bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomic analysis and characterization ofStaphylococcussp. AOAB, isolated from a notoriously invasiveMnemiopsis leidyigut revealed multiple antibiotic resistance determinants
Authors: Mariita Richard M. , Hossain Mohammad J. , Moss Anthony G.
Published: January 2021

Here, we describe the isolation and characterization of a coagulase-negative, vancomycin and oxacillin-susceptible novel bacterium of the genusStaphylococcus. Staphylococcussp. strain AOAB was isolated from the stomodeum (gut) of theMnemiopsis leidyifrom Mobile Bay, Alabama USA. A polyphasic taxonomic approach comprised of phenotypic, chemotaxonomic and genotypic characteristics was used for analysis. The dominant respiratory quinone detected was MK-7 (100%). Major cellular fatty acids were anteiso-C15:0(40.52%), anteiso-C17:0(13.04 %), C-18:0(11.53%) and C-20:0(10.45%). The polar lipid profile consisted of glycolipid, phospholipid, phosphatidylglycerol and diphosphatidylglycerol. Although strain AOAB had a 16SrRNA gene sequence similarity of 99% withS. warneriSG1,S. pasteuri, S. devrieseiKS-SP_60,S. lugdunensisHKU09-01,S. epidermidisRP62A,S. haemolyticusJCSC1435 andS. hominisDM 122, it was be distinguished from those species based on Multi-Locus Sequence Analysis (MLSA) using 6 marker genes (16S rRNA,hsp60, rpoB, dnaJ, sodAandtuf). MLSA revealed strain AOAB to be closely related toS. warneriSG1 andS. pasteuriSP1 but distinct from two hitherto known species. These results were confirmed by Average Nucleotide Identity (closest ANI of 84.93% and 84.58% identity againstS. warneriSG1 andS. pasteuriSP1 respectively).In-silicoDNA-DNA hybridization was <70% (33.1 % and 32.8% againstS. warneriSG1 andS. pasteuriSP1 respectively), which further confirmed that the strain was a potential novelStaphylococcusspecies.
Mapping the Promiscuous Binding Interface of HOX-A11 with KIX by Experimentally Guidedin-silicodocking
Authors: Ganguly Soumya , Wagner Günter P. , Meiler Jens
Published: January 2021

Transcription factors (TFs) regulate levels of transcription through a complex array of protein-protein interactions, thereby controlling key physiological processes such as development, stress response and cell growth. The transcription factor HOXA11 contains an intrinsically disordered regions (IDR) through which it interacts with CREB binding protein (CBP) and regulates endometrial development and function in eutherian mammals. The interaction between the IDR of HOXA11 and CBP was analyzed using computational docking guided by experimental constraints. HOXA11 IDR interacts with the KIX domain of CBP at two discrete sites – MLL and cMyb, mediated by sticky hydrophobic grooves on the surface of KIX. A five residue motif FDQFF on HOXA11 can interact both at cMyb and MLL site of KIX resulting in a promiscuous binding.

Author Summary

We demonstrate how the intrinsically disordered region (IDR) of transcription factor HOXA11 interacts at two distinct sites of the transcription coactivator CREB binding protein (CBP). By combining computational docking with limited experimental data we construct models of the complex of the KIX domain within CBP and a short helical segment within the IDR of HOXA11. The interaction between HOXA11 and CBP is believed to trigger the downstream expression of genes important in embryonic development.
Complex phyllosphere microbiome aids in the establishment of the invasive macrophyteHydrilla verticillata(L.) under conditions of nitrogen scarcity
Authors: Bárta Jiří , de Paula Caio Cesar Pires , Rejmánková Eliška , Lin Qiang , Kohoutová Iva , Sirová Dagmara
Published: January 2021

Despite the low availability of nitrogen (N), the highly productive macrophyteHydrilla verticillata(L.) is a successful invader of the littoral zones at lake Atitlán, Guatemala, with profound implications for lake ecology. To help answer the question of howHydrilla, accompanied by the filamentous green algaCladophoraKützing (Ulvophyceae), sustains fast growth under conditions of N scarcity, we studied the composition and potential biogeochemical function of the associated microbiomes. We combined results from next generation sequencing of associated bacterial and fungal assemblages with traditional microscopy-based taxonomical evaluation of algae and cyanobacteria. We focused on the presence of specific N2-fixing genera and their relative importance. Data on community composition are complemented with measurements of diazotrophic activity. The results expand our knowledge of the ecophysiology of these algae-plant-microbe consortia and suggest that several levels of biological complexity should be considered to fully understand aquatic plant ecology and the process of macrophyte invasions.
Dissecting lipid contents in the distinct regions of native retinal rod disk membranes
Authors: Sander Christopher L. , Sears Avery E. , Pinto Antonio F. M. , Choi Elliot H. , Kahremany Shirin , Jin Hui , Pardon Els , Suh Susie , Dong Zhiqian , Steyaert Jan , Saghatelian Alan , Skowronska-Krawczyk Dorota , Kiser Philip D. , Palczewski Krzysztof
Published: January 2021

Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in membrane content has not yet been expanded to lipids, due to the difficulty of isolating domain-specific samples. We have overcome this by using SMA to co-immunopurify membrane proteins and their native lipids from two regions of photoreceptor ROS disks. Each sample’s copurified lipids were subjected to untargeted lipidomic and fatty acid analysis. Extensive differences between center (rhodopsin) and rim (ABCA4 and PRPH2/ROM1) samples included a lower PC to PE ratio and increased LC- and VLC-PUFAs in the center relative to the rim region, which were enriched in shorter, saturated FAs. The comparatively few differences between the two rim samples likely reflect specific protein-lipid interactions. High-resolution profiling of the ROS disk lipid composition provides a model for future studies of other complex cellular structures, and gives new insights into how intricate membrane structure and protein activity are balanced within the ROS.

Sander et al. have parsed the lipid composition of native-source photoreceptor disks and find large differences in fatty acid unsaturation and chain length between the center and rim regions. They selectively copurify membrane proteins and lipids from each region in SMALPs using nanobodies and antibodies.
High levels of Dorsal transcription factor downregulate, not promote,snailexpression by regulating enhancer action
Authors: Irizarry Jihyun , McGehee James , Stathopoulos Angelike
Published: January 2021

InDrosophilaembryos, genes expressed along the dorsal-ventral axis are responsive to concentration of the Dorsal (Dl) transcription factor, which varies in space; however, levels of this morphogen also build over time. Since expression of high-threshold Dl target genes such assnail(sna) is supported before Dl levels peak, it is unclear what role increasing levels have if any. Here we investigated action of two enhancers that controlsnaexpression in embryos, demonstrating using genome editing that Dl binding sites within one enhancer located promoter proximally,sna.prox, can limit the ability of the other distally-located enhancer,sna.dis, to increasesnalevels. In addition, MS2-MCP live imaging was used to studysnatranscription rate in wildtype,dlheterozygote, and a background in which a photo-sensitive degron is fused to Dl (dl-BLID). The results demonstrate that, when Dl levels are high, Dl acts throughsna.proxto limit the activity ofsna.disand thereby influencesnatranscription rate. In contrast, when Dl levels are kept low usingdl-BLID, sna.proxpositively influencessnatranscription rate. Collectively, our data support the view that Dl’s effect on gene expression changes over time, switching from promotingsnaexpression at low concentration to dampeningsnaexpression at high concentration by regulating enhancer interactions. We propose this differential action of the Dl morphogen is likely supported by occupancy of this factor first to high and then low affinity binding sites over time as Dl levels rise to coordinate action of these two co-acting enhancers.

Significance statement

A gradient of the maternal transcription factor Dorsal is important for establishing spatial expression of target genes along the dorsal-ventral axis ofDrosophilaembryos. Dorsal levels are also dynamic as nuclear concentration builds in time. Surprisingly, expression of high-threshold target genes such assnailis supported before levels peak, raising the question why levels continue to build. Our data support the view that peak Dorsal levels act to preferentially support activity of one enhancer over another to effectively decreasesnailexpression. In addition, while the morphogen Dorsal acts early to support gene expression, later it effectively acts as a damper to limit gene expression. Our results suggest other morphogens also have effects on gene expression that change over time.
Evolving cryo-EM structural approaches for GPCR drug discovery
Authors: Zhang Xin , Johnson Rachel M. , Drulyte Ieva , Yu Lingbo , Kotecha Abhay , Danev Radostin , Wootten Denise , Sexton Patrick M. , Belousoff Matthew J.
Published: January 2021

G protein-coupled receptors (GPCRs) are the largest class of cell surface drug targets. Advances in biochemical approaches for the stabilisation of GPCR:transducer complexes together with improvements in the technology and application of cryo-EM has recently opened up new possibilities for structure-assisted drug design of GPCR agonists. Nonetheless, limitations in the commercial application of some of these approaches, including the use of nanobody 35 (Nb35) for stabilisation of GPCR:Gs complexes, and the high cost of 300kV imaging have restricted broad application of cryo-EM in drug discovery. Here, using the PF 06882961-bound GLP-1R as exemplar, we validated formation of stable complexes with a modified Gs protein in the absence of Nb35 that had equivalent resolution in the drug binding pocket to complexes solved in the presence of Nb35, while the G protein displayed increased conformational dynamics. In parallel, we assessed the performance of 200kV versus 300kV image acquisition using a Falcon 4 or K3 direct electron detector. We show that with 300kV Krios, both bottom mounted Falcon 4 and energy filtered (25eV slit) Bio-Quantum K3 produced similar resolution. Moreover, the 200kV Glacios with bottom mounted Falcon 4 yielded a 3.2 Å map with clear density for bound drug and multiple structurally ordered waters. Our work paves the way for broader commercial application of cryo-EM for GPCR drug discovery.
Cooperative Communication with Humans Evolved to Emerge Early in Dogs
Authors: Salomons Hannah , Smith Kyle , Callahan-Beckel Megan , Callahan Margaret , Levy Kerinne , Kennedy Brenda S. , Bray Emily , Gnanadesikan Gitanjali E. , Horschler Daniel J. , Gruen Margaret , Tan Jingzhi , White Philip , MacLean Evan , Hare Brian
Published: January 2021

While we know that dogs evolved from wolves through a process of domestication, it remains unclear how this process may have affected dog cognitive development. Here we tested dog (N=44) and wolf (N=37) puppies, 5-18 weeks old, on a battery of temperament and cognition tasks. Dog puppies were more attracted to humans, read human gestures more skillfully and made more eye contact with humans than wolf puppies. The two species were similarly attracted to objects and performed similarly on nonsocial measures of memory and inhibitory control. These results demonstrate the role of domestication in enhancing the cooperative communication skills of dogs through selection on attraction to humans, which altered developmental pathways.

One Sentence Summary

Domestication altered dogs’ developmental pathways to enhance their cooperative communication with humans.
Nucleus accumbens neurons encode initiation and vigor of reward approach behavior
Authors: Levcik David , Sugi Adam H. , Pochapski José A. , Baltazar Gabriel , Pulido Laura N. , Villas-Boas Cyrus , Aguilar-Rivera Marcelo , Fuentes-Flores Romulo , Nicola Saleem M. , Cunha Claudio Da
Published: January 2021

The nucleus accumbens (NAc) is considered an interface between motivation and action, with NAc neurons playing an important role in promoting reward approach. However, the encoding by NAc neurons that contribute to this role remains unknown. Here, we trained male rats to find rewards in an 8-arm radial maze. The activity of 62 neurons, mostly in the shell of the NAc, were recorded while rats ran towards each reward place. General linear model (GLM) analysis showed that variables related to the vigor of the locomotor approach, like speed and acceleration, and the fraction of the approach run completed were the best predictors of the firing rate for most NAc neurons. Nearly 23% of the recorded neurons, here named locomotion-off cells, were inhibited during the entire approach run, suggesting that reduction in firing of these neurons promotes initiation of locomotor approach. Another 24% of the neurons presented a peak of activity during acceleration followed by a valley during deceleration (peak-valley cells). Together, these neurons accounted for most of the speed and acceleration encoding identified in the GLM analysis. Cross-correlations between firing and speed indicated that the spikes of peak-valley cells were followed by increases in speed, suggesting that the activity of these neurons drives acceleration. In contrast, a further 19% of neurons presented a valley during acceleration followed by a peak just prior to or after reaching reward (valley-peak cells). These findings suggest that these three classes of NAc neurons control the initiation and vigor of the locomotor approach to reward.

Significance Statement

Deciphering the mechanisms by which the NAc controls the vigor of motivated behavior is critical to better understand and treat psychiatric conditions in which motivation is dysregulated. Manipulations of the NAc profoundly impair subjects’ ability to spontaneously approach reward-associated locations, preventing them from exerting effort to obtain reward. Here, we identify for the first time specific activity of NAc neurons in relation to spontaneous approach behavior. We discover three classes of neurons that could control initiation of movement and the speed vs. time trajectory during locomotor approach. These results suggest a prominent but heretofore unknown role for the NAc in regulating the kinematics of reward approach locomotion.
Novel RT-ddPCR Assays for determining the transcriptional profile of SARS-CoV-2
Authors: Telwatte Sushama , Kumar Nitasha , Vallejo-Gracia Albert , Kumar G. Renuka , Lu Chuanyi M. , Ott Melanie , Wong Joseph K. , Yukl Steven A.
Published: January 2021

The exact mechanism of coronavirus replication and transcription is not fully understood; however, a hallmark of coronavirus transcription is the generation of negative-sense RNA intermediates that serve as the templates for the synthesis of positive-sense genomic RNA (gRNA) and an array of subgenomic mRNAs (sgRNAs) encompassing sequences arising from discontinuous transcription.

Existing PCR-based diagnostic assays for SAR-CoV-2 are qualitative or semi-quantitative and do not provide the resolution needed to assess the complex transcription dynamics of SARS-CoV-2 over the course of infection. We developed and validated a novel panel of specially designed SARS-CoV-2 ddPCR-based assays to map the viral transcription profile. Application of these assays to clinically relevant samples will enhance our understanding of SARS-CoV-2 replication and transcription and may also inform the development of improved diagnostic tools and therapeutics.

Highlights

We developed a novel panel of 7 quantitative RT-ddPCRs assays for SARS-Cov-2

Our panel targets nongenic and genic regions in genomic and subgenomic RNAs

All assays detect 1-10 copies and are linear over 3-4 orders of magnitude

All assays correlated with the clinical Abbott SARS-CoV-2 Viral Load Assay

Clinical samples showed higher copy numbers for targets at the 3’ end of the genome
MR relaxometry-based analysis of brain hemorrhages: an experimental study on a rabbit model
Authors: Del Signore Francesca , Vignoli Massimo , Salda Leonardo Della , Tamburro Roberto , Cerasoli Ilaria , Paolini Andrea , Romanucci Mariarita , de Pasquale Francesco
Published: January 2021

Magnetic Resonance Relaxometry is a quantitative MRI-based technique able to estimate tissue relaxation times T1 and T2. This approach allows increasing the MRI diagnostic accuracy mostly in case of brain neoplasia or neurodegenerative disorders in human medicine. However, few reports are available on the application of this technique in the clinical field of veterinary medicine. For this reason, in this work, we developed a relaxometry based approach on experimentally induced brain hemorrhages on rabbits. Specifically, the methodology is based on a hierarchical clustering procedure driven by the T1 relaxometry signals from a set of regions of interest selected on the T2 map. The approach is multivariate since it combines both T1 and T2 information and allows the diagnosis at the subject level by comparing “suspected” pathological regions with healthy homologous ones within the same brain.

To validate the proposed technique, the scanned brains underwent histopathological analyses to estimate the performance of the proposed classifier in terms of Receiver Operator Curve analyses. The results showed that, in terms of identification of the lesion and its contours, the proposed approach resulted accurate and outperformed the standard techniques based on T1w and T2w images. Finally, since the proposed protocol in terms of the adopted scanner, sequences, and analysis tools, is suitable for the clinical practice, it can be potentially validated through large-scale multi-center clinical studies.
Ureterorenoscopic (URS) lithotripsy and balloon dilation cause acute kidney injury and distal renal tubule damage
Authors: Huang Ho-Shiang , Liu Chan-Jung
Published: January 2021

Ureterorenoscopy (URS) is believed to be a safe and effective procedure to treat ureteral stone or ureteral stricture. Rapidly increased intrarenal pressure during URS may have a negative impact on the kidney, but the effect on renal functions is not well known. The aim of this study is to evaluate whether URS balloon dilation or lithotripsy would cause acute kidney injury (AKI), which was evaluated by urine neutrophil gelatinase associated lipocalin (NGAL) and renal tubular damage, which was evaluated by urine α glutathione S-transferase (GST) and πGST. This prospective study consisted of 207 patients with mean age 53.8 years old between September 2012 and June 2013. Four groups were included: the ureteral stricture group (group 1), the ureteral stone group (group 2), and two control groups. URS induced increased uNGAL on both Days 1 and 14 in both groups, and only elevated u-πGST levels were noted on Day 14 after URSL. On Day 14, the difference between low-grade and high-grade hydronephrosis was significant in group 1 (p < 0.001) rather than group 2 (p = 0.150). By multivariate logistic regression analysis, age, baseline eGFR, and stone size > 1.0 cm were associated with complete recovery of hydronephrosis after URS on Day 14. Ureteral stone patients with preserved renal function suffered more AKI (uNGAL) than those with impaired renal function. However, URS-related AKI had no significant difference between stone ≤ 1 cm and > 1 cm subgroups. Besides, urine αGST and πGST were both significantly higher in stone > 1 cm subgroup when compared to ≤ 1 cm subgroup. In conclusion, URS laser lithotripsy and balloon dilatation all resulted in AKI and renal tubular damage on Day 14 though post-URS double-J (DBJ) stenting was performed in every patient.
Reduced axon caliber in the associative striatum of theSapap3knockout mouse
Authors: Lousada E. , Boudreau M. , Cohen-Adad J. , Oumesmar B. Nait , Burguière E. , Schreiweis C.
Published: January 2021

Pathological repetitive behaviors are a common feature of different neuropsychiatric disorders such as obsessive-compulsive disorder or Gilles de la Tourette syndrome. TheSapap3knockout mouse (Sapap3-KO) is the current reference model used in translational psychiatry to study co-morbid repetitive behaviors, presenting both compulsive-like as well as tic-like behaviors. Consistent with clinical and fundamental research literature relating compulsive-like symptoms to associative cortico-striatal dysfunctions and tic-like symptoms to sensorimotor cortico-striatal dysfunctions, abnormalities comprising both circuits have been described in this mouse model. Findings reported on these mice point towards not only macro-, but also micro-circuitry deficits, both of which can be affected by neuronal structural changes. As such, in the present study, we aimed to investigate structural changes in associative and sensorimotor striatal areas that could affect information conduction. We used AxonDeepSeg, an open-source software to automatically segment and measure myelin thickness and axon caliber, and found that axon caliber, the main contributor for changes in conduction speed, is specifically reduced in the associative but not the sensorimotor striatum of theSapap3-KO mouse. This smaller axon caliber inSapap3-KO mice is not a general neuronal feature of this region, but specific to a subpopulation of axons with large caliber. These results point to a primary structural deficit in the associative striatum, affecting signal conduction and consequent connectivity.
Brain Areas Affected by Intranasal Oxytocin Show Higher Oxytocin Receptor Expression
Authors: Habets Philippe C , Mclain Christabel , Meijer Onno C
Published: January 2021

Neuroimaging studies suggest that intranasal oxytocin (IN-OXT) may modulate emotional and social processes by altering neural activity patterns. The extent of brain penetration after IN-OXT is unclear, and it is currently under debate whether IN-OXT can directly bind central oxytocin receptors (OXTRs). We investigated oxytocin pathway gene expression in regions affected by IN-OXT on task-based fMRI. We found that OXTR is more highly expressed in affected than unaffected subcortical regions; this effect did not vary by task-type or sex. Cortical results revealed higher OXTR expression in regions affected by IN-OXT in emotional processing tasks and in male-only data. No significant differences were found in expression of the closely related vasopressin receptors. Our findings suggest that the mechanism by which IN-OXT may alter brain functionality involves direct activation of central OXTRs.
Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets
Authors: Francis Magen E. , Richardson Brian , McNeil Mara , Rioux Melissa , Foley Mary K. , Ge Anni , Pechous Roger D. , Kindrachuk Jason , Cameron Cheryl M. , Richardson Christopher , Lew Jocelyne , Cameron Mark J. , Gerdts Volker , Falzarano Darryl , Kelvin Alyson A.
Published: January 2021

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.
The potential of ryegrass as cover crop to reduce soil N2O emissions and increase the population size of denitrifying bacteria
Authors: Wang Haitao , Beule Lukas , Zang Huadong , Pfeiffer Birgit , Ma Shutan , Karlovsky Petr , Dittert Klaus
Published: January 2021

Nitrogen (N) fertilization is the major contributor to nitrous oxide (N2O) emissions from agricultural soil, especially in post‐harvest seasons. This study was carried out to investigate whether ryegrass serving as cover crop affects soil N2O emissions and denitrifier community size. A microcosm experiment was conducted with soil planted with perennial ryegrass (Lolium perenne L.) and bare soil, each with four levels of N fertilizer (0, 5, 10 and 20 g N m−2; applied as calcium ammonium nitrate). The closed‐chamber approach was used to measure soil N2O fluxes. Real‐time PCR was used to estimate the biomass of bacteria and fungi and the abundance of genes involved in denitrification in soil. The results showed that the presence of ryegrass decreased the nitrate content in soil. Cumulative N2O emissions of soil with grass were lower than in bare soil at 5 and 10 g N m−2. Fertilization levels did not affect the abundance of soil bacteria and fungi. Soil with grass showed greater abundances of bacteria and fungi, as well as microorganisms carrying narG, napA, nirK, nirS and nosZ clade I genes. It is concluded that ryegrass serving as a cover crop holds the potential to mitigate soil N2O emissions in soils with moderate or high NO3− concentrations. This highlights the importance of cover crops for the reduction of N2O emissions from soil, particularly following N fertilization. Future research should explore the full potential of ryegrass to reduce soil N2O emissions under field conditions as well as in different soils.

Highlights

This study was to investigate whether ryegrass serving as cover crop affects soil N2O emissions and denitrifier community size;

Plant reduced soil N substrates on one side, but their root exudates stimulated denitrification on the other side;

N2O emissions were lower in soil with grass than bare soil at medium fertilizer levels, and growing grass stimulated the proliferation of almost all the denitrifying bacteria except nosZ clade II;

Ryegrass serving as a cover crop holds the potential to mitigate soil N2O emissions.
Benefits and harms of the new prostate cancer grade grouping on the prediction of long‐term oncological outcomes in patients after radical prostatectomy
Authors: Milonas Daimantas , Muilwijk Tim , Venclovas Zilvinas , Devos Gaëtan , Joniau Steven
Published: January 2021

Objective

To investigate whether the new prostate cancer grade groups model provides significant predictive value and better patient stratification on tumor progression after radical prostatectomy compared with the former Gleason grading models.

Methods

Men treated at a tertiary center by radical prostatectomy between 2005 and 2017 were analyzed. The outcomes of interest were clinical progression‐free and cancer‐specific survival. Multivariate Cox regression analysis, C‐index and decision curve analysis were carried out using three‐tier (Gleason score 6, 7 and 8–10), four‐tier (Gleason score 6, 7, 8 and 9–10) and new grade groups model.

Results

In total, 1759 men were included in the analysis. At a median of 87 months (interquartile range 51–134 months) of follow up, clinical progression was detected in 78 (4.4%) and cancer‐related death in 42 (2.4%) patients. The hazard ratio of clinical progression‐free was 2.3, 5.7, 5.2 and 29.5; the hazard ratio of cancer‐specific survival was 1.7, 3.2, 4.8 and 11.8 in the grade groups 2–5, relative to grade group 1, respectively. The grade groups model had higher C‐index in comparison with four‐ and three‐tier grading models for clinical progression‐free survival 0.88 versus 0.85 versus 0.83 and for cancer‐specific survival 0.82 versus 0.80 versus 0.80, respectively. In the decision curve analysis, the grade groups model shows marginally better net benefit on clinical progression‐free and cancer‐specific survival.

Conclusions

The new model shows better performance in comparison with former Gleason grading models on the prediction of long‐term oncological outcomes.
A Preliminary Study on the Simulation of Vortex Flow in Pump Intake Based on LBM-VOF-LES Combined Model
Authors: Guo Miao , Tang Xuelin , Li Xiaoqin , Wang Fujun , Shi Xiaoyan
Published: January 2021

In this paper, the lattice Boltzmann method-large eddy simulation (LBM-LES) model was combined with the volume of fluid (VOF) method and used to simulate vortex flow in a typical pump intake. The strain rate tensor in the LES model is locally calculated utilizing nonequilibrium moments based on Chapman–Enskog expansion, and the bounce-back scheme is used for nonslip condition on the solid wall and VOF method for the free surface. The evolution of all kinds of cells on the free surface is based on the mass exchange in the VOF method, i.e., lattice Boltzmann-single phase (LB-SP) free surface model. The introduction of the external force terms is established through adding corresponding expressions on the right of the lattice Boltzmann equation (LBE), and by modifying the velocity. The predicted vortex flow patterns (core location and strength of the vortex) and velocity correlate with the experiments undertaken with the physical model. A comparison of the results demonstrates the feasibility and stability of the model and the numerical method in predicting vortex flows inside pump intakes. The model developed and presented in this paper provides a new analysis method of vortex flow patterns in pump intake from a mesoscopic perspective, enriches the relevant technologies, and makes corresponding contributions to further engineering applications.
Perceptuomotor compatibility effects in vowels: Effects of consonantal context and acoustic proximity of response and distractor
Authors: Ghaffarvand Mokari Payam , Gafos Adamantios , Williams Daniel
Published: January 2021

In a cue-distractor task, speakers' response times (RTs) were found to speed up when they perceived a distractor syllable whose vowel was identical to the vowel in the syllable they were preparing to utter. At a more fine-grained level, subphonemic congruency between response and distractor—defined by higher number of shared phonological features or higher acoustic proximity—was also found to be predictive of RT modulations. Furthermore, the findings indicate that perception of vowel stimuli embedded in syllables gives rise to robust and more consistent perceptuomotor compatibility effects (compared to isolated vowels) across different response–distractor vowel pairs.
GPER1 is required to protect fetal health from maternal inflammation
Authors: Harding Alfred T. , Goff Marisa A. , Froggatt Heather M. , Lim Jean K. , Heaton Nicholas S.
Published: January 2021

GPER1 in utero to the rescue!

Several common pathogens, including influenza A virus (IAV), can activate systemic type I interferon (IFN) signaling during pregnancy. Such infections would be expected to cause birth defects and fetal mortality, but maternal IAV infections rarely produce such effects, suggesting the presence of a protective mechanism in fetal tissues. Harding
et al.
used a CRISPR screen to uncover IFN regulators that can mediate differential IFN control across tissues in human cell lines. They found that G protein–coupled estrogen receptor 1 (GPER1), which is expressed in fetal tissues, acts as a protective suppressor of IFN responses in the placenta during maternal infection. In a mouse model, pharmacological activation of GPER1 shielded fetuses from maternal inflammation. Activation of GPER1 might be promising therapeutically to protect the fetus from both maternal and fetal infections.

Science
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A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols
Authors: Yan Renhong , Cao Pingping , Song Wenqi , Qian Hongwu , Du Ximing , Coates Hudson W. , Zhao Xin , Li Yaning , Gao Shuai , Gong Xin , Liu Ximing , Sui Jianhua , Lei Jianlin , Yang Hongyuan , Brown Andrew J. , Zhou Qiang , Yan Chuangye , Yan Nieng
Published: January 2021

A cellular cholesterol sensor

Cholesterol levels in cells are controlled by the sterol regulatory element–binding protein (SREBP) pathway. When the cell has sufficient cholesterol, the transcription factor that regulates cholesterol metabolism is sequestered at the endoplasmic reticulum membrane, but when cholesterol is depleted, the transcription factor is released to activate the expression of genes involved in cholesterol synthesis and uptake. Yan
et al.
determined the structure of a central complex in human SREBP containing the proteins Scap and Insig-2. These two membrane-embedded proteins undergo 25-hydroxycholesterol (25HC)–dependent association and must dissociate for the pathway to be activated. The structure shows that 25HC is sandwiched between Scap and Insig-2 to facilitate their association. A mutational analysis is consistent with the structural model.

Science
, this issue p.
eabb2224
Formation of α clusters in dilute neutron-rich matter
Authors: Tanaka Junki , Yang Zaihong , Typel Stefan , Adachi Satoshi , Bai Shiwei , van Beek Patrik , Beaumel Didier , Fujikawa Yuki , Han Jiaxing , Heil Sebastian , Huang Siwei , Inoue Azusa , Jiang Ying , Knösel Marco , Kobayashi Nobuyuki , Kubota Yuki , Liu Wei , Lou Jianling , Maeda Yukie , Matsuda Yohei , Miki Kenjiro , Nakamura Shoken , Ogata Kazuyuki , Panin Valerii , Scheit Heiko , Schindler Fabia , Schrock Philipp , Symochko Dmytro , Tamii Atsushi , Uesaka Tomohiro , Wagner Vadim , Yoshida Kazuki , Zenihiro Juzo , Aumann Thomas
Published: January 2021

α particles in stable nuclei

α Decay is a common mode of radioactivity in heavy elements such as uranium that entails the loss of particles comprising two protons and two neutrons. Despite more than a century of study, when and where these α particles form in stable and unstable nuclei alike remains an open question. Tanaka
et al.
bombarded a series of stable tin isotopes with high-energy protons and detected ejected α particles at an abundance inversely correlated with mass number (see the Perspective by Hen). This observation, relating α particle accumulation to the neutron skin thickness at the nuclear surface, bears on models spanning radioactive decay to neutron star dynamics.

Science
, this issue p.
260
; see also p.
232
Comment on “Boosted molecular mobility during common chemical reactions”
Authors: Günther Jan-Philipp , Fillbrook Lucy L. , MacDonald Thomas S. C. , Majer Günter , Price William S. , Fischer Peer , Beves Jonathon E.
Published: January 2021

The apparent “boosted mobility” observed by Wang
et al
. (Reports, 31 July 2020, p. 537) is the result of a known artifact. When signal intensities are changing during a nuclear magnetic resonance (NMR) diffusion measurement for reasons other than diffusion, the use of monotonically increasing gradient amplitudes produces erroneous diffusion coefficients. We show that no boosted molecular mobility is observed when shuffled gradient amplitudes are applied.
Plant roots sense soil compaction through restricted ethylene diffusion
Authors: Pandey Bipin K. , Huang Guoqiang , Bhosale Rahul , Hartman Sjon , Sturrock Craig J. , Jose Lottie , Martin Olivier C. , Karady Michal , Voesenek Laurentius A. C. J. , Ljung Karin , Lynch Jonathan P. , Brown Kathleen M. , Whalley William R. , Mooney Sacha J. , Zhang Dabing , Bennett Malcolm J.
Published: January 2021

Ethylene aplenty signals soil compaction

It's tough to drive a spade through compacted soil, and plant roots seem to have the same problem when growing in compacted ground. Pandey
et al.
found that the problem is not, however, one of physical resistance but rather inhibition of growth through a signaling pathway. The volatile plant hormone ethylene will diffuse through aerated soil, but compacted soil reduces such diffusion, increasing the concentration of ethylene near root tissues. The cellular signaling cascades triggered by too much ethylene stop root growth. Therefore, gaseous diffusion serves as a readout of soil compaction for plant roots growing in search of productive nutrition.

Science
, this issue p.
276
The Genotype-to-Phenotype Dilemma: How Should Laboratories Approach Discordant Susceptibility Results?
Authors: Yee Rebecca , Dien Bard Jennifer , Simner Patricia J.
Published: January 2021

Traditional culture-based methods for identification and antimicrobial susceptibility testing (AST) of bacteria take 2 to 3 days on average. Syndromic molecular diagnostic panels have revolutionized clinical microbiology laboratories as they can simultaneously identify an organism and detect some of the most significant antimicrobial resistance (AMR) genes directly from positive blood culture broth or from various specimen types (e.g., whole blood, cerebrospinal fluid, and respiratory specimens).
The Intact Noninducible Latent HIV-1 Reservoir Is Established in an
In Vitro
Primary T
CM
Cell Model of Latency
Authors: Sarabia Indra , Huang Szu-Han , Ward Adam R. , Jones R. Brad , Bosque Alberto
Published: January 2021

HIV-1 establishes a latent reservoir that persists under antiretroviral therapy. Antiretroviral therapy is able to stop the spread of the virus and the progression of the disease but does not target this latent reservoir.
Anisovolumetric weathering in granitic saprolite controlled by climate and erosion rate
Authors: Riebe Clifford S. , Callahan Russell P. , Granke Sarah B.-M. , Carr Bradley J. , Hayes Jorden L. , Schell Marlie S. , Sklar Leonard S.
Published: January 2021

Erosion at Earth’s surface exposes underlying bedrock to climate-driven chemical and physical weathering, transforming it into a porous, ecosystem-sustaining substrate consisting of weathered bedrock, saprolite, and soil. Weathering in saprolite is typically quantified from bulk geochemistry assuming physical strain is negligible. However, modeling and measurements suggest that strain in saprolite may be common, and therefore anisovolumetric weathering may be widespread. To explore this possibility, we quantified the fraction of porosity produced by physical weathering, FPP, at three sites with differing climates in granitic bedrock of the Sierra Nevada, California, USA. We found that strain produces more porosity than chemical mass loss at each site, indicative of strongly anisovolumetric weathering. To expand the scope of our study, we quantified FPP using available volumetric strain and mass loss data from granitic sites spanning a broader range of climates and erosion rates. FPP in each case is ≥0.12, indicative of widespread anisovolumetric weathering. Multiple regression shows that differences in precipitation and erosion rate explain 94% of the variance in FPP and that >98% of Earth’s land surface has conditions that promote anisovolumetric weathering in granitic saprolite. Our work indicates that anisovolumetric weathering is the norm, rather than the exception, and highlights the importance of climate and erosion as drivers of subsurface physical weathering.
Socioeconomic disparities in prehospital factors and survival after out-of-hospital cardiac arrest
Authors: Møller Sidsel , Wissenberg Mads , Starkopf Liis , Kragholm Kristian , Hansen Steen M , Ringgren Kristian Bundgaard , Folke Fredrik , Andersen Julie , Malta Hansen Carolina , Lippert Freddy , Koeber Lars , Gislason Gunnar Hilmar , Torp-Pedersen Christian , Gerds Thomas A
Published: January 2021

Objective

It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival.

Methods

From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001–2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders.

Results

We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups.

Conclusion

Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.
P-wave two-particle bound and scattering states in a finite volume including QED
Authors: Stellin Gianluca , Meißner Ulf-G.
Published: January 2021

The mass shifts for two-fermion bound and scattering P-wave states subject to the long-range interactions due to QED in the non-relativistic regime are derived. Introducing a short range force coupling the spinless fermions to one unit of angular momentum in the framework of pionless EFT, we first calculate both perturbatively and non-perturbatively the Coulomb corrections to fermion–fermion scattering in the continuum and infinite volume context. Motivated by the research on particle–antiparticle bound states, we extend the results to fermions of identical mass and opposite charge. Second, we transpose the system onto a cubic box with periodic boundary conditions and we calculate the finite volume corrections to the energy of the lowest bound and unbound$$T_1^{-}$$T1-eigenstates. In particular, power law corrections proportional to the fine structure constant and resembling the recent results for S-wave states are found. Higher order contributions in$$\alpha $$αare neglected, since the gapped nature of the momentum operator in the finite-volume environnement allows for a perturbative treatment of the QED interactions.
Classical and quantum $$(2+1)$$-dimensional spatially homogeneous string cosmology
Authors: Naderi F. , Rezaei-Aghdam A.
Published: January 2021

We introduce three families of classical and quantum solutions to the leading order of string effective action on spatially homogeneous$$(2+1)$$(2+1)-dimensional space-times with the sources given by the contributions of dilaton, antisymmetric gaugeB-field, and central charge deficit term$$\varLambda $$Λ. At the quantum level, solutions of Wheeler–DeWitt equations have been enriched by considering the quantum versions of the classical conditional symmetry equations. Concerning the possible applications of the obtained solutions, the semiclassical analysis of Bohm’s mechanics has been performed to demonstrate the possibility of avoiding the classical singularities at the quantum level.
Phase separation and exotic vortex phases in a two-species holographic superfluid
Authors: Yang Wei-Can , Xia Chuan-Yin , Zeng Hua-Bi , Zhang Hai-Qing
Published: January 2021

At finite temperature, the stable equilibrium states of coupled two-component Bose Einstein condensations (BECs) with the same conformal mass in both non-rotating and rotating condition can be obtained by studying its real dynamics via holography. The equilibrium state is the state where the free energy reaches the minimum and does not change any more. In the case of no rotation, the spatial phase separated states of the two components become more stable than the miscible condensates state when the direct repulsive inter-component coupling constant $$\eta>\eta _c>0$$

η
>

η
c

>
0

. Under rotation, the quantum fluid reveals four equilibrium structures of vortex states by varying the $$\eta $$
η
from the miscible region to the phase separated region. Among the four structures, the vortex sheet solution is the most exotic one that appears in the phase separated region.
Review of Kernelization
Authors: Jackman Tim , Homer Steve
Published: January 2021

On the surface, the concept of preprocessing may not seem particularly novel nor insightful. Indeed, the simple idea that putting in computational effort upfront may pay off in dividends of time saved later is not only advice that we have received countless times but it is also advice that we ourselves have given to countless others. It may well seem a clich´e, but it turns out to be more powerful than it first appears to be, and in fact plays a rich role in numerous areas of algorithmic research and is a powerful tool for myriad applications. This turns out to be particularly true in Computer Science where pattern repetition within and between algorithms is ubiquitous. The idea of storing results once to avoid repeating them innumerable times can pay huge dividends in computational problems of many kinds. So, while possibly overdone, the advice is still sound and often revelatory.
Open Problems Column Edited by William Gasarch This Issue's Column!
Authors: Gasarch William
Published: January 2021

In this column we state a class of open problems in Ramsey Theory. The general theme is to take Ramsey-type statements that are false and weaken them by allowing the homogenous set to use more than one color. This concept is not new, and the theorems we state and/or prove are not new; however, the open questions that request easier proofs of the known theorems (or weaker versions) may be new. We use the phrase an elementary proof. This is not meant to be a technical or rigorous term. What we really mean is a proof that can be taught in an undergraduate combinatorics course. A good example of what we mean is the proof of Theorem 9.3.
Electrochemical Study on the Kinetic Properties of Fe2+/Fe, Ni2+/Ni, Cr2+/Cr and Cr3+/Cr2+ in Molten MgCl2-KCl-NaCl Salts
Authors: Yang Qiufeng , Ge Jianbang , Zhang Jinsuo
Published: January 2021

The fundamental kinetic parameters of corrosion product ions (Fe, Ni and Cr ions) are of significant importance to understand the corrosion mechanisms of the structural materials in the molten salts. In the present study, the fundamental data of Fe2+, Ni2+, Cr2+ and Cr3+ (diffusion coefficient D, exchange current density i
0, charge transfer coefficient α, limiting current density i

L
and standard rate constant k
0) were measured at different concentrations (1.53 × 10−6−7.48 × 10−4 mol cm−3) and temperatures (600 °C–800 °C). The values of D are independent of concentrations and follow Arrhenius law with temperature, which descend in the order of

D

C

r

2
+

>

D

F

e

2
+

>

D

C

r

3
+

>

D

N

i

2
+

,

with values ranging from 0.94 × 10−5 to 3.31 × 10−5 cm2 s−1. Both i
0 and k
0 depend on the temperatures, which also follow Arrhenius law. The values of the estimated k
0 descend in the order of

k

C

r

2
+

0

>

k

F

e

2
+

0

>

k

N

i

2
+

0

>

k

C

r

3
+

0

,

which range from 1.88 × 10−5 to 9.06 × 10−4 cm s−1.
Exploring the sites and kinetics of bronchodilator response to β-2 agonists in asthma
Authors: Demey Lucas , Van Muylem Alain , Malinovschi Andrei , Haccuria Amaryllis , Perez-Bogerd Silvia , Michils Alain
Published: January 2021

FEV1 increase usually observed after tHe inhalation of short-acting β2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting β2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of β2-agonists in asthma should not be limited to studying its early impact on FEV1.