bluuebunny/crossref_metadata_2025_split huggingface dataset:
microRNA160 dictates stage‐specific auxin and cytokinin sensitivities and directs soybean nodule development
Authors: Nizampatnam Narasimha Rao , Schreier Spencer John , Damodaran Suresh , Adhikari Sajag , Subramanian Senthil 
Published: August 2015

SummaryLegume nodules result from coordinated interactions between the plant and nitrogen‐fixing rhizobia. The phytohormone cytokinin promotes nodule formation, and recent findings suggest that the phytohormone auxin inhibits nodule formation. Here we show that microRNA160 (miR160) is a key signaling element that determines the auxin/cytokinin balance during nodule development in soybean (Glycine max). miR160 appears to promote auxin activity by suppressing the levels of the ARF10/16/17 family of repressor ARF transcription factors. Using quantitative PCR assays and a fluorescence miRNA sensor, we show that miR160 levels are relatively low early during nodule formation and high in mature nodules. We had previously shown that ectopic expression of miR160 in soybean roots led to a severe reduction in nodule formation, coupled with enhanced sensitivity to auxin and reduced sensitivity to cytokinin. Here we show that exogenous cytokinin restores nodule formation in miR160 over‐expressing roots. Therefore, low miR160 levels early during nodule development favor cytokinin activity required for nodule formation. Suppression of miR160 levels using a short tandem target mimic (STTM160) resulted in reduced sensitivity to auxin and enhanced sensitivity to cytokinin. In contrast to miR160 over‐expressing roots, STTM160 roots had increased nodule formation, but nodule maturation was significantly delayed. Exogenous auxin partially restored proper nodule formation and maturation in STTM160 roots, suggesting that high miR160 activity later during nodule development favors auxin activity and promotes nodule maturation. Therefore, miR160 dictates developmental stage‐specific sensitivities to auxin and cytokinin to direct proper nodule formation and maturation in soybean.
Correlation of serum cardiac troponin I and acute phase protein concentrations with clinical staging in dogs with degenerative mitral valve disease
Authors: Polizopoulou Zoe S. , Koutinas Christos K. , Cerón José J. , Tvarijonaviciute Asta , Martínez‐Subiela Silvia , Dasopoulou Anastasia , York Malcolm J. , Roman Ian F. , Gandhi Mitul , Patel Sonal , O'Brien Peter J. 
Published: August 2015

BackgroundCardiac troponin I (cTnI) correlates with severity of myocardial injury. Nonspecific inflammation in congestive heart failure (CHF) could be assessed by C‐reactive protein (CRP), haptoglobin (Hp), and ceruloplasmin (Cp) measurements.ObjectivesThe aim of the study was to determine whether serum cTnI, CRP, Hp, and Cp concentrations differ among various stages of mitral valve disease (MVD) in dogs.Materials and methodsDogs with MVD were allocated to 3 groups (I – asymptomatic; II – mild to moderate CHF; III advanced CHF) according to the scheme of the International Small Animal Cardiac Healthy Council (ISACHC). Concentrations of cTnI, CRP, Cp, and Hp were measured in all dogs upon admission, and cTnI and CRP were measured bimonthly during a 4‐month follow‐up period.ResultsIn total 46 dogs with MVD were enrolled for the cross‐sectional part (21 Group I, 11 Group II, 14 Group III), and 35 dogs were included in the longitudinal study. Initial mean Cp concentrations were similar among all groups. There was a statistically significant difference in Hp and CRP concentrations between group I (n = 21, P = .019) and III (n = 14, P < .001). There was a statistically significant decrease in CRP (P = .033) and cTnI (P = .009) concentrations over the longitudinal study (all groups). CRP concentrations were significantly higher in group I than III (P = .004). During the 6‐month monitoring period of 35 dogs, there was a statistically significant positive correlation between cTnI and CRP (P < .001).ConclusionDifferences in CRP concentrations between clinical stages of MVD suggest a clinically and therapeutically relevant inflammatory component.
Determining canine skin concentrations of terbinafine to guide the treatment of Malassezia dermatitis
Authors: Gimmler Jacqueline R. , White Amelia G. , Kennis Robert A. , Cruz‐Espindola Crisanta , Boothe Dawn M. 
Published: August 2015

BackgroundTerbinafine (TBF) is known to concentrate and persist in human skin. Its use is increasing in veterinary medicine, but there are limited data concerning its tissue concentration and efficacy in dogs.Hypothesis/Objectives(i) Describe TBF accumulation in canine skin; (ii) Integrate pharmacokinetic data with historical minimum inhibitory concentration (MIC) results for Malassezia pachydermatis to verify the currently used dosage of TBF for the treatment of Malassezia dermatitis.AnimalsTen healthy, client‐owned dogs.MethodsDogs were given TBF (generic preparation, 250 mg tablets) 30 mg/kg per os (p.o.) once daily for 21 days. Serum, sebum and stratum corneum (SC) samples were collected on days 1, 5, 7, 11, 14, 21, 28 and 35. High‐pressure liquid chromatography was used to determine drug concentrations in samples.ResultsRelevant (mean ± standard deviation) parameters for TBF in serum, paw SC, thorax SC and sebum, respectively, were: maximum concentration (Cmax, μg/mL) 23.59 ± 10.41, 0.31 ± 0.26, 0.30 ± 0.32 and 0.48 ± 0.25; half‐life (t1/2, d) 4.49 ± 2.24, 6.34 ± 5.33, 4.64 ± 3.27 and 5.12 ± 3.33; time to maximum concentration (Tmax, d) 10.40 ± 6.98, 13.20 ± 5.16, 11.90 ± 8.62 and 10.60 ± 3.69.Conclusions and clinical importanceThese results suggest that TBF does not achieve high concentrations in canine SC or sebum compared to serum. The mean Cmax of all skin tissues (paw SC, thorax SC and sebum) barely exceeded the reported Malassezia MIC90, of 0.25 μg/mL, which indicates that doses higher than 30 mg/kg p.o. once daily may be necessary.
Fully iterative scatter corrected digital breast tomosynthesis using GPU‐based fast Monte Carlo simulation and composition ratio update
Authors: Kim Kyungsang , Lee Taewon , Seong Younghun , Lee Jongha , Jang Kwang Eun , Choi Jaegu , Choi Young Wook , Kim Hak Hee , Shin Hee Jung , Cha Joo Hee , Cho Seungryong , Ye Jong Chul 
Published: August 2015

Purpose:In digital breast tomosynthesis (DBT), scatter correction is highly desirable, as it improves image quality at low doses. Because the DBT detector panel is typically stationary during the source rotation, antiscatter grids are not generally compatible with DBT; thus, a software‐based scatter correction is required. This work proposes a fully iterative scatter correction method that uses a novel fast Monte Carlo simulation (MCS) with a tissue‐composition ratio estimation technique for DBT imaging.Methods:To apply MCS to scatter estimation, the material composition in each voxel should be known. To overcome the lack of prior accurate knowledge of tissue composition for DBT, a tissue‐composition ratio is estimated based on the observation that the breast tissues are principally composed of adipose and glandular tissues. Using this approximation, the composition ratio can be estimated from the reconstructed attenuation coefficients, and the scatter distribution can then be estimated by MCS using the composition ratio. The scatter estimation and image reconstruction procedures can be performed iteratively until an acceptable accuracy is achieved. For practical use, (i) the authors have implemented a fast MCS using a graphics processing unit (GPU), (ii) the MCS is simplified to transport only x‐rays in the energy range of 10–50 keV, modeling Rayleigh and Compton scattering and the photoelectric effect using the tissue‐composition ratio of adipose and glandular tissues, and (iii) downsampling is used because the scatter distribution varies rather smoothly.Results:The authors have demonstrated that the proposed method can accurately estimate the scatter distribution, and that the contrast‐to‐noise ratio of the final reconstructed image is significantly improved. The authors validated the performance of the MCS by changing the tissue thickness, composition ratio, and x‐ray energy. The authors confirmed that the tissue‐composition ratio estimation was quite accurate under a variety of conditions. Our GPU‐based fast MCS implementation took approximately 3 s to generate each angular projection for a 6 cm thick breast, which is believed to make this process acceptable for clinical applications. In addition, the clinical preferences of three radiologists were evaluated; the preference for the proposed method compared to the preference for the convolution‐based method was statistically meaningful (p < 0.05, McNemar test).Conclusions:The proposed fully iterative scatter correction method and the GPU‐based fast MCS using tissue‐composition ratio estimation successfully improved the image quality within a reasonable computational time, which may potentially increase the clinical utility of DBT.
Measuring retinal blood flow in rats using Doppler optical coherence tomography without knowing eyeball axial length
Authors: Liu Wenzhong , Yi Ji , Chen Siyu , Jiao Shuliang , Zhang Hao F. 
Published: August 2015

Purpose:Doppler optical coherence tomography (OCT) is widely used for measuring retinal blood flow. Existing Doppler OCT methods require the eyeball axial length, in which empirical values are usually used. However, variations in the axial length can create a bias unaccounted for in the retinal blood flow measurement. The authors plan to develop a Doppler OCT method that can measure the total retinal blood flow rate without requiring the eyeball axial length.Methods:The authors measured the retinal blood flow rate using a dual‐ring scanning protocol. The small and large scanning rings entered the eye at different incident angles (small ring: 4°; large ring: 6°), focused on different locations on the retina, and detected the projected velocities/phase shifts along the probing beams. The authors calculated the ratio of the projected velocities between the two rings, and then used this ratio to estimate absolute flow velocity. The authors tested this method in both Intralipid phantoms and in vivo rats.Results:In the Intralipid flow phantom experiments, the preset and measured flow rates were consistent with the coefficient of determination as 0.97. Linear fitting between preset and measured flow rates determined the fitting slope as 1.07 and the intercept as −0.28. In in vivo rat experiments, the measured average total retinal blood flow was 7.02 ± 0.31μl/min among four wild‐type rats. The authors’ measured flow rates were consistent with results in the literature.Conclusions:By using a dual‐ring scanning protocol with carefully controlled incident angle difference between the two scanning rings in Doppler OCT, the authors demonstrated that it is feasible to measure the absolute retinal blood flow without knowing the eyeball axial length.
The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate
Authors: Rozo Michelle , Gronvall Gigi Kwik 
Published: August 2015

ABSTRACT
The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.
An Alternative Terminal Step of the General Secretory Pathway in Staphylococcus aureus
Authors: Craney Arryn , Dix Melissa M. , Adhikary Ramkrishna , Cravatt Benjamin F. , Romesberg Floyd E. 
Published: August 2015

ABSTRACT

Type I signal peptidase (SPase) is essential for viability in wild-type bacteria because the terminal step of the bacterial general secretory pathway requires its proteolytic activity to release proteins from their membrane-bound N-terminal leader sequences after translocation across the cytoplasmic membrane. Here, we identify the
Staphylococcus aureus
operon
ayrRABC
(SA0337 to SA0340) and show that once released from repression by AyrR, the protein products AyrABC together confer resistance to the SPase inhibitor arylomycin M131 by providing an alternate and novel method of releasing translocated proteins. Thus, the derepression of
ayrRABC
allows cells to bypass the essentiality of SPase. We demonstrate that AyrABC functionally complements SPase by mediating the processing of the normally secreted proteins, albeit in some cases with reduced efficiency and either without cleavage or via cleavage at a site N-terminal to the canonical SPase cleavage site. Thus,
ayrRABC
encodes a secretion stress-inducible alternate terminal step of the general secretory pathway.

IMPORTANCE
Addressing proteins for proper localization within or outside a cell in both eukaryotes and prokaryotes is often accomplished with intrinsic signals which mediate membrane translocation and which ultimately must be removed. The canonical enzyme responsible for the removal of translocation signals is bacterial type I signal peptidase (SPase), which functions at the terminal step of the general secretory pathway and is thus essential in wild-type bacteria. Here, we identify a four-gene operon in
S. aureus
that encodes an alternate terminal step of the general secretory pathway and thus makes SPase nonessential. The results have important implications for protein secretion in bacteria and potentially for protein trafficking in prokaryotes and eukaryotes in general.
New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in
Bordetella
Virulence
Authors: Melvin Jeffrey A. , Scheller Erich V. , Noël Christopher R. , Cotter Peggy A. 
Published: August 2015

ABSTRACT

Bordetella
filamentous hemagglutinin (FHA), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. FHA is first synthesized as an ~370-kDa preproprotein called FhaB. Removal of an N-terminal signal peptide and a large C-terminal prodomain (PD) during secretion results in “mature” ~250-kDa FHA, which has been assumed to be the biologically active form of the protein. Deletion of two C-terminal subdomains of FhaB did not affect production of functional FHA, and the mutant strains were indistinguishable from wild-type bacteria for their ability to adhere to the lower respiratory tract and to suppress inflammation in the lungs of mice. However, the mutant strains, which produced altered FhaB molecules, were eliminated from the lower respiratory tract much faster than wild-type
B. bronchiseptica
, suggesting a defect in resistance to early immune-mediated clearance. Our results revealed, unexpectedly, that full-length FhaB plays a critical role in
B. bronchiseptica
persistence in the lower respiratory tract.

IMPORTANCE
The
Bordetella
filamentous hemagglutinin (FHA) is a primary component of the acellular pertussis vaccine and an important virulence factor. FHA is initially produced as a large protein that is processed during secretion to the bacterial surface. As with most processed proteins, the mature form of FHA has been assumed to be the functional form of the protein. However, our results indicate that the full-length form plays an essential role in virulence
in vivo
. Furthermore, we have found that FHA contains intramolecular regulators of processing and that this control of processing is integral to its virulence activities. This report highlights the advantage of studying protein maturation and function simultaneously, as a role for the full-length form of FHA was evident only from
in vivo
infection studies and not from
in vitro
studies on the production or maturation of FHA or even from
in vitro
virulence-associated activity assays.
The influence of neighbourhood-level socioeconomic deprivation on cardiovascular disease mortality in older age: longitudinal multilevel analyses from a cohort of older British men
Authors: Ramsay S E , Morris R W , Whincup P H , Subramanian S V , Papacosta A O , Lennon Lucy T , Wannamethee S G 
Published: August 2015

BackgroundEvidence from longitudinal studies on the influence of neighbourhood socioeconomic factors in older age on cardiovascular disease (CVD) mortality is limited. We aimed to investigate the prospective association of neighbourhood-level deprivation in later life with CVD mortality, and assess the underlying role of established cardiovascular risk factors.MethodsA socially representative cohort of 3924 men, aged 60–79 years in 1998–2000, from 24 British towns, was followed up until 2012 for CVD mortality. Quintiles of the national Index of Multiple Deprivation (IMD), a composite score of neighbourhood-level factors (including income, employment, education, housing and living environment) were used. Multilevel logistic regression with discrete-time models (stratifying follow-up time into months) were used.ResultsOver 12 years, 1545 deaths occurred, including 580 from CVD. The risk of CVD mortality showed a graded increase from IMD quintile 1 (least deprived) to 5 (most deprived). Compared to quintile 1, the age-adjusted odds of CVD mortality in quintile 5 were 1.71 (95% CI 1.32 to 2.21), and 1.62 (95% CI 1.23 to 2.13) on further adjustment for individual social class, which was attenuated slightly to 1.44 (95% CI 1.09 to 1.89), but remained statistically significant after adjustment for smoking, body mass index, physical activity and use of alcohol. Further adjustment for blood pressure, high-density lipoprotein cholesterol and prevalent diabetes made little difference.ConclusionsNeighbourhood-level deprivation was associated with an increased risk of CVD mortality in older people independent of individual-level social class and cardiovascular risk factors. The role of other specific neighbourhood-level factors merits further research.
Testing sterile neutrino extensions of the Standard Model at the Circular Electron Positron Collider
Authors: Antusch Stefan , Fischer Oliver 
Published: August 2015

Extending the Standard Model with sterile (“right-handed”) neutrinos is one of the best motivated ways to account for the observed neutrino masses. We discuss the expected sensitivity of the Circular Electron Positron Collider (CEPC) for testing such extensions. An interesting scenario is given by symmetry protected seesaw models, which theoretically allow for sterile neutrino masses around the electroweak scale with up to order one mixings with the active (SM) neutrinos.When the masses of the sterile neutrinos are well above the electroweak scale, they affect precision data via effective non-unitarity of the leptonic mixing matrix in a model independent way. The expected improvement of the electroweak precision observables from the CEPC may allow to test mixings between active and sterile neutrinos down to [Formula: see text] (using currently discussed CEPC performance parameters).For sterile neutrinos with masses around the electroweak scale, direct searches are possible. Such tests are given by the search for sterile neutrino decays at the [Formula: see text] pole, by deviations from the SM cross section for four leptons at and beyond the [Formula: see text] threshold, and by Higgs boson production and decays. The expected sensitivities at the CEPC could reach down to mixings as small as [Formula: see text].
A heuristic approach to the quantum measurement problem: How to distinguish particle detectors from ordinary objects
Authors: Merlin R. 
Published: August 2015

Elementary particle detectors fall broadly into only two classes: phase-transformation devices, such as the bubble chamber, and charge-transfer devices like the Geiger–Müller tube. Quantum measurements are seen to involve transitions from a long-lived metastable state (e.g., superheated liquid or a gas of atoms between charged capacitor plates) to a thermodynamically stable condition. A detector is then a specially prepared object undergoing a metastable-to-stable transformation that is significantly enhanced by the presence of the measured particle, which behaves, in some sense, as the seed of a process of heterogeneous nucleation. Based on this understanding of the operation of a conventional detector, and using results of orthogonality-catastrophe theory, we argue that, in the thermodynamic limit, the pre-measurement Hamiltonian is not the same as that describing the detector during or after the interaction with a particle and, thus, that superpositions of pointer states (Schrödinger’s cats) are unphysical because their time evolution is ill defined. Examples of particle-induced changes in the Hamiltonian are also given for ordinary systems whose macroscopic parameters are susceptible to radiation damage, but are not modified by the interaction with a single particle.
Prescribing the behavior of Weil–Petersson geodesics in the moduli space of Riemann surfaces
Authors: Modami Babak 
Published: August 2015

We study Weil–Petersson (WP) geodesics with narrow end invariant and develop techniques to control length-functions and twist parameters along them and prescribe their itinerary in the moduli space of Riemann surfaces. This class of geodesics is rich enough to provide for examples of closed WP geodesics in the thin part of the moduli space, as well as divergent WP geodesic rays with minimal filling ending lamination. Some ingredients of independent interest are the following: A strength version of Wolpert's Geodesic Limit Theorem proved in Sec. 4. The stability of hierarchy resolution paths between narrow pairs of partial markings or laminations in the pants graph proved in Sec. 5. A kind of symbolic coding for laminations in terms of subsurface coefficients presented in Sec. 7.