bluuebunny/crossref_metadata_2025_split huggingface dataset:
The plant defensin NaD1 induces tumor cell death via a non-apoptotic, membranolytic process
Authors: Baxter Amy A , Poon Ivan KH , Hulett Mark D 
Published: January 2017

AbstractCationic anti-microbial peptides (CAPs) have an important role in host innate defense against pathogens such as bacteria and fungi. Many CAPs including defensins also exhibit selective cytotoxic activity towards mammalian cells via both apoptotic and non-apoptotic processes, and are being investigated as potential anticancer agents. The anti-fungal plant defensin from ornamental tobacco, Nicotiana alata Defensin 1 (NaD1), was recently shown to induce necrotic-like cell death in a number of tumor cell types within 30 min of treatment, at a concentration of 10 μM. NaD1-mediated cell killing within these experimental parameters has been shown to occur via binding to the plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) in target cells to facilitate membrane destabilization and subsequent lysis. Whether NaD1 is also capable of inducing apoptosis in tumor cells has not been reported previously. In this study, treatment of MM170 (melanoma) and Jurkat T (leukemia) cells with subacute (<10 μM) concentrations of NaD1 over 6–24 h was investigated to determine whether NaD1 could induce cell death via apoptosis. At subacute concentrations, NaD1 did not efficiently induce membrane permeabilization within 30 min, but markedly reduced cell viability over 24 h. In contrast to other CAPs that have been shown to induce apoptosis through caspase activation, dying cells were not sensitive to a pancaspase inhibitor nor did they display caspase activity or DNA fragmentation over the 24 h treatment time. Furthermore, over the 24 h period, cells exhibited necrotic phenotypes and succumbed to membrane permeabilization. These results indicate that the cytotoxic mechanism of NaD1 at subacute concentrations is membranolytic rather than apoptotic and is also likely to be mediated through a PIP2-targeting cell lytic pathway.
Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites
Authors: Braig David , Nero Tracy L. , Koch Hans-Georg , Kaiser Benedict , Wang Xiaowei , Thiele Jan R. , Morton Craig J. , Zeller Johannes , Kiefer Jurij , Potempa Lawrence A. , Mellett Natalie A. , Miles Luke A. , Du Xiao-Jun , Meikle Peter J. , Huber-Lang Markus , Stark G. Björn , Parker Michael W. , Peter Karlheinz , Eisenhardt Steffen U. 
Published: January 2017

AbstractC-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions.
MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes
Authors: Liu Can , Liu Ruifang , Zhang Dingxiao , Deng Qu , Liu Bigang , Chao Hsueh-Ping , Rycaj Kiera , Takata Yoko , Lin Kevin , Lu Yue , Zhong Yi , Krolewski John , Shen Jianjun , Tang Dean G. 
Published: January 2017

AbstractMicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44+ and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis.
Combined immunotherapy with “anti-insulin resistance” therapy as a novel therapeutic strategy against neurodegenerative diseases
Authors: Takamatsu Yoshiki , Ho Gilbert , Koike Wakako , Sugama Shuei , Takenouchi Takato , Waragai Masaaki , Wei Jianshe , Sekiyama Kazunari , Hashimoto Makoto 
Published: January 2017

AbstractProtein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer’s disease, followed by similar studies of α-synuclein in Parkinson’s disease. Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer’s disease, but also for other neurodegenerative disorders, including Parkinson’s disease. Thus, it is expected that further refinement of immunotherapy against neurodegenerative diseases may lead to increasing efficacy. Meanwhile, type II diabetes mellitus has been associated with an increased risk of neurodegenerative disease, such as Alzheimer’s disease and Parkinson’s disease, and studies have shown that metabolic dysfunction and abnormalities surrounding insulin signaling may underlie disease progression. Naturally, “anti-insulin resistance” therapy has emerged as a novel paradigm in the therapy of neurodegenerative diseases. Indeed, incretin agonists, which stimulate pancreatic insulin secretion, reduce dopaminergic neuronal loss and suppress Parkinson’s disease disease progression in clinical trials. Similar studies are ongoing also in Alzheimer’s disease. This paper focuses on critical issues in “immunotherapy” and “anti-insulin resistance” therapy in relation to therapeutic strategies against neurodegenerative disease, and more importantly, how they might merge mechanistically at the point of suppression of protein aggregation, raising the possibility that combined immunotherapy and “anti-insulin resistance” therapy may be superior to either monotherapy.
An algorithm recommendation for the pharmacological management of allergic rhinitis in the UK: a consensus statement from an expert panel
Authors: Lipworth Brian , Newton Jon , Ram Bhaskar , Small Iain , Schwarze Jürgen 
Published: January 2017

AbstractAllergic rhinitis is a frequent presenting problem in primary care in the UK, and has increased in prevalence over the last 30 years. When symptomatic, patients report significant reduction in their quality of life and impairment in school and work performance. Achieving adequate symptom control is pivotal to successful allergic rhinitis management, and relies mostly on pharmacotherapy. While it is recognised that most mild-moderate allergic rhinitis symptoms can be managed successfully in primary care, important gaps in general practitioner training in relation to allergic rhinitis have been identified. With the availability of new effective combination therapies, such as the novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (Dymista®; Meda), the majority of allergic rhinitis symptoms can be treated in the primary care setting. The primary objective of this consensus statement is to improve diagnosis and treatment of allergic rhinitis in primary care, and offer guidance on appropriate referral of difficult-to-treat patients into secondary care. The guidance provided herein outlines a sequential treatment pathway for allergic rhinitis in primary care that incorporates a considered approach to improve the management of allergic rhinitis symptoms and improve compliance and patient satisfaction with therapy. Adherence with this care pathway has the potential to limit the cost of providing effective allergic rhinitis management in the UK by avoiding unnecessary treatments and investigations, and avoiding the need for costly referrals to secondary care in the majority of allergic rhinitis cases. The fundamentals presented in this consensus article should apply in most health-care settings.
Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity
Authors: Stephen J. , Scales H. E. , Benson R. A. , Erben D. , Garside P. , Brewer J. M. 
Published: January 2017

AbstractThere are over 6 billion vaccine doses administered each year, most containing aluminium-based adjuvants, yet we still do not have a complete understanding of their mechanisms of action. Recent evidence has identified host DNA and downstream sensing as playing a significant role in aluminium adjuvant (aluminium hydroxide) activity. However, the cellular source of this DNA, how it is sensed by the immune system and the consequences of this for vaccination remains unclear. Here we show that the very early injection site reaction is characterised by inflammatory chemokine production and neutrophil recruitment. Intravital imaging demonstrates that the Alum injection site is a focus of neutrophil swarms and extracellular DNA strands. These strands were confirmed as neutrophil extracellular traps due to their sensitivity to DNAse and absence in mice deficient in peptidylarginine deiminase 4. Further studies in PAD4−/− mice confirmed a significant role for neutrophil extracellular trap formation in the adjuvant activity of Alum. By revealing neutrophils recruited to the site of Alum injection as a source of the DNA that is detected by the immune system this study provides the missing link between Alum injection and the activation of DNA sensors that enhance adjuvant activity, elucidating a key mechanism of action for this important vaccine component.
Dynamics of Bemisia tabaci biotypes and insecticide resistance in Fujian province in China during 2005–2014
Authors: Yao Feng-Luan , Zheng Yu , Huang Xiao-Yan , Ding Xue-Ling , Zhao Jian-Wei , Desneux Nicolas , He Yu-Xian , Weng Qi-Yong 
Published: January 2017

AbstractThe whitefly Bemisia tabaci (Gennadius) is an important agricultural insect pest worldwide. The B and Q biotypes are the two most predominant and devastating biotypes prevalent across China. However, there are few studies regarding the occurrence of the Q biotype in Fujian Province, China, where high insecticide resistance has been reported in the B biotype. Differences in some biological characteristics between the B and Q biotypes, especially insecticide resistance, are considered to affect the outcome of their competition. Extensive surveys in Fujian revealed that the B biotype was predominant during 2005–2014, whereas the Q biotype was first detected in some locations in 2013 and widely detected throughout the province in 2014. Resistance to neonicotinoids (that have been used for more than 10 years) exhibited fluctuations in open fields, but showed a continual increasing trend in protected areas. Resistance to lambda-cyhalothrin, chlorpyrifos, and abamectin exhibited a declining trend. Resistance to novel insecticides, such as nitenpyram, pymetrozine, sulfoxaflor, and cyantraniliprole, in 2014 was generally below a moderate level. A decline in insecticide resistance in the B biotype and the rapid buildup of protected crops under global temperature increase may have promoted the establishment of the Q biotype in Fujian.
Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye
Authors: Gardner Peter J. , Liyanage Sidath E. , Cristante Enrico , Sampson Robert D. , Dick Andrew D. , Ali Robin R. , Bainbridge James W. 
Published: January 2017

AbstractHypoxia inducible factors (HIFs) are ubiquitously expressed transcription factors important for cell homeostasis during dynamic oxygen levels. Myeloid specific HIFs are crucial for aspects of myeloid cell function, including their ability to migrate into inflamed tissues during autoimmune disease. This contrasts with the concept that accumulation of myeloid cells at ischemic and hypoxic sites results from a lack of chemotactic responsiveness. Here we seek to address the role of HIFs in myeloid trafficking during inflammation in a mouse model of human uveitis. We show using mice with myeloid-specific Cre-deletion of HIFs that myeloid HIFs are dispensable for leukocyte migration into the inflamed eye. Myeloid-specific deletion of Hif1a, Epas1, or both together, had no impact on the number of myeloid cells migrating into the eye. Additionally, stabilization of HIF pathways via deletion of Vhl in myeloid cells had no impact on myeloid trafficking into the inflamed eye. Finally, we chemically induce hypoxemia via hemolytic anemia resulting in HIF stabilization within circulating leukocytes to demonstrate the dispensable role of HIFs in myeloid cell migration into the inflamed eye. These data suggest, contrary to previous reports, that HIF pathways in myeloid cells during inflammation and hypoxia are dispensable for myeloid cell tissue trafficking.
Electronic State of Sodium trans-[Tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) in Tumor, Liver and Kidney Tissue of a SW480-bearing Mouse
Authors: Blazevic Amir , Hummer Alfred A. , Heffeter Petra , Berger Walter , Filipits Martin , Cibin Giannantonio , Keppler Bernhard K. , Rompel Annette 
Published: January 2017

AbstractRuthenium complexes are promising candidates for anticancer agents, especially NKP-1339 (sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]), which is on the edge to clinical applications. The anticancer mechanism seems to be tightly linked to the redox chemistry but despite progress in human clinical trials the in vivo Ru oxidation state and the coordination of Ru remains unclear. The Ru-based anticancer drug NKP-1339 was studied applying XANES (Cl K- and Ru L2,3-edges) in tumor, kidney and liver tissue of a SW480 bearing mouse. Based on coordination charge and 3D XANES plots containing a series of model compounds as well as pre-edge analysis of the ligand Cl K-edge it is suggested that NKP-1339 remains in its +III oxidation state after 24 hours and at least one of the four chlorido ligands remain covalently bound to the Ru ion showing a biotransformation from RuIIIN2Cl4 to RuIIIClx(N/O)6−x (X = 1 or 2).
Cyclin I-like (CCNI2) is a cyclin-dependent kinase 5 (CDK5) activator and is involved in cell cycle regulation
Authors: Liu Chengcheng , Zhai Xiaoyan , Zhao Bin , Wang Yanfei , Xu Zhigang 
Published: January 2017

AbstractIn contrast to conventional cyclin-dependent kinases that are important for mitotic cell division, cyclin-dependent kinase 5 (CDK5) is predominantly activated in post-mitotic cells and is involved in various cellular events. The kinase activity of CDK5 is tightly regulated by specific activators including p35, p39, and cyclin I (CCNI). Here we show that cyclin I-like (CCNI2), a homolog of CCNI, interacts with CDK5 and activates the kinase activity of CDK5. Different from CCNI, which colocalizes with CDK5 in the nuclei in transfected cells, CCNI2 mainly retains CDK5 in the cytoplasm as well as on the cell membrane. Furthermore, although the expression level of CCNI2 mRNA and CCNI2 protein do not change significantly during cell cycle, depletion of CCNI2 with siRNA affects cell cycle progression as well as cell proliferation. In conclusion, our data strongly suggest that CCNI2 is a novel CDK5 activator and is involved in cell cycle regulation.
Serum vitamin D, intact parathyroid hormone, and Fetuin A concentrations were associated with geriatric sarcopenia and cardiac hypertrophy
Authors: Chang Wei-Ting , Wu Chih-Hsing , Hsu Ling-Wei , Chen Po-Wei , Yu Jia-Rong , Chang Chin-Sung , Tsai Wei-Chuan , Liu Ping-Yen 
Published: January 2017

AbstractWith aging, intact parathyroid hormone (iPTH) increases. It plays a crucial role in left ventricular hypertrophy (LVH). Also, 25-hydroxy vitamin D (Vit-D) and iPTH have been observed to be determinants of muscle wasting known as sarcopenia. Fetuin A (FetA), a systemic calcification inhibitor, involves in the development of diastolic heart failure. Hence, we hypothesized that the interplay among FetA, Vit-D and iPTH may contribute to sarcopenic LVH among the elders. We analyzed a database from the Tianliao Old People study with 541 elders (≥65 years) in a Taiwan’s suburban community. After excluding patients with renal function impairment, 120/449 (26.7%) patients were diagnosed with sarcopenia. Sarcopenic patients had lower serum Vit-D levels but higher FetA as well as iPTH. Notably, sarcopenic patients with LVH had significantly lower FetA and higher iPTH levels. In multivariate logistic regression analysis, only the increase in iPTH was independently associated with sarcopenic LVH (Odds ratio: 1.05; confidence interval: 1.03–1.08, p = 0.005). Using iPTH >52.3 ng/l as a cutoff point, the sensitivity and specificity was 66% and 84%, respectively. In conclusion, FetA, Vit-D, and iPTH levels were all associated with sarcopenia in this geriatric population. Among them, iPTH specifically indicates patients with sarcopenic LVH.
Neutron Radiation Tolerance of Two Benchmark Thiophene-Based Conjugated Polymers: the Importance of Crystallinity for Organic Avionics
Authors: Paternò G. M. , Robbiano V. , Fraser K. J. , Frost C. , García Sakai V. , Cacialli F. 
Published: January 2017

AbstractAviation and space applications can benefit significantly from lightweight organic electronics, now spanning from displays to logics, because of the vital importance of minimising payload (size and mass). It is thus crucial to assess the damage caused to such materials by cosmic rays and neutrons, which pose a variety of hazards through atomic displacements following neutron-nucleus collisions. Here we report the first study of the neutron radiation tolerance of two poly(thiophene)s-based organic semiconductors: poly(3-hexylthiophene-2,5-diyl), P3HT, and the liquid-crystalline poly(2,5-bis (3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene), PBTTT. We combine spectroscopic investigations with characterisation of intrinsic charge mobility to show that PBTTT exhibits significantly higher tolerance than P3HT. We explain this in terms of a superior chemical, structural and conformational stability of PBTTT, which can be ascribed to its higher crystallinity, in turn induced by a combination of molecular design features. Our approach can be used to develop design strategies for better neutron radiation-tolerant materials, thus paving the way for organic semiconductors to enter avionics and space applications.
Evidence for Intramolecular Antiparallel Beta-Sheet Structure in Alpha-Synuclein Fibrils from a Combination of Two-Dimensional Infrared Spectroscopy and Atomic Force Microscopy
Authors: Roeters Steven J. , Iyer Aditya , Pletikapić Galja , Kogan Vladimir , Subramaniam Vinod , Woutersen Sander 
Published: January 2017

AbstractThe aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson’s disease. Using a combination of techniques (AFM, UV-CD, XRD, and amide-I 1D- and 2D-IR spectroscopy) we show that the structure of αS fibrils varies as a function of ionic strength: fibrils aggregated in low ionic-strength buffers ([NaCl] ≤ 25 mM) have a significantly different structure than fibrils grown in higher ionic-strength buffers. The observations for fibrils aggregated in low-salt buffers are consistent with an extended conformation of αS molecules, forming hydrogen-bonded intermolecular β-sheets that are loosely packed in a parallel fashion. For fibrils aggregated in high-salt buffers (including those prepared in buffers with a physiological salt concentration) the measurements are consistent with αS molecules in a more tightly-packed, antiparallel intramolecular conformation, and suggest a structure characterized by two twisting stacks of approximately five hydrogen-bonded intermolecular β-sheets each. We find evidence that the high-frequency peak in the amide-I spectrum of αS fibrils involves a normal mode that differs fundamentally from the canonical high-frequency antiparallel β-sheet mode. The high sensitivity of the fibril structure to the ionic strength might form the basis of differences in αS-related pathologies.
Multi-omics analyses reveal metabolic alterations regulated by hepatitis B virus core protein in hepatocellular carcinoma cells
Authors: Xie Qi , Fan Fengxu , Wei Wei , Liu Yang , Xu Zhongwei , Zhai Linhui , Qi Yingzi , Ye Bingyu , Zhang Yao , Basu Sumit , Zhao Zhihu , Wu Junzhu , Xu Ping 
Published: January 2017

AbstractChronic hepatitis B virus (HBV) infection is partly responsible for hepatitis, fatty liver disease and hepatocellular carcinoma (HCC). HBV core protein (HBc), encoded by the HBV genome, may play a significant role in HBV life cycle. However, the function of HBc in the occurrence and development of liver disease is still unclear. To investigate the underlying mechanisms, HBc-transfected HCC cells were characterized by multi-omics analyses. Combining proteomics and metabolomics analyses, our results showed that HBc promoted the expression of metabolic enzymes and the secretion of metabolites in HCC cells. In addition, glycolysis and amino acid metabolism were significantly up-regulated by HBc. Moreover, Max-like protein X (MLX) might be recruited and enriched by HBc in the nucleus to regulate glycolysis pathways. This study provides further insights into the function of HBc in the molecular pathogenesis of HBV-induced diseases and indicates that metabolic reprogramming appears to be a hallmark of HBc transfection.
Coherent Terahertz Radiation from Multiple Electron Beams Excitation within a Plasmonic Crystal-like structure
Authors: Zhang Yaxin , Zhou Yucong , Gang Yin , Jiang Guili , Yang Ziqiang 
Published: January 2017

AbstractCoherent terahertz radiation from multiple electron beams excitation within a plasmonic crystal-like structure (a three-dimensional holes array) which is composed of multiple stacked layers with 3 × 3 subwavelength holes array has been proposed in this paper. It has been found that in the structure the electromagnetic fields in each hole can be coupled with one another to construct a composite mode with strong field intensity. Therefore, the multiple electron beams injection can excite and efficiently interact with such mode. Meanwhile, the coupling among the electron beams is taken place during the interaction so that a very strong coherent terahertz radiation with high electron conversion efficiency can be generated. Furthermore, due to the coupling, the starting current density of this mechanism is much lower than that of traditional electron beam-driven terahertz sources. This multi-beam radiation system may provide a favorable way to combine photonics structure with electronics excitation to generate middle, high power terahertz radiation.