bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems-wide analysis of the ROK-family regulatory gene
rokL6
and its role in the control of glucosamine toxicity in
Streptomyces coelicolor
Authors: Li Chao , Urem Mia , Du Chao , Zhang Le , van Wezel Gilles P. 
Published: November 2023

ABSTRACT

Streptomycetes are saprophytic bacteria that grow on complex polysaccharides, such as cellulose, starch, chitin, and chitosan. For the monomeric building blocks glucose, maltose, and
N
-acetylglucosamine, the metabolic pathways are well-documented, but that of glucosamine (GlcN) is largely unknown.
Streptomyces nagB
mutants, which lack glucosamine-6-phosphate deaminase activity, fail to grow in the presence of high concentrations of GlcN. Here, we report that mutations in the gene for the ROK-family transcriptional regulator RokL6 relieve the toxicity of GlcN in
nagB
mutants, as a result of elevated expression of the major facilitator superfamily (MFS) exporter SCO1448. Systems-wide analysis using RNA sequencing, ChIP-Seq, EMSAs, 5′RACE, bioinformatics, and genetics revealed that RokL6 is an autoregulator that represses the transcription of sco1448 by binding to overlapping promoters in the
rokL6
-sco1448 intergenic region. RokL6-independent expression of sco1448 fully relieved the toxicity of GlcN to
nagB
mutants. Taken together, our data show a novel system of RokL6 as a regulator that controls the expression of the MFS transporter SCO1448, which in turn protects cells against GlcN toxicity, most likely by exporting toxic metabolites out of the cell.

IMPORTANCE

Central metabolism plays a key role in the control of growth and antibiotic production in streptomycetes. Specifically, aminosugars act as signaling molecules that affect development and antibiotic production, via metabolic interference with the global repressor DasR. While aminosugar metabolism directly connects to other major metabolic routes such as glycolysis and cell wall synthesis, several important aspects of their metabolism are yet unresolved. Accumulation of
N
-acetylglucosamine 6-phosphate or glucosamine 6-phosphate is lethal to many bacteria, a yet unresolved phenomenon referred to as “aminosugar sensitivity.” We made use of this concept by selecting for suppressors in genes related to glucosamine toxicity in
nagB
mutants, which showed that the gene pair of
rok
-family regulatory gene
rokL6
and major facilitator superfamily transporter gene sco1448 forms a cryptic rescue mechanism. Inactivation of
rokL6
resulted in the expression of sco1448, which then prevents the toxicity of amino sugar-derived metabolites in
Streptomyces
. The systems biology of RokL6 and its transcriptional control of sco1448 shed new light on aminosugar metabolism in streptomycetes and on the response of bacteria to aminosugar toxicity.
CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA
Authors: Liu Ye , Binda Caroline S. , Berkhout Ben , Das Atze T. 
Published: November 2023

ABSTRACT
Several studies indicate that CRISPR-Cas gene-editing systems can be used to inactivate the HIV-1 proviral DNA in infected cells. Such gene editing introduces mutations, mostly small insertions and deletions (indels), at the targeted sites in the HIV genome or causes excision or inversion of the proviral DNA fragment between two target sites. To investigate whether CRISPR-Cas treatment of latently infected T cell lines can also cause large unintended deletions, we designed a PCR-based sequencing strategy with primer binding sites at various positions in the chromosomal DNA surrounding the integrated proviral DNA genome. We, here, demonstrate that both continuous and transient CRISPR-Cas attack on the integrated HIV DNA does not only result in the expected small indels, but also frequently causes much larger deletions that can include flanking cellular DNA sequences. Analysis of the breakpoint junction sites indicates that the deletions were triggered by an initial on-target attack by CRISPR-Cas. Upon continuous CRISPR-Cas treatment, small microhomologies were frequently observed at the junction sites, which indicates that microhomology-mediated end-joining DNA repair is involved in the generation of the large deletions. As the loss of chromosomal sequences may cause oncogenic cell transformation, unintended large deletions form a potential safety risk in clinical application of this antiviral application.

IMPORTANCE
Although HIV replication can be effectively inhibited by antiretroviral therapy, this does not result in a cure as the available drugs do not inactivate the integrated HIV-1 DNA in infected cells. Consequently, HIV-infected individuals need lifelong therapy to prevent viral rebound. Several preclinical studies indicate that CRISPR-Cas gene-editing systems can be used to achieve permanent inactivation of the viral DNA. It was previously shown that this inactivation was due to small inactivating mutations at the targeted sites in the HIV genome and to excision or inversion of the viral DNA fragment between two target sites. We, here, demonstrate that CRISPR-Cas treatment also causes large unintended deletions, which can include surrounding chromosomal sequences. As the loss of chromosomal sequences may cause oncogenic transformation of the cell, such unintended large deletions form a potential safety risk in clinical application of this antiviral application and possibly all CRISPR-Cas gene-editing approaches.
The dynamic nature of aTiO2: Implications for Ti-based thermometers in magmatic systems
Authors: Fonseca Teixeira L.M. , Troch J. , Bachmann O. 
Published: November 2023

Abstract
In recent decades, new Ti-based thermometers have found widespread use in geosciences, providing a convenient and powerful tool for investigating the crystallization temperatures of quartz and zircons in magmatic systems. However, a commonly overlooked aspect is the constraint of TiO2 activity (aTiO2liquid–rutile). Many studies assume aTiO2 to be constant or equate the presence of Ti-rich phases, such as ilmenite, with fixed activity levels. Using solubility models and data from natural systems, we demonstrate that aTiO2 is a dynamic parameter, influenced by temperature, mineral assemblage, and TiO2 content in the melt. Focusing on examples from several volcanic fields (Bishop Tuff, Fish Canyon Tuff, Yellowstone, and Shiveluch), we discuss the impact of these factors on aTiO2 and highlight how inadequate constraint of aTiO2 can lead to erroneous interpretations of magma storage conditions.
Effective field theory analysis of the Coulomb breakup of the one-neutron halo nucleus $$^{19}$$C
Authors: Capel Pierre , Phillips Daniel R. , Andis Andrew , Bagnarol Mirko , Behzadmoghaddam Behnaz , Bonaiti Francesca , Bubna Rishabh , Capitani Ylenia , Duerinck Pierre-Yves , Durant Victoria , Döpper Niklas , El Boustani Aya , Farrell Roland , Geiger Maurus , Gennari Michael , Goldberg Nitzan , Herko Jakub , Kirchner Tanja , Kubushishi Live-Palm , Li Zhen , Muli Simone S. Li , Long Alexander , Martin Brady , Mohseni Kamyar , Moumene Imane , Paracone Nicola , Parnes Elad , Romeo Beatriz , Springer Victor , Svensson Isak , Thim Oliver , Yapa Nuwan 
Published: November 2023

AbstractWe analyse the Coulomb breakup of $$^{19}$$

19

C measured at 67A MeV at RIKEN. We use the Coulomb-Corrected Eikonal (CCE) approximation to model the reaction and describe the one-neutron halo nucleus $$^{19}$$

19

C within Halo Effective Field Theory (Halo EFT). At leading order we obtain a fair reproduction of the measured cross section as a function of energy and angle. The description is insensitive to the choice of optical potential, as long as it accurately represents the size of $${}^{18}$$

18

C. It is also insensitive to the interior of the $${}^{19}$$

19

C wave function. Comparison between theory and experiment thus enables us to infer asymptotic properties of the ground state of $$^{19}$$

19

C: these data put constraints on the one-neutron separation energy of this nucleus and, for a given binding energy, can be used to extract an asymptotic normalisation coefficient (ANC). These results are confirmed by CCE calculations employing next-to-leading order Halo EFT descriptions of $${}^{19}$$

19

C: at this order the results for the Coulomb breakup cross section are completely insensitive to the choice of the regulator. Accordingly, this reaction can be used to constrain the one-neutron separation energy and ANC of $${}^{19}$$

19

C.
Probability measures of fermions on branes
Authors: Moreira A. R. P. , Dong Shi-Hai 
Published: November 2023

AbstractIn our research, we explore the impact of a geometric non-minimal coupling between fermions and curvature scalars on the positioning of fermions within a brane structure. Our investigation encompasses massless fermionic modes and massive modes, revealing that specifically fermionic modes with left chirality are situated within the brane. This insight allows us to gain a more direct understanding of how the system’s geometry influences the placement of fermion fields on the brane. To delve deeper into the precise localization of massless fermionic modes, we employ entropic information measurements. By varying the parameters that govern the curvature scalars, we observe the ability to adjust the localization of these fermionic modes on the brane. Importantly, the BBM uncertainty relation remains satisfied in all scenarios, particularly for $$f_{1,2,3}$$

f

1
,
2
,
3

. We leverage the Shannon entropy as a highly effective metric to yield accurate results regarding the positioning of massless fermionic modes within our model. In the case of massive fermionic modes, we utilize relative probability analysis to pinpoint the resonant modes, and we identify the existence of these resonant modes in both $$f_{1,2,3}$$

f

1
,
2
,
3

cases. Ultimately, we ascertain that these parameters influence the placement of resonant modes by increasing the amplitude of the massive modes in the core of the brane.
Fault-seal analysis in the Greater Bay du Nord area, Flemish Pass Basin, offshore Newfoundland
Authors: Bernal Asdrúbal J. 
Published: November 2023

A 3D subsurface structural model was built in a zone of the Greater Bay du Nord area, Flemish Pass Basin, offshore Newfoundland and Labrador, to carry out a post-drilled, fault-seal analysis in a multi-rift, geological complex setting; this aimed to test fault-seal predictions, calibrate computed static fault-zone attributes and estimate hydrocarbon contact depths.
Hydrocarbon exploration campaigns in the Greater Bay du Nord area have primarily targeted rotated fault blocks that often exhibit structural segmentation and compartmentalization. A comprehensive approach that combines empirical and deterministic methods for static fault-seal analysis has been implemented. This approach provides insights into open, base and tight fault-seal scenarios, aiding prospect evaluation in this region. Notably, shale gouge ratios (SGRs) in the range 16–25% serve as a crucial indicator of the transition between fault-rock sealing and non-sealing fault segments. Furthermore, it emphasizes the critical role of hydrodynamics when calibrating or evaluating fault-sealing properties.
In areas like the Greater Bay du Nord region, characterized by complex geology, it is imperative to regularly update fault-seal models. These updates should align with the availability of new subsurface data, comprehensive analyses and an improved understanding of the petroleum system.

Thematic collection:
This article is part of the Fault and top seals 2022 collection available at:
https://www.lyellcollection.org/topic/collections/fault-and-top-seals-2022
Evaluation of Left Atrial Function in Patients with Paroxysmal Atrial Fibrillation Using Left Atrial Automatic Myocardial Functional Imaging Ultrasonography
Authors: Liu Hailan , Chen Lili , Song Yan , Xu Yingying , Zhang Chunquan 
Published: November 2023

Aim. To evaluate volume and strain of the left atrium (LA) in people suffering from paroxysmal atrial fibrillation which is not valvular (NVPAF) using the new technology of left atrial automatic myocardial function imaging (AFILA) and to analyze prognostic factors in patients with NVPAF by follow-up. Methods. Between August 2019 and August 2022, a total of 80 NVPAF patients and 60 normal control patients who were hospitalized in the Department of Cardiology were included in the study. The LA volume and strain parameters of the two groups were analyzed. The differences in LA function (LAF) parameters were compared between the two groups to generate the receiver operating characteristic curve (ROC) and calculate the area under the curve (AUC), sensitivity, and specificity of each parameter. Follow-up was conducted on the 80 NVPAF patients included, their treatment methods after admission and their rehospitalization due to heart events were recorded, and independent risk factors influencing the prognosis of NVPAF were obtained. Results. A total of 140 patients participated in the study, including 80 in the NVPAF group and 60 in the normal control group. There was no statistically significant difference in age and sex between the two groups. Compared to the normal group, the LA minimum volume (LAVmin), LA maximum volume (LAVmax), and volume at onset of LA contraction (LAVpreA) in the NVPAF group were significantly increased. The LA emptying fraction (LAEF) was significantly decreased, and LA reservoir strain (S_R), LA conduit strain (S_CD), and LA contractile strain (S_CT) were significantly compromised (

P

< 0.05). There was no significant difference in LA evacuation volume (LAEV) reduction (

P

> 0.05). Logistic regression analysis of LAF parameters in NVPAF patients showed that LAEF and S_R were independently correlated with NVPAF (odds ratio values: 0.883 (0.827–0.943),

P

< 0.001; 0.916 (0.569–1.474),

P

= 0.047). The ROC curve results showed that LAEF had a high efficiency in the diagnosis of NVPAF, with

P

< 0.001, AUC of 0.843, sensitivity of 0.788, and specificity of 0.867. For the LA strain parameters, the S_R test efficiency was higher, with

P

< 0.001, AUC of 0.762, sensitivity of 0.713, and specificity of 0.783. There was a strong correlation between S_R and LAEF in patients with no end event and those with end event. The ROC curve revealed that the S_R was better than LAEF in predicting prognosis of patients with AF (AUC = 0.914,

P

< 0.0001 vs. AUC = 0.876,

P

< 0.0001). S_R of 10.5 and LAEF of 21 were the cut-off values for endpoint events in NVPAF patients, with sensitivity of 0.909 and 0.727 and specificity of 0.904 and 0.901, respectively. Conclusions. AFILA ultrasound technology comprehensively evaluated the LA size and function in patients with NVPAF. The LAEF and S_R were independently correlated with NVPAF and can determine the prognosis of patients with NVPAF.
Data from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella 
Published: November 2023

<div>AbstractBackground:<p>Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.</p>Methods:<p>Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study. Using data on 797 cases and 1,418 controls, two-stage polytomous logistic regression was used to evaluate etiologic heterogeneity between bladder cancer subtypes and quantitative, lifetime estimates of respirable elemental carbon (REC), a surrogate for diesel exposure. Poisson regression was used to evaluate associations between REC and mutational signatures.</p>Results:<p>We observed significant heterogeneity in the diesel-bladder cancer risk relationship, with a strong positive association among cases with high-grade, nonmuscle invasive <i>TP53</i>-mutated tumors compared with controls [OR<sub>Top Tertile vs.Unexposed</sub>, 4.8; 95% confidence interval (CI), 2.2–10.5; <i>P</i><sub>trend</sub> < 0.001; <i>P</i><sub>heterogeneity</sub> = 0.002]. In muscle-invasive tumors, we observed a positive association between diesel exposure and the nitro-PAH signatures of 1,6-dintropyrene (RR, 1.93; 95% CI, 1.28–2.92) and 3-nitrobenzoic acid (RR, 1.97; 95% CI, 1.33–2.92).</p>Conclusions:<p>The relationship between diesel exhaust and bladder cancer was heterogeneous based on the presence of <i>TP53</i> mutations in tumors, further supporting the link between PAH exposure and <i>TP53</i> mutations in carcinogenesis. Future studies that can identify nitro-PAH signatures in exposed tumors are warranted to add human data supporting the link between diesel and bladder cancer.</p>Impact:<p>This study provides additional insight into the etiology and possible mechanisms related to diesel exhaust-induced bladder cancer.</p></div>
Responses of Simulated Arctic Mixed-Phase Clouds to Parameterized Ice Particle Shape
Authors: Ong Chia Rui , Koike Makoto , Hashino Tempei , Miura Hiroaki 
Published: November 2023

Abstract
In simulations of Arctic mixed-phase clouds, cloud persistence and the liquid water path (LWP) are sensitive to ice particle number concentrations. Here, we explore sensitivities of cloud microphysical properties to the dominant ice particle shape (dendrites, plates, columns, or spheres) using the SCALE-AMPS large-eddy simulation model. AMPS is a bin microphysics scheme that predicts particle shapes based on the inherent growth ratio (IGR) of spheroids, which determines vapor depositional growth rates along the a and c axes, and the rimed and aggregate mass fractions. We examine the impacts of various IGR values on simulations of clouds observed during the M-PACE and SHEBA experiments. Under M-PACE (SHEBA) conditions, LWP varies between 49 (1.1) and 230 (6.7) g m−2, and the ice water path (IWP) varies between 3 (0.03) and 40 (0.12) g m−2, depending on the ice shape. The lowest LWP and the highest IWP are obtained when columnar particles dominate because their low terminal velocities and large capacitance and collisional area result in large vapor deposition and riming rates, whereas the highest LWP and lowest IWP are obtained when spherical particles dominate because their vapor deposition and riming rates are low. Because ice particle shape significantly influences simulated Arctic mixed-phase clouds, reliable simulations require accurately estimated IGR values under various atmospheric conditions. Finally, comparisons between the simulation results and observations show that the size distribution larger than 2000 μm is better reproduced when the increase in rimed mass that causes ice particles to become spherical is suppressed.

Significance Statement
Atmospheric models have difficulties in reproducing Arctic mixed-phase clouds because of uncertainties in the parameterization of microphysical processes. This is the first study to use a large-eddy simulation model implemented with a habit-predicting bin microphysics scheme to demonstrate the important role of ice particle shape on the microphysical properties of both heavy-riming and no-riming mixed-phase clouds. We found the vapor deposition and riming rates to be greatly influenced by ice particle shape. By comparing the ice particle size distribution, mass–diameter relationship, and area ratio between simulation results and observations, we show that a hexagonal ice shape model and a riming model that simply converts ice crystals to graupel may not accurately reproduce actual heavy-riming clouds.
Atmospheric Gravity Waves: Processes and Parameterization
Authors: Achatz Ulrich , Alexander M. Joan , Becker Erich , Chun Hye-Yeong , Dörnbrack Andreas , Holt Laura , Plougonven Riwal , Polichtchouk Inna , Sato Kaoru , Sheshadri Aditi , Stephan Claudia Christine , van Niekerk Annelize , Wright Corwin J. 
Published: November 2023

Abstract
Atmospheric predictability from subseasonal to seasonal time scales and climate variability are both influenced critically by gravity waves (GW). The quality of regional and global numerical models relies on thorough understanding of GW dynamics and its interplay with chemistry, precipitation, clouds, and climate across many scales. For the foreseeable future, GWs and many other relevant processes will remain partly unresolved, and models will continue to rely on parameterizations. Recent model intercomparisons and studies show that present-day GW parameterizations do not accurately represent GW processes. These shortcomings introduce uncertainties, among others, in predicting the effects of climate change on important modes of variability. However, the last decade has produced new data and advances in theoretical and numerical developments that promise to improve the situation. This review gives a survey of these developments, discusses the present status of GW parameterizations, and formulates recommendations on how to proceed from there.
Sensitivity of Internal-Tide Generation to Stratification and Its Implication for Deep Overturning Circulations
Authors: Lüschow Veit , von Storch Jin-Song 
Published: November 2023

Abstract
The simple scaling relation for internal-tide generation proposed by Jayne and St. Laurent is widely used for parameterizing turbulent mixing induced by breaking of internal tides. Based on the internal-tide generation derived from a 0.1° ocean general circulation model, we show that depending on which stratification is used, this relation produces different vertical distributions of internal-tide generation. When using the buoyancy frequency at the seafloor, which is a common practice, the scaling relation produces, relative to the model, too-strong internal-tide generation in the upper 2000 m and too-weak internal-tide generation in the lower 2000 m. Moreover, the different vertical distributions in the different ocean basins, characterized by a generally decreasing internal tide generation with increasing depth in the Indo-Pacific but not-decreasing or even increasing internal tide generation with increasing depth in the upper 3000 m of the Atlantic, cannot be captured when using bottom stratification. These unsatisfactory features can be easily removed by replacing the buoyancy frequency at the seafloor by a buoyancy frequency averaged over a large part of the water column. To our knowledge, this sensitivity to stratification has not been explicitly quantified for the global ocean. Because of this sensitivity, the scaling relation of Jayne and St. Laurent should be used with an averaged stratification to ensure a more adequate representation of turbulent diffusivity due to tidal mixing and water mass transformation in the deep oceans.