bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress-free Bioprinting of Human Primary and iPSC-derived Islets with Retained Functionality
Authors: Poklar Miranda , Ravikumar K , Wiegand Connor , Mizerak Ben , Wang Ruiqi , Florentino Rodrigo M. , Liu Zhenghao , Soto-Gutierrez Alejandro , Kumta Prashant N. , Banerjee Ipsita
Published: October 2024

Currently, Type 1 diabetes (T1D) can be treated through implantation of allogenic islets, which replenish the beta cell population, however this method requires an extensive post-implantation immunosuppressant regimen. Personalized cellular therapy can address this through implantation of an autologous cell population, induced pluripotent stem cells (iPSCs). Cellular therapy, however, requires an encapsulation device for implantation, and so to achieve this uniformly with cells in a clinical setting, bioprinting is required. Bioprinting is dependent on having a bioink that is printable, retains structural fidelity after printing, and is supportive of cell type and function. The objective of this study was to design and develop bioinks that were compatible with printing islets. Here, we detail the successful bioprinting of both primary human islets and iPSC-derived islets embedded in an alginate/methylcellulose bioink, with functionality sustained within the construct for both cell lineages. Sc-RNAseq analysis also revealed that printing did not adversely affect the genetic expression and metabolic functionality of the iPSC-derived islets. Importantly, the iPSC-derived islets displayed comparable functionality to the primary islets, indicating the potential to act as a cell source alternative for T1D implantation.
Paroxysmal Slow Wave Events as a diagnostic and predictive biomarker for post-traumatic epilepsy
Authors: van Hameren Gerben , Moradi Pooyan , Imtiaz Hamza , Parker Ellen , Mansoor Saara , Al Hadeed Laith , Albitar Mohammed , Alhosainy Ziad , Friedman Alon
Published: October 2024

Traumatic brain injury (TBI) is a major global health concern, affecting more than 40 million people annually. While most cases are mild and present with light symptoms, repeated mild injuries can result in delayed brain pathologies, including cognitive decline, neuropsychiatric complications, and post-traumatic epilepsy (PTE). PTE refers to recurring, unprovoked seizures occurring at least one week after TBI. While the link between moderate to severe TBI and PTE is well established, the epileptogenesis after repetitive mild TBI (rmTBI) is seldom studied.

Currently, there are no biomarkers to identify those at risk of developing PTE, and its diagnosis is challenging. Here, we used a rat model to study PTE following rmTBI and assessed human EEG data to identify potential biomarkers for PTE.

We employed a closed head TBI model to induce rmTBI, and recorded brain activity using electrocorticography (ECoG) between 2- and 6-months post-injury. Behavioral assessments and post-mortem analysis were also conducted. In humans, we analyzed EEG recordings from the Temple University database to investigate the potential of EEG-derived features for diagnosing PTE.

At 6 months post injury, 70% of rmTBI animals developed PTE, compared to 22% in the control group (P=0.01). While neurological assessments following injury did not predict PTE, paroxysmal slow wave events (PSWEs) were found to be a reliable biomarker for PTE prediction. In humans, the percentage time in PSWEs was significantly elevated in PTE patients with epileptiform activity.

In conclusion, we suggest PSWEs as a non-invasive, cost-effective biomarker for PTE in rodents and human patients.
Treadmill step training promotes corticospinal tract plasticity after incomplete spinal cord injury
Authors: Eisdorfer Jaclyn T. , Nacht Hannah D. , Kowalski Tess , Thackray Joshua T. , Martinez Alana M. , Zymoro Lance , Phu Megan V. , Hirpara Ridhi R. , Danish Burhanuddin S. , Wang Riley , Khondker Adyan , Eisdorfer Adam B. , Tischfield Max , Abraira Victoria E.
Published: October 2024

Spinal cord injury (SCI) often impairs motor functions such as voluntary movement and fine motor control, with the corticospinal tract (CST) being a crucial pathway affected. While CST-targeted rehabilitation, such as treadmill training, supports motor recovery, gaps remain in understanding the topographical changes within the CST and how they correlate with behavioral outcomes. In this study, we utilized a custom Emx1Cre;LSL-SynGFP mouse line to quantify CST plasticity following moderate contusion SCI, both with and without exercise (treadmill) training. Fluorescent labeling of cortical synapses allowed for detailed visualization of descending CST rewiring, and we assessed its relationship to behavioral outcomes, including kinematics analysis and motivational state. Mice were stratified by motivational state using the Progressive Ratio Assay, and locomotor recovery was evaluated through the Basso Mouse Scale (BMS), joint/limb kinematics, and Motion Sequencing (MoSeq) analysis. Our findings indicate that treadmill training enhances CST rewiring, especially in highly motivated animals, leading to increased synaptic density in the ventral horn and improved BMS subscores. Motivation further influenced specific kinematic parameters, such as toe clearance, while treadmill training significantly improved speed by reducing the stance phase. Results suggest that while treadmill training induces broad beneficial outcomes, motivation may fine-tune recovery, influencing neural circuit and behavioral changes. This suggests multiple mechanisms converge to promote recovery—those we cannot control and those we can. These results underscore the combined role of task-specific training and also perhaps motivation in driving CST plasticity and functional recovery after SCI.
PAF1C allosterically activates CDK12/13 kinase during RNAPII transcript elongation
Authors: Lopez Martinez David , Todorovski Izabela , Noe Gonzalez Melvin , Rusimbi Charlotte , Blears Daniel , Khallou Nessrine , Han Zhong , Dirac-Svejstrup A. Barbara , Svejstrup Jesper Q.
Published: October 2024

The mechanisms ensuring temporally correct, site-specific phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases (CDKs) during the transcription cycle remain poorly understood. Here, we present results fromin vitroreconstitution of CTD phosphorylation combined within vivoevidence to show that human CDK12 and CDK9 both co-phosphorylate CTD Serine 5 and Serine 2. However, only phosphorylation by CDK12 is stimulated by association with the elongation-specific factor PAF1C, in which the CDC73 subunit contains a short, conserved motif capable of association with and activation of CDK12/Cyclin K. This motif is necessary for cell proliferation and crucial for CTD phosphorylation and transcript elongation. Together, these data provide new insight into basic mechanisms ensuring CDK specificity in the RNAPII transcription cycle.

One-Sentence Summary

PAF1C facilitates RNAPII phosphorylation in gene bodies through direct contacts with the active site of CDK12/13.
Bumblebees increase their learning flight altitude in dense environments
Authors: Sonntag Annkathrin , Lihoreau Mathieu , Bertrand Olivier J.N. , Egelhaaf Martin
Published: October 2024

Bumblebees rely on visual memories acquired during the first outbound flights to relocate their nest. While these learning flights have been extensively studied in sparse environments with few objects, little is known about how bees adapt their flight in more dense, cluttered, settings that better mimic their natural habitats. Here we investigated how environmental complexity influences the first outbound flights of bumblebees. In a large arena we tracked the bees’ 3D positions to examine the flight patterns, body orientations, and nest fixations across environmental conditions characterised by different object constellations around the nest entrance.

In cluttered environments, bees prioritised altitude gain over horizontal distance, suggesting a strategy to overcome obstacles and visual clutter. Body orientation patterns became more diverse in dense environments, indicating a balance between nest-oriented learning and obstacle avoidance. Notably, bees consistently preferred to fixate the location of the nest entrance from elevated positions above the dense environment across all conditions.

Our results reveal significant changes in 3D flight structure, body orientations, and nest fixation behaviours as object density increases. This highlights the importance of considering three-dimensional space and environmental complexity in understanding insect navigation.

Summary Statement

Dense environments influence bumblebees’ first flights, during which they develop visual memories of their nest entrance. Manipulating nest-surrounding objects showed bees prioritise altitude gain over horizontal distance in cluttered environments.
Trade-off between search costs and accuracy in oculomotor and manual search tasks
Authors: Wagner Ilja , Tünnermann Jan , Schubö Anna , Schütz Alexander C.
Published: October 2024

Humans must weigh various factors when choosing between competing courses of action. In case of eye movements, for example, a recent study demonstrated that the human oculomotor system trades off the temporal costs of eye movements against their perceptual benefits, when choosing between competing visual search targets. Here, we compared such trade-offs between different effectors. Participants were shown search displays with targets and distractors from two stimulus sets. In each trial, they chose which target to search for, and, after finding it, discriminated a target feature. Targets differed in their search costs (how many target-similar distractors were shown) and discrimination difficulty. Participants were rewarded or penalized based on whether the target’s feature was discriminated correctly. Additionally, participants were given limited time to complete trials. Critically, they inspected search items either by eye movements only or by manual actions (tapping a stylus on a tablet). Results show that participants traded off search costs and discrimination difficulty of competing targets for both effectors, allowing them to perform close to the predictions of an ideal observer model. However, behavioral analysis and computational modelling revealed that oculomotor search performance was more strongly constrained by decision-noise (what target to choose) and sampling-noise (what information to sample during search) than manual search. We conclude that the trade-off between search costs and discrimination accuracy constitutes a general mechanism to optimize decision-making, regardless of the effector used. However, slow-paced manual actions are more robust against the detrimental influence of noise, compared to fast-paced eye movements.

New & Noteworthy

Humans trade off costs and perceptual benefits of eye movements for decision-making. Is this trade-off effector-specific or does it constitute a general decision-making principle? Here, we investigated this question by contrasting eye movements and manual actions (tapping a stylus on a tablet) in a search task. We found evidence for a costs-benefits trade-off in both effectors, however, eye movements were more strongly compromised by noise at different levels of decision-making.
Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors
Authors: Kelberman Michael A. , Rodberg Ellen , Arabzadeh Ehsan , Bair-Marshall Chloe J. , Berridge Craig W. , Berrocoso Esther , Breton-Provencher Vincent , Chandler Daniel J. , Che Alicia , Davy Oscar , Devilbiss David M. , Downs Anthony M. , Drummond Gabrielle , Dvorkin Roman , Fazlali Zeinab , Froemke Robert C. , Glennon Erin , Gold Joshua I. , Ito Hiroki , Jiang Xiaolong , Johansen Joshua P. , Kaye Alfred P. , Kim Jenny R. , Kuo Chao-Cheng , Liu Rong-Jian , Liu Yang , Llorca-Torralba Meritxell , McCall Jordan G. , McElligott Zoe A. , McKinney Andrew M. , Miguelez Cristina , Min Ming-Yuan , Nowlan Alexandra C. , Omrani Mohsen , Poe Gina R. , Pickering Anthony Edward , Ranjbar-Slamloo Yadollah , Razquin Jone , Rodenkirch Charles , Sales Anna C. , Satyasambit Rath , Shea Stephen D. , Sur Mriganka , Tkaczynski John Arthur , Torres-Sanchez Sonia , Uematsu Akira , Vazquez Chayla R. , Vreven Amelien , Wang Qi , Waterhouse Barry D , Yang Hsiu-Wen , Yang Jen-Hau , Zhao Liping , Zouridis Ioannis S. , Weinshenker David , Vazey Elena , Totah Nelson K.
Published: October 2024

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slicesex vivoor under different anesthetics or during wakefulnessin vivo. LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes (“tonic” or “phasic”), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders.
Fast and robust visual object recognition in young children
Authors: Ayzenberg Vladislav , Sener Sukran Bahar , Novick Kylee , Lourenco Stella F.
Published: October 2024

By adulthood, humans rapidly identify objects from sparse visual displays and across significant disruptions to their appearance. What are the minimal conditions needed to achieve robust recognition abilities and when might these abilities develop? To answer these questions, we investigated the upper-limits of children’s object recognition abilities. We found that children as young as 3 years successfully identified objects at speeds of 100 ms (both forward and backward masked) under sparse and disrupted viewing conditions. By contrast, a range computational models implemented with biologically informed properties or optimized for visual recognition did not reach child-level performance. Models only matched children if they received more object examples than children are capable of experiencing. These findings highlight the robustness of the human visual system in the absence of extensive experience and identify important developmental constraints for building biologically plausible machines.

Teaser

The visual recognition abilities of preschool children rival those of state-of-the-art artificial intelligence models.
Enhanced Hippocampal Spare Capacity in Q175DN Mice Despite Elevated mHTT Aggregation
Authors: Solem Melissa A , Pelzel Ross , Rozema Nicholas B. , Brown Taylor G. , Reid Emma , Mansky Rachel H. , Gomez-Pastor R
Published: October 2024

Background

Huntington’s disease (HD) is a neurodegenerative disease resulting in devastating motor, cognitive, and psychiatric deficits. The striatum is a brain region that controls movement and some forms of cognition and is most significantly impacted in HD. However, despite well-documented deficits in learning and memory in HD, knowledge of the potential implication of other brain regions such as the hippocampus remains limited.

Objective

Here, we study the comparative impact of enhanced mHTT aggregation and neuropathology in the striatum and hippocampus of two HD mouse models.

Methods

We utilized the zQ175 as a control HD mouse model and the Q175DN mice lacking the PGK-Neomycin cassette generated in house. We performed a comparative characterization of the neuropathology between zQ175 and Q175DN mice in the striatum and the hippocampus by assessing HTT aggregation, neuronal and glial pathology, chaperone expression, and synaptic density.

Results

We showed that Q175DN mice presented enhanced mHTT aggregation in both striatum and hippocampus compared to zQ175. Striatal neurons showed a greater susceptibility to enhanced accumulation of mHTT than hippocampal neurons in Q175DN despite high levels of mHTT in both regions. Contrary to the pathology seen in the striatum, Q175DN hippocampus presented enhanced spare capacity showing increased synaptic density, decreased Iba1+microglia density and enhanced HSF1 levels in specific subregions of the hippocampus compared to zQ175.

Conclusions

Q175DN mice are a valuable tool to understand the fundamental susceptibility differences to mHTT toxicity between striatal neurons and other neuronal subtypes. Furthermore, our findings also suggest that cognitive deficits observed in HD animals might arise from either striatum dysfunction or other regions involved in cognitive processes but not from hippocampal degeneration.
Individual variation in the functional lateralization of human ventral temporal cortex: Local competition and long-range coupling
Authors: Blauch Nicholas M. , Plaut David C. , Vin Raina , Behrmann Marlene
Published: October 2024

Abstract

The ventral temporal cortex (VTC) of the human cerebrum is critically engaged in high-level vision. One intriguing aspect of this region is its functional lateralization, with neural responses to words being stronger in the left hemisphere, and neural responses to faces being stronger in the right hemisphere; such patterns can be summarized with a signed laterality index (LI), positive for leftward laterality. Converging evidence has suggested that word laterality emerges to couple efficiently with left-lateralized frontotemporal language regions, but evidence is more mixed regarding the sources of the right-lateralization for face perception. Here, we use individual differences as a tool to test three theories of VTC organization arising from: 1) local competition between words and faces driven by long-range coupling between words and language processes, 2) local competition between faces and other categories, 3) long-range coupling with VTC and temporal areas exhibiting local competition between language and social processing. First, in an in-house functional MRI experiment, we did not obtain a negative correlation in the LIs of word and face selectivity relative to object responses, but did find a positive correlation when using selectivity relative to a fixation baseline, challenging ideas of local competition between words and faces driving rightward face lateralization. We next examined broader local LI interactions with faces using the large-scale Human Connectome Project (HCP) dataset. Face and tool LIs were significantly anti-correlated, while face and body LIs were positively correlated, consistent with the idea that generic local representational competition and cooperation may shape face lateralization. Last, we assessed the role of long-range coupling in the development of VTC lateralization. Within our in-house experiment, substantial positive correlation was evident between VTC text LI and that of several other nodes of a distributed text-processing circuit. In the HCP data, VTC face LI was both negatively correlated with language LI and positively correlated with social processing in different subregions of the posterior temporal lobe (PSL and STSp, respectively). In summary, we find no evidence of local face-word competition in VTC; instead, more generic local interactions shape multiple lateralities within VTC, including face laterality. Moreover, face laterality is also influenced by long-range coupling with social processing in the posterior temporal lobe, where social processing may become right-lateralized due to local competition with language.
Individual Differences in Policy Precision: Links to Suicidal Ideation and Default Mode Network Dynamics
Authors: Yoon Dayoung , Kim Jaejoong , Kim Do Hyun , Shin Dong Woo , Bong Su Hyun , Kim Jaewon , Park Hae-jeong , Jeon Hong Jin , Jeong Bumseok
Published: October 2024

Behavior modeling of decision-making processes has deepened our understanding of behavioral impairments in various psychiatric states. However, as research increasingly emphasizes building models to best explain observed decision-making behavior, it may overlook whether these decisions stem from biologically plausible brain functions. To address this, we developed a probabilistic two-armed bandit task model based on the active inference framework. This model was compared to established reinforcement learning (RL) models and demonstrated superior explanatory power in capturing individual choice variability. A key parameter in our model, policy precision, corresponding to the temperature parameter in the RL model, is also optimized based on previous outcomes. This process effectively explains the balance between model-free and model-based strategies. Incorporating the rate of change in policy precision enhanced the model's ability to explain multi-level brain signals and their inter-subject correlations. Notably, this signal positively correlates with the activation of the default mode network while negatively correlating with the dorsal attentional and frontoparietal networks. Lastly, we validated the relevance of behavioral parameters in a population including individuals with major depressive disorder.
Bridging the Gap in Immunotherapy Prediction: The AGAE Score as a Pan-Cancer Biomarker for Immune Checkpoint Inhibitor Response
Authors: Ye Bicheng , Fan Jun , Meng Qingren , Liang Qingxiao , Jiang Aimin , Zhang Pengpeng
Published: October 2024

Background

Immune checkpoint inhibitor (ICI) therapy efficacy varies among cancer patients, necessitating precise predictive biomarkers for optimized treatment strategies.

Methods

We developed the Adaptive best subset selection algorithm and Genetic algorithm Aided Ensemble learning (AGAE) score through multi-cohort transcriptomic analysis of ICI-treated patients. The AGAE score incorporated gene-pairing, Adaptive Best Subset Selection for feature optimization, and a Genetic Algorithm for optimal basic learner identification. We explored correlations between AGAE score and immune microenvironments using multi-omics data. Potential targets were screened using 17 CRISPR datasets and validated through in vitro and in vivo experiments.

Results

The AGAE score demonstrated robust predictive power for ICI therapy outcomes, with lower scores correlating with enhanced treatment response. The AGAE score outperformed published signatures and conventional biomarkers. Lower AGAE scores were associated with increased immune cell infiltration, higher immunogenicity, and enhanced antitumor immune activity. The CEP55 was identified as a potential key target driving immune evasion through AGAE scoring and CRISPR screening. Experimental validation showed CEP55 downregulation attenuated tumor cell malignancy and augmented ICI therapy efficacy by modulating T cell responses.

Conclusions

The AGAE score was a potent predictor of ICI therapy efficacy, facilitating refined patient stratification. CEP55’s role in the tumor microenvironment’s immune response highlights its potential as a therapeutic target. Targeted interventions against CEP55 may improve immunotherapy precision.
Autonomic and Immune Stress Response Networks in Patients Living With HIV
Authors: Mueller Bridget R. , Mehta Mitali , Campbell Maya , Neupane Niyati , Cedillo Gabriela , Lee Gina , Coyle Kaitlyn , Qi Jinging , Chen Zhihong , George Mary Catherine , Robinson-Papp Jessica
Published: October 2024

Background and Objectives

Stress response systems are frequently dysregulated in patients with chronic inflammatory disorders. Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. However, these connections have not been examined in humans. We hypothesized that the subtype and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics in people living with HIV.

Methods

This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10).

Results

Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman’s rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017).

Discussion

Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.
What matters to a mouse? Effects of internal and external context on male vocal response to female squeaks
Authors: Brunner Lauren R , Hurley Laura M
Published: October 2024

House mice adjust their signaling behavior depending on the social context of an interaction, but which aspects of context elicit the strongest responses from these individuals is often difficult to determine. To explore how internal and external contextual factors influence how of house mice produce and respond to social signals, we assessed how dominant and subordinate male mice differed in their ultrasonic vocalization (USV) production in response to playback of broadband vocalizations (BBVs, or squeaks) when given limited access to a stimulus female. We used a repeated measures design in which each male was exposed to two types of trials with different odor conditions: either just female odors (Fem condition) or female odors in addition to the odors of potential competitors, other males (Fem+Male condition). The presence of odors from other males in this assay served as a proxy for an “audience” as the male interacted with the stimulus female. These conditions were replicated for two distinct cohorts of individuals: males exposed to the odor of familiar competitors in the Fem+Male condition (Familiar odor cohort), and males exposed to the odor of unfamiliar competitors in the Fem+Male condition (Unfamiliar odor cohort). By assessing dominance status of the focal individual and familiarity of the “audience”, we are able to explore how these factors may affect one another as males respond to BBVs. Dominants and subordinates did not differ in their baseline vocal production (vocalizations produced prior to squeak playback) or response to squeaks. However, all groups, regardless of dominance status or odor condition, reduced their vocal production in response to BBV playback. The presence of unfamiliar male odor prompted mice to decrease their baseline level of calling and decrease the complexity of their vocal repertoire compared to trials that only included female odor, and this effect also did not differ across dominance status. Importantly, the presence of male odor did not affect vocal behavior when the male odor was familiar to the focal individual. These findings suggest that mice alter their vocal behavior during courtship interactions in response to cues that indicate the presence of potential competitors, and this response is modulated by the familiarity of these competitor cues.
Emergence of Dip2-mediated Specific DAG-based PKC Signalling Axis in Eukaryotes
Authors: Shambhavi Sakshi , Mondal Sudipta , Chakraborty Arnab , Shukla Nikita , Panda Bapin K. , Kumar Santhosh , Kinatukara Priyadarshan , Pal Biswajit , Kamat Siddhesh S. , Sankaranarayanan Rajan
Published: October 2024

Diacylglycerols (DAGs) are used for metabolic purposes and are tightly regulated secondary lipid messengers in eukaryotes. DAG subspecies with different fatty-acyl chains are proposed to be involved in the activation of distinct PKC isoforms, resulting in diverse physiological outcomes. However, the molecular players and the regulatory origin for fine-tuning the PKC pathway are unknown. Here, we show that Dip2, a conserved DAG regulator across Fungi and Animalia, has emerged as a modulator of PKC signalling in yeast. Dip2 maintains the level of a specific DAG subpopulation, required for the activation of PKC-mediated cell wall integrity pathway. Interestingly, the canonical DAG-metabolism pathways, being promiscuous, are decoupled from PKC signalling. We demonstrate that these DAG subspecies are sourced from a phosphatidylinositol pool generated by the acyl-chain remodelling pathway. Furthermore, we provide insights into the intimate coevolutionary relationship between the regulator (Dip2) and the effector (PKC) of DAG-based signalling. Hence, our study underscores the establishment of Dip2-PKC axis about 1.2 billion years ago in Opisthokonta, which marks the rooting of the first specific DAG-based signalling module of eukaryotes.
Notch induces transcription by stimulating release of paused RNA polymerase II
Authors: Rogers Julia M. , Mimoso Claudia A. , Martin Benjamin J.E. , Martin Alexandre P. , Aster Jon C. , Adelman Karen , Blacklow Stephen C.
Published: October 2024

Notch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cellular processes by regulating transcription. Despite years of study, however, how Notch induces the transcription of its target genes remains unclear. Here, we comprehensively examine the response to human Notch1 across a time course of activation using high-resolution genomic assays of chromatin accessibility and nascent RNA production. Our data reveal that Notch induces target gene transcription primarily by releasing paused RNA polymerase II (RNAPII). Moreover, in contrast to prevailing models suggesting that Notch acts by promoting chromatin accessibility, we found that open chromatin was established at Notch-responsive regulatory elements prior to Notch signal induction through SWI/SNF-mediated remodeling. Together, these studies show that the nuclear response to Notch signaling is dictated by the pre-existing chromatin state and RNAPII distribution at the time of signal activation.
Doubled Haploid Technology: Opportunities and Challenges for the Rapid Generation of Maize Homozygous Lines
Authors: Grüning Vencke K. , Lübberstedt Thomas , Frei Ursula K.
Published: October 2024

Maize is used for multiple purposes, including food, feed, and energy production, and since transitioning to hybrid cultivars at around 1930, maize yield has significantly increased. This is largely due to hybrid vigor, which refers to the superior performance of the progeny from two unrelated inbred parents. Consequently, nearly all maize cultivars grown in the United States are hybrids. Hybrid breeding programs comprise two essential components; namely, inbred line development and hybrid production. Traditionally, developing inbred lines takes a long time, requiring six to 10 generations of self-pollination. The doubled haploid (DH) technology, however, accelerates this process, enabling the derivation of fully homozygous lines within two generations. DH technology is applicable in several crop species and has been most successful in maize due to in vivo maternal haploid induction. Here, we review the origins of the DH technology, and discuss advantages and challenges of the technology as well as applications of DH lines.
Optimized Methods for Applying and Assessing Heat, Drought, and Nutrient Stress of Maize Seedlings in Controlled Environment Experiments
Authors: Quiñones Alejandra , Lima Leonardo W. , Murphy Katherine M. , Casto Anna L. , Gehan Malia A. , Hirsch Cory D.
Published: October 2024

Maize (Zea mays), also known as corn, is an important crop that plays a crucial role in global agriculture. The economic uses of maize are numerous, including for food, feed, fiber, and fuel. It has had a significant historical importance in research as well, with important discoveries made in maize regarding plant domestication, transposons, heterosis, genomics, and epigenetics. Unfortunately, environmental stresses cause substantial yield loss to maize crops each year. Yield losses are predicted to increase in future climate scenarios, posing a threat to food security and other sectors of the global economy. Developing efficient methods to study maize abiotic stress responses is a crucial step toward a more resilient and productive agricultural system. This review describes the importance of and methods for studying the effects of heat, drought, and nutrient deficiency on early developmental stages of maize grown in controlled environments. Studying the early effects of environmental stressors in controlled environments allows researchers to work with a variety of environmental conditions with low environmental variance, which can inform future field-based research. We highlight the current knowledge of physiological responses of maize to heat, drought, and nutrient stress; remaining knowledge gaps and challenges; and information on how standardized protocols can address these issues.
Criterion of perturbativity with the mass-dependent beta function in extended Higgs models
Authors: Kanemura Shinya , Mura Yushi
Published: October 2024

In order to realize an electroweak first-order phase transition, a category of extended Higgs models with relatively large self-coupling constants is often considered. In such a scenario, the running coupling constants can blow up at an energy scale much below the Planck scale. To clarify the allowed parameter space of the model, it is important to evaluate the scale where perturbative calculation breaks down. In the renormalization group equation analysis using the mass-independent renormalization scheme, we need a matching condition to connect the low energy theory and the high energy theory. Consequently, the analysis depends on the details of the matching condition. On the other hand, an analysis with the mass-dependent beta function can be performed in a simpler way because the threshold effect is automatically included in the beta function. In this paper, using the mass-dependent beta function, we discuss the application limit of perturbative calculations at the one-loop level. First, we explain the essence of our method and compare our results with those based on the mass-independent beta function in a toy model with two complex scalar fields. We then apply our method to a more realistic model, i.e., the inert doublet model. We find that, in our method, in which the threshold effect is automatically included, the energy scale where the perturbative calculation breaks down can be higher than the one using the mass-independent beta function, especially when the blowup scale is relatively low.

Published by the American Physical Society
2024
Hanle Effect for Lifetime Determinations in the Soft X-Ray Regime
Authors: Togawa Moto , Richter Jan , Shah Chintan , Botz Marc , Nenninger Joshua , Danisch Jonas , Goes Joschka , Kühn Steffen , Amaro Pedro , Mohamed Awad , Amano Yuki , Orlando Stefano , Totani Roberta , de Simone Monica , Fritzsche Stephan , Pfeifer Thomas , Coreno Marcello , Surzhykov Andrey , López-Urrutia José R. Crespo
Published: October 2024

By exciting a series of 1s2 S01→1snpP11 transitions in heliumlike nitrogen ions with linearly polarized monochromatic soft x rays at the Elettra facility, we found a change in the angular distribution of the fluorescence sensitive to the principal quantum number n. In particular it is observed that the ratio of emission in directions parallel and perpendicular to the polarization of incident radiation increases with higher n. We find this n dependence to be a manifestation of the Hanle effect, which served as a practical tool for lifetime determinations of optical transitions since its discovery in 1924. In contrast to traditional Hanle effect experiments, in which one varies the magnetic field and considers a particular excited state, we demonstrate a “soft x-ray Hanle effect” which arises in a static magnetic field but for a series of excited states. By comparing experimental data with theoretical predictions, we were able to determine lifetimes ranging from hundreds of femtoseconds to tens of picoseconds of the 1snpP11 levels, which find excellent agreement with atomic-structure calculations. We argue that dedicated soft x-ray measurements could yield lifetime data that are beyond current experimental reach and cannot yet be predicted with sufficient accuracy.

Published by the American Physical Society
2024
Using Bifluxon Tunneling to Protect the Fluxonium Qubit
Authors: Ardati Waël , Léger Sébastien , Kumar Shelender , Suresh Vishnu Narayanan , Nicolas Dorian , Mori Cyril , D’Esposito Francesca , Vakhtel Tereza , Buisson Olivier , Ficheux Quentin , Roch Nicolas
Published: October 2024

Encoding quantum information in quantum states with disjoint wave-function support and noise-insensitive energies is the key behind the idea of qubit protection. While fully protected qubits are expected to offer exponential protection against both energy relaxation and pure dephasing, simpler circuits may grant partial protection with currently achievable parameters. Here, we study a fluxonium circuit in which the wave functions are engineered to minimize their overlap while benefiting from a first-order-insensitive flux sweet spot. Taking advantage of a large superinductance (L∼1  μH), our circuit incorporates a resonant tunneling mechanism at zero external flux that couples states with the same fluxon parity, thus enabling bifluxon tunneling. The states |0⟩ and |1⟩ are encoded in wave functions with parities 0 and 1, respectively, ensuring a minimal form of protection against relaxation. Two-tone spectroscopy reveals the energy-level structure of the circuit and the presence of 4π quantum-phase slips between different potential wells corresponding to m=±1 fluxons, which can be precisely described by a simple fluxonium Hamiltonian or by an effective bifluxon Hamiltonian. Despite suboptimal fabrication, the measured relaxation (T1=177±3  μs) and dephasing (T2E=75±5  μs) times not only demonstrate the relevance of our approach but also open an alternative direction toward quantum computing using partially protected fluxonium qubits.

Published by the American Physical Society
2024
Learning Quantum States and Unitaries of Bounded Gate Complexity
Authors: Zhao Haimeng , Lewis Laura , Kannan Ishaan , Quek Yihui , Huang Hsin-Yuan , Caro Matthias C.
Published: October 2024

While quantum state tomography is notoriously hard, most states hold little interest to practically minded tomographers. Given that states and unitaries appearing in nature are of bounded gate complexity, it is natural to ask if efficient learning becomes possible. In this work, we prove that to learn a state generated by a quantum circuit with G two-qubit gates to a small trace distance, a sample complexity scaling linearly in G is necessary and sufficient. We also prove that the optimal query complexity to learn a unitary generated by G gates to a small average-case error scales linearly in G. While sample-efficient learning can be achieved, we show that under reasonable cryptographic conjectures, the computational complexity for learning states and unitaries of gate complexity G must scale exponentially in

G

. We illustrate how these results establish fundamental limitations on the expressivity of quantum machine-learning models and provide new perspectives on no-free-lunch theorems in unitary learning. Together, our results answer how the complexity of learning quantum states and unitaries relate to the complexity of creating these states and unitaries.

Published by the American Physical Society
2024
Management accounting practices going sustainable: the move toward sustainable risk management in ASEAN developing economies
Authors: Abu Afifa Malik , Nguyen Nha Minh , Bui Duong Van
Published: October 2024

Purpose

The purpose of this study will be to provide a comprehensive perspective on sustainable risk management (SRM) with internal components within enterprises. Particularly, this study aims to explore how sustainable management accounting practices mediate the influence of both risk-taking tendency (RTT) and sustainable core values on SRM. Additionally, it also examines the moderating influence of the RTT on the link between sustainable management accounting practices and SRM, as a mediated moderating model.

Design/methodology/approach

The study hypotheses have been appraised using partial least squares structural equation modeling with observed information from 495 sizeable listed enterprises in ASEAN developing economies, comprising Indonesia, Malaysia, the Philippines, Singapore, Thailand and Vietnam.

Findings

The findings have been as follows: (1) The RTT favorably influences sustainable management accounting practices (SMAPs), which, in turn, affects SRM; (2) Sustainable core values favorably affect SMAPs, which, in turn, affect SRM; (3) It can be specified that SMAPs mediate the influence of both RTT and sustainable core values on SRM; (4) When the RTT is strong, the influence of SMAPs on SRM has been enlarged.

Originality/value

The findings of this study demonstrate how the interaction between RTT and SMAPs can benefit to the success of large enterprises that use risk management systems in emerging economics. Furthermore, the present paper interprets the mechanism by which SMAPs influence SRM.
Experimental and numerical study of characteristic parameters of Taylor bubble in vertical pipe under short-time gas injection
Authors: Ren Yufeng , Bai Changqing , Zhang Hongyan
Published: October 2024

Purpose

This study aims to investigate the formation and characteristics of Taylor bubbles resulting from short-time gas injection in liquid-conveying pipelines. Understanding these characteristics is crucial for optimizing pipeline efficiency and enhancing production safety.

Design/methodology/approach

The authors conducted short-time gas injection experiments in a vertical rectangular pipe, focusing on Taylor bubble formation time and stable length. Computational fluid dynamics simulations using large eddy simulation and volume of fluid models were used to complement the experiments.

Findings

Results reveal that the stable length of Taylor bubbles is significantly influenced by gas injection velocity and duration. Specifically, high injection velocity and duration lead to increased bubble aggregation and recirculation region capture, extending the stable length. Additionally, a higher injection velocity accelerates reaching the critical local gas volume fraction, thereby reducing formation time. The developed fitting formulas for stable length and formation time show good agreement with experimental data, with average errors of 6.5% and 7.39%, respectively. The predicted values of the formulas in glycerol-water and ethanol solutions are also in good agreement with the simulation results.

Originality/value

This research provides new insights into Taylor bubble dynamics under short-time gas injection, offering predictive formulas for bubble formation time and stable length. These findings are valuable for optimizing industrial pipeline designs and mitigating potential safety issues.
Financial well-being, anxiety and payment delinquency among student loan holders in the United States: insights from the COVID-19 pandemic
Authors: Kim Kyoung Tae , Lee Jonghee
Published: October 2024

Purpose

The COVID-19 pandemic presented unprecedented challenges, particularly intensifying the financial and psychological burden for individuals with student loans in the United States. Firstly, this study examined the association between student loan ownership and financial well-being during the pandemic. Secondly, among student loan holders, we tested the association of financial anxiety and payment delinquency with COVID-19 shocks and financial knowledge. Lastly, we investigated the associations between the recipients of student loans and their financial well-being, anxiety and behaviors concerning student loans.

Design/methodology/approach

Utilizing data from the 2021 National Financial Capability Study, we explored how unprecedented economic disruptions have affected student loan holders' financial well-being, levels of debt anxiety and payment delinquency, considering financial knowledge as a critical factor. We conducted Ordinary Least Squares (OLS) and logistic regressions to examine the associations addressed in the purpose of the study.

Findings

The results of regression analyses indicate that individuals with student loans generally experienced lower financial well-being than those without loans. Among student loan holders, COVID-19 shocks were positively associated with student loan anxiety and payment delinquency. Additionally, subjective financial knowledge showed a positive association, while objective financial knowledge displayed a negative association with loan delinquency. Lastly, respondents who secured loans for themselves exhibited lower levels of financial well-being than other student loan holders.

Originality/value

This study represents one of the initial efforts to investigate the issues of financial well-being, debt anxiety and payment delinquency among student loan holders, along with their associations with the potential COVID-19 shocks they experienced. The research shed light on the acute financial stress and mental health challenges faced by student loan holders during global crises, highlighting the significance of effective policy development for student debt management and borrower support during times of economic uncertainty.