bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning Conjunctive Representations
Authors: Pettersen Markus , Rogge Frederik , Lepperød Mikkel Elle 
Published: May 2024

AbstractHippocampal place cells are known for their spatially selective firing patterns, which has led to the suggestion that they encode an animal’s location. However, place cells also respond to contextual cues, such as smell. Furthermore, they have the ability to remap, wherein the firing fields and rates of cells change in response to environmental changes. How place cell responses emerge, and how these representations remap is not fully understood. In this work, we propose a similarity-based objective function that translates proximity in space, to proximity in representation. We show that a neural network trained to minimize the proposed objective learns place-like representations. We also show that the proposed objective is trivially extended to include other sources of information, such as context information, in the same way. When trained to encode multiple contexts, networks learn distinct representations, exhibiting remapping behaviors between contexts. The proposed objective is invariant to orthogonal transformations. Such transformations of the original trained representation (e.g. rotations), therefore yield new representations distinct from the original, without explicit relearning, akin to remapping. Our findings shed new light on the formation and encoding properties of place cells, and also demonstrate an interesting case of representational reuse.
A thalamic perspective of (un)consciousness in pharmacological and pathological states in humans
Authors: Szocs Dorottya , Lyu Dian , Luppi Andrea I. , Coppola Peter , Woodrow Rebecca , Williams Guy B. , Allanson Judith , Pickard John D. , Owen Adrian M. , Naci Lorina , Menon David K. , Stamatakis Emmanuel A. 
Published: May 2024

SummaryCurrently, there is substantial ongoing discussion around the functional role of the thalamus in consciousness. What is missing in the literature, however, is a systematic investigation of the relevance of specific thalamic nuclei in pharmacologically and pathologically altered states of consciousness in humans. Using functional neuroimaging in both healthy anaesthetised volunteers and patients with disorders of consciousness (DOC), we sought to identify which specific thalamic subregions in both cohorts may be differentially significant for loss of consciousness. Our findings revealed that the pulvinar (Pu) and ventral-latero-ventral (VLV) nuclei, in anaesthesia, and the VLV, in DOC, had distinct functional connectivity patterns related to the default mode and somatomotor networks. Remarkably, among all nuclei, the Pu was found to have the strongest functional connectivity change with anaesthetic-induced loss of consciousness, while in DOC patients, we found the VLV revealed the strongest connectivity change in comparison with healthy controls. Furthermore, we provide evidence that this neural connectivity biomarker in patients also mirrors the changes observed at the behavioural level, which could have clinical implications for targeted deep brain stimulation in therapy for DOC.
Microbiota in the ptarmigan intestine - an Inuit delicacy and its potential in popular cuisine
Authors: Bjørnsen Mads Bjørn , Valerón Nabila Rodríguez , Vásquez Diego Prado , Velasco Esther Merino , Hansen Anders Johannes , Hauptmann Aviaja Lyberth 
Published: May 2024

AbstractThe consumption of prey intestines and their content, known as gastrophagy, is well-documented among Arctic Indigenous peoples, particularly Inuit. In Greenland, Inuit consume intestines from various animals, including the ptarmigan, a small herbivorous grouse bird. While gastrophagy provides the potential to transfer a large number of intestinal microorganisms from prey to predator, including to the human gut, its microbial implications remain to be investigated. This study addresses this gap by investigating the microbial composition of the Greenlandic rock ptarmigan’s gastrointestinal tract by analyzing the crop, stomach, and intestines while also comparing it with the microbiota found in garum, a fermented sauce made from ptarmigan meat and intestines. Through 16S rRNA gene sequencing, we assessed whether garum made from ptarmigan intestines provides access to microbial diversity otherwise only accessible through gastrophagy. Our findings reveal that garum made from ptarmigan intestines displayed distinct flavors and microbial composition similar to that found in the ptarmigan gut and intestines, highlighting the potential role of fermented products in mediating food microbial diversity associated with Indigenous food practices. Furthermore, our study underscores the broader importance of understanding microbial diversity in different food systems, particularly in the context of shifting dietary patterns and concerns about diminishing food microbial diversity. By elucidating the microbial richness gained through gastrophagy this research contributes to a deeper understanding of traditional and Indigenous foodways and their implications for human gut health.
Diverse perceptual biases emerge from Hebbian plasticity in a recurrent neural network model
Authors: Schönsberg Francesca , Giana Davide , Chopra Yukti , Diamond Mathew , Goldt Sebastian 
Published: May 2024

AbstractPerceptual biases offer a glimpse into how the brain processes sensory stimuli. While psycho-physics has uncovered systematic biases such as contraction (stored information shifts towards a central tendency), and repulsion (the current percept shifts away from recent percepts), a unifying neural network model for how such seemingly distinct biases emerge from learning is lacking. Here, we show that both contractive and repulsive biases emerge from continuous Hebbian plasticity in a single recurrent neural network. We test the model in four different datasets, two sensory modalities and three experimental paradigms: two working memory tasks, a reference memory task, and a novel “one-back task” that we designed to test the robustness of the model. We find excellent agreement between model predictions and experimental data without fine-tuning the model to any particular paradigm. These results show that apparently contradictory perceptual biases can in fact emerge from a simple local learning rule in a single recurrent region of the brain.
Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis
Authors: Blackwell Amanda Mixon , Jami-Alahmadi Yasaman , Nasamu Armiyaw S. , Kudo Shota , Senoo Akinobu , Slam Celine , Tsumoto Kouhei , Wohlschlegel James A. , Caaveiro Jose M. M. , Goldberg Daniel E. , Sigala Paul A. 
Published: May 2024

ABSTRACTMalaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection,Plasmodium falciparumparasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin. Parasites also express a divergent heme oxygenase (HO)-like protein (PfHO) that lacks key active-site residues and has lost canonical HO activity. The cellular role of this unusual protein that underpins its retention by parasites has been unknown. To unravel PfHO function, we first determined a 2.8 Å-resolution X-ray structure that revealed a highly α-helical fold indicative of distant HO homology. Localization studies unveiled PfHO targeting to the apicoplast organelle, where it is imported and undergoes N-terminal processing but retains most of the electropositive transit peptide. We observed that conditional knockdown of PfHO was lethal to parasites, which died from defective apicoplast biogenesis and impaired isoprenoid-precursor synthesis. Complementation and molecular-interaction studies revealed an essential role for the electropositive N-terminus of PfHO, which selectively associates with the apicoplast genome and enzymes involved in nucleic acid metabolism and gene expression. PfHO knockdown resulted in a specific deficiency in levels of apicoplast-encoded RNA but not DNA. These studies reveal an essential function for PfHO in apicoplast maintenance and suggest thatPlasmodiumrepurposed the conserved HO scaffold from its canonical heme-degrading function in the ancestral chloroplast to fulfill a critical adaptive role in organelle gene expression.
Carbapenem-induced β-lactamase-isoform expression trends inAcinetobacter baumannii
Authors: Benin Bogdan M. , Hillyer Trae , Aguirre Noah , Sham Yuk Yin , Willard Belinda , Shin Woo Shik 
Published: May 2024

AbstractCarbapenem-resistantAcinetobacter baumannii(CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a >50% fatality rate. Although several resistance mechanisms are understood, the appearance of these mutations is generally considered stochastic. Recent reports have, however, begun to challenge this assumption. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be somewhat non-stochastic. Specifically, several minor AmpC/ADC β-lactamase-isoforms were found to exhibit both dose- and carbapenem-dependent expression, suggesting the possibility of non-stochastic mutations. Additionally, these also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe somewhat antibiotic-directed by a hitherto unknown mechanism and further investigation may lead to new strategies for mitigating antibiotic resistance.TeaserThe emergence of antibiotic-resistant β-lactamase proteins from mutations may exhibit patterns based on specific antibiotics.
The pioneer transcription factor Zelda facilitates the exit from regeneration and restoration of patterning inDrosophila
Authors: Bose Anish , Schuster Keaton , Kodali Chandril , Sonam Surabhi , Smith-Bolton Rachel 
Published: May 2024

ABSTRACTFor a damaged tissue to regenerate, the injured site must repair the wound, proliferate, and restore the correct patterning and cell types. We found that Zelda, a pioneer transcription factor largely known for its role in embryonic zygotic genome activation, is dispensable for normal wing development but crucial for wing disc patterning during regeneration. Impairing Zelda function during disc regeneration resulted in adult wings with a plethora of cell fate errors, affecting the veins, margins, and posterior compartment identity. Using CUT&RUN, we identified and validated targets of Zelda including the cell fate genescut, Deltaandachaete, which failed to return to their normal expression patterns upon loss of Zelda. In addition, Zelda controls expression of factors previously established to preserve cell fate during regeneration liketaranisandosa,which stabilizesengrailedexpression during regeneration, thereby preserving posterior identity. Finally, Zelda ensures proper expression of the integrins encoded bymultiple edematous wingsandmyospheroidduring regeneration to prevent blisters in the resuting adult wing. Thus, Zelda is crucial for maintaining cell fate and structural architecture of the regenerating tissue.
Large-scale control over collective cell migration using light-controlled epidermal growth factor receptors
Authors: Suh Kevin , Thornton Richard , Farahani Payam E. , Cohen Daniel , Toettcher Jared 
Published: May 2024

AbstractReceptor tyrosine kinases (RTKs) are thought to play key roles in coordinating cell movement at single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggested these responses may be amenable to engineering-based control for sculpting tissue shape and function. Here, we report that a light-controlled EGF receptor (OptoEGFR) can be deployed in epithelial cell lines for precise, programmable control of long-range tissue movements. We show that in OptoEGFR-expressing tissues, light can drive millimeter-scale cell rearrangements to densify interior regions or produce rapid outgrowth at tissue edges. Light-controlled tissue movements are driven primarily by PI 3-kinase signaling, rather than diffusible signals, tissue contractility, or ERK kinase signaling as seen in other RTK-driven migration contexts. Our study suggests that synthetic, light-controlled RTKs could serve as a powerful platform for controlling cell positions and densities for diverse applications including wound healing and tissue morphogenesis.
Comparing Methods for Deriving the Auditory Brainstem Response to Continuous Speech in Human Listeners
Authors: Shan Tong , Maddox Ross K. 
Published: May 2024

AbstractSeveral tools have recently been developed to derive the Auditory Brainstem Response (ABR) from continuous natural speech, facilitating investigation into subcortical encoding of speech. These tools rely on deconvolution, which models the subcortical auditory pathway as a linear system, where a nonlinearly processed stimulus is taken as the input (i.e., regressor), the electroencephalogram (EEG) data as the output, and the ABR as the impulse response deconvolved from the recorded EEG and the regressor. In this study, we analyzed EEG recordings from subjects listening to both unaltered natural speech and synthesized “peaky speech.” We compared the derived ABRs using three regressors: the half-wave rectified stimulus (HWR) from Maddox and Lee (2018), the glottal pulse train (GP) from Polonenko and Maddox (2021), and the auditory nerve modeled response (ANM) from Shan et al. (2024). Our evaluation focused on the fidelity, efficiency, and practicality of each method in different scenarios. The results indicate that the ANM regressor for both peaky and unaltered speech and the GP regressor for peaky speech provided the best performance, whereas the HWR regressor demonstrated relatively poorer performance. The findings in this study will guide future research in selecting the most appropriate paradigm for ABR derivation from continuous, naturalistic speech.
Loss of the MeCP2 gene in parvalbumin interneurons leads to an inhibitory deficit in the amygdala and affects its functional connectivity
Authors: Liiwand Maj , Haikonen Joni , Kokinovic Bojana , Molchanova Svetlana M. , Aitta-aho Teemu , Lauri Sari E. , Ryazantseva Maria 
Published: May 2024

AbstractBackgroundMECP2gene is located in the X-chromosome and encodes a methyl-CpG-binding protein involved in transcription regulation. The loss-of-function mutation of theMECP2gene, leads to severe neurodevelopmental syndrome, Rett syndrome. Clinical picture of Rett syndrome includes, among other symptoms, social deficits and heightened anxiety. The amygdala is involved in the regulation of social behavior as well as fear and anxiety. Here, we investigated the effect of theMeCP2gene ablation in the parvalbumin interneurons on the microcircuit and functional connectivity of the amygdala.MethodsMales with conditional knock-out of theMeCP2gene in the parvalbumin interneurons were used as a genetic mouse model of MeCP2 loss in parvalbumin interneurons. Littermates with the intact gene were used as controls. Ex-vivo brain slice electrophysiology, combined with pharmacology and optogenetics, was used to characterize microcircuits within the lateral amygdala. Synaptic currents and excitability of parvalbumin interneurons and principal neurons were analyzed by a whole-cell patch clamp. In-vivo functional ultrasound was used to visualize the connectivity within the amygdala–ventral hippocampus–prefrontal cortex triad.ResultsLoss ofMeCP2in parvalbumin interneurons significantly reduced the GABAergic synaptic input to the principal neurons in the lateral amygdala. The decreased inhibitory drive was accompanied by an increase in the excitability of principal neurons in the lateral amygdala. The in vivo functional connectivity of the amygdala-ventral hippocampus and amygdala-prefrontal cortex was significantly reduced in conditional knock-outs compared to their littermates with the intact gene in the X chromosome.ConclusionsOur study characterized the consequences ofMeCP2gene loss in the parvalbumin interneurons on the amygdala connectivity and microcircuit and provided evidence supporting the previous findings on the role of interneurons in the functional deficit observed in animal models withMeCP2loss.
Cortical determinants of loudness perception and auditory hypersensitivity
Authors: Clayton Kameron K , McGill Matthew , Awwad Bshara , Stecyk Kamryn S , Kremer Caroline , Skerleva Desislava , Narayanan Divya P , Zhu Jennifer , Hancock Kenneth E , Kujawa Sharon G , Kozin Elliott D , Polley Daniel B 
Published: May 2024

SummaryParvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were “sticky”, such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.
Disrupted Hippocampal Theta-Gamma Coupling and Spike-Field Coherence Following Experimental Traumatic Brain Injury
Authors: Adam Christopher D. , Mirzakhalili Ehsan , Gagnon Kimberly G. , Cottone Carlo , Arena John D. , Ulyanova Alexandra V. , Johnson Victoria E. , Wolf John A. 
Published: May 2024

SUMMARYTraumatic brain injury (TBI) often results in persistent learning and memory deficits, likely due to disrupted hippocampal circuitry underlying these processes. Precise temporal control of hippocampal neuronal activity is important for memory encoding and retrieval and is supported by oscillations that dynamically organize single unit firing. Using high-density laminar electrophysiology, we discovered a loss of oscillatory power across CA1 lamina, with a profound, layer-specific reduction in theta-gamma phase amplitude coupling in injured rats. Interneurons from injured animals were less strongly entrained to theta and gamma oscillations, suggesting a mechanism for the loss of coupling, while pyramidal cells were entrained to a later phase of theta. During quiet immobility, we report decreased ripple amplitudes from injured animals during sharp-wave ripple events. These results reveal deficits in information encoding and retrieval schemes essential to cognition that likely underlie TBI-associated learning and memory impairments, and elucidate potential targets for future neuromodulation therapies.Abstract Figure
Red light responsive Cre recombinase for bacterial optogenetics
Authors: Jafarbeglou Fereshteh , Dunlop Mary J. 
Published: May 2024

AbstractOptogenetic tools have been used in a wide range of microbial engineering applications that benefit from the tunable, spatiotemporal control that light affords. However, the majority of current optogenetic constructs for bacteria respond to blue light, limiting the potential for multichromatic control. In addition, other wavelengths offer potential benefits over blue light, including improved penetration of dense cultures and reduced potential for toxicity. In this study, we introduce OptoCre-REDMAP, a red light inducible Cre recombinase system inEscherichia coli. This system harnesses the plant photoreceptors PhyA and FHY1 and a split version of Cre recombinase to achieve precise control over gene expression and DNA excision. We optimized the design by modifying the start codon of Cre and characterized the impact of different levels of induction to find conditions that produced minimal basal expression in the dark and induced full activation within four hours of red light exposure. We characterized the system’s sensitivity to ambient light, red light intensity, and exposure time, finding OptoCre-REDMAP to be reliable and flexible across a range of conditions. In co-culture experiments with OptoCre-REDMAP and the blue light responsive OptoCre-VVD, we found that the systems responded orthogonally to red and blue light inputs. Direct comparisons between red and blue light induction with OptoCre-REDMAP and OptoCre-VVD demonstrated the superior penetration properties of red light. OptoCre-REDMAP’s robust and selective response to red light makes it suitable for advanced synthetic biology applications, particularly those requiring precise multichromatic control.
TheIroquois(Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
Authors: Catela Catarina , Assimacopoulos Stavroula , Chen Yihan , Tsioras Konstantinos , Feng Weidong , Kratsios Paschalis 
Published: May 2024

AbstractTheIroquois (Iro/Irx)homeobox genes encode transcription factors with fundamental roles in animal development. Despite their link to various congenital conditions in humans, our understanding ofIro/Irxgene expression, function, and regulation remains incomplete. Here, we conducted a systematic expression analysis of all six mouseIrxgenes in the embryonic spinal cord. We found fiveIrxgenes (Irx1, Irx2, Irx3, Irx5,andIrx6) to be confined mostly to ventral spinal domains, offering new molecular markers for specific groups of post-mitotic motor neurons (MNs). Further, we engineeredIrx2, Irx5,andIrx6mouse mutants and uncovered essential but distinct roles forIrx2andIrx6in MN development. Last, we found that the highly conserved regulators of MN development across species, the HOX proteins, directly controlIrxgene expression both in mouse andC. elegansMNs, critically expanding the repertoire of HOX target genes in the developing nervous system. Altogether, our study provides important insights intoIro/Irxexpression and function in the developing spinal cord, and uncovers an ancient gene regulatory relationship between HOX andIro/Irxgenes.