bluuebunny/crossref_metadata_2025 huggingface dataset:
The distinctive jaw and alveolar bone regeneration
Authors: Akintoye SO
Published: February 2018

The skeletal system is structurally and functionally unique. It can be referred to as connective tissue that lost its ability to resist mineralization as mineralization in any other connective tissues is heterotopic. In addition to providing support for muscular attachments, the skeletal system protects nerves and harbors the hematopoietic and mesenchymal stem cells within the bone marrow compartment. However, there are distinct phenotypic and functional differences between the orofacial skeleton compared to axial and appendicular skeleton. How different is the jaw bone from other non‐craniofacial bones? Interestingly, developmental, biological, and clinical outcomes point to distinctive features that make the jaw bone unique.
Medication‐related osteonecrosis of the jaw: Surgical or non‐surgical treatment?
Authors: Favia G , Tempesta A , Limongelli L , Crincoli V , Maiorano E
Published: February 2018

Medication‐related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (bisphosphonates and denosumab) and anti‐angiogenic therapy used in the management of oncologic and, less frequently, osteoporotic patients. While there is good international agreement on the diagnostic and staging criteria of MRONJ and the cessation of antiresorptive/anti‐angiogenic treatments, the gold standard of treatment is still controversial, in particular between non‐surgical and surgical approaches. The former usually includes antiseptic mouth rinse, cyclic antibiotic therapy, low‐level laser therapy and periodic dental checks; the latter consists of surgical necrotic bone removal. The purpose of this retrospective study was to describe the therapeutic approaches and outcomes of 131 lesions from 106 MRONJ patients treated at the Policlinic of Bari. Non‐surgical treatments were chosen for 24 lesions that occurred in 21 patients who, due to comorbidities and/or the impossibility of stopping oncologic therapies, could not undergo surgical treatment. As to the outcome, all the surgically treated lesions (107) showed complete healing, with the exception of 13.5% of the lesions, all of which were stage III, which did not completely heal but showed reduction to stage I. The 24 non‐surgically treated lesions never completely healed and, rather, generally remained stable. Only two cases exhibited a reduction in staging. Based on our observations, MRONJ occurring both in neoplastic and non‐neoplastic patients benefits more from a surgical treatment approach, whenever deemed possible, as non‐surgical treatments do not seem to allow complete healing of the lesions.
Tissue eosinophilia in oral intraepithelial neoplasia as a probable indicator of invasion
Authors: Martinelli‐Kläy CP , Lombardi T , Mendis BRRN , Soares EG , Salvado F , Courvoisier DS , Mauricio P
Published: February 2018

Objective

To investigate the presence of eosinophils in oral intraepithelial neoplasia (OIN) and oral squamous cell carcinoma (OSCC) lesions and its relation to invasion.

Subjects and methods

Ninety‐nine oral biopsies were selected and subdivided into the following: OIN‐1(16 cases), OIN‐2 (18 cases), OIN‐3 (17 cases), microinvasive OSCC (10 cases), non‐metastatic OSCC (22 cases) and metastatic OSCC (16 cases). The tissue eosinophilia was evaluated histologically in slices stained with haematoxylin and eosin.

Results

Eosinophil distribution was associated with diagnosis severity (p < .01). A significant difference was found between OIN‐3 or microinvasive OSCC and non‐metastatic or metastatic OSCC. Stromal invasion threshold was 7 eos/10 high power field (hpf) (96.1% specificity and 62.5% sensitivity). Eosinophils were absent in OIN‐1; in OIN‐2, two cases were positive. In OIN‐3, five cases showed tissue eosinophilia, four of which had ≥3 eos/hpf or ≥7 eos/10 hpf. Three cases were suspected of invasion; two had a previous history of OSCC with elevated eosinophil infiltrate. In microinvasive OSCC, the four positive cases presented ≥3 eos/hpf and ≥7 eos/10 hpf. Although not significantly different, non‐metastatic invasive OSCC had a higher number of cases (68.2%) with ≥22 eos/10 hpf contrasting with 50% in metastatic OSCC.

Conclusion

Our results suggest that eosinophils can be considered an indicator of invasion in OIN, helping in cases of difficult diagnosis.
Response of epithelial cells infected by Treponema denticola
Authors: Kokubu E , Inoue T , Ishihara K
Published: February 2018

Objective

In the gingival crevice, the interaction between epithelial cells and periodontopathic bacteria is important for the development of periodontitis. Treponema denticola is a major pathogen of chronic periodontitis and possesses several virulence factors, such as major surface protein (Msp) and prolyl‐phenylalanine‐specific protease (dentilisin). Here, we investigated the behaviours of epithelial cells infected with T. denticola by measuring the expression of interleukin (IL)‐1β, IL‐6, β defensin 2 (BD‐2) and heat‐shock protein 70 (HSP70).

Methods

Epithelial cells were infected with T. denticola wild‐type strain, Msp‐deficient mutant or dentilisin‐deficient mutant, and the expression levels of the above targets were analysed by polymerase chain reaction.

Results

Infection with T. denticola wild‐type strain and mutants induced the production of IL‐6 and HSP70. The level of BD‐2 induced by T. denticola wild‐type strain at 24 hr was significantly higher than that of the dentilisin‐deficient mutant. The level of IL‐1β mRNA in the wild‐type strain and dentilisin‐deficient mutant was slightly lower than that in the uninfected control.

Conclusion

These results suggest that the levels of BD‐2 were affected by Msp and dentilisin. This effect may contribute to the disruption of the response of epithelial cells to eradicate T. denticola.
An oligosaccharyltransferase from Leishmania major increases the N‐glycan occupancy on recombinant glycoproteins produced in Nicotiana benthamiana
Authors: Castilho Alexandra , Beihammer Gernot , Pfeiffer Christina , Göritzer Kathrin , Montero‐Morales Laura , Vavra Ulrike , Maresch Daniel , Grünwald‐Gruber Clemens , Altmann Friedrich , Steinkellner Herta , Strasser Richard
Published: February 2018

N‐glycosylation is critical for recombinant glycoprotein production as it influences the heterogeneity of products and affects their biological function. In most eukaryotes, the oligosaccharyltransferase is the central‐protein complex facilitating the N‐glycosylation of proteins in the lumen of the endoplasmic reticulum (ER). Not all potential N‐glycosylation sites are recognized in vivo and the site occupancy can vary in different expression systems, resulting in underglycosylation of recombinant glycoproteins. To overcome this limitation in plants, we expressed LmSTT3D, a single‐subunit oligosaccharyltransferase from the protozoan Leishmania major transiently in Nicotiana benthamiana, a well‐established production platform for recombinant proteins. A fluorescent protein‐tagged LmSTT3D variant was predominately found in the ER and co‐located with plant oligosaccharyltransferase subunits. Co‐expression of LmSTT3D with immunoglobulins and other recombinant human glycoproteins resulted in a substantially increased N‐glycosylation site occupancy on all N‐glycosylation sites except those that were already more than 90% occupied. Our results show that the heterologous expression of LmSTT3D is a versatile tool to increase N‐glycosylation efficiency in plants.
Blocking amino acid transporter OsAAP3 improves grain yield by promoting outgrowth buds and increasing tiller number in rice
Authors: Lu Kai , Wu Bowen , Wang Jie , Zhu Wei , Nie Haipeng , Qian Junjie , Huang Weiting , Fang Zhongming
Published: February 2018

Amino acid transporters (AATs) play indispensable roles in nutrient allocation during plant development. In this study, we demonstrated that inhibiting expression of the rice amino acid transporter OsAAP3 increased grain yield due to a formation of larger numbers of tillers as a result of increased bud outgrowth. Elevated expression of OsAAP3 in transgenic plants resulted in significantly higher amino acid concentrations of Lys, Arg, His, Asp, Ala, Gln, Gly, Thr and Tyr, and inhibited bud outgrowth and rice tillering. However, RNAi of OsAAP3 decreased significantly Arg, Lys, Asp and Thr concentrations to a small extent, and thus promoted bud outgrowth, increased significantly tiller numbers and effective panicle numbers per plant, and further enhanced significantly grain yield and nitrogen use efficiency (NUE). The promoter sequences of OsAAP3 showed some divergence between Japonica and Indica rice, and expression of the gene was higher in Japonica, which produced fewer tillers than Indica. We generated knockout lines of OsAAP3 on Japonica ZH11 and KY131 using CRISPR technology and found that grain yield could be increased significantly. These results suggest that manipulation of OsAAP3 expression could be used to increase grain yield in rice.
Phacomatosis pigmentovascularis type 2b (phacomatosis cesioflammea) with double superior vena cava, abdominal varicosities, and natal tooth: Novel associations
Authors: Singal Archana , Mittal Hema , Aggarwal Anju , Das Saurabhi , Manchanda Smita
Published: February 2018

Phacomatosis pigmentovascularis is characterized by coexistent extensive cutaneous vascular (capillary) and pigmentary anomalies. We describe a 2‐month‐old infant presenting with classic features of phacomatosis pigmentovascularis 2b (phacomatosis cesioflammea). He was also found to have hitherto unreported associations in the form of extensive venous anomalies presenting as striking abdominal wall varicosities and persistent left superior vena cava and natal tooth.
Retronychia a little‐known cause of paronychia: A report of two cases in adolescent patients
Authors: Poveda‐Montoyo Inés , Vergara‐de Caso Eduardo , Romero‐Pérez David , Betlloch‐Mas Isabel
Published: February 2018

Retronychia is a clinical condition resulting from embedding of the nail plate into the proximal nail fold. We report two adolescent girls, 14 and 16 years of age, with a history of chronic proximal paronychia of the great toe, one of them developing osteomyelitis. After failure of treatment with several systemic antibiotics, nail avulsion was performed, leading us to the diagnosis of retronychia and with rapid and complete resolution of symptoms in both cases. Delay in diagnosis of retronychia can lead to local complications and prolonged discomfort.
Efficacy and safety of topical application of 15% and 10% potassium hydroxide for the treatment of Molluscum contagiosum
Authors: Teixidó Concepció , Díez Olga , Marsal Josep R. , Giner‐Soriano Maria , Pera Helena , Martinez Mireia , Galindo‐Ortego Gisela , Schoenenberger Joan A. , Real Jordi , Cruz Ines , Morros Rosa
Published: February 2018

Background/Objectives

Molluscum contagiosum is the most common skin infection in children. One topical treatment used for Molluscum contagiosum is potassium hydroxide. The objective of this study was to compare the efficacy of potassium hydroxide topical treatment at different concentrations with that of placebo in terms of complete clearing of Molluscum contagiosum lesions and to assess the safety and tolerance of potassium hydroxide topical treatment.

Methods

This was a double‐blind randomized clinical trial of three treatments (potassium hydroxide 10%, potassium hydroxide 15%, placebo) applied once daily up to complete clearing of lesions (maximum duration 60 days) in 53 children aged 2‐6 years in primary health care pediatric offices in Catalonia, Spain.

Results

In the intention‐to‐treat analysis, potassium hydroxide 10% (58.8%, P = .03) and potassium hydroxide 15% (64.3%, P = .02) had efficacy superior to that of placebo (18.8%). The number of Molluscum contagiosum lesions was significantly reduced with potassium hydroxide 10% and 15%. The main efficacy outcome was achieved in 58.8% of children in the potassium hydroxide 10% group (P = .03 vs placebo) and in 64.3% of children in the potassium hydroxide 15% group (P = .02 vs placebo). Potassium hydroxide 10% and 15% were not significantly different in efficacy from each other. Potassium hydroxide 10% and placebo were better tolerated than potassium hydroxide 15%. No adverse events were reported during the study period.

Conclusions

Potassium hydroxide 10% and 15% demonstrated high rates of efficacy in clearing Molluscum contagiosum lesions, with potassium hydroxide 10% being better tolerated.
Features of Large Magmatic–Hydrothermal Systems in Japan: Characteristics Similar to the Tops of Porphyry Copper Deposits
Authors: Hedenquist Jeffrey W. , Taguchi Sachihiro , Shinohara Hiroshi
Published: February 2018

Volcanic complexes in Japan such as Kusatsu Shirane, Honshu, and Kuju‐Hatchobaru and Kirishima, Kyushu, host active magmatic–hydrothermal systems that are several kilometers in diameter and typically asymmetric to the intrusive center. Their heat flow is driven by multiple intrusions at <5–10 km depth over a period on the order of ~105 years. These hydrothermal systems consist of advecting fluids of magmatic origin (either vapor with acidic components condensed into meteoric water, or a subsequent liquid of varying reactivity) that interact with convecting meteoric water. The amount of the magmatic component depends on location relative to the intrusive center, local controls on permeability, and the temporal evolution of the intrusions. The proportion of meteoric water diluent typically increases from proximal to distal locations (over several kilometer distance), and with time after intrusion (> several thousands of years). Some of the neutral pH solutions in these large hydrothermal systems, up to ~5 km from volcanic vents, support geothermal energy developments, with strong structural control on fluid flow. Near active volcanic vents, the magmatic vapor component of hydrothermal systems can form acidic condensates (pH ~ 1.5) that are responsible for strong alteration of the host rock. The resulting residual quartz and advanced argillic minerals are typical of shallow‐formed lithocap alteration that is associated with deeper porphyry copper deposits in similar arc‐hosted volcanic settings. Around the world, this near‐surface lithocap alteration, influenced by structures as well as lithology, may be barren in metals, even where associated with mineralized porphyry intrusions at depth. Such intrusion‐proximal alteration is widespread in both active and extinct settings in Japan. In addition, distal geothermal hot springs typically have a magmatic water component, albeit minor, with a pH that varies from ~3 to near‐neutral; deep alteration intersected in drill holes is characterized by alunite–dickite–pyrophyllite or chlorite–wairakite, respectively. These alteration assemblages are typical of their extinct equivalents, intermediate sulfidation epithermal veins, with mineralogical complexities caused by temporal evolution as well as spatial variation (e.g. along different structures). Such active and extinct magmatic–hydrothermal systems signify the presence of shallow degassing or degassed intrusions, respectively. Where similar intrusions in volcanic arcs around the world are eroded to ~1 to 2 km depth, the tops of porphyry copper deposits are commonly exposed, marked by a transition of white mica upward to pyrophyllite‐dominant alteration. Active magmatic–hydrothermal systems on the flanks of arc volcanoes in Japan are dynamic – both cycling as well as evolving – and share characteristics with extinct systems that host epithermal and porphyry ore deposits.
Selectivity Is Still in the Running: A Comment on Ifatunji's “Labor Market Disparities”
Authors: Model Suzanne
Published: February 2018

This comment is in response to Ifatunji's () article, “Labor Market Disparities Between African Americans and Afro Caribbeans: Reexamining the Role of Immigrant Selectivity,” published in this journal.
The Unnecessary Nudge: Education and Poverty Policy in a Cairo Slum
Authors: Gowayed Heba
Published: February 2018

Drawing on data collected from 2008 to 2013 in a low‐income Cairo neighborhood, this article examines the impact of a poverty alleviation program, a conditional cash transfer (CCT) that attempted to incentivize poor mothers, through a direct cash transfer, to send their children to school. The program met its goal. The mothers did send their children to school. I argue that only observing this outcome of school access, however, black‐boxes the causal pathway of how mothers sent their children to school in the Egyptian context, and how the program mattered. Public schools in Egypt are free on paper but expensive in practice due to an informal system of “private lesson” and “study group” fees imposed by teachers. Mothers had always managed this expense, using scarce gendered household resources, before, during, and after the program. Through ethnographic, interview, and survey data, this article shows that while the cash—transferred to the mothers and labeled for education—enabled the mothers to send their children to school, the program conditions were unnecessary. The mothers did not need to be nudged to send their children to school. This Egyptian case study has implications for the use of behavioral incentives and for the importance of qualitative methods to the study of policy impacts.
Populism as a Collective Action Master Frame for Transnational Mobilization
Authors: Aslanidis Paris
Published: February 2018

Occupy Wall Street, the Greek and Spanish indignados, and other important movements swept across the Western world from 2011 onward, redefining political and social conflict during the global economic meltdown of the Great Recession. These movements have earned well‐deserved academic attention, but the resulting scholarship is lacking a crucial pillar: a comparative analysis of the collective action frames employed by movement entrepreneurs. To identify the master frame at work and uncover shared processes of strategic meaning making and collective identity construction during this transnational cycle of contention, I analyze primary data, exploring diagnostic, prognostic, and adversarial framing elements as found in the movements’ widely circulated manifestos. The populist frame emerges as the master frame of the cycle, encapsulating the adversarial discourse of the dominant dichotomy of a noble “people” and a corrupt “elite” that resonated strongly with mobilized individuals and allowed movement entrepreneurs to construct a transnationally shared collective identity across populations of widely diverging social, political, and economic backgrounds.
The Effect of Political Parties on the Distribution of Income in the American States: 1917–2011
Authors: Widestrom Amy , Hayes Thomas J. , Dennis Christopher
Published: February 2018

Objectives

This article examines the effects of partisan control of government on income distribution within the United States.

Methods

Using newly available data, we estimate the effects of unified Democratic and Republican Party control at the state and national levels on the share of income going to the top 1 percent of income earners, by state, between 1917 and 2011.

Results

We find that unified party control at the state level has minimal impact on income going to the top 1 percent of income earners within the states, but that unified party control at the federal level does have an effect. Moreover, we find that over the long term, unified Democratic control at the federal level leads to less income going to the top 1 percent, while unified Republican control increases income going to top earners.

Conclusions

Despite the increased focus on federalism and state policy in studies of income inequality, our findings suggest that federal‐level political factors are important for understanding the share of income going to the top income earners in the United States, particularly in the contemporary era.
The Exceptionalism of the Open Space Issue in American Politics*
Authors: Lowry William R.
Published: February 2018

Objective

Our objective is to illustrate the need to differentiate specific issue types within broad policy categories by showing the exceptional support in American politics for open space issues.

Methods

We test this assertion with econometric analyses of outcomes from over 600 state ballot measures on environmental and energy issues.

Results

We find exceptional support for open space ballot measures in simple comparisons and in fuller models of ballot measure passage. As one example, over 80 percent of the open space measures pass, whereas 50 percent of all the other measures pass.

Conclusion

Exceptional support for open space is important for this policy area specifically but also as an illustration of the need to differentiate broad policy categories into specific issues.
Cultural Worldviews and Political Process Preferences*
Authors: Zanocco Chad M. , Jones Michael D.
Published: February 2018

Objectives

Cultural theory (CT) is often leveraged to explain policy preferences and risk perceptions. While scholars often make claims regarding CT's relationship with political process preferences, these remain largely untested. This study explores the relationship between CT and individual preferences toward the process in which political decisions are made.

Methods

Using national survey data (n = 900), we identify two political process preference dimensions in exploratory factor analysis: compromise and expediency. To operationalize CT, survey items from cultural cognition theory are formed into cultural measures. We use bivariate and multivariate analysis to explore key relationships.

Results

Those with more egalitarian/communitarian worldviews value compromise in political decision making, while those with individualist/hierarchical worldviews are less likely to value compromise. We find no relationship between expediency and cultural worldviews.

Conclusion

This research suggests that CT is useful for understanding some, but not all, dimensions of political process preferences. While those with egalitarians/communitarian worldviews may be more accepting of policy decisions produced under compromise, other common tropes regarding the relationship between CT and process preferences should be carefully applied.
‐Drink Or ‐Trunk, That Is The Question: The Distribution Of Selected Anglicisms And German Near‐Synonyms In Compounding
Authors: Baeskow Heike
Published: February 2018

In this article, it will be shown that lexical contrasts and similarities between selected anglicisms and potential German near‐synonyms are optimally revealed in compounding, where distinctive properties of the non‐native head are either matched or contextually overridden by the native modifier. The corpus‐based contrastive analyses involve N + N compounds headed by the well‐integrated nouns Drink, Dealer and Job and their potential German equivalents (e.g. Geburtstagsdrink vs. Geburtstagstrunk “birthday drink”, Autodealer vs. Autohändler ‘car dealer’, Ferienjob vs. ?Ferienberuf “holiday job”). The semantic description will be performed on the basis of Pustejovsky's Generative Lexicon, which allows for a context‐specific interpretation of lexical items. Connotative properties will mainly be described in relation to the stylistic functions they fulfil in journalistic contexts.
A novel HLA‐DQB1*03 variant, HLA‐DQB1*03:23:03, identified in a Chinese individual
Authors: Zhou Y. L. , Zhang Q.
Published: February 2018

HLA‐DQB1*03:23:03 has two nucleotide change from HLA‐DQB1*03:03:02:01 at position 254 and 260.
Electrochemical treatment of chemical oxygen demand in produced water using flow‐by porous graphite electrode
Authors: Abdel‐Salam Omar E. , Abou Taleb Enas M. , Afify Ahmed A.
Published: February 2018

Produced water is the largest wastewater stream generated in the oil and gas industries. In this study, experiments were carried out using a bench‐scale electrochemical cell using flow‐by porous graphite electrode, for oxidation of organic matter in produced water which was collected from natural gas processing field (real sample). The effect of anodic current density and influent feed flow rate on chemical oxygen demand (COD) removal efficiency, and energy consumption were investigated. The maximum removal efficiency of 66.52% was obtained for a flow rate of 50 mL/min, current density of 1.41 mA/cm2 and pH of 7.3 for an influent COD of 2845 mg O2/L. The energy consumption at these conditions was 2.12 kWh/kgCOD.
Effects of run‐of‐the‐river hydropower plants on the surface water quality in the Solakli stream watershed, Northeastern Turkey
Authors: Koralay Necla , Kara Omer , Kezik Ugur
Published: February 2018

In recent years, Turkey has turned its attention to alternative energy sources rather than fossil fuels. The Eastern Black Sea Region of Turkey has steep mountains with hilly topography and has large potential in terms of energy production with run‐of‐the‐river hydropower plants (RHPPs). In this study, the effects of two RHPPs on some water quality parameters were examined in the Solaklı stream watershed. This research was conducted over the course of 12 months (January–December 2014). In total, 12 sampling points were selected and various water quality parameters, such as temperature, pH, dissolved oxygen, total suspended solids, electrical conductivity, total dissolved solid, chloride and salinity, were monitered at each point. Statistically, significant changes occured in water quality parameters such as total suspended solids, pH and temperature. In particular, total suspended solids ranged from 10 to 440 mg/L.These results suggest that the RHPP negatively effect water quality and quantity in the main stream in both the operational and constructional phases.
Direct formation of graphene on dielectric substrate: Controlling the location of graphene formation adopting carbon diffusion barrier
Authors: Kim Ki-Ju , Cho Seong-Yong , Kim Hyun-Mi , Kim Ki-Bum
Published: February 2018

The authors report a method to form multilayered graphene directly on top of a dielectric SiO2/Si substrate by the solid-phase crystallization of amorphous carbon (a-C) using Ni as a catalyst and Ti as a carbon diffusion barrier layer; the layer sequence is Ti/Ni/a-C/SiO2/Si. During annealing, carbon diffuses through Ni and forms TiC at the Ti/Ni interface, blocking further carbon diffusion to the Ti layer. During cooling, the remnant carbon in the Ni layer precipitates out at the Ni/SiO2 interface, forming multilayers of graphene. Then, both Ti and Ni are etched away using Radio Corporation of America standard cleaning (SC-I) and FeCl3-based wet etching. The graphene layers formed on top of the dielectric substrate can be utilized without further transfer methods. The best-quality of graphene is formed at 600 °C with the Raman signal D- to G-peak intensity ratio of 0.29. Auger electron spectroscopy depth profiles and sequential etching tests with SC-I and FeCl3-based etchant confirms that the Ti layer is transformed to TiOxCy or TiC layer, which may reduce the carbon diffusion flux through this layer, as expected.
Head waves in ocean acoustic ambient noise: Measurements and modeling
Authors: Siderius Martin , Li Jie , Gerstoft Peter
Published: February 2018

Seismic interferometry recovers the Green's function between two receivers by cross-correlating the field measured from sources that surround the receivers. In the seismic literature, it has been widely reported that this processing can produce artifacts in the Green's function estimate called “spurious multiples” or the “virtual refracted wave.” The spurious multiples are attributed to the head wave and its multiples and travels in the seabed. The head wave phenomenon is shown to be observable from both controlled active sources and from ocean ambient noise and for both vertical and horizontal arrays. The processing used is a generalization of the passive fathometer to produce cross-beam correlations. This passive fathometer is equivalent to the seismic interferometry techniques for delay and sum beamforming but not for adaptive beamforming. Modeling and experimental data show the head wave is observed in ocean noise and can be used to estimate the seabed sound speed.
Can monaural temporal masking explain the ongoing precedence effect?
Authors: Freyman Richard L. , Morse-Fortier Charlotte , Griffin Amanda M. , Zurek Patrick M.
Published: February 2018

The precedence effect for transient sounds has been proposed to be based primarily on monaural processes, manifested by asymmetric temporal masking. This study explored the potential for monaural explanations with longer (“ongoing”) sounds exhibiting the precedence effect. Transient stimuli were single lead-lag noise burst pairs; ongoing stimuli were trains of 63 burst pairs. Unlike with transients, monaural masking data for ongoing sounds showed no advantage for the lead, and are inconsistent with asymmetric audibility as an explanation for ongoing precedence. This result, along with supplementary measurements of interaural time discrimination, suggests different explanations for transient and ongoing precedence.
Correspondence between sound propagation in discrete and continuous random media with application to forest acoustics
Authors: Ostashev Vladimir E. , Wilson D. Keith , Muhlestein Michael B. , Attenborough Keith
Published: February 2018

Although sound propagation in a forest is important in several applications, there are currently no rigorous yet computationally tractable prediction methods. Due to the complexity of sound scattering in a forest, it is natural to formulate the problem stochastically. In this paper, it is demonstrated that the equations for the statistical moments of the sound field propagating in a forest have the same form as those for sound propagation in a turbulent atmosphere if the scattering properties of the two media are expressed in terms of the differential scattering and total cross sections. Using the existing theories for sound propagation in a turbulent atmosphere, this analogy enables the derivation of several results for predicting forest acoustics. In particular, the second-moment parabolic equation is formulated for the spatial correlation function of the sound field propagating above an impedance ground in a forest with micrometeorology. Effective numerical techniques for solving this equation have been developed in atmospheric acoustics. In another example, formulas are obtained that describe the effect of a forest on the interference between the direct and ground-reflected waves. The formulated correspondence between wave propagation in discrete and continuous random media can also be used in other fields of physics.
A deep ocean acoustic noise floor, 1–800 Hz
Authors: Berger J. , Bidlot J.-R. , Dzieciuch M. A. , Farrell W. E. , Worcester P. F. , Stephen R. A.
Published: February 2018

The ocean acoustic noise floor (observed when the overhead wind is low, ships are distant, and marine life silent) has been measured on an array extending up 987 m from 5048 m depth in the eastern North Pacific, in what is one of only a few recent measurements of the vertical noise distribution near the seafloor in the deep ocean. The floor is roughly independent of depth for 1–6 Hz, and the slope (∼ f−7) is consistent with Longuet-Higgins radiation from oppositely-directed surface waves. Above 6 Hz, the acoustic floor increases with frequency due to distant shipping before falling as ∼ f−2 from 40 to 800 Hz. The noise floor just above the seafloor is only about 5 dB greater than during the 1975 CHURCH OPAL experiment (50–200 Hz), even though these measurements are not subject to the same bathymetric blockage. The floor increases up the array by roughly 15 dB for 40–500 Hz. Immediately above the seafloor, the acoustic energy is concentrated in a narrow, horizontal beam that narrows as f−1 and has a beam width at 75 Hz that is less than the array resolution. The power in the beam falls more steeply with frequency than the omnidirectional spectrum.
Mouse and Human Monoclonal Antibodies Protect against Infection by Multiple Genotypes of Japanese Encephalitis Virus
Authors: Fernandez Estefania , Kose Nurgun , Edeling Melissa A. , Adhikari Jagat , Sapparapu Gopal , Lazarte Susana M. , Nelson Christopher A. , Govero Jennifer , Gross Michael L. , Fremont Daved H. , Crowe James E. , Diamond Michael S.
Published: February 2018

Japanese encephalitis virus (JEV) remains a leading cause of viral encephalitis worldwide. Although JEV-specific antibodies have been described, an assessment of their ability to neutralize multiple genotypes of JEV has been limited. Here, we describe the development of a panel of mouse and human neutralizing monoclonal antibodies (MAbs) that inhibit infection in cell culture of four different JEV genotypes tested. Mechanism-of-action studies showed that many of these MAbs inhibited infection at a postattachment step, including blockade of virus fusion. Mapping studies using site-directed mutagenesis and hydrogen-deuterium exchange with mass spectrometry revealed that the lateral ridge on domain III of the envelope protein was a primary recognition epitope for our panel of strongly neutralizing MAbs. Therapeutic studies in mice demonstrated protection against lethality caused by genotype I and III strains when MAbs were administered as a single dose even 5 days after infection. This information may inform the development of vaccines and therapeutic antibodies as emerging strains and genotypic shifts become more prevalent.

IMPORTANCEAlthough Japanese encephalitis virus (JEV) is a vaccine-preventable cause of viral encephalitis, the inactivated and live attenuated platforms available are derived from strains belonging to a single genotype (GIII) due to its historical prevalence in areas of JEV epidemics. Related to this, studies with vaccines and antibodies have focused on assessing thein vitroandin vivoprotective responses to homologous or heterologous GIII strains. An epidemiological shift in JEV genotype distribution warrants the induction of broadly neutralizing antibody responses that inhibit infection of multiple JEV genotypes. Here, we generated a panel of mouse and human neutralizing monoclonal antibodies and evaluated their inhibitory activity, epitope location, and capacity for protection against multiple JEV genotypes in mice.
Widespread Distribution and Functional Specificity of the Copper Importer CcoA: Distinct Cu Uptake Routes for Bacterial Cytochrome
c
Oxidases
Authors: Khalfaoui-Hassani Bahia , Wu Hongjiang , Blaby-Haas Crysten E. , Zhang Yang , Sandri Federica , Verissimo Andreia F. , Koch Hans-Georg , Daldal Fevzi
Published: February 2018

Cytochrome
c
oxidases are members of the heme-copper oxidase superfamily. These enzymes have different subunits, cofactors, and primary electron acceptors, yet they all contain identical heme-copper (Cu
B
) binuclear centers within their catalytic subunits. The uptake and delivery pathways of the Cu
B
atom incorporated into this active site, where oxygen is reduced to water, are not well understood. Our previous work with the facultative phototrophic bacterium
Rhodobacter capsulatus
indicated that the copper atom needed for the Cu
B
site of
cbb
3
-type cytochrome
c
oxidase (
cbb
3
-Cox) is imported to the cytoplasm by a major facilitator superfamily-type transporter, CcoA. In this study, a comparative genomic analysis of CcoA orthologs in alphaproteobacterial genomes showed that CcoA is widespread among organisms and frequently co-occurs with cytochrome
c
oxidases. To define the specificity of CcoA activity, we investigated its function in
Rhodobacter sphaeroides
, a close relative of
R. capsulatus
that contains both
cbb
3
- and
aa
3
-Cox. Phenotypic, genetic, and biochemical characterization of mutants lacking CcoA showed that in its absence, or even in the presence of its bypass suppressors, only the production of
cbb
3
-Cox and not that of
aa
3
-Cox was affected. We therefore concluded that CcoA is dedicated solely to
cbb
3
-Cox biogenesis, establishing that distinct copper uptake systems provide the Cu
B
atoms to the catalytic sites of these two similar cytochrome
c
oxidases. These findings illustrate the large variety of strategies that organisms employ to ensure homeostasis and fine control of copper trafficking and delivery to the target cuproproteins under different physiological conditions.

IMPORTANCE
The
cbb
3
- and
aa
3
-type cytochrome
c
oxidases belong to the widespread heme-copper oxidase superfamily. They are membrane-integral cuproproteins that catalyze oxygen reduction to water under hypoxic and normoxic growth conditions. These enzymes diverge in terms of subunit and cofactor composition, yet they all share a conserved heme-copper binuclear site within their catalytic subunit. In this study, we show that the copper atoms of the catalytic center of two similar cytochrome
c
oxidases from this superfamily are provided by different copper uptake systems during their biogenesis. This finding illustrates different strategies by which organisms fine-tune the trafficking of copper, which is an essential but toxic micronutrient.
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in
Saccharomyces cerevisiae
Authors: Ernst Dustin C. , Downs Diana M.
Published: February 2018

A variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion. 2-Aminoacrylate is a reactive enamine generated by pyridoxal 5′-phosphate-dependent α,β-eliminases as an obligatory intermediate in the breakdown of serine. In prokaryotes, members of the broadly conserved RidA family (PF14588) prevent metabolic stress by deaminating 2-aminoacrylate to pyruvate. Here, we demonstrate that unmanaged 2-aminoacrylate accumulation in
Saccharomyces cerevisiae
mitochondria causes transient metabolic stress and the irreversible loss of mitochondrial DNA. The RidA family protein Mmf1p deaminates 2-aminoacrylate, preempting metabolic stress and loss of the mitochondrial genome. Disruption of the mitochondrial pyridoxal 5′-phosphate-dependent serine dehydratases (Ilv1p and Cha1p) prevents 2-aminoacrylate formation, avoiding stress in the absence of Mmf1p. Furthermore, chelation of iron in the growth medium improves maintenance of the mitochondrial genome in yeast challenged with 2-aminoacrylate, suggesting that 2-aminoacrylate-dependent loss of mitochondrial DNA is influenced by disruption of iron homeostasis. Taken together, the data indicate that Mmf1p indirectly contributes to mitochondrial DNA maintenance by preventing 2-aminoacrylate stress derived from mitochondrial amino acid metabolism.

IMPORTANCE
Deleterious reactive metabolites are produced as a consequence of many intracellular biochemical transformations. Importantly, reactive metabolites that appear short-lived
in vitro
have the potential to persist within intracellular environments, leading to pervasive cell damage and diminished fitness. To overcome metabolite damage, organisms utilize enzymatic reactive-metabolite defense systems to rid the cell of deleterious metabolites. In this report, we describe the importance of the RidA/YER057c/UK114 enamine/imine deaminase family in preventing 2-aminoacrylate stress in yeast.
Saccharomyces cerevisiae
lacking the enamine/imine deaminase Mmf1p was shown to experience pleiotropic growth defects and fails to maintain its mitochondrial genome. Our results provide the first line of evidence that uncontrolled 2-aminoacrylate stress derived from mitochondrial serine metabolism can negatively impact mitochondrial DNA maintenance in eukaryotes.
Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB
Authors: Filippova Ekaterina V. , Zemaitaitis Bozena , Aung Theint , Wolfe Alan J. , Anderson Wayne F.
Published: February 2018

RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010,
https://doi.org/10.1016/j.mib.2010.01.002
; D. J. Clarke, Future Microbiol 5:1173–1184, 2010,
https://doi.org/10.2217/fmb.10.83
). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6–17, 2012,
https://doi.org/10.1094/MPMI-08-11-0207
). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the
flhDC
operon from
Escherichia coli
determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of
in vitro
binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria.

IMPORTANCE
RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family
Enterobacteriaceae
, which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family
Enterobacteriaceae
.
Tracking Electron Uptake from a Cathode into
Shewanella
Cells: Implications for Energy Acquisition from Solid-Substrate Electron Donors
Authors: Rowe Annette R. , Rajeev Pournami , Jain Abhiney , Pirbadian Sahand , Okamoto Akihiro , Gralnick Jeffrey A. , El-Naggar Mohamed Y. , Nealson Kenneth H.
Published: February 2018

While typically investigated as a microorganism capable of extracellular electron transfer to minerals or anodes,
Shewanella oneidensis
MR-1 can also facilitate electron flow from a cathode to terminal electron acceptors, such as fumarate or oxygen, thereby providing a model system for a process that has significant environmental and technological implications. This work demonstrates that cathodic electrons enter the electron transport chain of
S. oneidensis
when oxygen is used as the terminal electron acceptor. The effect of electron transport chain inhibitors suggested that a proton gradient is generated during cathode oxidation, consistent with the higher cellular ATP levels measured in cathode-respiring cells than in controls. Cathode oxidation also correlated with an increase in the cellular redox (NADH/FMNH
2
) pool determined with a bioluminescence assay, a proton uncoupler, and a mutant of proton-pumping NADH oxidase complex I. This work suggested that the generation of NADH/FMNH
2
under cathodic conditions was linked to reverse electron flow mediated by complex I. A decrease in cathodic electron uptake was observed in various mutant strains, including those lacking the extracellular electron transfer components necessary for anodic-current generation. While no cell growth was observed under these conditions, here we show that cathode oxidation is linked to cellular energy acquisition, resulting in a quantifiable reduction in the cellular decay rate. This work highlights a potential mechanism for cell survival and/or persistence on cathodes, which might extend to environments where growth and division are severely limited.

IMPORTANCE
The majority of our knowledge of the physiology of extracellular electron transfer derives from studies of electrons moving to the exterior of the cell. The physiological mechanisms and/or consequences of the reverse processes are largely uncharacterized. This report demonstrates that when coupled to oxygen reduction, electrode oxidation can result in cellular energy acquisition. This respiratory process has potentially important implications for how microorganisms persist in energy-limited environments, such as reduced sediments under changing redox conditions. From an applied perspective, this work has important implications for microbially catalyzed processes on electrodes, particularly with regard to understanding models of cellular conversion of electrons from cathodes to microbially synthesized products.
Assessing the validity of surrogate endpoints in the context of a controversy about the measurement of effectiveness of hepatitis C virus treatment
Authors: Dobler Claudia C , Morgan Rebecca L , Falck-Ytter Yngve , Montori Victor M , Murad M Hassan
Published: February 2018

Surrogate endpoints are often used in clinical trials, as they allow for indirect measures of outcomes (eg, shorter trials with less participants). Improvements in surrogate endpoints (eg, reduction in low density lipoprotein cholesterol, normalisation of glycated haemoglobin) achieved with an intervention are, however, not always associated with improvements in patient-important outcomes. The common tendency in evidence-based medicine is to view results based on surrogate endpoints as less certain than results based on long term, final patient-important outcomes and rate them as ‘lower quality evidence’. However, careful appraisal of the validity of a surrogate endpoint as a measure of the final, patient-important outcome is more useful than an automatic judgement. In this guide, we use a contemporary and currently highly debated example of the surrogate endpoint ‘sustained viral response’ (ie, viral eradication considered to represent successful treatment) in patients treated for chronic hepatitis C virus. We demonstrate how the validity of a surrogate endpoint can be critically appraised to assess the quality of the evidence (ie, the certainty in estimates) and the implications for decision-making.