bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric inhibition of CXCR1 and CXCR2 abrogates Th2/Th17-associated Allergic Lung Inflammation in Mice
Authors: Hosoki Koa , Govindhan Annamalai , Knight John M , Sur Sanjiv 
Published: May 2024

AbstractBackgroundIL4, IL5, IL13, and IL17-producing CD4 T helper 2 (Th2)-cells and IL17-producing CD4 T helper 17 (Th17)-cells contribute to chronic eosinophilic and neutrophilic airway inflammation in asthma and allergic airway inflammation. Chemokines and their receptors are upregulated in Th2/Th17-mediated inflammation. However, the ability of CXCR1 and CXCR2 modulate Th2 and Th17-cell-mediated allergic lung inflammation has not been reported.MethodsMice sensitized and challenged with cat dander extract (CDE) mount a vigorous Th2-Th17-mediated allergic lung inflammation. Allosteric inhibitor of CXCR1 and CXCR2, ladarixin was orally administered in this model. The ability of ladarixin to modulate allergen-challenge induced recruitment of CXCR1 and CXCR2-expressing Th2 and Th17-cells and allergic lung inflammation were examined.ResultsAllergen challenge in sensitized mice increased mRNA expression levels ofIl4, Il5, Il13, Il6, Il1β, Tgfβ1, Il17, Il23, Gata3,andRorc, and induced allergic lung inflammation characterized by recruitment of CXCR1- and CXCR2-expressing Th2-cells, Th17-cells, neutrophils, and eosinophils. Allosteric inhibition of CXCR1 and CXCR2 vigorously blocked each of these pro-inflammatory effects of allergen challenge. CXCL chemokines induced a CXCR1 and CXCR2-dependent proliferation of IL4, IL5, IL13, and IL17 expressing T-cells.ConclusionAllosteric inhibition of CXCR1 and CXCR2 abrogates blocks recruitment of CXCR1- and CXCR2-expressing Th2-cells, Th17-cells, neutrophils, and eosinophils in this mouse model of allergic lung inflammation. We suggest that the ability of allosteric inhibition of CXCR1 and CXCR2 to abrogate Th2 and Th17-mediated allergic inflammation should be investigated in humans.
Knockout ofcryptochrome 1disrupts circadian rhythm and photoperiodic diapause induction in the silkworm,Bombyx mori
Authors: Tobita Hisashi , Kiuchi Takashi 
Published: May 2024

AbstractMost insects enter diapause, a state of physiological dormancy crucial for enduring harsh seasons, with photoperiod serving as the primary cue for its induction, ensuring proper seasonal timing of the process. Although the involvement of the circadian clock in the photoperiodic time measurement has been demonstrated through knockdown or knockout of clock genes, the precise molecular mechanisms in this context remain unclear. In bivoltine strains of the silkworm,Bombyx mori, embryonic diapause is maternally controlled and affected by environmental conditions experienced by mother moths during embryonic and larval stages. Previous research highlighted the role of core clock genes, includingperiod(per),timeless(tim),Clock(Clk) andcycle(cyc), in photoperiodic diapause induction inB. mori. In this study, we focused on another clock gene,cryptochrome 1(cry1), which functions as a photoreceptor implicated in photoentrainment of the circadian clock across various insect species. Phylogenetic analysis and conserved domain identification confirmed the presence of bothDrosophila-typecry(cry1) and mammalian-typecry(cry2) genes in theB. morigenome, akin to other lepidopterans. Temporal expression analysis revealed highercry1gene expression during the photophase and lower expression during the scotophase, with knockouts of core clock genes (per,tim,Clkandcyc) disrupting this temporal expression pattern. Using CRISPR/Cas9-mediated genome editing, we established acry1knockout strain in p50T, a bivoltine strain exhibiting clear photoperiodism during both embryonic and larval stages. Although the wild-type strain displayed circadian rhythm in eclosion under continuous darkness, thecry1knockout strain exhibited arrhythmic eclosion, implicatingB. mori cry1in the circadian clock feedback loop governing behavior rhythms. Females of thecry1knockout strain failed to induce photoperiodic diapause during both embryonic and larval stages, mirroring the diapause phenotype of the wild-type individuals reared under constant darkness, indicating thatB. moriCRY1 contributes to photoperiodic time measurement as a photoreceptor. Furthermore, photoperiodic diapause induction during the larval stage was abolished in acry1/timdouble-knockout strain, suggesting that photic information received by CRY1 is relayed to the circadian clock. Overall, this study represents the first evidence ofcry1involvement in insect photoperiodism, specifically in diapause induction.HighlightsKnockouts of core clock genes disrupted the rhythmic expression ofcryptochrome 1(cry1).Acry1knockout strain was established using CRISPR/Cas9.Thecry1knockout strain lost its eclosion rhythm.Knockout ofcry1disrupted photoperiodic diapause induction.Females of acry1/timdouble knockout strain produced only non-diapause eggs regardless of larval photoperiod.Graphical abstract
Successful Cardiac Resynchronization Therapy Reduces Negative Septal Work in Patient-Specific Models of Dyssynchronous Heart Failure
Authors: Craine Amanda , Krishnamurthy Adarsh , Villongco Christopher T. , Vincent Kevin , Krummen David E. , Narayan Sanjiv M. , Kerckhoffs Roy C. P. , Omens Jeffrey H. , Contijoch Francisco , McCulloch Andrew D. 
Published: May 2024

AbstractIn patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work.We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.
Parallel rapid phenotypic differentiation along climatic gradients in multiple introduced lineages of an alien plant species
Authors: Matsuhashi Saeko , Kudoh Hiroshi , Oguro Michio , Sakai Satoki 
Published: May 2024

AbstractWidespread plant species are faced with various climatic gradients and undergo clinal differentiation. Alien species which have been introduced repeatedly can be used to investigate the parallel processes of clinal differentiation during their range expansions.Cardamine hirsutaL. has been unintentionally introduced to Japan at least three times and has become widely distributed across Japan. To elucidate the processes of clinal differentiation, we conducted a common garden experiment using three lineages ofC. hirsuta(North, East, and West). We tested for phenotypic differentiation among and within the lineages, and for a common pattern of clinal variations in phenotypic traits. We detected differentiations of flowering phenology and body size within and among the lineages. The East lineage showed delayed flowering phenology and larger mass, whereas the West lineage showed rapid flowering phenology and smaller mass. In addition, three patterns of variation between climate factors in seed source habitats and phenotypic traits were detected in all three lineages: higher temperature was related to earlier flowering and lower leaf number at the start of flowering, and more hours of sunshine were related to shorter flowering period. These patterns imply independent and parallel differentiations in the three lineages. These results suggest that analyses of distinct lineages allow repeated observations of differentiation processes and rapid responses of species during successful distribution in new environments.
STEMorph: A Set of Morphed Emotional Face Stimuli from Angry to Happy Derived fromNimStim
Authors: Katebi Mohammad Ebrahim , Ghafari Mohammad Hossein , Ghafari Tara 
Published: May 2024

AbstractEmotion recognition through facial expressions is crucial for interpreting social cues. However, it is often influenced by biases, i.e, systematic recognition advantages for particular emotions. Nevertheless, these biases are inconsistently reported across studies, likely due to methodological variations which underline the necessity for a standardized approach. Traditional face morphing methods can create unnatural-looking stimuli, and may confound the interpretation of emotions. To address this issue, we here introduceSTEMorph, a validated stimulus set based on the NimStim set. We employed neutral-anchored morphing and neural-network-generated masks to ensure the natural appearance and integrity of the depicted emotions. We validated our stimulus set by having participants rate each face on a 9-point scale ranging from angry to happy, assessing the perceived emotional intensity.STEMorph’svalidity was confirmed through linear regression analysis, showing a strong correlation between subjective ratings and targeted emotional states. Moreover, aligning with previous research highlighting gender as a key factor in emotion recognition,STEMorphalso exhibits variations in ratings across gender subgroups.STEMorph’sreliability was confirmed through a two-week follow-up rating session with a subgroup of the same participants. By introducing a controlled, validated, and ecologically valid stimulus set of emotional faces,STEMorphpaves the way for further investigations into facial emotion recognition, deepening our understanding of this vital aspect of human interaction.
Time of first contact determines cooperator success in a cross-feeding consortium
Authors: Los Rachel , Fecker Tobias , van Touw P.A.M. , van Tatenhove-Pel Rinke J. , Idema Timon 
Published: May 2024

AbstractMicrobial communities are characterised by complex interaction, including cooperation and cheating, which have significant ecological and applied implications. However, the factors determining the success of cooperators in the presence of cheaters remain poorly understood. Here, we investigate the dynamics of cooperative interactions in a cross-feeding consortium using individual-based simulations and an engineeredL. cremoristoy consortium. Our simulations reveal first contact time between cooperators as a critical predictor for cooperator success. By manipulating the relative distances between cooperators and cheaters or the background growth rates, influenced by the cost of co-operation, we can modulate this first contact time and influence cooperator success. Our study underscores the importance of cooperators coming into contact with each other on time, which provides a simple and generalizable framework for understanding and designing cooperative interactions in microbial communities. These findings contribute to our understanding of cross-feeding dynamics and offer practical insights for synthetic and biotechnological applications.
Effects of systemic oxytocin receptor activation and blockade on risky decision making in female and male rats
Authors: Faraji Mojdeh , Viera-Resto Omar A. , Berrios Brenden J. , Bizon Jennifer L. , Setlow Barry 
Published: May 2024

AbstractThe neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, “safe” food reward and a large, “risky” food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Neither drug affected task performance in males. In females, however, both oxytocin and L-368,899 caused a dose-dependent reduction in preference for large risky reward. Control experiments showed that these effects could not be accounted for by alterations in food motivation or shock sensitivity. Together, these results reveal a sex-dependent effect of oxytocin signaling on risky decision making in rats.
plantMASST - Community-driven chemotaxonomic digitization of plants
Authors: Gomes Paulo Wender P. , Mannochio-Russo Helena , Schmid Robin , Zuffa Simone , Damiani Tito , Quiros-Guerrero Luis-Manuel , Caraballo-Rodríguez Andrés Mauricio , Zhao Haoqi Nina , Yang Heejung , Xing Shipei , Charron-Lamoureux Vincent , Chigumba Desnor N. , Sedio Brian E. , Myers Jonathan A. , Allard Pierre-Marie , Harwood Thomas V. , Tamayo-Castillo Giselle , Kang Kyo Bin , Defossez Emmanuel , Koolen Hector H. F. , da Silva Milton Nascimento , e Silva Consuelo Yumiko Yoshioka , Rasmann Sergio , Walker Tom W. N. , Glauser Gaëtan , Chaves-Fallas José Miguel , David Bruno , Kim Hyunwoo , Lee Kyu Hyeong , Kim Myeong Ji , Choi Won Jun , Keum Young-Sam , de Lima Emilly J. S. P. , de Medeiros Lívia Soman , Bataglion Giovana A. , Costa Emmanoel V. , da Silva Felipe M. A. , Carvalho Alice Rhelly V. , Reis José Diogo E. , Pamplona Sônia , Jeong Eunah , Lee Kyungha , Kim Geum Jin , Kil Yun-Seo , Nam Joo-Won , Choi Hyukjae , Han Yoo Kyong , Park Si Young , Lee Ki Yong , Hu Changling , Dong Yilun , Sang Shengmin , Morrison Colin R. , Borges Ricardo Moreira , Teixeira Andrew Magno , Lee Seo Yoon , Lee Bum Soo , Jeong Se Yun , Kim Ki Hyun , Rutz Adriano , Gaudry Arnaud , Bruelhart Edouard , Kappers Iris F. , Karlova Rumyana , Meisenburg Mara , Berdaguer Roland , Tello J. Sebastián , Henderson David , Cayola Leslie , Wright S. Joseph , Allen David N. , Anderson-Teixeira Kristina J. , Baltzer Jennifer L. , Lutz James A. , McMahon Sean M. , Parker Geoffrey G. , Parker John D. , Northen Trent R. , Bowen Benjamin P. , Pluskal Tomáš , van der Hooft Justin J. J. , Carver Jeremy J. , Bandeira Nuno , Pullman Benjamin S. , Wolfender Jean-Luc , Kersten Roland D. , Wang Mingxun , Dorrestein Pieter C. 
Published: May 2024

AbstractUnderstanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.
Optimizing Coarse-Grained Models for Large-Scale Membrane Protein Simulation
Authors: Wen Chen Yun , Luo Yun Lyna , Madsen Jesper J. 
Published: May 2024

AbstractCoarse-grained (CG) models have been developed for studying membrane proteins at physiologically relevant scales. Such methods, including popular CG lipid models, exhibit stability and efficiency at moderate scales, but they can become impractical or even unusable beyond a critical size due to various technical issues. Here, we report that these scale-dependent issues can arise from progressively slower relaxation dynamics and become confounded by unforeseen instabilities observed only at larger scales. To address these issues, we systemically optimized a 4-site solvent-free CG lipid model that is suitable for conducting micron-scale molecular dynamics simulations of membrane proteins under various membrane properties. We applied this lipid model to explore the long-range membrane deformation induced by a large mechanosensitive ion channel, PIEZO. We show that the optimized CG models are powerful in elucidating the structural and dynamic interplay between PIEZO and the membrane. Furthermore, we anticipate that our methodological insights can prove useful for resolving issues stemming from scale-dependent limitations of similar CG methodologies.
Patterning, regulation, and role of FoxO/DAF-16 in the early embryo
Authors: Mauro Michael S. , Martin Sophia L. , Dumont Julien , Shirasu-Hiza Mimi , Canman Julie C. 
Published: May 2024

AbstractInsulin resistance and diabetes are associated with many health issues including higher rates of birth defects and miscarriage during pregnancy. Because insulin resistance and diabetes are both associated with obesity, which also affects fertility, the role of insulin signaling itself in embryo development is not well understood. A key downstream target of the insulin/insulin-like growth factor signaling (IIS) pathway is the forkhead family transcription factor FoxO (DAF-16 inC. elegans). Here, we used quantitative live imaging to measure the patterning of endogenously tagged FoxO/DAF-16 in the early worm embryo. In 2-4-cell stage embryos, FoxO/DAF-16 initially localized uniformly to all cell nuclei, then became dramatically enriched in germ precursor cell nuclei beginning at the 8-cell stage. This nuclear enrichment in early germ precursor cells required germ fate specification, PI3K (AGE-1)- and PTEN (DAF-18)-mediated phospholipid regulation, and the deubiquitylase USP7 (MATH-33), yet was unexpectedly insulin receptor (DAF-2)- and AKT-independent. Functional analysis revealed that FoxO/DAF-16 acts as a cell cycle pacer for early cleavage divisions–without FoxO/DAF-16 cell cycles were shorter than in controls, especially in germ lineage cells. These results reveal the germ lineage specific patterning, upstream regulation, and cell cycle role for FoxO/DAF-16 during earlyC. elegansembryogenesis.
Low copy CRISPR-Cas13d mitigates collateral RNA cleavage
Authors: Hart Sydney K. , Wessels Hans-Hermann , Méndez-Mancilla Alejandro , Müller Simon , Drabavicius Gediminas , Choi Olivia , Sanjana Neville E. 
Published: May 2024

AbstractWhile CRISPR-Cas13 systems excel in accurately targeting RNA, the potential for collateral RNA degradation poses a concern for therapeutic applications and limits broader adoption for transcriptome perturbations. We evaluate the extent to which collateral RNA cleavage occurs whenRfxCas13d is delivered via plasmid transfection or lentiviral transduction and find that collateral activity only occurs with high levels ofRfxCas13d expression. Using transcriptome-scale and combinatorial CRISPR pooled screens in cell lines with low-copyRfxCas13d, we find high on-target knockdown, without extensive collateral activity regardless of the expression level of the target gene. In contrast, transfection ofRfxCas13d, which yields higher nuclease expression, results in collateral RNA degradation. Further, our analysis of a high-fidelity Cas13 variant uncovers a marked decrease in on-target efficiency, suggesting that its reduced collateral activity may be due to an overall diminished nuclease capability.
Perineuronal nets in motor circuitry regulate the performance of learned vocalizations in songbirds
Authors: Wan Xinghaoyun , Wang Angela S. , Storch Daria-Salina , Li Vivian Y. , Sakata Jon T. 
Published: May 2024

ABSTRACTThe accurate and reliable production of learned behaviors can be important for survival and reproduction; for example, the performance of learned vocalizations (e.g., speech and birdsong) modulates the efficacy of social communication in humans and songbirds. Consequently, it is critical to understand the factors that regulate the performance of learned behaviors. Across various taxa, neural circuits that regulate motor learning are replete with perineuronal nets (PNNs), extracellular matrices that surround neurons and shape neural dynamics and plasticity. Perineuronal nets in circuits for sensory and cognitive processes have been found to affect sensory processing and behavioral plasticity. However, the function of PNNs in motor circuits remains largely unknown. Here, we analyzed the causal contribution of PNNs in motor circuitry to the performance of learned vocalizations in songbirds. Songbirds like the zebra finch are powerful models for this endeavor because the performance of their learned songs is regulated by activity within discrete and specialized circuits (i.e., song system) that are dense with PNNs. We first report that developmental increases in the density and intensity of PNNs throughout the song system [including in the motor nucleus HVC (acronym used as proper name)] are associated with developmental increases in song performance. We next discovered that enzymatically degrading PNNs in HVC acutely affected song performance. In particular, PNN degradation caused song structure to deviate from pre-surgery song due to changes in syllable sequencing and production. Collectively, our data provide compelling evidence for a causal contribution of PNNs to the performance of learned behaviors.SIGNIFICANCE STATEMENTMotor circuits are replete with perineuronal nets (PNNs) but little is known about their contribution to motor performance. Here, we analyzed how PNNs within vocal motor circuits modulate the ability of songbirds to consistently produce their learned songs. We report that developmental increases in PNN expression in vocal circuitry were associated with developmental increases in the ability to consistently perform their learned song. Moreover, degrading PNNs in the vocal motor nucleus HVC reduced the ability of adult birds to accurately produce their learned song. Our findings indicate a causal contribution of PNNs in motor circuitry to the performance of learned behaviors and, because PNNs are expressed in brain areas regulating speech, suggest that PNNs could modulate speech production in humans.
Structural basis of 3′-tRNA maturation by the human mitochondrial RNAse Z complex
Authors: Gesé Genís Valentín , Martin Hällberg B. 
Published: May 2024

AbstractHuman mitochondrial tRNA maturation is essential for cellular energy production, yet the underlying mechanisms remain only partially understood. Here, we present several cryo-EM structures of the mitochondrial RNase Z complex (ELAC2/SDR5C1/TRMT10C) bound to different maturation states of mitochondrial tRNAHis, showing the molecular basis for tRNA-substrate selection and catalysis. Our structural insights provide a molecular rationale for the 5′-to-3′ tRNA processing order in mitochondria, the 3′-CCA antideterminant effect, and the basis for sequence-independent recognition of mitochondrial tRNA substrates. Furthermore, the study links mutations in ELAC2 to clinically relevant mitochondrial diseases, offering a deeper understanding of the molecular defects contributing to these conditions.