bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Distinct Neural Code Supports Prospection of Future Probabilities During Instrumental Information-Seeking
Authors: Singletary Nicholas M. , Horga Guillermo , Gottlieb Jacqueline 
Published: November 2023

AbstractTo make adaptive decisions, we must actively demand information, but relatively little is known about the mechanisms of active information gathering. An open question is how the brain estimates expected information gains (EIG) when comparing the current decision uncertainty with the uncertainty that is expected after gathering information. We examined this question using fMRI in a task in which people placed bids to obtain information in conditions that varied independently by prior decision uncertainty, information diagnosticity, and the penalty for an erroneous choice. Consistent with value of information theory, bids were sensitive to EIG and its components of prior certainty and expected posterior certainty. Expected posterior certainty was decoded above chance from multivoxel activation patterns in the posterior parietal and extrastriate cortices. This representation was independent of instrumental rewards and overlapped with distinct representations of EIG and prior certainty. Thus, posterior parietal and extrastriate cortices are candidates for mediating the prospection of posterior probabilities as a key step to estimate EIG during active information gathering.
Proneural – Mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in Glioblastoma
Authors: BV Harshavardhan , Jolly Mohit Kumar 
Published: November 2023

1AbstractThe aggressive nature of glioblastoma (GBM) – one of the deadliest forms of brain tumours – is majorly attributed to underlying phenotypic heterogeneity. Early attempts to classify this heterogeneity at a transcriptomic level in TCGA GBM cohort proposed the existence of four distinct molecular subtypes: Proneural, Neural, Classical and Mesenchymal. Further, a single-cell RNA-seq analysis of primary tumours also reported similar 4 subtypes mimicking neuro-developmental lineages. However, it remains unclear whether these 4 subtypes identified via bulk and single-cell transcriptomics are mutually exclusive or not. Here, we perform pairwise correlations among individual genes and gene signatures corresponding to these proposed subtypes, and show that the subtypes are not distinctly mutually antagonistic in either TCGA or single-cell RNA-sequencing data. We observed that the proneural (or neural progenitor-like) – mesenchymal axis is the most prominent antagonistic pair, with the other two subtypes lying on this spectrum. These results are reinforced through a meta-analysis of over 100 single-cell and bulk transcriptomic datasets as well as in terms of functional association with metabolic switching, cell cycle and immune evasion pathways. These results suggest rethinking GBM phenotypic characterization for more effective therapeutic targeting efforts.
The cryo-EM structure of trypanosome 3-methylcrotonyl-CoA carboxylase provides mechanistic and dynamic insights into enzymatic function
Authors: Plaza-Pegueroles Adrián , Aphasizheva Inna , Aphasizhev Ruslan , Fernández-Tornero Carlos , Ruiz Federico M. 
Published: November 2023

Abstract3-methylcrotonyl-CoA carboxylase (MCC) catalyzes the two-step, biotin-dependent production of 3-methylglutaconyl-CoA, an essential intermediate in leucine catabolism. Given its critical metabolic role, deficiencies in this enzyme associate with organic aciduria, while its overexpression is linked to tumor development. MCC is a dodecameric enzyme composed of six copies of each α- and β-subunit. We present the cryo-EM structure of the endogenous MCC holoenzyme fromTrypanosoma bruceiin its soluble, non-filamentous state at 2.5 Å resolution. We unambiguously observe the position of biotin, covalently-bound to the BBCP domain of α-subunits and occupying a novel binding pocket next to the active site of a neighboring β-subunit dimer. Moreover, flexibility of key residues at the α/α- and α/β-subunit interfaces enables pivoting of α-subunit trimers to sequentially approach the otherwise distant active sites for the two steps in MCC catalysis. Our results provide a structural framework to understand the enzymatic mechanism of eukaryotic MCCs and assist drug discovery against trypanosome infections.
TRIBAL: Tree Inference of B cell Clonal Lineages
Authors: Weber Leah L. , Reiman Derek , Roddur Mrinmoy S. , Qi Yuanyuan , El-Kebir Mohammed , Khan Aly A. 
Published: November 2023

AbstractB cells are a critical component of the adaptive immune system, responsible for producing antibodies that help protect the body from infections and foreign substances. Single cell RNA-sequencing (scRNA-seq) has allowed for both profiling of B cell receptor (BCR) sequences and gene expression. However, understanding the adaptive and evolutionary mechanisms of B cells in response to specific stimuli remains a significant challenge in the field of immunology. We introduce a new method, TRIBAL, which aims to infer the evolutionary history of clonally related B cells from scRNA-seq data. The key insight of TRIBAL is that inclusion of isotype data into the B cell lineage inference problem is valuable for reducing phylogenetic uncertainty that arises when only considering the receptor sequences. Consequently, the TRIBAL inferred B cell lineage trees jointly capture the somatic mutations introduced to the B cell receptor during affinity maturation and isotype transitions during class switch recombination. In addition, TRIBAL infers isotype transition probabilities that are valuable for gaining insight into the dynamics of class switching.Viain silicoexperiments, we demonstrate that TRIBAL infers isotype transition probabilities with the ability to distinguish between direct versus sequential switching in a B cell population. This results in more accurate B cell lineage trees and corresponding ancestral sequence and class switch reconstruction compared to competing methods. Using real-world scRNA-seq datasets, we show that TRIBAL recapitulates expected biological trends in a model affinity maturation system. Furthermore, the B cell lineage trees inferred by TRIBAL were equally plausible for the BCR sequences as those inferred by competing methods but yielded lower entropic partitions for the isotypes of the sequenced B cell. Thus, our method holds the potential to further advance our understanding of vaccine responses, disease progression, and the identification of therapeutic antibodies.AvailabilityTRIBAL is available athttps://github.com/elkebir-group/tribal
Oscillations in an Artificial Neural Network Convert Competing Inputs into a Temporal Code
Authors: Duecker Katharina , Idiart Marco , van Gerven Marcel AJ , Jensen Ole 
Published: November 2023

AbstractDeep convolutional neural networks (CNNs) resemble the hierarchically organised neural representations in the primate visual ventral stream. However, these models typically disregard the temporal dynamics experimentally observed in these areas. For instance, alpha oscillations dominate the dynamics of the human visual cortex, yet the computational relevance of oscillations is rarely considered in artificial neural networks (ANNs). We propose an ANN that embraces oscillatory dynamics with the computational purpose of converting simultaneous inputs, presented at two different locations, into a temporal code. The network was trained to classify three individually presented letters. Post-training, we added semi-realistic temporal dynamics to the hidden layer, introducing relaxation dynamics in the hidden units as well as pulsed inhibition mimicking neuronal alpha oscillations. Without these dynamics, the trained network correctly classified individual letters but produced a mixed output when presented with two letters simultaneously, elucidating a bottleneck problem. When introducing refraction and oscillatory inhibition, the output nodes corresponding to the two stimuli activated sequentially, ordered along the phase of the inhibitory oscillations. Our model provides a novel approach for implementing multiplexing in ANNs. It further produces experimentally testable predictions of how the primate visual system handles competing stimuli.
Biomolecular condensates in fungi are tuned to function at specific temperatures
Authors: Stormo Benjamin M. , McLaughlin Grace A. , Frederick Logan K. , Jalihal Ameya P. , Cole Sierra J , Seim Ian , Dietrich Fred S. , Gladfelter Amy S. 
Published: November 2023

SummaryTemperature can impact every reaction and molecular interaction essential to a cell. For organisms that cannot regulate their own temperature, a major challenge is how to adapt to temperatures that fluctuate unpredictability and on variable timescales. Biomolecular condensation offers a possible mechanism for encoding temperature-responsiveness and robustness into cell biochemistry and organization. To explore this idea, we examined temperature adaptation in a filamentous-growing fungus calledAshbya gossypiithat engages biomolecular condensates containing the RNA-binding protein Whi3 to regulate mitosis and morphogenesis. We collected wild isolates ofAshbyathat originate in different climates and found that mitotic asynchrony and polarized growth, which are known to be controlled by the condensation of Whi3, are temperature sensitive. Sequence analysis in the wild strains revealed changes to specific domains within Whi3 known to be important in condensate formation. Using anin vitrocondensate reconstitution assay we found that temperature impacts the relative abundance of protein to RNA within condensates and that this directly impacts the material properties of the droplets. Finally, we found that exchanging Whi3 genes between warm and cold isolates was sufficient to rescue some, but not all, condensate-related phenotypes. Together these data demonstrate that material properties of Whi3 condensates are temperature sensitive, that these properties are important for function, and that sequence optimizes properties for a given climate.
Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response
Authors: Prabhakar Amit , Kumar Rahul , Wadhwa Meetu , Ghatpande Prajakta , Zhang Jingkun , Zhao Ziwen , Lizama Carlos O. , Kharbikar Bhushan N. , Gräf Stefan , Treacy Carmen M. , Morrell Nicholas W. , Graham Brian B. , Lagna Giorgio , Hata Akiko 
Published: November 2023

AbstractPulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving the vascular remodeling in PVOD. We show that the administration of MMC in rats mediates the activation of protein kinase R (PKR) and the integrated stress response (ISR), which lead to the release of the endothelial adhesion molecule VE-Cadherin in the complex with Rad51 to the circulation, disruption of endothelial barrier, and vascular remodeling. Pharmacological inhibition of PKR or ISR attenuates the depletion of VE-Cadherin, elevation of vascular permeability, and vascular remodeling instigated by MMC, suggesting potential clinical intervention for PVOD. Finally, the severity of PVOD phenotypes was increased by a heterozygousBMPR2mutation that truncates the carboxyl tail of BMPR2, underscoring the role of deregulated BMP signal in the development of PVOD.
Characterizing breast cancer response to neoadjuvant therapy based on biophysical modeling and multiparametric magnetic resonance imaging data
Authors: Bowers Haley J. , Guthrie John A. , Krukoski Alaura , Thomas Alexandra , Weis Jared A. 
Published: November 2023

AbstractPersonalized medicine efforts are focused on identifying biomarkers to guide individualizing neoadjuvant therapy regimens. In this work, we aim to validate a previously developed image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy using a large, multi-site cohort. We retrospectively analyzed patients enrolled in the BMMR2 ACRIN 6698 subset at 10 institutions. Patients enrolled received four MRI examinations during neoadjuvant therapy with acquisitions at baseline (T0), 3-weeks/early-treatment (T1), 12-weeks/mid-treatment (T2), and completion of therapy prior to surgery (T3). A biophysical mathematical model of tumor growth is used extract metrics to characterize the dynamics of treatment response. Using predicted response at therapy conclusion and histogram summary metrics to quantify estimated tumor proliferation maps, we found univariate model-based metrics able to predict pathological response, with area under the receiver operating characteristic curve (AUC) ranging from 0.58 and 0.69 analyzing between T0and T1, and AUCs ranging from 0.72-0.76 analyzing between T0and T2. For hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients our model-based metrics achieved an AUC of 0.9 analyzing between T0and T1and AUC of 1.0 analyzing between T0and T2. This data shows the significant promise in developing these imaging-based biophysical mathematical modeling methods of dynamic characterization into a clinical decision support tool for individualizing treatment regimens based on patient-specific response.
Male cuticular pheromones stimulate removal of the mating plug and promote re-mating through pC1 neurons inDrosophilafemales
Authors: Yun Minsik , Kim Do-Hyoung , Ha Tal Soo , Lee Kang-Min , Park Eungyu , Knaden Markus , Hansson Bill S. , Kim Young-Joon 
Published: November 2023

AbstractIn birds and insects, the female uptakes sperm for a specific duration post-copulation known as the ejaculate holding period (EHP) before expelling unused sperm and the mating plug through sperm ejection. In this study, we found thatDrosophila melanogasterfemales shortens the EHP when incubated with males or mated females shortly after the first mating. This phenomenon, which we termedmale-inducedEHPshortening (MIES), requires Or47b+ olfactory and ppk23+ gustatory neurons, activated by 2-methyltetracosane and 7-tricosene, respectively. These odorants raise cAMP levels in pC1 neurons, responsible for processing male courtship cues and regulating female mating receptivity. Elevated cAMP levels in pC1 neurons reduce EHP and reinstate their responsiveness to male courtship cues, promoting re-mating with faster sperm ejection. This study established MIES as a genetically tractable model of sexual plasticity with a conserved neural mechanism.Significance StatementSexual plasticity, the adaptation of reproductive behavior to social changes, was explored in the fruit fly, a genetically tractable model insect. Our findings revealed that inseminated females, encountering another courting male post-mating, shorten the ejaculate holding period (EHP). Specific olfactory and gustatory pathways regulating this phenomenon were identified, converging on the pC1 neurons in the brain-a conserved neural circuit that regulates female mating activity. Odors associated with EHP shortening increased the second messenger cAMP. The transient elevation of cAMP heightened the excitability of pC1 neurons, facilitating the prompt removal of the male ejaculate and subsequent re-mating . This study established a behavioral model of sexual plasticity and provided a framework for understanding the neural circuit processes involved.
Towards an understanding of how school climate strikes work as public pedagogy
Authors: Sutton Bronwyn A. 
Published: November 2023

PurposeSchool climate strikes are opening spaces of appearance, becoming differently active forms of public pedagogy where new and previously unthought collective climate action is possible. This inquiry contributes to understanding school climate strikes as important forms of climate justice activism by exploring how they work as public pedagogy.Design/methodology/approachThe inquiry process involved poetic inquiry to produce an affective poetic witness statement to an event of school climate strikes, and then a performative enactment of diffractive reading using the poem created. The diffractive reading is used to conceptualise school climate strikes as public pedagogy and move towards an understanding of how school climate strikes work as public pedagogy. Diffused throughout is the question of where the more-than-human fits in public pedagogy and youth climate justice activism.FindingsSchool climate strikes are dynamic and differently acting (diffracting) public pedagogies that work by open spaces of appearance that enable capacities for collective action in heterogeneous political spaces. Consideration of entanglements and intra-actions between learner, place, knowledge and climate change are productive in understanding how phenomena work as public pedagogy.Originality/valueThis inquiry extends on important considerations in both climate change education and public pedagogy scholarship. It diffuses consideration of the more-than-human throughout the inquiry and enacts a move beyond the humanist limits of existing public pedagogy scholarship by introducing climate intra-action, heterogeneous political spaces and non-conforming learning to an understanding of activist public pedagogies and the educative agent.
Propounding an integrated solution ecosystem to effectuate CSR in India: an alternate framework
Authors: G. Rajan Soumya 
Published: November 2023

Purpose
Corporate social responsibility (CSR) was mandated and institutionalised in India through the Companies Act (2013), a decade ago. It is critical to understand the priorities of the models used by the companies to effectuate their CSR policy. This paper aims to understand the skewing of interest towards Education and Health interventions. The paper then proposes a framework to cross-level and effectuate CSR programme implementation.

Design/methodology/approach
The qualitative study conducted in-depth interviews of the stakeholders from the CSR environment. The findings are used to derive a model to effectuate CSR in India.

Findings
The findings may be divided into two sub-themes – (a) observations from the field study and (b) integrated solution ecosystem (ISE) framework. The qualitative study and the insights form the first component. The proposed framework which can enhance the efficiency of CSR practices may be found in the second sub-theme.

Research limitations/implications
Operationalisation of the proposed model, if adopted would require integrated efforts from multiple functional departments which could lead to an extended timeframe for implementation. This may eventually lead to a need to revise the model in the making. The research could also include perspectives from governmental stakeholders which is missing here.

Practical implications
The emerging model can present an opportunity for corporates and policymakers to revisit the CSR structure and frameworks. It can also be used to evaluate and audit the CSR practices of companies.

Social implications
The ISE posits a bunch of actionable themes which can deliver an impactful transition from the existing approach to CSR to a more far reaching one. While the ground rules are revisited, the approach also allows a critical departure from a corporate-driven model of engagement with the community. The modifications or corrections in this model would also mean a more inclusive layering of developmental interventions. The diversity which could potentially be brought in to designing interventions can be another key impact.

Originality/value
This paper presents insights for some of the pivotal stakeholders of CSR in countries like India. It presents a possible model of effective and optimal utilisation of CSR spending.
Changes in forest structure over 23 years under disturbances in a warm temperate rain forest on Yakushima Island, Japan
Authors: Niiyama Kaoru , Iida Yoshiko , Oguro Michio , Saito Satoshi 
Published: November 2023

AbstractClarifying the influence of disturbances by biotic and abiotic agents on long‐term changes in forest structure and demographic rates is an important task of forest ecology. Here, we investigated changes in forest structure and demographic rates and the effects of biotic and abiotic factors (sika deer, ambrosia beetle, neighborhood trees, and indices of strong wind and wetness) in a 4‐ha long‐term ecological study plot in a lowland warm temperate rain forest on Yakushima Island, Japan, from 1996 to 2019 for three regeneration groups related to gap dynamics (gap demander: GD, light shade tolerant: LS, and strong shade tolerant: SS). GD had relatively lower recruitment and survival than LS and/or SS. Changes in demographic rates were not significantly correlated with those in the index of strong wind in any regeneration group. The effects of sika deer on demographic rates did not differ among groups. Stems of Fagaceae species belonging to LS attacked by ambrosia beetles recorded in 2013 did not significantly differ in RGR and survival rates. Our results indicate that despite the relatively long monitoring period of 23 years, we did not detect significant effects of strong winds on demographic rates among regeneration groups, and shade‐tolerant species (LS and SS) showed better demographic performance than light‐demanding species (GD) and an increase in total basal area over time. We need longer monitoring of forest dynamics to understand forest responses to disturbances considering several factors, including the time lag of demographic responses to disturbances and the long‐term effects of disturbances.
Antifungal edible coatings for fruits based on zein and chitosan nanowhiskers
Authors: Almeida Carolina L. , Figueiredo Lucas R. F. , Ribeiro Diego V. M. , Santos Adillys M. C. , Souza Evandro L. , Oliveira Kataryne A. R. , Oliveira Juliano E. , Medeiros Eliton S. 
Published: November 2023

AbstractFresh produce have a more limited shelf life than processed ones. Their sensory attributes such as appearance and surface texture are important features in consumer perception and liking. The decomposition of fresh produce, which is caused by enzymes, chemical reactions, and microbial infections, often caused by Colletotrichum species, is inevitable. However, it can be slowed down. Several materials have been developed for this purpose, with an emphasis on active coatings using nanomaterials. In this study, the protective effects of a zein coating containing chitosan nanowhiskers (CSW) for the maintenance of fruit quality were investigated using guava (Psidium guajava L.) as a model fruit. CSW were previously characterized, and their antifungal effects against distinct Colletotrichum species (Colletotrichum asianum, Colletotrichum tropicale, Colletotrichum gloeosporioides, and Colletotrichum brevisporum) were proven. Coatings were characterized by thermogravimetric analysis, optical profilometry, and mechanical properties. Total soluble solids, pH, mass loss, and visual inspection of uncoated and coated guava fruits were also verified during 9 days. Results show that CSW length and aspect ratio decreased for longer extraction times. A similar behavior was found for x‐ray diffraction in which peak intensity decreases under the same conditions. CSW degradation (ca. 250–400°C) also depends on extraction time in which more crystalline whiskers are the most thermally stable ones. The addition of CSW did not significantly (p < 0.05) modify the homogeneity and continuity of coating but prevented microbial growth assuring fruit quality during storage. In summary, coatings protected guava fruits from post‐harvest spoilage while preserving quality and extending shelf life.Practical ApplicationFresh foods such as fruits and vegetables have a more limited shelf life than processed ones.