bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family
Authors: Trempe Jean-François , Šašková Klára Grantz , Sivá Monika , Ratcliffe Colin D. H. , Veverka Václav , Hoegl Annabelle , Ménade Marie , Feng Xin , Shenker Solomon , Svoboda Michal , Kožíšek Milan , Konvalinka Jan , Gehring Kalle 
Published: September 2016

AbstractThe eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.
Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock
Authors: Balakrishnan Arjun , DasSarma Priya , Bhattacharjee Oindrilla , Kim Jong Myoung , DasSarma Shiladitya , Chakravortty Dipshikha 
Published: September 2016

AbstractBactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs. Our results indicate that delivery of mBPIN-GVNPs increase the survival rate of mice challenged with lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine. Additionally, the mBPIN-GVNP-treated mice displayed reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels.
Oscillatory activity in auditory cortex reflects the perceptual level of audio-tactile integration
Authors: Plöchl Michael , Gaston Jeremy , Mermagen Tim , König Peter , Hairston W. David 
Published: September 2016

AbstractCross-modal interactions between sensory channels have been shown to depend on both the spatial disparity and the perceptual similarity between the presented stimuli. Here we investigate the behavioral and neural integration of auditory and tactile stimulus pairs at different levels of spatial disparity. Additionally, we modulated the amplitudes of both stimuli in either a coherent or non-coherent manner. We found that both auditory and tactile localization performance was biased towards the stimulus in the respective other modality. This bias linearly increases with stimulus disparity and is more pronounced for coherently modulated stimulus pairs. Analyses of electroencephalographic (EEG) activity at temporal–cortical sources revealed enhanced event-related potentials (ERPs) as well as decreased alpha and beta power during bimodal as compared to unimodal stimulation. However, while the observed ERP differences are similar for all stimulus combinations, the extent of oscillatory desynchronization varies with stimulus disparity. Moreover, when both stimuli were subjectively perceived as originating from the same direction, the reduction in alpha and beta power was significantly stronger. These observations suggest that in the EEG the level of perceptual integration is mainly reflected by changes in ongoing oscillatory activity.
Attribution of hydrological change in Heihe River Basin to climate and land use change in the past three decades
Authors: Luo Kaisheng , Tao Fulu , Moiwo Juana P. , Xiao Dengpan 
Published: September 2016

AbstractThe contributions of climate and land use change (LUCC) to hydrological change in Heihe River Basin (HRB), Northwest China were quantified using detailed climatic, land use and hydrological data, along with the process-based SWAT (Soil and Water Assessment Tool) hydrological model. The results showed that for the 1980s, the changes in the basin hydrological change were due more to LUCC (74.5%) than to climate change (21.3%). While LUCC accounted for 60.7% of the changes in the basin hydrological change in the 1990s, climate change explained 57.3% of that change. For the 2000s, climate change contributed 57.7% to hydrological change in the HRB and LUCC contributed to the remaining 42.0%. Spatially, climate had the largest effect on the hydrology in the upstream region of HRB, contributing 55.8%, 61.0% and 92.7% in the 1980s, 1990s and 2000s, respectively. LUCC had the largest effect on the hydrology in the middle-stream region of HRB, contributing 92.3%, 79.4% and 92.8% in the 1980s, 1990s and 2000s, respectively. Interestingly, the contribution of LUCC to hydrological change in the upstream, middle-stream and downstream regions and the entire HRB declined continually over the past 30 years. This was the complete reverse (a sharp increase) of the contribution of climate change to hydrological change in HRB.
Candida albicans Dbf4-dependent Cdc7 kinase plays a novel role in the inhibition of hyphal development
Authors: Lai Wei-Chung , Chang Tschen-wei , Wu Chang Hao , Yang Shu-Ya , Lee Tai-Lin , Li Wan Chen , Chien Ting , Cheng Yu-Che , Shieh Jia-Ching 
Published: September 2016

AbstractCandida albicans is an opportunistic human fungal pathogen. The ability to switch among multiple cellular forms is key to its pathogenesis. The Dbf4-dependent protein kinase gene CDC7 is conserved due to its role in initiating DNA replication. Because a C. albicans Cdc7 (Cacdc7) homozygous null was not viable, we generated a C. albicans strain with a deleted C. albicans CDC7 (CaCDC7) allele and an expression-repressible allele. Surprisingly, cells of the strain grew as hyphae under the repressed conditions. The in vitro kinase assays confirmed that CaCdc7 (K232) and CaCdc7 (T437) are critical for catalytic and phosphoacceptor of activation activity, respectively. C. albicans cells formed hyphae when expressing either the catalytically inactive CaCdc7 (K232R) or the phosphoacceptor-deficient CaCdc7 (T437A). While CaCdc7 interacted with CaDbf4, cells of the strain in which CaCDC7 was repressed were not rescued by constitutively expressing C. albicans DBF4 or vice versa. We conclude that CaDBF4-dependent CaCDC7 is an essential gene suppressing the hyphal development.
Increased PKCα activity by Rack1 overexpression is responsible for chemotherapy resistance in T-cell acute lymphoblastic leukemia-derived cell line
Authors: Lei Jie , Li Qi , Gao Ying , Zhao Lei , Liu Yanbo 
Published: September 2016

AbstractChemoresistant mechanisms in T-cell acute lymphoblastic leukemia (T-ALL) patients are not clarified. The apoptotic signaling mediated by receptor of activated C kinase 1 (Rack1), protein kinase C (PKC) and FEM1 homolog b (FEM1b) was investigated in two T-ALL-derived cell lines (Jurkat and CCRF-CEM) following treatment with chemotherapy drugs vincristine and prednisone. Serum starvation or chemotherapeutic drugs significantly reduced Rack1 level and PKC activation, while promoted cellular apoptosis in both cell lines. Rack1 overexpression protected T-ALL cell against starvation or chemotherapeutic drug-induced apoptosis. Moreover, Rack1 overexpression reduced the level of cytochrome c and active caspase 3 as well as FEM1b and apoptotic protease activating factor-1 (Apaf-1), and inhibited induction of cellular apoptosis in chemotherapeutic drug-treated Jurkat cell. Interaction of Rack1 and PKCα, not PKCβ, was detected in both cell lines. Of note, Rack1 overexpression abrogated reduction of PKC kinase activity in chemotherapeutic drug-treated T-ALL cell. PKC kinase inhibitor Go6976 or siPKCα inhibited downregulation of FEM1b and/or Apaf-1, and thus increased cellular apoptosis in Rack1-overexpressed T-ALL cell receiving chemotherapeutic drugs. Accordingly, our data provided evidence that increased Rack1-mediated upregulation of PKC kinase activity may be responsible for the development of chemoresistance in T-ALL-derived cell line potentially by reducing FEM1b and Apaf-1 level.
Mechanism Underlying Time-dependent Cross-phenomenon between Concentration-response Curves and Concentration Addition Curves: A Case Study of Sulfonamides-Erythromycin mixtures on Escherichia coli
Authors: Sun Haoyu , Ge Hongming , Zheng Min , Lin Zhifen , Liu Ying 
Published: September 2016

AbstractPrevious studies have identified a phenomenon in which the concentration-response curves (CRCs) for mixtures cross the curves for concentration addition model when predicting or judging joint toxic actions. However, mechanistic investigations of this phenomenon are extremely limited. In this study, a similar phenomenon was observed when we determined the joint toxic actions of sulfonamides (SAs) and erythromycin (ERY) on Escherichia coli (E. coli), which we named the “cross-phenomenon”, and it was characterized by antagonism in the low-concentration range, addition in the medium-concentration range, and synergism in the high-concentration range. The mechanistic investigation of the cross-phenomenon was as follows: SAs and ERY could form a double block to inhibit the bacterial growth by exhibiting a synergistic effect; however, the hormetic effect of SAs on E. coli led to antagonism in the low-concentration range, resulting from the stimulation of sdiA mRNA expression by SAs, which increased the expression of the efflux pump (AcrAB-TolC) to discharge ERY. Furthermore, this cross-phenomenon was observed to be a time-dependent process induced by the increase of both the concentration and extent of stimulation of sdiA mRNA with exposure time. This work explains the dose-dependent and time-dependent cross-phenomenon and provides evidence regarding the interaction between hormesis and cross-phenomenon.
Protein oxidation and degradation caused by particulate matter
Authors: Lai Ching-Huang , Lee Chun-Nin , Bai Kuan-Jen , Yang You-Lan , Chuang Kai-Jen , Wu Sheng-Ming , Chuang Hsiao-Chi 
Published: September 2016

AbstractParticulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD) and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.
SlARF2a plays a negative role in mediating axillary shoot formation
Authors: Xu Tao , Liu Xin , Wang Rong , Dong Xiufen , Guan Xiaoxi , Wang Yanling , Jiang Yun , Shi Zihang , Qi Mingfang , Li Tianlai 
Published: September 2016

AbstractSlARF2a is expressed in most plant organs, including roots, leaves, flowers and fruits. A detailed expression study revealed that SlARF2a is mainly expressed in the leaf nodes and cross-sections of the nodes indicated that SlARF2a expression is restricted to vascular organs. Decapitation or the application of 6-benzylaminopurine (BAP) can initially promote axillary shoots, during which SlARF2a expression is significantly reduced. Down-regulation of SlARF2a expression results in an increased frequency of dicotyledons and significantly increased lateral organ development. Stem anatomy studies have revealed significantly altered cambia and phloem in tomato plants expressing down-regulated levels of ARF2a, which is associated with obvious alterations in auxin distribution. Further analysis has revealed that altered auxin transport may occur via altered pin expression. To identify the interactions of AUX/IAA and TPL with ARF2a, four axillary shoot development repressors that are down-regulated during axillary shoot development, IAA3, IAA9, SlTPL1 and SlTPL6, were tested for their direct interactions with ARF2a. Although none of these repressors are directly involved in ARF2a activity, similar expression patterns of IAA3, IAA9 and ARF2a implied they might work tightly in axillary shoot formation and other developmental processes.
Myelinating glia differentiation is regulated by extracellular matrix elasticity
Authors: Urbanski Mateusz M. , Kingsbury Lyle , Moussouros Daniel , Kassim Imran , Mehjabeen Saraf , Paknejad Navid , Melendez-Vasquez Carmen V. 
Published: September 2016

AbstractThe mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their native environment or conditions found in injured tissue. We found that a rigid, lesion-like matrix inhibited branching and differentiation of OL in NMII-dependent manner. By contrast, SC developed normally in both soft and stiffer matrices. Although SC differentiation was not significantly affected by changes in matrix stiffness alone, we found that expression of Krox-20 was potentiated on rigid matrices at high laminin concentration. These findings are relevant to the design of biomaterials to promote healing and regeneration in both CNS and PNS, via transplantation of glial progenitors or the implantation of tissue scaffolds.
Loss of Lysyl Oxidase-like 3 Attenuates Embryonic Lung Development in Mice
Authors: Zhang Jian , Liu Ziyi , Zhang Tingting , Lin Zhuchun , Li Zhenzu , Zhang Aizhen , Sun Xiaoyang , Gao Jiangang 
Published: September 2016

AbstractLysyl oxidase-like 3 (LOXL3), a human disease gene candidate, is a member of the lysyl oxidase (LOX) family and is indispensable for mouse palatogenesis and vertebral column development. Our previous study showed that the loss of LOXL3 resulted in a severe cleft palate and spinal deformity. In this study, we investigated a possible role for LOXL3 in mouse embryonic lung development. LOXL3-deficient mice displayed reduced lung volumes and weights, diminished saccular spaces and deformed and smaller thoracic cavities. Excess elastic fibres were detected in LOXL3-deficient lungs, which might be related to the increased LOXL4 expression. Increased transforming growth factor β1 (TGFβ1) expression might be involved in the up-regulation of LOXL4 in LOXL3-deficient lungs. We concluded that the loss of LOXL3 attenuates mouse embryonic lung development.
Defining a Radiomic Response Phenotype: A Pilot Study using targeted therapy in NSCLC
Authors: Aerts Hugo J. W. L. , Grossmann Patrick , Tan Yongqiang , Oxnard Geoffrey R. , Rizvi Naiyer , Schwartz Lawrence H. , Zhao Binsheng 
Published: September 2016

AbstractMedical imaging plays a fundamental role in oncology and drug development, by providing a non-invasive method to visualize tumor phenotype. Radiomics can quantify this phenotype comprehensively by applying image-characterization algorithms, and may provide important information beyond tumor size or burden. In this study, we investigated if radiomics can identify a gefitinib response-phenotype, studying high-resolution computed-tomography (CT) imaging of forty-seven patients with early-stage non-small cell lung cancer before and after three weeks of therapy. On the baseline-scan, radiomic-feature Laws-Energy was significantly predictive for EGFR-mutation status (AUC = 0.67, p = 0.03), while volume (AUC = 0.59, p = 0.27) and diameter (AUC = 0.56, p = 0.46) were not. Although no features were predictive on the post-treatment scan (p > 0.08), the change in features between the two scans was strongly predictive (significant feature AUC-range = 0.74–0.91). A technical validation revealed that the associated features were also highly stable for test-retest (mean ± std: ICC = 0.96 ± 0.06). This pilot study shows that radiomic data before treatment is able to predict mutation status and associated gefitinib response non-invasively, demonstrating the potential of radiomics-based phenotyping to improve the stratification and response assessment between tyrosine kinase inhibitors (TKIs) sensitive and resistant patient populations.
Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells
Authors: Chen Ting , Xie Mei-Ying , Sun Jia-Jie , Ye Rui-Song , Cheng Xiao , Sun Rui-Ping , Wei Li-Min , Li Meng , Lin De-Lin , Jiang Qing-Yan , Xi Qian-Yun , Zhang Yong-Liang 
Published: September 2016

AbstractMilk-derived exosomes were identified as a novel mechanism of mother-to-child transmission of regulatory molecules, but their functions in intestinal tissues of neonates are not well-studied. Here, we characterized potential roles of porcine milk-derived exosomes in the intestinal tract. In vitro, treatment with milk-derived exosomes (27 ± 3 ng and 55 ± 5 ng total RNA) significantly promoted IPEC-J2 cell proliferation by MTT, CCK8, EdU fluorescence and EdU flow cytometry assays. The qRT-PCR and Western blot analyses indicated milk-derived exosomes (0.27 ± 0.03 μg total RNA) significantly promoted expression of CDX2, IGF-1R and PCNA and inhibited p53 gene expression involved in intestinal proliferation. Additionally, six detected miRNAs were significantly increased in IPEC-J2 cell, while FAS and SERPINE were significantly down-regulated relative to that in control. In vivo, treated groups (0.125 μg and 0.25 μg total RNA) significantly raised mice’ villus height, crypt depth and ratio of villus length to crypt depth of intestinal tissues, significantly increased CDX2, PCNA and IGF-1R’ expression and significantly inhibited p53′ expression. Our study demonstrated that milk-derived exosomes can facilitate intestinal cell proliferation and intestinal tract development, thus giving a new insight for milk nutrition and newborn development and health.
Ce3+/Yb3+/Er3+ triply doped bismuth borosilicate glass: a potential fiber material for broadband near-infrared fiber amplifiers
Authors: Chu Yushi , Ren Jing , Zhang Jianzhong , Peng Gangding , Yang Jun , Wang Pengfei , Yuan Libo 
Published: September 2016

AbstractErbium doped bismuth borosilicate (BBS) glasses, possessing the broadest 1.55 μm near infrared (NIR) emission band among oxide glasses, stand out as excellent fiber material for optical fiber amplifiers. In this work, we demonstrate that both broadened and enhanced NIR emission of Er3+ can be obtained by sensibly combining the effects such as mixed glass former effect, phonon-assisted energy transfer (PAET) and de-excitation effect induced by codopant. Specially, by codoping CeO2 in a controlled manner, it leads to not only much improved optical quality of the glasses, enhanced NIR emission, but also significantly suppressed energy transfer up-conversion (ETU) luminescence which is detrimental to the NIR emission. Cerium incorporated in the glasses exists overwhelmingly as the trivalent oxidation state Ce3+ and its effects on the luminescence properties of Er3+ are discussed. Judd-Ofelt analysis is used to evaluate gain amplification of the glasses. The result indicates that Ce3+/Yb3+/Er3+ triply doped BBS glasses are promising candidate for erbium doped fiber amplifiers. The strategy described here can be readily extended to other rare-earth ions (REs) to improve the performance of REs doped fiber lasers and amplifiers.
Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV
Authors: Jha S , Dong B E , Xue Y , Delotterie D F , Vail M G , Sakata K 
Published: September 2016

AbstractReduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.
Functional analysis of molecular interactions in synthetic auxin response circuits
Authors: Pierre-Jerome Edith , Moss Britney L. , Lanctot Amy , Hageman Amber , Nemhauser Jennifer L. 
Published: September 2016

Significance
Auxin-regulated transcription plays a role in almost every aspect of plant growth and development. Recent structural studies of domains from auxin-activated transcription factors and auxin-degraded repressors have raised fundamental questions about the protein complexes required for auxin response. Here, we leverage the power of a synthetic yeast system to identify and systematically characterize the simplest auxin response unit in the absence of the potentially confounding influence of other family members and interacting pathways.