bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle-dependent cues regulate temporal patterning of theDrosophilacentral brain neural stem cells
Authors: Chaya Gonzalo N. Morales , Syed Mubarak Hussain 
Published: January 2025

AbstractDuring nervous system development, diverse types of neurons and glia are sequentially generated by self-renewing neural stem cells (NSCs). Temporal changes in gene expression within NSCs are thought to regulate neural diversity; however, the mechanisms regulating the timing of these temporal gene transitions remain poorly understood.Drosophilatype II NSCs, like human outer radial glia, divide to self-renew and generate intermediate neural progenitors, amplifying and diversifying the population of neurons innervating the central complex, a brain region required for sensorimotor coordination. Type II NSCs express over a dozen genes temporally, broadly classified as early and late-expressed genes. A conserved gene, Seven-up mediates early to late gene expression by activating ecdysone receptor (EcR) expression. However, what determines the timing of EcR expression and, hence, early to late gene transition is unknown. This study investigates whether intrinsic mechanisms of cell cycle progression and cytokinesis are required to induce the NSC early-late transition. By generating mutant clones that arrest the NSC cell cycle or block cytokinesis, we show that both processes are necessary for the early-to-late transitions. When NSCs are cell cycle or cyto-kinesis arrested, the early gene Imp failed to be down-regulated and persisted into the old NSCs, while the late factors EcR and Syncrip failed to be expressed. Furthermore, we show that the early factor Seven-up is insufficient to drive the transition despite its normal expression in the cell cycle-or cytokinesis-inhibited NSCs. These results suggest that both intrinsic (cell cycle/cytokinesis) and extrinsic (hormone) cues are required for the early-late NSC gene expression transition.
Evolution of functional genomic diversity during a bottleneck
Authors: Schlichta Flávia , Peischl Stephan , Excoffier Laurent 
Published: January 2025

AbstractMost species have been through population bottlenecks and range expansions, and the impact of these events on patterns of diversity has been well studied. In particular, it has been shown that initially rare neutral variants could readily fix on the front of range expansions or during bottlenecks, giving genomic signatures looking like selective sweeps. Here we expand on previous work by considering the dynamics of genomic diversity in (functional) regions harbouring deleterious variants during bottlenecks or during range expansions modelled as serial founder effects. We find that regions with very low levels of diversity (troughs) looking like selective sweeps can also readily form in these functional regions. Additionally, their properties depend on the dominance level of deleterious mutations. Trough density is higher and increases more rapidly in regions with co-dominant deleterious mutations than in regions with recessive mutations. Interestingly, we find that genetic diversity declines less rapidly in regions with partially recessive mutations than in regions with codominant ones or in regions with only neutral mutations. These features are generally enhanced in low recombination regions and for intermediate selection coefficients. If most deleterious mutations in a genome are partially recessive, it follows that functional low recombination regions should better preserve genetic diversity during range expansions than neutral regions of the genome.Significance statementMost research on the effects of selection on genetic diversity have been done in equilibrium populations, leaving a gap in our understanding of how selection acting on functional regions interacts with demographic changes. Our study reveals strikingly different impacts of purifying selection on genetic diversity depending on the dominance coefficient of deleterious mutations. While codominant variants create diversity dips resembling selective sweeps, recessive mutations can preserve genetic diversity during bottlenecks through the relatively understudied phenomenon of pseudo-overdominance. Our findings show how selective and demographic forces interact in more complex ways than previously thought and emphasize the importance of further exploring these dynamics to accurately interpret genetic variation in natural populations.
Repetitive stimulation modifies network characteristics of neural organoid circuits
Authors: Chow Siu Yu A. , Hu Huaruo , Duenki Tomoya , Asakura Takuya , Sugimura Sota , Ikeuchi Yoshiho 
Published: January 2025

AbstractNeural organoids form complex networks but lack external stimuli and hierarchical structures crucial for refining functional microcircuits. In this study, we modeled the hierarchical and modular network organization by connecting multiple organoids and tested if the connection enhances the external stimuli-induced network refinement. We cultured networks of one, two, or three organoids on high-density microelectrode arrays, applied repetitive stimulation at two input locations from the microelectrodes, and monitored emergence of output signals that can decode the stimulus locations with machine learning algorithms. After two weeks of daily stimulation, networks of three organoids showed significantly higher stimulus decoding capability compared to the simpler one- or two-organoid networks. Long-term stimulation induced pronounced changes in the three-organoid network’s response patterns, spontaneous activity, and inter- and intra-organoid functional connectivity. These findings underscore the importance of hierarchical network organization, e.g. creating distinct subnetworks with specialized roles, for stimuli-induced formation of circuits with robust input-output functionality.
Phage defence system abundances vary across environments and increase with viral density
Authors: Meaden Sean , Westra Edze , Fineran Peter 
Published: January 2025

AbstractThe defence systems bacteria use to protect themselves from their viruses are mechanistically and genetically diverse. Yet the ecological conditions that predict when defences are selected for remain unclear, as substantial variation in defence prevalence has been reported. Experimental work in simple communities suggests ecological factors can determine when specific defence systems are most beneficial, but applying these findings to complex communities has been challenging. Here, we use a comprehensive and environmentally balanced collection of metagenomes to survey the defence landscape across complex microbial communities. We also assess the association between the viral community and the prevalence of defence systems. We identify strong environmental effects in predicting overall defence abundance, with animal-host-associated environments and hot environments harbouring more defences overall. We also find a positive correlation between the density and diversity of viruses in the community and the abundance of defence systems. This study provides insights into the ecological factors that influence the composition and distribution of bacterial defence systems in complex microbial environments and outlines future directions for the study of defence system ecology.
Molecular circuit betweenAspergillus nidulanstranscription factors MsnA and VelB to coordinate fungal stress and developmental responses
Authors: Bastakis Emmanouil , Gerke Jennifer , Özkan Seyma , Harting Rebekka , Lienard Tanja , Sasse Christoph , Xylakis Emmanouil S. , Aden Merle , Strohdiek Anja , Heinrich Gabriele , Grosse Verena , Braus Gerhard H. 
Published: January 2025

AbstractDevelopment and secondary metabolism of the filamentous fungusAspergillus nidulansare tightly controlled by concerted actions of several master regulator transcription factors. The connection between fungal development and cellular stress response programs is often elusive. Here we show that the MsnA zinc finger transcription factor, which controls salt-stress response, is a novel major player in fungal development. A molecular circuit among MsnA and the velvet domain regulator VelB was discovered, which mutually fosters the actions of both regulatory proteins during development. MsnA controls the expression of several genes encoding master transcriptional regulators of asexual as well as sexual development. In addition, MsnA affects directly and indirectly the synthesis of specific secondary metabolites relevant for fungal defense against other organisms and growth, in addition to salt-stress responses. Moreover, the expression of genes encoding the epigenetic regulators VapA and VipC are also directly controlled by MsnA. These subunits of the VapA-VipC-VapB methyltransferase signal transduction complex promote asexual differentiation. MsnA is therefore placed at a novel prominent position of the central regulatory network, which coordinates stress responses with the developmental and metabolic fate of the fungus.
Human and Rodent Seizures Demonstrate a Dynamic Interplay with Spreading Depolarizations
Authors: Norby Jacob H. , Hummel Daniel , Ricks Noah , Rolston John D. , Rahimpour Shervin , Voipio Juha , Trevelyan Andrew J. , Smith Elliot H. , Parrish R. Ryley 
Published: January 2025

AbstractSeizure termination has been linked to spreading depolarizations (SDs) in experimental epilepsy models, and SDs have recently been suggested to protect against seizures. The precise mechanism, however, remains unclear. Additionally, the co-occurrence of SDs with human seizures remains debated.In this study, we found that SDs are a prominent feature following ictal events in both human clinical recordings (n=20 seizures from 7 epilepsy patients) using direct-current amplifiers and in the 0 Mg2+model of ictogenesis from rodent brain slices (n=17).Approximately one-third of rodent seizure-like events (SLEs) were associated with SDs, while all human seizures analyzed had associated infraslow shifts, a hallmark of SDs. SDs were more prominent in the lateral frontal, medial frontal, and lateral temporal lobes, as well as the insular cortex in human patients, but were observed in all recorded brain regions. In rodents, SDs clustered toward the end of ictal events, resulting in significantly shorter SLEs (SLE without SD: 32.60 ± 5.31 s; SLE with SD: 16.03 ± 4.45 s) and delayed onset of subsequent SLEs. These SDs also caused significant AC band silencing compared to SLEs without SDs. Interestingly, SLEs with SDs displayed significantly more low gamma activity during ictal events. Using ion- selective microelectrodes, we found no significant correlation between extracellular [K+] levels and SLEs ending in SDs, questioning the role of [K+]oin SD induction during seizures.We observed more heterogeneity in human seizures than in rodent SLEs, with some human seizures showing SD-associated termination and others demonstrating SDs in the middle of ictal events; such intra-seizure SDs were never observed in our rodent model. The human data, collected from patients with intractable epilepsy, demonstrate clear SD propagation during seizures and show that SDs appear and propagate, in multiple brain regions simultaneously with ictal events.Collectively, these results indicate that SDs are a hallmark of ictal activity and may contribute to seizure termination in both experimental and clinical settings. Furthermore, these findings provide unique insight into the neuronal dynamics that promote SD induction by showing that increased low gamma activity during SLEs is more predictive of SD induction than extracellular [K+] levels. We also add further support for the hypothesis that SDs are both anti- seizure and anti-ictogenic as they not only limit and delay subsequent ictal activity but also reduce the duration of SLEs. Taken together, these findings provide rationale for further exploration of SDs as a means to prematurely terminate life-threatening seizures.
In situ light-driven pH modulation for NMR studies
Authors: Barde Aarav , Han Ruixian , Olson Martin A. , Tonelli Marco , Rienstra Chad M. , Henzler-Wildman Katherine , Ravula Thirupathi 
Published: January 2025

AbstractProton exchange is a fundamental chemical event, and NMR provides the most direct readout of protonation events with site-specific resolution. Conventional approaches require manual titration of sample pH to collect a series of NMR spectra at different pH values. This requires extensive sample handling and often results in significant sample loss, leading to reduced signal or the need to prepare additional samples. Here, we introduce a novel approach to control pH in NMR samples using water soluble photoacids, which alter the pH of the solution from near neutral to acidic pH upon in situ photo-illumination. We show that the solution pH can be precisely controlled by choice of illumination wavelength and intensity and sufficient protons are released from the photoacid to achieve meaningful pH change in samples where the molecule of interest has significant buffering capacity, such as a >100 μM protein sample. The pH is monitoredin situusing internal standards with pH-sensitive chemical shifts. This method enables precise, calibrated, non-invasive change of sample pH within an NMR magnet, dramatically reducing the necessary sample handling. These findings highlight the potential of light-induced pH control in NMR experiments and increase the robustness and reliability of pH-dependent studies. With pH playing a key role in modulating chemical behavior in both biological and synthetic systems, the ability to study protonation states and modulate sample pH in a simple and precise manner that is compatible with high-resolution NMR studies of molecular structure and function has wide applications.Entry for the Table of ContentsIn this work, we introduce a novel approach to control pH in NMR samples using light-activated photoacids. By combining light stimuli with pH-sensitive molecules, we demonstrate the ability to precisely modulate pH without physically manipulating the sample. This method enables non-invasive pH titration in NMR studies, where pH plays a key role in protein function. Our findings highlight the potential of light-induced pH control to overcome existing limitations in NMR, providing a powerful tool for advancing protein research under controlled pH conditions.
Persistent large-scale changes in alternative splicing in prefrontal cortical neuron types following psychedelic exposure
Authors: Hsiao Yungyi , Fonseca Marcos AS , Tiemroth Alina S , Vasquez Estefany J , Gomez Andrea M 
Published: January 2025

SummaryPsychedelics engage the serotonergic system as potent neuromodulators, increasing neuroplasticity in humans and rodents. Persistent changes in cognitive flexibility, emotional regulation, and social cognition are thought to underlie the therapeutic effects of psychedelics. However, the underlying molecular and cellular basis of psychedelic-induced plasticity remains unclear. Here, we identify persistent, cell type-specific alternative splicing changes in the mouse medial prefrontal cortex (mPFC) induced by a single dose of psychedelics. Combining deep RiboTag sequencing and bioinformatics, we find that a single dose of psychedelics modestly alters gene expression while dramatically shifting patterns of alternative splicing lasting at least a month. We connect our functional enrichment and alternative splicing analysis with changes in the extracellular matrix, synaptic physiology, and intrinsic physiology in parvalbumin interneurons days to a week after psychedelic treatment. Our dataset is an essential resource for understanding the persistent, cell type-specific effects of psychedelics on cortical cell types and functions.
Apolipoprotein E ε4exacerbates microglia-mediated complement-dependent synapse loss caused by neuronalTpkdeficiency
Authors: Du Pengyue , Jin Boru , Wang Zijie , Zhao Binqiao , Sang Shaoming , Zhong Chunjiu 
Published: January 2025

AbstractThiamine pyrophosphokinse-1 (TPK) is a key enzyme that converts thiamine to functional thiamine diphosphate (TDP). TPK insufficiency and hence TDP reduction in neurons induced by amyloid-β deposition and diabetes, an independent risk factor of Alzheimer’s disease (AD), recapitulate multi-pathophysiological features in the brain of mice, similar to those in human AD.Apolipoprotein Eε4 allele(APOE4) is the most well-known genetic risk factor for AD. Clinical trials by boosting TDP using benfotiamine, a derivative of thiamine that significantly elevates TDP level in human encrythrocytes, have shown the inferior clinical efficacies inAPOE4carriers compared to non-APOE4 carriers. Clarifying the relationship between APOE4 and TPK expression and multi-pathophysiological characteristics of AD induced byTpkdeficiency in neurons is imperative. Here, we find that humanizedAPOE4didn’t directly affectTpkexpression of mice, but markedly aggravates behavior abnormalities ofTpk-cKO mice. Pathologically, theTpk-cKO mice with humanizedAPOE4knock-in (AE-cKO mice) exhibit more synapse loss than the mice with only humanizedAPOE4knock-in and theTpk-cKO mice. Transcriptomics and pathologic analysis identified thatAPOE4promoted the overactivation of microglia and the transition of microglia to a disease-associated and phagocytosis stateviaa complement-mediated pathway. Further, the C3aR antagonist significantly repressed microglia phagocytosis and synaptic elimination of the AE-cKO mice. Our results demonstrate thatAPOE4exacerbates behavior dysfunction ofTpk-cKO mice through microglia-mediated complement-dependent synaptic elimination. These findings provide important insights into the role of APOE4 in the pathogenesis of AD.
Loss of excitatory inputs and decreased tonic and evoked activity of locus coeruleus neurons in aged P301S mice
Authors: Downs Anthony M. , Kmiec Gracianne , Catavero Christina M. , McElligott Zoé A. 
Published: January 2025

AbstractTau pathology in the locus coeruleus (LC) is associated with several neurodegenerative conditions including Alzheimer’s disease and frontotemporal dementia. Phosphorylated tau accumulates in the LC and results in inflammation, synaptic loss, and eventually cell death as the disease progresses. Loss of LC neurons and noradrenergic innervation is thought to contribute to the symptoms of cognitive decline later in disease. While loss and degeneration of LC neurons has been well studied, less is known about changes in LC physiology at advanced stages of tau pathology that precedes neurodegeneration. In this study, we investigated theex vivoelectrophysiological properties of LC neurons in male and female mice from the P301S mouse model of tauopathy at 9 months of age, a time-point when significant tau accumulation, cell death, and cognitive impairments are observed. We found a reduction in excitatory inputs and changes in excitatory post-synaptic current kinetics in male and female P301S. There was also a decrease in spontaneous discharge of LC neurons and an increase in AP threshold in P301S mice of both sexes. Finally, we observed a decrease in excitability and increase in rheobase current in P301S mice. Despite the decrease in LC activity in slice, we did not identify differences in total tissue norepinephrine (NE) or NE metabolites in prefrontal cortex or hippocampus. Together these findings demonstrate reductions in the activity and excitability of LC neurons at late stages of tau accumulation. However, compensatory mechanisms may maintain normal NE levels in LC projection regionsinvivo.
Mass spectra of full-heavy and double-heavy tetraquark states in the conventional quark model
Authors: Meng Qi , Wang Guang-Juan , Oka Makoto 
Published: January 2025

A comprehensive study of the S-wave heavy tetraquark states with identical quarks and antiquarks, specifically QQQ¯′Q¯′ (Q,Q′=c, b), QQs¯s¯/Q¯Q¯ss, and QQq¯q¯/Q¯Q¯qq (q=u, d), are studied in a unified constituent quark model. This model contains the one-gluon exchange and confinement potentials. The latter is modeled as the sum of all two-body linear potentials. We employ the Gaussian expansion method to solve the full four-body Schrödinger equations, and search bound and resonant states using the complex-scaling method. We then identify 3 bound and 62 resonant states. The bound states are all QQq¯q¯ states with the isospin and spin-parity quantum numbers I(JP)=0(1+): two bound bbq¯q¯ states with the binding energies, 153 MeV and 4 MeV below the BB* threshold, and a shallow ccq¯q¯ state at −15  MeV from the DD* threshold. The deeper bbq¯q¯ bound state aligns with the lattice QCD predictions, while ccq¯q¯ bound state, still has a much larger binding energy than the recently observed Tcc+ by LHCb collaboration. No bound states are identified for the QQQ¯′Q¯′, QQs¯s¯, and QQq¯q¯ with I=1. Our analysis shows that the bound QQQ¯′Q¯′ states are more probable with a larger mass ratio, mQ/mQ′. Experimental investigation for these states is desired, which will enrich our understanding of hadron spectroscopy and probe insights into the confinement mechanisms within tetraquarks.

Published by the American Physical Society
2025
Antecedents of entrepreneurial intention in an international business environment: a gender comparison
Authors: González-Ramos M. Isabel , Guadamillas Fátima , Ortiz Beatriz , Donate Mario J. 
Published: January 2025

PurposeThis paper aims to analyse the influence of contextual factors, such as educational, relational and structural support, on psychological dimensions of entrepreneurship – self-confidence and risk-taking propensity – , and their impact on Entrepreneurial Intention (EI). Further, a gender comparison is conducted on an international sample and analyses the moderating effect of family antecedents (an entrepreneurial parent) on the relationship between relational support and self-confidence and risk-taking propensity.Design/methodology/approachWe test the research hypotheses using a validated questionnaire in an international context through a survey submitted to 406 professionals from Spain, China and Latin-American countries, who had received entrepreneurial education and completed their studies at least two years beforehand.FindingsThe results show significant gender differences in self-confidence and risk-taking propensity, particularly when the antecedents are educational and structural support to start a business, and we also find differences when we consider an entrepreneurial family member (father, mother) as a moderator in the relationship between relational support and self-confidence, and risk-taking propensity.Practical implicationsThe findings shed new light on the overall picture regarding factors contributing to EI and provide valuable implications for the design of entrepreneurship education measures and policies to promote entrepreneurship in a global context.Originality/valueAs a novelty, this paper considers an international sample of professionals, including personal and psychological aspects as potential determinants of EI (in addition to traditional contextual factors), and also an analysis of the effects of entrepreneurial family members on the relational aspects of entrepreneurship that can affect psychological aspects of potential entrepreneurs. It also includes a gender comparison for the hypothesized model.