bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I
Authors: Shi Yuqian , Hellinga Homme W. , Beese Lorena S. 
Published: May 2017

Significance
Human exonuclease 1 (hExo1) is a 5′-structure–specific nuclease and a member of the RAD2/XPG superfamily that plays important roles in many aspects of genome maintenance. The means by which individual family members process multiple, structurally disparate substrates has been a long-standing question. The reaction intermediate structures reported here reveal that this remarkable feat is achieved by a series of orchestrated conformational changes that guide disparate substrates into a common, catalytically competent conformation, where they are cleaved by an enhanced variant of the two-metal, in-line hydrolysis mechanism. The observed motions not only enable exo- and endonucleolytic cleavage of gapped and 5′-flap substrates, respectively, but also encode unanticipated features, including mechanisms that enhance processing fidelity and account for processivity.
Bidirectional regulation of Aβ levels by Presenilin 1
Authors: Bustos Victor , Pulina Maria V. , Kelahmetoglu Yildiz , Sinha Subhash C. , Gorelick Fred S. , Flajolet Marc , Greengard Paul 
Published: May 2017

Significance
Alzheimer’s disease is the most common neurodegenerative disorder, affecting more than 5 million people in the United States. Multiple lines of evidence suggest that the accumulation of toxic oligomers and aggregates of β-amyloid (Aβ) peptide are the primary causes of neurodegeneration. Aβ originates from sequential cleavage of the amyloid precursor protein (APP). The APP first cleavage is by β-secretase and yields β-C-terminal fragment (βCTF). In turn, βCTF is cleaved by Presenilin 1 (PS1) to produce Aβ. In this work, we show that PS1, in addition to generating Aβ, can also decrease Aβ levels by directing βCTF degradation through autophagy. This previously unrecognized mechanism of regulation of Aβ by Presenilin 1 could provide an attractive target for potential Alzheimer’s disease therapies.
Blue fluorescent amino acid for biological spectroscopy and microscopy
Authors: Hilaire Mary Rose , Ahmed Ismail A. , Lin Chun-Wei , Jo Hyunil , DeGrado William F. , Gai Feng 
Published: May 2017

Significance
Herein, we report a tryptophan-based fluorophore that emits in the visible spectral region when excited with 355-nm light. Because this blue fluorescent amino acid has a small size and affords unique photophysical properties, we expect that it will find use in various biological studies, especially in spectroscopic and/or microscopic measurements where an amino acid-sized fluorescence reporter is required.
Visualization and characterization of individual type III protein secretion machines in live bacteria
Authors: Zhang Yongdeng , Lara-Tejero María , Bewersdorf Jörg , Galán Jorge E. 
Published: May 2017

Significance
Type III protein secretion systems are essential virulence factors for many bacterial pathogens. Cryo-electron microscopy has provided important details about the architecture and molecular organization of the type III secretion machine in isolation or in fixed samples. However, little information is available about the organization of the type III secretion machine and its individual substructures in live bacteria. Using 2D and 3D single-molecule switching superresolution microscopy, we have visualized individual type III secretion machines in live bacteria and obtained unique insight into the assembly and function of these machines. These studies bridge a major resolution gap in the visualization of type III secretion machines and may serve as a paradigm for the examination of other bacterially encoded molecular machines.
Applicability of ribosome engineering to vitamin B12 production by Propionibacterium shermanii
Authors: Tanaka Yukinori , Kasahara Ken , Izawa Masumi , Ochi Kozo 
Published: May 2017

Abstract
Ribosome engineering has been widely utilized for strain improvement, especially for the activation of bacterial secondary metabolism. This study assessed ribosome engineering technology to modulate primary metabolism, taking vitamin B12 production as a representative example. The introduction into Propionibacterium shermanii of mutations conferring resistance to rifampicin, gentamicin, and erythromycin, respectively, increased per cell production (μg/L/OD600) of vitamin B12 5.2-fold, although net production (μg/L) was unchanged, as the cell mass of the mutants was reduced. Real-time qPCR analysis demonstrated that the genes involved in vitamin B12 fermentation by P. shermanii were activated at the transcriptional level in the drug-resistant mutants, providing a mechanism for the higher yields of vitamin B12 by the mutants. These results demonstrate the efficacy of ribosome engineering for the production of not only secondary metabolites but of industrially important primary metabolites.
Effects of Brood Density and Spawning Substrate Type and Orientation on the Reproductive Output of Seminole Killifish in Tanks
Authors: Joseph Lindsay M V , Ohs Cortney L , DiMaggio Matthew A , Broach Jason S 
Published: May 2017

Abstract
Aquaculture of baitfish has the potential to produce and supply desired species and sizes to meet year-round market demand. The Seminole Killifish Fundulus seminolis is native to Florida and has recently emerged as a candidate for marine baitfish aquaculture because of its ability to survive acclimation to seawater, fast growth, and resilient larvae. Experiments were conducted to identify which spawning substrate materials and orientations were preferred by Seminole Killifish and to evaluate effects of broodfish stocking density on reproductive output. Results indicated that Seminole Killifish required a suitable substrate to be present for successful spawning and egg deposition. Broodstock spawned nearly all eggs onto fiber spawning mats when offered both mat and sand substrates. There was no significant difference in the number of eggs recorded among spawning mats regardless of orientation. Seminole Killifish held in outdoor tanks at a 2:1 (female : male) sex ratio had similar total egg production per tank per week irrespective of stocking density (10, 20, or 30 fish/m3). Consequently, the mean number of eggs produced per female was significantly different among the treatment densities, and an inverse relationship was noted between egg production and stocking density. Causes of observed fecundity differences among treatment densities are discussed along with other observations relevant to production.
Role of objectively measured sedentary behaviour in physical performance, frailty and mortality among older adults: A short systematic review
Authors: Mañas Asier , del Pozo‐Cruz Borja , García‐García Francisco José , Guadalupe‐Grau Amelia , Ara Ignacio 
Published: May 2017

AbstractSedentary behaviour (SB) has recently emerged as an independent risk factor for different health outcomes. Older adults accumulate long time in SB. Understanding the role that SB plays on health is crucial for a successful aging. This short systematic review summarizes the current evidence related to the effects of objectively measured SB on frailty, physical performance and mortality in adults ≥60 years old. The literature search produced 271 records for physical performance (n = 119), frailty (n = 31), and mortality (n = 121). Finally, only 13 articles fulfilled the inclusion criteria and were included in this review. All articles but one included in the physical performance section (n = 9) showed a negative association between longer time spent in SB and physical performance. A significant association of SB with higher odds of frailty was found, however this association disappeared after adjusting for cognitive status. Lastly, two of the three included studies showed positive associations between SB and mortality, but this effect decreased or even disappeared in the more adjusted models. In conclusion, there is consistency that SB is negatively associated with physical performance. However, the relationship between objectively measured SB and frailty incidence and mortality rates remains unclear and deserves further research. The use of homogenous criteria to assess SB and the inclusion of more robust research designs will help clarifying the independent effects that SB could have on physical performance, frailty, and mortality. This will ultimately help designing more efficient and comprehensive physical activity guidelines for older adults.
The Holy Maid of Wales: Visions, Imposture and Catholicism in Elizabethan Britain
Authors: Walsham Alexandra 
Published: May 2017

Abstract
This article explores the case of Elizabeth Orton of Overton in Flintshire, a young girl who experienced two ecstatic visions in February and March 1581 and was later exposed as a fraud. First, it uses this intriguing incident to illuminate the precarious stability of the Elizabethan polity at a moment of acute political crisis, when the fate of the Reformation itself seemed to be balanced on a knife-edge. It contends that religious developments in north Wales and the Marches were far more significant than has previously been recognised and investigates how far they were inflected by Welsh patriotism. Secondly, it focuses attention on the rhetorical strategies by which Elizabeth Orton was discredited—on the modes of argument that were utilised in the ensuing contest about her own authenticity and about the truth of the Catholic religion. Setting aside the question of whether or not she was guilty of faking her trances and revelations, it suggests that the incident sheds fresh light on the nature and evolution of the entangled concepts of imposture, hypocrisy and fraud. It shows how anxiety about the status and source of Elizabeth’s ecstatic experiences converged with intense concern about a second species of deceit and dissimulation: religious conformity.
The draft genome of blunt snout bream (Megalobrama amblycephala) reveals the development of intermuscular bone and adaptation to herbivorous diet
Authors: Liu Han , Chen Chunhai , Gao Zexia , Min Jiumeng , Gu Yongming , Jian Jianbo , Jiang Xiewu , Cai Huimin , Ebersberger Ingo , Xu Meng , Zhang Xinhui , Chen Jianwei , Luo Wei , Chen Boxiang , Chen Junhui , Liu Hong , Li Jiang , Lai Ruifang , Bai Mingzhou , Wei Jin , Yi Shaokui , Wang Huanling , Cao Xiaojuan , Zhou Xiaoyun , Zhao Yuhua , Wei Kaijian , Yang Ruibin , Liu Bingnan , Zhao Shancen , Fang Xiaodong , Schartl Manfred , Qian Xueqiao , Wang Weimin 
Published: May 2017

Abstract
The blunt snout bream Megalobrama amblycephala is the economically most important cyprinid fish species. As an herbivore, it can be grown by eco-friendly and resource-conserving aquaculture. However, the large number of intermuscular bones in the trunk musculature is adverse to fish meat processing and consumption. As a first towards optimizing this aquatic livestock, we present a 1.116-Gb draft genome of M. amblycephala, with 779.54 Mb anchored on 24 linkage groups. Integrating spatiotemporal transcriptome analyses, we show that intermuscular bone is formed in the more basal teleosts by intramembranous ossification and may be involved in muscle contractibility and coordinating cellular events. Comparative analysis revealed that olfactory receptor genes, especially of the beta type, underwent an extensive expansion in herbivorous cyprinids, whereas the gene for the umami receptor T1R1 was specifically lost in M. amblycephala. The composition of gut microflora, which contributes to the herbivorous adaptation of M. amblycephala, was found to be similar to that of other herbivores. As a valuable resource for the improvement of M. amblycephala livestock, the draft genome sequence offers new insights into the development of intermuscular bone and herbivorous adaptation.
Far-infrared metallicity diagnostics: application to local ultraluminous infrared galaxies
Authors: Pereira-Santaella M. , Rigopoulou D. , Farrah D. , Lebouteiller V. , Li J. 
Published: May 2017

AbstractThe abundance of metals in galaxies is a key parameter that permits to distinguish between different galaxy formation and evolution models. Most of the metallicity determinations are based on optical line ratios. However, the optical spectral range is subject to dust extinction and, for high-z objects (z > 3), some of the lines used in optical metallicity diagnostics are shifted to wavelengths not accessible to ground-based observatories. For this reason, we explore metallicity diagnostics using far-infrared (far-IR) line ratios which can provide a suitable alternative in such situations. To investigate these far-IR line ratios, we modelled the emission of a starburst with the photoionization code cloudy. The most sensitive far-IR ratios to measure metallicities are the [O iii]52 μm and 88 μm to [N iii]57 μm ratios. We show that this ratio produces robust metallicities in the presence of an active galactic nucleus and is insensitive to changes in the age of the ionizing stellar. Another metallicity-sensitive ratio is the [O iii]88 μm/[N ii]122 μm ratio, although it depends on the ionization parameter. We propose various mid- and far-IR line ratios to break this dependence. Finally, we apply these far-IR diagnostics to a sample of 19 local ultraluminous IR galaxies (ULIRGs) observed with Herschel and Spitzer. We find that the gas-phase metallicity in these local ULIRGs is in the range $0.7<Z_{\rm gas}/$ Z⊙ < 1.5, which corresponds to $8.5 <12 + \log ({\rm O / H}) < 8.9$. The inferred metallicities agree well with previous estimates for local ULIRGs and this confirms that they lie below the local mass–metallicity relation.
Preoperative Nomograms Predict Patient-Specific Cervical Spine Surgery Clinical and Quality of Life Outcomes
Authors: Lubelski Daniel , Alentado Vincent , Nowacki Amy S , Shriver Michael , Abdullah Kalil G , Steinmetz Michael P , Benzel Edward C , Mroz Thomas E 
Published: May 2017

Abstract

BACKGROUND
Clinical and quality of life (QOL) outcomes vary depending on the patient's demographics, comorbidities, presenting symptoms, pathology, and surgical treatment used. While there have been individual predictors identified, no comprehensive method incorporates a patient's complex clinical presentation to predict a specific individual postoperative outcome.

OBJECTIVE
To create tool that predicts patient-specific outcomes among those undergoing cervical spine surgery.

METHODS
A total of 952 patients at a single tertiary care institution who underwent anterior or posterior cervical decompression/fusion between 2007 and 2013 were retrospectively reviewed. Outcomes included postoperative emergency department visit or readmission within 30 d, reoperation within 90 d for infection, and changes in QOL outcomes. Nomograms were modeled based on patient demographics and surgical variables. Bootstrap was used for internal validation.

RESULTS
Bias-corrected c-index for emergency department visits, readmission, and reoperation were 0.63, 0.78, and 0.91, respectively. For the QOL metrics, the bias-corrected adjusted R-squared was EQ-5D (EuroQOL): 0.43, for PHQ-9 (Patient Health Questionnaire-9): 0.35, and for PDQ (Pain/Disability Questionnaire): 0.47. Variables predicting the clinical outcomes varied, but included race and median income, body mass index, comorbidities, presenting symptoms, indication for surgery, surgery type, and levels. For the QOL nomograms, the predictors included similar variables, but were significantly more affected by the preoperative QOL of the patient.

CONCLUSION
These prediction models enable referring physicians and spine surgeons to provide patients with personalized expectations regarding postoperative clinical and QOL outcomes following a cervical spine surgery. After appropriate validation, use of patient-specific prediction tools, such as nomograms, has the potential to lead to superior spine surgery outcomes and more cost effective care.
Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review
Authors: Bennett E Emily , Vogelbaum Michael A , Barnett Gene H , Angelov Lilyana , Chao Samuel , Murphy Erin , Yu Jennifer , Suh John H , Elson Paul , Stevens Glen H J , Mohammadi Alireza M 
Published: May 2017

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival.

OBJECTIVE
To evaluate prognostic factors, which may predict early death (within 90 d) after SRS.

METHODS
A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices.

RESULTS
Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable.

CONCLUSION
Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.
Risk Factors Associated With Outpatient Parenteral Antibiotic Therapy Program Failure Among Intravenous Drug Users
Authors: Buehrle Deanna J. , Shields Ryan K. , Shah Neel , Shoff Christopher , Sheridan Kathleen 
Published: May 2017

Abstract
Sixty-one percent of intravenous drug users (IVDUs) who received outpatient parenteral antibiotic therapy (OPAT) failed treatment. Hospital readmission and adverse drug reactions occurred in 25%. By multivariate analysis, time since last IVDU was associated with failure (P = .04). Intravenous drug users requiring OPAT are at high risk for failure; additional studies are needed to explore alternatives.
The bright-star masks for the HSC-SSP survey
Authors: Coupon Jean , Czakon Nicole , Bosch James , Komiyama Yutaka , Medezinski Elinor , Miyazaki Satoshi , Oguri Masamune 
Published: May 2017

Abstract
We present the procedure to build and validate the bright-star masks for the Hyper-Suprime-Cam Strategic Subaru Proposal (HSC-SSP) survey. To identify and mask the saturated stars in the full HSC-SSP footprint, we rely on the Gaia and Tycho-2 star catalogues. We first assemble a pure star catalogue down to GGaia &lt; 18 after removing ∼1.5% of sources that appear extended in the Sloan Digital Sky Survey (SDSS). We perform visual inspection on the early data from the S16A internal release of HSC-SSP, finding that our star catalogue is 99.2% pure down to GGaia &lt; 18. Second, we build the mask regions in an automated way using stacked detected source measurements around bright stars binned per GGaia magnitude. Finally, we validate those masks by visual inspection and comparison with the literature of galaxy number counts and angular two-point correlation functions. This version (Arcturus) supersedes the previous version (Sirius) used in the S16A internal and DR1 public releases. We publicly release the full masks and tools to flag objects in the entire footprint of the planned HSC-SSP observations at 〈ftp://obsftp.unige.ch/pub/coupon/brightStarMasks/HSC-SSP/〉.
Update on the pathogenesis and treatment of juvenile idiopathic arthritis
Authors: Giancane Gabriella , Alongi Alessandra , Ravelli Angelo 
Published: May 2017

Purpose of review
To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA).

Recent findings
In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process. There is a growing interest for the role of the gut microbiome in disease pathogenesis, which may open the way to future therapeutic manipulations of fecal microbial population. Recent therapeutic studies have provided important information in large patient samples on the effectiveness and toxicity profile of biologic medications used in JIA. Concomitant administration of methotrexate was found to increase the effectiveness of intra-articular corticosteroid therapy in children with oligoarticular JIA.

Summary
A great deal of work is being conducted to better define the molecular phenotype of the individual subsets of JIA and to identify potential new targets for therapeutic interventions. The results of the ongoing large-scale international data collections will help establish the long-term safety profiles of biologic medications, in particular the risk of malignancy.
Should All Massively Transfused Patients Be Treated Equally? An Analysis of Massive Transfusion Ratios in the Nontrauma Setting
Authors: Etchill Eric W. , Myers Sara P. , McDaniel Lauren M. , Rosengart Matthew R. , Raval Jay S. , Triulzi Darrell J. , Peitzman Andrew. B. , Sperry Jason L. , Neal Matthew D. 
Published: May 2017

Objectives:Although balanced resuscitation has become integrated into massive transfusion practice, there is a paucity of evidence supporting the delivery of high ratios of plasma and platelet to RBCs in the nontrauma setting. This study investigated the administration of blood component ratios in the massively transfused nontrauma demographic.Design:Retrospective analysis of a prospective, observational cohort of massively bleeding patients.Setting:Surgical and critically ill patients at a tertiary medical center between 2011 and 2015.Patients:Massively transfused nontrauma patients.Interventions:Patients receiving plasma, platelet, and RBC transfusions were categorized into high and low ratio groups and analyzed for differences in characteristics and clinical outcomes.Measurements and Main Results:The primary outcome was 30-day mortality. Secondary outcomes included 48-hour mortality, hospital length of stay, ICU length of stay, and ventilator-free days. Among 601 massively transfused nontrauma patients, cardiothoracic surgery and gastrointestinal or hepato-pancreatico-biliary bleeds were the most common indications for massive transfusion. Higher fresh frozen plasma ratios (> 1:2) were not associated with increased 30-day mortality. A high platelets-to-packed RBCs ratio (> 1:2) was associated with decreased 48-hour mortality (10.5% vs 19.3%;p= 0.032), but not 30-day mortality. Fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs ratios were not associated with 30-day mortality hazard ratios after controlling for baseline characteristics and disease severity.Conclusions:The benefits of higher ratios of fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs described in trials of trauma patients were not observed in this analysis of a nontrauma, massively transfused population. These data suggest that greater than 1:2 ratio transfusion in the setting of massive hemorrhage may not be appropriate for all patients, and that further research to guide appropriate resuscitation strategies in nontrauma patients is warranted.