bluuebunny/crossref_metadata_2025 huggingface dataset:
Tundra wolf spider (Araneae: Lycosidae) abundance and phenology shift with distance from a northern highway
Authors: Gagnon Stéphanie , Scott Catherine E , Buddle Christopher M
Published: April 2024

Climate change is disproportionately impacting the North, and northern arthropods are particularly vulnerable to disturbances. The Dempster Highway is a gravel road that crosses the northern Yukon Territory in Canada, and wolf spiders (Araneae: Lycosidae) are the top arthropod predators on the tundra in this region. We investigated the effects of the Dempster Highway on subarctic tundra wolf spider abundance, phenology, and community composition by actively sampling 8 paired plots near (20 m) and far (200 m) from the road. Species richness did not differ with distance from the road, but total wolf spider abundance was much lower near the road, and this was driven by decreased abundance of the dominant tundra wolf spider species, Pardosa lapponica (Thorell, 1872). The overall proportion of females carrying egg sacs was higher near the road, suggesting advanced phenology in response to increased temperatures near the road. Together, these results indicate that the Dempster Highway impacts tundra wolf spider communities, which may have important consequences for food web dynamics and ecosystem function.

Les changements climatiques ont un impact plus important sur le Nord, et les arthropodes nordiques sont particulièrement vulnérables aux perturbations. La route Dempster est une route de gravier qui traverse le nord du territoire du Yukon au Canada, et les araignées-loups (Araneae: Lycosidae) sont d’importants prédateurs d’arthropodes de la toundra de cette région. Nous avons étudié les effets de la route Dempster sur l’abondance, la phénologie et la composition de la communauté des araignées-loups de la toundra subarctique en échantillonnant activement huit parcelles appariées proches (20 m) et éloignées (200 m) de la route. La richesse des espèces ne différait pas avec la distance par rapport à la route, mais l’abondance totale d’araignées-loups était inférieure près de la route, et cela peut être attribué à une diminution de l’abondance de l’espèce dominante d’araignées-loups de la toundra, Pardosa lapponica (Thorell, 1872). La proportion globale des femelles portant des cocons était plus élevée près de la route, suggérant une phénologie avancée en réponse à l’augmentation des températures près de la route. Ces résultats indiquent que, globalement, la route Dempster a un impact sur les communautés d’araignées-loups de la toundra, ce qui peut avoir des conséquences importantes sur la dynamique du réseau trophique et le fonctionnement de l’écosystème.
Nonelectroactive clostridium obtains extracellular electron transfer-capability after forming chimera with Geobacter
Authors: Liu Xing , Ye Yin , Yang Naiming , Cheng Chen , Rensing Christopher , Jin Chao , Nealson Kenneth H , Zhou Shungui
Published: April 2024

Extracellular electron transfer (EET) of microorganisms is a major driver of the microbial growth and metabolism, including reactions involved in the cycling of C, N, and Fe in anaerobic environments such as soils and sediments. Understanding the mechanisms of EET, as well as knowing which organisms are EET-capable (or can become so) is fundamental to electromicrobiology and geomicrobiology. In general, Gram-positive bacteria very seldomly perform EET due to their thick non-conductive cell wall. Here, we report that a Gram-positive Clostridium intestinale (C.i) attained EET-capability for ethanol metabolism only after forming chimera with electroactive Geobacter sulfurreducens (G.s). Mechanism analyses demonstrated that the EET was possible after the cell fusion of the two species was achieved. Under these conditions, the ethanol metabolism pathway of C.i was integrated by the EET pathway of G.s, by which achieved the oxidation of ethanol for the subsequent reduction of extracellular electron acceptors in the coculture. Our study displays a new approach to perform EET for Gram-positive bacteria via recruiting the EET pathway of an electroactive bacterium, which suggests a previously unanticipated prevalence of EET in the microbial world. These findings also provide new perspectives to understand the energetic coupling between bacterial species and the ecology of interspecies mutualisms.
Development of novel indole–quinoline hybrid molecules targeting bacterial proton motive force
Authors: Seo Jinbeom , Kim Ji-Hoon , Ko Nayoung , Kim Jihyeon , Moon Kyeongwon , Kim In Su , Lee Wonsik
Published: April 2024

Aims

This study aimed to develop an editable structural scaffold for improving drug development, including pharmacokinetics and pharmacodynamics of antibiotics by using synthetic compounds derived from a (hetero)aryl-quinoline hybrid scaffold.

Methods and results

In this study, 18 CF3-substituted (hetero)aryl-quinoline hybrid molecules were examined for their potential antibacterial activity against Staphylococcus aureus by determining minimal inhibitory concentrations. These 18 synthetic compounds represent modifications to key regions of the quinoline N-oxide scaffold, enabling us to conduct a structure-activity relationship analysis for antibacterial potency. Among the compounds, 3 m exhibited potency against with both methicillin resistant S. aureus strains, as well as other Gram-positive bacteria, including Enterococcus faecalis and Bacillus subtilis. We demonstrated that 3 m disrupted the bacterial proton motive force (PMF) through monitoring the PMF and conducting the molecular dynamics simulations. Furthermore, we show that this mechanism of action, disrupting PMF, is challenging for S. aureus to overcome. We also validated this PMF inhibition mechanism of 3 m in an Acinetobacter baumannii strain with weaken lipopolysaccharides. Additionally, in Gram-negative bacteria, we demonstrated that 3 m exhibited a synergistic effect with colistin that disrupts the outer membrane of Gram-negative bacteria.

Conclusions

Our approach to developing editable synthetic novel antibacterials underscores the utility of CF3-substituted (hetero)aryl-quinoline scaffold for designing compounds targeting the bacterial proton motive force, and for further drug development, including pharmacokinetics and pharmacodynamics.
Clinician perspectives on how situational context and augmented intelligence design features impact perceived usefulness of sepsis prediction scores embedded within a simulated electronic health record
Authors: Payne Velma L , Sattar Usman , Wright Melanie , Hill Elijah , Butler Jorie M , Macpherson Brekk , Jeppesen Amanda , Del Fiol Guilherme , Madaras-Kelly Karl
Published: April 2024

Objective

Obtain clinicians’ perspectives on early warning scores (EWS) use within context of clinical cases.

Material and Methods

We developed cases mimicking sepsis situations. De-identified data, synthesized physician notes, and EWS representing deterioration risk were displayed in a simulated EHR for analysis. Twelve clinicians participated in semi-structured interviews to ascertain perspectives across four domains: (1) Familiarity with and understanding of artificial intelligence (AI), prediction models and risk scores; (2) Clinical reasoning processes; (3) Impression and response to EWS; and (4) Interface design. Transcripts were coded and analyzed using content and thematic analysis.

Results

Analysis revealed clinicians have experience but limited AI and prediction/risk modeling understanding. Case assessments were primarily based on clinical data. EWS went unmentioned during initial case analysis; although when prompted to comment on it, they discussed it in subsequent cases. Clinicians were unsure how to interpret or apply the EWS, and desired evidence on its derivation and validation. Design recommendations centered around EWS display in multi-patient lists for triage, and EWS trends within the patient record. Themes included a “Trust but Verify” approach to AI and early warning information, dichotomy that EWS is helpful for triage yet has disproportional signal-to-high noise ratio, and action driven by clinical judgment, not the EWS.

Conclusions

Clinicians were unsure of how to apply EWS, acted on clinical data, desired score composition and validation information, and felt EWS was most useful when embedded in multi-patient views. Systems providing interactive visualization may facilitate EWS transparency and increase confidence in AI-generated information.
A specific and sensitive GC–MS-MS method for the quantitative determination of 2-phenoxyethanol and selected metabolites in human blood and urine
Authors: Jäger Thomas , Eckert Elisabeth , Leibold Edgar , Bader Michael
Published: April 2024

2-Phenoxyethanol (PhE) is widely used as a preservative in consumer products such as cosmetics as well as at the workplace as a component of metal-working fluids and hydraulic fluids. Therefore, both industry workers and consumers may potentially be exposed to PhE. An analytical method for the quantification of PhE and three selected metabolites, namely phenoxyacetic acid (PhAA), 4-hydroxyphenoxyacetic acid (4-OH-PhAA), and 4-hydroxyphenoxyethanol (4-OH-PhE), in human urine and blood was developed and validated. The sample preparation includes enzymatic hydrolysis of urine samples or protein precipitation of blood samples, followed by liquid–liquid extraction and silylation of the target analytes. Analyses of the extracts were carried out by gas chromatography with tandem mass spectrometry (GC–MS-MS). 3,4-Hydroxyphenoxyethanol, a probably minor PhE metabolite, could not be reliably analyzed due to its instability. The limits of quantification (LOQ) of the analytes ranged between 0.5 and 6.1 μg/L and 2.0 and 3.9 μg/L in urine and blood, respectively. The method was successfully applied to spot urine samples of 50 individuals without occupational exposure to PhE and additionally to blood samples from seven volunteers. In urine, PhAA and 4-OH-PhAA could be quantified in all analyzed samples, whereas 4-OH-PhE and unchanged PhE were found in 36% and 32% of the samples, respectively. In blood, PhAA was also found in every sample in levels above the LOQ, whereas PhE itself was detected in three of seven samples only. Neither 4-OH-PhAA nor 4-OH-PhE was found in any of the analyzed blood samples. The developed method promises to be a valuable tool for PhE monitoring of urine and blood samples and may also enable an advanced investigation of PhE biotransformation pathways in humans.
Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis
Authors: Condurache Dorina-Gabriela , D’Angelo Stefania , Salih Ahmed M , Szabo Liliana , McCracken Celeste , Mahmood Adil , Curtis Elizabeth M , Altmann Andre , Petersen Steffen E , Harvey Nicholas C , Raisi-Estabragh Zahra
Published: April 2024

This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89–0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.
Noncompete agreements in a rigid labor market: the case of Italy
Authors: Boeri Tito , Garnero Andrea , Luisetto Lorenzo G
Published: April 2024

Noncompete agreements limiting the mobility of workers have been found to be widespread in the United States, a flexible and lightly regulated labor market. We explore the use of noncompete agreements in a rigid and highly regulated labor market, where labor mobility is low, and the labor market is highly regulated via legislation and collective bargaining. Based on a novel survey of Italian workers and an analysis of the regulatory framework, our study shows how trends and patterns in the use of noncompete agreements are not specific to a flexible labor market. Even in a rigid and highly regulated labor market, noncompete agreements are widespread, and often do not comply with the minimum legal requirements, and yet workers are not aware of their enforceability. This suggests that institutions and labor market regulations are not enough per se, especially when targeted groups are not properly informed, and incentives to comply are minimal.
Conquering illusions: Don Quixote and the educational significance of the novel
Authors: Koopal Wiebe , Oliverio Stefano
Published: April 2024

In this article we want to rethink the educational significance of the novel from the perspective of a ‘metanovelistic’ reading of Don Quixote, often acclaimed as the ‘first modern novel’. Our point of departure is two-fold: on the one hand, there is the controversial contemporary phenomenon of de-reading, and all the educational discussions it entails; on the other hand, there is the existing tradition of literary education, which has already extensively reflected upon the (moral, epistemological, ontological) relations between novel reading, education, and subjectification, but which perhaps also has exhausted its means for doing so. To problematize this double starting point in a new way, we propose to revisit the ‘origins’ of the (Western) novel and novel reading, at the dawn of modernity. Exploring the differences between the narratives of subjectification represented by the Cartesian cogito and Cervantes’ Don Quixote—which were near-contemporaries—we strongly argue for an educational–philosophical rehabilitation of the latter. In a first movement, and in dialogue with novelists Milan Kundera and Carlos Fuentes, we do so by focusing on the novel as a particular form or configuration of knowledge—one that is by nature experimental and pluralist. In a second movement, we link this to Jean Baudrillard’s famous distinction between ‘simulation’ and ‘illusion’, claiming that novel reading qua educational subjectification always involves a quixotic practice of adventurous, ‘playful’, and public negotiation between reality and its more or less illusory alternatives.
Melanoma – goes where it wants and does what it pleases. A case report of primary gastric melanoma
Authors: Corbitt Matthew , Vyas Vipul , Beardsley Christian J
Published: April 2024

Melanoma is a common global cancer, however, extracutaneous forms are most often from metastasis. Primary extracutaneous forms are rare, with primary gastric melanoma exceedingly so, with approximately only 50 cases reported worldwide in the literature. The mainstay of management is surgical resection with minimal data on adjuvant therapy. Its prognosis remains poor due to its aggressive behaviour and late presentation. Our case demonstrates a primary gastric melanoma presenting with gastric perforation requiring emergency operative management.
Heterotopic ossification postsuperficial medial collateral ligament pie-crusting: a case report
Authors: Aldhilan Mansour M , Alshahrani Abdullah H , Almogbil Ismail H
Published: April 2024

Anterior cruciate ligament and meniscus tears are common among sports injuries. There are different techniques for addressing anterior cruciate ligament and meniscus tears, with distinct indications, advantages, and disadvantages. We present the case of a 23-year-old male who underwent right anterior cruciate ligament reconstruction and posterior horn medial meniscus repair using an all-inside technique via superficial medial collateral ligament (sMCL) pie-crusting. Clinical examination and radiological investigations a few months later identified calcifications on the medial side of the right knee. We diagnosed the patient with heterotopic ossification post-sMCL pie-crusting; no apparent causal factors were present. To our knowledge, there have been no documented instances of heterotopic ossification following sMCL pie-crusting. In conclusion, heterotopic ossification may occur after sMCL pie-crusting; further studies are needed on this subject.
Anal extrusion of a ventriculoperitoneal shunt in a 1-month-old patient: a case report
Authors: Kencana I Gusti Ketut Agung Surya , Maliawan Sri , Lauren Christopher , Adityawarma Anak Agung Ngurah Agung Harawikrama , Japardi Denny
Published: April 2024

The ventriculoperitoneal shunt procedure represents a frequently conducted neurosurgical intervention; nevertheless, it harbors inherent risks that can precipitate complications in patients. Intestinal perforation accompanied by distal shunt protrusion through the anus is an uncommon phenomenon, observed in ~0.1% to 0.7% of cases, with mortality rates reaching up to 15%. Timely identification and comprehensive management of such complications are imperative to prevent further deterioration of the patient’s condition. Herein, we present a case involving a 1-month-old female infant who presented with a tube protruding from the anal orifice. Immediate surgical intervention was undertaken to remove the distal shunt and prevent further infection in the patient.
Olive reproductive biology: implications for yield, compatibility conundrum, and environmental constraints
Authors: Bashir Muhammad Ajmal , Bertamini Massimo , Gottardini Elena , Grando Maria Stella , Faralli Michele
Published: April 2024

Olive (Olea europaea L.) is an important Mediterranean tree species with a longstanding history of cultivation, boasting a diverse array of local cultivars. While traditional olive orchards are valued for their cultural and aesthetic significance, they often face economic sustainability challenges in the modern context. The success of both traditional and newly introduced cultivars (e.g. those obtained by cross-breeding) is hindered by self-incompatibility, a prevalent issue for this species that results in low fruit set when limited genetic diversity is present. Further, biological, environmental, and agronomic factors have been shown to interlink in shaping fertilization patterns, hence impacting on the final yield. Climatic conditions during pollination, such as excessive rainfall or high temperatures, can further exacerbate the problem. In this work, we provide an overview of the various factors that trigger the phenomenon of suboptimal fruit set in olive trees. This work provides a comprehensive understanding of the interplay among these factors, shedding light on potential mechanisms and pathways that contribute to the observed outcomes in the context of self-incompatibility in olive.
Cortical parenchyma wall width regulates root metabolic cost and maize performance under suboptimal water availability
Authors: Sidhu Jagdeep Singh , Lopez-Valdivia Ivan , Strock Christopher F , Schneider Hannah M , Lynch Jonathan P
Published: April 2024

We describe how increased root cortical parenchyma wall width (CPW) can improve tolerance to drought stress in maize by reducing the metabolic costs of soil exploration. Significant variation (1.0–5.0 µm) for CPW was observed in maize germplasm. The functional–structural model RootSlice predicts that increasing CPW from 2 µm to 4 µm is associated with a ~15% reduction in root cortical cytoplasmic volume, respiration rate, and nitrogen content. Analysis of genotypes with contrasting CPW grown with and without water stress in the field confirms that increased CPW is correlated with an ~32–42% decrease in root respiration. Under water stress in the field, increased CPW is correlated with 125% increased stomatal conductance, 325% increased leaf CO2 assimilation rate, 73–78% increased shoot biomass, and 92–108% increased yield. CPW was correlated with leaf mesophyll midrib parenchyma wall width, indicating pleiotropy. Genome-wide association study analysis identified candidate genes underlying CPW. OpenSimRoot modeling predicts that a reduction in root respiration due to increased CPW would also benefit maize growth under suboptimal nitrogen, which requires empirical testing. We propose CPW as a new phene that has utility under edaphic stress meriting further investigation.
Interplay of light and abscisic acid signaling to modulate plant development
Authors: Mahapatra Kalyan , Dwivedi Shubhi , Mukherjee Arpan , Pradhan Ajar Anupam , Rao Kavuri Venkateswara , Singh Deeksha , Bhagavatula Lavanya , Datta Sourav
Published: April 2024

Exogenous light cues and the phytohormone abscisic acid (ABA) regulate several aspects of plant growth and development. In recent years, the role of crosstalk between the light and ABA signaling pathways in regulating different physiological processes has become increasingly evident. This includes regulation of germination and early seedling development, control of stomatal development and conductance, growth, and development of roots, buds, and branches, and regulation of flowering. Light and ABA signaling cascades have various convergence points at both DNA and protein levels. The molecular crosstalk involves several light signaling factors such as HY5, COP1, PIFs, and BBXs that integrate with ABA signaling components such as the PYL receptors and ABI5. In particular, ABI5 and PIF4 promoters are key ‘hotspots’ for integrating these two pathways. Plants acquired both light and ABA signaling pathways before they colonized land almost 500 million years ago. In this review, we discuss recent advances in the interplay of light and ABA signaling regulating plant development and provide an overview of the evolution of these two pathways.
Glutathione: a key modulator of plant defence and metabolism through multiple mechanisms
Authors: Noctor Graham , Cohen Mathias , Trémulot Lug , Châtel-Innocenti Gilles , Van Breusegem Frank , Mhamdi Amna
Published: April 2024

Redox reactions are fundamental to energy conversion in living cells, and also determine and tune responses to the environment. Within this context, the tripeptide glutathione plays numerous roles. As an important antioxidant, glutathione confers redox stability on the cell and also acts as an interface between signalling pathways and metabolic reactions that fuel growth and development. It also contributes to the assembly of cell components, biosynthesis of sulfur-containing metabolites, inactivation of potentially deleterious compounds, and control of hormonal signalling intensity. The multiplicity of these roles probably explains why glutathione status has been implicated in influencing plant responses to many different conditions. In particular, there is now a considerable body of evidence showing that glutathione is a crucial player in governing the outcome of biotic stresses. This review provides an overview of glutathione synthesis, transport, degradation, and redox turnover in plants. It examines the expression of genes associated with these processes during pathogen challenge and related conditions, and considers the diversity of mechanisms by which glutathione can influence protein function and gene expression.
The survival and entrainment of molecules and dust in galactic winds
Authors: Chen Zirui , Oh S Peng
Published: April 2024

Recent years have seen excellent progress in modelling the entrainment of T ∼ 104 K atomic gas in galactic winds. However, the entrainment of cool, dusty T ∼ 10–100 K molecular gas, which is also observed outflowing at high velocity, is much less understood. Such gas, which can be 105 times denser than the hot wind, appears extremely difficult to entrain. We run 3D wind-tunnel simulations with photoionization self-shielding and evolve thermal dust sputtering and growth. Unlike almost all such simulations to date, we do not enforce any artificial temperature floor. We find efficient molecular gas formation and entrainment, as well as dust survival and growth through accretion. Key to this success is the formation of large amounts of 104 K atomic gas via mixing, which acts as a protective ‘bubble wrap’ and reduces the cloud overdensity to χ ∼ 100. This can be understood from the ratio of the mixing to cooling time. Before entrainment, when shear is large, tmix/tcool ≲ 1, and gas cannot cool below the ‘cooling bottleneck’ at 5000 K. Thus, the cloud survival criterion is identical to the well-studied purely atomic case. After entrainment, when shear falls, tmix/tcool > 1, and the cloud becomes multiphase, with comparable molecular and atomic masses. The broad temperature PDF, with abundant gas in the formally unstable $50 \, {\rm K} \lt T \lt 5000 \, {\rm K}$ range, agrees with previous ISM simulations with driven turbulence and radiative cooling. Our findings have implications for dusty molecular gas in stellar and active galactic nuclei outflows, cluster filaments, ‘jellyfish’ galaxies, and asymptomatic giant branch winds.
Time-varying double-peaked emission lines following the sudden ignition of the dormant galactic nucleus AT2017bcc
Authors: Ridley E J , Nicholl M , Ward C A , Blanchard P K , Chornock R , Fraser M , Gomez S , Mattila S , Oates S R , Pratten G , Runnoe J C , Schmidt P , Alexander K D , Gromadzki M , Lawrence A , Reynolds T M , Smith K W , Wyrzykowski Ł , Aamer A , Anderson J P , Benetti S , Berger E , de Boer T , Chambers K C , Chen T -W , Gao H , Gutiérrez C P , Inserra C , Kangas T , Leloudas G , Magnier E A , Makrygianni L , Moore T , Müller-Bravo T E , Smartt S J , Sokolovsky K V , Wainscoat R , Young D R
Published: April 2024

We present a pan-chromatic study of AT2017bcc, a nuclear transient that was discovered in 2017 within the skymap of a reported burst-like gravitational-wave candidate, G274296. It was initially classified as a superluminous supernova, and then reclassified as a candidate tidal disruption event. Its optical light curve has since shown ongoing variability with a structure function consistent with that of an active galactic nucleus, however, earlier data show no variability for at least 10 yr prior to the outburst in 2017. The spectrum shows complex profiles in the broad Balmer lines: a central component with a broad-blue wing, and a boxy component with time-variable blue and red shoulders. The H α emission profile is well modelled using a circular accretion disc component, and a blue-shifted double Gaussian which may indicate a partially obscured outflow. Weak narrow lines, together with the previously flat light curve, suggest that this object represents a dormant galactic nucleus which has recently been re-activated. Our time-series modelling of the Balmer lines suggests that this is connected to a disturbance in the disc morphology, and we speculate this could involve a sudden violent event such as a tidal disruption event involving the central supermassive black hole, though this cannot be confirmed, and given an estimated black hole mass of ≳ 107–108 M⊙ instabilities in an existing disc may be more likely. Although we find that the redshifts of AT2017bcc (z = 0.13) and G274296 (z > 0.42) are inconsistent, this event adds to the growing diversity of both nuclear transients and multimessenger contaminants.
Pred-O3, a web server to predict molecules, olfactory receptors and odor relationships
Authors: Ollitrault Guillaume , Achebouche Rayane , Dreux Antoine , Murail Samuel , Audouze Karine , Tromelin Anne , Taboureau Olivier
Published: April 2024

The sense of smell is a biological process involving volatile molecules that interact with proteins called olfactory receptors to transmit a nervous message that allows the recognition of a perceived odor. However, the relationships between odorant molecules, olfactory receptors and odors (O3) are far from being well understood due to the combinatorial olfactory codes and large family of olfactory receptors. This is the reason why, based on 5802 odorant molecules and their annotations to 863 olfactory receptors (human) and 7029 odors and flavors annotations, a web server called Pred-O3 has been designed to provide insights into olfaction. Predictive models based on Artificial Intelligence have been developed allowing to suggest olfactory receptors and odors associated with a new molecule. In addition, based on the encoding of the odorant molecule's structure, physicochemical features related to odors and/or olfactory receptors are proposed. Finally, based on the structural models of the 98 olfactory receptors a systematic docking protocol can be applied and suggest if a molecule can bind or not to an olfactory receptor. Therefore, Pred-O3 is well suited to aid in the design of new odorant molecules and assist in fragrance research and sensory neuroscience. Pred-O3 is accessible at ‘ https://odor.rpbs.univ-paris-diderot.fr/’.
Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB
Authors: Manthei Kelly A , Munson Lia M , Nandakumar Jayakrishnan , Simmons Lyle A
Published: April 2024

Mitomycin C (MMC) repair factor A (mrfA) and factor B (mrfB), encode a conserved helicase and exonuclease that repair DNA damage in the soil-dwelling bacterium Bacillus subtilis. Here we have focused on the characterization of MrfB, a DEDDh exonuclease in the DnaQ superfamily. We solved the structure of the exonuclease core of MrfB to a resolution of 2.1 Å, in what appears to be an inactive state. In this conformation, a predicted α-helix containing the catalytic DEDDh residue Asp172 adopts a random coil, which moves Asp172 away from the active site and results in the occupancy of only one of the two catalytic Mg2+ ions. We propose that MrfB resides in this inactive state until it interacts with DNA to become activated. By comparing our structure to an AlphaFold prediction as well as other DnaQ-family structures, we located residues hypothesized to be important for exonuclease function. Using exonuclease assays we show that MrfB is a Mg2+-dependent 3′–5′ DNA exonuclease. We show that Leu113 aids in coordinating the 3′ end of the DNA substrate, and that a basic loop is important for substrate binding. This work provides insight into the function of a recently discovered bacterial exonuclease important for the repair of MMC-induced DNA adducts.
The ABCF proteins in Escherichia coli individually cope with ‘hard-to-translate’ nascent peptide sequences
Authors: Chadani Yuhei , Yamanouchi Shun , Uemura Eri , Yamasaki Kohei , Niwa Tatsuya , Ikeda Toma , Kurihara Miku , Iwasaki Wataru , Taguchi Hideki
Published: April 2024

Organisms possess a wide variety of proteins with diverse amino acid sequences, and their synthesis relies on the ribosome. Empirical observations have led to the misconception that ribosomes are robust protein factories, but in reality, they have several weaknesses. For instance, ribosomes stall during the translation of the proline-rich sequences, but the elongation factor EF-P assists in synthesizing proteins containing the poly-proline sequences. Thus, living organisms have evolved to expand the translation capability of ribosomes through the acquisition of translation elongation factors. In this study, we have revealed that Escherichia coli ATP-Binding Cassette family-F (ABCF) proteins, YheS, YbiT, EttA and Uup, individually cope with various problematic nascent peptide sequences within the exit tunnel. The correspondence between noncanonical translations and ABCFs was YheS for the translational arrest by nascent SecM, YbiT for poly-basic sequence-dependent stalling and poly-acidic sequence-dependent intrinsic ribosome destabilization (IRD), EttA for IRD at the early stage of elongation, and Uup for poly-proline-dependent stalling. Our results suggest that ATP hydrolysis-coupled structural rearrangement and the interdomain linker sequence are pivotal for handling ‘hard-to-translate’ nascent peptides. Our study highlights a new aspect of ABCF proteins to reduce the potential risks that are encoded within the nascent peptide sequences.
Changes in Compliance With Bans on Tobacco Product Display and Advertising at Traditional and Modern Point-of-Sale Retailers in Depok, Indonesia, 2019–2021
Authors: Nian Qinghua , Kennedy Ryan David , Ariani Dina , Wright Kathy , Brown Jennifer L , Bam Tara Singh , Duana Made Kerta , Dewanti Diah Setyawati
Published: April 2024

Introduction

Banning Point-of-Sale (POS) advertising and product display is an important tobacco control strategy. Depok, Indonesia enacted some regional tobacco control policies regulating the POS environment in 2021. This study examined changes in compliance before and after the implementation of these policies as of 2021.

Methods

Data collectors visited 180 modern retailers (hyper/supermarkets/convenience stores) and 147 traditional retailers (warungs) in 2019. The same retailers were revisited in 2021. Data collectors assessed compliance with tobacco product display, and advertising regulations at POS, including if products were displayed in spaces to target minors (near candy or at a child’s eye level). Data were analyzed using McNemar and Mann–Whitney U tests.

Results

From 2019 to 2021, in modern retailers, tobacco product display (95.6% vs. 52.2%) and product advertising (36.1% vs. 3.9%) were significantly reduced (p < .001). In traditional retailers, tobacco product display (94.6% in 2019, 91.2% in 2021, p > .05) and product advertising (87.1% in 2019, 87.8% in 2021, p > .05) remained common during both data collection periods. Tobacco products were commonly displayed in spaces to target minors in both modern retailers (43.3% in 2019, 34.4% in 2021, p > .05) and traditional retailers (90.5% in 2019, 83.0% in 2021, p > .05).

Conclusions

Compliance with bans on tobacco product advertising and display at modern retailers improved significantly from 2019 to 2021; however, most modern retailers continue to display tobacco products in 2021. Traditional retailers remain largely noncompliant. Tobacco products are commonly displayed in areas that target minors. The enforcement of regional regulations should be strengthened, particularly among traditional retailers.

Implications

In Depok, Indonesia, tobacco advertising and product display bans have been implemented; however, more work is needed to support compliance. Enforcement efforts, such as those carried out by civil police, can focus on tobacco product display bans in traditional and modern retailers, and traditional retailers need additional support to remove tobacco product advertising. Retailers may receive money from the tobacco industry for these advertisements. Creative solutions may include supporting retailers in finding alternative advertising revenue.
Job stress and burnout among Finnish municipal employees without depression or anxiety
Authors: Kainalainen A , Korhonen P , Penttinen M A , Liira J
Published: April 2024

Background

Job burnout is associated with job stress but also with mental health symptoms, depression and anxiety.

Aims

This study aims to evaluate the effect of job stress on burnout without the effect of depression and anxiety.

Methods

A cross-sectional study was conducted in 2015 among 673 employees (88% female) from four public service sectors in Pori, Finland. Job burnout was assessed with the Bergen Burnout Indicator (BBI-15). Job stress was assessed by combining psychological risk factors (demand control, effort rewards and mental workload). Respondents who reported symptoms of depression and anxiety were excluded from the analyses.

Results

Of the eligible study subjects (n = 617), 10% reported symptoms of at least mild burnout but only 1% severe burnout. The burnout symptoms varied from 6% to 21% by sector of public service. Job burnout was cumulatively associated with job stress factors. One job stress factor increased the risk of burnout 2-fold (relative risk [RR] 2.13; confidence interval [CI] 0.97–4.68), two factors 6-fold (RR 6.56; 2.92–14.8Or), and three factors even more (RR 23.5; CI 8.67–63.8). Similar trends were observed in the analysis of job burnout components (exhaustion, cynicism and professional inadequacy).

Conclusions

Our results indicate that job burnout is also strongly associated with job stress in employees who do not have depressive or anxiety symptoms. As job burnout may precede clinical depression or reduce productivity and well-being at work, it is essential to perform surveys to monitor burnout symptoms among the workforce, and design interventions to prevent remarkable job strain.
Household durable goods and child health in China
Authors: Kerr Amanda
Published: April 2024

This article uses micro-level data from the China Health and Nutrition Survey to determine how ownership of time-saving household appliances impacts children’s health. Ownership of these appliances is found to decrease time allocated to household work by 56 min and increase the incidence of being overweight by 9.7 percentage points for children aged 5–18 years. When the sample is partitioned on the basis of gender, these outcomes are more pronounced among males. I instrument household ownership of time-saving appliances by average ownership rate among households with no children living in the same community as ownership of household durable goods is endogenous. With current concerns about rising rates of obesity and overweight in China, understanding some of the causes of these negative health outcomes is a crucial step in fighting childhood obesity.
Kernel-elastic autoencoder for molecular design
Authors: Li Haote , Shee Yu , Allen Brandon , Maschietto Federica , Morgunov Anton , Batista Victor
Published: April 2024

We introduce the kernel-elastic autoencoder (KAE), a self-supervised generative model based on the transformer architecture with enhanced performance for molecular design. KAE employs two innovative loss functions: modified maximum mean discrepancy (m-MMD) and weighted reconstruction (LWCEL). The m-MMD loss has significantly improved the generative performance of KAE when compared to using the traditional Kullback–Leibler loss of VAE, or standard maximum mean discrepancy. Including the weighted reconstruction loss LWCEL, KAE achieves valid generation and accurate reconstruction at the same time, allowing for generative behavior that is intermediate between VAE and autoencoder not available in existing generative approaches. Further advancements in KAE include its integration with conditional generation, setting a new state-of-the-art benchmark in constrained optimizations. Moreover, KAE has demonstrated its capability to generate molecules with favorable binding affinities in docking applications, as evidenced by AutoDock Vina and Glide scores, outperforming all existing candidates from the training dataset. Beyond molecular design, KAE holds promise to solve problems by generation across a broad spectrum of applications.
Social intelligence mediates the protective role of resting-state brain activity in the social cognition network against social anxiety
Authors: Ma Yingqiao , Zou Yuhan , Liu Xiqin , Chen Taolin , Kemp Graham J , Gong Qiyong , Wang Song
Published: April 2024

Background

Social intelligence refers to an important psychosocial skill set encompassing an array of abilities, including effective self-expression, understanding of social contexts, and acting wisely in social interactions. While there is ample evidence of its importance in various mental health outcomes, particularly social anxiety, little is known on the brain correlates underlying social intelligence and how it can mitigate social anxiety.

Objective

This research aims to investigate the functional neural markers of social intelligence and their relations to social anxiety.

Methods

Data of resting-state functional magnetic resonance imaging and behavioral measures were collected from 231 normal students aged 16 to 20 years (48% male). Whole-brain voxel-wise correlation analysis was conducted to detect the functional brain clusters related to social intelligence. Correlation and mediation analyses explored the potential role of social intelligence in the linkage of resting-state brain activities to social anxiety.

Results

Social intelligence was correlated with neural activities (assessed as the fractional amplitude of low-frequency fluctuations, fALFF) among two key brain clusters in the social cognition networks: negatively correlated in left superior frontal gyrus (SFG) and positively correlated in right middle temporal gyrus. Further, the left SFG fALFF was positively correlated with social anxiety; brain–personality–symptom analysis revealed that this relationship was mediated by social intelligence.

Conclusion

These results indicate that resting-state activities in the social cognition networks might influence a person's social anxiety via social intelligence: lower left SFG activity → higher social intelligence → lower social anxiety. These may have implication for developing neurobehavioral interventions to mitigate social anxiety.
Does Trade Reform Promote Economic Growth? A Review of Recent Evidence
Authors: Irwin Douglas A
Published: April 2024

Do trade reforms that significantly reduce import barriers lead to faster economic growth? In the twenty-five years since Rodríguez and Rodrik's (2000) critical survey of empirical work on this question, new research has tried to overcome the various methodological problems that have plagued previous attempts to provide a convincing answer. I examine three strands of recent work on this issue: cross-country regressions focusing on within-country growth, synthetic control methods on specific reform episodes, and empirical country studies looking at the channels through which lower trade barriers may increase productivity. A consistent finding is that trade reforms have had a positive impact on economic growth, on average, although the effect is heterogeneous across countries. Overall, these research findings should temper some of the previous agnosticism about the empirical link between trade reform and economic performance.
Increased susceptibility to ischemia causes exacerbated response to microinjuries in the cirrhotic liver
Authors: Leaker Ben D. , Sojoodi Mozhdeh , Tanabe Kenneth K. , Popov Yury V. , Tam Joshua , Anderson R. Rox
Published: April 2024

Fractional laser ablation is a technique developed in dermatology to induce remodeling of skin scars by creating a dense pattern of microinjuries. Despite remarkable clinical results, this technique has yet to be tested for scars in other tissues. As a first step toward determining the suitability of this technique, we aimed to (1) characterize the response to microinjuries in the healthy and cirrhotic liver, and (2) determine the underlying cause for any differences in response. Healthy and cirrhotic rats were treated with a fractional laser then euthanized from 0 h up to 14 days after treatment. Differential expression was assessed using RNAseq with a difference‐in‐differences model. Spatial maps of tissue oxygenation were acquired with hyperspectral imaging and disruptions in blood supply were assessed with tomato lectin perfusion. Healthy rats showed little damage beyond the initial microinjury and healed completely by 7 days without scarring. In cirrhotic rats, hepatocytes surrounding microinjury sites died 4‐6 h after ablation, resulting in enlarged and heterogeneous zones of cell death. Hepatocytes near blood vessels were spared, particularly near the highly vascularized septa. Gene sets related to ischemia and angiogenesis were enriched at 4 h. Laser‐treated regions had reduced oxygen saturation and broadly disrupted perfusion of nodule microvasculature, which matched the zones of cell death. Our results demonstrate that the cirrhotic liver has an exacerbated response to microinjuries and increased susceptibility to ischemia from microvascular damage, likely related to the vascular derangements that occur during cirrhosis development. Modifications to the fractional laser tool, such as using a femtosecond laser or reducing the spot size, may be able to prevent large disruptions of perfusion and enable further development of a laser‐induced microinjury treatment for cirrhosis.
Membrane phospholipids activate the inflammatory response in macrophages by various mechanisms
Authors: Cauvi David M. , Hawisher Dennis , Derunes Julia , Rodriguez Enrique , De Maio Antonio
Published: April 2024

Exosomes, which are small membrane‐encapsulated particles derived from all cell types, are emerging as important mechanisms for intercellular communication. In addition, exosomes are currently envisioned as potential carriers for the delivery of drugs to target tissues. The natural population of exosomes is very variable due to the limited amount of cargo components present in these small vesicles. Consequently, common components of exosomes may play a role in their function. We have proposed that membrane phospholipids could be a common denominator in the effect of exosomes on cellular functions. In this regard, we have previously shown that liposomes made of phosphatidylcholine (PC) or phosphatidylserine (PS) induced a robust alteration of macrophage (Mϕ) gene expression. We herewith report that these two phospholipids modulate gene expression in Mϕs by different mechanisms. PS alters cellular responses by the interaction with surface receptors, particularly CD36. In contrast, PC is captured by a receptor‐independent process and likely triggers an activity within endocytic vesicles. Despite this difference in the capture mechanisms, both lipids mounted similar gene expression responses. This investigation suggests that multiple mechanisms mediated by membrane phospholipids could be participating in the alteration of cellular functions by exosomes.
TCEB3 initiates ovarian cancer apoptosis by mediating ubiquitination and degradation of MCL‐1
Authors: Cai Ying , Li Yun , Xu Yingjie , Yang Wen , Huang Masha
Published: April 2024

Platinum resistance remains a major contributor to the poor prognosis of ovarian cancer. Anti‐apoptotic protein myeloid cell leukemia‐1 (MCL‐1) has emerged as a promising target for overcoming drug resistance, but different cancer cells utilize distinct protein degradation pathways to alter MCL‐1 level. We systematically investigated E3 ligases to identify novel candidates that mediate platinum resistance in ovarian cancer. Transcription Elongation Factor B (TCEB3) has been identified as a novel E3 ligase recognition subunit that targets MCL‐1 in the cytoplasm during platinum treatment other than its traditional function of targeting the Pol II in the nuclear compartment. TCEB3 expression is downregulated in platinum‐resistant cell lines and this low expression is associated with poor prognosis. The ubiquitination of MCL‐1 induced by TCEB3 leads to cell death in ovarian cancer. Moreover, platinum treatment increased the cytoplasm proportion of TCEB3, and the cytoplasm localization of TCEB3 is important for its targeting of MCL‐1. This study emphasizes the dual function of TCEB3 in homeostasis maintenance and in cell fate determination under different conditions, and provides a new insight into drug resistance in ovarian cancer.