bluuebunny/crossref_metadata_2025 huggingface dataset:
Neither the African-Centric S47 Nor P72 Variant of TP53 Is Associated With Reduced Risk of Febrile Malaria in a Malian Cohort Study
Authors: Bhardwaj Jyoti , Upadhye Aditi , Gaskin Erik L , Doumbo Safiatou , Kayentao Kassoum , Ongoiba Aissata , Traore Boubacar , Crompton Peter D , Tran Tuan M
Published: March 2023

Background

TP53 has been shown to play a role in inflammatory processes, including malaria. We previously found that p53 attenuates parasite-induced inflammation and predicts clinical protection to Plasmodium falciparum infection in Malian children. Here, we investigated whether p53 codon 47 and 72 polymorphisms are associated with differential risk of P. falciparum infection and uncomplicated malaria in a prospective cohort study of malaria immunity.

Methods

p53 codon 47 and 72 polymorphisms were determined by sequencing TP53 exon 4 in 631 Malian children and adults enrolled in the Kalifabougou cohort study. The effects of these polymorphisms on the prospective risk of febrile malaria, incident parasitemia, and time to fever after incident parasitemia over 6 months of intense malaria transmission were assessed using Cox proportional hazards models.

Results

Confounders of malaria risk, including age and hemoglobin S or C, were similar between individuals with or without p53 S47 and R72 polymorphisms. Relative to their respective common variants, neither S47 nor R72 was associated with differences in prospective risk of febrile malaria, incident parasitemia, or febrile malaria after parasitemia.

Conclusions

These findings indicate that p53 codon 47 and 72 polymorphisms are not associated with protection against incident P. falciparum parasitemia or uncomplicated febrile malaria.
Exploring the well-being of people affected by skin NTDs in Kaduna and Kwara States, Nigeria: a photovoice and scoping review study
Authors: Adekeye Oluwatosin , Chowdhury Shahreen , McRae Ayuba , Olorunfemi Temitope , Ozokede Edward , Dubukumah Linda , Makinde Oluwabunmi , Ewemade Jude , Abdulkadir Shuaibu , Ayuba Rebecca , Habibat Suleiman , Gurma Matthew , Thomson Rachael , Isiyaku Sunday , Dean Laura
Published: March 2023

People affected by skin neglected tropical diseases (NTDs) grapple with both physical and emotional reactions that compromise their health and well-being. Multiple studies with people affected by skin NTDs have shown high levels of poor mental well-being using self-report questionnaires or psychological measures. However, few have provided in-depth documentation of lived experiences from the perspective of affected persons and there is limited consideration of how their viewpoints can be used to shape intervention design. This article draws together findings from an international scoping review and a photovoice study conducted in Kaduna and Kwara States, Nigeria. Our combined analysis, which situates the lived realities of people affected by skin NTDs within the existing evidence base, was used to inform the design of a subsequent well-being intervention. Using Meyer's (2003) minority stress model, we have illustrated that there is a synergistic relationship between mental health, chronic morbidity and disability from skin NTDs. This relationship results from a complex interplay of factors including pain and discomfort and a reduced ability to function and participate in areas such as livelihoods, food provision and education. Stigma and discrimination act as a catalyst for these functional limitations and participation restrictions, resulting in feelings of being useless, broken, shame and sadness. The critical role of participatory methods in our study emphasises how people affected by skin NTDs have multiple coping mechanisms that can be galvanised in the provision of holistic NTD care. We recommend that NTD programmes should strengthen relationships with affected persons to identify pre-existing support platforms that can be used to support the emotional and physical health and well-being of affected persons. Working with affected persons and community actors to strengthen necessary intersectoral approaches is a first step in designing and delivering such holistic care.
Do Different Coercive Strategies Help or Hurt Deterrence?
Authors: Joseph Michael F
Published: March 2023

Powerful states build different coercive tools to manage their broad foreign policy agenda. Do different coercive strategies help or hurt deterrence success? I analyze a simple crisis model where the Defender seeks to deter a Challenger from investing in a novel coercive technology through hassling and preventive threats. Subtle differences between my model and those of Schram, Bas and Coe, and others generate different logics that clarify the Defender’s costs and benefits for building diverse coercive tools. Unlike others, I show that hassling can complement and undercut the threat of war in a one-shot, complete information crisis. I show that adverse effects arise when we want deterrence to hold the most: against technologically sophisticated rivals with moderately to severely opposed preferences. After I detail my model, I connect different core specifications to different empirical domains. This exercise helps connect formal theory to empirical research. I argue that my model best fits Defenders who want to deter Challengers from building novel coercive technologies in the modern era. I propose a novel approach for modeling policy implications.
The Problem with Trade Measurement in International Relations
Authors: Linsi Lukas , Burgoon Brian , Mügge Daniel K
Published: March 2023

Trade statistics are widely used in studies and policymaking focused on economic interdependence. Yet, researchers in International Relations (IR) have largely disregarded half the data available to study trade. Bilateral trade flows are usually recorded twice: by the sending economy as an export and by the receiving one as an import. These two values should match, but discrepancies between them tend to be large and pervasive. Most studies ignore this issue, which we label the “mirror problem” for short, by using only one entry. However, it is not self-evident which one is consistently most accurate. Hence, IR's reliance on error-prone trade statistics may be distorting its study of economic interdependence. This article explores this problem in three steps: first, we quantify the mirror problem in trade data. Second, we investigate the origins of the mirror problem, using statistical analyses, archival records, and interviews with statistical experts. Third, we illustrate the implications of the mirror problem through replications covering diverse topics in IR. We find that accounting for the mirror problem can variably strengthen, undermine, or overturn conclusions of such analyses. The findings underscore the severity of measurement problems in IR and suggest particular ways to address those problems.
Tetracycline resistance potential of heterotrophic bacteria isolated from freshwater fin-fish aquaculture system
Authors: Kusunur Ahamed Basha , Mogilipuri Shanmukha Sai , Moturu Dhamodher , Benala Manikantha , Vaiyapuri Murugadas , Panda Satyen Kumar , George Joshy Chalil , Badireddy Madhusudana Rao
Published: March 2023

Aims

This study investigated the tetracycline resistance potential of heterotrophic bacteria isolated from twenty-four freshwater fin-fish culture ponds in Andhra Pradesh, India.

Methods and results

A total of 261 tetracycline resistant bacteria (tetR) were recovered from pond water, pond sediment, fish gills, fish intestine, and fish feed. Bacteria with high tetracycline resistance (tetHR) (n = 30) that were resistant to tetracycline concentrations above 128  μg mL−1 were predominantly Lactococcus garvieae followed by Enterobacter spp., Lactococcus lactis, Enterobacter hormaechei, Staphylococcus arlettae, Streptococcus lutetiensis, Staphylococcus spp., Brevundimonas faecalis, Exiguobacterium profundum, Lysinibacillus spp., Stutzerimonas stutzeri, Enterobacter cloacae, and Lactococcus taiwanensis. Resistance to 1024 μg mL−1 of tetracycline was observed in L. garvieae, S. arlettae, Enterobacter spp., B. faecalis. Tet(A) (67%) was the predominant resistance gene in tetHR followed by tet(L), tet(S), tet(K), and tet(M). At similar concentrations of exposure, tetracycline procured at the farm level (69.5% potency) exhibited lower inhibition against tetHR bacteria compared to pure tetracycline (99% potency). The tetHR bacteria showed higher cross-resistance to furazolidone (100%) followed by co-trimoxazole (47.5%) and enrofloxacin (11%).

Conclusions

The maximum threshold of tetracycline resistance at 1024 μg mL−1 was observed in S. arlettae, Enterobacter spp., B. faecalis, and L. garvieae and tet(A) was the major determinant found in this study.
Lactiplantibacillus plantarumP101 alleviated lead-induced more severe hepatic injury in obese mice, by promoting fecal lead excretion and enhancing antioxidative defense system
Authors: Hu Liehai , Zhao Yu , You Tao , Xu Hengyi
Published: March 2023

Aims

Lead (Pb) is a toxic heavy metal that has been intensively studied, but its toxicity in sub-healthy people remains unclear. This study aims to investigate the adverse effects of Pb in the obese population and validate the feasibility of a potential probiotic strain for the treatment of Pb poisoning and diet-induced obesity.

Methods and Results

Male Kunming mice were fed a high-fat/high-sugar (HFHS) diet for 6 weeks, then received Pb exposure and Lactiplantibacillus plantarum P101 supplementation for 2 weeks. The histopathology of the liver and colon was observed, and biochemical indicators and gene expression levels were measured.

Conclusions

Here, we reported that Pb exposure exacerbated the existing oxidative stress and gut barrier injury in obese mice, leading to more severe Pb accumulation, and hepatic inflammatory injury compared with normal diet-fed mice. It is worth noting that the P101 treatment significantly reduced Pb accumulation by promoting fecal Pb excretion and enhanced the antioxidant capacity of mice. After P101 treatment, obesity-related indicators were downregulated, and the hepatic injury and gut barrier disruption in mice were alleviated effectively.
Torula yeast may improve intestinal health and immune function of weanling pigs
Authors: Espinosa Charmaine D , Torres-Mendoza Leidy J , Stein Hans H
Published: March 2023

An experiment was conducted to test the hypothesis that inclusion of a conventional torula yeast or a torula yeast produced from forestry byproducts (i.e., woody torula yeast) in diets for weanling pigs instead of fish meal and plasma protein improves growth performance and intestinal health of pigs. A total of 120 weanling pigs (6.53 ± 0.78 kg) were allotted to three treatments with ten replicate pens per diet. Pigs were fed one of three diets from days 1 to 14 post-weaning (phase 1), whereas all pigs were fed a common diet in phase 2 (days 15 to 28). The three treatments in phase 1 included a control diet with 5% fish meal, 3.5% plasma protein, and no torula yeast. The second diet contained 1.5% fish meal, 14% woody torula yeast, and no plasma protein, whereas the third diet contained 1.5% fish meal, 14% conventional torula yeast, and no plasma protein. Fecal scores were assessed every other day. On day 7, one pig per pen was euthanized to collect ileal tissue and mucosa for determination of morphology and for ribonucleic acid (RNA) sequencing analysis. At the end of phases 1 and 2, blood samples were collected and concentrations of cytokines, plasma urea nitrogen (PUN), peptide YY, immunoglobulin G, total protein, and albumin were analyzed. Results indicated that both torula yeast sources could replace fish meal and plasma protein without affecting growth performance, intestinal morphology, or blood characteristics of pigs. Pigs fed a diet containing torula yeast had improved (P < 0.05) fecal scores during phase 1. Pigs fed the conventional torula yeast diet had greater (P < 0.05) concentration of interleukin-2 compared with pigs fed the control diet. On day 14, greater (P < 0.05) concentrations of interleukin-4 and interleukin-10 were observed in pigs fed the diet containing the woody torula yeast or conventional torula yeast compared with pigs fed the control diet. Results from the RNA sequencing indicated that 19 of 24 analyzed genes involved in digestion and absorption of protein and vitamins were downregulated in pigs fed the diet containing woody torula yeast compared with pigs fed the control diet. However, only two genes (i.e., ANKS4B and FAM54A) were downregulated in pigs fed the woody torula yeast diet compared with the conventional torula yeast diet. In conclusion, using woody or conventional torula yeast instead of fish meal and plasma protein in the phase 1 diet for weanling pigs may improve intestinal health without influencing growth performance of pigs.
Consumer Desires and the Fluctuating Balance between Liquid and Solid Consumption: The Case of Finnish Clothing Libraries
Authors: Rosenberg Laura M , Weijo Henri A , Kerkelä Iina
Published: March 2023

The ongoing rise of liquid consumption manifests in the growing popularity of ephemeral, access-based, and dematerialized forms of consumption that contrast with traditional solid forms of consumption characterized by possession and strong object relationships. The literature already presents a robust understanding of what makes liquid and solid consumption appealing to consumers. What has received less attention is the co-existence of liquid and solid consumption in consumers’ lived experiences. Furthermore, the literature does not explain how the balance that consumers achieve between liquid and solid consumption fluctuates over time. This study illuminates the co-existence of liquid and solid consumption through a phenomenological inquiry of subscription-based clothing libraries, a context where solid personal possessions frequently mix with liquid accessed items in everyday use. Findings show that changes in consumer desire play a major role in consumer decisions to liquify or solidify consumption, especially over time. Overall, the study provides new theoretical insights into liquid and solid consumption, consumer desire, and burdens of access-based consumption.
Tracking Inattention
Authors: Goldstein Nathan
Published: March 2023

This study proposes a real-time estimate of inattention, based on micro-level data. I show that a simple specification that estimates the persistence of a forecaster's deviation from the mean provides a direct estimate of parameters of information frictions according to prominent models of expectations. The new estimate can also be interpreted as a hybrid measure of both information frictions and behavioral frictions. Using the new specification, I revise several key findings documented in the previous literature. I find higher levels of inattention and document new forms of variations over time and across variables, horizons, individuals, and types of agents. I also report new results from long-run forecasts and document an unprecedented response to COVID-19.
Learning torus PCA-based classification for multiscale RNA correction with application to SARS-CoV-2
Authors: Wiechers Henrik , Eltzner Benjamin , Mardia Kanti V , Huckemann Stephan F
Published: March 2023

Three-dimensional RNA structures frequently contain atomic clashes. Usually, corrections approximate the biophysical chemistry, which is computationally intensive and often does not correct all clashes. We propose fast, data-driven reconstructions from clash-free benchmark data with two-scale shape analysis: microscopic (suites) dihedral backbone angles, mesoscopic sugar ring centre landmarks. Our analysis relates concentrated mesoscopic scale neighbourhoods to microscopic scale clusters, correcting within-suite-backbone-to-backbone clashes exploiting angular shape and size-and-shape Fréchet means. Validation shows that learned classes highly correspond with literature clusters and reconstructions are well within physical resolution. We illustrate the power of our method using cutting-edge SARS-CoV-2 RNA.
Open questions in plant cell wall synthesis
Authors: McFarlane Heather E
Published: March 2023

Plant cells are surrounded by strong yet flexible polysaccharide-based cell walls that support cells while also allowing growth by cell expansion. Plant cell wall research has advanced tremendously in recent years. Sequenced genomes of model and crop plants have facilitated cataloguing and characterization of many enzymes involved in cell wall synthesis. Structural information has been generated for several important cell wall-synthesizing enzymes. Important tools have been developed including antibodies raised against a variety of cell wall polysaccharides and glycoproteins, collections of enzyme clones and synthetic glycan arrays for characterizing enzymes, herbicides that specifically affect cell wall synthesis, live-cell imaging probes to track cell wall synthesis, and an inducible secondary cell wall synthesis system. Despite these advances, and often because of the new information they provide, many open questions about plant cell wall polysaccharide synthesis persist. This article highlights some of the key questions that remain open, reviews the data supporting different hypotheses that address these questions, and discusses technological developments that may answer these questions in the future.
Modulatory effect ofOriganum vulgareessential oil and carvacrol onMalasseziaspp. virulence factors
Authors: Angiolella Letizia , Rojas Florencia , Mussin Javier , Giusiano Gustavo
Published: March 2023

Malassezia sympodialis and Malassezia furfur are recognized as an important part of the human and animals healthy skin microbiota, but also as an opportunistic fungus due to their association with a broad spectrum of skin and systemic infections. Human skin infections associated with Malassezia spp. are often chronic, recurrent, and topical or oral azole treatments are challenging with not always successful outcomes. A wide inter and intraspecies antifungal susceptibility variability that may suggest a combination of wild-type strains and resistant mutants was reported. The essential oils are complex hydrophobic mixtures of different compounds extracted from plants by distillation and have demonstrated antimicrobial activity. In this study, toxicity in the larvae model and the ability of Origanum vulgare essential oil (OVEO) and carvacrol to inhibit virulence factors such as hydrophobicity, adherence, and biofilm formation of M. sympodialis and M. furfur was evaluated. We have demonstrated the antifungal activity of OVEO and carvacrol against both species. Carvacrol was more active and less toxic than OVEO at low concentrations (< 1 mg/ml). Malassezia sympodialis showed a significant decrease in adherence and its ability to form biofilms when OVEO or carvacrol is present. Both Malassezia species showed reduced hydrophobicity in the presence of carvacrol. Further studies will have to be carried out to understand how these substances act, but the inhibition of some virulence factors could represent a new target to overcome the problem of drug resistance.
Type Ia supernovae SN 2013bz, PSN J0910 + 5003, and ASASSN-16ex: similar to 09dc-like?
Authors: Tiwari S , Chakradhari N K , Sahu D K , Anupama G C , Kumar B , Sahu K R
Published: March 2023

We present optical photometric and spectroscopic studies of three supernovae (SNe): SN 2013bz, PSN J0910 + 5003, and ASASSN-16ex (SN 2016ccj). UV–optical photometric data of ASASSN-16ex obtained with the Swift Ultraviolet/Optical Telescope (UVOT) are also analysed. These objects were initially classified as 09dc-like type Ia SNe. The decline-rate parameters (Δm15(B)true) are derived as 0.92 ± 0.04 (SN 2013bz), 0.70 ± 0.05 (PSN J0910 + 5003), and 0.73 ± 0.03 (ASASSN-16ex). The estimated B-band absolute magnitudes at maximum, −19.61 ± 0.20 mag for SN 2013bz, −19.44 ± 0.20 mag for PSN J0910 + 5003, and −19.78 ± 0.20 mag for ASASSN-16ex, indicate that all three objects are relatively bright. The peak bolometric luminosities for these objects are derived as $\log L_\text{bol}^\text{max} =$ 43.38 ± 0.07, 43.26 ± 0.07, and 43.40 ± 0.06 erg s−1, respectively. The spectral and velocity evolution of SN 2013bz is similar to that of a normal SN Ia, hence it appears to be a luminous, normal type Ia supernova. On the other hand, the light curves of PSN J0910 + 5003 and ASASSN-16ex are broad and exhibit properties similar to 09dc-like SNe Ia. Their spectroscopic evolution shows similarity with 09dc-like SNe: strong C ii lines are seen in the pre-maximum spectra of these two events. Their photospheric velocity evolution is similar to SN 2006gz. Further, in the UV bands, ASASSN-16ex is very blue, like other 09dc-like SNe Ia.
The multiwavelength view of shocks in the fastest nova V1674 Her
Authors: Sokolovsky K V , Johnson T J , Buson S , Jean P , Cheung C C , Mukai K , Chomiuk L , Aydi E , Molina B , Kawash A , Linford J D , Mioduszewski A J , Rupen M P , Sokoloski J L , Williams M N , Steinberg E , Vurm I , Metzger B D , Page K L , Orio M , Quimby R M , Shafter A W , Corbett H , Bolzoni S , DeYoung J , Menzies K , Romanov F D , Richmond M , Ulowetz J , Vanmunster T , Williamson G , Lane D J , Bartnik M , Bellaver M , Bruinsma E , Dugan E , Fedewa J , Gerhard C , Painter S , Peterson D-M , Rodriguez J E , Smith C , Sullivan H , Watson S
Published: March 2023

Classical novae are shock-powered multiwavelength transients triggered by a thermonuclear runaway on an accreting white dwarf. V1674 Her is the fastest nova ever recorded (time to declined by two magnitudes is t2 = 1.1 d) that challenges our understanding of shock formation in novae. We investigate the physical mechanisms behind nova emission from GeV γ-rays to cm-band radio using coordinated Fermi-LAT, NuSTAR, Swift, and VLA observations supported by optical photometry. Fermi-LAT detected short-lived (18 h) 0.1–100 GeV emission from V1674 Her that appeared 6 h after the eruption began; this was at a level of (1.6 ± 0.4) × 10−6 photons cm−2 s−1. Eleven days later, simultaneous NuSTAR and Swift X-ray observations revealed optically thin thermal plasma shock-heated to kTshock = 4 keV. The lack of a detectable 6.7 keV Fe Kα emission suggests super-solar CNO abundances. The radio emission from V1674 Her was consistent with thermal emission at early times and synchrotron at late times. The radio spectrum steeply rising with frequency may be a result of either free-free absorption of synchrotron and thermal emission by unshocked outer regions of the nova shell or the Razin–Tsytovich effect attenuating synchrotron emission in dense plasma. The development of the shock inside the ejecta is unaffected by the extraordinarily rapid evolution and the intermediate polar host of this nova.
Influence of the dynamic classification of asteroids on observation astrometric errors: a statistical analysis
Authors: Stronati N , Faggioli L , Micheli M , Ceccaroni M
Published: March 2023

The ephemerides of minor planets are computed on the basis of astrometric observations. The asteroid orbit determination process requires these observations to be properly weighted to take into account the expected accuracy of the data. If not directly provided by the observers, the weights are, in general, computed after a station-specific statistical analysis on the observation residuals, where the influence of external factors such as epoch of observation, magnitude, and employed catalogue has been proven. In this paper, we perform a statistical analysis on observation residuals of the major surveys taking into account a new factor, i.e. the dynamical classification of asteroids, to understand whether the observation quality may have a dependence on the different type of observed object. If an influence is actually found, then it will be possible to develop a new weighting system based on these results. The weights will be easily applicable once one knows the asteroid orbit. In particular, four stations have been found having different qualities depending on whether they are observing near-Earth asteroids or main-belt asteroids. Moreover, the cross-correlation between the dynamic classification and epoch, magnitude, and catalogue is investigated, as well as the influence of these factors on observations’ quality.
A search for compact object companions to high mass function single-lined spectroscopic binaries in Gaia DR3
Authors: Jayasinghe T , Rowan D M , Thompson Todd A , Kochanek C S , Stanek K Z
Published: March 2023

Gaia Data Release 3 (DR3) provides >181 000 radial velocity (RV) solutions for single-lined spectroscopic binaries (SB1s) that can be used to search for non-interacting compact object + star binary candidates by selecting systems with large mass functions. We selected 234 such systems and identified 115 systems with good RV solutions in DR3. We used light curves from the All-Sky Automated Survey for SuperNovae (ASAS-SN) and the Transiting Exoplanet Survey Satellite (TESS) to identify and remove 31 eclipsing binaries to produce a catalogue of 80 compact object + star candidates, including 38 ellipsoidal variables. The positions of these candidates on Gaia and Two Micron All-Sky Survey (2MASS) colour–magnitude diagrams (CMDs) suggest that many of these systems are binaries with luminous companions. We compared the periods and eccentricities of detached eclipsing binaries in Gaia DR3 and ASAS-SN, and found that ${\sim }11 {{\ \rm per\ cent}}$ and ${\sim }60 {{\ \rm per\ cent}}$ of the binaries had different periods and eccentricities. We also compared RV solutions for 311 binaries in both Gaia DR3 and the Ninth Catalogue of Spectroscopic Binary Orbits (SB9), and found similar results. We do not identify any strong candidates for non-interacting compact object + star binaries.
Magnetohydrodynamic simulations of the Tayler instability in rotating stellar interiors
Authors: Ji Suoqing , Fuller Jim , Lecoanet Daniel
Published: March 2023

The Tayler instability is an important but poorly studied magnetohydrodynamic (MHD) instability that likely operates in stellar interiors. The non-linear saturation of the Tayler instability is poorly understood and has crucial consequences for dynamo action and angular momentum transport in radiative regions of stars. We perform three-dimensional MHD simulations of the Tayler instability in a cylindrical geometry, including strong buoyancy and Coriolis forces as appropriate for its operation in realistic rotating stars. The linear growth of the instability is characterized by a pre-dominantly m = 1 oscillation with growth rates roughly following analytical expectations. The non-linear saturation of the instability appears to be caused by secondary shear instabilities and is also accompanied by a morphological change in the flow. We argue, however, that non-linear saturation likely occurs via other mechanisms in real stars where the separation of scales is larger than those reached by our simulations. We also observe dynamo action via the amplification of the axisymmetric poloidal magnetic field, suggesting that Tayler instability could be important for magnetic field generation and angular momentum transport in the radiative regions of evolving stars.
Validation of Urinary Thiocyanate as a Robust Biomarker of Active Tobacco Smoking in the Prospective Urban and Rural Epidemiological Study
Authors: Mathiaparanam Stellena , Gill Biban , Sathish Thirunavukkarasu , Paré Guillaume , Teo Koon K , Yusuf Salim , Britz-McKibbin Philip
Published: March 2023

Introduction

Tobacco smoking is a leading preventable cause of premature death globally. Urinary thiocyanate is a biomarker of cyanide exposure from tobacco smoke; however, few studies have evaluated its utility in diverse populations of smokers.

Aims and Methods

We examined the associations between urinary thiocyanate and self-reported never and current smokers among 1000 participants from 14 countries in the Prospective Urban and Rural Epidemiological study. We analyzed urinary thiocyanate in light and heavy smokers as compared to never-smokers from high- (HICs), middle- (MICs), and low-income countries (LICs) using a validated capillary electrophoresis method in conjunction with standardized questionnaires.

Results

The median urinary thiocyanate concentration was 31 μM, which ranged from 8.6 μM to 52 μM for never-smokers (n = 335) and current smokers (n = 660), respectively. Urinary thiocyanate was correlated with daily cigarette consumption (r = 0.621) and total nicotine equivalents (r = 0.514). Thiocyanate also displayed a better dose–response than urinary cotinine. A moderate association of urinary thiocyanate was found in biochemically verified never-smokers (r ~0.38) because of intake of vegetables, fruits, and dairy. Receiver-operating characteristic curves established cutoff values for urinary thiocyanate to differentiate current from never-smokers with an optimal threshold of 23.9 μM (Area Under the Curve or AUC = 0.861), which lowered progressively from HICs, MICs, and LICs.

Conclusions

Elevated thiocyanate was evident in current smokers from high-income countries likely reflecting differences in smoking topography and greater toxicant burden. Background urinary thiocyanate in never-smokers was associated with goitrogenic food intake that obscured detection of secondhand smoke exposure.

Implications

Urinary thiocyanate is a sensitive biomarker of active tobacco smoking relative to cotinine that can be measured by an inexpensive capillary electrophoresis assay. Regional cutoff values are demonstrated to improve discrimination of smoking status in developing countries because of differences in smoking habits and cigarette products consumed, as well as intake of goitrogenic foods. Urinary thiocyanate may allow for more reliable estimates of the hazards of tobacco smoking between countries with varying socioeconomic development as compared to self-reports.
Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis
Authors: Lortholary Olivier , El-Sissy Carine , Leporrier Jérémie , Sze Wah Wong Sarah , Dannaoui Eric , Fremeaux-Bacchi Véronique , Aimanianda Vishukumar
Published: March 2023

Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance. Administration of eculizumab has been reported to make patients more susceptible to infection by encapsulated bacteria. Here, we are reporting an adult case of disseminated infection due to the encapsulated yeast Cryptococcus neoformans following eculizumab therapy and discuss its pathogenesis.
RNA Polymerase III–Dependent BoNR8 and AtR8 lncRNAs Contribute to Hypocotyl Elongation in Response to Light and Abscisic Acid
Authors: Zhang Nan , Xu Kai , Liu Shengyi , Yan Rong , Liu Ziguang , Wu Ying , Peng Yifang , Zhang Xiaoxu , Yukawa Yasushi , Wu Juan
Published: March 2023

Hypocotyl elongation is inhibited by light and promoted by darkness. The plant hormone abscisic acid (ABA) also inhibits hypocotyl elongation. However, details of the molecular mechanism that regulates the integrated effects of light and ABA signaling on hypocotyl elongation remain unclear. Long non-coding RNAs (lncRNAs; >200 nt) do not encode proteins but play many physiological roles in organisms. Until now, only a few lncRNAs related to hypocotyl elongation have been reported. The lncRNAs BoNR8 (272 nt) and AtR8 (259 nt), both of which are transcribed by RNA polymerase III, are homologous lncRNAs that are abundantly present in cabbage and Arabidopsis, respectively. These lncRNAs shared 77% sequence identity, and their predicted RNA secondary structures were similar; the non-conserved nucleotides in both sequences were positioned mainly in the stem–loop regions of the secondary structures. A previous study showed that BoNR8 regulated seed germination along with ABA and that AtR8 may be involved in innate immune function in Arabidopsis. Our results show that the expression levels of BoNR8 and AtR8 were differentially affected by light and ABA and that overexpression (OX) of both BoNR8 and AtR8 in Arabidopsis regulated hypocotyl elongation depending on light and ABA.. The expression levels of light-related genes PHYB, COP1, HY5 and PIF4 and ABA-related genes ABI3 and ABI5 were altered in the AtR8-OX and BoNR8-OX lines, and, in an ABI3-defective mutant, hypocotyl elongation was greatly increased under dark condition with the addition of ABA. These results indicate that BoNR8 and AtR8 regulate hypocotyl elongation together with ABI3 and key downstream light signaling genes.
A Note on von Neumann Ordinals and Dependence
Authors: Werner Jonas
Published: March 2023

This note defends the reduction of ordinals to pure sets against an argument put forward by Beau Madison Mount. In the first part I will defend the claim that dependence simpliciter can be reduced to immediate dependence and define a notion of predecessor dependence. In the second part I will provide and defend a way to model the dependence profile of ordinals akin to Mount’s proposal in terms of immediate dependence and predecessor dependence. I furthermore show that my alternative dependence profile allows us to single out the reduction of ordinals to von Neumann ordinals as the only viable set-theoretic reduction.
Paralog editing tunes rice stomatal density to maintain photosynthesis and improve drought tolerance
Authors: Karavolias Nicholas G , Patel-Tupper Dhruv , Seong Kyungyong , Tjahjadi Michelle , Gueorguieva Gloria-Alexandra , Tanaka Jaclyn , Gallegos Cruz Ana , Lieberman Samantha , Litvak Lillian , Dahlbeck Douglas , Cho Myeong-Je , Niyogi Krishna K , Staskawicz Brian J
Published: March 2023

Rice (Oryza sativa) is of paramount importance for global nutrition, supplying at least 20% of global calories. However, water scarcity and increased drought severity are anticipated to reduce rice yields globally. We explored stomatal developmental genetics as a mechanism for improving drought resilience in rice while maintaining yield under climate stress. CRISPR/Cas9-mediated knockouts of the positive regulator of stomatal development STOMAGEN and its paralog EPIDERMAL PATTERNING FACTOR-LIKE10 (EPFL10) yielded lines with ∼25% and 80% of wild-type stomatal density, respectively. epfl10 lines with moderate reductions in stomatal density were able to conserve water to similar extents as stomagen lines but did not suffer from the concomitant reductions in stomatal conductance, carbon assimilation, or thermoregulation observed in stomagen knockouts. Moderate reductions in stomatal density achieved by editing EPFL10 present a climate-adaptive approach for safeguarding yield in rice. Editing the paralog of STOMAGEN in other species may provide a means for tuning stomatal density in agriculturally important crops beyond rice.
Restricting electron flow at cytochrome b6f when downstream electron acceptors are severely limited
Authors: Saroussi Shai , Redekop Petra , Karns Devin A J , Thomas Dylan C , Wittkopp Tyler M , Posewitz Matthew C , Grossman Arthur R
Published: March 2023

Photosynthetic organisms frequently experience abiotic stress that restricts their growth and development. Under such circumstances, most absorbed solar energy cannot be used for CO2 fixation and can cause the photoproduction of reactive oxygen species (ROS) that can damage the photosynthetic reaction centers of PSI and PSII, resulting in a decline in primary productivity. This work describes a biological “switch” in the green alga Chlamydomonas reinhardtii that reversibly restricts photosynthetic electron transport (PET) at the cytochrome b6f (Cyt b6f) complex when the capacity for accepting electrons downstream of PSI is severely limited. We specifically show this restriction in STARCHLESS6 (sta6) mutant cells, which cannot synthesize starch when they are limited for nitrogen (growth inhibition) and subjected to a dark-to-light transition. This restriction represents a form of photosynthetic control that causes diminished electron flow to PSI and thereby prevents PSI photodamage but does not appear to rely on a ΔpH. Furthermore, when electron flow is restricted, the plastid alternative oxidase (PTOX) becomes active, functioning as an electron valve that dissipates some excitation energy absorbed by PSII and allows the formation of a proton motive force (PMF) that would drive some ATP production (potentially sustaining PSII repair and nonphotochemical quenching [NPQ]). The restriction at the Cyt b6f complex can be gradually relieved with continued illumination. This study provides insights into how PET responds to a marked reduction in availability of downstream electron acceptors and the protective mechanisms involved.
The additive effects of bioactive glasses and photobiomodulation on enhancing bone regeneration
Authors: Huang Lidong , Gong Weiyu , Huang Guibin , Li Jingyi , Wu Jilin , Dong Yanmei
Published: March 2023

Bioactive glasses (BG) have been generally used in bone defects repair for its good osteoinductivity and osteoconductivity. However, the early angiogenesis of BG in the repair of large-sized bone defects may not be sufficient enough to support new bone formation, resulting in the failure of bone repair. Photobiomodulation (PBM) therapy, which is superior on promoting early angiogenesis, may contribute to the angiogenesis of BG and further enhance the repair of bone defects. Therefore, we applied BG and PBM in combination and preliminarily investigated their additive effects on bone regeneration both in vitro and in vivo. The in vitro results revealed that BG combined with PBM remarkably enhanced human bone marrow mesenchymal stem cells proliferation, osteogenic-related genes expression and mineralization, which was better than applying BG or PBM respectively. For in vivo studies, the histological staining results showed that BG induced new bone formation in the interior of defects and promoted new bone reconstruction at 6 weeks post-operation. The micro-computed tomography results further confirmed that BG combined with PBM accelerated bone formation and maturation, improved the speed and quality of bone regeneration, and promoted bone repair. In conclusion, with the optimum BG and PBM parameters, BG combined with PBM generated additive effects on promoting bone regeneration.
Characteristics of patients with difficult-to-treat rheumatoid arthritis in a French single-centre hospital
Authors: Hecquet Sophie , Combier Alice , Steelandt Alexia , Pons Marion , Wendling Daniel , Molto Anna , Miceli-Richard Corinne , Allanore Yannick , Avouac Jérôme
Published: March 2023

Objectives

To compare the features of difficult-to-treat rheumatoid arthritis (D2TRA) patients using two different definitions according to the previous failure of targeted therapies.

Methods

We stratified consecutive RA patients treated at Cochin Hospital into two groups, a D2TRA group and a non-D2TRA group, according to two definitions of D2TRA. Both definitions defined D2TRA as RAs failing at least two targeted therapies, with a different mechanism of action for the EULAR-D2TRA definition or without prejudging the mechanism of action and for the Alternative D2TRA definition.

Results

We included 320 consecutive RA patients. We identified 76 EULAR-D2TRA and 244 non-DTRA patients, and 120 Alternative D2TRA and 200 non-DTRA patients. Compared with non-D2TRA, D2TRA patients from both definitions were more likely to have lower socioeconomic level, positive rheumatoid factor, interstitial lung disease, higher DAS28-CRP and were more likely to respond to rituximab and Janus kinase inhibitors. Although EULAR and Alternative D2TRA patients displayed similar clinical and biological features, they were characterized by different therapeutic profiles. We observed fewer patients receiving methotrexate in the Alternative D2TRA group (53% vs 64%, P = 0.046). Patients with Alternative D2TRA not fulfilling the EULAR definition (n = 44) had all received two successive first-line TNF inhibitors, a monoclonal antibody and a soluble receptor, and were comparable to EULAR-D2TRA patients with regards to all other characteristics.

Conclusion

Low socioeconomic status, diabetes, interstitial lung disease and absence of combination with methotrexate allow identification of D2TRA. In addition, the inclusion as ‘early-D2TRA’ of patients failing two TNF inhibitors in the EULAR definition of D2TRA would facilitate the rapid identification of D2TRA patients.
Microneedle rollers for skin drug delivery of macromolecules
Authors: Kontogiannidou Eleni , Kalosakas George , Аndreadis Dimitrios A , Anastasiadou Pinelopi , Bouropoulos Nikolaos , Demiri Efterpi , Andriotis Eleftherios G , Fatouros Dimitrios G
Published: March 2023

Objectives

In the present study, a microneedle device (Dermaroller®) with different needle lengths (1 and 1.5 mm) were used to enhance the transport of a model macromolecular compound (FITC-Dextran 4.4 kDa) across the skin tissue.

Methods

Transport studies were followed by tape-stripping method, to monitor the drug distribution in the stratum corneum.

Key findings

The impact of dermarollers on morphology of the skin surface was examined by Scanning electron microscopy, which revealed a reduction of diameter of the induced skin pores caused by the dermarollers as a function of time, while optical microscopy studies revealed a disorganisation to the lower part of the dermis. Modelling has shown that an exponential, rather than a linear, dependence of the steady-state concentration on the thickness can qualitatively describe the tape-stripping data.

Conclusions

The transport of the macromolecule across skin was significantly enhanced proportional to needle length.
The psychometric properties and clinical utility of neural measures of reward processing
Authors: Amir Nader , Holbrook Amanda , Meissel Emily , Taboas William
Published: March 2023

Reward processing is implicated in the etiology of several psychological conditions including depressive disorders. In the current paper, we examined the psychometric properties of a neural measure of reward processing, the reward positivity (RewP), in 279 adult women at baseline and 187 women 8 weeks later. The RewP demonstrated excellent internal consistency at both timepoints and good test–retest reliability using estimates from both classical test theory and generalizability theory. Additionally, the difference between RewP following reward and loss feedback was marginally associated with depressive symptoms in a subsample of participants. We also examined the relationship between subject-level dependability estimates and depression severity, finding that depressive symptoms may contribute to lower dependability on reward trials. However, this finding did not survive correction for multiple comparisons and should be replicated in future studies. These findings support RewP as a useful measure of individual differences of reward processing and point to the potential utility of this measure for various forms of psychopathology.
Dispersal-Limited Symbionts Exhibit Unexpectedly Wide Variation in Host Specificity
Authors: Matthews Alix E , Wijeratne Asela J , Sweet Andrew D , Hernandes Fabio A , Toews David P L , Boves Than J
Published: March 2023

A fundamental aspect of symbiotic relationships is host specificity, ranging from extreme specialists associated with only a single host species to generalists associated with many different species. Although symbionts with limited dispersal capabilities are expected to be host specialists, some are able to associate with multiple hosts. Understanding the micro- and macro-evolutionary causes of variations in host specificity is often hindered by sampling biases and the limited power of traditional evolutionary markers. Here, we studied feather mites to address the barriers associated with estimates of host specificity for dispersal-limited symbionts. We sampled feather mites (Proctophyllodidae) from a nearly comprehensive set of North American breeding warblers (Parulidae) to study mite phylogenetic relationships and host–symbiont codiversification. We used pooled-sequencing (Pool-Seq) and short-read Illumina technology to interpret results derived from a traditional barcoding gene (cytochrome c oxidase subunit 1) versus 11 protein-coding mitochondrial genes using concatenated and multispecies coalescent approaches. Despite the statistically significant congruence between mite and host phylogenies, mite–host specificity varies widely, and host switching is common regardless of the genetic marker resolution (i.e., barcode vs. multilocus). However, the multilocus approach was more effective than the single barcode in detecting the presence of a heterogeneous Pool-Seq sample. These results suggest that presumed symbiont dispersal capabilities are not always strong indicators of host specificity or of historical host–symbiont coevolutionary events. A comprehensive sampling at fine phylogenetic scales may help to better elucidate the microevolutionary filters that impact macroevolutionary processes regulating symbioses, particularly for dispersal-limited symbionts. [Codiversification; cophylogenetics; feather mites; host switching; pooled sequencing; species delineation; symbiosis, warblers.]
Serotonin/5‐HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP‐PKA‐MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways
Authors: Tang Hui‐hao , Zhang Yi‐fan , Yang Li‐li , Hong Chen , Chen Kai‐xian , Li Yi‐ming , Wu Hua‐li
Published: March 2023

Serotonin (5‐HT), a neurotransmitter, is essential for normal and pathological pigmentation processing, and its receptors may be therapeutical targets. The effect and behavior of the 5‐HT7 receptor (5‐HT7R) in melanogenesis in high vertebrates remain unknown. Herein, we examine the role and molecular mechanism of 5‐HT7R in the pigmentation of human skin cells, human tissue, mice, and zebrafish models. Firstly, 5‐HT7R protein expression decreased significantly in stress‐induced depigmentation skin and vitiligo epidermis. Stressed mice received transdermal serotonin 5‐HT7R selective agonists (LP‐12, 0.01%) for 12 or 60 days. Mice might recover from persistent stress‐induced depigmentation. The downregulation of tyrosinase (Tyr), microphthalmia‐associated transcription factor (Mitf) expression, and 5‐HT7R was consistently restored in stressed skin. High‐throughput RNA sequencing showed that structural organization (dendrite growth and migration) and associated pathways were activated in the dorsal skin of LP‐12‐treated animals. 5‐HT7R selective agonist, LP‐12, had been demonstrated to enhance melanin production, dendrite growth, and chemotactic motility in B16F10 cells, normal human melanocytes (NHMCs), and zebrafish. Mechanistically, the melanogenic, dendritic, and migratory functions of 5‐HT7R were dependent on the downstream signaling of cAMP‐PKA‐ERK1/2, JNK MAPK, RhoA/Rab27a, and PI3K/AKT pathway activation. Importantly, pharmacological inhibition and genetic siRNA of 5‐HT7R by antagonist SB269970 partially/completely abolished these functional properties and the related activated pathways in both NHMCs and B16F10 cells. Consistently, htr7a/7b genetic knockdown in zebrafish could blockade melanogenic effects and abrogate 5‐HT‐induced melanin accumulation. Collectively, we have first identified that 5‐HT7R regulates melanogenesis, which may be a targeted therapy for pigmentation disorders, especially those worsened by stress.