bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structures of Staphylococcus aureus Ketol‐Acid Reductoisomerase in Complex with Two Transition State Analogues that Have Biocidal Activity
Authors: Patel Khushboo M. , Teran David , Zheng Shan , Kandale Ajit , Garcia Mario , Lv You , Schembri Mark A. , McGeary Ross P. , Schenk Gerhard , Guddat Luke W. 
Published: October 2017

AbstractKetol‐acid reductoisomerase (KARI) is an NAD(P)H and Mg2+‐dependent enzyme of the branched‐chain amino acid (BCAA) biosynthesis pathway. Here, the first crystal structures of Staphylococcus aureus (Sa) KARI in complex with two transition state analogues, cyclopropane‐1,1‐dicarboxylate (CPD) and N‐isopropyloxalyl hydroxamate (IpOHA) are reported. These compounds bind competitively and in multi‐dentate manner to KARI with Ki values of 2.73 μm and 7.9 nm, respectively; however, IpOHA binds slowly to the enzyme. Interestingly, intact IpOHA is present in only ≈25 % of binding sites, whereas its deoxygenated form is present in the remaining sites. This deoxy form of IpOHA binds rapidly to Sa KARI, but with much weaker affinity (Ki=21 μm). Thus, our data pinpoint the origin of the slow binding mechanism of IpOHA. Furthermore, we propose that CPD mimics the early stage of the catalytic reaction (preceding the reduction step), whereas IpOHA mimics the late stage (after the reduction took place). These structural insights will guide strategies to design potent and rapidly binding derivatives of these compounds for the development of novel biocides.
Early detection versus prevention in colorectal cancer screening: Methods estimates and public health implications
Authors: Segnan Nereo , Armaroli Paola 
Published: October 2017

The percentage of mortality reduction due to prevention via the removal of adenomatous polyps or to early detection using comparison of survivals in intervention and usual‐care groups is flawed by lead time. Herein, a simple alternative algorithm is used and approximately 79% of averted colorectal cancer deaths are found to be due to prevention in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Some implications for public health are discussed.See also pages 4815‐22.
Landscape‐scale genetic differentiation of a mycangial fungus associated with the ambrosia beetle,Xylosandrus germanus(Blandford) (Curculionidae:Scolytinae) in Japan
Authors: Ito Masaaki , Kajimura Hisashi 
Published: October 2017

AbstractIn this study, we examined the genetic structures of the ambrosia fungus isolated from mycangia of the scolytine beetle,Xylosandrus germanusto understand their co‐evolutionary relationships. We analyzed datasets of three ambrosia fungus loci (18SrDNA, 28SrDNA, and the β‐tubulin gene) and aX. germanuslocus dataset (cytochrome c oxidase subunit 1 (COI) mitochondrialDNA). The ambrosia fungi were separated into three cultural morphptypes, and their haplotypes were distinguished by phylogenetic analysis on the basis of the three loci. TheCOIphylogenetic analysis revealed three distinct genetic lineages (clades A, B, and C) withinX. germanus, each of which corresponded to specific ambrosia fungus cultural morphptypes. The fungal symbiont phylogeny was not concordant with that of the beetle. Our results suggest thatX. germanusmay be unable to exchange its mycangial fungi, but extraordinary horizontal transmission of symbiotic fungi between the beetle's lineages occurred at least once during the evolutionary history of this symbiosis.
Population structure and connectivity of the mountainous star coral, Orbicella faveolata, throughout the wider Caribbean region
Authors: Rippe John P. , Matz Mikhail V. , Green Elizabeth A. , Medina Mónica , Khawaja Nida Z. , Pongwarin Thanapat , Pinzón C. Jorge H. , Castillo Karl D. , Davies Sarah W. 
Published: October 2017

AbstractAs coral reefs continue to decline worldwide, it becomes ever more necessary to understand the connectivity between coral populations to develop efficient management strategies facilitating survival and adaptation of coral reefs in the future. Orbicella faveolata is one of the most important reef‐building corals in the Caribbean and has recently experienced severe population reductions. Here, we utilize a panel of nine microsatellite loci to evaluate the genetic structure of O. faveolata and to infer connectivity across ten sites spanning the wider Caribbean region. Populations are generally well‐mixed throughout the basin (FST = 0.038), although notable patterns of substructure arise at local and regional scales. Eastern and western populations appear segregated with a genetic break around the Mona Passage in the north, as has been shown previously in other species; however, we find evidence for significant connectivity between Curaçao and Mexico, suggesting that the southern margin of this barrier is permeable to dispersal. Our results also identify a strong genetic break within the Mesoamerican Barrier Reef System associated with complex oceanographic patterns that promote larval retention in southern Belize. Additionally, the diverse genetic signature at Flower Garden Banks suggests its possible function as a downstream genetic sink. The findings reported here are relevant to the ongoing conservation efforts for this important and threatened species, and contribute to the growing understanding of large‐scale coral reef connectivity throughout the wider Caribbean.
The role of species‐specific sensory cues in male responses to mating rivals in Drosophila melanogaster fruitflies
Authors: Bretman Amanda , Rouse James , Westmancoat James D. , Chapman Tracey 
Published: October 2017

AbstractComplex sets of cues can be important in recognizing and responding to conspecific mating competitors and avoiding potentially costly heterospecific competitive interactions. Within Drosophila melanogaster, males can detect sensory inputs from conspecifics to assess the level of competition. They respond to rivals by significantly extending mating duration and gain significant fitness benefits from doing so. Here, we tested the idea that the multiple sensory cues used by D. melanogaster males to detect conspecifics also function to minimize “off‐target” responses to heterospecific males that they might encounter (Drosophila simulans, Drosophila yakuba, Drosophila pseudoobscura, or Drosophila virilis). Focal D. melanogaster males exposed to D. simulans or D. pseudoobscura subsequently increased mating duration, but to a lesser extent than following exposure to conspecific rivals. The magnitude of rivals’ responses expressed by D. melanogaster males did not align with genetic distance between species, and none of the sensory manipulations caused D. melanogaster to respond to males of all other species tested. However, when we removed or provided “false” sensory cues, D. melanogaster males became more likely to show increased mating duration responses to heterospecific males. We suggest that benefits of avoiding inaccurate assessment of the competitive environment may shape the evolution of recognition cues.
The causes of disproportionate non‐random mortality among life‐cycle stages
Authors: Green Peter T. , Harms Kyle E. 
Published: October 2017

AbstractThe emergent properties of the collection of species in a natural community, such as diversity and the distribution of relative abundances, are influenced by both niche‐based and neutral (stochastic) processes. This pluralistic view of the natural world reconciles theory with empirical observations better than does either a strictly niche‐ or neutrality‐based perspective. Even so, rules (or rules of thumb) that govern the relative contributions that niche‐based and stochastic processes make as communities assemble remain only vaguely formulated and incompletely tested. For example, the translation of non‐random (non‐neutral) ecological processes, which differentially sort among species within a community, into species‐compositional patterns may occur more influentially within some demographic subsets of organisms than within others. In other words, the relative contributions of niche vs. neutral processes may vary among age‐, size‐, or stage‐classes. For example, non‐random patterns of mortality that occur among seedlings in a rain forest, or among newly settled juveniles in communities of sessile marine communities, could be more influential than non‐random mortality during later stages in determining overall community diversity. We propose two alternative, mutually compatible, hypotheses to account for different levels of influence from mortality among life‐cycle stages toward producing non‐random patterns in organismal communities. The Turnover Model simply posits that those demographic classes characterized by faster rates of turnover contribute greater influence in the short‐term as sufficient mortality gives rise to non‐random changes to the community, as well as over the longer‐term as multiple individuals of a given fast‐turnover demographic class transition into later classes compared to each individual that ratchets from a slow‐turnover starting class into a later class. The Turnover Model should apply to most communities of organisms. The Niche Model, which posits that niche‐based processes are more influential in some demographic classes relative to others, may alternatively or additionally apply to communities. We also propose several alternative mechanisms, especially relevant to forest trees, that could cause dynamics consistent with the Niche Model. These mechanisms depend on differences among demographic classes in the extent of demographic variation that individual organisms experience through their trait values or neighborhood conditions.
Salvinorin A reduces neuropathic nociception in the insular cortex of the rat
Authors: Coffeen U. , Canseco‐Alba A. , Simón‐Arceo K. , Almanza A. , Mercado F. , León‐Olea M. , Pellicer F. 
Published: October 2017

AbstractBackgroundNeuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors.MethodsWe evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats.ResultsWe found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist.ConclusionSalvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors.SignificanceWe show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief.
Effects of Temperature Differences Among Cells on the Discharging Characteristics of Lithium‐Ion Battery Packs with Series/Parallel Configurations during Constant Power Discharge
Authors: Yang Naixing , Zhang Xiongwen , Li Guojun , Cai Anjiang , Xu Yunhua 
Published: October 2017

AbstractThis work aims to make a comparative analysis of the unbalanced discharging phenomenon for battery packs with series/parallel configurations due to the temperature differences among the cells. A theoretically‐based model is developed for the battery pack and constant power discharging processes are simulated by the model. At a constant temperature difference, lowering the operating temperature increases the divergence among the cell terminal voltages for the series pack and the cell discharging currents for the parallel pack. Increasing the temperature differences decreases the dischargeable energy of the series battery pack, whereas it has little effect on that of the parallel configuration. Given the same temperature difference, the cell energy differences within the parallel battery pack are 5–10 times higher than those within the series configuration, which shows that the temperature can be maintained much more uniformly for a parallel battery pack than for series configuration.
Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase III controlled trials
Authors: Carreño Mar , Benbadis Selim , Rocha Francisco , Blum David , Cheng Hailong ,   the Study 301, 302 and 304 Investigators (Appendix 1)
Published: October 2017

SummaryObjectiveTo investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients.MethodsPost‐hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial‐onset seizures (POS). Following an 8‐week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2‐week titration, 12‐week maintenance, 2–4 week tapering‐off periods). Patient seizure diary data and seizure treatment‐emergent adverse event (TEAE) reports were pooled for analysis.ResultsThe modified intent‐to‐treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period: Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period: Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic‐clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering‐off period: Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo.SignificanceTreatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.
Exposure to a national multimedia Alzheimer's disease awareness campaign: Assessing stigmatic beliefs towards persons with the disease
Authors: Werner Perla , Kermel Schiffman Ile 
Published: October 2017

ObjectiveThe purpose of this study was to examine the impact of being exposed to a multimedia campaign on stigmatic beliefs towards a person with Alzheimer's disease (AD).MethodsA cross‐sectional posttest online survey was conducted immediately after the campaign among 510 Jewish participants aged 40 and above.ResultsMost the participants reported being exposed to the campaign. The campaign elicited significantly higher positive than negative emotions. Exposure to the campaign was not significantly associated with any of the stigmatic beliefs as a direct or moderating variable. Worry about developing AD was associated with increased stigmatic beliefs.ConclusionsMore research is needed to better understand which types of media campaigns work best to increase awareness and reduce stigma associated with AD.
Measuring the diffusion of housing prices across space and over time: Replication and further evidence
Authors: Shen Shulin , Pang Jindong 
Published: October 2017

SummaryBrady (Journal of Applied Econometrics, 2011, 26(2), 213–231) studies how fast and how long a change in housing prices in one region affects its neighbors by estimating the impulse response functions using a spatial autoregressive model (SAR). This paper replicates Brady's empirical results, but reports different SAR test statistics. Additional robustness checks are conducted by analyzing three different housing price indexes covering a more extensive period. Analysis shows that the model specifications and model estimates vary with the housing price indexes.
A genomic characterization of the influence of silver nanoparticles on bone differentiation in MC3T3‐E1 cells
Authors: Qing Tao , Mahmood Meena , Zheng Yuanting , Biris Alexandru S. , Shi Leming , Casciano Daniel A. 
Published: October 2017

AbstractSilver nanoparticles (AgNPs) have been widely used in a variety of biomedical applications. Previous studies demonstrated that AgNPs significantly enhanced bone cell mineralization and differentiation in MC3T3–1 cells, a model in vitro system, when compared to several other NPs. This increased bone deposition was evaluated by phenotypic measurements and assessment of the expression of miRNAs associated with regulation of bone morphogenic proteins. In the present study, we used RNA‐seq technology, a more direct measurement of gene expression, to investigate further the mechanisms of bone differentiation induced by AgNP treatment. Key factors associated with the osteoclast pathway were significantly increased in response to AgNP exposure including Bmp4, Bmp6 and Fosl1. In addition, genes of metabolism and toxicity pathways were significantly regulated as well. Although this study suggests the potential for AgNPs to influence bone morphogenesis in injury or disease applications, further investigation into the efficacy and safety of AgNPs in bone regeneration is warranted.
In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea
Authors: Downey Joseph , Bongarzone Salvatore , Hader Stefan , Gee Antony D. 
Published: October 2017

Cyclotron‐produced carbon‐11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon‐11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers.The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop‐based system used in 11C‐methylation and 11C‐carboxylation reactions inspired us to apply the [11C]CO2 fixation “in‐loop.” In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop‐based [11C]CO2 fixation method, enabling the fast and efficient, direct‐from‐cyclotron, in‐loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof‐of‐concept in‐loop flow radiosynthesis of N,N′‐[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio‐HPLC), giving an overall nonisolated radiochemical yield of 72% (decay‐corrected) within just 3 minutes from end of bombardment.This proof‐of‐concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low‐volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in‐loop flow radiosynthesis of carbon‐11–labelled products.This new in‐loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.
Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock
Authors: Qiao Zhi , Horst Klemens , Teuben Michel , Greven Johannes , Yin Luxu , Kalbas Yannik , Tolba René H. , Pape Hans‐Christoph , Hildebrand Frank , Pfeifer Roman ,   TREAT group
Published: October 2017

ABSTRACTPolytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1377–1382, 2018.
Healing in peri‐implant gap with BMP‐2 and systemic bisphosphonate is dependent on BMP‐2 dose—A canine study
Authors: Cleemann Rasmus , Sorensen Mette , Bechtold Joan E. , Soballe Kjeld , Baas Jorgen 
Published: October 2017

ABSTRACTThe bone–implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone–implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP‐2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push‐out and histomorphometry, depends on the dose of BMP‐2 when delivered as an anabolic agent with systemic administration of the anti‐resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface‐applied BMP‐2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone–implant specimens were evaluated by mechanical push‐out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP‐2 doses have opposite effects in bridging an empty peri‐implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406–1414, 2018.