bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFR1/p38αMAPK signaling in Nex+ supraspinal neurons regulates sex-specific chronic neuropathic pain
Authors: Swanson Kathryn A. , Nguyen Kayla L. , Gupta Shruti , Ricard Jerome , Bethea John R. 
Published: August 2023

ABSTRACTUpregulation of soluble tumor necrosis factor (sTNF) cytokine signaling through TNF receptor 1 (TNFR1) and subsequent neuronal hyperexcitability are observed in both animal models and human chronic neuropathic pain (CNP) (Clark et al., 2013; Empl et al., 2001; Ji et al., 2018; Lindenlaub and Sommer, 2003). To test the hypothesis that supraspinal circuitry is critical to pain chronification, we studied the intersect between supraspinal TNFR1 mediated neuronal signaling and sex specificity by selectively removing TNFR1 in Nex+ neurons in adult mice (NexCreERT2::TNFR1f/f). We determined that following chronic constriction injury (CCI), pain resolves in males; however, female acute pain transitions to chronic. Subsequently, we investigated two downstream pathways, p38MAPK and NF-κB, important in TNFR1 signaling and injury response. We detected p38αMAPK and NF-κB activation in male cortical tissue; however, p38αMAPK phosphorylation was reduced in NexCreERT2::TNFR1f/fmales. We observed similar behavioral results following CCI in NexCreERT2::p38αMAPKf/fmice. Previously, we established estrogen’s ability to modulate sTNF/TNFR1 signaling in CNP, which may contribute to female prevalence of CNP (Bouhassira et al., 2008; Claiborne et al., 2006; de Mos et al., 2007; Del Rivero et al., 2019; Li et al., 2009). To explore the intersection between estrogen and inflammation in CNP we used a combination therapy of an estrogen receptor β (ER β) inhibitor with a sTNF/TNFR1 or general p38MAPK inhibitor. We determined both combination therapies lend “male-like” therapeutic relief to females following CCI. These data suggest that TNFR1/p38αMAPK signaling in Nex+ neurons in CNP is male-specific and lack of therapeutic efficacy following sTNF inhibition in females is due to ER β interference. These studies highlight sex-specific differences in pathways important to pain chronification and elucidate potential therapeutic strategies that would be effective in both sexes.
Visual Sequence Encoding is Enhanced by Predictable Music Pairing via Modulating Medial Temporal Lobe and Its Connectivity with Frontostriatal Loops
Authors: Ren Yiren , Brown Thackery 
Published: August 2023

AbstractListening to music during cognitive activities, such as reading and studying, is very common in human daily life. Therefore, it is important to understand how music interacts with concurrent cognitive functions, particularly memory. Current literature has presented mixed results for whether music can benefit learning in other modalities. Evidence is needed for what neural mechanisms music can tap into to enhance concurrent memory processing. This fMRI study aimed to begin filling this gap by investigating how music of varying predictability levels influences parallel visual sequence encoding performance. Behavioral results suggest that overall, predictable music enhances visual sequential encoding, and this effect increases with the structural regularity and familiarity of music. fMRI results indicate that during visual sequence encoding, music activates traditional music-processing and motor-related areas, but decreases parahippocampal and striatal engagement. This deactivation may indicate a more efficient encoding of visual information when music is present. By comparing music conditions of different structural predictability and familiarity, we probed how this occurs. We demonstrate improved encoding with increased syntactical regularity, which was associated with decreased activity in default mode network and increased activity in inferior temporal gyrus. Furthermore, the temporal schema provided by music familiarity may influence encoding through altered functional connectivity between the prefrontal cortex, medial temporal lobe and striatum. Overall, we propose that pairing music with learning might facilitate memory by reducing neural demands for visual encoding and simultaneously strengthening the connectivity between the medial temporal lobe and frontostriatal loops important for sequencing information.Significance StatementThere is considerable interest in what mechanisms can be tapped to improve human memory. Music provides a potential modulator, but few studies have investigated music effects on encoding episodic memory. This study used a novel design to examine how music can influence concurrent visual item sequence encoding. We provided neural data to better understand mechanisms behind potential benefits of music for learning. Our results demonstrated predictable music may help guide parallel learning of sequences in another modality. We found that music might facilitate processing in neural systems associated with visual declarative long-term and working memory, and familiar music might modulate reward circuits and provide a temporal schema which facilitates better encoding of the temporal structure of new non-music information.
Acetic acid is a superior ion pairing modifier for sub-nanogram and single cell proteomics
Authors: Eberhard Colten D. , Orsburn Benjamin C. 
Published: August 2023

AbstractA recent study demonstrated a substantial increase in peptide signal and corresponding proteome coverage when employing 0.5% acetic acid (AA) as the ion pairing modifier in place of the 0.1% formic acid traditionally used in shotgun proteomics. In this study, we investigated the effect of modifier in the context of sub-nanogram and single cell proteomics (SCP). We first evaluated a tryptic digest standard down to 20 picograms total load on column on a TIMSTOF SCP system. In line with the previous results, we observed a signal increase when using AA, leading to increased proteome coverage at every peptide load assessed. Relative improvements were more apparent at lower concentrations, with a 20 picogram peptide digest demonstrating a striking 1.8-fold increase to over 2,000 protein groups identified in a 30 minute analysis. Furthermore, we find that this increase in signal can be leveraged to reduce ramp times, leading to 1.7x more scans across each peak and improvements in quantification as measured by %CVs. When evaluating single cancer cells, approximately 13% more peptide groups were identified on average when employing AA in the place of FA. All vendor raw and processed data are available through ProteomeXchange as PXD046002 and PXD051590.TOC Graphic
Oligo-PROTAC strategy for cell-selective and targeted degradation of activated STAT3
Authors: Hall Jeremy , Zhang Zhuoran , Wang Dongfang , Bhattacharya Supriyo , Alcantara Marice , Liang Yong , Swiderski Piotr , Forman Stephen , Kwak Larry , Vaidehi Nagarajan , Kortylewski Marcin 
Published: August 2023

ABSTRACTDecoy-oligodeoxynucleotides (D-ODNs) can target undruggable transcription factors, such as STAT3. However, challenges in D-ODN delivery and potency hampered their translation. To overcome these limitations, we conjugated STAT3-specific D-ODN to thalidomide (Tha), a known ligand to cereblon (CRBN, a component of E3 ubiquitin ligase) to generate a proteolysis-targeting chimera (STAT3DPROTAC). STAT3DPROTACdownregulated STAT3, but not STAT1 or STAT5, in target cells. Computational modeling of the STAT3DPROTACternary complex predicted two surface lysines on STAT3, K601 and K626 as potential ubiquitination sites for the PROTAC bound E3 ligase. Accordingly, K601/K626 point mutations in STAT3, as well as proteasome inhibitors, and CRBN deletion alleviated STAT3DPROTACeffect. Next, we conjugated STAT3DPROTACto a CpG ligand targeting Toll-like receptor 9 (TLR9) to generate myeloid/B-cell-selective C-STAT3DPROTACconjugate. Naked C-STAT3DPROTACwas spontaneously internalized by TLR9+myeloid cells, B cells as well as human Ly18 and mouse A20 lymphoma cells, but not by T cells. C-STAT3DPROTACdecreased STAT3 levels to 50% at 250 nM and over 85% at 2 µM dosing in myeloid cells. We also observed significantly improved downregulation of STAT3 target genes involved in lymphoma cell proliferation and/or survival (BCL2L1, CCND2, MYC). Finally, we assessed the antitumor efficacy of C-STAT3DPROTACcompared to C-STAT3D or scrambled control (C-SCR) against human lymphoma xenotransplants. Local C-STAT3DPROTACadministration triggered lymphoma regression while control treatments had limited effects. Our results underscore feasibility of using PROTAC strategy for cell-selective, decoy oligonucleotide-based targeting of STAT3 and potentially other tumorigenic transcription factors for cancer therapy.
Ophidian physique: the capacity of middle trunk vertebral shape for quantitative taxonomic delimitation in snakes
Authors: Jacisin John J. , Lawing A. Michelle 
Published: August 2023

AbstractSkeletal specializations in snakes have resulted in incredible locomotive adaptability, including oft-overlooked vertebral complexity. Snake vertebrae are usually identified via qualitative descriptions of morphological traits; however, identifying and describing snake vertebrae in a scientifically replicable way has long hindered fossil snake research, where attempts to identify between or within snake groups can be onerous. Here, we build a framework of extant snake middle trunk vertebral shape using 2D geometric morphometrics (GMM) and quantitative methods to explore the viability of using these tools to assign and identify snake trunk vertebrae taxonomically and ecologically. We use 23 landmarks to evaluate anterior vertebral shape variation in 504 snake trunk vertebrae representing 189 species across 11 families for delimiting taxonomy and primary foraging habitat. We found that snake vertebral shape variation of overall proportions and articular surfaces contained statistically significant taxonomic and ecomorphological information useful for group assignment. Differences in primary foraging habitat also resulted in similar morphological trends within taxonomic groups in shape space. We then used linear discriminant functions to test the reliability of taxonomic assignments based on the shape captured by our landmark scheme. Analysis of the full dataset had high overall accuracy for family and subfamily, but only moderate success for genus, species, and primary foraging habitat. When applied to a single subfamily, overall accuracy greatly increased for genus and primary foraging habitat, implying that iterative application of this method may improve results. This study presents the framework for a new replicable method to supplement qualitative morphological descriptions of taxa. We recommend that GMM is best employed alongside qualitative descriptions for the optimal and reproducible delimitation of snake vertebrae. Finally, this method will allow non-expert diagnosticians to have more confidence in identifying fossil snake vertebrae, helping increase the number of snake fossils identified in museum collections.
Identification of Key Yeast Species and Microbe-Microbe Interactions Impacting Larval Growth ofDrosophilain the Wild
Authors: Mure Ayumi , Sugiura Yuki , Maeda Rae , Honda Kohei , Sakurai Nozomu , Takahashi Yuuki , Watada Masayoshi , Katoh Toshihiko , Gotoh Aina , Gotoh Yasuhiro , Taniguchi Itsuki , Nakamura Keiji , Hayashi Tetsuya , Katayama Takane , Uemura Tadashi , Hattori Yukako 
Published: August 2023

ABSTRACTMicrobiota consisting of various fungi and bacteria have a significant impact on the physiological functions of the host. However, it is unclear which species are essential to this impact and how they affect the host. This study analyzed and isolated microbes from natural food sources ofDrosophilalarvae, and investigated their functions.Hanseniaspora uvarumis the predominant yeast responsible for larval growth in the earlier stage of fermentation. As fermentation progresses,Acetobacter orientalisemerges as the key bacterium responsible for larval growth, although yeasts and lactic acid bacteria must coexist along with the bacterium to stabilize this host-bacterial association. By providing nutrients to the larvae in an accessible form, the microbiota contributes to the upregulation of various genes that function in larval cell growth and metabolism. Thus, this study elucidates the key microbial species that support animal growth under microbial transition.
Effect of percutaneous ventricular assisted device on post-cardiac arrest myocardial dysfunction in swine model with prolonged cardiac arrest
Authors: Nakashima Takahiro , Tiba Mohamad Hakam , Hsu Cindy H. , Gottula Adam L. , McCracken Brendan M. , Greer Nicholas L. , Cramer Traci A. , Sutton Nadia R. , Ward Kevin R. , Neumar Robert W 
Published: August 2023

AbstractBackgroundPercutaneous left ventricular assist device (pLVAD) can provide hemodynamic support during and after cardiac arrest, but it remains unclear if pLVAD reduces post-cardiac arrest myocardial dysfunction.MethodsThis is an analysis of a subset of animals that achieved return of spontaneous circulation (ROSC) in a study comparing pLVAD, transient aortic occlusion (AO), or both during cardiopulmonary resuscitation (CPR) after prolonged cardiac arrest. pLVAD, AO, or both were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to <1.0 L/min while maintaining a mean arterial pressure >70 mmHg, and subsequently removed at 240 minutes when feasible. The primary outcome was the recovery of cardiac index (CI), stroke volume index (SVI), and left ventricular ejection fraction (LVEF) at 240 minutes post-ROSC. Data are shown as mean (standard error).ResultsSeventeen animals achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 and standard care group, n = 6). For the primary outcome, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m2 (p=0.043) and LVEF 60(3) vs. 49(4) % (p=0.029) at 240 minutes after ROSC, respectively, when compared with the standard care group, while SVI was not significant difference (2[3] vs. 23[4] mL/min/m2,p=0.054). During the first 60 minutes after ROSC with maximum pLVAD flow, the pLVAD group had significantly higher coronary perfusion pressure (62[4] vs. 47[5] mmHg, p=0.019), lower LV stroke work index (3.9[3.0] vs. 14.9[4.4] cJ/m2, p=0.043), and lower total pulmonary resistance index (13.2[4.8] vs. 21.5[14.4] Wood Unit, p=0.001).ConclusionThese results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.
Cine phase contrast magnetic resonance imaging of calf muscle contraction in pediatric patients with cerebral palsy and healthy children: comparison of voluntary motion and electrically evoked motion
Authors: Weidensteiner Claudia , Deligianni Xeni , Haas Tanja , Madoerin Philipp , Bieri Oliver , Garcia Meritxell , Romkes Jacqueline , Rutz Erich , Santini Francesco , Brunner Reinald 
Published: August 2023

AbstractThe aim of this study is to investigate the feasibility of phase contrast imaging for assessment of muscle function in children with cerebral palsy. Time-resolved cine phase contrast MRI at 3T was synchronized with (a) electrical muscle stimulation (EMS) of the calf muscle and (b) voluntary plantarflexion following visual instructions. Fourteen ambulatory pediatric patients with equinus and 13 normally developing, healthy children were scanned. Ten patients were scanned pre and post botulinum toxin treatment. Four patients and four healthy children performed voluntary plantarflexion additionally to EMS. The achieved force was higher for the voluntary task for both patients and healthy controls, but its periodicity was worse compared to the stimulated contraction in patients. Therefore, it was possible to acquire contraction velocity time courses showing two distinct velocity peaks – the first for voluntary muscle contraction and the second for release – in four out of four healthy controls but in none of the patients. During EMS, two distinct velocity peaks could be resolved if the tolerated current was high enough to evoke sufficient contraction. That was achieved in 21% of the scans in patients (15 out of 72 scans during EMS in total) compared to 82% (14 out of 17) in healthy children. Then, the data quality was sufficient to generate strain maps. However, it was not possible to detect an effect of botulinum toxin in these patients since we did not succeed in acquiring data with sufficient quality both pre- and post-treatment. In conclusion, both EMS and voluntary motion worked well in healthy, normally developing children. Compliance was higher for the voluntary task for both patients and healthy controls. In conclusion, it was necessary to use EMS for a successful measurement of contraction/release velocity and strain in CP patients and although in this cohort the results were inconclusive, in the future optimization of the stimulation protocol could increase the acceptance and improve the output.
Insect population dynamics underWolbachia-induced cytoplasmic incompatibility: puzzle more than buzz inDrosophila suzukii
Authors: Auguste Alexandra , Ris Nicolas , Belgaidi Zainab , Kremmer Laurent , Mouton Laurence , Fauvergue Xavier 
Published: August 2023

AbstractIn theory, the introduction of individuals infected with an incompatible strain ofWolbachia pipientisinto a recipient host population should result in the symbiont invasion and reproductive failures caused by cytoplasmic incompatibility (CI). Modelling studies combiningWolbachiainvasion and host population dynamics show that these two processes could interact to cause a transient population decline and, in some conditions, extinction. However, these effects could be sensitive to density dependence, with the Allee effect increasing the probability of extinction, and competition reducing the demographic impact of CI. We tested these predictions with laboratory experiments in the fruit flyDrosophila suzukiiand the transinfectedWolbachiastrainwTei. Surprisingly, the introduction ofwTei intoD. suzukiipopulations at carrying capacity did not result in the expectedwTei invasion and transient population decline. In parallel, we found no Allee effect but strong negative density dependence. From these results, we propose that competition interacts in an antagonistic way withWolbachia-induced cytoplasmic incompatibility on insect population dynamics. If future models and data support this hypothesis, pest management strategies usingWolbachia-induced CI should target populations with negligible competition but a potential Allee effect, for instance at the beginning of the reproductive season.
Nitric oxide feedback to ciliary photoreceptor cells gates a UV avoidance circuit
Authors: Jokura Kei , Ueda Nobuo , Gühmann Martin , Yañez-Guerra Luis Alfonso , Słowiński Piotr , Wedgwood Kyle C. A. , Jékely Gáspár 
Published: August 2023

AbstractNitric oxide (NO) produced by nitric-oxide synthase (NOS) is a key regulator of animal physiology. Here we uncover a function for NO in the integration of UV exposure and the gating of a UV-avoidance circuit. We studied UV/violet avoidance mediated by brain ciliary photoreceptors (cPRCs) in larvae of the annelidPlatynereis dumerilii. In the larva, NOS is expressed in interneurons (INNOS) postsynaptic to cPRCs. UV stimulation of cPRCs triggers INNOS activation and NO production. NO signals retrogradely to cPRCs to induce their sustained post-stimulus activation through an unconventional guanylate cyclase. This late activation inhibits serotonergic ciliomotor neurons to induce downward swimming. InNOSmutants, retrograde signalling, circuit output and UV avoidance are defective. By mathematical modelling, we recapitulate phototransduction and circuit dynamics in wild-type and mutant larvae. Our results reveal how NO-mediated retrograde signalling gates a synaptic circuit and induces short-term memory of UV exposure to orchestrate light-avoidance behaviour.
Gorse (Ulex europeaus) wastes with 5,6-dimethyl benzimidazole supplementation can support growth of vitamin B12producing commensal gut microbes
Authors: Iyer Ajay , Soto-Martín Eva C. , Cameron Gary A. , Louis Petra , Duncan Sylvia H. , Bestwick Charles S. , Russell Wendy R. 
Published: August 2023

AbstractMany commensal gut microbes are recognized for their potential to synthesize vitamin B12, offering a promising avenue to address deficiencies through probiotic supplementation. While bioinformatics tools aid in predicting B12biosynthetic potential, empirical validation remains crucial to confirm production, identify cobalamin vitamers, and establish biosynthetic yields.This study investigates vitamin B12production in three human colonic bacterial species:Anaerobu-tyricum halliiDSM 3353,Roseburia faecisDSM 16840, andAnaerostipes caccaeDSM 14662, along withPropionibacterium freudenreichiiDSM 4902 as a positive control. These strains were selected for their potential use as probiotics, based on speculated B12production from prior bioinformatic analyses. Cultures were grown in M2GSC, chemically defined media (CDM), and Gorse extract medium (GEM). The composition of GEM was similar to CDM, expect that the carbon and nitrogen source was replaced with protein-depleted liquid wastes obtained after subjecting Gorse to a leaf protein extraction process. B12yields were quantified using liquid chromatography with tandem mass spectrophotometry.The results suggest that the three butyrate-producing strains could indeed produce B12, although the yields were notably low, and with no B12being detected in the extracellular media. Next, GEM outperformed the conventional M2GSC growth medium in enhancing B12production. The positive control,P. freudenreichiiDSM 4902 produced B12at concentrations ranging from 7 ng·mL−1to 12 ng·mL−1. Univariate-scaled Principal Component Analysis of data from previous publications investigating B12production inP. freudenreichiirevealed that B12yields diminished when the carbon source concentration was≤30 g·L−1.In conclusion, the protein-depleted wastes from the leaf protein extraction process from Gorse can be valorised as a viable substrate for culturing B12-producing colonic gut microbes. Furthermore, this is the first report attesting to the ability ofA. hallii, R. faecis, andA. caccaeto produce B12. However, these microbes seem unsuitable for industrial applications owing to low B12yields.
Assessment of tobacco andN. benthamianaas biofactories of irregular monoterpenes for sustainable crop protection
Authors: Mateos-Fernández Rubén , Vacas Sandra , Navarro-Fuertes Ismael , Navarro-Llopis Vicente , Orzáez Diego , Gianoglio Silvia 
Published: August 2023

ABSTRACTIrregular monoterpenes are important precursors of different compounds employed in pest control such as insecticides and insect sex pheromones. Metabolically engineered plants are appealing as biofactories of such compounds, but specially as potential live biodispensers of related bioactive volatiles, which could be continuously emitted to the environment from different plant tissues. Here we assess the use of cultivated tobacco and Nicotiana benthamiana as biofactories for the irregular monoterpenes chrysanthemol and lavandulol. We evaluate the impact of high levels of constitutive metabolite production on the plant physiology and biomass, and their biosynthetic dynamics for different plant tissues and developmental stages. As an example of an active pheromone compound, we super-transformed the best lavandulol-producing tobacco line with an acetyl transferase gene to obtain a tobacco lavandulyl acetate biodispenser emitting up to 0.63 mg of lavandulyl acetate per plant every day. We estimate that with these volatile emission levels, between 200 and 500 plants per hectare would be sufficient to ensure a daily emission of pheromones comparable to commercial lures. This is an important step towards plant-based sustainable solutions for pest control, and it lays the ground for further developing biofactories for other irregular monoterpenoid pheromones, whose biosynthetic genes are yet unknown.