bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive magnetic stimulation induces plasticity of excitatory synapses through cooperative pre- and postsynaptic activity
Authors: Galanis Christos , Lenz Maximilian , Farahani Mohammadreza Vasheghani , Vlachos Andreas 
Published: November 2024

AbstractTranscranial magnetic stimulation (TMS) is a widely used non-invasive technique in research and clinical settings. Despite its success, the cellular and molecular mechanisms underlying TMS-induced changes in the brain remain incompletely understood. Current protocols are largely heuristic, based on system-level observations. This study employed in vitro repetitive magnetic stimulation (rMS) in mouse brain tissue cultures, combined with computational modeling to develop an experimentally validated approach for predicting TMS effects. Unlike electrical or optogenetic stimulation, rTMS uniquely enhances plasticity by activating both pre- and postsynaptic neurons, with brain-derived neurotrophic factor (BDNF) playing a crucial role. Our simulations accurately predicted the frequency-dependent effects of rTMS, providing a critical step towards developing robust, validated tools that will enhance the precision and effectiveness of TMS applications across both research and clinical settings.Significance StatementThis study elucidates the mechanisms by which TMS promotes neural plasticity, specifically long-term potentiation (LTP) of excitatory neurotransmission. By demonstrating that rMS engages both pre- and postsynaptic neurons with BDNF as a key mediator, it provides a mechanistic basis for the therapeutic effects of rTMS. These insights advance our understanding of rTMS-induced brain plasticity and support the development of predictive computer models, paving the way for more effective and standardized TMS protocols in research and clinical applications.
An alpine plant shows no decrease in genetic diversity associated with rapid post-glacial range expansion
Authors: Urquhart-Cronish Mackenzie , Berg Colette S. , Moxley Dylan , Rahn Olivia J. , Fishman Lila , Angert Amy L. 
Published: November 2024

AbstractWhile range expansion is hypothesized to be a mechanism for species persistence under climate change, many eco-evolutionary models describe demographic and genetic processes during range expansion that may decrease genetic variation and increase genetic load at the leading edge (i.e., expansion load). These predictions are related to dispersal limitation at the leading edge driving colonization dynamics, a scenario common in post-glacial range expansion at the continental scale (∼20,000 years ago). However, post-glacial range expansion can also occur on contemporary time scales, such as alpine glacier recession following the end of The Little Ice Age (∼150 years ago) and our understanding of dispersal limitation structuring these instances of rapid range expansion are relatively understudied. Here, we test whether there is evidence supporting the role of dispersal limitation during range expansion following alpine glacier retreat using the native alpine plantErythranthe (Mimulus) lewisiiby examining patterns of neutral genetic diversity (single nucleotide polymorphisms) across the history of glacier recession (i.e., glacier chronosequence) across two glacier forelands in Garibaldi Provincial Park, BC. We find weak support for the prediction of increasing clines in genetic differentiation towards the range edge, and no support for decreasing clines in genetic diversity, suggesting dispersal limitation is not characterizing colonization during range expansion, with the implication that the accumulation of expansion load at the range edge is likely not applicable on these spatiotemporal scales. Together, our results suggest that loss of genetic diversity for range-shifting species in the alpine is likely not a key contributing factor to any decreased fitness over time.
ASD-AssociatedCNTNAP2Variants Disrupt Neuronal Arborization Through Impaired Regulation by Ectodomain Shedding
Authors: Lobete Miguel , Dionisio Leonardo E. , McCoig Emmarose , Piguel Nicolas H. , Spielman Benjamin P. , Socas Silvia , dos Santos Marc , Boers-Escuder Cristina , Penzes Peter , Martin-de-Saavedra M. Dolores 
Published: November 2024

ABSTRACTEctodomain shedding (ES) is a process by which a protease cleaves the extracellular portion of membrane-bound proteins, releasing soluble fragments that influence diverse cellular functions. ES is critical in neurodevelopment, plasticity, and neurodegenerative disorders, such as Alzheimer’s disease, and has recently been implicated in neurodevelopmental conditions, including autism spectrum disorders (ASD). Contactin-associated protein-like 2 (CNTNAP2) is an adhesion molecule regulated by ES, releasing a soluble ectodomain (sCNTNAP2) that enhances neuronal synchrony. CNTNAP2 is implicated in ASD, schizophrenia, and cortical dysplasia focal epilepsy syndrome (CDFE) and it is known to regulate neuronal arborization, as well as dendritic spine maturation and maintenance. However, little is known about how neuroplasticity impacts ES or the role of CNTNAP2 ES in dendritic arborization. Here, we show that the brain sheddome is enriched in shed ectodomains that regulate neuronal projections, and that its molecular and functional composition is modulated by sensory deprivation in a sex dependent manner, with a decrease in sCNTNAP2 levels observed only in male mice. Furthermore, we demonstrate that sCNTNAP2 promotes dendritic arborization, while ASD-associated CNTNAP2 variants present reduced sCNTNAP2 levels in culture and decreased neuronal branching. Together, these findings underscore the role of ES in neuroplasticity and ASD and reveal how CNTNAP2 genetic variations disrupt its regulation by ES, leading to altered dendritic branching.
Volume conductor models for magnetospinography
Authors: O’Neill George C. , Spedden Meaghan E. , Schmidt Maike , Mellor Stephanie , Stenroos Matti , Barnes Gareth R. 
Published: November 2024

AbstractThe recent development of small, wearable, magnetic field sensors allow for the investigation of biomagnetic fields with a flexibility previously unavailable. We test models to describe how current flow in the spinal cord and thorax gives rise to measurable magnetic fields outside the torso. We compare various open-access volume conductor models, in order to select the most parsimonious and accurate descriptor of the magnetic fields due to source current in the spinal cord.We find that fields produced due to current flow along the superior-inferior axis of the cord are relatively insensitive to the choice of volume conductor model. However, fields produced by current flow in predominantly left-right or anterior-posterior direction are significantly attenuated by the presence of bone in the forward model. Furthermore, volume conductors with bone demonstrate larger differences in field topographies for nearby sources compared to bone-free models. These findings suggest that precise modelling of spinal cord location and surrounding vertebrae will be important a-priori knowledge going forward.
Aerobic carbon metabolism modulates nitrite ammonifiers for inhibiting nitrogen loss as revealed by microcosm experiment of agricultural upland soil
Authors: Wu Xiaogang , Yu Siyu , Sui Weikang , Zhang Xinyu , Li Ji , Wu Qiaoyu , Zhang Xiaojun 
Published: November 2024

ABSTRACTDenitrification and dissimilatory nitrate reduction to ammonium (DNRA), two divergent nitrogen metabolism pathways, share nitrite as a common intermediate during anaerobic reduction. However, these pathways influence the environment and soil nutrients differently. Unlike denitrification, which involves nitrogen loss through gaseous nitrogen emission and nitrate leaching, DNRA is beneficial for the conservation of nitrogen. Nevertheless, the key mechanism underlying the joint regulation of aerobic carbon metabolism to nitrite ammonifiers in soil is still unclear, although previous studies have reported factors such as carbon and oxygen can independently affect DNRA. Here, microcosm experiments with agricultural upland soil were conducted under different aeration conditions supplemented with labile carbon to analyze the process of anaerobic nitrogen metabolism. The results indicated that denitrification exclusively dominated nitrite reduction when the soil was directly placed in an anaerobic environment. Nonetheless, a significant increase in DNRA activity and the attenuation of denitrification were detected when the soil was incubated aerobically with the addition of glucose prior to anaerobic incubation. Specifically, up to 55.8% of nitrite reduction switched to nitrogen conservation mainly via DNRA under high-carbon conditions. Quantitative assays of thenrfAgene and metagenomic data revealed a significant increase in DNRA-related genes after aerobic carbon metabolism. Furthermore,nrfAgene sequence analysis revealed a significant shift in the composition of nitrite ammonifiers community. These results indicate that nitrate/nitrite metabolic flux in the soil could be regulated to enhance DNRA by stimulating facultative anaerobic nitrite ammonifiers such asSedimentibacterunder alternating aerobic and anaerobic environments with carbon metabolism.IMPORTANCEThis study revealed that aerobic conditions with a carbon supply strongly influence the community assembly of nitrite ammonifiers. Nitrite ammonifiers such asSedimentibacterenriched under sufficient carbon and aeration conditions promoted the subsequent DNRA process under anaerobic conditions. Therefore, regulating the competition between DNRA and denitrification by altering functional microbiota would be a promising approach for improving the efficiency of fertilizer application and for reducing greenhouse gas emissions from denitrification. These findings are essential for understanding the biological mechanism of nitrogen cycling in dryland agricultural soil. Based on these findings, we may design a strategy to increase the abundance of nitrite ammonifiers in agricultural soil, which might promote DNRA metabolism to improve nitrogen retention. This strategy would ultimately enhance fertilizer use efficiency and mitigate the detrimental environmental effects of nitrogen fertilizer abuse.
Opportunistic pathogens are prevalent across the culturable exogenous and endogenous microbiota of stable flies captured at a dairy facility
Authors: Sommer Andrew J. , Deblois Courtney L. , Tu Andrew D. J. , Suen Garret , Coon Kerri L. 
Published: November 2024

AbstractStable flies in the genusStomoxysare highly abundant, blood-feeding pests on dairy farms; however, their role in the carriage and potential transmission of pathogens is largely understudied. Here, we report on the frequency and distribution of culturable bacteria collected fromStomoxysflies captured in free stall barns and nearby calf hutches over a three-month period on a focal research farm in Wisconsin, USA. Mastitis-associated bacterial taxa, includingStaphylococcus,Escherichia,Enterobacter, andKlebsiellaspp., were frequently isolated from pooled samples of the internal or external portions of the flies. Conversely, selective enrichment protocols from these samples yielded only a single isolate ofSalmonellaand no enterohemorrhagicEscherichia coliO157. Neither trap location nor time of capture had a significant impact on the observed frequency of most bacterial genera isolated from the flies. Our results confirm thatStomoxysflies harbor both mastitis-associated bacterial taxa and bacterial taxa associated with opportunistic infections in humans. Further research into the transmission of fly-associated microbes could be important in the control of mastitis or other bacterial diseases on dairy farms.
A global dopaminergic learning rate enables adaptive foraging across many options
Authors: Grima Laura L. , Guo Yipei , Narayan Lakshmi , Hermundstad Ann M. , Dudman Joshua T. 
Published: November 2024

AbstractIn natural environments, animals must efficiently allocate their choices across multiple concurrently available resources when foraging, a complex decision-making process not fully captured by existing models. To understand how rodents learn to navigate this challenge we developed a novel paradigm in which untrained, water-restricted mice were free to sample from six options rewarded at a range of deterministic intervals and positioned around the walls of a large (∼2m) arena. Mice exhibited rapid learning, matching their choices to integrated reward ratios across six options within the first session. A reinforcement learning model with separate states for staying or leaving an option and a dynamic, global learning rate was able to accurately reproduce mouse learning and decision-making. Fiber photometry recordings revealed that dopamine in the nucleus accumbens core (NAcC), but not dorsomedial striatum (DMS), more closely reflected the global learning rate than local error-based updating. Altogether, our results provide insight into the neural substrate of a learning algorithm that allows mice to rapidly exploit multiple options when foraging in large spatial environments.
A consensus definition for deep layer 6 excitatory neurons in mouse neocortex
Authors: Kim Su-Jeong , Babola Travis A. , Lee Kihwan , Matney Chanel J. , Spiegel Alina C. , Liew Michael H. , Schulteis Eva M. , Coye Austin E. , Proskurin Mikhail , Kang Hyunwook , Kim Julia A. , Chevée Maxime , Lee Kiwoong , Kanold Patrick O. , Goff Loyal A. , Kim Juhyun , Brown Solange P. 
Published: November 2024

AbstractTo understand neocortical function, we must first define its cell types. Recent studies indicate that neurons in the deepest cortical layer play roles in mediating thalamocortical interactions and modulating brain state and are implicated in neuropsychiatric disease. However, understanding the functions of deep layer 6 (L6b) neurons has been hampered by the lack of agreed upon definitions for these cell types. We compared commonly used methods for defining L6b neurons, including molecular, transcriptional and morphological approaches as well as transgenic mouse lines, and identified a core population of L6b neurons. This population does not innervate sensory thalamus, unlike layer 6 corticothalamic neurons (L6CThNs) in more superficial layer 6. Rather, single L6b neurons project ipsilaterally between cortical areas. Although L6b neurons undergo early developmental changes, we found that their intrinsic electrophysiological properties were stable after the first postnatal week. Our results provide a consensus definition for L6b neurons, enabling comparisons across studies.
Aging drives a program of DNA methylation decay in plant organs
Authors: Dai Dawei , Chen Ken , Tao Jingwen , Williams Ben P. 
Published: November 2024

AbstractHow organisms age is a question with broad implications for human health. In mammals, DNA methylation is a biomarker for biological age, which may predict age more accurately than date of birth. However, limitations in mammalian models make it difficult to identify mechanisms underpinning age-related DNA methylation changes. Here, we show that the short-lived model plantArabidopsis thalianaexhibits a loss of epigenetic integrity during aging, causing heterochromatin DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing lifespan, and that shoot apical meristems are protected from this aging process. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging, and that mutants of this mechanism display a complete absence of epigenetic decay. This presents a new paradigm in which a gene regulatory program sets the rate of epigenomic information loss during aging.
PII interactions with BADC and BCCP proteins co-regulate lipid and nitrogen metabolism in Arabidopsis
Authors: Garneau Matthew G. , Jorge Gabriel Lemes , Shockey Jay , Thelen Jay J. , Bates Philip D. 
Published: November 2024

AbstractIn plants the initiation of fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACCase) which produces malonyl-CoA. The heteromeric form of ACCase (htACCase) is a holoenzyme consisting of biotin carboxylase and carboxyltransferase sub-complexes, both of which are subject to extensive regulation. Biotin carboxylase activity is controlled in part by the presence of the catalytic biotin carboxyl carrier proteins (BCCP1/2) and/or the non-catalytic, non-biotinylated, biotin/lipoyl attachment domain-containing proteins (BADC1/2/3) that associate with backbone biotin carboxylase (BC) protein. However, the mechanisms regulating BADC and BCCP interaction with BC and thus ACCase activityin plantaare not clear. Here we demonstrate theArabidopsis thalianaregulatory protein PII modulates htACCase activity through independent interactions with BADC and BCCP proteins in a selective manner. Analysis ofbadc1/2andbadc1/3mutant lines and the respectivepiitriple mutants reveal that changes in seed oil and protein accumulation ofbadcdouble mutants are PII/nitrogen dependent. Absolute quantification of htACCase subunits and PII in developing seeds suggests that Arabidopsis exerts tight regulation over individual protein stoichiometry to balance oil and protein accumulation. The effects on vegetative and seed development indicate PII and BADC proteins have distinct but overlapping roles in the regulation of plant metabolism.
Structural Analysis of a Metamorphic Protein using AlphaFold2
Authors: Tyree Soren , Kim Yongick 
Published: November 2024

ABSTRACTMetamorphic proteins, which can adopt multiple stable conformations, challenge the traditional understanding of protein structure and function. KaiB is a metamorphic protein that regulates the circadian clock, a central regulator governing gene expression in most light-perceiving organisms on Earth. An interesting aspect is that the circadian clock can be reconstituted in vitro by mixing Kai proteins (KaiA, KaiB, and KaiC) with ATP and Mg2+. The phosphorylation state of KaiC oscillates with a 24-hour period. The fold-switched form of KaiB binds to KaiC to activate the dephosphorylation of KaiC, while the other fold of KaiB dissociates from KaiC, allowing phosphorylation to be activated by the binding of KaiA to KaiC. To understand the metamorphic process of KaiB, we utilized AlphaFold2, a protein structure prediction program, and sequence alignments. We found that a proline residue determines the fold of KaiB. We also confirmed that mutating this proline to lysine changes KaiB to a fold-switched conformation. This validates that AlphaFold2 can be used for the study of metamorphic proteins.
Consolidation of sequential experience into a deep generative network explains human memory, prediction and planning
Authors: Spens Eleanor , Burgess Neil 
Published: November 2024

AbstractThe consolidation of sequential experience is thought to enable efficient schema-based reconstruction of the past and prediction of the future, but the mechanism is unknown. Here, we present a computational model in which sequences are rapidly encoded in the hippocampus and replayed to train a neocortical deep generative network to predict the next item in each sequence. This is simulated using generative pre-trained transformers (GPTs), a variety of large language model. As well as capturing the gist of specific episodes, the neocortical network extracts statistical patterns that generalise to new situations. This model explains human performance on statistical learning and structural inference tasks, and accounts for gist or schema-based distortions in memories of narratives. It also shows how recent memory can contribute to inference and planning, capturing hippocampal and neocortical interactions as ‘retrieval-augmented generation’, in which specific memories retrieved from the hippocampus provide the context in working memory for prediction using the ‘general knowledge’ of the neocortical network. Furthermore, it shows how hippocampal traces could combine gist and detail for efficient encoding. The model suggests how episodic, semantic and working memory interact in the consolidation, (re)construction and planning of sequential experience.
Variations in kinase and effector signaling logic in a bacterial two component signaling network
Authors: Swingle Danielle , Epstein Leah , Aymon Ramisha , Isiorho Eta A. , Abzalimov Rinat R. , Favaro Denize C. , Gardner Kevin H. 
Published: November 2024

AbstractThe general stress response (GSR) protects bacteria from a wide range of stressors. InAlphaproteobacteria, GSR activation is coordinated by HWE/HisKA2 family histidine kinases (HKs), which can exhibit non-canonical structure and function. For example, while most light-oxygen-voltage sensor-containing HKs are light activated dimers, theRubellimicrobium thermophilumRT-HK has inverted “dark on, light off” signaling logic with a tunable monomer/dimer equilibrium. Here, we further investigate these atypical behaviors of RT-HK and characterize its downstream signaling network. Using hydrogen-deuterium exchange mass spectrometry, we find that RT-HK uses a signal transduction mechanism similar to light-activated systems, despite its inverted logic. Mutagenesis reveals that RT-HK autophosphorylatesin trans, with changes to the Jα helix linking sensor and kinase domains affecting autophosphorylation levels. Exploring downstream effects of RT-HK, we identified two GSR genetic regions, each encoding a copy of the central regulator PhyR.In vitromeasurements of phosphotransfer from RT-HK to the two putative PhyRs revealed that RT-HK signals only to one, and does so at an increased intensity in the dark, consistent with its reversed logic. X-ray crystal structures of both PhyRs revealed a substantial shift within the receiver domain of one, suggesting a basis for RT-HK specificity. We probed further down the pathway using nuclear magnetic resonance to determine that the single NepR homolog interacts with both unphosphorylated PhyRs, and this interaction is decoupled from activation in one PhyR. This work expands our understanding of HWE/HisKA2 family signal transduction, revealing marked variations from signaling mechanisms previously identified in other GSR networks.
Tomato roots exhibit distinct, development-specific responses to bacterial-derived peptides
Authors: Leuschen-Kohl Rebecca , Roberts Robyn , Stevens Danielle M. , Zhang Ning , Buchanan Silas , Pilkey Brooke , Coaker Gitta , Iyer-Pascuzzi Anjali S. 
Published: November 2024

SUMMARYPlants possess cell-surface recognition receptors that detect molecular patterns from microbial invaders and initiate an immune response. Understanding the conservation of pattern-triggered immunity within different plant organs and across species is crucial to its sustainable and effective use in plant disease management but is currently unclear.We examined the activation and immune response patterns of three pattern recognition receptors (PRRs:SlFLS2,SlFLS3, andSlCORE) in different developmental regions of roots and in leaves of multiple accessions of domesticated and wild tomato (Solanum lycopersicumandS. pimpinellifolium) using biochemical and genetic assays.Roots from different tomato accessions differed in the amplitude and dynamics of their immune response, but all exhibited developmental-specific PTI responses in which the root early differentiation zone was the most sensitive to molecular patterns. PRR signaling pathways also showed distinct but occasionally overlapping responses downstream of each immune receptor in tomato roots.These results reveal that each PRR initiates a unique PTI pathway and suggest that the specificity and complexity of tomato root immunity are tightly linked to the developmental stage, emphasizing the importance of spatial and temporal regulation in PTI.