bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall
Authors: Liu Xiaoping , El-Mahdy Mohamed A. , Boslett James , Varadharaj Saradhadevi , Hemann Craig , Abdelghany Tamer M. , Ismail Raed S. , Little Sean C. , Zhou Danlei , Thuy Le Thi Thanh , Kawada Norifumi , Zweier Jay L. 
Published: April 2017

AbstractThe identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease.
Effects of walnut oil on lipid profiles in hyperlipidemic type 2 diabetic patients: a randomized, double-blind, placebo-controlled trial
Authors: Zibaeenezhad M J , Farhadi P , Attar A , Mosleh A , Amirmoezi F , Azimi A 
Published: April 2017

Abstract
Background:
The role of herbal medicine is now well documented in preventing and controlling diabetes mellitus. The main aim of this study was to evaluate the effects of walnut oil consumption on lipid profiles of hyperlipidemic patients with type 2 diabetes.

Methods:
In a randomized, double-blind, placebo-controlled clinical trial, 100 hyperlipidemic type 2 diabetic patients aged 35–75 years were assigned to receive 15 cc Persian walnut oil or placebo every day for 90 days. The primary outcomes were the lipid profiles.

Results:
Consumption of walnut oil by type 2 hyperlipidemic diabetic patients resulted in a significant decrease in total cholesterol levels (treatment difference (TD)=−30.04, P<0.001), triglyceride (TG) level (TD=−15.04, P=0.021), low-density lipoprotein (LDL) level (TD=−30.44, P<0.001) and total cholesterol to high-density lipoprotein (HDL) ratio (TD=−0.72, P<0.001) compared to the control group. There was a trend toward increasing HDL level with consumption of walnut oil (TD=2.28, P=0.06). Frequency of patients reaching a LDL level below 100 was higher in the case group (20 vs 0%).

Conclusions:
Addition of walnut oil in the daily diet of type 2 diabetic patients improves lipid profiles. Thus, it may be associated with a coronary artery disease risk factor modulation. Also, walnut oil may serve as a helpful natural remedy for hyperlipidemic patients with type 2 diabetes.
Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner
Authors: Wamsley J J , Gary C , Biktasova A , Hajek M , Bellinger G , Virk R , Issaeva N , Yarbrough W G 
Published: April 2017

AbstractChemotherapy and radiation, the two most common cancer therapies, exert their anticancer effects by causing damage to cellular DNA. However, systemic treatment damages DNA not only in cancer, but also in healthy cells, resulting in the progression of serious side effects and limiting efficacy of the treatment. Interestingly, in response to DNA damage, p53 seems to play an opposite role in normal and in the majority of cancer cells—wild-type p53 mediates apoptosis in healthy tissues, attributing to the side effects, whereas mutant p53 often is responsible for acquired cancer resistance to the treatment. Here, we show that leucine zipper-containing ARF-binding protein (LZAP) binds and stabilizes p53. LZAP depletion eliminates p53 protein independently of its mutation status, subsequently protecting wild-type p53 cells from DNA damage-induced cell death, while rendering cells expressing mutant p53 more sensitive to the treatment. In human non-small-cell lung cancer, LZAP levels correlated with p53 levels, suggesting that loss of LZAP may represent a novel mechanism of p53 inactivation in human cancer. Our studies establish LZAP as a p53 regulator and p53-dependent determinative of cell fate in response to DNA damaging treatment.
Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression
Authors: Tseng H-Y , Chen Y-A , Jen J , Shen P-C , Chen L-M , Lin T-D , Wang Y-C , Hsu H-L 
Published: April 2017

AbstractTumor cells often produce high levels of reactive oxygen species (ROS) and display an increased ROS scavenging system. However, the molecular mechanism that balances antioxidative and oxidative stress in cancer cells is unclear. Here, we determined that oncogenic multiple copies in T-cell malignancy 1 (MCT-1) activity promotes the generation of intracellular ROS and mitochondrial superoxide. Overexpression of MCT-1 suppresses p53 accumulation but elevates the manganese-dependent superoxide dismutase (MnSOD) level via the YY1-EGFR signaling cascade, which protects cells against oxidative damage. Conversely, restricting ROS generation and/or targeting YY1 in lung cancer cells effectively inhibits the EGFR-MnSOD signaling pathway and cell invasiveness induced by MCT-1. Significantly, MCT-1 overexpression in lung cancer cells promotes tumor progression, necrosis and angiogenesis, and increases the number of tumor-promoting M2 macrophages and cancer-associated fibroblasts in the microenvironment. Clinical evidence further confirms that high expression of MCT-1 is associated with an increase in YY1, EGFR and MnSOD expression, accompanied by tumor recurrence, poor overall survival and EGFR mutation status in patients with lung cancers. Together, these data indicate that the MCT-1 oncogenic pathway is implicated in oxidative metabolism and lung carcinogenesis.
Twist1/Dnmt3a and miR186 establish a regulatory circuit that controls inflammation-associated prostate cancer progression
Authors: Zhao X , Deng R , Wang Y , Zhang H , Dou J , Li L , Du Y , Chen R , Cheng J , Yu J 
Published: April 2017

AbstractIncreasing evidences suggest that inflammatory microenvironment has a crucial role in prostate cancer (PCa) progression; however, the underlying mechanisms are unclear. Here, we used the inflammation-associated prostate cellular transformation model to screen out a crucial microRNA, miR186, which was significantly downregulated in the transformed cells and effectively rescued the transformed phenotype. On stimulation of inflammatory cytokines, the activated nuclear factor kappa B (NF-κB)/p65 was able to induce miR186 expression through binding to its promoter in non-transformed cells, whereas this pathway was lost in transformed cells. Interestingly, Twist1, which is a reported downstream target of miR186, was responsible for the loss of NF-κB/p65-miR186 pathway. Twist1 downregulated miR186 expression in a novel negative feedback loop binding to the E-box and simultaneously recruiting Dnmt3a, which facilitated the site-specific CpG methylation of the miR186 promoter, thereby blocked the transcriptional activity of NF-κB/p65 and the responsiveness of miR186 to inflammatory signals. The high level of Twist1 triggered this feedback loop that underlies the epigenetic switch, which was essential for maintaining transformed and advanced PCa state. Finally, our clinical data confirmed that the CpG methylation and miR186 expression levels were closely related with inflammation-associated human PCa progression.
MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation
Authors: Jin X , Pan Y , Wang L , Zhang L , Ravichandran R , Potts P R , Jiang J , Wu H , Huang H 
Published: April 2017

AbstractHepatocellular carcinoma (HCC) is one of the leading cause of cancer death in the world. Fructose-1,6-biphosphatase (FBP1), a rate-limiting enzyme in gluconeogenesis, has been identified recently as a tumor suppressor in HCC and other cancer types. In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28. We further showed that expression of TRIM28 increased glucose consumption and lactate production by promoting FBP1 degradation in HCC cells and that FBP1 is a key mediator of TRIM28-induced HCC growth in culture and in mice. Moreover, we demonstrated that FBP1 and TRIM28 protein levels inversely correlated in HCC patient specimens. Finally, we showed that the proteasome inhibitor bortezomib mitigated the Warburg effect by inhibiting FBP1 degradation in HCC. Collectively, our findings not only identify oncogenic MAGE-TRIM28 complex-mediated proteasome degradation of FBP1 as a key mechanism underlying downregulation of FBP1 proteins in HCC, but also reveal that MAGE-TRIM28-regulated reprogramming of cancer cell metabolism and HCC tumorigenesis is mediated, at least in part, through FBP1 degradation.
The Breathing, Thinking, Functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease
Authors: Spathis Anna , Booth Sara , Moffat Catherine , Hurst Rhys , Ryan Richella , Chin Chloe , Burkin Julie 
Published: April 2017

AbstractRefractory breathlessness is a highly prevalent and distressing symptom in advanced chronic respiratory disease. Its intensity is not reliably predicted by the severity of lung pathology, with unhelpful emotions and behaviours inadvertently exacerbating and perpetuating the problem. Improved symptom management is possible if clinicians choose appropriate non-pharmacological approaches, but these require engagement and commitment from both patients and clinicians. The Breathing Thinking Functioning clinical model is a proposal, developed from current evidence, that has the potential to facilitate effective symptom control, by providing a rationale and focus for treatment.
Energy-efficient quantum computing
Authors: Ikonen Joni , Salmilehto Juha , Möttönen Mikko 
Published: April 2017

AbstractIn the near future, one of the major challenges in the realization of large-scale quantum computers operating at low temperatures is the management of harmful heat loads owing to thermal conduction of cabling and dissipation at cryogenic components. This naturally raises the question that what are the fundamental limitations of energy consumption in scalable quantum computing. In this work, we derive the greatest lower bound for the gate error induced by a single application of a bosonic drive mode of given energy. Previously, such an error type has been considered to be inversely proportional to the total driving power, but we show that this limitation can be circumvented by introducing a qubit driving scheme which reuses and corrects drive pulses. Specifically, our method serves to reduce the average energy consumption per gate operation without increasing the average gate error. Thus our work shows that precise, scalable control of quantum systems can, in principle, be implemented without the introduction of excessive heat or decoherence.
Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal
Authors: González Raquel , Moffatt Garrett , Hagner Andrew , Sinha Sarthak , Shin Wisoo , Rahmani Waleed , Chojnacki Andrew , Biernaskie Jeff 
Published: April 2017

AbstractHair follicle regeneration is dependent on reciprocal signaling between epithelial cells and underlying mesenchymal cells within the dermal papilla. Hair follicle dermal stem cells reside within the hair follicle mesenchyme, self-renew in vivo, and function to repopulate the dermal papilla and regenerate the connective tissue sheath with each hair cycle. The identity and temporal pattern of signals that regulate hair follicle dermal stem cell function are not known. Here, we show that platelet-derived growth factor signaling is crucial for hair follicle dermal stem cell function and platelet-derived growth factor deficiency results in a progressive depletion of the hair follicle dermal stem cell pool and their progeny. Using αSMACreER
T2
:Rosa
YFP
:Pdgfrα
flox
mice, we ablated Pdgfrα specifically within the adult hair follicle dermal stem cell lineage. This led to significant loss of hair follicle dermal stem cell progeny in connective tissue sheath and dermal papilla of individual follicles, and a progressive reduction in total number of anagen hair follicles containing YFP+ve cells. As well, over successive hair cycles, fewer hair follicle dermal stem cells were retained within each telogen hair follicle suggesting an impact on hair follicle dermal stem cell self-renewal. To further assess this, we grew prospectively isolated hair follicle dermal stem cells (Sox2GFP+ve αSMAdsRed+ve) in the presence or absence of platelet-derived growth factor ligands. Platelet-derived growth factor-BB enhanced proliferation, increased the frequency of Sox2+ve hair follicle dermal stem cell progeny and improved inductive capacity of hair follicle dermal stem cells in an ex vivo hair follicle formation assay. Similar effects on proliferation were observed in adult human SKPs. Our findings impart novel insights into the signals that comprise the adult hair follicle dermal stem cell niche and suggest that platelet-derived growth factor signaling promotes self renewal, is essential to maintain the hair follicle dermal stem cell pool and ultimately their regenerative capacity within the hair follicle.
Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop
Authors: Cobbaut Mathias , Derua Rita , Döppler Heike , Lou Hua Jane , Vandoninck Sandy , Storz Peter , Turk Benjamin E. , Seufferlein Thomas , Waelkens Etienne , Janssens Veerle , Van Lint Johan 
Published: April 2017

AbstractProtein kinases are essential molecules in life and their crucial function requires tight regulation. Many kinases are regulated via phosphorylation within their activation loop. This loop is embedded in the activation segment, which additionally contains the Mg2+ binding loop and a P + 1 loop that is important in substrate binding. In this report, we identify Abl-mediated phosphorylation of a highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during oxidative stress. Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loop Tyr phosphorylation and we identify one of the molecular determinants for this divergence. This is paralleled by a different activation mechanism of PKD1 and PKD2 during oxidative stress. Tyr phosphorylation in the P + 1 loop of PKD2 increases turnover for Syntide-2, while substrate specificity and the role of PKD2 in NF-κB signaling remain unaffected. Importantly, Tyr to Phe substitution renders the kinase inactive, jeopardizing its use as a non-phosphorylatable mutant. Since large-scale proteomics studies identified P + 1 loop Tyr phosphorylation in more than 70 Ser/Thr kinases in multiple conditions, our results do not only demonstrate differential regulation/function of PKD isoforms under oxidative stress, but also have implications for kinase regulation in general.
Male New Zealand robins (Petroica longipes) cater to their mate’s desire when sharing food in the wild
Authors: Shaw Rachael C. , MacKinlay Regan D. , Clayton Nicola S. , Burns Kevin C. 
Published: April 2017

AbstractIn many species that have bi-parental care, food-sharing males provide vital nutritional resources to their mates during reproduction. However, it is currently unknown whether females can signal specific desires to their mates, or if males can cater to female desire in the wild. Here we investigate whether and how wild male North Island robins (Petroica longipes) respond to changes in their mates’ desires and nutritional need when sharing food. We demonstrate that wild female robins’ desire for particular foods changes over short time periods; when given the choice between two types of insect larvae, females prefer the type they have not recently eaten. In our experiments, wild male robins preferentially shared the larvae type that their mate was most likely to desire and also increased the quantity of food shared if she had begun incubating. Males catered to their mates’ desire when female behaviour was the only cue available to guide their choices. This is the first evidence that females may behaviourally communicate their specific food desires to their mates, enabling males to cater to fine-scale changes in their mates’ nutritional requirements in the wild. Such a simple behaviour-reading mechanism has the potential to be widespread among other food-sharing species.
Balancing Speed and Coverage by Sequential Seeding in Complex Networks
Authors: Jankowski Jarosław , Bródka Piotr , Kazienko Przemysław , Szymanski Boleslaw K. , Michalski Radosław , Kajdanowicz Tomasz 
Published: April 2017

AbstractInformation spreading in complex networks is often modeled as diffusing information with certain probability from nodes that possess it to their neighbors that do not. Information cascades are triggered when the activation of a set of initial nodes – seeds – results in diffusion to large number of nodes. Here, several novel approaches for seed initiation that replace the commonly used activation of all seeds at once with a sequence of initiation stages are introduced. Sequential strategies at later stages avoid seeding highly ranked nodes that are already activated by diffusion active between stages. The gain arises when a saved seed is allocated to a node difficult to reach via diffusion. Sequential seeding and a single stage approach are compared using various seed ranking methods and diffusion parameters on real complex networks. The experimental results indicate that, regardless of the seed ranking method used, sequential seeding strategies deliver better coverage than single stage seeding in about 90% of cases. Longer seeding sequences tend to activate more nodes but they also extend the duration of diffusion. Various variants of sequential seeding resolve the trade-off between the coverage and speed of diffusion differently.
The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells
Authors: Hiramatsu Hiroaki , Kobayashi Kazuyoshi , Kobayashi Kyousuke , Haraguchi Takeshi , Ino Yasushi , Todo Tomoki , Iba Hideo 
Published: April 2017

AbstractGlioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs. The serum-induced differentiation of GICs downregulated the endogenous expression of DPF1 and DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming ability and tumor-forming activity in a mouse xenograft model. Rescue experiments revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have previously reported that d4-family members can function as adaptor proteins between the SWI/SNF complex and NF-κB dimers, this does not significantly contribute to maintaining the stemness properties of GICs. Instead, these proteins were found to link a corepressor complex containing the nuclear receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our results indicate that DPF1 and DPF3a are potential therapeutic targets for glioblastoma.
Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
Authors: Garza-Cervantes Javier A. , Chávez-Reyes Arturo , Castillo Elena C. , García-Rivas Gerardo , Antonio Ortega-Rivera Oscar , Salinas Eva , Ortiz-Martínez Margarita , Gómez-Flores Sara Leticia , Peña-Martínez Jorge A. , Pepi-Molina Alan , Treviño-González Mario T. , Zarate Xristo , Elena Cantú-Cárdenas María , Enrique Escarcega-Gonzalez Carlos , Morones-Ramírez J. Rubén 
Published: April 2017

AbstractDue to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.
Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
Authors: Han Seungrie , Yang Soo Hyun , Kim Jin Yong , Mo Seojung , Yang Esther , Song Ki Myung , Ham Byung-Joo , Mechawar Naguib , Turecki Gustavo , Lee Hyun Woo , Kim Hyun 
Published: April 2017

AbstractDysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).