bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decomposed Linear Dynamical Systems (dLDS) models reveal context-dependent dynamic connectivity inC. elegans
Authors: Yezerets Eva , Mudrik Noga , Charles Adam S. 
Published: June 2024

AbstractDespite innumerable efforts to characterizeC. elegansneural activity and behavior, the roles of each individual neuron and the compositional mechanisms of all their interactions are still not completely known. In particular, there is evidence thatC. elegansneurons perform changing roles over time, in different behavioral contexts, etc.; however, existing stationary anatomical and functional connectivity can average across time and obfuscate the nonstationary nature of the neural dynamics. We contribute to these efforts by leveraging recent advances in decomposed linear dynamical systems (dLDS) models. dLDS models neural dynamics in a latent space with a set of linear operators that can be recombined and reused over time, enabling the discovery of multiple parallel neural processes on different timescales. We leverage the ability to identify reused patterns of dynamical neural interactions, which we call “dynamical connectivity,” to 1) identify contextually dependent roles of neurons; 2) discover the underlying variability of neural representations even under discrete behaviors; 3) quantify differences between anatomical, functional, and dynamical connectivity; and 4) learn a single aligned latent space underlying multiple individual worms’ activity. These results highlight the importance of defining a neuron’s functions not solely by its internal activity or place in a time-averaged network, but by its evolving interactions across context-dependent circuits.
Real-World Effectiveness of Deltamethrin-Clothianidin (FLUDORA FUSION) in Indoor Residual Spraying in Sub-Saharan Africa: A Systematic Review Protocol
Authors: Ocan Moses , Loyce Nakalembe , Ojiambo Kevin Ouma , Kinalwa Geofrey , Kinengyere Alison A. , Nsobya Sam , Arinaitwe Emmanuel , Mawejje Henry 
Published: June 2024

ABSTRACTBackgroundIndoor residual spraying (IRS) is a core insecticide-based vector control tool employed in most malaria-affected settings globally. However, mosquito vectors have developed resistance to nearly all the insecticides currently used in IRS. This has necessitated a transition to new classes of insecticides from mostly using Dichlorodiphenyltrichloroethane (DDT) and pyrethroids from 1997 to 2010, to carbamates from 2011 and organophosphates from 2013. In addition, other vector control measures like the use of long-lasting insecticide-treated bed nets (LLINs) have also been employed for malaria control. Despite the implementation of these mosquito vector control interventions, malaria remains a disease of public health concern especially in sub-Saharan Africa which bears over 90% of the disease burden. This review will thus collate evidence on the effectiveness of IRS for malaria control in sub-Saharan Africa.Methods and analysisThe systematic review will be done followinga prioricriteria developed using PRISMA guidelines. Articles will be obtained through a search of Medline via PubMed, Scopus, and Embase databases. The Mesh terms and Boolean operators (“AND,” “OR”) will be used in the article search. Additionally, websites of malaria research institutions will be searched. Article search will be done by two independent librarians (AAK and RS). All identified articles will be transferred to Epi-reviewer v6.15.1.0 software. Article screening and data abstraction will be done in duplicate by four reviewers (KO, LN, GK and MO) and any further disagreements will be resolved through discussion and consensus. Data analysis will be done using STATAv17.0. Heterogeneity in the articles will be assessed using the I2statistic. Publication bias will be assessed using a funnel plot.ResultsThe findings of this review will help generate evidence on the effectiveness of indoor residual spraying using WHO pre-qualified insecticides in malaria control in sub-Saharan Africa.This protocol was registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) registration number CRD42024517119
A melancholy machine: simulated synapse loss induces depression-like behaviors in deep reinforcement learning
Authors: Chalmers Eric , Duarte Santina , Al-Hejji Xena , Devoe Daniel , Gruber Aaron , McDonald Robert 
Published: June 2024

AbstractDeep Reinforcement Learning is a branch of artificial intelligence that uses artificial neural networks to model reward-based learning as it occurs in biological agents. Here we modify a Deep Reinforcement Learning approach by imposing a suppressive effect on the connections between neurons in the artificial network - simulating the effect of dendritic spine loss as observed in major depressive disorder (MDD). Surprisingly, this simulated spine loss is sufficient to induce a variety of MDD-like behaviors in the artificially intelligent agent, including anhedonia, increased temporal discounting, avoidance, and an altered exploration/exploitation balance. Furthermore, simulating alternative and longstanding reward-processing-centric conceptions of MDD (dysfunction of the dopamine system, altered reward discounting, context-dependent learning rates, increased exploration) does not produce the same range of MDD-like behaviors. These results support a conceptual model of MDD as a reduction of brain connectivity (and thus information-processing capacity) rather than an imbalance in monoamines - though the computational model suggests a possible explanation for the dysfunction of dopamine systems in MDD. Reversing the spine-loss effect in our computational MDD model can lead to rescue of rewarding behavior under some conditions. This supports the search for treatments that increase plasticity and synaptogenesis, and the model suggests some implications for their effective administration.Significance statementSimulating dendritic spine loss in a deep reinforcement learning agent causes the agent to exhibit a surprising range of depression-like behaviors. Simulating spine restoration allows rewarding behavior to be re-learned. This computational model sees Major Depressive Disorder as a reversible loss of brain capacity, providing some insights on pathology and treatment.
Sex Differences in Morphine Sensitivity of Neuroligin-3 Knockout Mice
Authors: Brandner Dieter D. , Mashal Mohammed A. , Grissom Nicola M. , Rothwell Patrick E. 
Published: June 2024

ABSTRACTSex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical research favoring analysis of male subjects, and the exclusion of female subjects. For example, studies of male mice carrying autism-associated mutations in neuroligin-3 are over-represented in the literature, including our own prior work showing diminished responses to chronic morphine exposure in male neuroligin-3 knockout mice. We therefore studied how constitutive and conditional genetic knockout of neuroligin-3 affects morphine sensitivity of female mice. In contrast to male mice, female neuroligin-3 knockout mice showed normal psychomotor sensitization after chronic morphine exposure. However, in the absence of neuroligin-3 expression, both female and male mice show a similar change in the topography of locomotor stimulation produced by morphine. Conditional genetic deletion of neuroligin-3 from dopamine neurons increased the locomotor response of female mice to high doses of morphine, contrasting with the decrease in psychomotor sensitization caused by the same manipulation in male mice. Together, our data reveal that knockout of neuroligin-3 has both common and distinct effects on morphine sensitivity in female and male mice. These results also support the notion that female sex can confer resilience against the impact of autism-associated gene variants.
Endocytic adaptor AP-2 maintains Purkinje cell function by balancing cerebellar parallel and climbing fiber synapses
Authors: Tolve M. , Tutas J. , Özer- Yildiz E. , Klein I. , Koletsu E , Petzold A. , Liebsch F. , Silverman Q. , Overhoff M. , Schwarz G. , Korotkova T. , Valtcheva S. , Gatto G. , Kononenko NL 
Published: June 2024

AbstractThe selective loss of cerebellar Purkinje cells is a hallmark of various neurodegenerative movement disorders, yet the precise mechanism driving their degeneration remains enigmatic. Here, we show that the endocytic adaptor protein complex 2 (AP-2) is essential for the survival of Purkinje cells. Employing a multidisciplinary approach encompassing mouse genetics, viral tracing, ex vivo calcium imaging, and kinematic analysis, we demonstrate that mice lacking the µ-subunit of AP-2 in cerebellar Purkinje cells exhibit early-onset ataxia associated with progressive Purkinje cell degeneration. Importantly, we uncover that synaptic input dysfunctions, characterized by a predominance of parallel fiber (PF) over climbing fiber (CF) synapses, precede Purkinje cell loss. Mechanistically, we find that AP-2 localizes to Purkinje cell dendrites, where it interacts with the PF synapse-enriched protein GRID2IP. The loss of AP-2 results in proteasome-dependent degradation of GRID2IP and accumulation of the glutamate δ2 receptor (GLURδ2) in distal Purkinje cell dendrites, leading to an excess of PF synapses while CF synapses are drastically reduced. The overrepresentation of PF synaptic input induces Purkinje cell hyperexcitation, which can be alleviated by enhancing synaptic glutamate clearance using the antibiotic ceftriaxone. Our findings demonstrate the critical role of AP-2 in preventing motor gait dysfunctions by regulating GRID2IP levels in Purkinje cells, thereby preserving the equilibrium of PF and CF synaptic inputs in a cell-autonomous manner.
Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement
Authors: Vierkant Valerie , Xie Xueyi , Huang Zhenbo , He Lian , Bancroft Eric , Wang Xuehua , Srinivisan Rahul , Zhou Yubin , Wang Jun 
Published: June 2024

ABSTRACTBackgroundAlcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another.MethodsUsing FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant-self administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations.ResultsWe found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement.ConclusionsOur findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.
Generalized cue reactivity in dopamine neurons after opioids
Authors: Lehmann Collin M. , Miller Nora E. , Nair Varun S. , Costa Kauê M. , Schoenbaum Geoffrey , Moussawi Khaled 
Published: June 2024

AbstractCue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. The leading hypothesis is that dopamine release by addictive drugs represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation compared to non-drug reward alternatives. However, this hypothesis has not been directly tested. Here we developed Pavlovian and operant procedures to measure firing responses, within the same dopamine neurons, to drug versus natural reward cues, which we found to be similarly enhanced compared to cues predicting natural rewards in drug-naïve controls. This enhancement was associated with increased behavioral reactivity to the drug cue, suggesting that dopamine release is still critical to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting new models of dopaminergic function in drug addiction, and provide critical insights into the neurobiology of cue reactivity with potential implications for relapse prevention.
Stimulus-specificity of surround-induced responses in primary visual cortex
Authors: Cuevas Nisa , Sotomayor-Gómez Boris , Tzanou Athanasia , Broggini Ana , Uran Cem , Vinck Martin 
Published: June 2024

AbstractRecent studies in mice challenge the traditional notion of the V1 receptive field (RF) showing increases in V1 firing rates for stimuli presented in the surround, in the absence of a visual input into the classical RF. While this effect has been interpreted as a prediction of the occluded content or a prediction error, an alternative explanation is that it reflects the representation of the uniform achromatic (gray) surface itself. To study this, we systematically investigated the dependence of V1 rate increases on the properties of distal surround stimuli. We recorded V1 and LGN neurons using Neuropixels in awake mice and demonstrated surround-induced responses in V1. That is, V1 firing rates increase by presenting a grating stimulus in the distal surround, while the RF is covered by a large gray patch up to 90° of diameter. LGN firing rates decreased for the same stimuli. V1 response latencies showed a systematic increase with the size of the gray patch. Surround-induced responses did not require spatial continuity or motion coherence of the surround stimulus and generalized to noisy textures and black/white luminance surfaces. Responses to black/white surfaces on a gray background had a similar magnitude and response latency as surround-induced responses with a black/white background. Based on these findings, we suggest that surround-induced responses primarily reflect the representation of the achromatic surface itself, which can contribute to image segmentation.
Rearrangements and accelerated mutation rates on Dendrodorididae mitogenomes rumble their evolution
Authors: Galià-Camps Carles , Schell Tilman , Enguídanos Alba , Pegueroles Cinta , Arnedo Miquel , Ballesteros Manuel , Valdés Ángel , Greve Carola 
Published: June 2024

ABSTRACTThe systematics of the family Dendrodorididae poses a challenge to evolutionary biologists, as their mitochondrial and nuclear markers provide contradictory phylogenetic signals. Nuclear pseudogenes or exogenous contamination are hypothesized to cause the molecular discordance. However, these hypotheses have not been tested. We used genomic data from seven Dendrodorididae species to investigate the evolution of this family. Two mitogenomes displayed a novel structural rearrangement in nudibranchs, involving the translocation of three collinear genes and five surrounding tRNAs. Additionally, we found numerous mitogenomic regions with non-synonymous mutations and multiple indels in both coding and ribosomal genes. Protein modeling resulted in similar structures, suggesting that functionality is conserved. Phylogenies using mitogenomic data confirmed a specific clade membership for the rearranged mitogenomes. The incorporation of nuclear data did not fully resolve the systematic relationships of Dendrodorididae, acknowledging the evolutionary complexity of this group. The present study provides novel evidence on sudden molecular changes in mitogenomes, and highlights the relevance of using genomic data to unveil rare evolutionary processes, which is critical for understanding evolution of neglected taxa.
Seasonal niche overlap of diverse facultative antagonistic bacteria of diatoms in a productive coastal ecosystem
Authors: Branscombe Laura , Roberts Cordelia , Widdicombe Claire , Swink Courtney , Wilson William H. , Cunliffe Michael , Helliwell Katherine 
Published: June 2024

AbstractBiotic interactions between microbes underpin marine ecosystem health, governing the flux of carbon and other nutrients in the ocean. However, studying aquatic microbial interactions is challenging. Model systems can provide in depth understanding of the mechanisms driving such associations. Yet, insights of the prevalence and co-occurrence dynamics of laboratory model systems in natural ecosystems remain limited. By leveraging 16S and 18S metabarcoding combined with phylogenetic analysis, we assessed the environmental presence of facultative bacterial pathogens of one of the most globally abundant phytoplankton groups, the diatoms. Sampling microbial assemblages in a productive coastal ecosystem over the course of an annual cycle, we detected multiple algicidal bacteria that frequently exhibited overlapping co-occurrences. Together, these bacteria positively correlated with members of the potentially toxic genusPseudo-nitzchia, as well as temperature. Our study indicates that antagonistic bacteria occupy shared temporal niches and demonstrates the need to consider their cumulative impacts on diatom population health, including in future ocean conditions.
Uncoupling the CRMP2-CaV2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model
Authors: Allen Heather N. , Hestehave Sara , Duran Paz , Nelson Tyler S. , Khanna Rajesh 
Published: June 2024

AbstractOsteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple FDA-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics-invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. We have identified a key regulator of CaV2.2 channels, collapsing response mediator protein 2 (CRMP2), that allows us to indirectly regulate CaV2.2 expression and function. We developed a peptidomimetic modulator of CRMP2, CBD3063, that effectively reverses neuropathic and inflammatory pain without negative side effects by reducing membrane expression of CaV2.2. Using a rodent model of OA, we demonstrate the intraperitoneal administration of CBD3063 alleviates both evoked and non-evoked behavioral hallmarks of OA pain. Further, we reveal that CBD3063 reduces OA-induced increased neural activity in the parabrachial nucleus, a key supraspinal site modulating the pain experience. Together, these studies suggest CBD3063 is an effective analgesic for OA pain.
Recycling Materials for Sustainable DNA Origami Manufacturing
Authors: Neuhoff Michael J. , Wang Yuchen , Vantangoli Nicholas J. , Poirier Michael G. , Castro Carlos E. , Pfeifer Wolfgang G. 
Published: June 2024

AbstractDNA origami nanotechnology has great potential in multiple fields including biomedical, biophysical, and nanofabrication applications. However, current production pipelines lead to single-use devices incorporating a small fraction of initial reactants, resulting in a wasteful manufacturing process. Here, we introduce two complementary approaches to overcome these limitations by recycling the strand components of DNA origami nanostructures (DONs). We demonstrate reprogramming entire DONs into new devices, re-using scaffold strands. We validate this approach by reprogramming DONs with complex geometries into each other, using their distinct geometries to verify successful scaffold recycling. We reprogram one DON into a dynamic structure and show both pristine and recycled structures display similar properties. Second, we demonstrate the recovery of excess staple strands post-assembly and fold DONs with these recycled strands, showing these structures exhibit the expected geometry and dynamic properties. Finally, we demonstrate the combination of both approaches, successfully fabricating DONs solely from recycled DNA components.
Social learning of navigational routes in tandem running acorn ants (Temnothorax nylanderi)
Authors: Colomer-Vilaplana Aina , Williams Tara , Glaser Simone M. , Grüter Christoph 
Published: June 2024

AbstractTandem running in ants is a form of social learning that involves an informed leader guiding a naïve nestmate to a valuable resource, such as a nest site or a food source. Little is currently known about what tandem followers learn and how socially acquired navigational information affects future trips. While some studies suggest that tandem followers learn the resource position but not the route taken by the tandem pair to reach the resource, more recent evidence contradicts this view. We studied tandem running in foraging acorn antsTemnothorax nylanderiand provide evidence that tandem followers socially learn routes from their leaders and later use these routes when travelling between their nest and a food source. Followers that became tandem leaders themselves then guided their follower along the same routes in 90% of tandem runs, demonstrating that navigational information can spread in a forager population through sequential social learning. Ants increased their travelling speed, but not path straightness over successive trips. We also found that ants needed less time on subsequent trips if they experienced longer-lasting tandem runs, suggesting that longer lasting tandem runs allow followers to learn routes more efficiently. Adding visual cues did not affect most of the quantified variables, and we currently know little about the cues used byT. nylanderiduring navigation. We discuss how the visual environment inhabited by different species might affect the importance of route learning during tandem running.
Evaluation of the adaptability of cassava genotypes in three different agro-ecological zones of Gabon
Authors: Effa Effa Branly Wilfrid , Moto Rostand Abaga , Zeh Nguema Yves Landry , Ifada Anaclé , Demikoyo Kanghou Dick Sadler , Guibinga Stéphane Mibemu , Akoubou Sidoine , Ngouang Louis Clotaire 
Published: June 2024

AbstractCassava is a staple food in over twenty African countries, including Gabon. However, current production cannot meet the needs of the Gabonese people. Studies are being carried out to find ways of increasing national production throughout the country. Our study of sixteen cassava genotypes planted in different agro-ecological zones of Gabon focuses on three quantitative variables: number of lobes per leaf, petiole length and plant height at the vegetative stage. This study was carried out to see which introduced cassava genotypes were adapted to environments with different rainfall levels.