bluuebunny/crossref_metadata_2025 huggingface dataset:
Click‐Chemistry‐Enabled Nanopipettes for the Capture and Dynamic Analysis of a Single Mitochondrion inside One Living Cell
Authors: Liu Kang , Zhang Zheng , Liu Rujia , Li Jie P. , Jiang Dechen , Pan Rongrong
Published: June 2023

The in‐depth study of single cells requires the dynamically molecular information in one particular nanometer‐sized organelle in a living cell, which is difficult to achieve using current methods. Due to high efficiency of click chemistry, a new nanoelectrode‐based pipette architecture with dibenzocyclooctyne at the tip is designed to realize fast conjugation with azide group‐containing triphenylphosphine, which targets mitochondrial membranes. The covalent binding of one mitochondrion at the tip of the nanopipette allows a small region of the membrane to be isolated on the Pt surface inside the nanopipette. Therefore, the release of reactive oxygen species (ROS) from the mitochondrion is monitored, which is not interfered by the species present in the cytosol. The dynamic tracking of ROS release from one mitochondrion reveals the distinctive “ROS‐induced ROS release” within the mitochondria. Further study of RSL3‐induced ferroptosis using nanopipettes provides direct evidence for supporting the noninvolvement of glutathione peroxidase 4 in the mitochondria during RSL3‐induced ROS generation, which has not previously been observed at the single‐mitochondrion level. Eventually, this established strategy should overcome the existing challenge of the dynamic measurement of one special organelle in the complicated intracellular environment, which opens a new direction for electroanalysis in subcellular analysis.
Copper‐Phosphido Catalysis: Enantioselective Addition of Phosphines to Cyclopropenes**
Authors: Daniels Brian S. , Hou Xintong , Corio Stephanie A. , Weissman Lindsey M. , Dong Vy M. , Hirschi Jennifer S. , Nie Shaozhen
Published: June 2023

We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a CuI‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by a syn‐protodemetalation.
Beobachtung der ersten Schlüsselschritte eines titanbasierten Photoredox‐Katalysezyklus in Echtzeit
Authors: Schmidt Jonas , Domenianni Luis I. , Leuschner Marcel , Gansäuer Andreas , Vöhringer Peter
Published: June 2023

Die titanbasierte Katalyse mit Ein‐Elektronentransfer‐Schritten (SET) hat sich zu einem vielseitigen Ansatz für die Synthese von Feinchemikalien entwickelt. Kürzlich wurden erste Versuche unternommen, ihre Nachhaltigkeit zu verbessern, indem sie mit der Photoredox (PR) Katalyse kombiniert wird. Hier untersuchen wir die photochemischen Prinzipien der SET‐PR‐Katalyse auf Basis von Ti und in Abwesenheit eines Edelmetall PR−Co‐Katalysators. Durch Kombination von zeitaufgelöster Emissionsspektroskopie mit Ultraviolett‐Anregungs‐/Infrarot‐Abfrage‐Spektroskopie auf Zeitskalen von Femtosekunden bis Mikrosekunden quantifizieren wir die Dynamik der kritischen Ereignisse bei der Initiierung des Katalysezyklus, nämlich die Singulett‐Triplett‐Umwandlung des Titanocen(IV) PR‐Universalkatalysators und seine Ein‐Elektronen‐Reduktion durch einen Amin‐Elektronendonator. Die Ergebnisse unterstreichen die Bedeutung der Singulett‐Triplett‐Energielücke des PR‐Katalysators als Leitfaden für künftige Verbesserungen.
Bottom‐up Solution Synthesis of Graphene Nanoribbons with Precisely Engineered Nanopores
Authors: Niu Wenhui , Fu Yubin , Serra Gianluca , Liu Kun , Droste Jörn , Lee Yeonju , Ling Zhitian , Xu Fugui , Cojal González José D. , Lucotti Andrea , Rabe Jürgen P. , Ryan Hansen Michael , Pisula Wojciech , Blom Paul W. M. , Palma Carlos‐Andres , Tommasini Matteo , Mai Yiyong , Ma Ji , Feng Xinliang
Published: June 2023

The incorporation of nanopores into graphene nanostructures has been demonstrated as an efficient tool in tuning their band gaps and electronic structures. However, precisely embedding the uniform nanopores into graphene nanoribbons (GNRs) at the atomic level remains underdeveloped especially for in‐solution synthesis due to the lack of efficient synthetic strategies. Herein we report the first case of solution‐synthesized porous GNR (pGNR) with a fully conjugated backbone via the efficient Scholl reaction of tailor‐made polyphenylene precursor (P1) bearing pre‐installed hexagonal nanopores. The resultant pGNR features periodic subnanometer pores with a uniform diameter of 0.6 nm and an adjacent‐pores‐distance of 1.7 nm. To solidify our design strategy, two porous model compounds (1 a, 1 b) containing the same pore size as the shortcuts of pGNR, are successfully synthesized. The chemical structure and photophysical properties of pGNR are investigated by various spectroscopic analyses. Notably, the embedded periodic nanopores largely reduce the π‐conjugation degree and alleviate the inter‐ribbon π–π interactions, compared to the nonporous GNRs with similar widths, affording pGNR with a notably enlarged band gap and enhanced liquid‐phase processability.
An Artificial Intelligence Approach for Tackling Conformational Energy Uncertainties in Chiroptical Spectroscopies
Authors: Marton Gabriel , Koenis Mark A. J. , Liu Hong‐Bing , Bewley Carole A. , Buma Wybren Jan , Nicu Valentin Paul
Published: June 2023

Determination of the absolute configuration of chiral molecules is a prerequisite for obtaining a fundamental understanding in any chirality‐related field. The interaction with polarised light has proven to be a powerful means to determine this absolute configuration, but its application rests on the comparison between experimental and computed spectra for which the inherent uncertainty in conformational Boltzmann factors has proven to be extremely hard to tackle. Here we present a novel approach that overcomes this issue by combining a genetic algorithm that identifies the relevant conformers by accounting for the uncertainties in DFT relative energies, and a hierarchical clustering algorithm that analyses the trends in the spectra of the considered conformers and identifies on‐the‐fly when a given chiroptical technique is not able to make reliable predictions. The effectiveness of this approach is demonstrated by considering the challenging cases of papuamine and haliclonadiamine, two bis‐indane natural products with eight chiral centres and considerable conformational heterogeneity that could not be assigned unambiguously with current approaches.
Neutrino physics: Experimental and theoretical challenges
Authors: Felipe Ricardo González
Published: June 2023

The existence of massive neutrinos is the first solid evidence of physics beyond the standard model of particle physics. A remarkable progress has been achieved in solar, atmospheric, reactor, and accelerator neutrino experiments during the last decades. On the theoretical side, several questions are being addressed, namely the Dirac or Majorana nature of neutrinos, the mechanisms for neutrino mass generation, and the relation between neutrinos and the matter–antimatter asymmetry observed in the Universe, among others. This article provides a brief overview on some of the current experimental and theoretical aspects in neutrino physics.
Investigating the Influence of the Effective Ionic Transport on the Electrochemical Performance of Si/C‐Argyrodite Solid‐State Composites
Authors: Rudel Yannik , Rana Moumita , Ruhl Justine , Rosenbach Carolin , Müller Jannes , Michalowski Peter , Kwade Arno , Zeier Wolfgang G.
Published: June 2023

Solid‐state batteries have the potential to outperform conventional lithium‐ion batteries, as they offer higher energy densities, necessary for the increasing demand for portable energy storage. Silicon‐graphite composites are considered to be one of the most promising alternatives to the lithium metal anode due to their low lithiation potential and resistance against dendrite formation. Since these composites show insufficient ionic conductivity, a fast‐conducting solid electrolyte is needed to facilitate the charge carrier transport. Optimizing the volume fractions of the solid electrolyte is crucial to ensure sufficient charge carrier transport and achieve the optimal performance. In this work, the influence of the charge carrier transport in a silicon on graphite (Si/C)/argyrodite solid electrolyte composite on the electrochemical performance is studied. By systematically varying the ratio of the Si/C to solid electrolyte, it was found that the effective ionic conductivity of the electrode composite improves exponentially with increasing content of the solid electrolyte, which in turn leads to an increase in the specific capacity of the composite across all C‐rates. This study highlights the importance of understanding and customizing charge carrier transport properties in solid‐state anode composites to achieve optimum electrochemical performance.
Gadolinium during human pregnancy following administration of gadolinium chelate before pregnancy
Authors: Coyte Rachel M. , Darrah Thomas , Olesik John , Barrett Emily , O'Connor Thomas G. , Brunner Jessica , Love Tanzy , Perez‐D'Gregorio Rogelio , Wang Henry Z. , Aleksunes Lauren M. , Buckley Brian , Doherty Cathleen , Miller Richard K.
Published: June 2023

Gadolinium (Gd), a toxic rare earth element, has been shown to dissociate from chelating agents and bioaccumulate within tissues, raising concerns about the possibility of their remobilization during pregnancy with subsequent free Gd exposures to developing fetuses. Gd chelates are among the most commonly used magnetic resonance imaging (MRI) contrast agents. This investigation was undertaken after the detection of elevated Gd (800–1000× higher than the usual rare earth element levels) in preliminary unpublished studies from the placentae of subjects in the NIH ECHO/UPSIDE Rochester Cohort Study and unpublished studies from placentae analyzed in formalin‐fixed placental specimens from Surgical Pathology at the University of Rochester. Fifteen pregnancies with elevated Gd were studied (12 first pregnancies and 3 second pregnancies). Maternal bloods were collected from all three trimesters, maternal, and cord (fetal) bloods at delivery as well as placental tissue. Breastmilk was also collected from selected mothers. It was determined that Gd was present in maternal bloods from all three trimesters, and in cord bloods and breastmilk in both first and second pregnancies. These results emphasize the need to fully appreciate the implications of pre‐pregnancy exposure to Gd chelates and its potential effects on maternal and fetal health.
Cost‐efficient cell clarification using an intensified fluidized bed centrifugation platform approach
Authors: Saballus Martin , Filz Thomas Josef , Pollard David , Kampmann Markus
Published: June 2023

The intensification of industrial biopharmaceutical production and the integration of process steps pave the way for patients to access affordable treatments. The predominantly batchwise biomanufacturing of established cell clarification technologies, stainless steel disc stack centrifugation (DSC) and single‐use (SU) depth filtration (DF), pose technological and economical bottlenecks, that include low biomass loading capacities and low product recoveries. Therefore, a novel SU‐based clarification platform was developed combining fluidized bed centrifugation (FBC) with integrated filtration. The feasibility of this approach was investigated for high cell concentration with more than 100E6 cells/mL. Furthermore, scalability to 200 L bioreactor scale was tested for moderate cell concentrations. In both trials, low harvest turbidities (4 NTU) and superior antibody recoveries (95%) were achieved. The impact on the overall economics of industrial SU biomanufacturing using an up‐scaled FBC approach was compared with DSC and DF technologies for different process parameters. As a result, the FBC showed to be the most cost‐effective alternative for annual mAb production below 500 kg. In addition, the FBC clarification of increasing cell concentrations was found to have minimal impact on overall process costs, in contrast to established technologies, demonstrating that the FBC approach is particularly suitable for intensified processes.
Neural shifts in alpha rhythm's dual functioning during empathy maturation
Authors: Zebarjadi Niloufar , Levy Jonathan
Published: June 2023

Introduction

Empathy is a social–cognitive process that operates by relying mainly on the suppression of the cortical alpha rhythm. This phenomenon has been evidenced in dozens of electrophysiological studies targeting adult human subjects. Yet, recent neurodevelopmental studies indicated that at a younger age, empathy involves reversed brain responses (e.g., alpha enhancement patterns). In this multimodal study, we capture neural activity at the alpha range, and hemodynamic response and target subjects at approximately 20 years old as a unique time window in development that allows investigating both low‐alpha suppression and high‐alpha enhancement. We aim to further investigate the functional role of low‐alpha power suppression and high‐alpha power enhancement during empathy development.

Methods

Brain data from 40 healthy individuals were recorded in two consecutive sessions of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) while subjects perceived vicarious physical pain or no pain.

Results

MEG revealed that the alpha pattern shift during empathy happens in an all‐or‐none pattern: power enhancement before 18 and suppression after 18 years of age. Additionally, MEG and fMRI highlight a correspondence between high‐alpha power increase and blood‐oxygen‐level‐dependent (BOLD) decrease before 18, but low‐alpha power decrease and BOLD increase after 18. Importantly, this neurodevelopmental transition was not revealed by four other measures: self‐reported (a) ratings of the task stimuli, (b) ratings of naturalistic vignettes of vicarious pain, (c) trait empathy, or neural data from (d) a control neuroimaging task.

Discussion

Findings suggest that at the critical age of around 18, empathy is underpinned by an all‐or‐none transition from high‐alpha power enhancement and functional inhibition to low‐alpha power suppression and functional activation in particular brain regions, possibly indicating a marker of maturation in empathic ability. This work advances a recent neurodevelopmental line of studies and provides insight into the functional maturation of empathy at the coming of age.
A Bayesian network meta‐analysis of ALK inhibitor treatments in patients with ALK‐positive non‐small cell lung cancer
Authors: Zheng Bei , Jiang Hong , Yang Wenjuan , Li Ying , Liang Bingqing , Zhu Jun , Chen Nanmei , Chen Miao , Zhang Meiling
Published: June 2023

Objective

To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK‐positive non‐small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK‐positive NSCLC.

Methods

The effectiveness of ALKis was evaluated by assessing progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety. We conducted an indirect treatment comparison between all ALKis by using a Bayesian model.

Results

Twelve eligible trials including seven treatments were identified. All of the ALKis improved PFS and ORR relative to chemotherapy. Consistent with alectinib, brigatinib, lorlatinib, and ensartinib showed significant differences versus crizotinib and ceritinib. Lorlatinib seemed to prolong PFS compared with alectinib (0.64, 0.37 to 1.07), brigatinib (0.56, 0.3 to 1.05), and ensartinib (0.53, 0.28 to 1.02). No significant difference was found among them in OS except for alectinib versus crizotinib. Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR. Subgroup analyses based on BM indicated that PFS was dramatically lengthened by lorlatinib. Compared with other ALKis, alectinib notably reduced the rate of SAEs. There was no striking difference between discontinuation for AEs, except for ceritinib versus crizotinib. The ranking of validity showed that lorlatinib had the longest PFS (98.32%) and PFS with BM (85.84%) and the highest ORR (77.01%). The rank of probabilities showed that alectinib had the potentially best safety in terms of SAEs (97.85%), and ceritinib had less discontinuation (95.45%).

Conclusion

Alectinib was the first choice for patients with ALK‐positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long‐term follow‐up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.
Addressing social determinants of mental health in therapy: A thematic synthesis
Authors: Pauling Naomi
Published: June 2023

Background

The importance of addressing social determinants of mental health in therapy is well‐documented. However, there appears to be limited research on what this actually involves in practice and how best to prepare therapists to work with individuals experiencing adverse social determinants.

Aims

The aim of this review was to draw implications for practice and training from reviewing research on addressing social determinants of mental health in therapy.

Methodology

A qualitative systematic review of the research on addressing social determinants of mental health in therapy was conducted, extracting papers from eight databases: Cochrane Library, ASSIA, CINAHL Plus, PsycInfo, Psychoanalytic Electronic Publishing, Science Direct, Scopus and Web of Science. Out of 127 papers found, five met the eligibility criteria and were quality‐assessed and analysed thematically.

Findings

The thematic synthesis generated three main themes: “the therapeutic relationship,” “adapting to client context” and “community as a resource,” with eight subthemes.

Conclusion

This thematic synthesis highlights the importance of the therapeutic relationship and adapting mental health support to client frame of reference and context to address social determinants of mental health in therapy. It emphasises community as a helpful resource for informing training and therapeutic interventions, as well as a significant resource for people experiencing adverse social determinants.
Why should we care about emotional intelligence?
Authors: Hodges Dawn Z.
Published: June 2023

Generally speaking, I don’t read articles about emotional intelligence. As a matter of course, I avoid them. If I see EI, I just keep scrolling. Why? Well, I haven’t really wanted to know if I’m emotionally intelligent or unintelligent.
Protecting controversial speakers plays key role in protecting free speech
Authors: Lyerly Eric
Published: June 2023

Colleges and universities commonly host controversial speakers on campus, typically invited by a student organization. Student protests of controversial speakers are almost just as common. Such protests often involve students shouting down, interrupting, or engaging in disruptions that are aimed at canceling the event. These disruptions are commonly referred to as a “heckler's veto.”
Did court dismiss Title IX claim against university?
Authors: Lyerly Eric
Published: June 2023

Tel Aviv University is a public university located in Israel. A TAU student, who was also a U.S. citizen, was called to appear before the university's professionalism committee after he was accused of “sexually inappropriate behavior” and unprofessionalism.
Understand the intersection of disability harassment and free speech
Authors: Lyerly Eric
Published: June 2023

Disability harassment is a common problem on college campuses. However, colleges and universities sometimes have difficulty identifying and addressing such harassment, especially when it involves speech.
A novel peptide derived from the mannose binding lectin inhibits LPS‐activated TLR4/NF‐κB signaling and suppresses ocular inflammation
Authors: Lu Yi , Wang Ruonan , Jin Huiyi , Xie Jiamin , Gu Qing , Yang Xiaolu
Published: June 2023

Uveitis is a major cause of vision impairment worldwide. Current treatments have limited effectiveness but severe complications. Mannose binding lectin (MBL) is an important protein of the innate immune system that binds to TLR4 and suppresses LPS‐induced inflammatory cytokine secretion. MBL‐mediated inhibition of inflammation via the TLR4 pathway and MBL‐derived peptides might be a potential therapeutics. In this study, we designed a novel MBL‐derived peptide, WP‐17, targeting TLR4. Bioinformatics analysis was conducted for the sequence, structure and biological properties of WP‐17. The binding of WP‐17 to THP‐1 cells was analyzed using flow cytometry. Signaling molecules were analyzed by western blotting, and activation of NF‐κB was measured by immunofluorescence‐histochemical analysis. Effects of WP‐17 were studied in vitro using LPS‐stimulated THP‐1 cells and in vivo in endotoxin‐induced uveitis (EIU). Our results showed that WP‐17 could bind to TLR4 expressed on macrophages, thus downregulating the expression levels of MyD88, IRAK‐4, and TRAF‐6, and inhibiting the downstream NF‐kB signaling pathway and LPS‐induced expression of TNF‐α and IL‐6 in THP‐1 cells. Moreover, in EIU rats, intravitreal pretreatment with WP‐17 demonstrated significant inhibitory effects on ocular inflammation, attenuating the clinical and histopathological manifestations of uveitis, reducing protein leakage and cell infiltration into the aqueous humor, and suppressing TNF‐α and IL‐6 production in ocular tissues. In summary, our study provides the first evidence of a novel MBL‐derived peptide that suppressed activation of the NF‐кB pathway by targeting TLR4. The peptide effectively inhibited rat uveitis and may be a promising candidate for the management of ocular inflammatory diseases.
Defective Prussian Blue Analogue with Cobalt for Fabrication of An Electrochemical Sensor for Detecting Ascorbic Acid, Dopamine and Uric Acid
Authors: Xu Yanxue , Qin Yunting , Gao Xilan , Li Jing , Xiao Dan
Published: June 2023

A Prussian blue analogue with cobalt (Na2‐xCo[Fe(CN)6]1‐y, PB‐Co), which is often used as sodium‐ion battery material, was found to be an excellent sensing material toward some biomolecules by calcination. PB‐Co calcined at 750 °C for 1 h (PB‐Co750‐1) has the improved defects to facilitate the adsorption and the catalytic oxidation of ascorbic acid (AA), dopamine (DA) and uric acid (UA). PB‐Co750‐1 modified on screen printed carbon electrode (SPE) for the ultrasensitively simultaneous determination of AA, DA and UA demonstrates the wide linear range, the low limit of detection (LOD) and the good reproducibility. In addition, the redox of the analytes was confirmed as the diffusion‐controlled process via the kinetic study. The recoveries of AA, DA and UA in real samples were found between 91 % to 114 %. AA and UA in tablets, serums and urines could be determined by PB‐Co750‐1/SPE with the satisfactory results.
Jörg Kärger: Diffusion Is His Life
Authors: Caro Jürgen
Published: June 2023

Jörg Kärger is a pioneer in the field of diffusion and his work has contributed significantly to the understanding of molecular mass transfer in porous systems. He has been actively researching diffusion in nanoporous materials for more than 50 years and, according to the Web of Science, is the most productive author in the field of diffusion, with 247 entries (search for diffusion in the title). He also has the highest total local citation score in the field of diffusion, which indicates not only the high number but also the high quality of his publications.
Bioequivalence of a Pediatric Fixed‐Dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Compared With Coadministration of the Separate Agents in Healthy Adults: An Open‐Label, Randomized, Replicate Crossover Study
Authors: Van Hemelryck Sandy , Van Landuyt Erika , Ariyawansa Jay , Vanveggel Simon , Palmer Martyn
Published: June 2023

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a fixed‐dose combination (FDC) for the treatment of HIV‐1 infection in adults and adolescents weighing 40 kg or greater. This Phase 1, randomized, open‐label, 2‐treatment, 2‐sequence, 4‐period replicate crossover study (NCT04661397) evaluated the pivotal bioequivalence of a pediatric D/C/F/TAF 675/150/200/10‐mg FDC compared with coadministration of the separate commercially available formulations in healthy adults under fed conditions. During each period, participants received either a single oral dose of D/C/F/TAF 675/150/200/10‐mg FDC (test) or a single oral dose of darunavir 600 and 75 mg, cobicistat 150 mg, and emtricitabine/tenofovir alafenamide 200/10‐mg FDC (reference). Thirty‐seven participants were randomly assigned to one of 2 treatment sequence groups: test‐reference‐reference‐test or reference‐test‐test‐reference, with 7 days or more washout between periods. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the concentration–time curve from time zero to last measurable concentration, and area under the concentration–time curve extrapolated to infinity for darunavir, cobicistat, emtricitabine, and tenofovir alafenamide fell within conventional bioequivalence limits (80%–125%). No Grade 3/4 adverse events, serious adverse events, or deaths occurred. In conclusion, administration of D/C/F/TAF 675/150/200/10‐mg FDC was bioequivalent to coadministration of the separate commercially available formulations.
Customized flex‐path degrees bring value — and challenges
Authors: Sutton Halley
Published: June 2023

CHICAGO — Creating customized degrees is a way to serve the needs of your local marketplace, both by providing skilled workers and by offering adult learners a chance to pursue something directly in line with their own career goals and interests. But scaling these programs — making it possible to have a wide range of options or your students, without competing internally with your own programs — can prove to be a challenge.
Pesticide exposure enhances dominance patterns in a zooplankton community
Authors: Almeida Rafaela A. , Fajgenblat Maxime , Lemmens Pieter , De Meester Luc
Published: June 2023

Exposure to pesticides can profoundly alter community dynamics. It is expected that dominance patterns will be enhanced or reduced depending on whether the dominant species is less or more sensitive to the pesticide than the subdominant species. Community dynamics are, however, also determined by processes linked to population growth as well as competition at carrying capacity. Here, we used a mesocosm experiment to quantify the effect of chlorpyrifos exposure on the population dynamics of four cladoceran species (Daphnia magna, Daphnia pulicaria, Daphnia galeata and Scapholeberis mucronata) in mixed cultures, testing for direct effects of chlorpyrifos and indirect effects mediated by interactions with other species on the timing of population growth and dominance at carrying capacity. We also quantified whether the pesticide‐induced changes in community dynamics affected top‐down control of phytoplankton. By adding a treatment in which we used different genotype combinations of each species, we also tested to what extent genetic composition affects community responses to pesticide exposure. Immobilization tests showed that D. magna is the least sensitive to chlorpyrifos of the tested species. Chlorpyrifos exposure first leads to a reduction in the abundance of D. galeata to the benefit of D. pulicaria, and subsequently to a reduction in densities of D. pulicaria to the benefit of D. magna. This resulted in D. magna being more dominant in the pesticide than in the control treatment by the end of the experiment. There was no effect of genotypic differences on community patterns, and top‐down control of phytoplankton was high in all treatments. Our results suggest that in this community dominance patterns are enhanced in line with the observed among‐species differences in sensitivity to the pesticide. Our results also show that the development of the community in pesticide treatment is a complex interaction between direct and indirect effects of the pesticide.
Contaminants reach everywhere: Fish dietary samples should be surface decontaminated prior to molecular diet analysis
Authors: Rijal Dilli Prasad , Hanebrekke Tanja , Arneberg Per , Johansen Torild , Sint Daniela , Traugott Michael , Skern‐Mauritzen Mette , Westgaard Jon‐Ivar
Published: June 2023

Knowledge of trophic interaction is necessary to understand the dynamics of ecosystems and develop ecosystem‐based management. The key data to measure these interactions should come from large‐scale diet analyses with good taxonomic resolution. To that end, molecular methods that analyze prey DNA from guts and feces provide high‐resolution dietary taxonomic data. However, molecular diet analysis may also produce unreliable results if the samples are contaminated by external sources of DNA. Employing the freshwater European whitefish (Coregonus lavaretus) as a tracer for sample contamination, we studied the possible route of whitefish in beaked redfish (Sebastes mentella) guts sampled in the Barents Sea. We used whitefish‐specific COI primers for diagnostic analysis, and fish‐specific 12S and metazoa‐specific COI primers for metabarcoding analyses of intestine and stomach contents of fish samples that were either not cleaned, water cleaned, or bleach cleaned after being in contact with whitefish. Both the diagnostic and COI metabarcoding revealed clear positive effects of cleaning samples as whitefish were detected in significantly higher numbers of uncleaned samples compared to water or bleach‐cleaned samples. Stomachs were more susceptible to contamination than intestines and bleach cleaning reduced the frequency of whitefish contamination. Also, the metabarcoding approach detected significantly more reads of whitefish in the stomach than in intestine samples. The diagnostic analysis and COI metabarcoding detected contaminants in a higher and comparable number of gut samples than the 12S‐based approach. Our study underlines thus the importance of surface decontamination of aquatic samples to obtain reliable diet information from molecular data.
Behavioral thermoregulation of caterpillars is altered by temperature, but not parasitism: An empirical field study
Authors: Moore M. Elizabeth , Alston Meggan A. , Kingsolver Joel G.
Published: June 2023

Laboratory assays show that parasites often have lower heat tolerance than their hosts. But how physiological tolerances and behavioral responses of hosts and parasites combine to affect their ecological interactions in heterogeneous field environments is largely unknown. We addressed this challenge using the model insect system of the braconid wasp parasitoid, Cotesia congregata, and its caterpillar host, Manduca sexta. We used experimental manipulations of microclimate in the field to determine how elevated daytime temperatures altered the behavior, performance, and survival of host and parasite. Our experimental manipulation increased daily maximum temperatures on host plants, but had negligible effects on overall mean temperature. These increased maximum temperatures resulted in subtle, biologically relevant, changes in physiology and behavior of the host and parasitoid. We found that parasitism by the wasp did not significantly alter caterpillar thermoregulatory behavior, while experimentally increased daily maximum temperatures resulted in both parasitized and unparasitized caterpillars to be found more frequently in cooler microhabitats. Overall, we did not observe the complete parasitoid mortality seen at extreme temperatures in laboratory studies, but gained insight into the sublethal effects of increased daily maximum temperatures on host and parasitoid behavior and physiology. Climate change will alter both the biotic and abiotic environments that organisms face, and we show here that empirical experiments in the field are important for understanding organismal response to these new environments.
Temperature moderates eDNA–biomass relationships in northern pike
Authors: Ogonowski M. , Karlsson E. , Vasemägi A. , Sundin J. , Bohman P. , Sundblad G.
Published: June 2023

Support for eDNA as a quantitative monitoring tool is growing worldwide. Despite advances, there are still uncertainties regarding the representability of the eDNA signal over varying spatiotemporal scales, the influence of abiotic forcing, and phenological changes affecting the behavior of the study organism, particularly in open environments. To assess the spatiotemporal variability and predictive power of quantitative eDNA analysis, we applied species‐specific real‐time quantitative PCR on water filtrates during two visits to 22 coastal bays in the Baltic Sea. Within bays, we collected water along four transects across each bay and compared the pooled eDNA concentration to temporally matched catches from standardized angling targeting the northern pike (Esox lucius), a species for which reliable monitoring data is lacking. We found the variability in eDNA concentrations between transects to be moderate (21%) but still considerably lower than across bays and visits (52%), suggesting small‐scale spatial differences are of less importance during spring when pike spawn. Standardized angling catches, bay area, and water temperature together explained 48% of the variance in eDNA concentrations. DNA concentrations decreased with the increasing bay area, likely indicating a dilution effect. Notably, the relationship between eDNA and standardized catches was positive but varied with temperature and the eDNA‐abundance relationship was only significant at higher temperatures, which also coincided with a higher proportion of spawning/spent fish. We conclude that temperature is a key moderating factor driving changes in pike behavior and spring DNA‐dynamics. We recommend that future surveys focus on larger spatiotemporal scales during times when the influence of changing temperatures is minimized.
Observing the Arctic: A comparison of environmental DNA (eDNA) and electrofishing for monitoring Arctic char and Atlantic salmon
Authors: Jacobsen Magnus W. , Nygaard Rasmus , Hansen Brian K. , Broberg Mala , Hansen Michael M. , Hedeholm Rasmus , Nielsen Einar E.
Published: June 2023

The current knowledge about fish biodiversity and species distributions in Arctic freshwater systems is generally limited. This contrasts the clear urgency for more accurate biodiversity data to assess the effects of future ecosystem challenges such as climate change and other anthropogenic effects. Here we compare traditional electrofishing surveys with environmental DNA (eDNA) for monitoring species distribution of Atlantic salmon (Salmo salar) and Arctic char (Salvelinus alpinus) in the West Greenlandic sub‐Arctic river system of Kapisillit, which contains the only known population of Atlantic salmon in Greenland. Overall, electrofishing and eDNA surveys show high compatibility in regard to species detection and quantification, with Arctic char confirming a significant relationship between eDNA concentration and observed fish abundance. Both methods confirm a shift in species occurrence and relative species abundance through the river system. Specifically, salmon is restricted to the lower warmer sections of the river system while Arctic char is found throughout the system but dominates the upper parts. In total, the study supports eDNA as a promising tool for fish community assessment, which may serve a wide array of applications for Arctic freshwater monitoring. These applications include analyzing species occurrence and distribution of native and invasive species, as well as documenting potential shifts in relative species abundance as shown here. Given the ease of sampling and high sensitivity of the method, eDNA provides a powerful cost‐effective approach capable of detecting species in remote areas as well as corroborating fish community monitoring programs. This may especially be valuable for monitoring in the Arctic where logistic complications with sampling and high operational costs so far constrains routine monitoring.
Transience of public attention in conservation science
Authors: Jarić Ivan , Correia Ricardo A , Bonaiuto Marino , Brook Barry W , Courchamp Franck , Firth Josh A , Gaston Kevin J , Heger Tina , Jeschke Jonathan M , Ladle Richard J , Meinard Yves , Roberts David L , Sherren Kate , Soga Masashi , Soriano‐Redondo Andrea , Veríssimo Diogo , Roll Uri
Published: June 2023

Societal awareness of, and engagement with, environmental problems is a critical prerequisite for effective conservation programs. Research has revealed a strong general pattern whereby public attention received by cultural products diminishes over time. If transposed to conservation, this transience of societal attention is likely to be of major importance because it can limit motivation to support conservation efforts. We address the concept of attention transience applied to conservation, discuss its major drivers and mechanisms, and provide a short overview of conservation issues for which this phenomenon is expected to be particularly relevant. Attention transience leaves a brief window of opportunity for conservationists to focus public awareness and to mobilize necessary support. In this context, it is critical to maximize the conservation benefits generated during these short bursts of attention, especially through tailored conservation marketing campaigns with targeted message framing and regular efforts to refocus attention on key issues.
Association of physical activity with overall mortality among long‐term testicular cancer survivors: A longitudinal study
Authors: Thorsen Lene , Courneya Kerry S. , Steene‐Johannessen Jostein , Gran Jon Michael , Haugnes Hege S. , Negaard Helene F. S. , Kiserud Cecilie E. , Fosså Sophie D.
Published: June 2023

Physical activity (PA) has been associated with reduced mortality among cancer survivors, but no study has focused on testicular cancer survivors (TCSs). We aimed to investigate the association of PA measured twice during survivorship with overall mortality in TCSs. TCSs treated during 1980 to 1994 participated in a nationwide longitudinal survey between 1998 to 2002 (S1: n = 1392) and 2007 to 2009 (S2: n = 1011). PA was self‐reported by asking for the average hours per week of leisure‐time PA in the past year. Responses were converted into metabolic equivalent task hours/week (MET‐h/wk) and participants were categorized into: Inactives (0 MET‐h/wk), Low‐Actives (2‐6 MET‐h/wk), Actives (10‐18 MET‐h/wk) and High‐Actives (20‐48 MET‐h/wk). Mortality from S1 and S2, respectively, was analyzed using the Kaplan‐Meier estimator and Cox proportional hazards models until the End of Study (December 31, 2020). Mean age at S1 was 45 years (SD 10.2). Nineteen percent (n = 268) of TCSs died between S1 and EoS, with 138 dying after S2. Compared to Inactives at S1, the mortality risk among Actives was 51% lower (HR 0.49, 95% CI: 0.29‐0.84) with no further mortality reduction among High‐Actives. At S2, the mortality risk was at least 60% lower among the Actives, High‐Actives and even the Low‐Actives compared to the Inactives. Persistent Actives (≥10 MET‐h/wk at S1 and S2) had a 51% lower mortality risk compared to Persistent Inactives (<10 MET‐h/wk at S1 and S2; HR 0.49, 95% CI: 0.30‐0.82). During long‐term survivorship after TC treatment, regular and maintained PA were associated with an overall mortality risk reduction of at least 50%.
Preptin Deficiency Does Not Protect against High‐Fat Diet‐Induced Metabolic Dysfunction or Bone Loss in Mice
Authors: Buckels Emma J. , Tan Joey , Hsu Huai‐Ling , Zhu Yuting , Buchanan Christina M. , Matthews Brya G. , Lee Kate L.
Published: June 2023

Preptin is derived from the cleavage of the E‐peptide of pro‐insulin‐like growth factor (IGF)‐II and is an insulin secretagogue. Observational studies have linked elevated circulating preptin to metabolic dysfunction in humans; however, a causal role for preptin in metabolic dysfunction has not been established. Additionally, preptin can promote osteoblast proliferation and differentiation, suggesting a link with skeletal health. We previously described a global preptin knockout (KO) model. In this study, we sought to uncover the impact of preptin KO in mice on the response to a moderately high‐fat diet (HFD) and low‐fat diet (LFD). HFD groups had higher weight and fat mass gain, lower trabecular and cortical bone volume and fracture load, and higher liver triglycerides. In males, preptin deficiency led to lower blood glucose than wild‐type (WT) mice under LFD conditions. This was accompanied by differences in bone microarchitecture, including lower trabecular bone volume fraction, trabecular number, and lower cortical thickness. These differences were absent in female mice, although KO females had a HFD‐driven increase in fat mass and liver triglycerides that was absent in WT mice. Female WT mice had increased glucose‐stimulated insulin secretion under HFD conditions that was absent in female KO mice. Overall, preptin may have a detrimental impact on metabolism and a positive impact on bone health in male mice and may protect against liver fat storage in females while enabling islet compensation under HFD conditions. When we consider that serum preptin levels are elevated in humans of both sexes in pathological states in which insulin levels are elevated, the impact of preptin on comorbidity risk needs to be better understood. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Cabozantinib‐induced edema in zebrafish represents an adverse effect characterized by defects in lymphatic vasculature and renal function
Authors: Medishetti Raghavender , C. Mallikarjuna Rao , Chatti Kiranam
Published: June 2023

Tyrosine kinase inhibitors (TKIs) are a major class of targeted cancer therapy drugs. Overcoming the limitations of approved TKIs and the development of new TKIs continues to be an important need. The adoption of higher throughput and accessible animal models to evaluate TKI adverse effects will help in this regard. We exposed zebrafish larvae to a set of 22 Food and Drug Administration‐approved TKIs and assessed mortality, early developmental abnormalities, and gross morphological abnormalities posthatching. We found edema posthatching as a consistent and prominent consequence of VEGFR inhibitors, and of cabozantinib in particular. The edema occurred at concentrations that did not cause lethality or any other abnormality, and was independent of the developmental stage. Further experiments identified loss of blood and lymphatic vasculature, and suppression of renal function in larvae exposed to 10 µM cabozantinib. Molecular analysis showed downregulation of the vasculature marker genes vegfr, prox1a, sox18, and the renal function markers nephrin and podocin as the potential molecular basis for the above defects, implicating them in the mechanism of cabozantinib‐induced edema. Our findings reveal edema as a previously unreported phenotypic effect of cabozantinib and identify the likely mechanistic basis. These findings also highlight the need for studies investigating edema due to vascular and renal dysfunction as a potential clinical adverse effect of cabozantinib, and possibly other VEGFR inhibitors.
Fibroblast‐derived exosomal microRNA regulates NKX3‐1 expression in androgen‐sensitive, androgen receptor‐dependent prostate cancer cells
Authors: Matsuda Chise , Ishii Kenichiro , Nakagawa Yasuhisa , Shirai Taku , Sasaki Takeshi , Hirokawa Yoshifumi S. , Iguchi Kazuhiro , Watanabe Masatoshi
Published: June 2023

Androgen deprivation therapy (ADT) targeting androgen production and androgen receptor (AR) signaling is the primary antihormonal therapy in the treatment of advanced prostate cancer (PCa). However, no clinically established molecular biomarkers have been identified to predict the effectiveness of ADT before starting ADT. The tumor microenvironment of PCa contains fibroblasts that regulate PCa progression by producing multiple soluble factors. We have previously reported that AR‐activating factor‐secreted fibroblasts increase the responsiveness of androgen‐sensitive, AR‐dependent PCa cells to ADT. Thus, we hypothesized that fibroblast‐derived soluble factors may affect cancer cell differentiation by regulating cancer‐related gene expression in PCa cells and that the biochemical characteristics of fibroblasts may be used to predict the effectiveness of ADT. Here, we investigated the effects of normal fibroblasts (PrSC cells) and three PCa patient‐derived fibroblast lines (pcPrF‐M5, ‐M28, and ‐M31 cells) on the expression of cancer‐related genes in androgen‐sensitive, AR‐dependent human PCa cells (LNCaP cells) and three sublines showing different androgen sensitivities and AR dependencies. The mRNA expression of the tumor suppressor gene NKX3‐1 in LNCaP cells and E9 cells (which show low androgen sensitivity and AR dependency) was significantly increased by treatment with conditioned media from PrSC and pcPrF‐M5 cells but not from pcPrF‐M28 and pcPrF‐M31 cells. Notably, no upregulation of NKX3‐1 was observed in F10 cells (AR‐V7‐expressing, AR‐independent cells with low androgen sensitivity) and AIDL cells (androgen‐insensitive, AR‐independent cells). Among 81 common fibroblast‐derived exosomal microRNAs that showed 0.5‐fold lower expression in pcPrF‐M28 and pcPrF‐M31 cells than in PrSC and pcPrF‐M5 cells, miR‐449c‐3p and miR‐3121‐3p were found to target NKX3‐1. In only LNCaP cells, the NKX3‐1 mRNA expression was significantly increased by transfection of an miR‐3121‐3p mimic but not that of the miR‐449c‐3p mimic. Thus, fibroblast‐derived exosomal miR‐3121‐3p may be involved in preventing the oncogenic dedifferentiation of PCa cells by targeting NKX3‐1 in androgen‐sensitive, AR‐dependent PCa cells.
Existence of small ordered orthogonal arrays
Authors: Schmidt Kai‐Uwe , Weiß Charlene
Published: June 2023

We show that there exist ordered orthogonal arrays, whose sizes deviate from the Rao bound by a factor that is polynomial in the parameters of the ordered orthogonal array. The proof is nonconstructive and based on a probabilistic method due to Kuperberg, Lovett and Peled.
Exercise‐regulated white adipocyte differentitation: An insight into its role and mechanism
Authors: Yan Linjing , Guo Liang
Published: June 2023

White adipocytes play a key role in the regulation of fat mass amount and energy balance. An appropriate level of white adipocyte differentiation is important for maintaining metabolic homeostasis. Exercise, an important way to improve metabolic health, can regulate white adipocyte differentiation. In this review, the effect of exercise on the differentiation of white adipocytes is summarized. Exercise could regulate adipocyte differentiation in multiple ways, such as exerkines, metabolites, microRNAs, and so on. The potential mechanism underlying the role of exercise in adipocyte differentiation is also reviewed and discussed. In‐depth investigation of the role and mechanism of exercise in white adipocyte differentiation would provide new insights into exercise‐mediated improvement of metabolism and facilitate the application of exercise‐based strategy against obesity.