bluuebunny/crossref_metadata_2025_split huggingface dataset:
CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research
Authors: Merrill Kris , Muller Leah , Beim Jordan A. , Hehrmann Phillipp , Swan Dean , Alfsmann Daniel , Spahr Tony , Litvak Leo , Oxenham Andrew J. , Tward Aaron D. 
Published: December 2023

AbstractObjectiveCochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale.Study DesignQuasi-experimentalSettingVirtualMethodsCompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform’s flexibility in experimental design and its wide range of applications in sound processing research.ResultsPerformance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com).ConclusionThe CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.
Sunfish as zooplankton control agents to improve yields of wastewater-cultivated algae
Authors: Rakowski Chase J. , Leibold Mathew A. , Manning Schonna R. 
Published: December 2023

AbstractWastewater algal cultivation (WAC) in outdoor raceway ponds is a promising means of removing polluting nutrients from water while producing biomass feedstock for products like fertilizer or biofuel. However, algal cultivation in open ponds is often plagued by underproduction due to contamination by zooplankton. The use of biological controls, i.e., natural predators to control zooplankton, was evaluated as a potential low-cost solution in this study. Eighteen pilot-scale raceway ponds were inoculated with cultured algae and naturally-occurring zooplankton; bluegill sunfish (Lepomis macrochirus) were tested as biological control agents to suppress zooplankton. We installed cages in the ponds to protect the fish from the paddlewheels and control the area the fish could access. The cage either surrounded the paddlewheel – in which case the fish had access to the remaining area – or the cage was opposite the paddlewheel, in which case the fish had access to the smaller area inside the cage. We also implemented fishless controls. After 19 days, ponds with cages surrounding the paddlewheel had 93% more zooplankton, but the fish had reduced zooplankton by 89% on average across cage treatments. Cage placement did not affect algal biomass, but ponds with fish had 45% higher algal dry weight and 84% higher algal biovolume. However, no differences in nutrient levels were recorded among treatments after 19 days. We concluded hardy zooplanktivorous fish represent a promising means of boosting algal production in WAC, although further research is needed to determine whether the change in algal biomass could eventually translate to improved nutrient removal.
Decoding the Epigenetics and Chromatin Loop Dynamics of Androgen Receptor-Mediated Transcription
Authors: Altıntaş Umut Berkay , Seo Ji-Heui , Giambartolomei Claudia , Ozturan Dogancan , Fortunato Brad J. , Nelson Geoffrey M. , Goldman Seth Raphael , Adelman Karen , Hach Faraz , Freedman Matthew L. , Lack Nathan A. 
Published: December 2023

ABSTRACTAndrogen receptor (AR)-mediated transcription plays a critical role in normal prostate development and prostate cancer growth. AR drives gene expression by binding to thousands of cis-regulatory elements (CRE) that loop to hundreds of target promoters. With multiple CREs interacting with a single promoter, it remains unclear how individual AR bound CREs contribute to gene expression. To characterize the involvement of these CREs, we investigated the AR-driven epigenetic and chromosomal chromatin looping changes. We collected a kinetic multiomic dataset comprised of steady-state mRNA, chromatin accessibility, transcription factor binding, histone modifications, chromatin looping, and nascent RNA. Using an integrated regulatory network, we found that AR binding induces sequential changes in the epigenetic features at CREs, independent of gene expression. Further, we showed that binding of AR does not result in a substantial rewiring of chromatin loops, but instead increases the contact frequency of pre-existing loops to target promoters. Our results show that gene expression strongly correlates to the changes in contact frequency. We then proposed and experimentally validated an unbalanced multi-enhancer model where the impact on gene expression of AR-bound enhancers is heterogeneous, and is proportional to their contact frequency with target gene promoters. Overall, these findings provide new insight into AR-mediated gene expression upon acute androgen simulation and develop a mechanistic framework to investigate nuclear receptor mediated perturbations.
Modulators of MAPK pathway activity during filamentous growth inSaccharomyces cerevisiae
Authors: Pujari Atindra N. , Cullen Paul J. 
Published: December 2023

ABSTRACTMitogen-activated protein kinase (MAPK) pathways control the response to intrinsic and extrinsic stimuli. In the budding yeastSaccharomyces cerevisiae, cells undergo filamentous growth, which is regulated by the fMAPK pathway. To better understand the regulation of the fMAPK pathway, a genetic screen was performed to identify spontaneous mutants with elevated activity of an fMAPK-pathway dependent growth reporter (ste4 FUS1-HIS3). In total, 159 mutants were isolated and analyzed by secondary screens for invasive growth by the plate-washing assay, and filament formation by microscopy. Thirty-two mutants were selected for whole-genome sequencing, which identified new alleles in genes encoding known regulators of the fMAPK pathway. These included gain-of-function alleles inSTE11,which encodes the MAPKKK, as well as loss-of-function alleles inKSS1,which encodes the MAP kinase, andRGA1,which encodes a GTPase activating protein (GAP) forCDC42. New alleles in previously identified pathway modulators were also uncovered inALY1, AIM44, RCK2, IRA2, REG1and in genes that regulate protein folding (KAR2), glycosylation (MNN4), and turnover (BLM10). C-terminal truncations in the transcription factor Ste12p were also uncovered that resulted in elevated reporter activity, presumably identifying an inhibitory domain in the C-terminus of the protein. We also show that a wide variety of filamentous growth phenotypes result from mutations in different regulators of the response. The alleles identified here expand the connections surrounding MAPK pathway regulation and reveal new features of proteins that function in the signaling cascade.ARTICLE SUMMARYSignaling pathways control the response to stimuli. In yeast, a signaling (MAPK) pathway controls a fungal behavioral response called filamentous growth. A genetic screen was performed to identify spontaneous mutants that show hyperactivity of a MAPK pathway-dependent reporter. Select mutants were analyzed by whole-genome sequencing. New alleles in known regulatory proteins were identified. A potential inhibitory domain in the C-terminus of the transcription factor Ste12p was also uncovered. Our results indicate that filamentous growth is determined by the combinatorial effects of multiple positive and negative regulatory inputs.
TGM6, a helminth secretory product, mimics TGF-β binding to TβRII to antagonize TGF-β signaling in fibroblasts
Authors: White Stephen E. , Schwartze Tristin A. , Mukundan Ananya , Schoenherr Christina , Singh Shashi P. , van Dinther Maarten , Cunningham Kyle T. , White Madeleine P. J. , Campion Tiffany , Pritchard John , Hinck Cynthia S. , ten Dijke Peter , Inman Gareth , Maizels Rick M. , Hinck Andrew P. 
Published: December 2023

ABSTRACTThe murine helminth parasiteHeligmosomoides polygyrusexpresses a family of proteins structurally related to TGF-β Mimic 1 (TGM1), a secreted five domain protein that activates the TGF-β pathway and converts naïve T lymphocytes to immunosuppressive Tregs. TGM1 signals through the TGF-β type I and type II receptors, TβRI and TβRII, with domains 1-2 and 3 binding TβRI and TβRII, respectively, and domains 4-5 binding CD44, a co-receptor abundant on T cells. TGM6 is a homologue of TGM1 that is co-expressed with TGM1, but lacks domains 1 and 2. Herein, we show that TGM6 binds TβRII through domain 3, but does not bind TβRI, or other type I or type II receptors of the TGF-β family. In TGF-β reporter assays in fibroblasts, TGM6, but not truncated TGM6 lacking domains 4 and 5, potently inhibits TGF-β- and TGM1-induced signaling, consistent with its ability to bind TβRII but not TβRI or other receptors of the TGF-β family. However, TGM6 does not bind CD44 and is unable to inhibit TGF-β and TGM1 signaling in T cells. To understand how TGM6 binds TβRII, the X-ray crystal structure of the TGM6 domain 3 bound to TβRII was determined at 1.4 Å. This showed that TGM6 domain 3 binds TβRII through an interface remarkably similar to the TGF-β:TβRII interface. These results suggest that TGM6 has adapted its domain structure and sequence to mimic TGF-β binding to TβRII and function as a potent TGF-β and TGM1 antagonist in fibroblasts. The coexpression of TGM6, along with the immunosuppressive TGMs that activate the TGF-β pathway, may prevent tissue damage caused by the parasite as it progresses through its life cycle from the intestinal lumen to submucosal tissues and back again.
Electrostatic-driven Interactions Enhance Intratumoral Retention and Antitumor Efficacy of Immune Checkpoint Blockade Antibodies
Authors: Mohanty Rashmi P , Pan Yuting , Lewis Mae M , Soto Melissa , Maier Esther Y , Alzhrani Riyad F , Ghosh Debadyuti 
Published: December 2023

ABSTRACTTumor extracellular matrix (ECM) forms a net negative charged network that interacts with and hinders the transport of molecules partly based on electrostatic interactions. The focus on drug delivery in solid tumors has traditionally been on developing neutral charge coatings to minimize interactions with the ECM for improved transport. In contrast to this prior work, we recently found a cationic peptide that interacted electrostatically with the negatively charged components of the ECM, resulting in enhanced uptake and retention of nanoparticles in tumor ECM and tumor tissue. Based on this previous study, here, we hypothesize that the electrostatically driven interactions of the cationic peptide will improve the binding and retention of immune checkpoint blockade antibodies (ICBs), ultimately enhancing their antitumor immunogenic responses. We prepared peptide antibody (Ab) conjugates by conjugating the cationic peptide to ICBs, anti-cytotoxic T lymphocyte antigen 4 (∝-CTLA4) and anti-programmed cell death ligand-1 (∝-PD-L1) Abs, using copper-free click chemistry. We confirmed an average of 1 – 2 peptides per Ab. The cationic peptide electrostatically interacted with the net negatively charged tumor ECM and improved the binding of the Abs to the tumor ECM without affecting their antigen recognition capacities. Modifying the Abs due to cationic peptide conjugation reduced the systemic exposure of the Abs and did not induce treatment-related toxicities. We quantified a significantly higher population of tumor-infiltrating CD8+T cells and a significant depletion of regulatory T cells in the tumor and tumor-draining lymph nodes upon peptide conjugation, which resulted in a better therapeutic outcome of the ICBs.ONE SENTENCE SUMMARYElectrostatic interaction-based intratumoral retention enhances antitumor responses of immune checkpoint blockade antibodies upon local administration.
Piezo-dependent surveillance of matrix stiffness generates transient cells that repair the basement membrane
Authors: Stricker Aubrie M. , Hutson M. Shane , Page-McCaw Andrea 
Published: December 2023

SummaryBasement membranes are extracellular matrix sheets separating tissue layers and providing mechanical support, and Collagen IV (Col4) is their most abundant protein. Although basement membranes are repaired after damage, little is known about repair, including whether and how damage is detected, what cells repair the damage, and how repair is controlled to avoid fibrosis. Using the intestinal basement membrane of adultDrosophilaas a model, we show that after basement membrane damage, there is a sharp increase in enteroblasts transiently expressing Col4, or “matrix mender” cells. Enteroblast-derived Col4 is specifically required for matrix repair. The increase in matrix mender cells requires the mechanosensitive ion channel Piezo, expressed in intestinal stem cells. Matrix menders are induced by the loss of matrix stiffness, as specifically inhibiting Col4 crosslinking is sufficient for Piezo-dependent induction of matrix mender cells. Our data suggest that epithelial stem cells control basement membrane integrity by monitoring stiffness.
Sleep-Deep-Net learns sleep wake scoring from the end-user and completes each record in their style
Authors: Katsuki Fumi , Spratt Tristan J. , Brown Ritchie E. , Basheer Radhika , Uygun David S. 
Published: December 2023

ABSTRACTSleep-wake scoring is a time-consuming, tedious but essential component of clinical and pre-clinical sleep research. Sleep scoring is even more laborious and challenging in rodents due to the smaller EEG amplitude differences between states and the rapid state transitions which necessitate scoring in shorter epochs. Although many automated rodent sleep scoring methods exist, they do not perform as well when scoring new data sets, especially those which involve changes in the EEG/EMG profile. Thus, manual scoring by expert scorers remains the gold-standard. Here we take a different approach to this problem by using a neural network to accelerate the scoring of expert scorers. Sleep-Deep-Net (SDN) creates a bespoke deep convolution neural network model for individual electroencephalographic or local-field-potential records via transfer learning of GoogleNet, by learning from a small subset of manual scores of each EEG/LFP record as provided by the end-user. SDN then automates scoring of the remainder of the EEG/LFP record. A novel REM scoring correction procedure further enhanced accuracy. SDN reliably scores EEG and LFP data and retains sleep-wake architecture in wild-type mice, in sleep induced by the hypnotic zolpidem, in a mouse model of Alzheimer’s disease and in a genetic knock-down study, when compared to manual scoring. SDN reduced manual scoring time to 1/12. Since SDN uses transfer learning on each independent recording, it is not biased by previously scored existing data sets. Thus, we find SDN performs well when used on signals altered by a drug, disease model or genetic modification.STATEMENT OF SIGNIFICANCESleep medicine is often critically advanced by translational research based onin vivoelectrophysiologic mouse data. A necessary but time-consuming step in this field is scoring epochs of recordings into wakefulness, non-rapid-eye-movement sleep and non-rapid-eye-movement sleep. Despite efforts to automate this, manual scoring remains the gold-standard since automatic methods poorly handle data that is not similar enough to data used during development. Here, we describe a novel automated sleep scoring method that involves retraining a deep-convolution-neural-net capable of computer vision to score sleep-wake patterns after learning from a small set of manual scores within a record. This avoids biasing the model to expect data to be the same as its training set from previous records.
Distinct transcriptional programs define a heterogeneous neuronal ensemble for social interaction
Authors: Walker Hailee , Frost Nicholas A. 
Published: December 2023

AbstractReliable representations of information regarding complex behaviors including social interactions require the coordinated activity of heterogeneous cell types within distributed brain regions. Activity in the medial prefrontal cortex is critical in regulating social behavior, but our understanding of the specific cell types which comprise the social ensemble has been limited by available mouse lines and molecular tagging strategies which rely on the expression of a single marker gene. Here we sought to quantify the heterogeneous neuronal populations which are recruited during social interaction in parallel in a non-biased manner and determine how distinct cell types are differentially active during social interactions. We identify distinct populations of prefrontal neurons activated by social interaction by quantification of immediate early gene (IEG) expression in transcriptomically clustered neurons. This approach revealed variability in the recruitment of different excitatory and inhibitory populations within the medial prefrontal cortex. Furthermore, evaluation of the populations of IEGs recruited following social interaction revealed both cell-type and region-specific transcriptional programs, suggesting that reliance on a single molecular marker is insufficient to quantify activation across all cell types. Our findings provide a comprehensive description of cell-type specific transcriptional programs invoked by social interactions and reveal new insights into the heterogeneous neuronal populations which compose the social ensemble.
Multicellularity and increasing Reynolds number impact on the evolutionary shift in photo-induced ciliary response in Volvocales
Authors: Ueki Noriko , Wakabayashi Ken-ichi 
Published: December 2023

ABSTRACTVolvocales include species with different cell numbers and sizes, reflecting a history of gradual size increase evolution. Unicellular species live in low Reynolds-number (Re) environments where viscous forces dominate, whereas multicellular species live in higherReenvironments with nonnegligible inertial forces. Despite significant changes in the physical environment, during the evolution of multicellularity they maintained photobehaviors (i.e., photoshock and phototactic responses), which allows them to survive under changing light conditions. In this study, we classified photo-induced ciliary responses in Volvocales into four patterns: temporal waveform conversion, no obvious response, pause in ciliary beating, temporal changes in ciliary beating directions. We found that which species exhibit which pattern depends onReassociated with the individual size of each species rather than phylogenetic relationships. These results suggest that species with increased cell numbers acquired their responses adapted to higherRefluid environments.Significance StatementVolvocales green algae include species with various cell numbers and are excellent organisms for studying the evolution of multicellularity. They exhibit photobehaviors by changing the pattern of ciliary beating, which could be categorized into four patterns. We found that the difference in patterns among the organisms is due to the Reynolds number, the ratio of viscous and inertia forces, rather than their phylogenetic relationships. This study indicates that the fluid environment was an important factor in natural selection for behavioral changes in microalgae during evolution. The results link evolution and physics while contributing to the design of micromachines.
Detection of genetically modified organisms using highly multiplexed amplicon sequencing
Authors: Reyes-Avila C. Sarai , Waldvogel Dominique , Pradervand Nicolas , Aubry Sylvain , Croll Daniel 
Published: December 2023

ABSTRACTThe circulation of products based on genetically modified (GM) organisms is highly regulated by some governments having implemented strict rules on the breeding, planting, marketing, labelling, and trading of such products. To ensure compliance, accurate detection methods for GM events are necessary, along with assurance that GM material falls within relevant threshold levels. The increasing complexity and potential of undocumented GM are a growing challenge for genetic screening. In this study, we developed and assessed a highly multiplexed amplicon sequencing assay for the detection of GM events based on a microfluidics platform and next-generation sequencing (NGS). To probe GM events comprehensively, we designed a total of 230 new amplicons to cover flanking, promoter, junction and coding sequences of GM sequences. In addition, we designed and implemented parallel amplification of ribosomal and chloroplast markers to define crop species identity from potentially mixed samples. Using reference GM material of 11 crop species and multiple amplicons, we successfully detected the presence of 10 known modifications per GM event. We also find that reported flanking sequences of GM events may not be all useful for diagnostic. We assessed the assay’s potential to detect GM events in mixed samples as well as in highly diluted DNA. Finally, we performed a prospective search of potentially undocumented GM events in plant material. Our microfluidics-based amplicon GM detection approach fills important gaps in detecting potentially undocumented and complex GM events by recovering a wide range of specific amplicon sequences for evaluation. Integrating highly parallel amplicon assays in GM screening efforts should be an effective complement to aid post-market monitoring and regulatory compliance efforts.
News without the buzz: reading out weak theta rhythms in the hippocampus
Authors: Agarwal Gautam , Lustig Brian , Akera Seiji , Pastalkova Eva , Lee Albert K. , Sommer Friedrich T. 
Published: December 2023

AbstractLocal field potentials (LFPs) reflect the collective dynamics of neural populations, yet their exact relationship to neural codes remains unknown1. One notable exception is the theta rhythm of the rodent hippocampus, which seems to provide a reference clock to decode the animal’s position from spatiotemporal patterns of neuronal spiking2or LFPs3. But when the animal stops, theta becomes irregular4, potentially indicating the breakdown of temporal coding by neural populations. Here we show that no such breakdown occurs, introducing an artificial neural network that can recover position-tuned rhythmic patterns (pThetas) without relying on the more prominent theta rhythm as a reference clock. pTheta and theta preferentially correlate with place cell and interneuron spiking, respectively. When rats forage in an open field, pTheta is jointly tuned to position and head orientation, a property not seen in individual place cells but expected to emerge from place cell sequences5. Our work demonstrates that weak and intermittent oscillations, as seen in many brain regions and species, can carry behavioral information commensurate with population spike codes.