bluuebunny/crossref_metadata_2025 huggingface dataset:
Potency of the novel PolC DNA polymerase inhibitor CRS0540 in a disseminated Listeria monocytogenes intracellular hollow-fibre model
Authors: Patel Swati , Chapagain Moti , Mason Clifford , Gingrich Matthew , Athale Shruti , Ribble Wendy , Hoang Teresa , Day Joshua , Sun Xicheng , Jarvis Thale , Ochsner Urs A , Howe David , Gumbo Tawanda
Published: August 2022

Background

Listeriosis is an orphan disease, which is nevertheless fatal in immunocompromised people. CRS0540 is a novel PolC DNA polymerase inhibitor that has demonstrated good in vitro and in vivo activity against Listeria monocytogenes.

Methods

Rodent-to-human allometry projection-based human population pharmacokinetics of CRS0540 were used for all studies. CRS0540 pharmacokinetics/pharmacodynamics studies in an intracellular hollow-fibre system model of disseminated listeriosis (HFS-Lister) examined the effect of eight treatment doses, administered daily over 7 days, in duplicate units. Total bacterial burden versus AUC/MIC exposures on each day were modelled using the inhibitory sigmoid Emax model, while CRS0540-resistant bacterial burden was modelled using a quadratic function. Ten thousand-subject Monte Carlo simulations were used to predict an optimal clinical dose for treatment.

Results

The mean CRS0540 intracellular/extracellular AUC0–24 ratio was 34.07 (standard error: 15.70) as measured in the HFS-Lister. CRS0540 demonstrated exposure-dependent bactericidal activity in the HFS-Lister, with the highest exposure killing approximately 5.0 log10 cfu/mL. The free drug AUC0–24/MIC associated with 80% of maximal kill (EC80) was 36.4. Resistance emergence versus AUC/MIC was described by a quadratic function, with resistance amplification at an AUC/MIC of 54.8 and resistance suppression at an AUC/MIC of 119. Monte Carlo simulations demonstrated that for the EC80 target, IV CRS0540 doses of 100 mg/kg achieved PTAs of >90% at MICs up to 1.0 mg/L.

Conclusions

CRS0540 is a promising orphan drug candidate for listeriosis. Future PK/PD studies comparing it with penicillin, the standard of care, could lead to this drug as a new treatment in immunocompromised patients.
A geometric modelling framework to support the design of heterogeneous lattice structures with non-linearly varying geometry
Authors: Letov Nikita , Zhao Yaoyao Fiona
Published: August 2022

Geometric modelling has been a crucial component of the design process ever since the introduction of the first computer-aided design systems. Additive Manufacturing (AM) pushes design freedom to previously unachievable limits. AM allows the manufacturing of lattice structures which are otherwise close to impossible to be manufactured conventionally. Yet, the geometric modelling of heterogeneous lattice structures is still greatly limited. Thus, the AM industry is now in a situation where the manufacturing capabilities exceed the geometric modelling capabilities. While there have been advancements in the modelling of heterogeneous lattice structures, the review of relevant literature revealed critical limitations of the existing approaches. These limitations include their inability to model non-linear variation of geometric parameters, as well as the limited amount of controllable geometric parameters. This work presents a novel geometric modelling methodology based on function representation as an attempt to bridge this gap. The proposed approach avoids the manual definition of geometric parameters and provides a method to control them with mathematical functions instead. A software prototype implementing the proposed approach is presented, and several use-cases are analysed.
Molecular and Toxicological Characterization of aBacillus thuringiensisStrain Expressing a Vip3 Protein Highly Toxic toSpodoptera frugiperda(Lepidoptera: Noctuidae)
Authors: Fernanda Vázquez-Ramírez María , Ibarra Jorge E , Edith Casados-Vázquez Luz , Eleazar Barboza-Corona J , Rincón-Castro Ma Cristina Del
Published: August 2022

The characterization of the Bacillus thuringiensis (Berliner) LBIT-418 strain was based on a previous work which indicated its high insecticidal potential. Therefore, toxicological, molecular, and biochemical characterizations were conducted in this work to identify its unique features and its potential to be developed as a bioinsecticide. This strain, originally isolated from a healthy mosquito larva, was identified within the subspecies kenyae by sequencing of the hag gene and by the multilocus sequence typing (MLST) technique. Genes cry1Ac2, cry1Ea3, cry2Aa1 and cry2Ab4, and a cry1Ia were detected in its genome, in addition to a vip3Aa gene. In this research, the latter protein was successfully cloned, expressed, and purified and showed high toxicity towards the fall armyworm, Spodoptera frugiperda (J.E. Smith), fourth instar larvae in bioassays using the microdroplet ingestion technique, estimating an LD50 of 21.38 ng/larva. Additional bioassays were performed using the diet surface inoculation technique of the strain’s spore-crystal complex against diamondback moth larvae, Plutella xylostella (Linnaeus), estimating an LC50 of 10.22 ng/cm2. Its inability to produce β-exotoxin was demonstrated by bioassays against the nematode Caenorhabditis elegans Maupas and by HPLC analysis. These results support the high potential of this strain to be developed as a bioinsecticide.
The Oral Microbiome and Lung Cancer Risk: An Analysis of 3 Prospective Cohort Studies
Authors: Vogtmann Emily , Hua Xing , Yu Guoqin , Purandare Vaishnavi , Hullings Autumn G , Shao Dantong , Wan Yunhu , Li Shilan , Dagnall Casey L , Jones Kristine , Hicks Belynda D , Hutchinson Amy , Caporaso J Gregory , Wheeler William , Sandler Dale P , Beane Freeman Laura E , Liao Linda M , Huang Wen-Yi , Freedman Neal D , Caporaso Neil E , Sinha Rashmi , Gail Mitchell H , Shi Jianxin , Abnet Christian C
Published: August 2022

Background

Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered.

Methods

Using a case-cohort design, 1306 incident lung cancer cases were identified in the Agricultural Health Study; National Institutes of Health-AARP Diet and Health Study; and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Referent subcohorts were randomly selected by strata of age, sex, and smoking history. DNA was extracted from oral wash specimens using the DSP DNA Virus Pathogen kit, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatics were conducted using QIIME 2. Hazard ratios and 95% confidence intervals were calculated using weighted Cox proportional hazards models.

Results

Higher alpha diversity was associated with lower lung cancer risk (Shannon index hazard ratio = 0.90, 95% confidence interval = 0.84 to 0.96). Specific principal component vectors of the microbial communities were also statistically significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of 3 genera and presence of 1 genus were associated with greater lung cancer risk, whereas presence of 3 genera were associated with lower risk. For example, every SD increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% confidence interval = 1.06 to 1.22). Associations were strongest among squamous cell carcinoma cases and former smokers.

Conclusions

Multiple oral microbial measures were prospectively associated with lung cancer risk in 3 US cohort studies, with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.
Pox, Prose, and Prostitution: Masculine Anxiety, the Myth of the Male Author, and the Late-Victorian ‘Exchange Economy’ in George Gissing’s New Grub Street
Authors: Whiting Stephen
Published: August 2022

George Gissing’s friend and fellow novelist, H. G Wells, would remember the ‘last decade of the nineteenth century’ as ‘an extraordinarily favourable time for new writers’(H. G. Wells, Experiment in Autobiography: Discoveries of a Very Ordinary Brain, Volume II (Since 1866) (London: Gollancz, 1934), p. 506.). His experience fits neatly with the myths of the successful Victorian male author that were in circulation throughout the century. For the vast majority of writers, however, the reality was quite different. As many scholars have recognized, George Gissing’s 1891 novel, New Grub Street, presents a realistic portrayal of the travails of the average writer trying to live by their pen at the turn of the century. Nonetheless, little work has examined these economic travails against the backdrop of nineteenth-century images of male authorship. Bringing together work on Victorian masculinities, research on cultural depictions of syphilis, and work on the nineteenth-century marketplace alongside current Gissing scholarship and primary sources, this article will argue that Gissing’s novel foregrounds the shared ‘exchange economy’ of prostitution and the literary market to explore specifically masculine anxieties around the male author at the fin de siècle (Monika Pietrzak-Franger, Syphilis in Victorian Literature and Culture: Medicine, Knowledge and the Spectacle of Victorian Invisibility (Cham: Palgrave Macmillan, 2017), p. 131.). In tracing the interconnections of pox, prose, and prostitution, this article re-negotiates the novel’s relationship with other images of Victorian authorship, as well as using work on cultural depictions of syphilis to position the text in a new field.
The Sclerotinia sclerotiorum-inducible promoter pBnGH17
D7 in Brassica napus: isolation, characterization, and application in host-induced gene silencing
Authors: Lin Li , Fan Jialin , Li Panpan , Liu Dongxiao , Ren Sichao , Lin Keyun , Fang Yujie , Lin Chen , Wang Youping , Wu Jian
Published: August 2022

Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum, is among the most devastating diseases in Brassica napus worldwide. Conventional breeding for SSR resistance in Brassica species is challenging due to the limited availability of resistant germplasm. Therefore, genetic engineering is an attractive approach for developing SSR-resistant Brassica crops. Compared with the constitutive promoter, an S. sclerotiorum-inducible promoter would avoid ectopic expression of defense genes that may cause plant growth deficits. In this study, we generated a S. sclerotiorum-inducible promoter. pBnGH17D7, from the promoter of B. napus glycosyl hydrolase 17 gene (pBnGH17). Specifically, 5'-deletion and promoter activity analyses in transgenic Arabidopsis thaliana plants defined a 189 bp region of pBnGH17 which was indispensable for S. sclerotiorum-induced response. Compared with pBnGH17, pBnGH17D7 showed a similar response upon S. sclerotiorum infection, but lower activity in plant tissues in the absence of S. sclerotiorum infection. Moreover, we revealed that the transcription factor BnTGA7 directly binds to the TGACG motif in pBnGH17D7 to activate BnGH17. Ultimately, pBnGH17D7 was exploited for engineering Sclerotinia-resistant B. napus via host-induced gene silencing. It induces high expression of siRNAs against the S. sclerotiorum pathogenic factor gene specifically during infection, leading to increased resistance.
Candida auris PCR for high-throughput infection control screening
Authors: Crawford Lucy C , Kidd Sarah E , Anninos Terry M , Turra Mark , Weldhagen Gerhard F
Published: August 2022

Candida auris has significant implications for infection control due to its multidrug resistance and spread in healthcare settings. Current culture-based screening methods are laborious and risk muco-cutaneous colonisation of laboratory staff. We describe the adaptation of a published real-time PCR for the identification of C. auris in skin swabs for high-throughput infection control screening. Two published primer and probe sets were analysed utilising serial 10-fold dilutions of 15 C. auris strains to assess the PCR limit of detection. One primer and probe set was compatible with our laboratory workflow and was selected for further development yielding a limit of detection of 1 colony forming unit per reaction. Non-C. auris isolates as well as routine skin swabs (n = 100) were tested by culture and PCR to assess specificity, where no cross-reactivity was detected. Skin swabs from a proven C. auris case (n = 6) were all both culture positive and PCR positive, while surveillance swabs from close contacts (n = 46) were all both culture negative and PCR negative. Finally, the use of a lysis buffer comprising 4 m guanidinium thiocyanate rendered swab-equivalent quantities of C. auris non-viable, providing assurance of the safety benefit of PCR over culture. The development of a PCR assay for high-throughput infection control screening is a promising method for rapid detection of C. auris with utility in an outbreak setting.

Lay Summary

Candida auris, a difficult to treat yeast-like fungus, has spread through healthcare facilities globally, posing a serious threat to the health of patients. We evaluated a PCR-based method suitable for screening large numbers of patient samples to rapidly and accurately detect C. auris.
The sources of apparently non-repeating FRB
Authors: Katz J I
Published: August 2022

Repeating and apparently non-repeating fast radio bursts (FRBs) differ qualitatively and are produced by distinct classes of sources. Apparently non-repeating FRBs must actually repeat many times in their lifetimes because there are insufficient catastrophic events to explain their rate. Yet no such infrequent repetitions, in contrast to the frequent activity of FRBs known to repeat, have been observed, constraining their repetition rates. The large gap in energy between FRB 200428 and its much weaker repetitions resembles the large gap in energy between rare giant outbursts of soft gamma repeaters (SGRs) and their lesser outbursts. This phenomenological similarity suggests that the sources of apparently non-repeating FRBs are related to SGRs. Apparently non-repeating FRBs are associated with SGR outbursts more energetic than the 2020 April 28 outburst of SGR 1935+2154 associated with FRB 200428 but less energetic than the 2004 outburst of SGR 1806−20 that had no associated FRB. At 20–1000 times its actual distance, FRB 200428 would have been an apparent non-repeater.
Forecasting cosmological parameter constraints using multiple sparsity measurements as tracers of the mass profiles of dark matter haloes
Authors: Corasaniti P S , Le Brun A M C , Richardson T R G , Rasera Y , Ettori S , Arnaud M , Pratt G W
Published: August 2022

The dark matter halo sparsity, i.e. the ratio between spherical halo masses enclosing two different overdensities, provides a non-parametric proxy of the halo mass distribution that has been shown to be a sensitive probe of the cosmological imprint encoded in the mass profile of haloes hosting galaxy clusters. Mass estimations at several overdensities would allow for multiple sparsity measurements, which can potentially retrieve the entirety of the cosmological information imprinted on the halo profile. Here, we investigate the impact of multiple sparsity measurements on the cosmological model parameter inference. For this purpose, we analyse N-body halo catalogues from the Raygal and M2Csims simulations and evaluate the correlations among six different sparsities from spherical overdensity halo masses at Δ = 200, 500, 1000, and 2500 (in units of the critical density). Remarkably, sparsities associated to distinct halo mass shells are not highly correlated. This is not the case for sparsities obtained using halo masses estimated from the Navarro-Frenk-White (NFW) best-fitting profile, which artificially correlates different sparsities to order one. This implies that there is additional information in the mass profile beyond the NFW parametrization and that it can be exploited with multiple sparsities. In particular, from a likelihood analysis of synthetic average sparsity data, we show that cosmological parameter constraints significantly improve when increasing the number of sparsity combinations, though the constraints saturate beyond four sparsity estimates. We forecast constraints for the CHEX-MATE cluster sample and find that systematic mass bias errors mildly impact the parameter inference, though more studies are needed in this direction.
Systematic evaluation of Copper(II)-loaded immobilized metal affinity chromatography for selective enrichment of copper-binding species in human serum and plasma
Authors: Janisse Samuel E , Sharma Vibha A , Caceres Amanda , Medici Valentina , Heffern Marie C
Published: August 2022

Copper is essential in a host of biological processes, and disruption of its homeostasis is associated with diseases including neurodegeneration and metabolic disorders. Extracellular copper shifts in its speciation between healthy and disease states, and identifying molecular components involved in these perturbations could widen the panel of biomarkers for copper status. While there have been exciting advances in approaches for studying the extracellular proteome with mass spectrometry–based methods, the typical workflows disrupt metal–protein interactions due to the lability of these bonds either during sample preparation or in gas-phase environments. We sought to develop and apply a workflow to enrich for and identify protein populations with copper-binding propensities in extracellular fluids using an immobilized metal affinity chromatography (IMAC) resin. The strategy was optimized using human serum to allow for maximum quantity and diversity of protein enrichment. Protein populations could be differentiated based on protein load on the resin, likely on account of differences in abundance and affinity. The enrichment workflow was applied to plasma samples from patients with Wilson’s disease and protein IDs and differential abundancies relative to healthy subjects were compared to those yielded from a traditional proteomic workflow. While the IMAC workflow preserved differential abundance and protein ID information from the traditional workflow, it identified several additional proteins being differentially abundant including those involved in lipid metabolism, immune system, and antioxidant pathways. Our results suggest the potential for this IMAC workflow to identify new proteins as potential biomarkers in copper-associated disease states.
LOCL-11 EGFR-MUTATED NON-SMALL CELL LUNG CANCER (NSCLC) LEPTOMENINGEAL DISEASE (LMD) IN A LARGE STEREOTACTIC RADIOSURGERY PATIENT COHORT: INCIDENCE AND OUTCOME
Authors: Mullen Reed , Donahue Bernadine , Alzate Juan , Silverman Joshua , Berger Assaf , Bernstein Kenneth , Kondziolka Douglas
Published: August 2022

AIM

Patients with EGFR-mutated NSCLC brain metastases (BM) treated with targeted agents +/- radiosurgery (SRS) have increasing life expectancies. Systemic treatment may become less effective in preventing CNS progression as survival is prolonged. We sought to identify subsequent LMD in patients with EGFR-mutated NSCLC treated initially with SRS for BM and describe the associated features, treatment, and outcome.

METHODS

Review of our prospective Gamma Knife registry identified 177 patients with EGFR-mutated NSCLC between 2005 and 2021 treated with SRS. The EMR was queried for development of LMD, and type of LMD was recorded (focal/nodular or diffuse).

RESULTS

38 (21%) of the 177 patients developed LMD at a median of 10 months (range 1-25 IQR) following SRS. 27 (71%) of these were on tyrosine kinase inhibitors (TKI) at time of LMD diagnosis. Median overall survival (OS) from initial SRS for the entire cohort was 21 months (18-27 95%CI). Median OS after LMD diagnosis was 5 months (2-32 95%CI). LMD was diagnosed radiographically in 35 patients (92%); 20 patients had diffuse, 15 had focal/nodular, and 3 had positive CSF cytology. 26 (68%) had systemic progression synchronously with LMD. 33 (87%) had treatment for LMD including 19 with whole brain radiation therapy, 16 with the addition of or increased dosing of TKI, 6 with SRS for nodular disease, and 9 with intraventricular chemotherapy. The one- and two-year survival rates following the diagnosis of LMD was 21% and 3%, respectively.

CONCLUSION

LMD developed in a substantial subset of our patients, and despite the use of a variety of salvage therapies, survival was poor. Investigation to identify factors correlating with the development of LMD and those related to outcome are ongoing. The development of LMD on TKI in several of our patients supports efforts to pursue development of therapeutic agents with long-lasting CNS efficacy.
All-electrical switching of a topological non-collinear antiferromagnet at room temperature
Authors: Deng Yongcheng , Liu Xionghua , Chen Yiyuan , Du Zongzheng , Jiang Nai , Shen Chao , Zhang Enze , Zheng Houzhi , Lu Hai-Zhou , Wang Kaiyou
Published: August 2022

Non-collinear antiferromagnetic Weyl semimetals, combining the advantages of a zero stray field and ultrafast spin dynamics, as well as a large anomalous Hall effect and the chiral anomaly of Weyl fermions, have attracted extensive interest. However, the all-electrical control of such systems at room temperature, a crucial step toward practical application, has not been reported. Here, using a small writing current density of around 5 × 106 A·cm–2, we realize the all-electrical current-induced deterministic switching of the non-collinear antiferromagnet Mn3Sn, with a strong readout signal at room temperature in the Si/SiO2/Mn3Sn/AlOx structure, and without external magnetic field or injected spin current. Our simulations reveal that the switching originates from the current-induced intrinsic non-collinear spin-orbit torques in Mn3Sn itself. Our findings pave the way for the development of topological antiferromagnetic spintronics.
Consideration of others and consideration of future consequences predict cooperation in an acute social dilemma: an application to COVID-19
Authors: van Hulsen M A J , Rohde K I M , van Exel N J A
Published: August 2022

In the Netherlands, the COVID-19 pandemic raised an acute social dilemma where citizens could decide whether to comply with the precautionary measures recommended by the government. This paper examines the role of consideration of others (COO) and consideration of the future in explaining cooperation in a social dilemma. Through an online survey (N = 1019), consideration of future consequences (CFC), COO and compliance with the precautionary measures were measured. The data were analyzed by means of Tobit regressions and ordinal logistic regressions. Results show that COO and CFC are both positively correlated with compliance with recommended precautionary measures. Moreover, COO and CFC-future do not interact, although they are positively correlated. Gender, age, perceived risk of COVID-19 infection for others, perceived compliance by others and opinion about government response to the pandemic also have a significant association with compliance. These findings emphasize the importance of COO as well as consideration of the future in the prediction of cooperation in social dilemmas.
TANDEM ZINC-FINGER/PLUS3 regulates phytochrome B abundance and signaling to fine-tune hypocotyl growth
Authors: Fang Weiwei , Vellutini Elisa , Perrella Giorgio , Kaiserli Eirini
Published: August 2022

TANDEM ZINC-FINGER/PLUS3 (TZP) is a transcriptional regulator that acts at the crossroads of light and photoperiodic signaling. Here, we unveil a role for TZP in fine-tuning hypocotyl elongation under red light and long-day conditions. We provide genetic evidence for a synergistic action between TZP and PHOTOPERIODIC CONTROL OF HYPOCOTYL 1 (PCH1) in regulating the protein abundance of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and downstream gene expression in response to red light and long days (LDs). Furthermore, we show that TZP is a positive regulator of the red/far-red light receptor and thermosensor phytochrome B (phyB) by promoting phyB protein abundance, nuclear body formation, and signaling. Our data therefore assign a function to TZP in regulating two key red light signaling components, phyB and PIF4, but also uncover a new role for PCH1 in regulating hypocotyl elongation in LDs. Our findings provide a framework for the understanding of the mechanisms associated with the TZP signal integration network and their importance for optimizing plant growth and adaptation to a changing environment.
The Arabidopsis Rab protein RABC1 affects stomatal development by regulating lipid droplet dynamics
Authors: Ge Shengchao , Zhang Ruo-Xi , Wang Yi-Fei , Sun Pengyue , Chu Jiaheng , Li Jiao , Sun Peng , Wang Jianbo , Hetherington Alistair M , Liang Yun-Kuan
Published: August 2022

Lipid droplets (LDs) are evolutionarily conserved organelles that serve as hubs of cellular lipid and energy metabolism in virtually all organisms. Mobilization of LDs is important in light-induced stomatal opening. However, whether and how LDs are involved in stomatal development remains unknown. We show here that Arabidopsis thaliana LIPID DROPLETS AND STOMATA 1 (LDS1)/RABC1 (At1g43890) encodes a member of the Rab GTPase family that is involved in regulating LD dynamics and stomatal morphogenesis. The expression of RABC1 is coordinated with the different phases of stomatal development. RABC1 targets to the surface of LDs in response to oleic acid application in a RABC1GEF1-dependent manner. RABC1 physically interacts with SEIPIN2/3, two orthologues of mammalian seipin, which function in the formation of LDs. Disruption of RABC1, RABC1GEF1, or SEIPIN2/3 resulted in aberrantly large LDs, severe defects in guard cell vacuole morphology, and stomatal function. In conclusion, these findings reveal an aspect of LD function and uncover a role for lipid metabolism in stomatal development in plants.
Tic12, a 12-kDa essential component of the translocon at the inner envelope membrane of chloroplasts in Arabidopsis
Authors: Zhao Xueyang , Higa Takeshi , Nakai Masato
Published: August 2022

The complexes translocon at the outer envelope membrane of chloroplasts and translocon at the inner envelope membrane of chloroplasts (TIC) mediate preprotein translocation across the chloroplast outer and inner envelope membranes, respectively. Tic20, Tic56, Tic100, and Tic214 form a stable one-megadalton TIC whose function is essential for Arabidopsis thaliana and Chlamydomonas reinhardtii. Tic20 plays a central role in preprotein translocation by forming a protein-conducting channel. Tic56, Tic100, and Tic214 are also indispensable for TIC function, but whether other components are required for this process remain unclear. Here, we demonstrate that a 12-kDa protein named Tic12 is part of the TIC in A. thaliana and participates in preprotein translocation across the inner envelope membrane. Tic12 was tightly associated with the TIC but disassociated under high-salt conditions in combination with Triton X-100. Site-specific UV crosslinking experiments revealed that Tic12 and Tic20 directly interact with the transit peptide of a translocating preprotein. The tic12 null mutants are albino and seedling lethal, similar to the other tic null mutants. Tic12 and Tic20 were also involved in preprotein translocation in (Pisum sativum) pea chloroplasts. Thus, Tic12 is an essential constituent that forms the functional core together with Tic20 in the one-megadalton TIC.
HPCA1 is required for systemic reactive oxygen species and calcium cell-to-cell signaling and plant acclimation to stress
Authors: Fichman Yosef , Zandalinas Sara I , Peck Scott , Luan Sheng , Mittler Ron
Published: August 2022

Reactive oxygen species (ROS), produced by respiratory burst oxidase homologs (RBOHs) at the apoplast, play a key role in local and systemic cell-to-cell signaling, required for plant acclimation to stress. Here we reveal that the Arabidopsis thaliana leucine-rich-repeat receptor-like kinase H2O2-INDUCED CA2+ INCREASES 1 (HPCA1) acts as a central ROS receptor required for the propagation of cell-to-cell ROS signals, systemic signaling in response to different biotic and abiotic stresses, stress responses at the local and systemic tissues, and plant acclimation to stress, following a local treatment of high light (HL) stress. We further report that HPCA1 is required for systemic calcium signals, but not systemic membrane depolarization responses, and identify the calcium-permeable channel MECHANOSENSITIVE ION CHANNEL LIKE 3, CALCINEURIN B-LIKE CALCIUM SENSOR 4 (CBL4), CBL4-INTERACTING PROTEIN KINASE 26 and Sucrose-non-fermenting-1-related Protein Kinase 2.6/OPEN STOMATA 1 (OST1) as required for the propagation of cell-to-cell ROS signals. In addition, we identify serine residues S343 and S347 of RBOHD (the putative targets of OST1) as playing a key role in cell-to-cell ROS signaling in response to a local application of HL stress. Our findings reveal that HPCA1 plays a key role in mediating and coordinating systemic cell-to-cell ROS and calcium signals required for plant acclimation to stress.
Phytochrome interacting factor regulates stomatal aperture by coordinating red light and abscisic acid
Authors: Li Qian , Zhou Luyan , Chen Yanan , Xiao Ning , Zhang Dongping , Zhang Mengjiao , Wang Wenguo , Zhang Changquan , Zhang Anning , Li Hua , Chen Jianmin , Gao Yong
Published: August 2022

Stomata are crucial valves coordinating the fixation of carbon dioxide by photosynthesis and water loss through leaf transpiration. Phytochrome interacting factors (PIFs) are negative regulators of red light responses that belong to the basic helix–loop–helix family of transcription factors. Here, we show that the rice (Oryza sativa) PIF family gene OsPIL15 acts as a negative regulator of stomatal aperture to control transpiration in rice. OsPIL15 reduces stomatal aperture by activating rice ABSCISIC ACID INSENSITIVE 5 (OsABI5), which encodes a critical positive regulator of ABSCISIC ACID (ABA) signaling in rice. Moreover, OsPIL15 interacts with the NIGT1/HRS1/HHO family transcription factor rice HRS1 HOMOLOG 3 (OsHHO3) to possibly enhance the regulation of stomatal aperture. Notably, we discovered that the maize (Zea mays) PIF family genes ZmPIF1 and ZmPIF3, which are homologous to OsPIL15, are also involved in the regulation of stomatal aperture in maize, indicating that PIF-mediated regulation of stomatal aperture may be conserved in the plant lineage. Our findings explain the molecular mechanism by which PIFs play a role in red-light-mediated stomatal opening, and demonstrate that PIFs regulate stomatal aperture by coordinating the red light and ABA signaling pathways.
An LCO-responsive homolog of NODULE INCEPTION positively regulates lateral root formation in Populus sp.
Authors: Irving Thomas B , Chakraborty Sanhita , Maia Lucas Gontijo Silva , Knaack Sara , Conde Daniel , Schmidt Henry W , Triozzi Paolo M , Simmons Carl H , Roy Sushmita , Kirst Matias , Ané Jean-Michel
Published: August 2022

The transcription factor NODULE INCEPTION (NIN) has been studied extensively for its multiple roles in root nodule symbiosis within plants of the nitrogen-fixing clade (NFC) that associate with soil bacteria, such as rhizobia and Frankia. However, NIN homologs are present in plants outside the NFC, suggesting a role in other developmental processes. Here, we show that the biofuel crop Populus sp., which is not part of the NFC, contains eight copies of NIN with diversified protein sequence and expression patterns. Lipo-chitooligosaccharides (LCOs) are produced by rhizobia and a wide range of fungi, including mycorrhizal ones, and act as symbiotic signals that promote lateral root formation. RNAseq analysis of Populus sp. treated with purified LCO showed induction of the PtNIN2 subfamily. Moreover, the expression of PtNIN2b correlated with the formation of lateral roots and was suppressed by cytokinin treatment. Constitutive expression of PtNIN2b overcame the inhibition of lateral root development by cytokinin under high nitrate conditions. Lateral root induction in response to LCOs likely represents an ancestral function of NIN retained and repurposed in nodulating plants, as we demonstrate that the role of NIN in LCO-induced root branching is conserved in both Populus sp. and legumes. We further established a visual marker of LCO perception in Populus sp. roots, the putative sulfotransferase PtSS1 that can be used to study symbiotic interactions with the bacterial and fungal symbionts of Populus sp.
Sexual Functioning Among Adults with Chronic Pain: Prevalence and Association with Pain-Related Outcomes
Authors: Flegge Lindsay G , Barr Aex , Craner Julia R
Published: August 2022

Background

Prior research indicates that sexual functioning and chronic pain commonly coexist and impact each other; however, there are limitations in current research as to the prevalence and severity of sexual dysfunction in patients with chronic pain.

Method

This study used detailed measures across multiple domains of sexual functioning to describe the prevalence and correlates of self-reported sexual functioning among individuals with chronic pain presenting for treatment at a multidisciplinary pain management center (N = 247). Domains included sexual interest, satisfaction with sexual functioning, vaginal lubrication, vaginal discomfort, and erectile function. Individuals with and without sexual dysfunction were compared on pain-related outcome variables.

Results

Results from this study showed a high prevalence of sexual dysfunction in populations with chronic pain and a positive association between sexual problems and pain severity and psychological concerns. Sex differences were noted, with female participants exhibiting significantly lower sexual satisfaction associated with higher levels of pain, pain-related life interference, depression, and anxiety, whereas these relationships were not significant for male participants.

Conclusion

Findings demonstrated that patients with chronic pain experience significant sexual dysfunction, including lack of interest in sexual activity and low satisfaction with their sex lives. Compared with patients without sexual dysfunction, patients with sexual dysfunction reported higher average pain levels and higher depressive symptoms, along with greater anxiety in patients with at least one area of sexual dysfunction. Adding to these findings are the pain-relevant correlates of sexual functioning domains and sex differences in these relationships, with women experiencing additional pain-related problems. Limitations and future research directions are discussed.
Historical prevalence of slavery predicts contemporary American gun ownership
Authors: Buttrick Nicholas , Mazen Jessica
Published: August 2022

American gun-owners, uniquely, view firearms as a means of keeping themselves safe from dangers both physical and psychological. We root this belief in the experience of White Southerners during Reconstruction—a moment when a massive upsurge in the availability of firearms co-occurred with a worldview threat from the emancipation and the political empowerment of Black Southerners. We show that the belief-complex formed in this historical moment shapes contemporary gun culture: The prevalence of slavery in a Southern county (measured in 1860) predicts the frequency of firearms in the present day. This relationship holds above and beyond a number of potential covariates, including contemporary crime rates, police spending, degree of racial segregation and inequality, socioeconomic conditions, and voting patterns in the 2016 Presidential election; and is partially mediated by the frequency of people in the county reporting that they generally do not feel safe. This Southern origin of gun culture may help to explain why we find that worries about safety do not predict county-level gun ownership outside of historically slave-owning counties, and why we find that social connection to historically slaveholding counties predicts county-level gun ownership, even outside of the South.
The Bacillus anthracis S-layer is an exoskeleton-like structure that imparts mechanical and osmotic stabilization to the cell wall
Authors: Fioravanti Antonella , Mathelie-Guinlet Marion , Dufrêne Yves F , Remaut Han
Published: August 2022

Surface layers (S-layers) are 2D paracrystalline protein monolayers covering the cell envelope of many prokaryotes and archaea. Proposed functions include a role in cell support, as scaffolding structure, as molecular sieve, or as virulence factor. Bacillus anthracis holds two S-layers, composed of Sap or EA1, which interchange in early and late exponential growth phase. We previously found that acute disruption of B. anthracis Sap S-layer integrity, by means of nanobodies, results in severe morphological cell surface defects and cell collapse. Remarkably, this loss of function is due to the destruction of the Sap lattice structure rather than detachment of monomers from the cell surface. Here, we combine force nanoscopy and light microscopy observations to probe the contribution of the S-layer to the mechanical, structural, and functional properties of the cell envelope, which have been so far elusive. Our experiments reveal that cells with a compromised S-layer lattice show a decreased compressive stiffness and elastic modulus. Furthermore, we find that S-layer integrity is required to resist cell turgor under hypotonic conditions. These results present compelling experimental evidence indicating that the S-layers can serve as prokaryotic exoskeletons that support the cell wall in conferring rigidity and mechanical stability to bacterial cells.
No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals
Authors: Sironi Manuela , Cagliani Rachele , Biasin Mara , Lo Caputo Sergio , Saulle Irma , Forni Diego , Real Luis Miguel , Pineda Juan Antonio , Exposito Almudena , Saez María Eugenia , Sinangil Faruk , Forthal Donald , Caruz Antonio , Clerici Mario
Published: August 2022

An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.
Immunity-induced criticality of the genotype network of influenza A (H3N2) hemagglutinin
Authors: Williams Blake J M , Ogbunugafor C Brandon , Althouse Benjamin M , Hébert-Dufresne Laurent
Published: August 2022

Seasonal influenza kills hundreds of thousands every year, with multiple constantly changing strains in circulation at any given time. A high mutation rate enables the influenza virus to evade recognition by the human immune system, including immunity acquired through past infection and vaccination. Here, we capture the genetic similarity of influenza strains and their evolutionary dynamics with genotype networks. We show that the genotype networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed distributions of module sizes and connectivity indicative of critical behavior. We argue that (i) genotype networks are driven by mutation and host immunity to explore a subspace of networks predictable in structure and (ii) genotype networks provide an underlying structure necessary to capture the rich dynamics of multistrain epidemic models. In particular, inclusion of strain-transcending immunity in epidemic models is dependent upon the structure of an underlying genotype network. This interplay is consistent with self-organized criticality where the epidemic dynamics of influenza locates critical regions of its genotype network. We conclude that this interplay between disease dynamics and network structure might be key for future network analysis of pathogen evolution and realistic multistrain epidemic models.
Nature-inspired delivery of mitochondria-targeted angiotensin receptor blocker
Authors: Phillip Jude M , Lin Ran , Cheetham Andrew , Stern David , Li Yukang , Wang Yuzhu , Wang Han , Rini David , Cui Honggang , Walston Jeremy D , Abadir Peter M
Published: August 2022

Mitochondria are critical regulators of cellular function and survival. We have previously demonstrated that functional angiotensin receptors embedded within the inner mitochondrial membrane modulate mitochondrial energy production and free radical generation. The expression of mitochondrial angiotensin II type-1 receptors increases during aging, with a complementary decrease in angiotensin II type-2 receptor density. To address this age-associated mitochondrial dysfunction, we have developed a mitochondria-targeted delivery system to effectively transport angiotensin type-1 receptor blocker—Losartan (mtLOS) into the inner mitochondrial membrane. We engineered mtLOS to become active within the mitochondria after cleavage by mitochondrial peptidases. Our data demonstrate effective and targeted delivery of mtLOS into the mitochondria, compared to a free Losartan, or Losartan conjugated to a scrambled mitochondrial target signal peptide, with significant shifts in mitochondrial membrane potential upon mtLOS treatment. Furthermore, engineered mitochondrial-targeting modalities could open new avenues to transport nonmitochondrial proteins into the mitochondria, such as other macromolecules and therapeutic agents.
Ancient dental calculus preserves signatures of biofilm succession and interindividual variation independent of dental pathology
Authors: Velsko Irina M , Semerau Lena , Inskip Sarah A , García-Collado Maite I , Ziesemer Kirsten , Ruber Maria Serrano , Benítez de Lugo Enrich Luis , Molero García Jesús Manuel , Valle David Gallego , Peña Ruiz Ana Cristina , Salazar-García Domingo C , Hoogland Menno L P , Warinner Christina
Published: August 2022

Dental calculus preserves oral microbes, enabling comparative studies of the oral microbiome and health through time. However, small sample sizes and limited dental health metadata have hindered health-focused investigations to date. Here, we investigate the relationship between tobacco pipe smoking and dental calculus microbiomes. Dental calculus from 75 individuals from the 19th century Middenbeemster skeletal collection (Netherlands) were analyzed by metagenomics. Demographic and dental health parameters were systematically recorded, including the presence/number of pipe notches. Comparative data sets from European populations before and after the introduction of tobacco were also analyzed. Calculus species profiles were compared with oral pathology to examine associations between microbiome community, smoking behavior, and oral health status. The Middenbeemster individuals exhibited relatively poor oral health, with a high prevalence of periodontal disease, caries, heavy calculus deposits, and antemortem tooth loss. No associations between pipe notches and dental pathologies, or microbial species composition, were found. Calculus samples before and after the introduction of tobacco showed highly similar species profiles. Observed interindividual microbiome differences were consistent with previously described variation in human populations from the Upper Paleolithic to the present. Dental calculus may not preserve microbial indicators of health and disease status as distinctly as dental plaque.
Risk of adverse pregnancy outcomes prior to the onset of an autoimmune rheumatic disease: a systematic review
Authors: Muñoz Candido Muñoz , Goulden Bethan , Ahmed Kawser , Alijotas-Reig Jaume , Giles Ian
Published: August 2022

Objectives

An increased risk of adverse maternal and foetal pregnancy complications (including pre-eclampsia, intrauterine growth restriction, and small for gestational age) is well described in women with autoimmune rheumatic disease (ARD) compared with the general population (GenPop). It is less clear, however, whether this risk of adverse pregnancy outcome (APO) also exists in women with ‘preclinical ARD’ (pre-ARD) before they are diagnosed with an ARD many years post-partum. Therefore, we have undertaken a systematic review of the available evidence on APO in patients who subsequently were diagnosed with a rheumatic disease to identify whether there is an increased risk in pre-ARD.

Methods

The present study was reported in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using the online PubMed database. Pre-SLE and pre-RA patients were defined as those who, over the subsequent years, developed SLE or RA according to international classification criteria.

Results

A total of 176 articles were screened, and 27 original articles were selected for final analysis. Pre-RA was the most studied group, with 15 studies and a total of >1600 pregnancies, and pre-SLE was the second-most studied pre-ARD in pregnancy, with 14 studies and a total of >1000 pregnancies. We found that patients who subsequently developed SLE had an increased burden of poor pregnancy outcomes compared with pregnant women from the GenPop, but fewer APOs compared with pregnancies of women with SLE. In contrast, a similar rate of APOs was found when pre-RA pregnancies were compared with GenPop pregnancies.

Conclusion

Our findings of an increased risk of APO in certain pre-ARDs highlights the relevance of taking an obstetric history during the first rheumatology appointment and the need for novel screening strategies for the prediction of APOs. Further research is required to elucidate the immune basis of APOs in preclinical and clinical ARD.
Detection of neutralizing antibodies against flaviviruses in free-ranging birds, Paraguay (2016–2018)
Authors: Cardozo Fátima , Bernal Cynthia , Rojas Alejandra , Diaz Adrián , Spinsanti Lorena , Páez Malvina , Guillén Yvalena , Lesterhuis Arne , Yanosky Alberto , Contigiani Marta , Mendoza Laura
Published: August 2022

Saint Louis encephalitis virus (SLEV), West Nile virus (WNV) and Ilheus virus (ILHV) are flaviviruses maintained by enzootic transmission networks between mosquitoes and birds. They have been detected in South America, with no records for Paraguay. We detected the presence of neutralizing antibodies for SLEV, WNV and ILHV in free-ranging birds collected in Paraguay (2016–2018). Four positive samples were detected in resident birds: one SLEV (rufous-bellied thrush), one WNV (barred antshrike) and two ILHV (white-tipped dove and shiny cowbird). These results bring new information about enzootic activity of flaviviruses in Paraguay.