bluuebunny/crossref_metadata_2025_split huggingface dataset:
POMC Neuron BBSome Regulation of Body Weight is Independent of its Ciliary Function
Authors: Guo Deng-Fu , Williams Paul A , Laule Connor , Seaby Charles , Zhang Qihong , Sheffield Val C , Rahmouni Kamal 
Published: December 2023

Abstract
The BBSome, a complex of several Bardet-Biedl syndrome (BBS) proteins including BBS1, has emerged as a critical regulator of energy homeostasis. Although the BBSome is best known for its involvement in cilia trafficking, through a process that involve BBS3, it also regulates the localization of cell membrane receptors underlying metabolic regulation. Here, we show that inducible Bbs1 gene deletion selectively in proopiomelanocortin (POMC) neurons cause a gradual increase in body weight, which was associated with higher fat mass. In contrast, inducible deletion of Bbs3 gene in POMC neurons failed to affect body weight and adiposity. Interestingly, loss of BBS1 in POMC neurons led to glucose intolerance and insulin insensitivity, whereas BBS3 deficiency in these neurons is associated with slight impairment in glucose handling, but normal insulin sensitivity. BBS1 deficiency altered the plasma membrane localization of serotonin 5-HT2C receptor (5-HT2CR) and ciliary trafficking of neuropeptide Y2 receptor (NPY2R).In contrast, BBS3 deficiency, which disrupted the ciliary localization of the BBSome, did not interfere with plasma membrane expression of 5-HT2CR, but reduced the trafficking of NPY2R to cilia. We also show that deficiency in BBS1, but not BBS3, alters mitochondria dynamics and decreased total and phosphorylated levels of dynamin-like protein 1 (DRP1) protein. Importantly, rescuing DRP1 activity restored mitochondria dynamics and localization of 5-HT2CR and NPY2R in BBS1-deficient cells. The contrasting effects on energy and glucose homeostasis evoked by POMC neuron deletion of BBS1 versus BBS3 indicate that BBSome regulation of metabolism is not related to its ciliary function in these neurons.
No Evidence that Selection on Synonymous Codon Usage Affects Patterns of Protein Evolution in Bacteria
Authors: Moutinho Ana Filipa , Eyre-Walker Adam 
Published: December 2023

Abstract
Bias in synonymous codon usage has been reported across all kingdoms of life. Evidence suggests that codon usage bias is often driven by selective pressures, typically for translational efficiency. These selective pressures have been shown to depress the rate at which synonymous sites evolve. We hypothesize that selection on synonymous codon use could also slow the rate of protein evolution if a non-synonymous mutation changes the codon from being preferred to unpreferred. We test this hypothesis by looking at patterns of protein evolution using polymorphism and substitution data in two bacterial species, Escherichia coli and Streptococcus pneumoniae. We find no evidence that non-synonymous mutations that change a codon from being unpreferred to preferred are more common than the opposite. Overall, selection on codon bias seems to have little influence over non-synonymous polymorphism or substitution patterns.
Variational Bayesian experimental design for geophysical applications: seismic source location, amplitude versus offset inversion, and estimating CO2 saturations in a subsurface reservoir
Authors: Strutz Dominik , Curtis Andrew 
Published: December 2023

SUMMARYIn geophysical surveys or experiments, recorded data are used to constrain properties of the planetary subsurface, oceans, atmosphere or cryosphere. How the experimental data are collected significantly influences which parameters can be resolved and how much confidence can be placed in the results. Bayesian experimental design methods characterize, quantify and maximize expected information post-experiment—an optimization problem. Typical design parameters that can be optimized are source and/or sensor types and locations, and the choice of modelling or data processing methods to be applied to the data. These may all be optimized subject to various physical and cost constraints. This paper introduces variational design methods, and discusses their benefits and limitations in the context of geophysical applications. Variational methods have recently come to prominence due to their importance in machine-learning applications. They can be used to design experiments that best resolve either all model parameters, or the answer to specific questions about the system to be interrogated. The methods are tested in three schematic geophysical applications: (i) estimating a source location given arrival times of radiating energy at sensor locations, (ii) estimating the contrast in seismic velocity across a stratal interface given measurements of the amplitudes of seismic wavefield reflections from that interface, and (iii) designing a survey to best constrain CO2 saturation in a subsurface storage scenario. Variational methods allow the value of expected information from an experiment to be calculated and optimized simultaneously, which results in substantial savings in computational cost. In the context of designing a survey to best constrain CO2 saturation in a subsurface storage scenario, we show that optimal designs may change substantially depending on the particular questions of interest. We also show that one method, so-called DN design, can be effective at substantially lower computational cost than other methods. Overall, this work demonstrates that optimal design methods could be used more widely in Geophysics, as they are in other scientifically advanced fields.
Chlamydia trachomatis T3SS Effector CT622 Induces Proinflammatory Cytokines Through TLR2/TLR4-Mediated MAPK/NF-κB Pathways in THP-1 Cells
Authors: Lei Wenbo , Wen Yating , Yang Yewei , Liu Shuangquan , Li Zhongyu 
Published: December 2023

Abstract

Background
The pathogenesis of Chlamydia trachomatis is associated with the induction of the host inflammatory response; however, the precise underlying molecular mechanisms remain poorly understood.

Methods
CT622, a T3SS effector protein, has an important role in the pathogenesis of C trachomatis; however, whether CT622 can induce a host inflammatory response is not understood. Our findings demonstrate that CT622 induces the expression of interleukins 6 and 8 (IL-6 and IL-8). Mechanistically, these effects involve the activation of the MAPK/NF-κB signaling pathways (mitogen-activated protein kinase/nuclear factor κB).

Results
Interestingly, we demonstrated that the suppression of toll-like receptor 4 using small interfering RNA markedly reduced the phosphorylation of ERK, p38, JNK, and IκBα, concomitant with a significant decrease in IL-6 and IL-8 secretion. Conversely, disruption of toll-like receptor 2 abrogated the CT622-induced upregulation of IL-8 and activation of ERK, whereas IL-6 expression and p38, JNK, and IκBα phosphorylation were unaffected.

Conclusions
Taken together, these results indicate that CT622 contributes to the inflammatory response through the toll-like receptor 2/4–mediated MAPK/NF-κB pathways, which provides insight into the molecular pathology of C trachomatis infection.
Thermostability optimization of the aspartate/alanine exchange transporter from Tetragenococcus halophilus
Authors: Kunii Kota , Yamanaka Takashi , Miyamoto Akari , Nanatani Kei , Abe Keietsu 
Published: December 2023

Abstract
Aspartate/alanine exchange transporter (AspT) is a secondary transporter isolated from the lactic acid bacterium Tetragenococcus halophilus D10 strain. This transporter cooperates with aspartate decarboxylase to produce proton-motive force through decarboxylative phosphorylation. A method that successfully analyzes the AspT mechanism could serve as a prototype for elucidating the substrate transport mechanism of other exchange transporters; therefore, the purpose of this study was to search for conditions that improve the thermal stability of AspT for 3D structure analysis. We used the fluorescence size-exclusion chromatography-based thermostability assay to evaluate conditions that contribute to AspT stability. We found that the AspT thermostability was enhanced at pH 5.0 to 6.0 and in the presence of Na+ and Li+. Pyridoxal phosphate, a coenzyme of aspartate decarboxylase, also had a thermostabilizing effect on AspT. Under the conditions obtained from these results, it was possible to increase the temperature at which 50% of dimer AspT remained by 14°C. We expect these conditions to provide useful information for future structural analysis of AspT.
Precision dosing of venlafaxine during pregnancy: a pharmacokinetics modelling approach
Authors: Alenezi Mona , Badhan Raj K S 
Published: December 2023

Abstract

Objectives
Venlafaxine exposure through gestation is affected by the longitudinal changes in maternal physiology. Confounding treatment is also the impact of CYP2D6 polymorphisms affecting plasma concentrations of venlafaxine.

Methods
A pharmacokinetic modelling approach was employed to assess variations in maternal and foetal cord venlafaxine levels throughout gestation and to identify appropriate doses to maintain venlafaxine levels within the therapeutic range.

Key findings
Throughout gestation, there was a significant decrease in simulated venlafaxine trough plasma concentrations in both extensive metaboliser (EM) and ultra-rapid metaboliser (UM) phenotypes. Approximately 70%–87% of EM and UM phenotypes exhibited trough venlafaxine plasma concentrations below the therapeutic level (&lt;25 ng/ml), which increased to 96% at week 30. While for poor metabolizer (PM) phenotypes, the percentage was approximately 4%.

Conclusion
The standard daily dose of 75 mg required adjustment for all phenotypes examined during gestation. A daily dose of 37.5–112.5 mg is appropriate for PM throughout pregnancy. For EM, a dose of 225 mg daily in the first trimester, 262.5 mg daily in the second trimester, and 375 mg daily in the third trimester is suggested to be optimal. For UM, a dose of 375 mg daily throughout gestation is suggested to be optimal.
Particle acceleration by sub-proton cyclotron frequency spectrum of dispersive Alfven waves in inhomogeneous solar coronal plasmas
Authors: Tsiklauri D 
Published: December 2023

ABSTRACT
The problem of explaining observed soft X-ray fluxes during solar flares, which invokes acceleration of large fraction of electrons, if the acceleration takes places at the solar coronal loop-top, can potentially be solved by postulating that flare at loop-top creates dispersive Alfven waves (DAWs) which propagate towards the foot-points. As DAWs move in progressively denser parts of the loop (due to gravitational stratification) the large fraction of electrons is no longer needed. Here, we extend our previous results by considering f−1 frequency spectrum of DAWs and add He++ ions using fully kinetic particle-in-cell (PIC) simulations. We consider cases when transverse density gradient is in the range 4–40c/ωpe and DAW driving frequency is 0.3–0.6ωcp. We find that (i) The frequency spectrum case does not affect electron acceleration fraction in the like-to-like cases, but few times larger percentage of He++ heating is seen due to ion cyclotron resonance; (ii) In cases when counter propagating DAWs collide multiple-times, much larger electron and ion acceleration fractions are found, but the process is intermittent in time. This is because intensive heating (temperature increase) makes the-above-thermal-fraction smaller; Also more isotropic velocity distributions are seen; (iii) Development of kink oscillations occurs when DAWs collide; (iv) Scaling of the magnetic fluctuations power spectrum steepening in the higher-density regions is seen, due to wave refraction. Our PIC runs produce much steeper slopes than the orginal spectrum, indicating that the electron-scale physics has a notable effect on DAW spectrum evolution.
Comparing indirect methods for black hole masses in AGN: the good, the bad, and the ugly
Authors: Gliozzi M , Williams J K , Akylas A , Papadakis I E , Shuvo O I , Halavatkar A , Alt A 
Published: December 2023

ABSTRACT
The black hole mass MBH is crucial in constraining the growth of supermassive black holes within their host galaxies. Since direct measurements of MBH with dynamical methods are restricted to a limited number of nearly quiescent nearby galaxies and a small minority of active galactic nuclei (AGN), we must rely on indirect methods. In this work, we utilize an unbiased, volume-limited, hard X-ray selected sample of AGN to compare the reliability of some commonly used indirect methods, emphasizing those that can be applied to obscured AGN. Based on a subsample of AGN with MBH determined via dynamical methods, our study suggests that X-ray-based techniques, such as the scaling method and the one based on the variability measured through the excess variance, are in good agreement with the dynamical methods. On the other hand, the M–σ⋆ correlation based on inactive galaxies tends to systematically overestimate MBH, regardless of the level of obscuration. We provide a correcting factor that produces an acceptable agreement with dynamical values and can be used to quickly correct the MBH computed with this method. We also derive an alternative M–σ⋆ correlation based on this unbiased sample of AGN with a slope considerably shallower than the ones obtained using inactive galaxies, suggesting that the latter may not be appropriate to compute the MBH in AGN. Finally, we find that no quick fix can be applied to correct the MBH obtained from the fundamental plane of black hole activity, casting doubts on the reliability of this method.
Evolution of eccentric stellar discs around supermassive black holes: the complex disc disruption dynamics and the milliparsec stars
Authors: Rantala Antti , Naab Thorsten 
Published: December 2023

ABSTRACT
We study the 10 Myr evolution of parsec-scale stellar discs with initial masses of Mdisc = 1.0–$7.5 \times 10^4\, \mathrm{M}_\odot$ and eccentricities einit = 0.1–0.9 around supermassive black holes (SMBHs). Our disc models are embedded in a spherical background potential and have top-heavy single and binary star initial mass functions (IMF) with slopes of 0.25–1.7. The systems are evolved with the N-body code BIFROST, including post-Newtonian (PN) equations of motion and simplified stellar evolution. All discs are unstable and evolve on Myr time-scales towards similar eccentricity distributions peaking at e⋆ ∼ 0.3–0.4. Models with high einit also develop a very eccentric (e⋆ ≳ 0.9) stellar population. For higher disc masses Mdisc ≳ 3 × 104 M⊙, the disc disruption dynamics is more complex than the standard secular eccentric disc instability with opposite precession directions at different disc radii – a precession direction instability. We present an analytical model describing this behaviour. A milliparsec population of N ∼ 10–100 stars forms around the SMBH in all models. For low einit, stars migrate inward while for einit ≳ 0.6 stars are captured by the Hills mechanism. Without PN, after 6 Myr, the captured stars have a sub-thermal eccentricity distribution. We show that including PN effects prevents this thermalization by suppressing resonant relaxation effects and cannot be ignored. The number of tidally disrupted stars is similar or larger than the number of milliparsec stars. None of the simulated models can simultaneously reproduce the kinematic and stellar population properties of the Milky Way centre clockwise disc and the S-cluster.
OGHReS: star formation in the outer galaxy (ℓ = 250°–280°)
Authors: Urquhart J S , König C , Colombo D , Karska A , Wyrowski F , Menten K M , Moore T J T , Brand J , Elia D , Giannetti A , Leurini S , Figueira M , Lee M -Y , Dumke M 
Published: December 2023

ABSTRACT
We have used data from the Outer Galaxy High-Resolution Survey (OGHReS) to refine the velocities, distances, and physical properties of a large sample of 3584 clumps detected in far-infrared/submillimetre emission in the Hi-GAL survey located in the ℓ = 250°–280° region of the Galactic plane. Using 12CO and 13CO spectra, we have determined reliable velocities to 3412 clumps (95 per cent of the sample). In comparison to the velocities from the Hi-GAL catalogue, we find good agreement for 80 per cent of the sample (within 5 km s−1). Using the higher resolution and sensitivity of OGHReS has allowed us to correct the velocity for 632 clumps and provide velocities for 687 clumps for which no velocity had been previously allocated. The velocities are used with a rotation curve to refine the distances to the clumps and to calculate the clumps’ properties using a distance-dependent gas-to-dust ratio. We have determined reliable physical parameters for 3200 outer Galaxy dense clumps (∼90 per cent of the Hi-GAL sources in the region). We find a trend of decreasing luminosity-to-mass ratio with increasing Galactocentric distance, suggesting the star formation efficiency is lower in the outer Galaxy or that it is resulting in more lower mass stars than in the inner Galaxy. We also find a similar surface density for protostellar clumps located in the inner and outer Galaxy, revealing that the surface density requirements for star formation are the same across the Galactic disc.
Light curve and hardness tests for millilensing in GRB 081122A, GRB 081126A, GRB 110517B, and GRB 210812A
Authors: Mukherjee Oindabi , Nemiroff Robert 
Published: December 2023

ABSTRACT
Analyses are given on four recent gravitational millilensing claims on gamma-ray bursts (GRBs): GRB 081122A, GRB 081126A, GRB 110517B, and GRB 210812A. Two tests, a light curve similarity test and a hardness similarity test, compare different temporal sections of a single GRB to see if they are statistically similar. The hardness similarity test shows that the ratio between the second and the first emission episodes in each energy channel differed from the same ratio averaged over all energy channels at above 90 per cent confidence level in GRB 081122A. Additionally, the light curve similarity test applied to GRB 081122A, GRB 081126A, and GRB 110517B separately indicated a high likelihood that the two emission episodes in each GRB were not from the same parent emission episode. This conclusion was reached with confidence levels of 4.8σ for GRB 081122A, 3.08σ for GRB 081126A, and 8.45σ for GRB 110517B. However, these tests did not detect a significant difference between the pulses of GRB 210812A. Consequently, our results suggest that while GRB 210812A could not be conclusively ruled out, the other three GRBs do not show clear evidence of millilensing.
Lyricist as Analyst: Rhyme Scheme as Music-Setting in the Great American Songbook
Authors: Lawrence John Y 
Published: December 2023

AbstractAlthough most songwriting teams in the Great American Songbook wrote music first and lyrics second, most studies of music-text interaction in this repertoire still evince a lyrics-first mindset, in which the music is viewed as text-setting. In this article, I propose the opposite approach: considering lyrics as a form of music-setting, in which the lyricist’s superimposition of a verbal form (the rhyme scheme) upon the composer’s pre-existing musical form counts as an act of analysis. I examine in turn: (1) the most common phrase structures and their associated rhyme schemes in songs from 1919 to 1943; (2) Lorenz Hart’s negotiation of the unusual XYYZ phrase structure that Richard Rodgers frequently employed; and (3) special cases where the lyricist contests the composer’s form and the effect that this can have on performers’ choices.
BG4 antibody can recognize telomeric G-quadruplexes harboring destabilizing base modifications and lesions
Authors: Johnson Samuel A , Paul Tapas , Sanford Samantha L , Schnable Brittani L , Detwiler Ariana C , Thosar Sanjana A , Van Houten Bennett , Myong Sua , Opresko Patricia L 
Published: December 2023

Abstract
BG4 is a single-chain variable fragment antibody shown to bind various G-quadruplex (GQ) topologies with high affinity and specificity, and to detect GQ in cells, including GQ structures formed within telomeric TTAGGG repeats. Here, we used ELISA and single-molecule pull-down (SiMPull) detection to test how various lengths and GQ destabilizing base modifications in telomeric DNA constructs alter BG4 binding. We observed high-affinity BG4 binding to telomeric GQ independent of telomere length, although three telomeric repeat constructs that cannot form stable intramolecular GQ showed reduced affinity. A single guanine substitution with 8-aza-7-deaza-G, T, A, or C reduced affinity to varying degrees depending on the location and base type, whereas two G substitutions in the telomeric construct dramatically reduced or abolished binding. Substitution with damaged bases 8-oxoguanine and O6-methylguanine failed to prevent BG4 binding although affinity was reduced depending on lesion location. SiMPull combined with FRET revealed that BG4 binding promotes folding of telomeric GQ harboring a G to T substitution or 8-oxoguanine. Atomic force microscopy revealed that BG4 binds telomeric GQ with a 1:1 stoichiometry. Collectively, our data suggest that BG4 can recognize partially folded telomeric GQ structures and promote telomeric GQ stability.
The disordered N-terminal tail of SARS-CoV-2 Nucleocapsid protein forms a dynamic complex with RNA
Authors: Cubuk Jasmine , Alston Jhullian J , Incicco J Jeremías , Holehouse Alex S , Hall Kathleen B , Stuchell-Brereton Melissa D , Soranno Andrea 
Published: December 2023

Abstract
The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific and specific RNA results in a modulation of the tail configurations, which respond in an RNA length-dependent manner. Not only does the disordered NTD increase affinity for RNA, but mutations that occur in the Omicron variant modulate the interactions, indicating a functional role of the disordered tail. Finally, we found that the NTD-RBD preferentially interacts with single-stranded RNA and that the resulting protein:RNA complexes are flexible and dynamic. We speculate that this mechanism of interaction enables the Nucleocapsid protein to search the viral genome for and bind to high-affinity motifs.