to objectively select a model of least complexity that best characterizes the failure data. Results indicate this heuristic approach often identifies the model possessing the best model selection criteria.aAcronyms are not pluralized.
Absoluteness via resurrection
Authors: Audrito Giorgio , Viale Matteo 
Published: April 2017

The resurrection axioms are forcing axioms introduced recently by Hamkins and Johnstone, developing on ideas of Chalons and Veličković. We introduce a stronger form of resurrection axioms (the iterated resurrection axioms [Formula: see text] for a class of forcings [Formula: see text] and a given ordinal [Formula: see text]), and show that [Formula: see text] implies generic absoluteness for the first-order theory of [Formula: see text] with respect to forcings in [Formula: see text] preserving the axiom, where [Formula: see text] is a cardinal which depends on [Formula: see text] ([Formula: see text] if [Formula: see text] is any among the classes of countably closed, proper, semiproper, stationary set preserving forcings). We also prove that the consistency strength of these axioms is below that of a Mahlo cardinal for most forcing classes, and below that of a stationary limit of supercompact cardinals for the class of stationary set preserving posets. Moreover, we outline that simultaneous generic absoluteness for [Formula: see text] with respect to [Formula: see text] and for [Formula: see text] with respect to [Formula: see text] with [Formula: see text] is in principle possible, and we present several natural models of the Morse–Kelley set theory where this phenomenon occurs (even for all [Formula: see text] simultaneously). Finally, we compare the iterated resurrection axioms (and the generic absoluteness results we can draw from them) with a variety of other forcing axioms, and also with the generic absoluteness results by Woodin and the second author.
Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML
Authors: Reichenbach Frank , Wiedenmann Cornelius , Schalk Enrico , Becker Diana , Funk Kathrin , Scholz-Kreisel Peter , Todt Franziska , Wolleschak Denise , Döhner Konstanze , Marquardt Jens U. , Heidel Florian , Edlich Frank 
Published: April 2017

Abstract
Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death.
Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort.
Results: This study shows that relative BAX localization determines the predisposition of different AML cell lines to apoptosis. Human AML displays a surprising variety of relative BAX localizations. In a test cohort of 48 patients with AML, mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients treated with myelosuppressive chemotherapy confirmed that relative BAX localization correlates with probability of disease progression, FLT3-ITD status, and leukocytosis. Relative BAX localization could therefore be helpful to identify elderly or frail patients who may benefit from cytotoxic therapy.
Conclusions: In this retrospective analysis of two independent AML cohorts, our data suggest that Bax localization may predict prognosis of patients with AML and cellular predisposition to apoptosis, combining the actual contribution of known and unknown factors to a final “common path.” Clin Cancer Res; 23(16); 4805–16. ©2017 AACR.
A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis
Authors: Liu Caifeng , Zhang Yunjian , Lim Sharon , Hosaka Kayoko , Yang Yunlong , Pavlova Tatiana , Alkasalias Twana , Hartman Johan , Jensen Lasse , Xing Xiaoming , Wang Xinsheng , Lu Yongtian , Nie Guohui , Cao Yihai 
Published: April 2017

Abstract
Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes.
Experimental Design: Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor–educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis.
Results: We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non–metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity.
Conclusions: Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. Clin Cancer Res; 23(16); 4769–79. ©2017 AACR.
Metamorfismo de temperatura ultra-alta de granulitos com safirina de 2,0 Ga do Bloco Itabuna-Salvador-Curaçá, Bahia, Brasil
Authors: Barbosa Johildo Salomão Figueiredo , Leal Angela Beatriz de Menezes , Fuck Reinhardt Adolfo , Oliveira Jailma Santos de Souza de , Gonçalves Philippe , Leite Carlson de Matos Maia 
Published: April 2017

A área de pesquisa se situa no Cráton do São Francisco, no sul da Bahia, Brasil. Nessa região, no segmento crustal Bloco Itabuna-Salvador-Curaçá (BISC), ocorrem rochas supracrustais associadas a gnaisses tonalíticos/trondhjemíticos a monzoníticos e rochas máficas subordinadas, de idades arqueana e paleoproterozoica, todos fortemente deformados e reequilibrados na fácies granulito em 2,07 a 2,08 Ga. As rochas supracrustais incluem granulitos com safirina constituídos por quartzo, ortopiroxênio, silimanita, granada, mesopertita, plagioclásio, biotita e cordierita. Com base nos arranjos microestruturais entre os minerais constituintes dos granulitos com safirina, a paragênese de pico metamórfico é Grt1 + Opx1 + Bt1 + Qtz + Sil1 + Spr1 + Mp. Microestruturas de reações entre minerais, como coroas de simplectitos ao redor de porfiroblastos, permitiram identificar as seguintes paragêneses retrógradas, interpretadas como formadas durante a ascensão tectônica dessas rochas: Grt1 ± Qtz = Opx2 + Sil2, Grt1 = Opx2 + Spr2 (+ Sil2); Opx1 + Sil1 + Qtz = Crd e Grt1 + Qtz = Opx3 + Crd. Por sua vez, simplectitos de Bt2 + Qtz formados pela reação Opx1-2 + Mp + H2O = Bt2 + Qtz estão relacionados à evolução retrógrada durante resfriamento. Cálculos termobarométricos realizados com aplicação de termobarômetros clássicos e método de multiequilíbrios (THERMOCALC, por exemplo) indicaram P = 7-11 kbar e T ≥ 900°C para os granulitos com safirina. Um dos mecanismos associados à elevada temperatura está relacionado à adição de material radioativo com a presença de magmas basálticos durante a formação do BISC. A cristalização fracionada desses magmas produziu intrusões tonalíticas que datam de aproximadamente de 2,15 a 2,13 Ga, próximo do pico do metamorfismo de 2,07 a 2,08 Ga.