bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel leucine‐rich repeat protein, CaLRR51, acts as a positive regulator in the response of pepper toRalstonia solanacearuminfection
Authors: Cheng Wei , Xiao Zhuoli , Cai Hanyang , Wang Chuanqing , Hu Yang , Xiao Yueping , Zheng Yuxing , Shen Lei , Yang Sheng , Liu Zhiqin , Mou Shaoliang , Qiu Ailian , Guan Deyi , He Shuilin 
Published: July 2016

SummaryThe leucine‐rich repeat (LRR) proteins play important roles in the recognition of corresponding ligands and signal transduction networks in plant defence responses. Herein, a novel LRR protein fromCapsicum annuum, CaLRR51, was identified and characterized. It was localized to the plasma membrane and transcriptionally up‐regulated byRalstonia solanacearuminfection (RSI), as well as the exogenous application of salicylic acid (SA), jasmonic acid (JA) and ethephon (ETH). Virus‐induced gene silencing ofCaLRR51significantly increased the susceptibility of pepper to RSI. By contrast, transient overexpression ofCaLRR51in pepper plants activated hypersensitive response (HR)‐like cell death, and up‐regulated the defence‐related marker genes, includingPO2,HIR1,PR1,DEF1andACO1. Moreover, ectopic overexpression ofCaLRR51in transgenic tobacco plants significantly enhanced the resistance to RSI. Transcriptional expression of the corresponding defence‐related marker genes in transgenic tobacco plants was also found to be enhanced by the overexpression ofCaLRR51, which was potentiated by RSI. These loss‐ and gain‐of‐function assays suggest that CaLRR51 acts as a positive regulator in the response of pepper to RSI. In addition, the putative signal peptide and transmembrane region were found to be required for plasma membrane targeting of CaLRR51, which is indispensable for the role of CaLRR51 in plant immunity.
Different association between renal hyperfiltration and mortality by sex
Authors: Yoo Kyung Don , Yoon Hyung‐Jin , Hwang Seung‐sik , Heo Nam Ju , Chin Ho Jun , Yang Seung Hee , Joo Kwon Wook , Kim Yon Su , Lee Hajeong 
Published: July 2016

AbstractAimRenal hyperfiltration (RHF) is a marker of early kidney injury that was recently shown to be a novel marker of mortality. However, it has no clear definition. In this study, we suggested an age‐ and sex‐adjusted RHF definition and explored the association between RHF and mortality by sex.MethodsWe analyzed data from individuals receiving routine health examinations from 1995 to 2009. RHF was defined as an estimated glomerular filtration rate over the 95th percentile matched for age and sex.ResultsA total of 114 966 individuals were included. During the 75‐month of observation period, 2559 (2.2%) participants died. Among those, 71.4% were men. Because sex and RHF had a significant interaction for mortality (P for interaction < 0.001), we performed survival analysis according to sex. RHF was related to lower body weight and a higher proportion of cigarette smoking in men, whereas these relationships were not found in women. In the Kaplan–Meier curve, RHF was associated with higher mortality rate than non‐RHF in both sexes, but this relationship was more prominent in men. In the multivariate analysis, RHF remained as an independent risk factor for all‐cause mortality even after adjustment for confounding in men (hazard ratio, 1.34; 95% confidence interval, 1.12–1.59; P = 0.001). In women, RHF was not associated with increased mortality.ConclusionsWe demonstrated that RHF was a significant risk factor for mortality in men but not in women. The mechanisms and clinical implications of these different associations according to sex require a further clarification.
Muckle–Wells Syndrome: A Case Report with an NLRP3 T348M Mutation
Authors: Naz Villalba Elena , Gomez de la Fuente Enrique , Caro Gutierrez Dolores , Pinedo Moraleda Fernando , Yanguela Rodilla Julio , Mazagatos Angulo Diana , López Estebaranz Jose Luis 
Published: July 2016

AbstractAutoinflammatory syndromes are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin‐associated periodic syndromes are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticaria syndrome, Muckle–Wells syndrome (MWS), and neonatal‐onset multisystem inflammatory disease. MWS is characterized by a moderate phenotype with fever, rash, arthralgia, conjunctivitis, sensorineural deafness, and potentially life‐threatening amyloidosis. We report a 5‐year‐old girl with MWS that manifested as a recurrent skin rash without fever episodes or intracranial hypertension with papilledema. Genetic analysis revealed a T348M mutation of the NLRPR 3 gene in the patient and her mother. She was successfully treated with the interleukin‐1β antagonist receptor anakinra.
Effect of Angiofibromas on Quality of Life and Access to Care in Tuberous Sclerosis Patients and Their Caregivers
Authors: Crall Cary , Valle Molly , Kapur Kush , Dies Kira A. , Liang Marilyn G. , Sahin Mustafa , Huang Jennifer T. 
Published: July 2016

AbstractBackground/ObjectivesFacial angiofibromas (AF) have the potential to cause disfigurement in children with tuberous sclerosis complex (TSC). Facial disfigurement can impact the quality of life (QoL) of individuals and their families, leading to negative psychosocial outcomes. QoL has not been studied in TSC patients with AF.MethodsWe conducted a cross‐sectional survey study to investigate QoL of TSC patients with AF and their caregivers and to explore the current state of access to treatment for AF. TSC patients and caregivers in TSC clinic at Boston Children's Hospital and through the Tuberous Sclerosis Alliance were recruited to complete QoL surveys including the CADIS, CDLQI, and Skindex‐teen questionnaires, and a survey on access to treatment of AF.ResultsFifty‐eight patients with TSC and 161 caregivers participated in the study. Caregivers of patients with AF had significantly poorer QoL scores compared to caregivers of those without AF, as measured by a modified CADIS questionnaire (mean 31.7 vs. 11.7, p = 0.004). Among patients with AF, those who received treatment had significantly better QoL scores compared with those without treatment, as measured by the CDLQI (mean 3.8 vs. 9.5, p = 0.001). Forty‐one and two‐tenths percent of subjects reported never receiving treatment for AF. Forty‐seven and three‐tenths percent of subjects were prescribed topical rapamycin, 47.7% of whom experienced difficulty with insurance coverage.ConclusionsPresence and lack of treatment of AF significantly impacts QoL in TSC patients and their caregivers. Access to care for AF is limited by multiple factors and should be addressed by clinicians working with this patient population.
Influenza‐associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S‐deficient boy
Authors: Tsujii Nobuyuki , Nogami Keiji , Yoshizawa Hiroyuki , Hayakawa Masaki , Isonishi Ayami , Matsumoto Masanori , Shima Midori 
Published: July 2016

AbstractInfluenza infections often cause pneumonia, but there is limited information on thrombotic microangiopathy (TMA) in these circumstances. We report the case of an 11‐year‐old boy who developed TMA during the acute phase of H1N1 influenza. Plasma von Willebrand factor (VWF) was elevated, whereas a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was mildly reduced in the absence of ADAMTS13‐neutralizing autoantibody, resulting in low ratio of ADAMTS13 to VWF. The patient was treated intensively, including plasma exchange, and he recovered from the TMA. He developed pulmonary embolism (PE), however, after removal of the central venous catheter. The findings suggested that influenza‐associated cytokines enhanced the release of unusually large VWF multimers from vascular endothelial cells and promoted the formation of platelet thrombi and TMA. Subsequent analysis further indicated the presence of familial protein S deficiency, and it seemed likely that the PE was more related to this heterozygous protein S defect.
Diapause induction as an interplay between seasonal token stimuli, and modifying and directly limiting factors: hibernation in Chymomyza costata
Authors: Koštál Vladimír , Mollaei Maedeh , Schöttner Konrad 
Published: July 2016

AbstractLarvae of wild type (WT) strain of Chymomyza costata Zetterstedt (Diptera: Drosophilidae) enter diapause (stop developing) in response to short‐day signal at a constant 18 °C, whereas larvae of a non‐photoperiodic‐diapause (NPD) strain do not respond to photoperiodic signalling and continue in larval development irrespective of daylength. The present study shows that WT larvae also respond reliably to thermoperiodic signalling (daily cycles of temperature) under constant darkness, whereas the NPD larvae do not, suggesting that the pathways transducing the environmental token stimuli (photoperiod and thermoperiod) onto the diapause developmental programme might merge functionally in the central biological clock system known to be mutated in NPD strain. Temperature and larval population density modify the output of token stimuli signalling. High temperatures (>24 °C) tend to avert, whereas low temperatures (<18 °C), especially in combination with constant darkness, stimulate diapause induction in WT strain. Overcrowding (>200 larvae per 5 g of larval diet) lengthens the duration of larval development and induces a ‘diapause‐like’ developmental arrest of relatively weak intensity in up to 60% of larvae of both strains. At high temperatures (>30 °C), all WT larvae continue direct development but subsequently die during the pupal stage. Low temperature exposure (<12 °C) causes quiescence in the majority of the larvae of both strains. Starvation blocks development and causes mortality when applied in larvae younger than day 3 of the third instar. Older larvae survive starvation and their photoperiodically‐induced developmental pre‐programming is not affected. Collectively, the results show that diapause induction in C. costata is a result of various interacting effects of multiple environmental factors.
Phylogeny of the subfamilyLarentiinae (Lepidoptera:Geometridae): integrating molecular data and traditional classifications
Authors: ÕUNAP ERKI , VIIDALEPP JAAN , TRUUVERK ANDRO 
Published: July 2016

AbstractLarentiinae are the second largest subfamily ofGeometridae, with more than 6200 described species. Despite recent advances in molecular systematics of geometrid moths, phylogenetic relationships between the numerous subgroups ofLarentiinae are poorly known. In this study we present the most comprehensive attempt to date to resolve the phylogeny ofLarentiinae, having sampled at least one species from all currently recognized 23 tribes. Fragments of one mitochondrial (COI) and eight nuclear (EF‐1α,WGL,GAPDH,RPS5,IDH,MDH,CADand28S) genes were sequenced, for a total of 6939 bp. Maximum likelihood andBayesian analyses resulted in identical well‐resolved phylogenetic trees, which had maximum or near‐maximum support values at most nodes. Almost all conventionally recognized tribes represented by more than one genus were found to be monophyletic. Close to the root ofLarentiinae, six tribes branch off the main lineage one after another, withDyspteridini being sister to all other members of the subfamily. The rest of larentiines are divided into two very diverse lineages, comprising eight and at least ten tribes, respectively. There were just three findings incongruent with the conventional tribal subdivision of the subfamily. First, the generaCollixGuenée andAnticollixProut formed a separate, previously unrecognized but well‐supported clade at the tribe level. Second, thePalaearctic genusPelurgaHübner was placed apart fromLarentiaTreitschke andMesoleucaHübner, which were the other members ofLarentiini in this analysis. Third,Cataclysmini appeared together with genera belonging toXanthorhoini, leaving the latter paraphyletic. TheNeotropic genusOligopleuraHerrich‐Schäffer is shown to belong to the tribeEuphyiini (comb.n.) according to both molecular data and male genital morphology. The results and the tribal classification ofLarentiinae are discussed with reference to the principal publications since the end of the 19thCentury. We conclude that the current tribal classification ofLarentiinae is not controversial from the phylogenetic point of view and that its increasing complexity has merely reflected the accumulation of information, mainly through different methods of biosystematic study having become available for researchers. Our results indicate that diurnal lifestyle, accompanied by conspicuous coloration, has evolved independently in several subgroups ofLarentiinae.
Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus
Authors: Swanstrom J. A. , Plante J. A. , Plante K. S. , Young E. F. , McGowan E. , Gallichotte E. N. , Widman D. G. , Heise M. T. , de Silva A. M. , Baric R. S. 
Published: July 2016

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC
50
], <1:100 serum dilution; 18%) or moderate to high (EC
50
, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV.

IMPORTANCE
ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.
Transformations to granular zircon revealed: Twinning, reidite, and ZrO2 in shocked zircon from Meteor Crater (Arizona, USA)
Authors: Cavosie Aaron J. , Timms Nicholas E. , Erickson Timmons M. , Hagerty Justin J. , Hörz Friedrich 
Published: July 2016

Abstract
Granular zircon in impact environments has long been recognized but remains poorly understood due to lack of experimental data to identify mechanisms involved in its genesis. Meteor Crater in Arizona (USA) contains abundant evidence of shock metamorphism, including shocked quartz, the high-pressure polymorphs coesite and stishovite, diaplectic SiO2 glass, and lechatelierite (fused SiO2). Here we report the presence of granular zircon, a new shocked-mineral discovery at Meteor Crater, that preserve critical orientation evidence of specific transformations that occurred during formation at extreme impact conditions. The zircon grains occur as aggregates of sub-micrometer neoblasts in highly shocked Coconino Sandstone (CS) comprised of lechatelierite. Electron backscatter diffraction shows that each grain consists of multiple domains, some with boundaries disoriented by 65° around &lt;110&gt;, a known {112} shock-twin orientation. Other domains have {001} in alignment with {110} of neighboring domains, consistent with the former presence of the high-pressure ZrSiO4 polymorph reidite. Additionally, nearly all zircon preserve ZrO2 + SiO2, providing evidence of partial dissociation. The genesis of CS granular zircon started with detrital zircon that experienced shock twinning and reidite formation at pressures from 20 to 30 GPa, ultimately yielding a phase that retained crystallographic memory; this phase subsequently recrystallized to systematically oriented zircon neoblasts, and in some areas partially dissociated to ZrO2. The lechatelierite matrix, experimentally constrained to form at &gt;2000 °C, provided the ultrahigh-temperature environment for zircon dissociation (∼1670 °C) and neoblast formation. The capacity of granular zircon to preserve a cumulative pressure-temperature record has not been recognized previously, and provides a new method for investigating histories of impact-related mineral transformations in the crust at conditions far beyond those at which most rocks melt.
Linagliptin monotherapy compared with voglibose monotherapy in patients with type 2 diabetes undergoing hemodialysis: a 12-week randomized trial
Authors: Mori Katsuhito , Emoto Masanori , Shoji Tetsuo , Inaba Masaaki 
Published: July 2016

ObjectiveFocusing on efficacy and tolerability, we compared linagliptin monotherapy with voglibose monotherapy in patients with type 2 diabetes undergoing hemodialysis (HD).Research design and methodsIn this multicenter, randomized, open-label, parallel-group, active-controlled study, 78 patients were randomized (1:1) to receive a 12-week treatment with 5 mg linagliptin once daily or 0.2 mg voglibose three times a day. To assess whether linagliptin was superior to voglibose, the primary efficacy end point was the change in glycated hemoglobin (HbA1c) level between baseline and week 12. Secondary efficacy end points included changes between baseline and week 12 in glycated albumin (GA) and casual plasma glucose (PG) levels.ResultsAt week 12, the adjusted mean HbA1c levels had decreased by −0.60% after treatment with linagliptin and by −0.20% after treatment with voglibose (treatment difference: −0.40%, 95% CI −0.74% to −0.06%, p=0.022). A significant reduction in casual PG level was also observed after treatment with linagliptin compared with treatment with voglibose. Relative to voglibose, linagliptin tended to elicit reductions in GA, although without statistical significance. No hypoglycemic symptoms or severe hypoglycemia occurred during the study.ConclusionsIn patients with type 2 diabetes undergoing HD, linagliptin monotherapy provided significantly better glycemic control without severe hypoglycemia than voglibose monotherapy. Linagliptin represents a promising agent for glycemic management in patients with type 2 diabetes undergoing HD.Trial registration numberUMIN000007635; results.
IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells
Authors: McMichael Elizabeth L. , Jaime-Ramirez Alena Cristina , Guenterberg Kristan D. , Luedke Eric , Atwal Lakhvir S. , Campbell Amanda R. , Hu Zhiwei , Tatum Armika S. , Kondadasula Sri Vidya , Mo Xiaokui , Tridandapani Susheela , Bloomston Mark , Ellison E. Christopher , Williams Terence M. , Bekaii-Saab Tanios , Carson William E. 
Published: July 2016

AbstractPurpose: Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status.Experimental Design: NK cells from normal donors or donors with pancreatic cancer were used to assess ADCC, IFN-γ release, and T-cell chemotaxis toward human pancreatic cancer cell lines. The in vivo efficacy of IL-21 in combination with cetuximab was evaluated in a subcutaneous and intraperitoneal model of pancreatic cancer.Results: NK cell lysis of cetuximab-coated wild-type and mutant kras pancreatic cancer cell lines were significantly higher following NK cell IL-21 treatment. In response to cetuximab-coated pancreatic tumor cells, IL-21–treated NK cells secreted significantly higher levels of IFN-γ and chemokines, increased chemotaxis of T cells, and enhanced NK cell signal transduction via activation of ERK and STAT1. Treatment of mice bearing subcutaneous or intraperitoneal EGFR-positive pancreatic tumor xenografts with mIL-21 and cetuximab led to significant inhibition of tumor growth, a result further enhanced by the addition of gemcitabine.Conclusions: These results suggest that cetuximab treatment in combination with IL-21 adjuvant therapy in patients with EGFR-positive pancreatic cancer results in significant NK cell activation, irrespective of KRAS mutation status, and may be a potential therapeutic strategy. Clin Cancer Res; 23(2); 489–502. ©2016 AACR.
Overestimating the Role of Environment in Cancers
Authors: Noble Robert , Kaltz Oliver , Nunney Leonard , Hochberg Michael E. 
Published: July 2016

Abstract
In a recent article, Wu and colleagues (Nature 2016;529:43–47) review previous studies and present new estimates for the contribution of extrinsic factors to cancer development. The new estimates are generally close to 100%, even for bone and brain cancers that have no known associations with lifestyle and are typically not considered to be preventable. We find that the results of Wu and colleagues are incompatible with previous estimates derived from epidemiological and genetic data. We further argue that their methods are fundamentally flawed because they overlook important effects of tissue type on cancer risk. We therefore conclude that their results give a misleading view of cancer etiology and preventability. Cancer Prev Res; 9(10); 773–6. ©2016 AACR.